diff options
Diffstat (limited to 'old/69874-h/69874-h.htm')
| -rw-r--r-- | old/69874-h/69874-h.htm | 28883 |
1 files changed, 0 insertions, 28883 deletions
diff --git a/old/69874-h/69874-h.htm b/old/69874-h/69874-h.htm deleted file mode 100644 index a64ca45..0000000 --- a/old/69874-h/69874-h.htm +++ /dev/null @@ -1,28883 +0,0 @@ -<!DOCTYPE html> -<html xmlns="http://www.w3.org/1999/xhtml" xml:lang="en" lang="en"> - <head> - <meta charset="UTF-8"> - <title> - The Project Gutenberg eBook of Gout, by Llewellyn Jones Llewellyn. - </title> - - <link rel="icon" href="images/cover.jpg" type="image/x-cover"> - - <style> - -a { - text-decoration: none; -} - -body { - margin-left: 10%; - margin-right: 10%; -} - -h1,h2,h3,h4 { - text-align: center; - clear: both; -} - -h2.nobreak { - page-break-before: avoid; -} - -hr.chap { - margin-top: 2em; - margin-bottom: 2em; - clear: both; - width: 65%; - margin-left: 17.5%; - margin-right: 17.5%; -} - -img.w100 { - width: 100%; -} - -.illowp100 { - width: 100%; -} - -div.chapter { - page-break-before: always; -} - -ul { - list-style-type: none; -} - -li, li.indx { - margin-top: .5em; - padding-left: 2em; - text-indent: -2em; -} - -li.ifrst { - margin-top: 2em; - padding-left: 2em; - text-indent: -2em; -} - -li.isub1 { - padding-left: 4em; - text-indent: -2em; -} - -li.isub2 { - padding-left: 6em; - text-indent: -2em; -} - -li.isub3 { - padding-left: 8em; - text-indent: -2em; -} - -p { - margin-top: 0.5em; - text-align: justify; - margin-bottom: 0.5em; - text-indent: 1em; -} - -table { - margin: 1em auto 1em auto; - max-width: 40em; - border-collapse: collapse; -} - -th { - padding: 0.25em; - font-weight: normal; - font-size: 90%; -} - -td { - padding-left: 2.25em; - padding-right: 0.25em; - vertical-align: top; - text-indent: -2em; -} - -.tdc { - text-align: center; -} - -.tdr { - text-align: right; -} - -.borders td { - border-right: thin solid black; -} - -.borders th { - border-right: thin solid black; - border-top: thin solid black; - border-bottom: thin solid black; -} - -.borders td:last-child, .borders th:last-child { - border-right: none; -} - -.borders tr:last-child td { - border-bottom: thin solid black; -} - -.contents td { - padding-left: 2.25em; - padding-right: 0.25em; - vertical-align: top; - text-indent: -2em; - text-align: justify; -} - -.contents .tdc { - text-align: center; - padding-left: 0.25em; - text-indent: 0; -} - -.contents .pad { - padding-top: 1em; - padding-bottom: 0.25em; -} - -.contents .tdpg { - vertical-align: bottom; - text-align: right; - white-space: nowrap; -} - -.rx { - max-width: 25em; -} - -.rx td { - padding-left: 0.25em; - text-indent: 0; -} - -td.bt, tr.bt td { - border-top: thin solid black; -} - -.blockquote { - margin: 1.5em 10%; -} - -.caption { - text-align: center; - margin-top: 1em; - font-size: 90%; - text-indent: 0em; -} - -.center { - text-align: center; - text-indent: 0em; -} - -.ditto { - margin-left: 2em; - margin-right: 2em; -} - -.figcenter { - margin: auto; - text-align: center; -} - -.footnotes { - margin-top: 1em; - border: dashed 1px; -} - -.footnote { - margin-left: 10%; - margin-right: 10%; - font-size: 0.9em; -} - -.footnote .label { - position: absolute; - right: 84%; - text-align: right; -} - -.fnanchor { - vertical-align: super; - font-size: .8em; - text-decoration: none; -} - -.larger { - font-size: 125%; -} - -.noindent { - text-indent: 0em; -} - -.nw { - white-space: nowrap; -} - -.pagenum { - position: absolute; - right: 4%; - font-size: smaller; - text-align: right; - font-style: normal; -} - -.poetry-container { - text-align: center; -} - -.poetry { - display: inline-block; - text-align: left; -} - -.poetry .stanza { - margin: 1em 0em 1em 0em; -} - -.poetry .verse { - padding-left: 3em; -} - -.poetry .indent0 { - text-indent: -3em; -} - -.poetry .indent2 { - text-indent: -2em; -} - -.poetry .indent12 { - text-indent: 3em; -} - -.poetry .indent20 { - text-indent: 7em; -} - -.poetry .indent24 { - text-indent: 9em; -} - -.right { - text-align: right; -} - -.smaller { - font-size: 80%; -} - -.smcap { - font-variant: small-caps; - font-style: normal; -} - -.sp2 { - padding-right: 0.75em; -} - -.sp3 { - padding-right: 1em; -} - -.sp4 { - padding-right: 1.25em; -} - -.sp5 { - padding-right: 1.75em; -} - -.titlepage { - text-align: center; - margin-top: 3em; - text-indent: 0em; -} - -.x-ebookmaker img { - max-width: 100%; - width: auto; - height: auto; -} - -.x-ebookmaker .poetry { - display: block; - margin-left: 1.5em; -} - -.x-ebookmaker .blockquote { - margin: 1.5em 5%; -} - - </style> - </head> -<body> -<p style='text-align:center; font-size:1.2em; font-weight:bold'>The Project Gutenberg eBook of Gout, by Llewellyn Jones Llewellyn</p> -<div style='display:block; margin:1em 0'> -This eBook is for the use of anyone anywhere in the United States and -most other parts of the world at no cost and with almost no restrictions -whatsoever. You may copy it, give it away or re-use it under the terms -of the Project Gutenberg License included with this eBook or online -at <a href="https://www.gutenberg.org">www.gutenberg.org</a>. If you -are not located in the United States, you will have to check the laws of the -country where you are located before using this eBook. -</div> - -<p style='display:block; margin-top:1em; margin-bottom:0; margin-left:2em; text-indent:-2em'>Title: Gout</p> -<p style='display:block; margin-left:2em; text-indent:0; margin-top:0; margin-bottom:1em;'>With a section on ocular disease in the gouty by W. M. Beaumont</p> -<p style='display:block; margin-top:1em; margin-bottom:0; margin-left:2em; text-indent:-2em'>Author: Llewellyn Jones Llewellyn</p> -<p style='display:block; margin-top:1em; margin-bottom:0; margin-left:2em; text-indent:-2em'>Contributor: W. M. Beaumont</p> -<p style='display:block; text-indent:0; margin:1em 0'>Release Date: January 24, 2023 [eBook #69874]</p> -<p style='display:block; text-indent:0; margin:1em 0'>Language: English</p> - <p style='display:block; margin-top:1em; margin-bottom:0; margin-left:2em; text-indent:-2em; text-align:left'>Produced by: Mark C. Orton and the Online Distributed Proofreading Team at https://www.pgdp.net (This file was produced from images generously made available by The Internet Archive)</p> -<div style='margin-top:2em; margin-bottom:4em'>*** START OF THE PROJECT GUTENBERG EBOOK GOUT ***</div> - -<p><span class="pagenum"><a id="Page_i"></a>[i]</span></p> - -<div class="figcenter illowp100" id="frontispiece" style="max-width: 43.75em;"> - <p class="caption"><span class="smcap">Gouty Arthritis.</span></p> - <p class="caption">Note large tuberous swellings on knuckle and - metacarpo-phalangeal joints due to uratic deposits.</p> - <img class="w100" src="images/frontispiece.jpg" alt=""> -</div> - -<p><span class="pagenum"><a id="Page_ii"></a>[ii]</span></p> - -<hr class="chap x-ebookmaker-drop"> - -<p><span class="pagenum"><a id="Page_iii"></a>[iii]</span></p> - -<h1>GOUT</h1> - -<p class="titlepage larger"><span class="smaller">BY</span><br> -LLEWELLYN JONES LLEWELLYN, M.B. Lond.</p> - -<p class="center smaller">GOVERNOR AND SENIOR PHYSICIAN, ROYAL MINERAL WATER HOSPITAL, BATH;<br> -FELLOW OF ROYAL SOCIETY OF MEDICINE; AUTHOR OF “ARTHRITIS DEFORMANS”;<br> -CO-AUTHOR OF “FIBROSITIS”; CO-AUTHOR OF “MALINGERING, OR THE SIMULATION<br> -OF DISEASE”; CO-AUTHOR OF “PENSIONS AND THE PRINCIPLES OF THEIR<br> -EVALUATION”; CONTRIBUTOR TO LATHAM AND ENGLISH’S “SYSTEM OF TREATMENT,”<br> -ALSO TO “OXFORD ENCYCLOPÆDIA OF TREATMENT” AND TO “STUDENT’S<br> -TEXT-BOOK OF SURGERY.”</p> - -<p class="titlepage larger"><span class="smaller">WITH A SECTION ON</span><br> -OCULAR DISEASE IN THE GOUTY<br> -<span class="smaller">BY</span><br> -W. M. BEAUMONT</p> - -<p class="center smaller">CONSULTING OPHTHALMIC SURGEON TO THE SOUTH-WESTERN<br> -REGION OF THE MINISTRY OF PENSIONS; AUTHOR OF “INJURIES<br> -OF THE EYES OF THE UNEMPLOYED, PROBLEMS IN PROGNOSIS,” ETC.</p> - -<p class="titlepage"><span class="smaller">ST. LOUIS</span><br> -C. V. MOSBY COMPANY<br> -<span class="smaller">1921</span></p> - -<p><span class="pagenum"><a id="Page_iv"></a>[iv]</span></p> - -<p class="titlepage smaller"><i>Printed in Great Britain.</i></p> - -<hr class="chap x-ebookmaker-drop"> - -<p><span class="pagenum"><a id="Page_v"></a>[v]</span></p> - -<p class="center"><span class="smaller">Dedicated<br> -TO</span><br> -MY WIFE</p> - -<p><span class="pagenum"><a id="Page_vi"></a>[vi]</span></p> - -<hr class="chap x-ebookmaker-drop"> - -<div class="chapter"> - -<p><span class="pagenum"><a id="Page_vii"></a>[vii]</span></p> - -<h2 class="nobreak">PREFACE</h2> - -</div> - -<p>“A knowledge of the real nature of gout ... is, in my -opinion, at the very foundation of all sound pathology,” wrote -Todd many years since; and the passing years have but invested -his reflection with deeper significance and something of prophetic -insight. For who can doubt that he who would elucidate the -pathological groundwork of gout must be at once a clinical -physician, a bio-chemist, a bacteriologist, a morbid anatomist? -and well may we ask, Who is sufficient for all this?</p> - -<p>How vivid the light thrown upon the problems of clinical -medicine by the bio-chemists! The story of the fate of protein -and purin substances in the animal body, at one time a medley of -guesses and gaps, is gradually evolving into one of relative certitude -and completeness. Revolutionary, in truth, the change, and -many a cherished shibboleth has been ruthlessly cast aside! -With admiration not unmingled with awe we see them laying -well and truly the foundations upon which in the ultimate -scientific medicine must inevitably rest.</p> - -<p>Of these the very corner-stones are <i>chemical physiology</i> and -<i>chemical pathology</i>, the rapid evolution of which is profoundly -altering our conceptions of health and disease. Those vital processes -of the organism that but yesterday we saw “as through a -glass, darkly,” are now in great part illumined, and the distortions -wrought in them by disease made more manifest.</p> - -<p>How pregnant, too, with warning their findings! Processes -that to our untutored minds seem simple are revealed as infinitely -complex. Through what a maze must we thread our way if we -would disentangle the intricacies of metabolism! Intricate -enough, forsooth, in health, but how much more so in disease! -For, as Sir Archibald Garrod eloquently phrases it, “it is becoming -evident that special paths of metabolism exist, not only for -proteins, fats, and carbohydrates as such, but that even the individual -primary fractions of the protein molecule follow their several -katabolic paths, and are dealt with in successive stages by series -of enzymes until the final products of katabolism are formed. Any -of these paths may be locked while others remain open.”</p> - -<p>It is with chastening reflections such as these that we may best -approach our study of gout, that riddle of the ages upon which -so many physicians from time immemorial have expended their -dialectic skill. But, vast though the increase in our knowledge<span class="pagenum"><a id="Page_viii"></a>[viii]</span> -of the chemical structure of uric acid and its allies, uncertainty -still dogs our steps, and, doubtful of the pathway to solution of -the pathological mystery of gout, we must perforce approach the -problem in a more strictly catholic attitude.</p> - -<p><i>Uric acid</i> has apparently failed us as the <i>causa causans</i>. Neither -this substance nor its precursors can be held responsible for the -fever, local inflammation and constitutional disturbances in gout, -being, as they are, practically <i>non-toxic</i>. Albeit, though I hold -this view, I do not for one moment suggest that <i>uric acid</i> has -nothing whatever to do with gout. The fact that <i>tophi</i>, its pathognomonic -stigmata, are compounded of <i>biurate of soda</i>, would -<i>per se</i> stamp such an attitude as untenable. On the other hand, -<i>uric acid</i> must be viewed at its proper perspective as a <i>concomitant</i> -or <i>sequel</i> of <i>gouty inflammation</i>, the essential cause of which must -be sought elsewhere.</p> - -<p>“The old order changeth, giving place to new,” and happily -with the advent of <i>bacteriology</i> our views, or rather our hazards, -as to the nature of joint diseases underwent profound modification. -But, strange to say, though quick to apprehend the significance -of infection, its causal relation to other joint disorders, we -still seem unaccountably loth to discard our timeworn conception -of “gouty” arthritis as of purely <i>metabolic</i> origin. This to my -mind is the more remarkable in that the onset, clinical phenomena, -and course of acute gout, and no less the life history of the -disorder as a whole, are emphatically indicative of the intrusion -of an <i>infective element</i> in its genesis.</p> - -<p>The extreme frequency with which <i>infective foci</i> are met with -in the victims of gout, the frequency, too, with which exacerbations -of the disorder are presaged by <i>acute glandular affections</i> of -undeniably <i>infective</i> source, is by no means adequately realised. -For our forefathers gout began, and, forsooth, often ended, in the -“stomach,” or it was the “liver” that was impeached. But the -portal to the alimentary canal was for them only a cavity, the -contained structures of which, albeit, to their mind often betrayed -evidences of a “gouty diathesis.” They distinguished “gouty” -teeth, “gouty” tonsillitis, “gouty” pharyngitis, even “gouty” -parotitis; but all these they classed as tokens or sequelæ of gout, -not possible causes or <i>excitants</i> thereof.</p> - -<p>Now as to the true significance of these acute glandular affections -held by clinicians of repute to be of “gouty” origin. What -of “gouty” tonsillitis, pharyngitis, parotitis? Still more, what -of our deductions regarding the relationship of these same when -met with in association with <i>non-gouty</i> forms of arthritis? Do we -not hold them each and all as evidences of <i>infection</i>? and, we may -well ask, why not in gout?</p> - -<p><span class="pagenum"><a id="Page_ix"></a>[ix]</span></p> - -<p>The marvel then is that even to-day many still hold that the -tonsillitis, pharyngitis, even the gingivitis, like the subsequent -articular lesions, are one and all attributable to the underlying -<i>gout</i>. We certainly should not do so in the case of any arthritis -other than “gouty,” and to my mind the time is ripe for a change -of attitude.</p> - -<p>The “gouty” throats, like the “gouty” teeth, should be -regarded not as symptomatic of gout, but <i>etiologically</i> related -thereto. We should cease to talk of “gouty” throats, teeth, -etc., should renounce the prefix, for there is nothing <i>specific</i> of -<i>gout</i> either in the tonsillar, pharyngeal, or dental lesions. We -should instead view these various local disorders in their true -perspective as <i>foci</i> of <i>infection, causally</i> related to the subsequent -and <i>secondary</i> “gouty” arthritis.</p> - -<p>Similarly, when we come to analyse the component elements of -an acute paroxysm of gout, how strongly indicative of the intrusion -of an <i>infective</i> element the following features: the onset, -temperature curve, character of local articular changes of the -disorder, the presence of <i>leucocytosis</i>, with secondary anæmia -and enlargement of the lymphatic glands! Again, how suggestive -the occasional complication of acute gout by <i>lymphangitis</i> -and <i>phlebitis</i>! Of like significance, too, the paroxysmal nature -and periodicity of the disorder, and the compatibility of the -morbid anatomical changes and the cytological content of the -aspirated joint fluid with their genesis by <i>infection</i>.</p> - -<p>As to correlation of the metabolic phenomena of gout with the -postulated infective element, I would suggest that, although -abnormalities of metabolism form an integral part of gout, they -are of themselves inadequate to achieve its efflorescence. As we -shall see when we come to consider those elemental manifestations -of gout, <i>i.e.</i>, uratic deposits, or <i>tophi</i>, neither the purely physical -nor the purely chemical theory of their origin will suffice, nor, -for that matter, can any solution of their formation be gleaned -from even a blend of the twain. In short, such hypotheses are -too <i>mechanical</i>.</p> - -<p>The intrusion of some other factor, “something vital, something -biological,” seems essential for the elucidation of <i>uratosis</i>, -<i>i.e.</i>, uratic deposition. For this, <i>not uricæmia</i>, is the specific -characteristic phenomenon of gout. If we cannot explain uratosis -on physical or chemical grounds, then how much less, in view of -the <i>non-toxicity</i> of <i>uric acid</i>, can we on this basis account for the -<i>inflammatory</i> phenomena of the disorder!</p> - -<p>Now <i>inflammatory reaction</i> is, I hold, an invariable <i>antecedent</i> -in all gouty processes, whether of <i>articular</i> or <i>ab-articular</i> site. -Granted that inflammatory reaction is a necessary prelude, the<span class="pagenum"><a id="Page_x"></a>[x]</span> -specificity of gout is attested by the fact that the same is followed -by local deposition of urates. But while this sequential uratic -deposition invests all forms of “gouty” inflammation with a -specific character unshared by any other disease, it follows that -the cause of the said inflammation must, if possible, be ascertained.</p> - -<p>Now, as I believe, “gouty” subjects are <i>ab initio</i> victimised by -innate tissue peculiarities, doubtless reflected in corresponding -obliquities of tissue function and metamorphosis, and through -their medium the general resistance of the body to invasion by -<i>infections</i> is lowered; in other words, under the influence of -these morbific agencies the latent morbid potentialities of the -gouty become overt and manifest. For in the gouty, as Walker -Hall observes, “a slight injury or indiscretion of diet, an overloaded -intestine, or increased toxicity of the intestinal flora, may -be followed by a disturbance of the general nuclein metabolism -and a local reaction in certain tissues.”</p> - -<p>Enough has been said to disclose the dominant trend of this -work, and although there are many aspects of the subject in -regard to which I hold somewhat iconoclastic views, yet exigencies -of space forbid me even to allude to them in this foreword. I -hasten therefore to discharge the pleasing duty of acknowledging -my great indebtedness to the acumen and discrimination which -has been brought to bear on this subject by a long succession of -eminent physicians, in proof of which I need only adduce the -names of those giants of the past the illustrious Sydenham, Sir -Thomas Watson, Sir Charles Scudamore, Jonathan Hutchinson, -not to mention Trousseau, Charcot, Lecorche, and Rendu. But -I should fail in my duty did I not in a special sense express my -deep indebtedness to the classic and epoch-making work of Sir -Alfred Garrod. For the rest, too, I have derived much enlightenment -from Sir Dyce Duckworth’s treatise and the various works -on the subject by Luff, Lindsay, and others.</p> - -<p>From the bio-chemical aspect I owe much to the researches of -Walker Hall, and to those of our American <i>confrères</i> Folin, Denis, -Benedict, Pratt, McLeod, Walker Jones, Gideon Wells, etc.</p> - -<p>Reverting to my own colleagues at the Royal Mineral Water -Hospital, Bath, I would tender my deep thanks to the Honorary -Physicians, Drs. Waterhouse, Thomson, Lindsay, and King -Martyn, for the uniformly generous manner in which they afforded -me opportunities for studying cases under their care.</p> - -<p>To Dr. Munro, our senior pathologist, I am especially beholden -for invaluable, nay indispensable, help in the matter of blood -examinations, the cytological study of joint fluids, and the -microscopic verifications of tophi. To Dr. MacKay also my<span class="pagenum"><a id="Page_xi"></a>[xi]</span> -cordial thanks are due for the skiagraphs contained in this -work.</p> - -<p>For the section dealing with the ocular disorders met with in the -gouty my most sincere thanks are due to Mr. W. M. Beaumont, -of Bath, whose singularly wide experience in this sphere renders -him unusually equipped to deal with this highly controversial -aspect of gout. To Drs. Cave and Gordon, of Bath, also I am -indebted for many valuable suggestions kindly afforded me while -writing this volume. To my brother Dr. Bassett Jones I am -under deep obligation for unwearying assistance in our joint -endeavour to ascertain the exact relationship of gout to lumbago, -sciatica, and other types of fibrositis.</p> - -<p>For the preparation of the index of this work I would proffer my -grateful thanks to Mr. Charles Hewitt and to Miss Donnan and -Miss Crosse for having undertaken the arduous task of typing the -manuscript thereof.</p> - -<p>Lastly, I would express my thanks to my publisher, Mr. Heinemann, -for much consideration and many courtesies.</p> - -<p class="right">LL. J. LL.</p> - -<p><span class="smcap">31, Upper Brook Street, W. 1.</span></p> - -<p><span class="pagenum"><a id="Page_xii"></a>[xii]</span></p> - -<hr class="chap x-ebookmaker-drop"> - -<div class="chapter"> - -<p><span class="pagenum"><a id="Page_xiii"></a>[xiii]</span></p> - -<h2 class="nobreak">TABLE OF CONTENTS</h2> - -</div> - -<table class="contents"> - <tr> - <td class="tdc pad">CHAPTER I<br>HISTORICAL AND INTRODUCTORY</td> - <td></td> - </tr> - <tr> - <td>The Antiquity of Gout. Prevalence of Gout in the Anglo-Saxon Period. - Views of the Humoralist. The Aphorisms of Hippocrates. Introduction - of the Word Gout. Early Views as to the Nature of Tophi. - The “Honour of the Gout.” That Gout confers Immunity from other - Disorders. Growing Infrequency and Attenuation of Gout</td> - <td class="tdpg"><a href="#CHAPTER_I"><i>pp.</i> 1-13</a></td> - </tr> - <tr> - <td class="tdc pad">CHAPTER II<br>THE PEDIGREE OF GOUT</td> - <td></td> - </tr> - <tr> - <td>Tardy Dissociation of Chronic Gout. Identification of Muscular Rheumatism. - Differentiation of Chronic Gout from Arthritis Deformans. - Cleavage of Arthritis Deformans into Two Types. Elimination of the - Infective Arthritides</td> - <td class="tdpg"><a href="#CHAPTER_II"><i>pp.</i> 14-20</a></td> - </tr> - <tr> - <td class="tdc pad">CHAPTER III<br>EARLIER THEORIES OF PATHOGENESIS</td> - <td></td> - </tr> - <tr> - <td>Garrod’s Theory. Antagonistic Views. Histogenous Theories. Antecedent - Structural Changes. Hepatic Inadequacy. Hyperpyræmia. - Nervous Theories. Growing Scepticism as to Garrod’s Pathogeny - of Gout</td> - <td class="tdpg"><a href="#CHAPTER_III"><i>pp.</i> 21-34</a></td> - </tr> - <tr> - <td class="tdc pad">CHAPTER IV<br>DEFINITION, CLASSIFICATION, ETIOLOGY, AND MORBID ANATOMY</td> - <td></td> - </tr> - <tr> - <td>Definition. Classification. Suggested Classification of Articular Gout. - Etiology and Morbid Anatomy. Bodily Conformation and Individual - Temperament. Locality, Race, Climate. Food, Drink, Occupation. - Lead Poisoning. Mental and Physical Over-exertion. Summary. - Morbid Anatomy</td> - <td class="tdpg"><a href="#CHAPTER_IV"><i>pp.</i> 35-58</a></td> - </tr> - <tr> - <td class="tdc pad">CHAPTER V<br>PATHOLOGY OF GOUT-PROTEIN METABOLISM</td> - <td></td> - </tr> - <tr> - <td>Revelations of the Bio-chemist. The Formation of Urea. Fate of the - Amino-acids. Seat of Formation of Urea. Amino-acids in Relation - to Gout. The Glycocoll Theory of Gout. Urea Excretion in Gout. - Creatine and Creatinine. Inborn Errors of Metabolism</td> - <td class="tdpg"><a href="#CHAPTER_V"><i>pp.</i> 59-70</a></td> - </tr> - <tr> - <td class="tdc pad">CHAPTER VI<br>NUCLEIN METABOLISM</td> - <td></td> - </tr> - <tr> - <td>The Isolation of Nucleic Acid. Researches on Spermatozoa. The Discovery - of Purins. Uric Acid a Derivative of Nucleic Acid. The - Chemistry of Uric Acid and the Purin Bodies. Chemical Constitution. - Properties of Uric Acid. Uric Acid in the Blood. Gudzent and - Schade’s Theories. Organic Combinations. Complexity of the - Problem</td> - <td class="tdpg"><a href="#CHAPTER_VI"><i>pp.</i> 71-82</a><span class="pagenum"><a id="Page_xiv"></a>[xiv]</span></td> - </tr> - <tr> - <td class="tdc pad">CHAPTER VII<br>SOURCES OF URIC ACID</td> - <td></td> - </tr> - <tr> - <td>Exogenous Purins. Exogenous Uric Acid Excretion. Fate of the Unexcreted - Purins. Endogenous Purins. Source of Endogenous Purins. - Proteins and their Derivatives. Amino-acids and Dicarboxylic - Amino-acids. Endogenous Uric Acid Excretion. Factors influencing - Endogenous Uric Acid Excretion. Physiological Conditions. Pathological - States. Ingestion of Certain Drugs. Synthetic Formation of - Uric Acid</td> - <td class="tdpg"><a href="#CHAPTER_VII"><i>pp.</i> 83-97</a></td> - </tr> - <tr> - <td class="tdc pad">CHAPTER VIII<br>FORMATION AND DESTRUCTION OF URIC ACID</td> - <td></td> - </tr> - <tr> - <td>Distribution of the Enzymes. Stages in Disruption of Nucleic Acid. - Destruction of Uric Acid</td> - <td class="tdpg"><a href="#CHAPTER_VIII"><i>pp.</i> 98-106</a></td> - </tr> - <tr> - <td class="tdc pad">CHAPTER IX<br>URIC ACID IN RELATION TO GOUT</td> - <td></td> - </tr> - <tr> - <td>Uric Acid Excretion in Gout. Uric Acid Variations in Acute Gout. Uric - Acid Variations in Chronic Gout. Retarded Exogenous Uric Acid - Output. Lowered Endogenous Uric Acid Output. Other Anomalies - in Excretion in Gout. Purin Metabolism in other Disorders. Purin - Metabolism in Chronic Alcoholism and Plumbism</td> - <td class="tdpg"><a href="#CHAPTER_IX"><i>pp.</i> 107-116</a></td> - </tr> - <tr> - <td class="tdc pad">CHAPTER X<br>THE RENAL THEORY OF GOUT</td> - <td></td> - </tr> - <tr> - <td>Anomalies in Uric Acid Excretion in Gout. Uricæmia in Nephritis. The - Relationship, if any, between the Amounts of Uric Acid and of Urea, - and Total Non-protein Nitrogen in Human Blood. Uricæmia not - necessarily due to Renal Defect. Uricæmia not Peculiar to Nephritis. - Uricæmia does not necessarily Portend Gout. To what may be ascribed - the Deficient Eliminating Capacity of the Kidney for Uric Acid. - Uratic Deposits in Nephritis. Differentiation of Uratic Deposits in - Gout and Nephritis. Clinical Associations of Gout and Granular - Kidney</td> - <td class="tdpg"><a href="#CHAPTER_X"><i>pp.</i> 117-132</a></td> - </tr> - <tr> - <td class="tdc pad">CHAPTER XI<br>URICÆMIA IN GOUT</td> - <td></td> - </tr> - <tr> - <td>Folin and Denis’s Method. Uric Acid a Normal Constituent of Blood. - Effect of Exogenous Purins. Uric Acid Content of Blood in Gout. - Hyperuricæmia in Non-gouty Arthritis. Variations in Uric Acid - Content of Blood independently of Diet. What Relationship, if any, - Exists between the Uric Acid Content of the Blood and Attacks of - Gout. Discussion of the Foregoing Data. The Significance of Uricæmia. - Sources of Fallacy in Uric Acid Estimation. Disabilities of Modern - Tests. Need for further Investigations</td> - <td class="tdpg"><a href="#CHAPTER_XI"><i>pp.</i> 133-148</a></td> - </tr> - <tr> - <td class="tdc pad">CHAPTER XII<br>URATOSIS IN RELATION TO GOUT</td> - <td></td> - </tr> - <tr> - <td>Constitution of Tophi. Mode of Formation. Localisation of Uratic - Deposits. The Causation of Tophi. Solubilities of Uric Acid. Tophi - in Relation to Uricæmia. Tissue Affinities for Uric Acid. Retention - Capacity of Tissues for Uric Acid. Clinical Evolution of Tophi. The - Cause of the Inflammatory Phenomena. Non-toxicity of Uric Acid. - Are the Precursors of Uric Acid Toxic?</td> - <td class="tdpg"><a href="#CHAPTER_XII"><i>pp.</i> 149-170</a><span class="pagenum"><a id="Page_xv"></a>[xv]</span></td> - </tr> - <tr> - <td class="tdc pad">CHAPTER XIII<br>THE RISE OF THE INFECTIVE THEORY</td> - <td></td> - </tr> - <tr> - <td>Boerhaave’s Forecast of the Infective Theory. Ringrose Gore on Infective - Origin. Leucocytosis in Acute Gouty Polyarthritis. Chalmers - Watson’s Researches on Gout in a Fowl. Trautner’s Suggestion of a - Specific Infection</td> - <td class="tdpg"><a href="#CHAPTER_XIII"><i>pp.</i> 171-176</a></td> - </tr> - <tr> - <td class="tdc pad">CHAPTER XIV<br>GOUT AS AN INFECTION</td> - <td></td> - </tr> - <tr> - <td>Local Foci of Infection: Dental, Nasal, Pharyngeal, etc. Gastro-intestinal - Disorders. Variation in Free HCL. Intestinal Disorders. - Infection or Sub—infection</td> - <td class="tdpg"><a href="#CHAPTER_XIV"><i>pp.</i> 177-187</a></td> - </tr> - <tr> - <td class="tdc pad">CHAPTER XV<br>GOUT AS AN INFECTION (<i>continued</i>)</td> - <td></td> - </tr> - <tr> - <td>Analysis of the Acute Paroxysm. The Evolution and Life History of - Gout. Analogies between Gout and the Specific Infective Arthritides. - Correlation of the Metabolic Phenomena of Gout with the Postulated - Infective Element</td> - <td class="tdpg"><a href="#CHAPTER_XV"><i>pp.</i> 188-199</a></td> - </tr> - <tr> - <td class="tdc pad">CHAPTER XVI<br>CLINICAL ACCOUNT</td> - <td></td> - </tr> - <tr> - <td>Acute Localised Gout. Prodromal Symptoms. Dyspepsia. Premonitory - Symptoms of Tophus Formation. Premonitory Articular Pains. - The Acute Paroxysm. Detailed Consideration of Phenomena. Mode - of Onset. Localisation. Nature of Pain. General Phenomena. - Pyrexia. Changes in the Blood. Uric Acid Excretion. Local Phenomena. - Tophus Formation</td> - <td class="tdpg"><a href="#CHAPTER_XVI"><i>pp.</i> 200-213</a></td> - </tr> - <tr> - <td class="tdc pad">CHAPTER XVII<br>CLINICAL ACCOUNT (<i>continued</i>)</td> - <td></td> - </tr> - <tr> - <td>Acute Gouty Polyarthritis. Mode of Invasion. Distribution of Lesions. - Local Characters. Constitutional Symptoms. Changes in the Blood. - Leucocytosis. Collateral Phenomena of Gout. Lumbago, Sciatica, - etc. Incidence of Gouty Stigmata in Various Types of Fibrositis</td> - <td class="tdpg"><a href="#CHAPTER_XVII"><i>pp.</i> 214-224</a></td> - </tr> - <tr> - <td class="tdc pad">CHAPTER XVIII<br>CLINICAL ACCOUNT (<i>continued</i>)</td> - <td></td> - </tr> - <tr> - <td>Chronic Articular Gout. The Joint Deformities of Chronic Gout. Tophi: - Their Evolution and Distribution. Other Sites of Tophi. Affinities - between Gout and other Diseases. Gout in Relation to Glycosuria. - Gout in Relation to Phlebitis. Cutaneous Disorders. Gout and - Nephritis. Prognosis in Gout</td> - <td class="tdpg"><a href="#CHAPTER_XVIII"><i>pp.</i> 225-246</a></td> - </tr> - <tr> - <td class="tdc pad">CHAPTER XIX<br>ETIOLOGICAL AND CLINICAL DIAGNOSIS.</td> - <td></td> - </tr> - <tr> - <td>Articular Gout. Etiological Diagnosis. Clinical Diagnosis. Introductory - Remarks. The Diagnostic Status of Tophi. Tophi in Relation to - Arthritis. Frequency of Tophi in True Gouty Arthritis Underestimated. - Difficulty of Detecting Tophi</td> - <td class="tdpg"><a href="#CHAPTER_XIX"><i>pp.</i> 247-257</a><span class="pagenum"><a id="Page_xvi"></a>[xvi]</span></td> - </tr> - <tr> - <td class="tdc pad">CHAPTER XX<br>CLINICAL DIAGNOSIS (<i>continued</i>)</td> - <td></td> - </tr> - <tr> - <td>Acute Articular Gout. Localised Variety. Differential Diagnosis. Infections. - Acute Gonococcal Arthritis. Traumatic Lesions. Acute - Osteoarthritis. Static Foot Deformities. Hallux Valgus with Inflamed - Bunion. Hallux Rigidus. Metatarsalgia. Gout in the Instep. - Gonococcal Arthritis. Tuberculosis and Syphilitic Disease of the - Tarsal Joints or the Related Joints. Pes Planus. Gout in the Heel. - Referred Pain. Local Sources of Fallacy. Post-calcaneal Bursitis. - Synovitis of the Tendo Achillis. Gout in the Sole. Plantar Neuralgia. - Erythromelalgia. Anomalous Sites for Initial Outbreaks</td> - <td class="tdpg"><a href="#CHAPTER_XX"><i>pp.</i> 258-267</a></td> - </tr> - <tr> - <td class="tdc pad">CHAPTER XXI<br>CLINICAL DIAGNOSIS (<i>continued</i>)</td> - <td></td> - </tr> - <tr> - <td>Acute Gouty Polyarthritis. Differential Diagnosis. Acute Articular - Rheumatism. Acute Gonococcal Arthritis. Etiology. Onset. - General Symptoms. Distribution of Lesions. Local Characters. - Associated Phenomena. Secondary Syphilitic Arthritis. Acute - Rheumatoid or Atrophic Arthritis. Age and Sex. Onset. General - Symptoms. Distribution of Lesions. Local Characters. Associated - Phenomena. Infective Arthritis of Undifferentiated Type</td> - <td class="tdpg"><a href="#CHAPTER_XXI"><i>pp.</i> 268-274</a></td> - </tr> - <tr> - <td class="tdc pad">CHAPTER XXII<br>CLINICAL DIAGNOSIS (<i>continued</i>)</td> - <td></td> - </tr> - <tr> - <td>Chronic Articular Gout. Chronic Monarticular Gout. Monarticular Gout - in Large Articulation a Rarity. Chronic Gout of Oligo-articular - Distribution. Its Confusion with Chronic Villous Synovitis. Villous - Synovitis Static and Non-gouty in Origin. Clinical Symptoms of - Villous Synovitis. Bilateral Hydrarthrosis. Peri-synovial and Peri-bursal - Gummata. Chronic Gout of Polyarticular Distribution. Differential - Diagnosis. Osteoarthritis. Local Characters of Joint - Swellings. Rheumatoid Arthritis. Local Characters of Joint Swellings. - Nerve Arthropathies. Hæmophilic Arthritis</td> - <td class="tdpg"><a href="#CHAPTER_XXII"><i>pp.</i> 275-285</a></td> - </tr> - <tr> - <td class="tdc pad">CHAPTER XXIII<br>CLINICAL DIAGNOSIS (<i>continued</i>)</td> - <td></td> - </tr> - <tr> - <td>Skiagraphy. Significance of Local Areas of Rarefaction. The Radiographic - Types of Gouty Arthritis. Differential Diagnosis. Infective - Arthritis. Hypertrophic or Osteoarthritis. Rheumatoid or Atrophic - Arthritis</td> - <td class="tdpg"><a href="#CHAPTER_XXIII"><i>pp.</i> 286-292</a></td> - </tr> - <tr> - <td class="tdc pad">CHAPTER XXIV<br>IRREGULAR GOUT</td> - <td></td> - </tr> - <tr> - <td>Historical Account. Murchison’s Views. Retrocedent Gout. Gout in the - Stomach. Cardiac and Cerebral Forms. Other Irregular Manifestations. - Conclusions. Infantile Gout</td> - <td class="tdpg"><a href="#CHAPTER_XXIV"><i>pp.</i> 293-307</a></td> - </tr> - <tr> - <td class="tdc pad">CHAPTER XXV<br>OCULAR DISEASE IN THE GOUTY</td> - <td></td> - </tr> - <tr> - <td>Evidence of Gout in the Eye. Deposition of Urates. Gouty Diathesis. - Significance and Location of Tophi. Relative Incidence of Iritis. - Metastasis. Arthritic Iritis. Gouty Iritis not a Clinical Entity. - Ocular Symptoms in Hyperuricæmia. False Gout. Retinal Hæmorrhage. - Neuro-retinitis. Glaucoma. Conclusions</td> - <td class="tdpg"><a href="#CHAPTER_XXV"><i>pp.</i> 308-326</a><span class="pagenum"><a id="Page_xvii"></a>[xvii]</span></td> - </tr> - <tr> - <td class="tdc pad">CHAPTER XXVI<br>TREATMENT OF GOUT</td> - <td></td> - </tr> - <tr> - <td>Radical Treatment of Local Foci of Infection or Toxic Absorption. Diet - in Acute and Chronic Gout. The Fallacy of Fixed Dietaries. Thorough - Physical Examination a necessary Prelude to Dieting. Need for - Collaboration of Clinician and Bio-chemist</td> - <td class="tdpg"><a href="#CHAPTER_XXVI"><i>pp.</i> 327-341</a></td> - </tr> - <tr> - <td class="tdc pad">CHAPTER XXVII<br>TREATMENT OF GOUT (<i>continued</i>)</td> - <td></td> - </tr> - <tr> - <td>Regulation of Diet in the Gouty. The Individual Foodstuffs, Proteins, - Carbohydrates, Fats, Vegetables, Fruits, Condiments. Special - Dietaries. Amylaceous Dyspepsia. Hyperchlorhydria</td> - <td class="tdpg"><a href="#CHAPTER_XXVII"><i>pp.</i> 342-371</a></td> - </tr> - <tr> - <td class="tdc pad">CHAPTER XXVIII<br>MEDICINAL AND OTHER MODES OF - THERAPY—ACUTE GOUT</td> - <td></td> - </tr> - <tr> - <td>Initial Purgation. Colchicum in Acute Gout. Method of Administration. - Preparations and Dosage. Colchicine, Salicylate of Colchicine. - Atophan. Alternative Remedies in Acute Gout. Salicylates. Alkalies. - Quinine. Thyminic Acid. Anodynes in Acute Gout. Local Measures. - Analgesics. Liniments, etc. Ionisation. Massage. Surgical Methods</td> - <td class="tdpg"><a href="#CHAPTER_XXVIII"><i>pp.</i> 372-388</a></td> - </tr> - <tr> - <td class="tdc pad">CHAPTER XXIX<br>MEDICINAL AND OTHER MODES OF - THERAPY (<i>continued</i>)—INTER-PAROXYSMAL PERIOD</td> - <td></td> - </tr> - <tr> - <td>Prophylactic Measures. Treatment of Atonic Dyspepsia. Hyperacidity - due to Organic Acids. Treatment of Hypochlorhydria. Alkalies, - Atophan, and Colchicum as Prophylactics</td> - <td class="tdpg"><a href="#CHAPTER_XXIX"><i>pp.</i> 389-396</a></td> - </tr> - <tr> - <td class="tdc pad">CHAPTER XXX<br>MEDICINAL AND OTHER MODES OF - THERAPY (<i>continued</i>)—CHRONIC ARTICULAR GOUT AND ASSOCIATED MORBID CONDITIONS</td> - <td></td> - </tr> - <tr> - <td>Alkalies. Contrasts between Salts of Sodium and Potash. Differential - Indications for their Usage. Alternatives. Salicylates. Benzoates. - Hexamine. Iodides. Iodine. Albumen Compounds. Collosol Preparations - of Iodine. Guaiacum. Local Measures in Chronic Articular - Gout. Treatment of Tophi. Ionisation. Surgical Measures. Treatment - of Associated Morbid Conditions. Fibrositis. Lumbago. - Sciatica. Acute Brachial Fibrositis. Local Massage. Oxaluria. - Glycosuria. Hyperchlorhydria. Gouty Phlebitis. Gouty Eczema. - Gouty Nephritis</td> - <td class="tdpg"><a href="#CHAPTER_XXX"><i>pp.</i> 397-417</a></td> - </tr> - <tr> - <td class="tdc pad">CHAPTER XXXI<br>CLIMATO-THERAPY, HYDRO-THERAPY, ETC.</td> - <td></td> - </tr> - <tr> - <td>Climate. Choice of Residence. Clothing. Exercise. Massage. General - Hydro-therapy. Importance of thorough Physical Examination. - Individual Reactive Peculiarities. Prophylactic Measures. Contra-indications - and Untoward Complications. Methods of Application of - General Hydro-therapy. Immersion Baths. Aix and Vichy Massage. - Vapour Baths. Indications for Sub-thermal Baths. Local Hydro-therapy. - Varieties of Douche. Treatment by Hyperæmia</td> - <td class="tdpg"><a href="#CHAPTER_XXXI"><i>pp.</i> 418-430</a><span class="pagenum"><a id="Page_xviii"></a>[xviii]</span></td> - </tr> - <tr> - <td class="tdc pad">CHAPTER XXXII<br>MINERAL SPRINGS AND CHOICE OF SPA</td> - <td></td> - </tr> - <tr> - <td>Difficulties of Definition and Classification. Radio-activity. General - Principles of Spa Treatment. Physiological Action of Radium Emanation. - Activation of Body Ferments. Influence of Uric Acid Metabolism. - Increased Excretion of Uric Acid. Subjective Phenomena of - Gout in Relation to Blood Content and Excretion of Uric Acid. - Therapeutic Action and Application. Alimentary Disorders. Glycosuria. - Raised Blood Pressure. Choice of Spa. The Spare and the - Obese. Waters Suitable for Various Types of Dyspepsia. Bickel’s - Experiments. Mineral Waters in Associated Morbid Conditions. - Glycosuria. Oxaluria. Phlebitis. Respiratory Disorders. Fibrositis. - Gouty Eczema. Uric Acid Gravel. Arterio-sclerosis. Chronic - Nephritis. Concluding Remarks on Spa Treatment</td> - <td class="tdpg"><a href="#CHAPTER_XXXII"><i>pp.</i> 431-465</a></td> - </tr> - <tr> - <td class="pad">INDEX</td> - <td class="tdpg pad"><a href="#INDEX"><i>pp.</i> 457-469</a></td> - </tr> -</table> - -<hr class="chap x-ebookmaker-drop"> - -<div class="chapter"> - -<p><span class="pagenum"><a id="Page_1"></a>[1]</span></p> - -<h2 class="nobreak" id="CHAPTER_I">CHAPTER I<br> -<span class="smaller">HISTORICAL AND INTRODUCTORY</span></h2> - -</div> - -<h3><span class="smcap">The Antiquity of Gout</span></h3> - -<p>“Teeth, bones, and hair,” quoth the Sage of Norwich, “give the -most lasting defiance to corruption,” and were it not that “Time -which antiquates antiquities and hath an art to make dust of -all things hath yet spared these minor monuments,” it might -perhaps have been inferred that gout was the primordial arthritic -disease that afflicted mankind.</p> - -<p>That it was the first articular affection to achieve clinical -individuality may be allowed, but, from the aspect of antiquity, -gout is relatively modern—the appanage of civilisation. True, -Hippocrates, discoursing in the famous Asclepion at Cos, enunciated -his aphorisms on gout some 300 years before the Christian -Era, the dawn of which moreover found Cicero in his discussions at -Tusculum lamenting its excruciating tortures “doloribus podagræ -cruciari” and the peculiar burning character of its pains “cum -arderet podagræ doloribus.”</p> - -<p>But what of that? For did not Flinders Petrie in the hoary -tombs of Gurob (dating back to the 28th Dynasty 1300 B.C.) find -in mouldering skeletons of bygone civilisations unequivocal -evidence of <i>osteoarthritis</i>.<a id="FNanchor_1" href="#Footnote_1" class="fnanchor">[1]</a> But despite these sure though silent -witnesses of the prevalence of this disorder among the ancient -people of Egypt, yet in contrast with gout, no hint transpires in -the writings of Greek or Roman physicians, nor those of much<span class="pagenum"><a id="Page_2"></a>[2]</span> -later date, that the condition was recognised <i>clinically</i>, as a joint -disorder, distinct from others of the same category.</p> - -<p>Small call to marvel thereat, for how much more arresting the -clinical <i>facies</i> of gout, with its classic insignia—tumor, robor, -calor, et dolor—than of osteoarthritis, its etiolate tokens indicative -rather of infirmity than of disease. Apart from this, it may well -be that the early Egyptians owed their relative immunity from -gout, and alike their proneness to osteoarthritis, to living hard -laborious days, unenervated by that luxury and sloth, which in -the first century A.D. drew upon the ancient Romans the caustic -reproofs of Pliny and Seneca. For the old philosophers lamented -the growing prevalence of the disorder, almost unknown in the -early, more virile days of the Empire, rightly seeing in it but -another harbinger of impending decadence, clearly attributable -as it was to riotous living and debauchery.</p> - -<p>Indeed, we have it on the authority of Galen that “In the time -of Hippocrates there were only a few who suffered from podagra, -such was the moderation in living, but in our own times, when -sensuality has touched the highest conceivable point, the number -of patients with the gout has grown to an extent that cannot be -estimated.”</p> - -<p>Nothing, in truth, seems more clearly established than this, that -gout is the Nemesis that overtakes those addicted to luxurious -habits and dietetic excesses. On the testimony of eminent -travellers we are assured that amongst aborigines the disease is -unknown. The indigenous native tribes of India are immune, -but not so the immigrant flesh-loving Parsees. Strange to relate, -Anglo-Indians of gouty habit, while resident in the Orient, seem -exempt, some say, owing to cutaneous activity, but more probably -because <i>quâ</i> Rendu “these are countries in which we cannot survive -unless we are frugal.”</p> - -<p>Nations too, like individuals, when fallen on hard times, lose -their gout. Thus the Arabs, at the zenith of their mediæval -Empire, were prone thereto, but in these latter days are almost -exempt from its ravages. But, on the other hand, if we are to -believe Professor Cantani, in no other disorder are the “sins of the -fathers visited upon the children” with such pertinacity, claiming -as he does that its marked incidence in Southern Italians is a -direct heritage from the ancient Greeks and Romans.</p> - -<h3><span class="smcap">Prevalence of Gout in the Anglo-Saxon Period</span></h3> - -<p>Reverting to our own country, what evidences as to its antiquity -are forthcoming? This much may at any rate be affirmed, -that according to Mason Good “Gout is one of the maladies -which seem to have been common in England in its earliest ages<span class="pagenum"><a id="Page_3"></a>[3]</span> -of barbarism. It is frequently noticed by the Anglo-Saxon -historian, and the name assigned to it is Fot-adl.”</p> - -<p>Cockayne, in his “Leechdoms Wortcumming and Starcraft,” of -early England, has it that the word “addle” appears to have been -a synonym for ailment, thus “Shingles was hight circle addle.” -That gout should have flourished so among our Anglo-Saxon forbears -is perhaps a matter for regret but not for astonishment, -when we recall their coarse Gargantuan feasts, washed down with -doughty draughts of ale, “sack and the well spic’d hippocras.”</p> - -<p>Gout, we see then, even in our own land, is full ancient, and the -word, as Bradley as shown, may be traced in the English tongue -right through the literature of the various periods.<a id="FNanchor_2" href="#Footnote_2" class="fnanchor">[2]</a> This not -only in the brochures of physicians, but also as in the days of -Lucian in the works of historians, and the satires of poets, which -indeed abound with allusions to the disease.</p> - -<h3><span class="smcap">Views of the Humoralists</span></h3> - -<p>The Greek physicians, quite familiar as they were with the -overt manifestations of gout, did not, as far as its nosology was -concerned, commit themselves to any appellation that might -imply their adherence to any theory as to its causation. They -contented themselves with a mere <i>topographical</i> designation, -terming the affection, <i>podagra</i>, <i>chirargra</i>, etc., according as foot or -hand was the seat of the disorder, while for polyarticular types -the generic term <i>arthritis</i> was invoked.</p> - -<p>Nevertheless the old Greek physicians had their views as to its -pathology. Thus the source of the peccant humours resided for -them in the <i>brain</i>, which they had invested with all the functions -of an absorbent and secreting gland. This hypothesis in time -was displaced by the true humoral theory, according to which the<span class="pagenum"><a id="Page_4"></a>[4]</span> -bodily fluids, those found in the alimentary canal, the blood -stream, and the glandular organs, were the primordial agents of -disease. No need, albeit, for gibes on our part, for how true much -of their conception of the genesis of disease even to-day. Indeed, -what else than a fusion of the foregoing views? the modern theory -of Sir Dyce Duckworth, who would ascribe gout to the combined -influence of <i>neural</i> and <i>humoral</i> factors. And now to consider -briefly the individual views of the fathers of medicine.</p> - -<h3><span class="smcap">The Aphorisms of Hippocrates</span></h3> - -<p>In the eyes of the pioneer priest-physician, the disorder was -attributable to a retention of humours, and many of his dicta -have stood the corroding test of time. He noted, like Sydenham, -its tendency to periodicity, its liability to recur at spring and fall. -Also that eunuchs are immune and youths also, <i>ante usum -veneris</i>, while in females its incidence is usually delayed until after -the menopause.</p> - -<p>The curability of the disease in its earlier stages was affirmed, -but that after the deposit of chalk in the joints it proved rebellious -to treatment, which for him resided in purgation and the local -application of cooling agents.</p> - -<p>In the first and second centuries Celsus, Galen, and Aretæus the -Cappadocian recounted their views as to its nature and therapy, -while the Augustan poet in his Pontic epistles, like Hippocrates, -laments that his gouty swellings defy the art of medicine.</p> - -<div class="poetry-container"> -<div class="poetry"> - <div class="stanza"> - <div class="verse indent0">“Tollere nodosam nescit medicina podogram.”</div> - </div> - <div class="stanza"> - <div class="verse right"><i>Ovid</i>, <i>Ep. ex Pont.</i>, I, 3, 23.</div> - </div> -</div> -</div> - -<p>To Celsus, venesection at the onset of an attack seemed both -curative and prophylactic. Corpulence of habit a state to be -avoided, and conformably he prescribed frugality of fare and -adequate exercise. Galen (130-200), more venturesome than his -contemporaries, voiced his belief that tophi were compact of -phlegm, blood, or bile, singly or in combination. For the rest, he -enjoined bleeding and purgation and local applications, contravening, -by the bye, Hippocrates’ claim as to the immunity of -eunuchs in that in his (Galen’s) day their sloth and intemperance -were such as readily begat the disorder.</p> - -<p>About this period Lucian of Saramosta enumerated the various -anti-gout nostrums vaunted as specifics in his day. Though in -his comic poems, the Trago-podagra and Ocypus he rightly holds -up to scorn the charlatanism rampant at the time, still it is quite -clear that he possessed no mean knowledge of the clinical vagaries -of gout and was quite alive to the mischief of too meddlesome -treatment thereof.</p> - -<p><span class="pagenum"><a id="Page_5"></a>[5]</span></p> - -<p>Said the hero of the Trago-podagra:</p> - -<div class="poetry-container"> -<div class="poetry"> - <div class="stanza"> - <div class="verse indent12">“Irritantibus me</div> - <div class="verse indent0">Soleo occupere multo iracundior</div> - <div class="verse indent0">His vero qui cogitant nihil adversum mihi</div> - <div class="verse indent0">Benignam adhibeo mentem, facilisque fio.”</div> - </div> -</div> -</div> - -<p>Again, Seneca, in a jeremiad on the decadent habits of Roman -ladies of the patrician order, observes: “The nature of women is -not altered but their manner of living, for while they rival the men -in every kind of licentiousness, they equal them too in their very -bodily disorders. Why need we then be surprised at seeing so -many of the female sex afflicted with gout.” That the old philosopher’s -misgivings were but too well founded is obvious when we -recall that so widespread were the ravages of gout among the -Romans in the third century that Diocletian, by an edict, -exempted from the public burdens those severely crippled thereby, -in sooth a blatant illustration of political pandering to national -vice.</p> - -<p>But to return to the researches of physicians, those of Aretæus -seem to have been the most enlightened of his time. A succinct -account of the mode of invasion of gout and its centripetal spread -in later stages to the larger joints is followed by enumeration of -the exciting causes of outbreaks. Anent these, he quaintly notes -the reluctance which the victims display to assigning the malady -to its true cause—their own excesses—preferring to attribute it -to a new shoe, a long walk, or an injury. Noting that men are -more liable than women, he tells us, too, that between the gouty -attacks the subject has even carried off the palm in the Olympic -games. The white hellebore, to his mind, at any rate in early -attacks, was the remedy <i>par excellence</i>. But, for the true nature -of the disease, he, with humility and piety, avows that its secret -origin is known only to the gods.</p> - -<p>Not so his successor Cælius Aurelianus, who affirmed it to be not -only hereditary but due to indigestion, over-drinking, debauchery, -and exposure. Under their maleficent influence morbid humours -were generated which sooner or later found a vent in one or other -foot, with a predilection for tendons and ligaments; these structures -he averred being the locus morbi. An abstemious dietary -with exercise was his sheet anchor in therapy, with local scarification -in preference to cupping and leeching, but violent purging -and emetics he decried, and drugs to him made little appeal.</p> - -<p>More ambitious than his predecessors, Alexander of Tralles, in -the sixth century, held that there were many varieties of gout, -some due to intra-articular effusions of blood, reminding us of -Rieken’s view (1829) that hæmophilia is an anomalous variant -of gout. Other cases, Alexander averred, were the outcome of<span class="pagenum"><a id="Page_6"></a>[6]</span> -extravasation of bile or other peccant fluids between tendons and -ligaments. Abstinence, especially from wine and blood-forming -foods, was enjoined and a plentiful use of drastic purgatives, -elaterium, etc., with local sinapisms and blisters. For the absorption -of chalk stones he commended unguents containing oil, -turpentine, ammoniacum, dragon’s blood, and litharge.</p> - -<p>Aetius, a contemporary, is noteworthy in that during the intervals -of attacks he highly eulogised the use of friction while, like -Alexander of Tralles, he seems to have been much impressed with -the virtues of colchicum, of which he says, “Hermodactylon -confestim minuit dolores.” Planchon, in 1855, in his treatise, -“De hermodactes au point de vue botanique et pharmaceutique,” -claims to have proved that the hermodactylon of the ancients was -<i>Colchicum variegatum</i>, of similar properties to the <i>Colchicum -autumnale</i>.</p> - -<p>Paulus Ægineta, like most of his <i>confrères</i>, regarded gout and -rheumatism as the same disorder, differing only in their location. -He subscribed whole heartedly to the prevailing humoral theory, -but inclined to think the site of the discharged humours was -influenced by weakness or injury of the parts. He noted, too, -that mental states, sorrow, anxiety, etc., might act as determining -causes.</p> - -<p>Nor will any historical <i>résumé</i> rest complete without a reference -to the numerous works of the Arabian physicians—Avicenna, -Rhazes, Serapion, and Haly Abbas—who one or other all maintained -gout to be hereditary, rare in women and due to peccant -humours, developed in the train of depletions, debaucheries, and -the like.</p> - -<h3><span class="smcap">Introduction of the Word “Gout”</span></h3> - -<p>In the thirteenth century the Greek terms “podagra,” -“chirargra,” etc., were to a large extent abandoned, and following -Radulfe’s lead gave way to the use of the generic term -“gout,” derived from the Latin “gutta.” Its adoption was -doubtless traceable to the prevailing humoral views of the origin -of the disorder, as due to some morbid matter exuding by -“drops” into the joint cavities. Indeed, according to Johnson, -the word “gut” was used as a synonym for “drop” by -Scottish physicians even in his day.</p> - -<p>In any case, the term found little difficulty in installing itself -among all nations, taking in French the form “goutte,” in German -“gicht,” in Spanish “gota,” etc. Trousseau thought it “an admirable -name, because in whatever sense it may have been originally -employed by those by whom it was invented, it is not now given -to anything else than that to which it is applied.” In contrast<span class="pagenum"><a id="Page_7"></a>[7]</span> -therewith, that trenchant critic Pye-Smith complained of the -laxity with which the Germans invoked the word “gicht.” He -says it is popularly credited with all the pains which are called -“rheumatics” in England. “Sometimes ‘gicht’ is nothing but -bad corns and is rarely true gout.” Albeit, Pye-Smith did not, -as we shall see later, hold even his English <i>confrères</i> in this respect -void of offence.</p> - -<p>From these remote times onwards through the Middle Ages to -the present day, an almost continuous series of historical records -testify that not only has gout always been with us, but that its -clinical characters throughout the ages have remained unaltered, -conforming ever to the primitive type. During the seventeenth -and eighteenth centuries many physicians, both British and -continental, ventilated their views as to the nature of gout, all -swearing allegiance to the old humoral pathology, notably -Sydenham, Boerhaave, Van Swieten, Hoffmann, Cadogan, etc.</p> - -<p>The English Hippocrates, as Trousseau christened the illustrious -Sydenham, displayed his catholic outlook by the pregnant words: -“No very limited theory and no one particular hypothesis can be -found applicable to explain the whole nature of gout.” A live-long -martyr himself thereto, he brought all the strength of his -dominating intellect to bear upon its elucidation. As to its -causation, he held it to be due to a “morbific matter,” the outcome -of imperfect “coctions” in the <i>primæ viæ</i> and in the -secondary assimilating organs. He refrained from speculating as -to the constitution of the <i>materia peccans</i>, but as Trousseau -observes, “he made his <i>morbi seminium</i> play the part which -modern chemistry attributes to the products it has discovered. -Take it all in all,” he says, “the theory of the great English -physician is much more medical than the theories of modern -chemists.”</p> - -<h3><span class="smcap">Early Views as to the Nature of Tophi</span></h3> - -<div class="poetry-container"> -<div class="poetry"> - <div class="stanza"> - <div class="verse indent0">“Et tophus scaber, et nigris exesa chelydris Creta.”</div> - </div> - <div class="stanza"> - <div class="verse right"><i>Georg.</i>, ii., 214.</div> - </div> -</div> -</div> - -<p>The word “tophus” or “tofus,” the Greek τοφος, seems to have -been applied to rough crumbling rock, the disintegrated volcanic -tufa. As to its constitution it is clear from the above quotation that -Virgil evidently associated it with chalk, a shrewder guess than the -fanciful hypothesis of Galen, though the views of Paracelsus -(1493-1541) enunciated some centuries subsequently, were even -more grotesque, a “mucous essence,” a “Tartarus” burning -“like hell fire.”</p> - -<p>Nevertheless, our contempt need be chastened when we recollect<span class="pagenum"><a id="Page_8"></a>[8]</span> -that, up to the latter half of the eighteenth century, equally weird -assumptions found acceptance. By some “various excrementitial -humours,” by others “checked and decomposing sweat” were -deemed the basis of tophi.</p> - -<p>A mucilaginous extract, derived from the solid and liquid -intake, appealed to some as an explanation of their formation, -while to others, tophi were compounds of subtle and penetrating -salts.</p> - -<p>But the later view, doubtless the reflex of <i>etiological</i> hypotheses, -was that tophi were of <i>tartareous</i> nature, closely similar to that -encrusting the interior of wine casks. Hoffmann declared that the -<i>materies morbi</i> actually was a salt of tartar circulating in the -blood. His investigations of tophi and also of the stools, saliva, -and urine of gouty subjects, convinced him that the peccant -matter was tartar of wine.</p> - -<p>Hoffmann’s views, however, were laughed to scorn by M. Coste -as being obviously absurd, inasmuch as gout was not uncommon -amongst those who had never partaken of wine, <i>ergo</i>, never of -tartar. How infinitely more physicianly the inference of Sydenham, -who, like some of the older humoralists held the tophus to be -“undigested gouty matter thrown out around the joints in a -liquid form and afterwards becoming hardened.”</p> - -<p>So it went on until, alchemy being displaced by chemistry, uric -acid was in 1775 discovered by Scheele, and in 1787 Wollaston -established its existence in tophi, and to the further elaboration -of our knowledge of this substance we shall allude later. Here -we would only observe that Wollaston’s researches marked the -coming substitution of the humoral and solidist theories by a -chemical hypothesis as to the etiology of gout.</p> - -<h3><span class="smcap">The “Honour of the Gout”</span></h3> - -<p>The absurd delusion, not wholly dissipated even to-day, that -to have the gout, “Morbus Dominorum,” was highly creditable, -a mark of good breeding, was firmly ingrained in our forefathers. -We all recall the story of the old Scottish gentlewoman who would -never allow that any but people of family could have <i>bonâ fide</i> -gout. Let but the <i>roturier</i> aspire to this privilege, and she scouted -the very idea—“Na, na, it is only my father and Lord Gallowa’ -that have the regular gout.” As to the origin of this mistaken -ambition, it most probably was the outcome of the fact that it was -peculiarly an appanage of the great, the wealthy, and alas! those -of intellectual distinction!</p> - -<p>Statesmen, warriors, literary men and poets loom large amongst -its victims. Lord Burleigh suffered greatly therefrom, and good<span class="pagenum"><a id="Page_9"></a>[9]</span> -Queen Bess on that account always bid him sit in her presence, -and was wont to say, “My Lord, we make much of you, not for -your bad legs, but for your good head!” With more humour, -Horace Walpole complained, “If either my father or mother had -had it I should not dislike it so much! I am herald enough to -approve it, if descended genealogically, but it is an absolute -upstart in me, and what is more provoking, I had trusted in my -great abstinence for keeping it from me, but thus it is!”<a id="FNanchor_3" href="#Footnote_3" class="fnanchor">[3]</a></p> - -<p>Of warriors, Lord Howe, Marshal Saxe, Wallenstein, and Condé -were among its victims; while of literary men and poets thus -afflicted may be mentioned Milton, Dryden, Congreve, Linnæus, -Newton, and Fielding. Of physicians, the great Harvey was a -martyr to gout, and was wont to treat it after the following heroic -fashion. Sitting, in the coldest weather, with bare legs on the -leads of Cockaine House, he would immerse them in a pail of -water until he nearly collapsed from cold. Mrs. Hunter, wife of -John Hunter, in a letter to Edward Jenner about her distinguished -husband, dated Bath, September 18th, 1785, laments that “He -has been tormented with the flying gout since last March!” In -short, the disorder, with a notable frequency, figures in the life -history of some of the ablest men in all ages, hence the complacency -with which lesser men, often without good reason, -affect to have the gout.</p> - -<p>“But nothing,” as Sir Thomas Watson says, “can show more -strongly the power of fashion than this desire to be thought to -possess, not only the tone and manners of the higher orders of -society, not their follies merely and pleasant vices, but their very -pains and aches, their bodily imperfections and infirmities. All -this is more than sufficiently ludicrous and lamentable, but so it -is. Even the philosophic Sydenham consoled himself under the -sufferings of the gout with the reflection that it destroys more rich -men than poor, more wise men than fools.”</p> - -<div class="blockquote"> - -<p>“At vero (quod mihi aliisque licet, tam fortunæ quam Ingenii dotibus -mediocriter instructis, hoc morbo laborantibus solatio esse possit) ita -vixerunt atque ita tandem mortem obierunt magni Reges, Dynastæ, -exercituum classiumque Duces, Philosophi, aliique his similes haud pauci.</p> - -<p>“Verbo dicam, articularis hicce morbus (quod vix de quovis alio adfirmaveris) -divites plures interemit quam pauperes, plures sapientes quam -fatuos.”</p> - -</div> - -<p>The Scotch at one time regarded gout as fit and meet punishment -for the luxurious living of the English. But, as was pointed -out, the cogency of the moral was somewhat spoilt by the fact -that the disorder was found to exist even among the poor and<span class="pagenum"><a id="Page_10"></a>[10]</span> -temperate Faroe Islanders. In truth, although “the taint may -be hereditary, it may be generated by a low diet and abstinence -carried to extremes.”</p> - -<h3><span class="smcap">That Gout confers Immunity from other Disorders</span></h3> - -<p>The fallacy that longevity and freedom from other maladies -was ensured by gout was prevalent among our forefathers. In -satire of this, one Philander Misaurus issued a brochure entitled -“The Honour of the Gout,” and purporting to be writ, “Right in -the Heat of a violent Paroxysm; and now publish’d for the -common Good” (1735). “Bless us,” says he, “that any man -should wish to be rid of the Gout; for want of which he may -become obnoxious to fevers and headache, be blinded in his -understanding, loose the best of his Health and the Security of his -Life”; and forthwith in his zeal for the common good gives us -the following invocation:—</p> - -<div class="poetry-container"> -<div class="poetry"> - <div class="stanza"> - <div class="verse indent0">“Blessed Gout, most desirable Gout, Sovereign Antidote</div> - <div class="verse indent0">Of murdering Maladies; powerful corrector of Intemperance;</div> - <div class="verse indent0">Deign to visit me with thy purging Fires, and throw off the</div> - <div class="verse indent0">Tophous Injury which I may have suffer’d by Wine and Wit,</div> - <div class="verse indent0">Too hard for the Virtue of a Devotee upon a Holy Festival.</div> - <div class="verse indent0">But fail not thy humble Supplicant, who needs thy</div> - <div class="verse indent0">Friendly Help, to keep his tottering Tenement in</div> - <div class="verse indent0">Order: Fail him not, every Vernal and Autumnal</div> - <div class="verse indent0">Æquinox.”</div> - </div> -</div> -</div> - -<p>He quaintly suggests that Paracelsus, if he would ensure men -against death, had but to inoculate them with gout. Gout, -indeed, was held to be a jealous disorder, intolerant of usurpation -by any other disease, recalling the remark of Posthumus to his -gaolers:—</p> - -<div class="poetry-container"> -<div class="poetry"> - <div class="stanza"> - <div class="verse indent24">“Yet am I better</div> - <div class="verse indent0">Than one that’s sick o’ the Gout: since he had rather</div> - <div class="verse indent0">Groan so in perpetuity, than be cur’d</div> - <div class="verse indent0">By the sure physician, death: who is the key</div> - <div class="verse indent0">To unbar these locks.”</div> - </div> - <div class="stanza"> - <div class="verse right"><i>Cymbeline.</i></div> - </div> -</div> -</div> - -<p>Still the fallacy that gout was salutary died hard, and although -it seems incredible, yet, Archbishop Sheldon is said not only to -have longed for gout but actually to have offered £1,000 to any -one who would procure him this blessing; for he regarded gout -as “the only remedy for the distress in his head.” How ingrained -the notion may be gathered from the fact that in the early part -of the last century, M. Coste in his “Traité Pratique de la Goutte,” -observed: “A popular error, which I wish to expose in a few -words, is this prejudice, which has already lasted more than two<span class="pagenum"><a id="Page_11"></a>[11]</span> -thousand years, and which has reached even the thrones of princes, -where the disease commonly shows itself, viz., that gout prolongs -life (<i>que la goutte prolonge la vie</i>). This error,” says he, “has -taken the surest method of introducing itself, by making flattering -promises, by persuading its victims that there is a singular -advantage in having gout, and that the malady drives away -all other evils, and that it ensures long life to those whom it -attacks.”</p> - -<p>In like refrain, our own countryman Heberden deplores that -people “are neither ashamed nor afraid of it; but solace themselves -with the hope that they shall one day have the gout; or, -if they have already suffered it, impute all their other ails, not to -having had too much of that disease, but to wanting more. The -gout, far from being blamed as the cause, is looked up to as the -expected deliverer from these evils.” Such deluded views being -prevalent, it is hardly a matter for surprise that misguided persons -deliberately courted a “fit of the gout” by resorting to excess -and intemperance.</p> - -<p>But alas, while the initial visitations of gout, after their passing, -may leave behind them a renewed sense of well-being, it is no less -certain that, when once installed, the intervals of respite grow -shorter and shorter. Crippledom grows apace, the general health -breaks and untimely senescence overtakes the worn-out victim, -and, as Heberden puts it, “that gout causes premature death, -when all the comforts of life ...</p> - -<div class="poetry-container"> -<div class="poetry"> - <div class="stanza"> - <div class="verse indent0">‘Multæ formæ infortunatorum,</div> - <div class="verse indent0">Meditatio pœnæ, et consuetudo,</div> - <div class="verse indent0">Podagros miseros consolentur.’</div> - </div> - <div class="stanza"> - <div class="verse right"><i>Lucian.</i></div> - </div> -</div> -</div> - -<p class="noindent">are destroyed, and the physical powers either insensibly undermined -or suddenly crushed by an attack of paralysis or apoplexy, -should hardly be reckoned among the misfortunes attending the -disease.”</p> - -<p>But for our encouragement it may be observed that not always -does gout carry with it such a terrible Nemesis. “Gout is the -disease of those who <i>will</i> have it,” said a wise physician, and -though the inbred gouty tendency may be so strong as to cast -defiance at abstinence, yet it is by no means always so. A -man may inherit gout, but he need not foster it by self-indulgence. -Much less need he, as so often happens, acquire it by -depraved habits of life. In no disease do sobriety and virtuous -living ensure so great a reward. As Sir Thomas Watson long -since said to those inheriting this unwelcome legacy: “Let the -son of a rich and gouty nobleman change places with the son -of a farm servant, and earn his temperate meal by the daily<span class="pagenum"><a id="Page_12"></a>[12]</span> -sweat of his brow, and the chance of his being visited with gout -will be very small.”</p> - -<div class="poetry-container"> -<div class="poetry"> - <div class="stanza"> - <div class="verse indent0">“O fortunatos nimium, sua si bona norint</div> - <div class="verse indent0">Agricolas!”</div> - </div> - <div class="stanza"> - <div class="verse right"><i>Georg.</i>, ii., 458.</div> - </div> -</div> -</div> - -<h3><span class="smcap">Growing Infrequency and Attenuation of Gout</span></h3> - -<p>So accurate and graphic were the clinical pictures of gout -depicted by the ancient physicians that there is no doubt the gout -of to-day conforms to the primitive type as met with among the -Greeks and Romans. This certainly as regards the <i>arthritic</i> -phenomena of the disease; for in those remote ages little or no -account seems to have been taken of its <i>irregular</i> or <i>ab-articular</i> -manifestations. While disregard of the latter group renders more -credible their claims as to the widespread prevalence of the -affection, nevertheless, I think there can be no doubt that the -frequency of <i>gout</i> amongst the ancient Greeks and Romans was -probably over-estimated.</p> - -<p>Can it be questioned that a large percentage of the cases of -gout in those bygone times consisted of undifferentiated <i>infective</i> -forms of <i>arthritis</i>. <i>Syphilis</i> and <i>gonorrhœa</i> must have existed -then as now, and their <i>specific</i> forms of <i>arthritis</i>, how easily confused -with “rich man’s gout!” Surely too, they, like ourselves, -must have suffered with states of <i>oral sepsis</i>, <i>pyorrhœa alveolaris</i>, -etc., not to speak of <i>infective disorders</i>, with their correlated -<i>arthritides</i>. In short, the <i>differentiation</i> of arthritic disorders -was then hardly in its infancy, and it is in light of this disability -that we must appraise their clearly extravagant assertions as to -the widespread ravages of gout in their day.</p> - -<p>But passing to more recent times, there is little doubt that the -classical type of <i>podagra</i> is very much rarer to-day than, say, in the -time of Sydenham. Indeed, it may be said to be becoming progressively -infrequent. Thus, writing in 1890, Sir Dyce Duckworth -tells us that some twenty-six years prior to that date, Sir -George Burrows informed him that “he then saw fewer cases of -acute gout than he was accustomed to see in his earlier practice.” -It may be recalled, too, that Sir Charles Scudamore, in retrospect -of his own experience, of still earlier date, was led to much the -same conclusion. Moreover, not only is the disorder less frequent, -but its virulence seems to have suffered attenuation, and this to a -marked degree.</p> - -<p>Again, Ewart, writing in 1896, observed that “goutiness” is -becoming relatively more common than declared gout. This, he -thought, by reason of the increasing attenuation in transmission -of the “gouty” taint. In this, as well as the more mitigated<span class="pagenum"><a id="Page_13"></a>[13]</span> -character of the arthritic manifestations, he saw hope of “an -ultimate extinction of the bias in ‘gouty’ families.” For, as he -rightly says, side by side with “the tendency to a reproduction -of morbid parental peculiarities, there is a yet stronger tendency -in Nature to reproduce the healthy type of the race in each -successive generation.”</p> - -<p>But while there is a general consensus of opinion as to the growing -rarity of acute regular gout, on the other hand, many, as if loth -to part with the disorder, claim that <i>pari passu</i> with the decline -of regular types the incidence of <i>irregular</i> manifestations grew -proportionately.</p> - -<p>In my experience the incidence of <i>regular</i> gout has appreciably -diminished during the past twenty years. Moreover, such -examples as one has met with incline much more in character to -the <i>asthenic</i> than to the sthenic variety of <i>podagra</i>. But, in contrast -to many, I have observed no increase in the <i>irregular</i> manifestations -of gout. On the contrary, a steady diminution in the -nebulous content of this category, but to this vexed subject we -shall recur in a subsequent chapter dealing with the propriety or -not of retaining this ill-defined term in medical nomenclature.</p> - -<p>My conclusion, then, is that not only is arthritic gout becoming -less prevalent, but that the type of the disease also has suffered -attenuation. Probably this dual change is the outcome of many -factors, not the least of these an increase in national sobriety. For -as Sir Alfred Garrod long since observed, “There is no truth in -medicine better established than the fact that the use of fermented -liquors is the most powerful of all the predisposing causes -of gout; nay, so powerful, that it may be a question whether -gout would ever have been known to mankind had such beverages -not being indulged in.</p> - -<div class="poetry-container"> -<div class="poetry"> - <div class="stanza"> - <div class="verse indent0">“Αυσιμελου Βάκχου, και λυσιμελους Αφοδίτης,</div> - <div class="verse indent0">Γένναται θυχατηρ, λυσιμελὴς, Ποδὰγρα.”</div> - </div> -</div> -</div> - -<hr class="chap x-ebookmaker-drop"> - -<div class="chapter"> - -<p><span class="pagenum"><a id="Page_14"></a>[14]</span></p> - -<h2 class="nobreak" id="CHAPTER_II">CHAPTER II<br> -<span class="smaller">THE PEDIGREE OF GOUT</span></h2> - -</div> - -<p>Under the vague term “articulorum passio” or “arthritis” -the physicians of antiquity handed down to posterity the clinical -description of a disease in the varied symptomatology of which we -may descry at one time the features of gout and anon those of -rheumatism. But centuries had to elapse before gout became -differentiated from rheumatism. For there is no doubt that not -only the Greek and Roman physicians, but those also of the -Græco-Arabian school, confounded these two disorders, or more -accurately failed to differentiate rheumatism.</p> - -<p>So it is that Charcot, reviewing the antiquity of gout, while he -pays a graceful tribute to the ancient physicians for their masterly -disquisitions thereon, at the same time deplored their silence on -the subject of articular rheumatism.</p> - -<p>This absence of allusion thereto is the more remarkable in that -the term “rheumatism” or “rheumes” dates from a very -remote period. Both words, in truth, were indifferently enlisted -to denote all those diseases deemed attributable to the defluxion -of some acrid humour upon one or other part of the body. Used -by the ancients more in accordance with its etymological sense, -the term “rheumes” or “rheumatism,” finds a place even in -the writings of Pliny and Ovid. But our modern conception of -the disorder differs widely from “the flux of humours” which the -Greeks named rheumatism, or “the sharpe and eager flux of -fleam” which for them characterised an attack of the “rheumes.”</p> - -<p>The early English authors, too, invoked the word as a general -term descriptive of various forms of disease. Sir Thomas Elyot, -in his “Castel of Health,” so scoffed at by the faculty in his day, -inculcates abstemiousness in those afflicted with the “rheumes,” -and in “Julius Caesar,” Brutus is warned by Portia not to tempt -“the rheumy unpurged ayre of night,” a clear indication that the -term was used as a synonym for fluxions, humours and catarrhs of -all sorts. But as to the malign <i>articular</i> forms of the affection, -never a word; and this almost inexplicable silence led Sydenham, -Haecker and Leupoldt to surmise that articular rheumatism was -a modern disease unknown amongst the ancients.</p> - -<p><span class="pagenum"><a id="Page_15"></a>[15]</span></p> - -<h3><span class="smcap">Isolation of Acute Articular Rheumatism From Gout</span></h3> - -<p>Hallowed by tradition, this erroneous conception of the identity -of gout and rheumatism endured until 1642, when Baillon, in his -treatise “De Rheumatismo et Pleuritide,” effected a cleavage, -at any rate between the acute varieties of these two diseases.</p> - -<p>Dissociating the term “rheumatism” from its primitive interpretation, -Baillon restricted its usage to that particular group of -symptoms we now call <i>acute articular rheumatism</i>. In the same -century Sydenham, in his “Classical Observations,” materially -clarified the existing clinical confusion, defining with his customary -lucidity the essential differences between the two disorders.</p> - -<h3><span class="smcap">Tardy Dissociation of Chronic Gout From Chronic -Rheumatism</span></h3> - -<p>Bearing in mind the centuries that elapsed before the <i>acute</i> -articular forms of gout and rheumatism were dissociated, one -ceases to marvel that the task, incomparably more difficult, of -discriminating between the <i>chronic</i> forms of these diseases is even -now barely accomplished.</p> - -<p>“Rheumatissimus agnatus podagræ” said our forefathers, the -axiom postulating not the actual identity of the two affections, but -a near relationship, and in this non-committal phrase we may, I -think, descry the birth of that modern term “<i>L’arthritisme</i>,” so -beloved of the French physicians. Even as late as the beginning -of the nineteenth century Chomel at the Saltpetrière taught his -pupils that gout and rheumatism were but clinical variants of an -underlying “arthritic diathesis,” his successor Pidoux being still -more insistent that the two disorders sprang from one common -root. Even Charcot and Trousseau, convinced as they were of -the essential distinctness of the two disorders, nevertheless admitted -that at the bedside their <i>chronic</i> manifestations were with -difficulty dissociated, the former pointing to the terms “rhumatisme -goutteux” and “rheumatic gout” as tacit acknowledgments -of our impotence.</p> - -<p>Nor did this view that <i>gout</i> and alike <i>rheumatism</i> are the outcome -of a <i>basic arthritic diathesis</i> fail of doughty supporters in this -country. Thus Hutchinson, in his “Pedigree of Disease,” -observes “gout is but rarely of pure breed, and often a complication -of rheumatism. It so often mixes itself up with rheumatism, -and the two, in hereditary transmission, become so intimately -united, that it is a matter of considerable difficulty to ascertain -how far rheumatism pure can go ... when this complication -exists. It shows its power, we may suspect, by inducing a permanent -modification of tissue, and it is to this modification that<span class="pagenum"><a id="Page_16"></a>[16]</span> -the peculiarities in the processes (transitory rheumatic pains in -joints, fasciæ, and muscles, chronic crippling arthritis, destructive -arthritis with eburnation, lumbago, sciatica) are due. Hence -the impossibility under many conditions of discriminating between -gout and rheumatism.”</p> - -<p>Laycock also subscribed to Charcot’s view, and Sir Dyce Duckworth -confesses that the conception of “a basic diathetic habit of -body called <i>arthritic</i> has well commended itself to my mind,” -while as to the clinical commingling of the two disorders Sir Charles -Scudamore spoke with no uncertain voice. That an individual -may in youth suffer from <i>acute articular rheumatism</i>, and later in -life develop <i>gout</i>, is undeniable, as also the reverse, that a gouty -subject may be harassed by manifestations of chronic rheumatism -or <i>fibrositis</i>. But this mutual trenching of the one upon the clinical -territory of the other must not be allowed to impair our views as -to the essential distinctness of <i>gout</i> and <i>rheumatism</i>. It is undeniable -that the difficulty of differentiating between the <i>chronic</i> -forms of these two disorders is great, for not even the revelations -of <i>skiagraphy</i>, in the absence of a clinical history, will suffice to -effect a discrimination. But to a further consideration of this -vexed matter we refer the reader to the coming chapters on -Diagnosis.</p> - -<h3><span class="smcap">Identification of Muscular Rheumatism</span></h3> - -<p>But to resume our thread, one great step forward we owe to -Cullen, who not only differentiated <i>acute</i> from <i>chronic</i> articular -rheumatism, but also clearly portrayed the clinical distinctness -from both of <i>muscular</i> rheumatism. In so doing, he materially -assisted in the differentiation of these same disorders from <i>gout</i>. -But at the same time, owing to his immoderate advocacy of -“chill” as the one great cause of <i>rheumatism</i> in all its forms, he -undoubtedly retarded progress. For immediately there arose a -cloud of witnesses who claimed a “rheumatic kinship” for a -myriad <i>visceral</i> disorders, the victims of which had suffered -exposure. Thus throughout the seventeenth and eighteenth -centuries many of the conditions now assigned to <i>irregular gout</i> -were affiliated instead to <i>rheumatism</i>.</p> - -<h3><span class="smcap">Differentiation of Chronic Gout From Arthritis -Deformans</span></h3> - -<p>Apart from Cullen’s contribution the eighteenth century was -unmarked by any further advance in differentiating the mass of -heterogenous joint affections, indifferently classed as gout and<span class="pagenum"><a id="Page_17"></a>[17]</span> -rheumatism. The physicians of this period, indeed, appear not -only to have done little themselves, but had omitted to utilise the -useful indications furnished by their predecessors.</p> - -<p>Thus how much more swiftly would the clinical distinctness of -chronic articular gout from <i>rheumatoid arthritis</i> have been realised -had Sydenham’s dicta in the seventeenth century regarding this -intricate problem been duly appreciated. Up to his time, the -clinical descriptions of rheumatoid arthritis appeared now under -gout, now under rheumatism. As for Sydenham himself, he -placed the disorder, nosologically speaking, under <i>chronic rheumatism</i>, -of which he believed it to be an <i>apyretic</i> variety. But the -importance of his researches resides in this—he pointed out that it -differed essentially from <i>gout</i>, but that, in resemblance thereof, it -might endure throughout life, its course diversified by remissions -and exacerbations. Also he tells us that its excruciating pains, -even when of prolonged standing, sometimes cease spontaneously, -noting also that the joints are, so to speak, turned over, and that -there are nodosities, especially on the inside of the fingers.</p> - -<p>Nevertheless, if we except Musgrave’s work (1703), “Arthritis -ex Chlorosi,” which included some undoubted examples of -<i>rheumatoid</i> or atrophic arthritis, no note was taken of Sydenham’s -contention until a century afterwards. True, John Hunter in -1759 described the morbid anatomy of <i>osteoarthritis</i> or the hypertrophic -forms of arthritis deformans, but not until 1868 was the -true significance of Sydenham’s work appreciated, a most generous -tribute being then accorded him by the great French physician -Trousseau.</p> - -<p>In 1800 Landre Beauvais published his clinical description of -<i>rheumatoid</i> arthritis under the title “goutte asthenique primitif.” -That Beauvais, as Sir Archibald Garrod contends, included under -this title some cases of true <i>gout</i> is beyond doubt. But the words -“Doit admettre une nouvelle espèce de goutte,” go far to justify -Charcot in his claim that Beauvais, despite the title of his -brochure, fully realised that the disease differed from gout.</p> - -<p>A few years later (1804-1816), Heberden, in his Commentaries, -insisted on the essential distinctness of rheumatoid arthritis from -gout. Thus he wrote, “The disease called chronical rheumatism, -which often passes under the general name of rheumatism and is -sometimes supposed to be <i>gout</i>, is in reality a very different distemper -from the genuine gout, and from the acute rheumatism, -and ought to be carefully distinguished from both.” As to its -salient features he noted its afebrile nature, the lack of redness in -the skin over the affected joints, the relative absence of pain, and -that it displayed no special tendency to begin in the feet. It was -further marked by a protracted course involving severe crippling,<span class="pagenum"><a id="Page_18"></a>[18]</span> -while the peculiar nodosities on the fingers are still associated -with his name.</p> - -<p>In 1805 Haygarth published his classical essay, “A Clinical -History of the Nodosity of the Joints,” the opening sentence of -which shows that, comparably with his successors, he lamented -the laxity with which the term “rheumatism” was invoked and -applied “to a great variety of disorders which beside pain, have -but few symptoms that connect them together.” A purist in -nosology, he equally deplored the term “rheumatick gout” as -tending to perpetuate its confusion with gout and rheumatism, -and suggested the term “Nodosities,” in the hope that “as a -distinct genus it will become a more direct object of medical -attention.”</p> - -<p>Alas, even as late as 1868 Trousseau deplored the retention of -the term “rheumatic gout” by Garrod and Fuller and his own -countryman Trastour. But, in common justice to Garrod, it must -be allowed that in the third edition of his work he definitely applied -the term <i>rheumatoid</i> arthritis to the disorder in question. Nor -can we refrain from recording Fuller’s words that “the natural -history of <i>rheumatic gout</i> accords but little with that of <i>acute -rheumatism</i>, and is equally inconsistent with that of true gout.”</p> - -<h3><span class="smcap">Cleavage of Arthritis Deformans into Two Types</span></h3> - -<p>In reviewing the researches of the foregoing writers it will be -clearly seen that though they did yeoman service in differentiating -broadly <i>gout</i> from the disorders grouped under <i>Arthritis Deformans</i>, -there is little doubt that not for many years afterwards was their -distinctiveness sufficiently realised. This may be in large part -attributed to the fact that they still awaited the next great -process of fission as applied to chronic joint disorders.</p> - -<p>I allude in the first place to Charcot’s momentous discovery of -the <i>nerve arthropathies</i>, and secondly, to the cleavage of arthritis -deformans into the <i>rheumatoid</i> or <i>atrophic</i>, and the <i>osteoarthritic</i> -or <i>hypertrophic</i> varieties.</p> - -<p>It is to Vidal that we are indebted for the first clinical description -of the <i>atrophic</i> type. Charcot in his lectures refers to it as the -“Atrophic form of Vidal,” noting that in this variety “induration -of the skin, a sort of scleroderma develops, the cutaneous -covering is cold, pale, smooth, polished, and will not wrinkle, -adding also that in such cases atrophy of the bones and muscles -accompanies the wasting of the soft tissues.”</p> - -<p>Notwithstanding this, Charcot, to our mind, unquestionably -refers to the category of <i>chronic articular gout</i> certain of these -examples of Vidal’s <i>atrophic</i> type of <i>arthritis deformans</i>. The<span class="pagenum"><a id="Page_19"></a>[19]</span> -reasons he adduces for their <i>gouty</i> nature are, to say the least of it, -both conflicting and unconvincing. On the one hand, he admits -that they are clinically indistinguishable from Vidal’s type, in -respect of their pronounced <i>atrophic</i> changes; on the other, he -postulates them as <i>gouty</i> even though the <i>uratic deposits</i> “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 must -be conceded that <i>chronic articular gout</i> and <i>rheumatoid</i> or <i>atrophic -arthritis</i> are totally distinct affections.</p> - -<p>Now as to the <i>hypertrophic</i> variety, or osteoarthritis, which, of -the twain, more closely resembles gout, and whose confusion -therewith is far from infrequent even at the present time. Sir -Dyce Duckworth, while he recognises with Charcot a <i>tophaceous</i> -form of chronic articular gout, postulates the existence of another -type, <i>arthritis deformans uratica</i>. Unlike Charcot, however, he -seems only to have included under this term instances of the osteoarthritic -or <i>hypertrophic</i> variety. But like Charcot, his claim that -this particular variety is of <i>gouty</i> nature seems to rest on equally -frail foundations, as witness his statement that they “may be -complicated with visible or invisible tophaceous deposits!”</p> - -<p>That osteoarthritis and gout may coexist in the same individual -is certain, and equally sure is it that uratic deposits may supervene -in joints the seat of osteoarthritis. But it is now, I think, -generally conceded that, despite these coincidences, <i>gouty arthritis</i> -and <i>osteoarthritis</i> are wholly distinct disorders, of wholly different -origin.</p> - -<p>At this period of our historical <i>résumé</i> we see that by the withdrawal -of these three great groups—<i>rheumatism</i>, the <i>nerve arthropathies</i> -and <i>arthritis deformans</i>—the domain of gout has, through -these several allotments, undergone substantial shrinkage.</p> - -<h3><span class="smcap">Elimination of the Infective Arthritides</span></h3> - -<p>Yet again was the territory of gout destined to undergo further -restriction, and this largely owing to the rise of the science of -<i>bacteriology</i>. For in light of recent improvements in <i>diagnostic</i> -methods, who can escape the conviction that under the term -“gout” had been wrongfully included many forms of arthritis, -now known to be due to <i>specific infections</i>. What, for example, -of Hippocrates’ aphorism that gout was unknown in youths—<i>ante -usum veneris</i>—who can doubt that some of his reputed cases of -gout were examples of <i>gonococcal</i> or <i>syphilitic</i> arthritis?</p> - -<p>What, too, of all the other infective arthritides—<i>influenzal</i>, -<i>pneumoccocal</i>, <i>scarlatinal</i>, <i>typhoidal</i>, <i>meningococcal</i>—to mention -only those actually affiliated to some specific organism. For gout,<span class="pagenum"><a id="Page_20"></a>[20]</span> -be it noted, confers no exemption from other arthritic diseases, -but how in time past were such to be differentiated therefrom?</p> - -<p>Again, gouty subjects, as has been recently emphasised, are -notoriously prone to <i>pyorrhœa alveolaris</i>, and how difficult, given -the supervention of an <i>arthritis</i> in such to define the causal agent—<i>gout</i> -or <i>sepsis</i>, which? Small wonder then, that the clinical -content of gout, not only to ancient, but also to latter day physicians, -loomed large, swollen as it undoubtedly was by the inclusion -of infective arthritides, not to mention those of <i>traumatic</i> or <i>static</i> -origin.</p> - -<p>That more of these alien joint disorders—<i>les pseudo-rheumatismes -infectieux</i>, as M. Bouchard terms them, were relegated to the -“rheumatic” than to the “gouty” category, may perhaps be -allowed, but still gout was undoubtedly allotted its full share and -to boot. Moreover, if to “rheumatism” was wrongly affiliated -the lion’s share of the <i>infective arthritides</i>, on the other hand to -“gout” accrued a host of unrelated <i>visceral</i> disorders, not to -mention affections of the <i>nervous</i> and <i>vascular</i> structures, etc.</p> - -<p>In endeavouring to summarise the results of our brief retrospect, -the somewhat chastening fact emerges, viz., that the -isolation of articular gout has been achieved not so much by an -increase in our knowledge as to what <i>is</i> gout, but through our -growing perception of what is <i>not</i> gout. For of the <i>causa causans</i> -of gout we are still as ignorant as in the days of Sydenham. But, -in contrast, our enlightenment as to the clinical and pathological -features of other forms of arthritis has steadily progressed. In -this way, shorn of many alien joint disorders, gouty arthritis has -slowly but surely asserted itself as a specific joint affection, distinct -both from rheumatism and arthritis deformans.</p> - -<p>In the course of our sketch, too, we have traced the evolution -of the modern opinion that at least two separate conditions, -“rheumatoid arthritis” and “osteoarthritis,” are comprised -under arthritis deformans. This most tardily arrived at differentiation -has done more than any other to clarify our conceptions -as to what constitutes true “gouty arthritis.”</p> - -<p>If to this be added the further differentiation, not only of the -<i>nerve arthropathies</i>, but also of the <i>infective arthridites</i>—both -specific and undifferentiated forms—it will be seen that the term -“gouty arthritis,” once the most comprehensive perhaps in all -medical nomenclature, has now been brought within, at any rate, -reasonable distance of more or less exact definition.</p> - -<hr class="chap x-ebookmaker-drop"> - -<div class="chapter"> - -<p><span class="pagenum"><a id="Page_21"></a>[21]</span></p> - -<h2 class="nobreak" id="CHAPTER_III">CHAPTER III<br> -<span class="smaller">EARLIER THEORIES OF PATHOGENESIS</span></h2> - -</div> - -<p>The fanciful views of the humoralists as to the etiology of gout -exercised almost undisputed sway up to the latter half of the -eighteenth century. At that time the great Scottish physician, -Cullen, took up arms against a doctrine which appeared to him -unjustifiable in conception and baneful in practice. He inclined -to the solidists rather than to the humoralists, claiming that gout -was the outcome of a peculiar bodily conformation, and more -especially of an affection of the nervous system. While he -categorically denied that any <i>materia peccans</i> was the cause of -gout, he yet admitted that in prolonged cases a peculiar matter -appeared in gouty patients. But, in view of latter day revelations, -Cullen, with singular prescience, maintained that the said matter -was the <i>effect</i> and not the cause of gout.</p> - -<p>Albeit, notwithstanding the almost universal deference accorded -to Cullen, his theory, promulgated in 1874, though previously -adumbrated by Stahl and afterwards reinforced by Henle, secured -but few adherents. The source of this was not far to seek. For -ever since the discovery of uric acid by Scheele in 1776, and its -detection in tophi by Wollaston, an increasing body of opinion -inclined to the view, that in some obscure way the life history of -gout was bound up with that of <i>uric acid</i>.</p> - -<p>Still, despite able advocacy in this country by Sir Henry Holland, -Wollaston, and others, not to mention Continental authorities, -such as Cruveilhier, it was felt that scientific proof of the truth of -their contention was still lacking. But not for long were they -left in doubt. For, in 1848, Sir Alfred Garrod’s momentous and -epoch-making discovery of the presence of <i>uric acid</i> in the <i>blood</i> -of the victims of <i>gout</i> allayed all doubts, and seemed then and for -long after an all-sufficient explanation of the protean manifestations -of the disease.</p> - -<p>This distinguished physician enunciated his views in a series of -propositions which embodied the result of his researches and -incidentally laid the foundations of the <i>uric acid</i> theory.</p> - -<p><span class="pagenum"><a id="Page_22"></a>[22]</span></p> - -<h3><span class="smcap">Garrod’s Theory</span></h3> - -<p>This great physician held that, in true gout, uric acid in the -form of urate of soda was, both prior to and during an attack, -invariably present in the <i>blood in abnormal quantities</i>, and was -moreover essential to its production; but with this reservation, -that occasionally for a short time uric acid might be present in -the circulating fluid without exciting inflammatory symptoms. -This comparably with what obtains in <i>lead poisoning</i>, and on this -account therefore he did not claim that the mere presence of uric -acid therein would explain the occurrence of the gouty paroxysm.</p> - -<p>He further averred that gouty inflammation is <i>always</i> accompanied -by a <i>deposition</i> of <i>urate of soda</i>, crystalline and interstitial, -in the inflamed part. Also that “the deposited urate of soda -may be looked upon as the <i>cause</i> and not the effect of the gouty -inflammation. Moreover, that the said inflammation tends to -destruction of the urate of soda not only in the blood of the inflamed -part, but also in the system generally.”</p> - -<p>In addition, Garrod postulated implication of the <i>kidneys</i>, -probably in the early, and certainly in the chronic stages of gout; -and that the renal affection, though possibly only <i>functional</i> at -first, subsequently became <i>organic</i>, with alterations in the urinary -secretions.</p> - -<p>As to the anomalous symptoms met with in gouty subjects, -and alike those premonitory of a paroxysm, he ascribed them to -the impure state of the blood, and due principally to the presence -therein of urate of soda. Of causes predisposing to gout, if we -except those attaching to individual peculiarities, they are either -such as will lead to increased formation of uric acid or to retention -of the same in the blood.</p> - -<p>On the other hand, the determining causes of a gouty fit are -those which induce a <i>less alkaline condition of the blood</i>, or which -greatly augment for the time the formation of uric acid or such as -temporarily check the eliminating powers of the kidneys. Lastly, -his final axiom was that—in <i>no disease but true gout is there a -deposition of uric acid</i>.</p> - -<p>No tribute to Garrod’s masterly achievement could err on the -side of generosity. A truly scientific physician, he built on the -rock of sound clinical and pathological observations. For -measured restraint, he stands out in pleasing contrast to those -who, lacking his clinical acumen and sound judgment, brought -not grist to the mill, but vain imaginings based on Garrod’s hard-won -facts. His researches in truth constitute a landmark in the -history of the pathology of gout, with their substitution of facts -for pure hypotheses. True, though it was that, for half a century<span class="pagenum"><a id="Page_23"></a>[23]</span> -before, there was a growing suspicion that lithic (<i>uric</i>) acid was -the malign factor in the induction of gout, still it was not till -Garrod’s discovery of <i>uric acid</i> in the <i>blood</i> and <i>tissues</i> of the -“gouty,” that any definite step towards the elucidation of the -problem presented by gout was attained.</p> - -<h3><span class="smcap">Antagonistic Views</span></h3> - -<p>One aspect of Garrod’s theory that much exercised the minds -of his contemporaries was that for him <i>uric acid</i> was the alpha and -omega of the disease, and as Ewart remarks, “If we are not over-anxious -as to the stability of this mid-air foundation, everything -is evolved smoothly from it on the lines of the theory.” Fortunately, -however, for the progress of the art of medicine, men <i>were</i> -over-anxious as to the why and wherefore of that accumulation of -uric acid in the blood which Garrod held to be a necessary antecedent -of gout. He himself, as we know, attributed it to a <i>functional -renal defect</i> which may be inherited or acquired. To others, however, -this assumption of renal inadequacy was not wholly satisfying, -hence the origin of the many widely differing hypotheses from -time to time advanced as to the pathogeny of the disorder.</p> - -<p>Broadly speaking, the various conceptions proffered as to the -causation of gout fall into one or other of the following categories. -The primary alteration in gout is variously assumed to be:—</p> - -<p>(1) In the blood or tissues, the so-called histogenous theories.</p> - -<p>(2) In the bodily structures, either inborn or induced.</p> - -<p>(3) In hepatic inadequacy.</p> - -<p>(4) In hyperpyræmia.</p> - -<p>(5) In the nervous system.</p> - -<h3><span class="smcap">Histogenous Theories</span></h3> - -<p>In his classic work, “On Urine” (1860), Parkes expressed his -scepticism as to the valency of Garrod’s assumption of a <i>primary -renal inadequacy</i>. In shrewd forecast of latter day views he was -of opinion that both uric and phosphoric acids existed in some -untoward combination in the <i>blood</i> or <i>organs</i>, and that this same -impeded its excretion. As he says, “If this be the case, the deficient -elimination is, as it were, only a consequence of more important -antecedent aberrations in metamorphosis of which impeded -excretion is a natural sequence. What these are, however, is -quite unknown; but an unnatural formation of uric acid, either -from food or tissues, may possibly be part of them.”</p> - -<p>In 1866 Barclay lodged another objection to Garrod’s hypothesis, -viz., that the baneful influence of uric acid was <i>exercised -passively and physically</i>. Not only did he regard it as “far too -mechanical,” but he also strongly dissented from his axiom that<span class="pagenum"><a id="Page_24"></a>[24]</span> -gouty inflammation was invariably attended by <i>uratic deposits</i>. -Thus he asks, “Must we of necessity find urate of soda in the -stomach and the bronchi before we can admit gouty gastritis, or -gouty bronchitis?” Seemingly he believed in the existence of -these two clinical entities, and inasmuch as urate of soda had not -been detected <i>in situ</i> in these disorders, he felt justified in denying -that “true gouty inflammation is always associated with, or caused -by, the deposit.” Moreover, this conclusion, he considered, -derived colour from the fact that, “though the deposit and the -inflammation were associated together in the joints, the urate of -soda was seen in other parts without any evidence of its exciting -inflammation there.”</p> - -<p>His own view was that the <i>primary change lay in the blood -corpuscles</i>, this being induced by the serial ingress of “gout producing -elements” into the blood stream. As to the retention of -uric acid, he deemed it not the cause, but merely a <i>symptom</i>, a -consequence of gout. Thus he says, “The good living and the -stimulants do not simply cause an excess of uric acid to form, but -they end by causing some more permanent change, and probably -one affecting the blood globules, which reacts on the kidney, -putting a stop to the excretion of uric acid, and causing its retention -in the serum, where, passing in the round of the circulation, -it is very apt to become deposited as urate of soda.” Moreover, -his observations of the effect of colchicum in checking a gouty -paroxysm, seem to indicate, “that there is a disease to which the -name ‘gout’ is applied, distinct from the excess of uric acid in -the blood serum which attends its progress.”</p> - -<p>The imaginative insight of Barclay is very remarkable. If we -substitute the <i>white</i> for the red corpuscles we see how closely his -views accord with those prevalent at the present time, when so -important a <i>rôle</i> in the genesis of gout is attributed to the <i>leucocytes</i>. -Moreover, as Ewart observed, the views of Barclay and -Parkes approximate in principle to those afterwards propounded -by Ord and Ebstein, that the bodily tissues “take an active share -in determining the deposition of uric acid.”</p> - -<p>It is, however, but fair to note that, long prior (1854) to Barclay, -Gairdner held that “the disappearance of urea and uric acid in -the urine and their accumulation in the blood” was but <i>symptomatic</i> -and not causative of gout, coupling with it the suggestion -that there was some antecedent <i>nerve</i> influence at work.</p> - -<p>Laycock, too, it may be noted, considered Garrod’s theory -inadequate, adding that “Gout is characterised not by urates -in the blood but by the genesis of uric acid <i>in the tissues</i>, and its -action thereon, and is especially characterised by <i>peculiar changes -in the innervation of the individual</i>.”</p> - -<p><span class="pagenum"><a id="Page_25"></a>[25]</span></p> - -<h3><span class="smcap">Antecedent Structural Changes</span></h3> - -<p>In 1872 Ord took up the novel standpoint that there was an -inborn tendency in the fibroid tissues of gouty subjects to undergo -a special type of <i>degeneration</i>, which same might be inherited or -acquired. Also that this innate peculiarity was attended by -excessive formation of urate of soda in these tissues, and which -subsequently gaining entry therefrom into the blood, was deposited -promiscuously in the body with a predilection for relatively non-vascular -structures, viz., <i>cartilages</i>.</p> - -<p>As to the <i>local</i> inflammations typical of gout, Ord’s attitude was -somewhat ambiguous. Thus he maintains, “The local inflammations -do not necessarily depend upon the deposit of urate and the -deposit is not a consequence of inflammation; at the same time, -it is probable that excess of urate in the blood produces irritation -of tissues.” Neither did he believe that the local inflammatory -reactions were of necessity in every instance <i>specific</i>, viz., due -invariably to mechanical irritation by <i>uratic deposits</i>, but that -they might be initiated by injuries, exposure to cold, etc. Lastly, -as to the migration of the disorder from place to place, he believed -that for its explanation direct or reflex <i>nervous</i> agencies had to be -invoked, for he held the opinion that the local gouty “degeneration -and inflammation tend to infect the rest of the system -through the blood, and to set up similar actions elsewhere through -reflex nervous influence.”</p> - -<p>We see, therefore, that for Ord gout, as Ewart observes, was -“a mode of decay” or a “disease of degenerations.” “The local -tissue degeneracies supply a basis for the uratic deposits and -the general degenerative changes multiply the sites exposed to -an infiltration from the contaminated blood; whilst reflex -mechanisms step in as additional determining agents.”<a id="FNanchor_4" href="#Footnote_4" class="fnanchor">[4]</a></p> - -<p>Reminiscent of Ord’s view is the hypothesis associated with the -name of Ebstein. As the outcome of experimental study he -arrived at the conclusion that the primary factor in the causation -of gout was a disturbance of tissue nutrition culminating in death -or <i>necrosis</i> of the damaged textures. The initial nutritional -derangement was ascribed by him to the irritant effect of soluble -<i>neutral sodium urate</i>. This necrotising agent, following the -development of “free acid” during the process of necrosis, was -transmuted into the acid urate. Subsequently this same was -deposited in crystalline form in the necrosed area. He held these -areas of necrosis quite as typical of gout as the uratic deposits, and -postulated their combinations to be necessary for the production<span class="pagenum"><a id="Page_26"></a>[26]</span> -of a true gouty focus, claiming that he had detected such foci in -cartilage, tendons, kidneys, and connective tissue.</p> - -<p>Experimentally, Ebstein endeavoured to induce a gouty condition -in fowls by ligaturing both <i>ureters</i>, thus thrusting upon the -circulation the dammed-up uratic secretion. In other instances -he administered to the same animals subcutaneous injections of -neutral <i>chromate</i> of <i>potassium</i>, attributing to this substance the -power of inhibiting the excretion of uric acid <i>viâ</i> the kidneys -through its action on the renal parenchyma. Subsequently, after -death he noted the incidence of <i>uratic deposits</i> in joints, muscles, -tendon sheaths, and liver, the same being more copious in those -animals subjected to chromate injections.</p> - -<p>His conclusions were: (1) That necrosing and necrotic processes -are developed in various organs as a result of some irritant. -(2) That uratic deposits occur in the necrosed area resembling -those met with in gouty subjects. (3) That an inflammatory -reaction with small cell infiltration ensues in the vicinity of such -necrotic areas.</p> - -<p>But, in regard to these experimental investigations, they are -obviously incomparable to the morbid processes that presumably -occur in gout in man. Moreover, as shrewdly pointed out by -Levison, experimental ligation of both ureters would certainly -engender <i>uræmia</i> rather than anything approximating to gout.</p> - -<p>Again, his experiments with urates and uric acid, by which he -claims to have demonstrated their action as chemical irritants -capable of inducing necroses in tissues, have proved fallacious. -This, for the very cogent reasons pointed out by Luff, which run -as follows: “Not only is there no proof that the neutral sodium -urate upon which he depends for the starting of the gouty changes, -ever exists in the human body, but, on the other hand, very strong -evidence to show that it never can exist in the human body.”... -“The neutral sodium urate is an extremely caustic and -unstable compound, and is decomposed in the presence of carbonates, -so that it is impossible for it to exist in the blood. The -first factor upon which Ebstein relied for his theory for the -causation of gout therefore disappears.”</p> - -<p>Again, Ebstein’s fundamental proposition that in gout uric acid -was produced in many tissues not normally concerned in its production, -was ruled out by Horbaczewski’s establishing the fact that -in health uric acid is a by-product of the metabolism of almost -all tissues. Lastly, the strong <i>toxic</i> properties accredited by him -to solutions of the urates was disproved by Pfeiffer’s experiments. -This observer showed that urates, in such degrees of concentration -as may exist in the human body, are incapable, when injected into -the tissues, of inducing <i>necrosis</i>.</p> - -<p><span class="pagenum"><a id="Page_27"></a>[27]</span></p> - -<p>In summarising the doctrines of Ord and Ebstein, it may be -observed that if the latter’s contentions have been disproved, -Ord’s claim that the tissues of gouty subjects exhibit a specific -tendency to <i>degeneration</i> has also as yet not been substantiated. -Albeit, we must not forget that in 1883 Ralfe subscribed to Ord’s -views as to the tendency to <i>textural degenerations</i> in gouty subjects, -either through heredity or acquirement. For this observer, however, -the basal factor in the production of the disease was a -diminished <i>alkalinity of the blood</i>, due to a surcharging of it with -acid and acid salts. Disagreeing with Garrod’s assumption that -<i>deficient renal elimination</i> was the prime cause of the retention -of uric acid, he was of opinion that “the first step in the -process lies in the failure of the <i>tissues</i> to reduce the acid, as it -occurs in health.”... “In the large glands or where the current -of the circulation is free, the uric acid is carried into the blood -and gradually reduced to urea; in tissues outside the current of -the circulation, the insoluble uric acid is not so readily carried -off, and so on the slightest disturbance is deposited, as is the -case in cartilages of the joint, the ear, etc.” As to the determining -cause of the gouty attack, he invokes the agency of the -<i>nervous</i> system to explain its incidence, for he held it probable -that the primitive failure of the tissues to reduce uric acid -eventually led to derangement of some special nerve centre, -which disturbance occasioned the gouty outbreak, with resultant -“accumulation of uric acid in the blood and deposition of urate -of soda in the tissues.”</p> - -<p>In 1895 Berkart propounded a mode of genesis which may be -regarded as a variant of Ord’s theory. The severity of the symptoms -of acute gout were such as he deemed incompatible with -their production as a result of simple mechanical irritation by -crystals of biurate of soda. Uric acid, he held, must be afforded -a humbler <i>rôle</i> than that of a proximate cause. It was, for him, -but an <i>epi-phenomenon</i>, the accompaniment of a <i>panarthritis</i>, the -origin of which was as follows:—</p> - -<p>While not postulating the identity of rheumatoid arthritis in -gout, he yet held that both disorders originated in some obscure -form of <i>atrophy</i> of the bone substance, and that the degenerative -change also overtook the cartilages and fibrous tissues of the -joints. Subsequently, there ensued a <i>necrosis</i> in the tissues in -and around the joint. The degeneration and subsequent necrosis, -he held, were the outcome of a profound “vice of nutrition.” The -pain, inflammatory reaction, œdema, and cuticular desquamation -were the direct result, he thought, of the necrosis. The -excess of uric acid in the blood he referred to <i>leucocytosis</i>, and in -part to disintegration of the tissues.</p> - -<p><span class="pagenum"><a id="Page_28"></a>[28]</span></p> - -<h3><span class="smcap">Hepatic Inadequacy</span></h3> - -<p>That some obscure connection obtained between gout and -hepatic disorder has been for long an axiom in high favour, with -both clinicians and pathologists. This hypothesis found its chief -exponents in Murchison and subsequently Latham, and to discussion -of their individual views we now proceed. The first named -authority held gout to be either merely a result or a variety of -what he termed <i>lithæmia</i>. In other words, gout was the outcome -of a depraved condition of the blood, due to faulty digestion and -functional disturbance of the liver.</p> - -<p>Now the conditions that lead to functional derangement of the -liver are in the main such as favour the development of gout. -Nevertheless, such hepatic disturbances do not inevitably culminate -in outbreaks of gout, at any rate of classical type; but, -unquestionably, such may eventuate in symptoms currently -recognised as distinctive of <i>incomplete</i> gout, <i>e.g.</i>, headache, -palpitation, cramps, dizziness, sleeplessness, etc. Moreover, if -the faulty habits leading to such hepatic derangement be persisted -in, they are but too likely to induce outbreaks of frank gout. -“Articular gout,” said Murchison, “is so to speak a local accident -which, though sometimes determined by an injury, yet may occur -at any time in persons in whom the normal process by which -albuminous matter becomes disintegrated in the liver into urea -is persistently deranged.” Following such hepatic disturbance, -the secretion of bile decreased with resultant abnormal metabolism -of proteins, and in this way was produced an <i>accumulation of uric -acid</i>. This, moreover, according to Murchison, was, especially in -the later stages of gout, reinforced by the concurrence of <i>renal -inadequacy</i>, which he also postulated as a factor in the production -of the disorder.</p> - -<p>The tendency to lithæmia Murchison held to be <i>hereditary</i>, and -in this was supported by Goodhart, who, discussing its occurrence -in young children, was strongly of the opinion that it was due not -to dietetic irregularities but to a “constitutional tendency on the -part of the individual”; a conclusion, as he thought, strongly -supported by the fact that it is more commonly met with in the -children or descendants of the “gouty.”</p> - -<p>But we have to recollect, as Duckworth observes, that lithæmia, -“even when persistent and not due to accidental causes, is not by -itself gout.” Moreover, gout is not the only morbid condition in -which urates are in excess in the blood, for such obtains, <i>e.g.</i>, in -<i>leukæmia</i>, pneumonia, anæmia, Bright’s disease, etc. Also, underlying -Murchison’s theory is the further unwarrantable assumption, -viz., that the “gouty” diathesis is identical with the “uric acid” -diathesis.</p> - -<p><span class="pagenum"><a id="Page_29"></a>[29]</span></p> - -<p>Now, as we hope to show later, whatever be the proximate cause -of gout it is at any rate <i>not uric acid</i>. The fact, too, that higher -degrees of <i>lithæmia</i> are to be met with in conditions, not even -remotely connected with gout, renders it impossible to accept the -view that the excess of urates in the blood is responsible for all the -varied symptoms accredited by Murchison and his followers to -lithæmia. For the same reason, it is difficult to uphold the -hypothesis that “the tendency to lithæmia in early life may be an -early expression of the ‘gouty’ diathesis.”</p> - -<p>In short, excess of uric acid in the blood or lithæmia is not -pathognomonic of gout, much less of “potential” gout. But -further discussion of this assumed relationship of lithæmia to -gout may well be postponed until, in the light of recent blood -analyses, we come to consider more narrowly the contention at -one time widely held, that lithæmia is an <i>irregular</i> manifestation -of gout.</p> - -<p>If we are compelled to adopt a more judicial attitude in regard -to lithæmia, what of the similar assumptions as to the relationship -of <i>lithuria</i> or <i>lithiasis</i> to gout? Now lithuria, like lithæmia, was -and probably still is by some held to be an inherited “gouty” -proclivity. Sufferers in youth from lithiasis were deemed likely -to develop gout in later years. Not only was lithiasis observed -to precede but also to be a concomitant or sequel to gout. Nevertheless, -although uric acid, gravel and calculi, sometimes arise in -those of “gouty” diathesis, these instances are but isolated, so -rare indeed as to entitle them to be regarded as mere coincidences. -Moreover, when we recall the fact that the formation of calculi -takes place in the urinary passages, <i>i.e.</i>, <i>outside</i> the economy, it -renders even more improbable the hypothesis that the two morbid -phenomena are diverse expressions of the “gouty” diathesis.</p> - -<p>As a matter of fact, the large bulk of “gouty” subjects are -immune from gravel. Conversely, only a negligible percentage of -the victims of gravel develop gout. The geographical distribution -of the two disorders is wholly distinct one from the other. -The Indian native is a martyr to stone, but notably exempt from -gout. Coming nearer home, we find stone relatively common in -Scotland, but gout rare. Plowright’s researches, too, revealed no -correspondence between the incidence of gout and the prevalence -of stone in the several counties of England. In some counties in -which the mortality from gout was high that from stone was -low, and Norfolk, the one most prolific of stone in England, enjoys -comparative immunity from gout.</p> - -<p>Reverting now to Latham’s views as to the <i>hepatic</i> origin of gout, -we find them very similar to those formulated by Murchison. He -held that the defective transmutation of glycocine into urea was<span class="pagenum"><a id="Page_30"></a>[30]</span> -responsible for the occurrence of uric acid in the urine. These -chemical irregularities were attributed by him to functional disturbance -or partial suspension of the normal hepatic metabolism. -This, again, was referred back by him to some obscure change in -the central system, viz., that part of the medulla oblongata from -which the vagus takes origin.</p> - -<h3><span class="smcap">Hyperpyræmia</span></h3> - -<p>Excess of carbonaceous materials in the blood was considered -by Hare to be an essential, though by no means the sole factor in -the genesis of gout. This same “hyperpyræmia,” as he terms it, -was also, he believed, responsible for migraine, asthma, epilepsy, -and other paroxysmal neuroses. For the alternation of attacks of -acute articular gout with paroxysms of migraine, asthma, and -epilepsy, seemed to him to indicate a kindred origin. The same -inference, also, he deemed might be drawn from the well-ascertained -fact that the temporary or even permanent cessation of -long standing asthma, migraine, and epilepsy, might exactly -coincide with the onset of acute gout.</p> - -<p>These alternations and substitutions seem to suggest that the -preceding alterations in metabolism are similar in nature, finding -expression indifferently in gout, asthma, epilepsy, etc. Carbon -foods, he considered, are much more likely to accumulate in the -blood than the nitrogenous. Ingestion of the latter is swiftly -reflected in increased elimination of nitrogenous excreta. On -the other hand, following the intake of carbonaceous foodstuffs, no -such rapid and proportionate increase in the excretion of carbonic -acid ensues. In other words, the capacity of the organism to deal -with or katabolise in response to the absorption of excess of carbon -foods, is strictly limited. Muscular exercise and exposure to cold, -factors which but slightly influence protein katabolism, are largely -responsible for adequate carbon katabolism. Accordingly, given -deficient exercise, excess of carbonaceous food and a warm -temperature, an accumulation of the carbon content of the blood -is favoured.</p> - -<p>Hare considered that present day habits of warm clothing, warm -rooms combined with excessive intake of starch and sugar, are -precisely the favourable conditions for producing a state of hyperpyræmia. -Increased fat formation would of course tend to -diminish such a tendency to carbon accumulation, but this capacity -in many subjects is conspicuously lacking, and may already -have attained its limit.</p> - -<p>Hare contended also that excessive intake of starch and sugar -by inducing a state of “glycogenic distension” of the liver, might<span class="pagenum"><a id="Page_31"></a>[31]</span> -through compression of the intra-hepatic portal capillaries, lead to -congestion of the retro-hepatic portal venous system, and sequentially -of the gastric and intestinal mucosa. Through consequent -inhibition of digestion and absorption, a condition of hyperpyræmia -is induced. This, under varying conditions, may eventuate -in acute gout, the coincident pyrexia of which is curative -of the underlying hyperpyræmic state, and of all those hyperpyræmic -manifestations (irregular or suppressed gout) which so -often are the harbingers of an on-coming articular outbreak.</p> - -<h3><span class="smcap">Nervous Theories</span></h3> - -<p>It may be noted <i>en passant</i> that the influence of the nervous -system was frequently invoked directly or indirectly in many of -the theories already discussed. Stahl, it will be recalled, was the -pioneer in this direction, and later Cullen and Henle propounded -the view that “the origin of the affection was probably to be found -in the central nervous system.” Gairdner, too, by implication, as -also Laycock, postulated a neural origin for at any rate some of, -the phenomena of gout.</p> - -<p>But it was reserved for Edward Liveing (1873) explicitly to -advocate the nervous origin of the disease, his reflections on the -paroxysmal nature of the attacks, its tendency to periodicity -leading him to suspect its kinship with other neuroses.</p> - -<p>Those inclining towards the neural conception were later -strengthened in their convictions by Charcot’s momentous identification -of the nervous origin of certain arthropathies. Accordingly, -in 1880, we find Sir Dyce Duckworth advocating the view that -gout was “a primary neurosis,” “a functional disorder of a -definite tract of the nervous system.”</p> - -<p>The gouty neurosis, Duckworth contended, may “be acquired, -intensified, and transmitted; also that it may be modified -variously and commingled with other neuroses; that it may -suffer metamorphic transformations, or be altogether repressed.” -Arguing by analogy, Duckworth saw in the paroxysmal attacks, -the tendency to periodicity and alternation in the manifestations, -evidence of an alliance between gout and the various neuroses.</p> - -<p>He further postulated that “this diathetic neurosis determined -a disorder of nutrition and led to the perverted relations of uric -acid and sodium salts in the economy.” He also held that the -localisation of attacks, and the determination of urate of soda to -the affected part was also due, in all probability to nervous -influence. And the temporary renal incapacity for excretion of -uric acid was also attributed by him to the same nerve inhibition.</p> - -<p>We see, therefore, from the above, that Duckworth was well<span class="pagenum"><a id="Page_32"></a>[32]</span> -justified in describing his view as a combine of the humoral and -neural hypotheses. His pathological differentiation between -primary or inherited gout and secondary or acquired gout is as -follows: In the <i>primary</i> type “the toxæmia is dependent on the -gouty neurosis ... and is therefore a secondary manifestation.”</p> - -<p>In <i>secondary</i> or <i>acquired</i> gout, “the toxæmia is directly induced -by such habits as overload the digestive and excretory organs, and -consequently prevents complete secondary disposal of nutritional -elements of food; that if, together with such toxæmia, distinctly -depressing and exhausting agencies, affecting the nervous system, -come into operation, the special neurotic manifestations of the -gouty diathesis will occur, and be impressed more or less deeply -upon the individual and his offspring.” It is generally conceded -that Duckworth’s theory as to the genesis of gout is pre-eminently -catholic in conception, because, as Ewart rightly remarks, “it -represents the most complete theory published in this country on -the general pathology of gout,” and because “the able advocacy -of its propounder has given it the support of arguments derived -from pathological analogy and from clinical influence which will -demand careful examination and searching criticism before they -can be either disproved or adopted.”</p> - -<p>Albeit, it must be frankly admitted that Duckworth’s perception -of gout as a <i>tropho-neurosis</i> of central nervous origin has never -gained wide acceptance; this no doubt largely because it was -insusceptible of proof. In an endeavour to remove this reproach. -Sir Willoughby Wade promulgated the view that the causal -change in gout was partly in the central nervous system, partly in -the <i>peripheral</i> nerves of the inflamed limb. In other words, he -regarded gouty arthritis as the outcome of a local <i>neuritis</i>, this -latter being set up in the first instance by the faulty blood state, -viz., uricæmia. On the other hand, the central nerve centres might -occasion or aggravate the general gouty tendency through their -influence over “recognised seats of metabolic activity.” Also -the same might, through the medium of the vaso-motor nerves, -determine the incidence of local attacks. It will be seen that -Wade’s theory is but a variant of that propounded by Duckworth, -viz., neuro-humoral.</p> - -<h3><span class="smcap">Growing Scepticism as to Garrod’s Pathogeny of Gout</span></h3> - -<p>It will be recalled that as far back as 1889 Duckworth displayed -disquietude as to the adequacy of the purely chemical or purely -physical view of the pathogeny of gout, as sufficing for an explanation -of all its varied phenomena. Thus he writes: “It is incumbent, -I believe, to invoke not only a chemical and physical basis -for gouty disease, but to include also, in a comprehensive view,<span class="pagenum"><a id="Page_33"></a>[33]</span> -the marked determining influence of the <i>nervous</i> factor in the -problem.”</p> - -<p>Whether we agree or not with Duckworth’s view of gout “as a -diathetic neurosis, due to a central neurotic taint, and originating -from prolonged toxæmia,” it does, I think, mark the dawn of a -reaction from the uric acid theory of its causation. Still, this -latter conception continued to dominate the field until seriously -called in question by the results of Magnus Levy’s researches. -His revelations were, in truth, almost revolutionary, and doubts -now accumulated as to the propriety of the terms “uric acid -diathesis,” “uric acid intoxications,” “lithæmia,” etc., so long -credited as being responsible for not only nearly all the minor -ailments flesh is heir to, but especially those relating to joints and -muscles, all alike attributable to the presence of excess of uric acid -or urates in the blood.</p> - -<p>To hasten the process of disillusionment there came from the -side of the physiologists the announcement, almost unanimous, -that <i>uric acid</i>, though in minimal amounts, is a normal constituent -of the blood, organs, and tissues. Thoroughly purged now of their -obsession as to the pathological potency of <i>uric acid</i>, there awoke a -spirit of inquiring scepticism. On all sides it was felt that the -whole problem must be looked at afresh, untrammelled by previous -conceptions, no matter how high the sanction. How else, -indeed, could the chaff be winnowed from the grain, the illusions -born of inaccurate observations be replaced by the substantial -form of truth?</p> - -<p>Still, it would be ungracious to withhold our due meed of admiration -for the masterly manner in which the views of the earlier -physicians as to the causation of gout were elaborated, the shrewd -and often prophetic inferences, well buttressed by arguments based -on clinical and pathological analogies; these the more wonderful -when we recall the meagreness of the positive material at their -disposal, and that little, alas! how often ambiguous!</p> - -<p>In light of latter day views, too, we may well admire the swiftness -with which the inadequacy of Garrod’s theory to explain all the -protean phenomena of gout was realised. Like Duckworth, they -rightly apprehended gout to be “something beyond the resultant -effects of aberrant relations of uric acid; that it consists in something -more than a perversion of animal chemistry; that it is not to -be explained as a mere outcome of gastric or hepatic distemper; -and that it is not the appanage only of the middle-aged or elderly -high liver, and intemperate drinker, because, as is well known, it -affects also sometimes in early life the high thinker and the -laborious bread-winner.”</p> - -<p>That the <i>uric acid theory</i> should more than any other have found<span class="pagenum"><a id="Page_34"></a>[34]</span> -ready acceptance, is not so much to be wondered at. The one -solitary pathological fact that emerged out of the mist of -hypotheses was that established by Garrod, viz., the <i>excess of uric -acid in the blood</i>. It survived and still survives the corroding test -of time. Surely such must be the <i>fons et origo mali</i>, and how -obtrusive <i>the uratic deposits</i>, so ready to hand, objective affirmations -of the truth of their contention.</p> - -<p>This apparent simplicity how delusive! yet not wholly unprofitable. -For if in these latter days our knowledge of the life-history -of <i>uric acid</i> and <i>purin bodies</i> in the organism has evolved -from “a state of chaos and guesswork to one of system and -scientific accuracy,” the seeds thereof were sown by these hardy -pioneers, their, to us crude, researches in the dark regions of bio-chemistry.</p> - -<p>Here it would appear opportune to outline our plan of procedure -in approaching this abstruse subject—<i>gout</i>. In the coming -chapter we shall attempt to define and classify the various types -of the disorder before passing on to discuss its <i>etiology</i> and <i>morbid -anatomy</i>.</p> - -<p>Now all will agree that the more recent revelations of <i>chemical -physiology</i> and <i>chemical pathology</i> have an intimate bearing on the -problem to be considered. We shall therefore, before proceeding -to the more purely <i>clinical</i> aspects of the disease, deal with the -modern conceptions of <i>protein</i> and <i>purin metabolism</i>, more -especially the latter. Subsequently our scrutiny will be narrowed -to consideration of the <i>chemical</i> structure of <i>uric acid</i>, its solubility, -sources, mode of formation and destruction. In possession -of these facts the relationship of uric acid to gout will be dealt -with, in regard to respectively <i>uric acid excretion</i>, <i>uricæmia</i>, and -<i>uratosis</i>.</p> - -<p>The inadequacy of the uric acid theory of the causation of gout -will then be discussed and the possible intrusion of an <i>infective</i> -element in its genesis advocated. This accomplished, we shall -proceed to the section dealing with the clinical aspects of the disorder, -its <i>regular</i> and so-called <i>irregular</i> manifestations. Thence -we shall proceed to the diagnosis of gout, while the terminal -chapter will be devoted to that all-important subject—the prophylaxis -and treatment of the affection.</p> - -<hr class="chap x-ebookmaker-drop"> - -<div class="chapter"> - -<p><span class="pagenum"><a id="Page_35"></a>[35]</span></p> - -<h2 class="nobreak" id="CHAPTER_IV">CHAPTER IV<br> -<span class="smaller">DEFINITION, CLASSIFICATION, ETIOLOGY, AND MORBID ANATOMY</span></h2> - -</div> - -<h3><span class="smcap">Definition and Classification</span></h3> - -<p>Said Locke long since, “There are some words which will not -be defined,” and surely of these is gout; for reflection upon the -proffered definitions thereof is apt to leave one with the depressing -impression that the disorder is both “incomprehensible and -infinite.”</p> - -<p>But have we not by unjustifiable and unwarrantable assumptions -deliberately complicated the issue, in recklessly relegating -to the <i>gouty</i> category a myriad affections of the intimate nature of -which we are as ignorant as we are of gout? Doubtless, this is in -part the outcome of a too slavish adherence to tradition, an undue -reverence for authority. In all deference, our forefathers were -somewhat too hasty in their speculations as to the causation of -gout. Dominated by the prevalent philosophy of their days, they -strove to interpret the phenomena of gout through its lights, -endeavouring to reduce the study of its pathology to philosophical -order when the very elements of philosophical order were lacking.</p> - -<p>The same is reflected in the earlier, and to a lesser extent in the -latter day definitions or <i>descriptions</i>, as some of them more aptly -may be designated, notably that put forward by Sir Charles -Scudamore.</p> - -<div class="blockquote"> - -<p>“A constitutional disease, producing an external local inflammation of -a specific kind; the susceptibility to it often depending on hereditary -bodily conformation and constitution, but with great frequency wholly -acquired; almost never occurring before the age of puberty, not frequently -under the age of five-and-twenty, and most commonly between the ages -of twenty-five and forty; affecting chiefly the male sex, and particularly -persons of capacious chest and plethoric habit; in the first attack invading -usually one foot only, and most frequently at the first joint of the great -toe; but in its returns, affecting both feet or other situations, as the hands, -knees, and elbows; and not only in the articular structure, but also in the -other textures belonging to the moving powers, different parts being -affected together or in succession; often accompanied with sympathetic -inflammatory fever, which is usually marked by nocturnal exacerbations -and morning remissions; much disposed to return at periodical intervals, -and for the most part preceded by some premonitory symptoms.”</p> - -<p>In extenuation of this prolixity, Scudamore observed that, “In an -attempt to mark the general characters of gout, I feel the necessity of -entering into a description rather in detail, instead of confining myself to<span class="pagenum"><a id="Page_36"></a>[36]</span> -a brief definition, because the disease is too complex in its nature to be -distinguishable with certainty by a few signs alone.”</p> - -<p>Trousseau, in his lectures on gout, refrains, perhaps wisely, from attempting -any definitions of the disorder, resting content with the reflection that, -“The production in excess of uric acid is a pathological phenomenon, -inherent, like all others, in the disease, and, like all the others, it is dominated -by a specific cause, which we know only by its effects, and which we term -the <i>gouty diathesis</i>.”</p> - -<p>Sir William Roberts defines gout “as a constitutional disorder characterised -by paroxysmal attacks of inflammation of the joints, associated -with the formation of chalk-like concretions in and about the joints.”</p> - -<p>Sir William Osler regards gout as “a nutritional disorder, one factor of -which is an excessive formation of uric acid, characterised clinically by -attacks of acute arthritis, by the gradual deposition of urate of soda in and -about the joints, and by the occurrence of irregular constitutional -symptoms.”</p> - -</div> - -<p>For myself, I would proffer the following definition, which, of -course, the reader must accept provisionally, viz., pending the -perusal of subsequent chapters, dealing with the pathology and -clinical features of gout, and the inferences drawn therefrom as to -the nature of the disease.</p> - -<p><i>Definition.</i>—Gout is an hereditary disorder, the <i>intrinsic</i> element -of which is an inborn instability of nuclein metabolism which may -remain latent, but under the influence of <i>extrinsic</i> factors, <i>infections</i>, -becomes manifest, as betokened by local inflammatory -tissue reactions in joints or elsewhere the specific character of -which is attested by the associated <i>uratic deposition</i>.</p> - -<h3><span class="smcap">Classification</span></h3> - -<p>At the present time, under the most liberal interpretation, the -word “gout” comprises the following conditions, viz., acute and -chronic articular gout, and the so-called ab-articular forms. But -it is clear that not only the latter or <i>irregular</i> manifestations, but -even the former or <i>regular</i> varieties of the disorder seem destined -to undergo considerable pruning.</p> - -<p>As to the classical podagra—<i>acute</i> articular gout—no question -can arise as to the propriety of its retention in this category. But -as to the <i>chronic</i> articular types we are on less certain ground, and -to discussion of this vexed question we now proceed.</p> - -<p>Let us take, for example, Sir Dyce Duckworth’s classification -of the <i>arthritic</i> types of gout. He distinguishes the following -forms:—</p> - -<ul> -<li>(1) Acute articular gout.</li> -<li>(2) Chronic articular gout</li> -</ul> - -<p class="noindent">the latter (2) further subdivided into—</p> - -<ul> -<li>(<i>a</i>) the “tophaceous” variety.</li> -<li>(<i>b</i>) the “deforming” variety.</li> -</ul> - -<p><span class="pagenum"><a id="Page_37"></a>[37]</span></p> - -<p>Of these twain the “tophaceous” form need not detain us, and -why? Simply and solely this—the <i>uratic deposits</i> stamp the seal -of specificity on the disorder. In short, the presence of <i>tophi</i> -places the “gouty” origin of the arthritis beyond the pale of -cavil.</p> - -<p>Now, if we accept, as we must, the fact that <i>uratic deposition is -the solitary unequivocal clinical criterion of gout</i>, we are not, I contend, -justified in classing any <i>chronic</i> arthritis as “gouty,” the -victim of which does not exhibit <i>tophi</i> of articular or ab-articular -site, either clinically demonstrable or deducible from skiagraphic -revelations.</p> - -<p>Nevertheless, be it noted <i>tophi</i> do but bespeak the “gouty -diathesis,” not necessarily the “<i>gouty</i>” nature of an associated -arthritis. For clearly tophi, of <i>ab-articular</i> location, may coexist -with an arthritis of <i>gonococcal</i> or other origin. But given uratic -deposits, either in the joint proper or its related structures, all -reasonable doubts as to the true “gouty” nature of the arthritis -are disposed of. On the other hand, in <i>the absence of tophi</i>, the -diagnosis of an arthritis as “gouty” is <i>presumptive</i>, not absolute. -This even in acute classical outbreaks in the <i>big toe</i>, viz., pending -the finding or subsequent eruption of <i>tophi</i>.</p> - -<p>In saying this, I do not for one moment depreciate the diagnostic -value of the clue afforded by location of the initial outbreak -of the disorder, in the vast majority of instances, in the <i>big -toe</i>. It is an invaluable, but not an <i>infallible</i> clue; for, unfortunately, -acute arthritic diseases other than gout may elect to -announce themselves in the great toe.</p> - -<p>Moreover, there is nothing <i>specific</i> in the external characters of -acute “gouty” inflammation, nothing in the objective changes -which would stamp them on sight as “gouty,” save only their -<i>location in the great toe</i>; nothing distinctive about the angry -blush, œdema, and engorged veins, all of which may be met with -in <i>infective</i> arthritis. There may be, as Garrod with good reason -affirms, a local <i>intra-articular</i> deposit of urate of soda, but this lies -beyond our ken, presumptive but undemonstrable.</p> - -<p>Let but the <i>initial</i> outbreak of gout occur elsewhere than at the -<i>big toe</i>, say, <i>e.g.</i>, in the <i>wrist</i>, <i>hand</i>, <i>ankle</i>, or <i>knee</i>, and we are at -once, diagnostically speaking, <i>en l’air</i>. In this <i>impasse</i> how -impotent are we, and how painfully we realise that our diagnosis -of acute gout is largely <i>topographical</i>, not <i>etiological</i>! Not, -strictly speaking, etiologically diagnosable pending the eruption -and detection of <i>tophi</i>. In short, location <i>per se</i> in the big toe is -strongly suggestive but not <i>diagnostic</i> of “gout.” (<i>Vide</i> Chapters -on Diagnosis.)</p> - -<p>If this be done in the green, what then shall be done in the dry?<span class="pagenum"><a id="Page_38"></a>[38]</span> -In other words, if so precarious our diagnostic foothold in <i>acute</i>, -how much more so in <i>chronic</i> articular gout! for in the latter -even <i>topography</i> may wholly fail us, what then our diagnostic -criterion?—<i>tophi</i> and <i>tophi</i> alone—aye, and demonstrable at -that.</p> - -<p>Yet both Charcot and Duckworth would have us recognise not -only a tophaceous but a <i>non-tophaceous</i> variety of chronic articular -gout, for that is what it amounts to. They apparently feel justified -in labelling a chronic arthritis as “gouty” even though <i>tophi</i> -“may not exist” or “be invisible”! <i>Deformity</i>, say they, is its -hall-mark, not <i>tophi</i>, and its character forsooth, they add, is not -only <i>not peculiar to gout</i>, but clinically indistinguishable from the -similar defacements met with in <i>arthritis deformans</i>. Nor is -Duckworth alone in his contention, for both Ewart and Luff also -recognise what they term “chronic deforming gout.”</p> - -<p><i>Tophi</i>, I contend, notwithstanding, are essential for the diagnosis -of gout. In their absence, the designation of an arthritis as -“gouty” is unjustifiable. Either tophi are, or tophi are not the -sole pathognomonic feature of gout. If the latter, then gout -ceases to exist as a clinically recognisable entity.</p> - -<p>Holding tophi indispensable for the diagnosis of gout, I maintain -that Charcot and Duckworth’s plea for the recognition of a -chronic type of articular gout, apart from the <i>tophaceous</i> variety, -is untenable. Fraught, moreover, with risk, as I am satisfied that -their so-called, “deforming” type is largely made up of the -<i>atrophic</i> and <i>hypertrophic</i> forms of arthritis deformans.</p> - -<h3><span class="smcap">Suggested Classification of Articular Gout</span></h3> - -<p>For myself, as to the classification of the articular types of gout, -I would divide them into:</p> - -<ul> -<li>(1) Acute articular gout.</li> -<li>(2) Chronic articular gout.</li> -</ul> - -<p>Under the first group I would place not only the acute <i>localised</i> -type, but also those acute varieties of <i>polyarticular</i> distribution. -As to the second category, I would exclude therefrom, for the -reasons cited, the so-called “<i>deforming</i>” varieties of chronic -articular gout, recognising only the so-called <i>tophaceous</i> form. But -I would place a different interpretation on this term in opposition -to that generally accepted; for, by most writers the word -<i>tophaceous</i> is apparently limited in its application to examples -which, so to speak, exhibit <i>tophi</i> of phenomenal size or number. -Scudamore was the chief offender in this respect. As a consequence, -he found tophi in only 10 per cent. of his cases of gout. -Accordingly, he went so far as to postulate for such victims as did -present this peculiarity an <i>idiosyncratic</i> tendency to chalk-stones!<span class="pagenum"><a id="Page_39"></a>[39]</span> -In other words, he would seem to suggest that there is a gout within -gout, that one displays <i>chalk-stones</i>, the other <i>not</i>. By inference, -Duckworth and his followers, by differentiating <i>tophaceous</i> gout, -tacitly concur, and so “confusion twice confounded” results.</p> - -<p>This usage of the term “tophaceous” is unjustifiable and misleading. -The significance of tophi is <i>qualitative</i> not <i>quantitative</i>. -One tophus bespeaks the “gouty diathesis” as surely as a myriad -concretions. Solitary though it be, the same, given elimination of -all other sources of arthritis, will suffice to establish the “gouty” -nature of an associated joint disorder. It is in this more catholic -sense that I would translate the term “<i>tophaceous</i> gout.” The conclusion, -then, to my mind, is obvious—there is but one form of -articular gout, and one only, viz., an arthritis, the victim of which -exhibits <i>uratic deposits in situ or elsewhere in his body</i>. On this -and on no other grounds can a chronic arthritis, with any show of -certitude, be certified as truly “uratic” or “gouty.”</p> - -<p>This rigid attitude may not commend itself to some, but I feel -convinced that, only by holding on grimly to the tophus, shall we -steer a safe course through all the pitfalls that beset the diagnosis -of the chronic arthritides. Only in this way, too, can we preserve -for ourselves a clear conception of <i>gouty arthritis</i> as a specific -disorder, the which otherwise loses its identity, submerged in a -medley of joint diseases. Prior to the differentiation of gout, -on the one hand, from <i>rheumatism</i> and <i>arthritis deformans</i>, and on -the other from the <i>nerve arthropathies</i> and the <i>infective arthritides</i>, -such laxity might be condonable, but not, we think, in the present -stage of our knowledge.</p> - -<p>In drawing to a close my remarks on the classifications of -articular gout, it will be noted that I have made no reference to -that variety known as <i>retrocedent</i> gout, but to this I shall allude -at a more favourable juncture, viz., in the chapter devoted to the -clinical account of articular gout. Conformably, too, it will, I -think, be more convenient, to defer any criticisms of the term -“irregular gout” to the chapter I purpose devoting to consideration -of the varied clinical content of the same.</p> - -<h3><span class="smcap">Etiology and Morbid Anatomy</span></h3> - -<p>To the antiquity of gout and no less its distinctive clinical <i>facies</i>, -when of classic type, we owe not a little. Its salient phenomena -have endured unchanged from the time of Hippocrates onward -through the ages. So it is that, even allowing for the enhanced -powers of discrimination of latter days, we are in no doubt that -the gout of the ancients is the gout of to-day. How signal the -advantage thus accruing, when we come to consider the conditions<span class="pagenum"><a id="Page_40"></a>[40]</span> -which engender or tend to engender the disease! For, <i>quâ</i> its -broad etiological factors, we find ourselves in accord with the -physicians of old, our experience a confirmation of their old-time -findings.</p> - -<p>Our forefathers, like ourselves, realised the innate complexity -of the problem, that in the development of the disorder both -<i>heredity</i> and <i>environment</i> played a <i>rôle</i>. In other words, that -in the genesis of gout not only <i>intrinsic</i> but <i>extrinsic</i> agencies -were concerned. Of the intrinsic influences the most important -are age, sex, heredity, bodily conformation, and individual -peculiarities.</p> - -<p><i>Age.</i>—Gout is slow in evolution, tardy of appearance, confined -in the main to the middle and declining years of life. Said Sir -Thomas Browne, “Leprosie awakes not sometimes before forty, -the gout and stone often later.” Experience but confirms the -dictum, for, as Cullen long since observed, it rarely declares itself -under the age of five-and-thirty. This relative immunity of youth -is not the least striking feature of the disorder; whence the -Hippocratic aphorism, “Puer non laborat podagra, ante veneris -usum.” Both Sydenham and Heberden were also doubtful of its -occurrence before the age of puberty. Gairdner, however, records -the incidence of fits of gout even in <i>infants</i> at the breast! and in -one death therefrom. Garrod, too, met with two cases of classical -type in <i>girls</i>, both of them under <i>ten</i> years of age. But Scudamore -states that he never witnessed more than one example of -a first attack before twenty, or any after sixty-six.</p> - -<p>For myself, I have never seen a case under thirty-five years of -age, and am sceptical as to the occurrence of <i>infantile</i> gout of -<i>regular</i> type, believing with Scudamore that “the commonly -asserted cases which represent the existence of the gout in very -early youth are really examples of <i>rheumatism</i>.” Nor am I less -but more inclined to cavil at the claims of Comby and others, as -to the frequency in <i>children</i> of <i>irregular</i> manifestations. As -Osler dryly observes, “The tendency in some families is to call -every affection gouty. Even infantile complaints such as scald-head, -naso-pharyngeal vegetations, and enuresis, are often regarded, -without sufficient grounds, I believe, as evidences of the -family ailment.”</p> - -<p>To sum up, the majority of cases of gout ensue between thirty-five -and fifty years of age. But, given a strong <i>hereditary</i> taint, it -may break out in <i>youths</i> and <i>young adults</i>, or haply even in <i>children</i>. -But such, in my experience, are phenomenally rare. Indeed, it -may be said of gout that only exceptionally is it met with at either -extreme of life; though Garrod records several examples in which -the initial attack was postponed until nigh eighty years of age;<span class="pagenum"><a id="Page_41"></a>[41]</span> -while in one instance, a lady experienced her first classical attack -of podagra in her ninety-first year.</p> - -<p><i>Sex.</i>—In the matter of liability to gout the sexes stand in marked -contrast, the disorder being infinitely more common in males. -Out of eighty cases submitted to the French Academy, seventy-eight -were men and only two women; but according to other -authorities, this is an under-estimate. Thus in James Lindsay’s -series of cases of gout, 84·7 per cent. were males, 15·3 per cent. -females, percentages which he notes “are in accordance with the -observations of other writers.” J. Lambert, out of 125 examples -of gout, noted that 102 were men, <i>i.e.</i>, 81·6 per cent., twenty-three -women, <i>i.e.</i>, 18·4 per cent.</p> - -<p>From my own experience, the figures submitted to the French -Academy probably represent the ratio of incidence in males as -opposed to females. This certainly, if <i>regular</i>, in opposition to -“irregular,” types of gout be the criterion; for it must be -admitted that regular gout does occur in women, though exceptionally -rare either prior or subsequent to the climacteric.</p> - -<p>As to the current opinion that the <i>regular</i> manifestations of -gout in women are of <i>asthenic</i> as opposed to sthenic character, -this has, I think, often proved a source of fallacy. At any rate, -in many of these cases the assumed <i>gouty</i> inflammation resolves -itself into one of inflamed <i>bunion</i>. Again, in but too many -instances, women, showing <i>Heberden’s nodes</i>, are held to have -gout or “rheumatic gout.” The latter term, as Pye-Smith -observed, “is a bad name for <i>osteoarthritis</i>,” to which category -Heberden’s nodes belong.</p> - -<p>Judged by the one unequivocal diagnostic criterion, <i>i.e.</i>, <i>tophi</i>, -gout in women is extremely rare. If to this be added the further -fact, viz., the rarity in their sex of classical attacks in the <i>great -toe</i>, we see clearly that the diagnosis of gout in women is often a -matter of <i>assumption</i> rather than of certitude.</p> - -<p>Moreover, having regard to the fact that the diagnosis of gout -in women is frequently based on so-called “masked and irregular -manifestations,” I must admit that, to my mind, statistics, purporting -to indicate the percentage incidence of gout in women and -men, are not very convincing.</p> - -<p>As to the why and wherefore of the relative immunity of <i>women</i> -it may be due to the fact that their habits and mode of life are less -calculated to evoke the disorder. There is also the further possibility -that the <i>catamenial</i> discharges to a certain extent are protective -against gout, for most authorities support Hippocrates’ -aphorism, “Mulier podagra non laborat nisi ipsi menstrua -defecerint.”</p> - -<p><i>Heredity.</i>—By the ancient physicians gout was held to be<span class="pagenum"><a id="Page_42"></a>[42]</span> -hereditary, and even to-day most will agree that “From father to -son its seeds are transmitted, and bear fruit in exact proportion -to the degree in which circumstances prove favourable to their -growth.” Cullen, indeed, went further and held it <i>purely hereditary</i>; -but, on the other hand, the belief, that it is often <i>acquired</i> -is widely countenanced.</p> - -<p>That gout is an <i>hereditary</i> disease is, I think, beyond question, -and certainly, of all <i>arthritic</i> disorders, gout furnishes by far the -greater number of instances in which <i>parents</i> and <i>children</i> are -victimised by the same articular affection. Scudamore in 522 -cases found that 332 could trace their disease to the father, -mother, grandfather, grandmother, or aunt. But in the remaining -190 no evidence of the existence of gout in their forbears could -be elicited. Out of eighty examples submitted to the French -Academy an hereditary predisposition was established in thirty-four, -and in the residue it appeared to have been <i>acquired</i>. Garrod -found that 50 per cent. of his hospital examples of gout were -hereditary, and of his private patients nearly 75 per cent. came -of gouty stock. Again, Sir William Roberts found that “fully -three-fourths of the cases of gout occurring among the easy classes, -can be traced back distinctly to a gouty ancestry.” Luff’s -estimate is even higher, inasmuch as analysis of a series of 300 -examples disclosed a “definite family history of gout in 81·3 per -cent.”</p> - -<p>Nevertheless, Garrod’s experience, he tells us, convinced him -that “in this country gout is frequently <i>acquired</i> even at a moderately -early age, for in many most inveterate cases not the least -hereditary influence could be discovered.” For myself, I find it -difficult to appreciate the attitude of those who, like this observer, -postulate <i>innate</i> or <i>static</i> morbid proclivities on the part of the -“gouty,” and in the same breath, as it were, are equally insistent -that it may be “acquired” <i>de novo</i>. Now, in the taking of family -histories <i>positive</i> evidence is more valuable than negative. Surely, -therefore, in the light of Garrod’s and Luff’s findings, it is obvious -that <i>heredity</i> plays not merely an important, but an <i>essential</i> and -<i>indispensable rôle</i> in the genesis of gout. To my mind, accordingly, -the balance of evidence is more in favour of the same -ancestral taint, though apparently undiscoverable, being present -in the remaining 20 or 25 per cent., than that the disease in their -instance was wholly and newly <i>acquired</i>.</p> - -<p>Personally, I therefore question whether the alleged acquisition -<i>de novo</i> of gout is not <i>apparent</i> rather than real. My own opinion -is that the <i>innate predisposition</i> thereto is <i>always inherited</i>, and the -predisposing factors, that we presume may originate gout, are in -reality merely <i>excitants</i> or <i>determining</i> agents. In other words,<span class="pagenum"><a id="Page_43"></a>[43]</span> -the remote, the primary or essential cause of gout, is an <i>inborn</i> -morbid tissue potentiality, and in the absence of this intrinsic -warp the various contributory or exciting causes are impotent to -evoke the disorder.</p> - -<p>Apart from <i>statistical</i> proof of heredity, how else, save on the -basis of an <i>organic predisposition</i> to the disease, can we explain -the fact that of a large number of individuals, of slothful habit, -and given to alcoholic and dietetic excesses, not one may get -<i>gout</i>; while others who lead literally “a godly, sober, and righteous -life,” become martyrs thereto. How escape then the conviction -that in gout “breed is stronger than pasture”? for, apart -from gluttony and indolence, gout is much more prone to -arise in persons in whose pedigree it can be traced than in -others.</p> - -<p>It is not gout, but the <i>predisposition</i> thereto, that is inherited. -This proclivity, moreover, may descend to the children of those -who, in their own persons, have never suffered from the disease. -In Luff’s series it was so in 27 per cent. of the cases, <i>i.e.</i>, the disease -was transmitted from grandparents to grandchildren without the -fathers or mothers suffering from “active gout.” In other words, -the morbid potentiality may lie <i>latent</i> until <i>evoked</i>. Thus, the -<i>females</i> of “gouty” families, infinitely more often than not, -escape overt gout, but hand on nevertheless their inborn liability -thereto to their offspring. Looked at in this light, I see no difficulty -in accepting the fact that gout may skip a generation. The -son of a gouty parent, happily warned by the excesses of his father, -may remain immune, while in turn his son, forgetful of his evil -heritage, may bring it again to fruition.</p> - -<p>The more one reflects on the essential cause of gout, the more -inevitable seems the conclusion that gouty individuals, as Walker-Hall -contends, “possess some inborn defect or alteration of nuclein -metabolism.” And the vague phrases “constitutional” or -“nutritional,” as applied by older writers to the disorder, are only -explicable on the basis of <i>inherited structural peculiarities</i>, with -their correlated perversions of tissue function.</p> - -<p>That such constitute the pathological groundwork of gout, is, I -think, further indicated by the fact that <i>“gouty” inflammation</i>, -in virtue of its associated <i>uratic deposition</i>, is <i>sui generis</i>. No -tissues, other than the <i>gouty</i>, react in this <i>specific</i> fashion. Does -not this seem to indicate that the <i>inborn tissue peculiarities</i> dictate, -so to speak, the <i>character</i> of the pathological reaction; this -indifferently, whatever the nature of the so-called <i>predisposing</i> -causes which, if our assumption be correct, are merely <i>provocative</i> -of gout, in other words, do but evoke or make <i>manifest</i> what is -already latent.</p> - -<p><span class="pagenum"><a id="Page_44"></a>[44]</span></p> - -<p>To sum up, on statistical, and more cogently, general clinical -and pathological grounds, my own conclusions are that—</p> - -<div class="blockquote"> - -<p>(1) Gout is always an hereditary disease.</p> - -<p>(2) The factors currently regarded as predisposing agencies -are in reality merely <i>determining</i> agents, not the cause of -gout, but the <i>occasion of its appearance</i>.</p> - -<p>(3) In the absence of an hereditary taint, these same are -powerless to evoke the <i>specific</i> manifestations of true -<i>“gouty” inflammation</i> as estimated by associated <i>uratic -deposition</i>.</p> - -</div> - -<p><i>Bodily Conformation and Individual Temperament.</i>—Of the -hereditary character of gout no doubt remains, but as to the -influence of physical build and temperament no such certainty -prevails. Said Cullen, “Gout attacks especially men of robust -and large bodies, men of large heads, of full and corpulent habit, -and men whose skins are covered with a thicker <i>rete mucosum</i>, -which gives a coarser surface.” Doubtless, in its more sthenic -form, gout affects persons like Falstaff, of sanguine temperament -and corpulent habit. But its milder or more asthenic manifestations -occur often in men like Cassius, of lean and nervous -type.<a id="FNanchor_5" href="#Footnote_5" class="fnanchor">[5]</a></p> - -<p>Of objective stigmata, I know of none, save <i>tophi</i>, that can be<span class="pagenum"><a id="Page_45"></a>[45]</span> -truly regarded as pathognomonic of the outward semblance of the -“gouty.” The skin of the face may be coarse, unctuous, and -studded with ramifying venules. Such appearances, though not -always, betray the tippler. Indeed, such stigmata as these are -only of value as indicating the habits of the individual, favourable -or not, to the development of gout.</p> - -<p>Again, it has become a tradition with us that gout produces -characteristic <i>teeth</i>. The mere fact that they are “ground down” -so as to display the dentine in section is held as evidence of a -“gouty” diathesis, or of lithæmia. The teeth of the gouty, it is -true, often appear long and square-topped; but the gouty, no -more than others, are immune from early <i>recession of the gums</i>. -Again, we must recollect that there are several causes which may -lead to the teeth being worn down more quickly than normally. -Thus the <i>formation of the jaw</i> may be such that the upper and -lower incisors meet edge to edge instead of overlapping. This -so-called “edge to edge bite” subjects the incisors to marked -attrition. Also we must recall that these effects may be aggravated -by the nature of the diet. All of us are familiar with the -fact that in old horses the teeth are ground down to the gums. -The same also is observed in races condemned to live on coarsely -prepared flour and hard vegetable food.</p> - -<p>In conclusion, having regard to the marked frequency with -which disorders leading to early recession of the gums are met with -in the “gouty,” and the ease with which the early attrition of the -teeth is explicable on tangible mechanical reasons, I am inclined -to refer such changes to their combined agency, rather than to the -nebulous “gouty” diathesis.</p> - -<p>Again, despite Duckworth’s assertion that “the gouty throat -is like no other,” I am convinced that it presents no specific -appearances. Nor have I been able to satisfy myself that striated -and fluted nails of, it is usually affirmed, exceptionally brittle -nature, are distinctive of gout any more than the premature -whitening of the hair so frequently accredited to the subjects of -this diathesis.</p> - -<p>One point, however, I would emphasise is, the frequency with -which potentially gouty persons suffer from local <i>syncopes</i> and -<i>asphyxias</i> of the hands. They are precisely similar to those met -with in <i>rheumatoid</i> or <i>atrophic arthritis</i>, certain cases of which, as -we shall see later, have another affinity with gout, viz., <i>retardation -in the output of exogenous purin</i>.</p> - -<p><i>Locality, Race, Climate, etc.</i>—As to the geographical distribution -of gout, the salient fact would appear to be the almost complete -restriction of the disorder to the <i>temperate</i> zone. Among the -natives of Africa gout, according to Livingstone, is unknown.<span class="pagenum"><a id="Page_46"></a>[46]</span> -Neither apparently is it to be met with in Turkey, China, Japan, -Peru, and the Brazils. The indigenous peoples of India, and the -East Indian Archipelago, also seem exempt, though the immunity -does not extend to Europeans resident in these tropical climes.</p> - -<p>It is significant that Duckworth, inquiring of practitioners -from foreign parts as to their experience of gout, found that little -or none was forthcoming “save where Europeans have formed part -of the community.” This statement, to my mind, does but add -cogency to my contention that gout is always <i>hereditary</i>.</p> - -<p>If we restrict our purview to the British Isles and the Continent, -we find that as a nation we have achieved the unenviable distinction -of being <i>facile princeps</i> in point of the liability to and incidence -of gout. The bulk of examples, too, are met with in England, the -disorder being much less frequent in Scotland and Ireland. Moreover, -in the two latter countries, the disorder is practically restricted -to the upper classes. By contrast, in England it has -extended to the lower orders also, in respect of which peculiarity -we stand unique as compared with all other countries.</p> - -<p>Reverting to the Continent, gout appears to be more common in -France than in Germany, Austria, and Italy. Indeed, it is said to -be endemic in Normandy, Burgundy, and the Rhone Valleys. In -Holland, according to Duckworth, there is practically no gout, and -the same is true of Russia, save in Petrograd and the Baltic -Provinces.</p> - -<p>In Belgium, also, gout is not common, and in Greece it is much -less prevalent than in France or England.</p> - -<p>In regard to the incidence of gout, its greater prevalence in -<i>temperate</i> as opposed to tropical climes, and the disparities between -different countries, it would be unsafe to assume that the variations -are the outcome solely of <i>climate</i>. Thus the immunity of, <i>e.g.</i>, -strict Mohammedans is attributable in part to their sobriety and -the less highly nitrogenous character of their food. But, if -seduced into the ways of the “infidel,” their exemption, it is said, -ceases. Europeans, of “gouty” heritage, may, if temperate, -escape gout when resident in the tropics, otherwise they fall -victims thereto just as surely as at home.</p> - -<p>Gout, indeed, is more a matter of <i>morals</i> than climate. In the -palmy days of the Roman Empire, when luxury and indolence -were rampant, gout flourished, but declined following the installation -of a republican form of government. In like fashion and for -similar reasons, the inhabitants of modern Greece suffer infinitely -less from the ravages of gout than of yore. In short, the climate -of Italy and Greece has presumably endured unchanged, but the -“habits” of their peoples have altered.</p> - -<p>Formerly it was held that the incidence of gout in any country<span class="pagenum"><a id="Page_47"></a>[47]</span> -or district varied according as to whether the population drank -wine and malt liquors, or distilled spirits. Where the taste for -the latter predominated, the disease was relatively rare, whence -the comparative immunity of Scotland, Russia, Poland, and Denmark. -But what of the rarity of gout in the wine-producing -country Spain? Nor for that matter have I ever seen it claimed -that gout was especially prevalent in Portugal, the home of -“port,” that <i>bête noir</i> of the “gouty.” In truth, dogmatism is -here out of place, for though overeating and overdrinking are -undeniably important factors in eliciting gout, they are not the -<i>sole</i> factors.</p> - -<p>In reviewing the statements made as to the geographical distribution -and the race incidence of gout it is but too manifest that -they are largely provisional; indeed, such information as we do -possess as to its relative frequency in various countries, must be -taken <i>cum grano salis</i>. Thus, who can doubt that the various -affirmations must have been very largely influenced by the -“personal equation,” that what one authority would define as -gout would by another be deemed inadmissible to this category. -Moreover, many of the original statements were made at a time -when the differentiation of arthritic disorders, as we now know it, -was but in its infancy. For obvious reasons, therefore, no -researches in this sphere can ever be satisfactory, until the opinion -of the profession at home and abroad be crystallised into some -definite pronouncement, some precise definition, of the exact -criteria by which the diagnosis of gout stands or falls.</p> - -<p>In justification of these strictures, may I cite some opinions as -to the frequency of gout in the United States. In 1890, Sir Dyce -Duckworth affirmed that in America gout was “practically -unknown.” But a few years later, we find Sir William Osier convinced -that gout was often <i>unrecognised</i> in the United States. -More pertinent still, only twenty years after Duckworth’s affirmation, -Luff quoted the statistics of the Johns Hopkins Hospital, -Baltimore, from which it appeared that during a period of fourteen -years 0·26 per cent. of the total admissions thereto were examples -of gout. This he contrasts with the number of cases of gout -admitted to St. Bartholomew’s Hospital, London, during a similar -period. <i>Mirabile dictu</i>, the percentage was only 0·37, but a third -more than that of the Johns Hopkins Hospital!</p> - -<p>Yet again, J. H. Pratt, of Boston, writing in 1916, observes -“the greatest confusion exists in the minds of many practitioners -in America to-day regarding this disease (gout) and its diagnosis. -In some parts of the country the diagnosis is frequently made in -conditions that are not gout; in other sections there seems to be a -skepticism in the minds of many practitioners regarding the<span class="pagenum"><a id="Page_48"></a>[48]</span> -existence of such a disease. In New England I have found that -chronic gout, even when tophi occur, is often mistaken for rheumatism -or arthritis deformans. Some physicians of large experience -assert that they see gout frequently. Enquiry has shown that they -mistake typical cases of arthritis deformans for gout, and the -swellings about the joints and even Heberden’s nodes for ‘gouty’ -deposits.”</p> - -<p>Can it for one moment be denied that even to ourselves, living -in England, the so-called “home of gout,” these trenchant -criticisms are but too applicable. So long, then, as such confusion -exists as to what does and what does not constitute gout, how can -we, with any show of scientific precision, presume to discuss, much -less lay down, dogmatic statements as to the geographical distribution -and the race incidence of gout?</p> - -<p><i>Food, Drink, and Occupation.</i>—Gout, it has been well said, is the -“Nemesis of high living,” for, unquestionably <i>overeating</i> is most -fertile in evoking any latent tendency thereto. Attempts to -throw all the blame on particular foodstuffs, <i>e.g.</i>, red meats, etc., -on the ground that these highly nitrogenous substances engender -excessive formation of uric acid, have failed of their object. Even -the much-maligned “purin bodies” have of late been largely -absolved of blame, and the virtues of a “purin-free” diet, <i>e.g.</i>, -milk, are probably referable to the <i>intestinal asepsis</i> that such a -regimen promotes.</p> - -<p>My experience, like that of others, is, that it is not the quality, -but the <i>quantity</i> of the food that is responsible. Moreover, I -believe that the <i>toxicity</i> of the blood plasma thus produced exerts -its evil effects <i>indirectly</i>, viz., by lowering the <i>vis resistantiæ</i> of the -individual to <i>microbic</i> invasion. Nor have I any doubt that it -is this same but too common tendency to gluttony on the part of -the “gouty” which is in part responsible for the <i>cardio-vascular</i>, -<i>hepatic</i>, and renal changes so frequently associated with gout in -its later stages.</p> - -<p>Reverting to <i>alcohol</i>, there are many who regard it as <i>par -excellence</i> the predisposing cause of gout, and some even question -whether gout would have evolved had alcohol been unknown to -mankind. But the interesting point is, that <i>all</i> forms of alcohol -are not equally pernicious in this respect, and the difference in -their potency in this direction is apparently little or at all referable -to their <i>percentage content of alcohol</i>. Port, madeira, sherry, -burgundy, strong ales, and stout are far more provocative of -gout than distilled spirits. In England, where gout is prevalent, -malt liquors are the common drink, whereas in Scotland, where -the predilection is for whisky, the disorder is much more rare, and -the same applies to Ireland. In the Burgundian province of<span class="pagenum"><a id="Page_49"></a>[49]</span> -France gout is common, but exceptional in the Rhenish district -of Germany, where hock is largely consumed. The why and the -wherefore of these vagaries is not as yet explicable; but of those -forms of alcohol, most conducive to gout, neither their <i>acidity</i>, -<i>sugar content</i>, etc., can be impeached as imparting to the alcohol -its predisposing influence in this direction. Incidentally, to those -who advocate the primary <i>renal</i> origin of gout, one would propound -the question, why is it that <i>distilled spirits</i> are less provocative of -gout than wines, seeing these particular liquors are so fruitful of -<i>granular kidney</i>?</p> - -<p>Again, if alcohol be such a potent factor in gout, why is it so -rarely met with in habitual drunkards, and how account for the -comparative rarity in gouty subjects of <i>hepatic cirrhosis</i>, or for -that matter of other disorders of alcoholic origin? Beset by these -eccentricities of behaviour, Sir William Roberts was tempted to -regard gout as “rather an incident of the legitimate dietetic use -of alcoholic beverages.”</p> - -<p>The relationship of <i>alcohol</i> to gout is as erratic as it is to <i>atrophic -cirrhosis</i>. Thus an individual may drink hard through life, and -escape cirrhosis; another luckless wight, though he be quite -temperate, yet falls a prey thereto; still another, who may never -have tasted alcohol, acquires cirrhosis; lastly, cirrhosis is -occasionally met with in the lower animals, into whose diet alcohol -does not enter.</p> - -<p>In like fashion, an habitually intemperate man may pass -through life without incurring gout. Another, handicapped by -his heritage, though he be strictly abstemious, yet falls a prey -thereto. Even a total abstainer, when coming of gouty stock, -may develop gout, haply through overeating.</p> - -<p>To my mind, the only supposition deducible from these facts is -that some individuals are born with a tendency to gout, and that -this tendency may never assert itself as actual disease; that in -others the dormant proclivity, under the influence of alcohol, -forthwith becomes manifest; lastly, in some again, so nicely -poised is the equilibrium of their <i>nuclein</i> metabolism, that the -most venial alcoholic indulgence suffices to evoke an outbreak.</p> - -<p>I incline, therefore, to the view that alcohol <i>per se</i> is not a cause -of gout; in other words, alcohol will not, in the absence of a -<i>gouty heredity</i>, produce gout. On the other hand, given an innate -proclivity thereto, alcohol, especially certain forms of it, will -almost infallibly evoke the disease; this often though the subject -be conspicuously moderate in its use.</p> - -<p>That alcohol will produce the disorder even more swiftly and -surely if reinforced by <i>overeating</i> also, cannot, I think, be gainsaid. -As to the <i>modus operandi</i> of alcohol in inducing gout, I believe that<span class="pagenum"><a id="Page_50"></a>[50]</span> -it acts <i>indirectly</i>, viz., by slowly sapping the protective mechanisms -of the body, and so paving the way to <i>infections</i>.</p> - -<p>Much stress has been laid on the fact that certain <i>occupations</i> -conduce to gout; but, if we exclude <i>plumbers</i>, <i>painters</i>, or other -workers in <i>lead</i>, no other callings in life can be held to entail a -specific predisposition to its development, save in so far as they -promote <i>overeating</i>, <i>overdrinking</i>, and <i>inactivity</i>.</p> - -<p>It is well established that workers in <i>lead</i> are specially prone to -develop gout. I take pride in noting that two of my predecessors -at the Royal Mineral Water Hospital, Bath, William Falconer -(1772) and Caleb Hillier Parry (1807), drew attention to the -frequent occurrence of gout in those exposed to the action of -<i>lead</i>; nevertheless the major part of our knowledge of lead as a -predisposing cause of gout we owe to Sir Alfred Garrod (1854). -This authority noted that at least one out of every four gouty -patients that had come under his care at King’s College Hospital -had at some time in their lives been the subjects of <i>plumbism</i>, and -for the most part were plumbers or painters. Out of 136 undoubted -examples of gout, Sir Dyce Duckworth noted that of -these twenty-five males showed signs of lead poisoning, and were -either plumbers, painters, compositors, or workers in lead mills. -My colleague, James Lindsay, out of a total of 482 instances of -males afflicted with gout, found that 108, or 22·4 per cent., were -workers in lead.</p> - -<p>In light of these findings the question naturally arose as to -whether lead impregnation <i>per se</i> could produce gout. It was -then elicited that the association of lead with gout was noticeably -less frequent in Scotland and in the North of England than in -London. On this interesting point Dr. T. Oliver observes, “We -do not see in the north that intimate relationship between gout -and saturnine poisoning. Workmen from the south develop it in -the North of England. The natives of the north, though equally -exposed, seldom become gouty even when the kidneys are affected.” -Again, Osler tells us that in America lead-gout is comparatively -rare, though chronic lead poisoning is frequently met with in that -country in association with arterio-sclerosis and contracted kidneys. -Again, Frerichs, out of 163 cases of plumbism in the Berlin -Hospital, found not a single case of true gout.</p> - -<p>Some remarkable instances illustrating the influence even of -medicinal doses of lead in determining outbreaks of gout are on -record. In a man aged 25-30, suffering from chronic diarrhœa, -Sir Lauder Brunton prescribed lead and opium pills. In less than -ten days he returned with gout in one of his joints, though he had -never previously suffered from an attack. My colleague, Dr. -Munro, tells me of an even more striking case. A lady under his<span class="pagenum"><a id="Page_51"></a>[51]</span> -care had used a hair wash, for many years, with apparently no ill -effects. She recommended a friend of hers to try the same lotion, -and within a few days she developed acute arthritic gout, though -she had never previously experienced the disorder. Analysing the -preparation, Dr. Munro found the clue in the contained lead.</p> - -<p>As to proffered explanations of lead-gout some have sought it -in the production by this poison of <i>arterio-sclerosis</i> and <i>chronic -nephritis</i>. But this is scarcely satisfying when we contrast the -frequency of chronic plumbism and associated arterio-sclerosis -and contracted kidneys with the relative rarity of lead gout.</p> - -<p>The balance of evidence would appear to be in favour of the view -that lead <i>per se</i> cannot produce gout. For the incidence of lead-gout -is scarcely appreciable, save in a population amongst whom -from other causes gout is prevalent. In short, lead in the absence -of an hereditary bias, is impotent to evoke gout.</p> - -<p>As to its <i>modus operandi</i>, I think it exerts its effect through -derangement of the intestinal secretions, and so favours the -migration inwards into the system of pathogenic <i>bacteria</i>.</p> - -<p>As for occupations other than those concerned with lead, it is -certainly notorious that gout is extremely frequent in those that -are rich in opportunities for overeating, overdrinking, and sluggish -habits. This point has never been more clearly illustrated -than by James Lindsay, whose analysis I take the liberty of transcribing.</p> - -<p>Thus, out of 482 males the victims of gout, eighty-one were -cabmen, coachmen, grooms, stablemen, and bus drivers; fifty-one -were draymen, publicans, barmen, cellarmen, potmen, innkeepers, -maltsters, coopers, storekeepers, brewers’ travellers, and -brewers’ labourers; twenty-five butlers, men servants, ship’s -stewards, and hotel servants; while forty-five were labourers, -and of the residue, although all kinds of trades and occupations -were represented, yet no other class reached ten in number.</p> - -<p>Of these various stations and occupations, it cannot be held -that, in themselves, these callings necessarily contain the -“seeds of the gout.” The banefulness resides in the <i>associated -habits of living</i>; for but too frequently repletion, intemperance, -and indolence go hand in hand with these vocations. In other -words, dietetic excesses, overloaded intestines, and too much -alcohol, what more likely to impair the digestive functions, to -increase the toxicity of the intestinal flora, and in turn to upset the -equilibrium of general nuclein metabolism, with its associated -specific local reaction in certain tissues?</p> - -<p><i>Mental and Physical Over-exertion, etc.</i>—Sydenham said of gout -that it destroys “more wise men than fools,” and in a letter to -Dr. Short, he complains, “I send you a short tract upon Gout and<span class="pagenum"><a id="Page_52"></a>[52]</span> -Dropsy instead of the thicker volume, which in my own mind I had -determined on, viz., a history of such chronic diseases as my -practice has most especially met with. By applying my mind, -however, to its utmost, and by bringing all my powers of thought -on the subject, I brought on a fit of gout, such as I had never before -suffered from; so that the fact itself warned me to lay aside, even -against my own will, such lucubrations, and to take care of myself; -well satisfied with having, in some measure, dealt with these two -diseases. Whenever I returned to my studies, gout returned to -me.”</p> - -<p>It is doubtful if, in the absence of an <i>hereditary</i> proclivity, -intellectual strain would promote the development of gout. On -the other hand, there is, I think, no doubt that immoderate -mental exertion will indirectly precipitate an outbreak. I can -well understand that the illustrious Sydenham, absorbed in his life -study, forgot to take a normal amount of exercise. Perhaps, like -the renowned Jenner, he would have said, “I never walk at all -except from my house into my carriage. I hate walking, and if I -could, I would get my servants to carry me to bed.” Nevertheless, -I doubt not that Sydenham’s intellectual efforts necessarily -entailed sedentary habits, which brought in their wake digestive -and intestinal derangements, whence his occasional gouty outbreaks.</p> - -<p>Gout, indeed, has taken its full toll of the “Intellectuals.” Thus -Scudamore tells us that “The late Mr. Pitt and his father had gout -at a very early period of life. The father was never a votary of -Bacchus, and neither of Venus (as we are told), but both were -<i>ardent students</i>.” Probably, in many instances, however, the -evils of immoderate study are reinforced by more reprehensible -excesses. The ancients insisted on sexual debauchery as favouring -outbreaks of gout. Whence the Latin verse:</p> - -<div class="poetry-container"> -<div class="poetry"> - <div class="stanza"> - <div class="verse indent0">“Ut Venus enervat vires, sic copia vini,</div> - <div class="verse indent0">Et tentat gressus, debilitatque pedes.”</div> - </div> -</div> -</div> - -<p>Doubtless, in some instances of this supposed origin, a <i>gonococcal</i> -arthritis was confused with gout. Doubtless sexual neurasthenia -with diatetic excess favours the onset of gout. In the same -way grief, anxiety, and other depressing emotions are provocative -of gout in that they impair the digestive functions, lead to hepatic -torpor, and sluggish bowels.</p> - -<h3><span class="smcap">Summary</span></h3> - -<p>In conclusion, we have now dealt with those factors currently -regarded as <i>predisposing</i> causes of gout. Personally, as I have -before said, the differentiation of the foregoing from the so-called<span class="pagenum"><a id="Page_53"></a>[53]</span> -<i>exciting</i> causes of gout is purely arbitrary. Thus even those who -countenance such division are forced to admit that many of the -predisposing causes will, “if at any time suddenly increased,” -immediately excite a fit of gout.</p> - -<p>In other words, the difference is <i>quantitative</i> rather than qualitative. -Thus, a moderate drinker, if perchance he exceed his usual -limits, pays the penalty by an outbreak. Another habitually -addicted to the fleshpots eclipses himself, and a similar retribution -is exacted. Or, he exposes himself to a chill, with subsequent -gastro-intestinal or hepatic functional derangement. Yet again, -the cessation of wonted exercise, and more often the taking of it -when unaccustomed, may determine the onset of a paroxysm.</p> - -<p>But far more arresting are the numerous and well authenticated -instances in which local <i>trauma</i> not only determines an outbreak -but also its locality. How frequently, too, have blows, strains, -sprains, <i>fractures</i>, <i>dislocations</i>, or other trivial or severe injuries, -been the signal for an attack. Now, as we hope to show later, <i>local -foci of infection</i> are extremely <i>common</i> in the <i>gouty</i>. Such are -especially frequent in the <i>teeth</i>, <i>tonsils</i>, <i>naso-pharynx</i>, etc. Is it -not then extremely probable that organisms may, <i>viâ</i> the <i>blood-stream</i>, -find their way to a <i>joint</i>, the resistance of whose tissues -has been lowered by a <i>trauma</i>, however slight its degree? This I -apprehend to be the true explanation of the undoubted intimate -connection between traumatisms and arthritic outbreaks of gout.</p> - -<p>Of similar significance, too, the numerous instances on record in -which acute attacks of gout have followed acute <i>tonsillitis</i>, acute -<i>pharyngitis</i>, acute <i>parotitis</i>, etc. How frequently, also, competent -observers, such as Garrod, noted that <i>boils</i> and <i>carbuncles</i> -frequently appeared to be excitant of acute attacks. But to this -important point, the intrusion of an <i>infective</i> element in the -genesis of gout, we shall return in a later chapter entitled “Gout -as an Infection.” It will suffice here if we record our belief that—</p> - -<div class="blockquote"> - -<p>(1) Heredity is the sole <i>predisposing</i> factor in gout.</p> - -<p>(2) That the differentiation between the usually cited predisposing -and exciting causes is unwarrantable.</p> - -<p>(3) That both alike are merely <i>determinants</i>.</p> - -<p>(4) That their influence as such in exciting outbreaks is exerted -through the medium of <i>infection</i>, this achieved either -directly or indirectly.</p> - -</div> - -<h3><span class="smcap">Morbid Anatomy</span></h3> - -<p>It has been truthfully affirmed that we know more of the <i>results</i> -or products of gout, and less of its <i>essential</i> nature, than of almost -any other disease. Thus the post-mortem history of the disorder -is concerned almost exclusively with more or less graphic<span class="pagenum"><a id="Page_54"></a>[54]</span> -accounts of the <i>uratic deposits</i>, their sites of predilection, and the -changes that they induce. Hence it is that the morbid anatomy -of gout relates for the most part to its <i>regular</i> or <i>articular</i> manifestations, -for it is in and around the joint structures that the deposits -for the main part occur.</p> - -<p>As to the assumed localisations of the disease in the <i>internal</i> -organs, there is no <i>anatomical</i> evidence that they are due to an -invasion of the “gouty” inflammation. Not even the <i>renal</i> -changes, despite the attestation, as it were, of the gouty process by -<i>uratic deposits</i> in the <i>papillæ</i>, can be held as distinctive of gout. -Norman Moore found them present in only twelve out of eighty -cases. As Osler said, “The presence of uratic concretions at the -apices of the pyramids is not a positive indication of gout. They -are not infrequent in this country [U.S.], in which gout is rare.... -It is not possible to say in a given case that the condition has been -due to gout unless marked evidence of the disease co-exists.”</p> - -<p>If, then, nothing distinctive can be claimed of the <i>renal</i>, how -much less can we construe as “gouty” the anatomical alterations -that may or may not be met with in other organs in this disorder. -In short, it may be said of the <i>renal</i> as well as the other <i>visceral</i> -lesions, so often met with in association with gout, that they are -met with even more frequently in its absence, and most certainly -fail to attest their “gouty” nature by the appearances which -they present.</p> - -<p>The only morbid structural changes, therefore, that can legitimately -be defined as <i>specific</i> of gout relate to its <i>regular</i> or <i>articular</i> -lesions. As to the <i>anatomical</i> alterations in the articulations, their -specificity depends essentially on the <i>uratic deposits</i>, rather than -upon the associated inflammatory and degenerative processes.</p> - -<p>Given death during an <i>acute</i> paroxysm, examination reveals the -usual tokens of inflammation, hyperæmia, effusion, and swelling -of the ligamentous tissues. The synovial lining is injected and -spongy, while the exuded fluid is thick, scanty and turbid, containing -polymorphonuclear leucocytes as well as <i>crystalline -deposits</i>. Charged therewith, not only is the synovia thick, but -of a milky appearance. Examined microscopically, it is found -to contain the acicular crystals of <i>sodium biurate</i>. The synovia -has occasionally been found covered with blood, but no <i>pus</i> formation -has ever been known to occur in uncomplicated acute gouty -arthritis. The reaction of the synovial fluid is generally neutral -or alkaline, but exceptionally Garrod found it acid.</p> - -<p>Uratic deposit has a predilection for <i>cartilage</i>, and in some -instances is strictly confined thereto; but in the more <i>chronic</i> -forms it permeates all the component elements of the articulation. -In the synovial membrane and fringes deposition takes place in<span class="pagenum"><a id="Page_55"></a>[55]</span> -the subepithelial and subserous layers. It invades also the ligaments, -the tendons, and even the periarticular fibrous tissues -become impregnated with biurate. Moreover, like the synovial -sheaths of the tendons, the neighbouring bursæ are specially prone -to deposits, which again encroaching upon the subcutaneous connective -tissues, infiltrate the skin itself, forming chalk stones or -tophi.</p> - -<p>Inspected after death, the articular cartilages are seemingly -overlaid with a white mortar or chalk-like material, <i>i.e.</i>, sodium -biurate. Their surfaces, however, though defaced by stains, -streaks, or dull patches, nevertheless, at any rate at first, retain -their pristine smoothness. This because closer scrutiny reveals -that the deposit is not in reality <i>upon</i> the surface of the cartilage, -but is located <i>interstitially</i> in its substance.</p> - -<p>Microscopic examination of a vertical section, taken at the site -of the deposit, shows clearly that it is composed of felted masses -of acicular crystals. Lying in the matrix of the cartilage, they are -more densely packed just below its free surface. The crystals -do not penetrate further than one-third or one-half of the depth -of the cartilage. Becoming more and more sparse towards the -deeper layers, those near the bone are entirely free from deposit. -This clearly indicates that the uratic matter originated from the -synovial fluid bathing the articular ends and was precipitated -therefrom.</p> - -<p>As to the primary site of the deposition, it usually takes place -at the centre of the articular cartilage. Opinions differ as to -whether the cartilage cells are foci of deposition. Garrod thought -so, but Duckworth found no relationship between it and any histological -elements, while others locate it in the matrix.</p> - -<p>While, as before stated, the cartilage at first retains its smoothness, -later it becomes pitted in patches. Ultimately the cartilage, -through atrophic changes and erosions, may disappear, the joint -cavity becomes filled with a plaster-like material, and the joint -structures undergo more or less disorganisation. <i>Pari passu</i> with -the central atrophy of the cartilage, hypertrophic outgrowths form -at its free margin. In late stages the bones, too, undergo changes; -their outer layers become more dense through proliferative -osteitis, while their spongy tissue becomes rarefied, and the cells -of the marrow fatty. Duckworth held that uratic deposits might -occur <i>primarily</i> in the bone without any similar implication of -the related cartilage. On the other hand, Garrod dissented, -claiming that when the bone was involved, it was only <i>secondarily</i> -to uratic deposition in the cartilage, of which indeed it was but an -extension.</p> - -<p>In reviewing the foregoing findings, it must be admitted that<span class="pagenum"><a id="Page_56"></a>[56]</span> -morbid anatomy fails to shed light on the <i>essential</i> cause of gout. -This, at any rate, is true of the older studies with which, up to the -present, we have been engaged. Still, as Berkart’s more recent -researches show, our knowledge of even the <i>morbid anatomy</i> of -gout is as yet but in its infancy.</p> - -<p><i>Histological</i> examination of the <i>articular ends</i> adjacent to gouty -joints reveals the presence of certain <i>cystic</i> changes in the <i>diaphyses</i>. -Thereupon Berkart propounded an hypothesis, explanatory of the -acute phenomena of a paroxysm of gout. His view was that -these cysts in the bone, at first minute, gradually enlarge. Ultimately, -through concomitant thinning of the surface bone, there -comes a day when the cyst bursts into the joint, its content voided -into the cavity thereof.</p> - -<p>An interesting point noted by Berkart was that in many cases -of “acute” gout the articular cartilage was found apparently -normal and devoid of <i>uratic deposits</i>, and this although the attack -had been sufficiently severe. This would appear to contravene -Garrod’s dictum that “gouty inflammation is invariably attended -with deposition of urate of soda.” The same inference was drawn -from a case of Sir Dyce Duckworth’s. The subject had had two -attacks of gout in the right great toe joint. Yet at the autopsy -neither toe joint contained a speck of uratic deposit. Nevertheless, -this does not prove that uratic deposition had not ensued -during the gouty attacks. All it can be held to prove is, that such -deposits are not always permanent, and that, under certain conditions, -they may undergo resolution. That this is so is almost -certain, seeing that tophi in the ear have been seen to come and go, -and equally certainly, after an acute attack, tophi in the neighbourhood -of a joint may lessen even though fresh ones form coincidently -at another site.</p> - -<p>Albeit, the importance of Berkart’s hypothesis and histological -findings resides in the fact that they suggest strongly that a -pathological process, more vital and biological than the mechanical -uric acid theory, is at the root of the clinical phenomena of a -gouty paroxysm. It does not put out of court Garrod’s assumption -that uric acid is an invariable <i>accompaniment</i> of acute gouty -inflammation, but it militates strongly against his contention that -uric acid deposition is the <i>cause</i> of acute gouty inflammation. -It indicates the reverse, viz., that the uratic deposition is the -<i>consequence</i> of a more vital underlying morbid process.</p> - -<p>Let us revert now more in detail to Berkart’s findings. The -bones adjacent to gouty joints were fully prepared for microscopic -examination. Investigation of the first metatarsals, and -in some instances of the phalanges also, revealed the presence of -<i>cystoid degeneration</i>. Its starting point is in the <i>epiphyses</i>. Thence<span class="pagenum"><a id="Page_57"></a>[57]</span> -it extends to the articular cartilage, through which it bores at one -or more points. The contents of the cyst then find their way into -the joint through the fistulous openings in the cartilage, with a -resultant acute “perforative synovitis.”</p> - -<p>The cysts, at first minute, may be either single or multiple. -Small in size, they are easily concealed by the fat marrow, unless -the bone is properly prepared for microscopic examination. The -isolated cysts eventually coalesce, and so lead to considerable -excavation.</p> - -<p>As to the contents of the cysts little is known, as, save through -accidents or surgical operations, they are rarely available for -examination. When of relatively recent origin they apparently -consist of a coagulable substance which later on become serous or -hæmorrhagic. So long as the fistulæ thus formed in the cartilage -remain pervious, a direct way into the articular cavity is provided, -and through this, if of sufficient calibre, the necrotic matter periodically -gains entry into the joint, with ensuing periodic outbreaks of -acute synovitis. In other instances in which the cysts are located -in proximity to, or within, the diaphysis they may fail to extend -to the cartilage, and no perforation ensues. In this event, -through accumulation of its contents, the cyst enlarges, and the -bone is gradually expanded through pressure.</p> - -<p>Berkart holds that the histological changes in the affected -epiphyses indicate that the cystoid degeneration is the outcome -of an <i>anomaly</i> of the <i>vascular</i> and <i>osseous</i> structures. The -degenerative area contains an abundance of dilated and thin-walled -veins, evidence of a condition of chronic congestion. In consequence -thereof, the trabeculæ undergo decalcification, and the -adjacent fat marrow becomes fibrous. The areas of fibrosis thus -formed, owing to thrombosis of the related veins, become softened -and transmuted into cysts.</p> - -<p>Now, as we all know, some persons, after indulging in wine, -almost immediately experience sharp twinges in the small bones -of their hands or feet. Garrod attached diagnostic importance to -such swift response as a sign of gout. These pains he attributed -to uric acid deposition. In contrast, Berkart attributes the -twinges to atony and consequent over-distension of the related -vessels, which lack the normal support afforded by the osseous -trabeculæ.</p> - -<p>As far as we are aware, these findings of Berkart’s are as yet -unconfirmed. Nevertheless they provide us with a much more -probable explanation of the phenomena of acute gout than -the older <i>uric acid theory</i>, which, not to mention the many other -obstacles to its acceptance, has always laboured under the aspersion -of being too “mechanical” in conception.</p> - -<p><span class="pagenum"><a id="Page_58"></a>[58]</span></p> - -<p>Moreover, his studies clearly indicate that not only the intra-articular -surfaces but the adjacent <i>bone-ends</i> and <i>marrow</i> must, as -the somewhat rare opportunities present themselves, be exhaustively -investigated. For myself, I cannot believe that so passive -an agent as an “anomaly of the vascular and osseous systems” is -the <i>fons et origo mali</i> in gout. Some more vital element must, -I feel convinced, intrude, and I incline to think an <i>infection</i>. -Berkart himself brings forth evidence in favour of this contention, -inasmuch as he noted the frequent co-existence of <i>lymphangitis</i>, -so pronounced that the whole of the affected leg became the seat -of a <i>leuco-phlegmatic œdema</i>.</p> - -<hr class="chap x-ebookmaker-drop"> - -<div class="chapter"> - -<p><span class="pagenum"><a id="Page_59"></a>[59]</span></p> - -<h2 class="nobreak" id="CHAPTER_V">CHAPTER V<br> -<span class="smaller">PATHOLOGY OF GOUT—PROTEIN METABOLISM</span></h2> - -</div> - -<p>Not only is the proximate cause of gout unknown, but the -essential nature of the disease is still shrouded in obscurity; for -the obliquity in trend of protein metabolism, manifested though -it be by striking phenomena, is clearly only the outcome of some, -as yet undetermined, derangement in the mechanism of <i>intermediary</i> -metabolic or bio-chemical change.</p> - -<p>This is, of course, but to restate the problem we are confronted -with. Wholly to solve the enigma would postulate ability on our -part to trace ingested foodstuffs through all their vicissitudes -from the moment of entry into the blood or lymph-stream till -flung out as effete matter through the various avenues of excretion; -but, unhappily, we know the story only in part, its beginning -and end, but not what lies between.</p> - -<p>We know much of the complex changes that take place in food -prior to absorption, and of the <i>modus operandi</i> of the latter not a -little. Comparably, too, we can gauge the quality and quantity -of end-products, the chemical outcasts, as they escape in the -urine, sweat or breath, and largely how achieved; but of the -intermediate steps between absorption and excretion we catch but -a glimpse here and there. The sequestered path by which the -inanimate molecules of food uprise to Life, and anon go down -to decay and death, are still hidden.</p> - -<p>In other words, little do we know of the relationship of <i>labile</i>, or -food-protein, to <i>tissue</i> protein. True, the coarse fact of abnormal -protein loss in <i>renal</i> disease may be revealed in the urine, as likewise -the waste of albumoses in <i>myeloma</i>, etc., and the incidence -of amino-acids in disease of the <i>liver</i>. Similarly, the appearance -of <i>cystin</i> or of <i>alkapton</i> in the urine bespeaks flaws in protein -metabolism, failures in the normal disruption of amino-acids. All -these are of the grosser anomalies of protein metabolism, but more -subtle those of gout!</p> - -<p>Complex, in truth, the problem here presented, than which none -more subtle exists in the realm of bio-chemistry. True, <i>quantitative</i> -variations in the content of the urine as to <i>urea</i>, <i>uric acid</i>, -etc., undoubtedly bear a direct relation to <i>protein</i> metabolism, -but they give us little, if any, substantial clue as to the particular<span class="pagenum"><a id="Page_60"></a>[60]</span> -metabolic warp responsible. We see this particularly in regard -to uric acid, so long accredited with an essential <i>rôle</i> in gout.</p> - -<p>Thus we cannot, on the basis of the <i>variations</i> in its <i>excretion</i> -only, presume to diagnose “gout.” This because even more -extensive variations occur in <i>healthy</i> persons. On the other hand, -attacks of gout never occur when urates are absent from the -<i>blood</i>. To reduce the amount of these urates is clearly then of -importance, and obviously to this end a knowledge of their -source is essential. We have an analogy to hand in diabetes, in -which the somewhat similar problem relating to <i>glycosuria</i> has been -partially solved.</p> - -<h3><span class="smcap">Revelations of the Bio-Chemist</span></h3> - -<p>But before proceeding to the more strictly biological aspect -of the relationship of uric acid to gout, we must, as in the study -of any other problem of metabolism, place ourselves in possession -of the main facts relating to the chemistry of <i>protein</i>, and more -particularly of <i>purin</i> or <i>nuclein</i> metabolism; for it was just this -same lack of even the most rudimentary facts, especially regarding -the chemistry of uric acid, that vitiated the conclusions arrived -at by the earlier workers in this sphere. Disabilities of technique -of necessity rendered inaccurate the results obtained by these -pioneers in research, while the significance of the facts they -laboriously gleaned was likewise misinterpreted.</p> - -<p>But with the advent of highly trained organic chemists, well -skilled in the investigation of bio-chemical problems, a basis of -accurate chemical facts was established. The story of the fate of -protein and purin substances in the animal body, at one time a -medley of guesses and gaps, was brought to one of relative certitude -and completeness. The change involved has proved in truth -revolutionary, and many the cherished shibboleth that has been -ruthlessly cast aside.</p> - -<p>How vivid the light thrown upon the problems of clinical -medicine by the bio-chemists! With admiration not unmingled -with awe we see them laying well and truly the foundations upon -which in the ultimate scientific medicine must inevitably rest. Of -these the very corner stones are <i>chemical physiology and chemical -pathology</i>, the rapid evolution of which is profoundly altering our -conceptions of health and alike disease. Those vital processes of -the organism that but yesterday we saw “as through a glass -darkly,” are now in great part illumined, and the distortions -wrought in them by disease made more manifest.</p> - -<p>How pregnant, too, with warning their findings! Processes -that, to our untutored minds, seemed simple are revealed as -infinitely complex. Through what a labyrinth must we thread<span class="pagenum"><a id="Page_61"></a>[61]</span> -our way if we would unravel the intricacies of metabolism! -Intricate enough, forsooth, in health, but how much more so in -disease!—for as Sir Archibald Garrod eloquently phrases it, “It -is becoming evident that special paths of metabolism exist, not -only for proteins, fats and carbohydrates as such, but that even -the individual primary fractions of the protein molecule follow -their several catabolic paths, and are dealt with in successive -stages by series of enzymes until the final products of catabolism -are formed. Any of these paths may be blocked, while others -remain open.”</p> - -<p>It is with chastening reflections such as these that we may best -approach our study of gout, that Riddle of the Ages, upon the -elucidation of which so many physicians from time immemorial -have expended their dialectic skill. Would that we could affirm -that the bio-chemists of to-day had found the “Open Sesame!” -But, alas, it is not so! The chamber is still sealed.</p> - -<p>Vast though the increase in our knowledge of the chemical -structure of uric acid and its allies, uncertainty still dogs our steps. -Doubtful of the pathway to solution of the pathological mystery of -gout, we must perforce approach the problem in a more strictly -catholic attitude. <i>Uric acid</i> has apparently failed us as the <i>causa -causans</i>. We can, therefore, no longer restrict our enquiry to -<i>purin</i>, but must take cognisance of <i>protein</i> metabolism as a whole, -for some, perhaps not unnaturally despairing of the <i>uric acid</i> -hypothesis, are turning therefrom to other end-products of metabolism, -<i>e.g.</i>, <i>creatinine</i>. In keeping with this altered outlook, it -will not be out of place if we, at this juncture, allude, though in -brief, to the later revelations as to protein metabolism, before we -pass on to more detailed consideration of those relating to the -<i>purin</i> bodies.</p> - -<h3><span class="smcap">Protein Metabolism</span></h3> - -<p>No longer can we, like the older physiologists, envisage <i>protein</i> -as being absorbed as such from the alimentary canal and forthwith -incorporated with the body tissue, for the researches of Fischer -have revealed that the complex <i>protein</i> molecule must previously -undergo complete disruption into the <i>a-amino-acids</i>, its ultimate -“building stones,” this through the hydrolytic action of the -digestive enzymes of the alimentary tract. The fact that -Fischer<a id="FNanchor_6" href="#Footnote_6" class="fnanchor">[6]</a> was able to maintain nitrogen equilibrium in animals<span class="pagenum"><a id="Page_62"></a>[62]</span> -fed with completely digested protein mixtures is, of course, direct -evidence in favour of his contention, viz., that proteins undergo -disruption into amino-acids.</p> - -<h3><span class="smcap">The Formation of Urea</span></h3> - -<p>The question as to whether urea, the end-product of general -nitrogenous catabolism, was derived from the <i>amino-acids</i>, brought -in the portal blood to the liver, was for long a vexed one. This -because the earlier attempts to detect amino-acids in the <i>portal -blood</i>, during the digestion of copious amounts of protein, proved -futile. On the other hand, the same workers found that free -<i>ammonia</i> was present in greater amounts in the portal vein than -in the systemic circulation.</p> - -<p>This, to their mind, seemed to indicate that the amino-acids, -during their passage through the intestinal mucous membrane, -underwent <i>deaminisation</i>. According to this view the <i>ammonia</i>, -thus split off from the amino-acids, was the precursor of <i>urea</i>.</p> - -<p>But the claim that more free ammonia was present in the portal -vein than in the systemic circulation was disproved by Folin and -Denis. Invoking more delicate methods of hæmo-analysis, they -found that the amount of ammonia and urea in the portal blood -was not increased during the absorption of amino-acids from the -lumen of the intestine. Moreover, they found that the ammonia -present was of minimal amount, produced in the main by putrefactive -bacteria. Lastly, they discovered that <i>amino-acids</i> were -actually present in the <i>portal blood</i>.</p> - -<h3><span class="smcap">Fate of the Amino-Acids</span></h3> - -<p>In the gastro-intestinal tract the complex food proteins, under -the hydrolytic action of enzymes, break down into a variety of -substances, all of which belong to the group of a-amino-acids. -These same absorbed from thence into the blood are transported -to the various organs and tissues. Arrived thither the -amino-acids are subjected to a process of sifting. Thus -some are invoked for the reconstruction of broken down proteins, -<i>i.e.</i>, are re-synthesised into the body’s own characteristic -tissues.</p> - -<p>The surplus amino-acids, viz., those not required for purposes -of cell repair, undergo deaminisation. Two residues then result,<span class="pagenum"><a id="Page_63"></a>[63]</span> -one represented by ammonia, and the other by the remaining -relics of the amino-acid molecule. The former is excreted as -<i>urea</i> and the latter is oxidised to produce energy.</p> - -<p>But there is yet another source of amino-acids, viz., the disintegration -of tissue protein. To this end almost all bodily tissues -possess intracellular enzymes capable of converting their proteins -into the same simple products from which they took origin.</p> - -<p>Comparably with those of exogenous origin, these amino-acids -of <i>endogenous</i> formation undergo a like deaminisation; in other -words, the bulk of their carbon, oxygen, and hydrogen is oxidised -to form CO₂ and water, the residue combining with nitrogen to -form <i>urea</i>, etc.</p> - -<p>The main end-product, then, of protein metabolism is <i>urea</i>, with -traces of its forerunner <i>ammonia</i>. But there are also other waste -nitrogenous metabolites. Thus, of the various amino-acids that -become built up into tissue protein, some subsequently break -down into products not belonging to the amino-acid category, -viz., <i>creatine</i> and <i>creatinine</i>. Some of the amino-acids, too, are -excreted unchanged in the urine. Lastly, to these must be added -those closely related substances, the <i>purin</i> bodies, the end-products -of <i>nuclein</i> as opposed to general protein metabolism, of -which latter <i>urea</i> is the terminal product. To sum up, in a man -on ordinary diet about 90 per cent. of his total nitrogen is excreted -as urea, about 3 per cent. as ammonia, the residue of the nitrogen -appearing in the form of other nitrogenous metabolites.</p> - -<h3><span class="smcap">Seat of Formation of Urea</span></h3> - -<p>The <i>liver</i>, it is generally held, is the main centre wherein urea -is produced from the amino-acids; but not exclusively so, for it -has been definitely established that, <i>even after removal of the entire -liver in animals</i>, its production may not cease.</p> - -<p>Moreover, some researches of Otto Folin and W. Denis into -<i>urea formation</i> seem to indicate that the older views call for -revision. Experimenting on cats, they injected them with <i>alanine</i> -and <i>glycocoll nitrogen</i> and other amino-acids as well as Witte’s -<i>peptone</i>. They were able to prove definitely that, at the end of an -hour or more, the formation of <i>urea</i> from the absorbed amino-acids -was unmistakably demonstrable. Also they noted that -interesting fact, that the “<i>urea nitrogen</i> obtained from the -<i>hepatic blood</i> is not larger than the urea in the blood obtained at -about the same time from the <i>iliac artery</i>.” This they claim -indicates that “<i>the liver has not brought about any demonstrable -specialised deaminisation</i>.”</p> - -<p>The experimental data forthcoming in their researches, while<span class="pagenum"><a id="Page_64"></a>[64]</span> -they prove that the absorption of <i>amino-acids</i> is very swiftly -followed by the formation of urea, does not afford any definite -evidence as to the <i>site</i> of urea formation; but, as they rightly -contend, we have no satisfactory proof that <i>deaminisation</i> and <i>urea -formation</i> is <i>localised</i>. Consequently “we are not justified in -assuming that the process is a specialised process in the sense of -being confined to some particular organ.”</p> - -<p>Indeed, they bring forward evidence that the process of urea -formation, far from being localised to any particular organ, <i>i.e.</i>, -the liver, is almost ubiquitous.</p> - -<p>Thus, experimenting with the injection of <i>alanine</i>, they noted -that prior to the same the muscle content of <i>non-protein nitrogen</i> -and <i>urea nitrogen</i> was respectively 194 and 26 mg.; but -180 minutes after the injection the non-protein content in muscle -had risen to 232 and that of urea nitrogen to 41 mg. Working -with <i>glycocoll</i>, the non-protein and urea nitrogen in muscle before -injection of the same was 248 and 42 mg. respectively, while 240 -minutes after injection the figures were 304 and 54 mg.</p> - -<p>The significance of these figures is more striking when contrasted -with the fact that in the same subjects the urea nitrogen -content of the <i>hepatic</i> blood did not exceed that obtained almost -simultaneously from the <i>iliac</i> artery. The deduction made by -Folin and Denis is that—</p> - -<p>(1) “<i>The urea-forming process is one characteristic of all the -tissues, and by far the greatest amount of the urea is, therefore, -probably formed in the muscles.</i>”</p> - -<p>(2) “<i>The negative results, so far as any localised urea formation -is concerned, is almost satisfactory proof that there is none, for if -there were one central focus from which all or nearly all of the urea -originated we could scarcely fail to find it.</i>”</p> - -<h3><span class="smcap">Amino-Acids in Relation to Gout</span></h3> - -<p>The vista opened up by these advances in physiology suggested -investigations into the <i>amino-acids</i>, their association with the output -of <i>uric acid</i> in <i>gouty</i> patients. No less than eighteen different -amino-acids enter into the constitution of protein, but of these -the most interesting from our point of view is <i>glycocoll</i> or amino-acetic-acid. -Now, glycocoll plays a great <i>rôle</i> in the organism -as a <i>detoxicating</i> agent, rendering innocuous, <i>e.g.</i>, benzoic and -cholic acids by transmuting them into <i>hippuric</i> and <i>glycocholic</i> -acids. In short, the body always has glycocoll at its disposal for -coupling or combination purposes.</p> - -<p>Now it appears likely that glycocoll can be split off from all -the amino-acids, a probability reinforced by the results of the<span class="pagenum"><a id="Page_65"></a>[65]</span> -researches of Embden and Reese and Lipstein, these observers -having shown that amino-acids are present in all urines to about -1 per cent. of the total nitrogen output.</p> - -<p>Ignatowski, working with the urine of <i>gouty</i> patients, found -<i>amino-acids</i> present in large amounts; not that it was peculiar -to such subjects, for he found it in other diseases, but only traces -were detectable in the urine of <i>healthy</i> individuals. Again, -Walker Hall, investigating urines drawn from the subjects of -gout, the victims of other diseases, as well as healthy and diseased -children, determined the presence of <i>glycocoll</i> in about 70 per cent. -of the cases. His researches, to his mind, confirmed the conclusion -that “normally a certain amount of glycocoll escapes through -or is eliminated by the renal filter.”</p> - -<p>Burger and Schweriner, from their researches on gouty subjects, -have confirmed Walker Hall’s findings as to the excretion in -excess of amino-acids, especially <i>glycocoll</i>. Lastly, Almagia has -in gouty urines detected the presence of <i>glyoxylic</i> acid. What its -significance may be is uncertain, but it is at least interesting to -note that, as MacLeod suggests, the synthetic formation within -the body of glycocoll may very probably result from the interaction -of ammonia and glyoxylic acid.</p> - -<h3><span class="smcap">The Glycocoll Theory of Gout</span></h3> - -<p>Excessive meat feeding in dogs, according to Kochmann, induces -degenerative changes in the liver and kidneys. Similar tissue -alterations were noted by Walker Hall in rabbits, after injection -with <i>hypoxanthine</i>, while the same was observed by Kionka in -mice. These findings suggest that, although <i>anatomical lesions</i> -are not apparent in the <i>livers</i> of “gouty” men, it is at least -probable that <i>functional</i> damage results from the overeating of -meat.</p> - -<p>Now, if glycocoll be added to a solution of (neutral) dialkali-urate, -it expedites the appearance of the (acid) mono-alkali-urate, -a reaction more noticeable with the sodium salt. <i>Urea</i>, in contrast -to glycocoll, markedly inhibits the formation of the acid salt. But -if <i>glycocoll</i> be added to a solution of the (neutral) dialkali-urate -and urea, the latter parts to some extent with its powers in this -respect, and the mono-alkali-urate is deposited.</p> - -<p>It is reasonable, then, to suppose that if, as testified by Ignatowski -and Walker Hall, glycocoll is present in gouty <i>urine</i>, it is also -present in the <i>tissue fluids</i> of the gouty individual, and so the -<i>precipitation</i> of <i>uric acid</i> is favoured. Glycocoll, normally, -is almost entirely transmuted into <i>urea</i> by the urea-forming -ferment of the liver.</p> - -<p><span class="pagenum"><a id="Page_66"></a>[66]</span></p> - -<p>Impressed by these considerations, Kionka advances the -hypothesis that gout is due to:</p> - -<div class="blockquote"> - -<p>(1) Functional changes in the liver, a depressed urea-ferment -action.</p> - -<p>(2) A deficient uric acid excretion by the kidney, possibly due -to the changed uric acid combinations in the blood.</p> - -<p>(3) These pathological conditions may be “hereditary” or -“acquired,” from overeating, alcohol, lead, etc.</p> - -</div> - -<p>In other words, given deficient action of the urea ferment in the -liver, then more glycocoll will be present in the blood-stream, and -the uric acid may be thrown out of solution.<a id="FNanchor_7" href="#Footnote_7" class="fnanchor">[7]</a></p> - -<p>For it is possible, as Kionka suggests, that normally uric acid, -on its way to urea, may pass through a <i>glycocoll</i> stage. Now, in the -gouty individual the glycocoll may not be entirely transformed to -<i>urea</i>, and its excess in the <i>tissue fluids</i> may lead to <i>uric acid -deposits</i>. Perhaps, as Walker Hall observes, “since hepatic deficiency -is generally admitted in the gouty, diminished destruction -of uric acid and glycocoll may go hand in hand.”</p> - -<p>In healthy <i>cartilage</i> glycocoll is undemonstrable. But, according -to Kionka, if bruised or damaged, a considerable amount -thereof is formed. Now, when blood, rich in uric acid, circulates -through injured cartilage, the presence of glycocoll favours precipitation -of the urates, a possible explanation of the formation of -<i>tophi</i>. Unfortunately for the valency of this theory, Aberhalden -and Schittenhelm show that the methods employed by Frey, to -isolate glycocoll from cartilage, were such as yield errors which -would quite account for the amount obtained by this worker. -They, therefore, deny the presence of glycocoll in damaged cartilages. -But, in conclusion, Kionka’s plea for a primary <i>hepatic -functional disability</i> derives colour from the fact that the drugs -which have gained most approval in the treatment of gout are -those which increase the quantity of bile without augmenting the -amount of bile acids; and the which are excreted in combination -with <i>glycocoll</i>, for instance, salicyclic acid combines with glycocoll, -and is excreted as salicyluric acid, and benzoic acid, which -combines with glycocoll to form hippuric acid. Albeit, we -must not overlook the fact that the presence of glycocoll is -not peculiar to <i>gouty</i> urine, but, as shown by Walker Hall -and Embden, is met with in other disorders. The glycocoll -hypothesis as to the origin of gout is, though attractive, therefore -still unproven.</p> - -<p><span class="pagenum"><a id="Page_67"></a>[67]</span></p> - -<h3><span class="smcap">Urea Excretion in Gout</span></h3> - -<p>According to Tilden Brown, the rhythm of urea excretion -constitutes a warning as to the approach of gout. A very lowered -elimination thereof he holds to be an excellent and pathognomonic -symptom. The excretion of urea may at times run so low as to -lead to a suspicion of <i>renal</i> disease. He considers that this sign -may find a place in the prophylaxis of gout, a signal for the -initiation of treatment with the object of lessening the severity -of symptoms (viz., extent of toxic action as manifested by -destruction of proteid, etc.).</p> - -<p>This point was advanced by Brown (1905) during a discussion -at the Harvard Medical Society, but as far as we know it has not -been confirmed. Presumably it rested upon the assumed existence -of a normal ratio of uric acid elimination to that of urea with -the corollary that every deviation therefrom was due to a pathological -cause. Haig held this view, which was, however, disproved -by Herringham, Groves and Luff. The latter authority estimated -the daily eliminations of uric acid and urea in a healthy adult man -on a mixed diet for a period of fifty days, and clearly showed that -no constant ratio exists in a given individual between the excretion -of uric acid and urea.</p> - -<p>Also, it is obvious that, before attaching any valency to Tilden -Brown’s dictum, it is essential that it be established that the cases -were instances of pure gout, unaccompanied by <i>nephritis</i>. Moreover, -modern workers tend more and more to rely not on analyses -of the urine but of the <i>blood</i>, especially in the unravelling of so-called -metabolic disorders. Also, it may be added, that their -findings in this sphere indicate no harmony between the urea and -the uric acid content of the blood. Thus, Otto Folin observes, -“One most interesting fact which we constantly meet with in -blood analysis is that there is no correspondence between uric acid -and the total non-protein nitrogen in the blood. In gout or lead -poisoning, or leukæmia, the blood is uniformly rich in uric acid, yet -the total non-protein nitrogen or <i>urea</i> nitrogen may be normal.”</p> - -<h3><span class="smcap">Creatine and Creatinine</span></h3> - -<p>As before pointed out, it has been suggested that these substances -may be in some obscure way related to the genesis of <i>gout</i>. -To this end a great amount of research has been expended on the -metabolism of creatine and creatinine. But although, as far as -I am aware, the revelations hitherto forthcoming have disclosed -no link between these substances and the development of gout, -still, by reason of the potentialities possibly resident therein, a -brief digression is permissible.</p> - -<p><span class="pagenum"><a id="Page_68"></a>[68]</span></p> - -<p>The exact origin of creatine and creatinine is still obscure. All -we know is that they are, in the main, the outcome of chemical -processes in the tissues, viz., products of <i>endogenous</i> metabolism. -Also of the creatine and creatinine present in food a moiety may -appear as creatine in the urine.</p> - -<p><i>Creatinine</i> occurs in the urine of adults, and is practically independent -of the protein intake. The amount excreted varies with the -size, and not with the weight of the body. In other words, it varies -with the <i>volume</i> or <i>mass</i> of the <i>voluntary muscles</i>, which structures -have the highest content of creatinine and creatine. MacLeod, discussing -this relationship, tells us that, “in the muscular atrophies -creatine excretion is distinctly below normal.” It must, he adds, -be the “mass of the muscles rather than their activities that is -the determining factor, for the creatine excretion does not become -increased by muscular exercises.” Otto Folin, discussing the -clinical application of pathological chemistry, observes, “Nothing -definite is as yet known concerning the creatinine output in -abnormal metabolism, except that in fevers and other diseases -there is an increase, sometimes a very large increase.” But -this much we do know that creatine, after ingestion, is almost -quantitatively excreted in the urine. <i>Creatine</i>, in considerable -amount, is a normal constituent of children’s urine, but in normal -adults hardly a trace occurs, though in some diseases it is met with -even in their case. In boys it gradually dwindles and disappears -at about seven years of age. On the contrary, in girls creatine is -excreted until puberty. Subsequently, its presence in the urine -is intermittent, its incidence confined to the menstrual cycles, the -period of pregnancy, and for some days after parturition.</p> - -<p>From our point of view, the most interesting of the above -revelations is the fact that the largest percentage amount of -creatine and creatinine is located in the <i>muscular tissues</i>. On -this point we cannot do better than quote the following words -of Otto Folin:—</p> - -<p>“It is to be noted that we are as yet entirely ignorant of the -origin and significance of the creatine which is so abundant in -muscles, and it is scarcely to be doubted that fundamentally -important metabolism problems somehow are connected with the -muscle creatine and urinary creatinine, but these are as yet -problems of normal metabolism, and it is too early to say whether, -or in what way, light may be thrown on clinical problems by -studies of these products. The fact that the muscles of mammals, -including man, contain 0·3-0·4 per cent. of creatine, and only -traces of the chief nitrogenous waste product urea, constitutes to -my mind strong presumptive evidence that creatine serves some -important function, and it is quite conceivable that metabolism<span class="pagenum"><a id="Page_69"></a>[69]</span> -diseases of one kind or another may be associated with this -curious substance, but investigations rather than hypotheses are -needed in the study of such obscure problems.”</p> - -<h3><span class="smcap">Inborn Errors of Metabolism</span></h3> - -<p>Apart from its intrinsic fascination, the tracing out of analogies, -clinical or pathological, between diseases apparently diverse has -often proved a fruitful source of enlightenment, for the natural -history of disease is such that one disorder trenches upon the -clinical territory of another, symptoms overlap and similarity if -not community of origin is revealed.</p> - -<p>Few will gainsay that gouty individuals are the victims of some -inborn defect or eccentricity of metabolism, and instinctively the -thought arises, are there no other disorders of like character? -Immediately we bethink ourselves of alkaptonuria, cystinuria -and pentosuria. Sir Archibald Garrod, as we know, classed these -disorders as “chemical malformation” of hereditary origin. In -other words, all are the outcome of an abnormality in intermediary -metabolism.</p> - -<p>In alkaptonuria the metabolic warp concerns the <i>aromatic</i> -groups, in cystinuria the sulphur-containing radicles of the -<i>protein</i> molecule. On the other hand, in pentosuria the origin of -the endogenous pentose is variously ascribed to the <i>nucleo-protein</i> -of the cell nuclei or to galactose. Lastly, in gout it is in the metabolism -of <i>nucleo-protein</i>, or rather of the <i>nucleic acids</i> of the cell -nuclei that the flaw resides.</p> - -<p>We see, therefore, that Langdon Brown, discussing gout, is well -justified in observing that, “We may look upon a person who is -readily poisoned by purins in the same light as the person who -has cystinuria, alkaptonuria, or pentosuria, <i>i.e.</i>, they all lack a -link in the chain of protein katabolism, so that intermediate -products appear in the urine instead of the usual end-products.” -In other words, they all display a pathological kinship, viz., in -that they are all due to inborn errors of metabolism.</p> - -<p>Certain broad clinical resemblances also obtain. All members -of the group, including gout, display <i>hereditary</i> tendencies. All -occur much more often in <i>males</i> than in females. They all -alike tend to persist through life. Lastly, their distinctive -chemical products, including uric acid, are all apparently of <i>low -toxicity</i>.</p> - -<p>But when we pass to the realm of their symptomatology, resemblance, -if it does not cease, becomes relatively obscured. Cystinuria -and pentosuria appear to be “harmless anomalies,” and the same -is true of alkaptonuria. The cystinuric, albeit, does suffer with<span class="pagenum"><a id="Page_70"></a>[70]</span> -<i>urinary</i> concretions, and we may recall that some authorities hold -that gout and uric acid <i>calculi</i> are not unrelated. As to alkaptonuria, -it has this attenuated link with gout that in its later stages -the victims thereof tend to develop a degenerative type of <i>arthritis</i>, -while the frequently associated pigmentary change, <i>ochronosis</i>, -has a predilection for deposition in the cartilages of the ears and -<i>joints</i>.</p> - -<p>But how colourless the clinical features of alkaptonuria, etc., -as contrasted with the vivid arresting phenomena of gout! how -remote the latter disorder from these “harmless anomalies”!</p> - -<p>Apart from this general distinction, before gout could with -justice be relegated to the same category of disorders, it would be -necessary to prove that uric acid was an <i>intermediary</i> and not a -terminal product of metabolism. All modern research, however, -tends to indicate that uric acid is an <i>end-product</i>, and, moreover, -that there are no <i>uricolytic</i> ferments within the body whereby its -destruction can be accomplished. The term “chemical malformation,” -therefore, though strictly applicable to alkaptonuria, -cystinuria, etc., is inapplicable to gout. In other words, though, -for example, the <i>homogentisic acid</i> met with in alkaptonuria is a -“chemical malformation,” <i>uric acid</i> cannot be regarded as such. -We see, therefore, that though gout may, superficially regarded, -appear to have kinship with alkaptonuria and its congeners, yet -in reality there is a profound and essential difference between it -and this fascinating group of disorders.</p> - -<hr class="chap x-ebookmaker-drop"> - -<div class="chapter"> - -<p><span class="pagenum"><a id="Page_71"></a>[71]</span></p> - -<h2 class="nobreak" id="CHAPTER_VI">CHAPTER VI<br> -<span class="smaller">NUCLEIN METABOLISM</span></h2> - -</div> - -<p>No hard and fast line can be drawn between the metabolism of -protein and that of nuclein. For though, morphologically speaking, -the <i>nuclei</i> of cells are sharply differentiated from the circumambient -<i>cytoplasm</i>, and exhibit equally distinct staining reactions, -yet, <i>chemically</i>, the differences between them are <i>quantitative</i> rather -than qualitative.</p> - -<p>But while, as far as chemical changes are concerned, nuclein -metabolism is comparable with that of protein, nevertheless the -former in respect of its “energy” and its bearing upon growth and -production, is infinitely more vital, incomparably more active; -for it is in <i>nuclear</i> changes that we may best discern evidence of -the initiation of <i>oxidation</i> processes and other varieties of enzymatic -activity. Moreover, as Walker Hall points out, “the -presence of masked iron phosphorus and certain forms of fat in -the cell nucleus strengthens this view, and thus we are led to -recognise the important part played by the nucleus in the life of -the cell, and to appreciate the influence of nuclein heredity in -cellular exchanges.”</p> - -<p>So much by way of prelude, but the story of the growth of our -knowledge of <i>nuclein</i> as opposed to protein is so fascinating as to -be worthy of a slight digression.</p> - -<h3><span class="smcap">The Isolation of Nucleic Acid</span></h3> - -<p>Functionally regarded, the <i>nucleus</i> is the essential element of -the cell. Embedded within the cytoplasm, its isolation therefrom, -and this in quantities sufficient for analysis, may well have dismayed -the earlier workers. But the resources of Friedrich -Miescher were equal thereto. Treating surgical bandages soaked -with pus with a dilute solution of sodium sulphate, he extracted -the heavy pus cells. These, then, by careful decantation, were -easily disengaged. The pus cells, still intact, were then subjected -to the digestive action of artificial gastric juice. The protoplasm -was thus dissolved, but not the more resistant <i>nuclei</i>, which -remained as an insoluble grey powder. In this manner cell nuclei, -<i>free from protoplasm</i>, became available for chemical analysis. -Treating the insoluble nuclei thus obtained with dilute sodium carbonate, -a solution was formed. Acetic acid added thereto produced<span class="pagenum"><a id="Page_72"></a>[72]</span> -a flocculent precipitate which was found to contain phosphorus, -and responded to protein colour tests. This substance Miescher -christened by the name of <i>nuclein</i>. Subsequent observers prepared -nuclein from the nuclei of <i>yeast</i> cells and the <i>red blood -corpuscles</i> of birds. All nucleins are insoluble acids which form -soluble salts with sodium. But while they respond to protein -colour reactions they differ from <i>protein</i> in that they contain -<i>phosphorus</i> and <i>resist the solvent action of artificial gastric juice</i>.</p> - -<p>Migrating some ten years afterwards (1897) from Tubingen to -Basle, Miescher entered upon his celebrated researches into the -habits of the Rhine salmon. He found the belief had long been -current that the fish, during their passage from the sea up the -Rhine to their spawning haunts, never partook of food. That -this belief was well founded he was able to prove; for, saving -isolated and easily explicable exceptions, he noted that their -alimentary canal was devoid of food <i>débris</i>, while their digestive -juices were as a rule inert. One startling change he noted, that -while, on the one hand, their <i>muscular</i> tissue profoundly wasted -during their migration, their <i>organs of reproduction</i> enlarged -enormously, the inevitable conclusion being that eggs and -spermatozoa had been created from muscle protein.</p> - -<h3><span class="smcap">Researches on Spermatozoa</span></h3> - -<p>Struck by the opportunities for scientific investigation during -the spawning season, Miescher determined to resume his work -upon <i>nuclein</i>. Spermatic fluid or <i>lachsmilch</i>, being readily obtainable -in great quantities, he had to hand a mass of material admirably -adapted for chemical examination of the cell <i>nucleus</i>. The -conclusion that the <i>heads</i> of the spermatozoa might be regarded -as a <i>metamorphosed nucleus</i> seemed obvious, and the opportunity -too good to be lost.</p> - -<p>On examination he found the “sperm heads” protein-free, -made up almost entirely of a single chemical entity, a salt of an -organic base rich in nitrogen and an organic acid containing -phosphorus. The former was <i>protamine</i>, the latter <i>nucleic acid</i>.</p> - -<p>The presence of this salt protamine nucleate led to the conclusion -that nuclein was merely a salt of protein and nucleic acid.</p> - -<h3><span class="smcap">The Discovery of Purins</span></h3> - -<p>Miescher, who had already isolated nuclein and nucleic acid, -came nigh to one other equally important discovery. Heating a -specimen of protamine with nitric acid, he noted that a yellow spot -formed which turned to bright red when moistened with alkali.</p> - -<p>Alive to the import of the reaction, Miescher requested Piccard<span class="pagenum"><a id="Page_73"></a>[73]</span> -to examine salmon sperm for <i>purin</i> bases. Extracting the same -with hydrochloric acid, Piccard found <i>guanine</i>, and what he thought -was <i>hypoxanthine</i>, but which was in truth <i>adenine</i>.</p> - -<p>Another distinguished worker in this sphere, Kossel, noted that, -subjected to the action of hydrolytic agents, nucleins always yield -<i>purin derivatives</i>; also that the same were derived, not from -the <i>protein</i> of the nuclein, but from the <i>nucleic acid</i>. Thus it was -to Kossel that we are indebted for the discovery of the purin -bases, hypoxanthine, xanthine, guanine, and lastly adenine. It -was, indeed, through his brilliant achievements that <i>nucleic acid</i> -became recognisable as a definite entity, distinguishable from -proteins and other body elements, this latter differentiation by -token of the <i>purin bases</i> which are contained in nucleic acid.</p> - -<p>Moreover, it led to the dissipation of the old belief that <i>uric acid</i> -was an intermediate product of <i>protein</i> metabolism, for the -revelation of purin bases as decomposition products of <i>nucleic -acid</i> carried with it the inference that uric acid also had chemical -affinities therewith. The chemical structure of the purin bases -and that of uric acid betrayed a common likeness, and, therefore, -a presumptive physiological connection; in other words, that a -chemical <i>nexus</i> obtained between the cell nucleus or <i>nucleic acid</i> -and uric acid.</p> - -<p>The physiological derivation of uric acid from nucleic acid did -not long lack experimental proof. In 1886 Minkowski found that, -given extirpation of their livers, the urine of birds contained -ammonium lactate, evidently a substitute for the uric acid normally -present, notwithstanding the uric acid never entirely disappeared -from the urine. This indicated the derivation of uric -acid from two sources:—</p> - -<ul> -<li>(1) Conversion in the liver of ammonium lactate into uric acid.</li> -<li>(2) Some other, though unknown, process of formation.</li> -</ul> - -<p>To clear up the obscurity regarding the latter, V. Mach, after -extirpating the livers of geese, injected them subcutaneously with -hypoxanthine, finding that the same was converted into uric acid, -which was excreted in the urine. In this way the capacity of the -organism to elaborate uric acid from a purin precursor was -demonstrated.</p> - -<h3><span class="smcap">Uric Acid a Derivative of Nucleic Acid</span></h3> - -<p>Despite V. Mach’s revelation, the origin of uric acid from -nucleic acid was still to seek. In the year following (1889) -Horbaczewski traced it to this source, and in the following manner. -Mixed with water, the pulp of the calf’s spleen was put to digest -at 50° until putrefaction began. The fluid was then sterilised<span class="pagenum"><a id="Page_74"></a>[74]</span> -with a solution of lead acetate, and arterial blood being added it -was kept at 50°, a current of air meanwhile being passed slowly -through the mixture. Subsequently the fluid was found to -contain <i>uric acid</i>; but the experiment being repeated, without -the passage of air, <i>xanthine and hypoxanthine</i> and not uric acid -resulted.</p> - -<p>While Horbaczewski’s experimental findings were amply confirmed, -some of his deductions therefrom were subsequently -proved faulty. (Thus, he thought putrefaction an essential factor; -also he believed that the formation of uric acid ensued <i>before</i> the -purin groups were disengaged from the nucleic acid, and definitely -affirmed that the uric acid was not produced by the oxidation of -<i>free</i> xanthine or hypoxanthine.)</p> - -<p>But, nevertheless, this pioneer established that in both <i>man</i> and -rabbits <i>uric acid</i> was derived from <i>nucleic acid</i>. Also, having -observed that when after starvation the food intake was resumed, -a <i>leucocytosis</i> occurred, he announced his belief in the following -theory. Thus, he noted that <i>leukæmics</i>, whose blood showed a -high leucocyte count, excreted an unusually large amount of uric -acid; consequently, he came to the conclusion that <i>uric acid</i> was -formed from <i>defunct leucocytes</i>. Also that nuclein-rich food, -when ingested, contributed to the formation of uric acid only in -so far as it induced leucocytosis. Hence the origin of the increased -uric acid excretion which occurs when feeding is resumed after -starvation.</p> - -<p>This increased excretion of uric acid after the ingestion of -food rich in <i>nucleic acid</i> has been amply confirmed; but all -the earlier attempts to achieve an increased excretion by the -ingestion of <i>free</i> purin bases, as opposed to the <i>combined</i> purin -bases, existing as such in <i>nucleic acid</i>, failed, although tried -repeatedly.</p> - -<p>So much for the various stages by which our knowledge of the -purin derivatives of nucleic acid has been gradually acquired, -for though <i>purin bases</i> had, from early times, been known to -exist in <i>animal</i> tissues, their presence there could not be rationally -accounted for prior to the discovery of <i>nucleic acid</i>.</p> - -<p>It still remains for us to deal in detail with the further developments -of our knowledge which concern the <i>disruption of nucleic -acid in the body</i> and the process by which <i>uric acid</i> is derived -therefrom.</p> - -<p>But before proceeding to consider in detail the complex -series or <i>enzymatic</i> transformation that this entails, it will, I -think, be wiser to deal first with the <i>chemistry</i> of uric acid, its -<i>solubilities</i>, and its <i>sources</i>, whether exogenous, endogenous or -synthetic.</p> - -<p><span class="pagenum"><a id="Page_75"></a>[75]</span></p> - -<h3><span class="smcap">The Chemistry of Uric Acid and the Purin Bodies</span></h3> - -<p>Much of the vague philosophy of disease in past times may -fairly be attributed to the complexity and mystery of action -inherent in living matter. The subjects of physics, chemistry and -biology, in their wider acceptation, were unevolved, and scientific -pathology, the offspring of this ancestry, was yet unborn. How -much we owe to physics, chemistry, and biology, those handmaids -of medicine, is inestimable! But something at least of our debt -thereto will be revealed in the following pages.</p> - -<p>Of the purins in human urine, the most important is <i>uric acid</i>, -and far behind comes xanthine, while traces of hypoxanthine, -guanine, and adenine are also detectable. Some years ago the -current view was that the metabolism of any <i>protein</i> gave rise to -<i>uric acid</i>. This assumption has now proved to be erroneous, -for it is known that only certain foodstuffs lead to an increase -in the uric acid excretion; in other words, on a diet rich in -<i>purin</i> the output thereof is considerably higher than on a purin-free -diet, this being due to the large amount of <i>nuclein</i> and purin -bases in flesh foods, especially those containing glandular substances. -Under ordinary conditions the excretion of uric acid -ranges from 0·3-1·2 gm. per diem, or 0·02-0·10 per cent. The -oscillations in output vary with the state of health, diet, and personal -idiosyncrasy.</p> - -<h3><span class="smcap">Chemical Constitution</span></h3> - -<p>The empirical formula of the uric acid molecule, C₅H₄N₄O₃, has -for long been known, but it was reserved for Emil Fischer to -reveal the chemical structure thereof. Through his labours we -now know that uric acid is one of a group of substances which owe -their kinship to their possession in common of the heterocyclic -ring termed by Fischer the “purin nucleus” (1898).</p> - -<p>The intimate relations of the purins of bio-chemical interest -to the purin nucleus, and alike to each other, will be rendered -more intelligible by examination of their structural formulæ as -hereafter given. All, as will be seen, are derivatives of a synthetically -formed body <i>purin</i> which, though unimportant in itself, is -yet interesting in that it is the basic substance from which the -following take origin:—</p> - -<table> - <tr> - <td>Purin</td> - <td>C₅H₄N₄</td> - <td></td> - <td></td> - <td></td> - </tr> - <tr> - <td>Hypoxanthine</td> - <td>C₅H₄N₄O</td> - <td>Monoxy-purin</td> - <td>}</td> - <td></td> - </tr> - <tr> - <td>Adenine</td> - <td>C₅H₃N₄NH₂</td> - <td>Amino-purin</td> - <td>}</td> - <td></td> - </tr> - <tr> - <td>Xanthine</td> - <td>C₅H₄N₄O₂</td> - <td>Dioxy-purin</td> - <td>}</td> - <td>Purin Bases.</td> - </tr> - <tr> - <td>Guanine</td> - <td>C₅H₃N₄ONH₂</td> - <td>Aminooxy-purin</td> - <td>}</td> - <td></td> - </tr> - <tr> - <td>Uric acid</td> - <td>C₅H₄N₄O₃</td> - <td>Trioxy-purin</td> - <td>}</td> - <td></td> - </tr> -</table> - -<p><span class="pagenum"><a id="Page_76"></a>[76]</span></p> - -<p>It now devolves upon us to note the arrangement of the atoms -in the purin nucleus. To each atom is affixed a number indicating -the exact location of the various atoms and groups attached to the -said nucleus. The manner in which the various purin bodies are -built up around the <i>purin nucleus</i> C₅N₄ will become apparent -from a study of the following structural formulæ culled from -Wells’ “Chemical Pathology”:—</p> - -<h3><span class="smcap">Structural Formulæ</span></h3> - -<div class="figcenter illowp100" id="formula01" style="max-width: 31.25em;"> - <img class="w100" src="images/formula01.jpg" alt=""> -</div> - -<p>To describe the individual <i>derivatives of purin</i> we have to indicate -to which particular atom of the <i>purin nucleus</i> the combining -groups are attached. Thus, for example, <i>adenine</i> in structure is -classed as a 6-amino-purin, and accordingly has the following -formula:</p> - -<div class="figcenter illowp100" id="formula02" style="max-width: 12.5em;"> - <img class="w100" src="images/formula02.jpg" alt=""> -</div> - -<p>Other important bodies built up round the purin nucleus C₅N₄, -variously designated as xanthine, alloxuric and nuclein bodies:—</p> - -<div class="figcenter illowp100" id="formula03" style="max-width: 31.25em;"> - <img class="w100" src="images/formula03.jpg" alt=""> -</div> - -<p><span class="pagenum"><a id="Page_77"></a>[77]</span></p> - -<div class="figcenter illowp100" id="formula04" style="max-width: 31.25em;"> - <img class="w100" src="images/formula04.jpg" alt=""> -</div> - -<p>It will be seen that the <i>purin bases</i> stand in very close chemical -relationship to <i>uric acid</i> in that the latter also is marked by the -possession of a group called the <i>purin nucleus</i>; indeed, the -relationship of uric acid to the purin bases is more intimate than -to <i>urea</i> (CON₂H₄), close though this latter be as may be seen from -the study of its constitutional formula. (For uric acid may be -regarded as composed of two urea radicles, linked by a tricarbon -chain. By oxidation and hydrolysis, two molecules of urea may -be obtained from one of uric acid, and conversely uric acid is produced -by the condensation of urea with hydroxy acids).</p> - -<p>The first product of the <i>oxidation</i> of purin is <i>hypoxanthine</i>, -long recognised as a constituent of meat extracts. <i>Adenine</i>, the -amino derivative of hypoxanthine, is met with in combination -with other substances in <i>nuclear</i> material. The second oxidation -product of purin is <i>xanthine</i>, and its amino derivative <i>guanine</i>, -both of which are found in the same substances as hypoxanthine -and adenine. Further oxidation of purin gives rise to <i>uric acid</i>. -We have to recognise, also, that in addition to the purins of animal -origin there are some also derived from <i>vegetables</i>, viz., the <i>methyl</i> -purins, caffeine, theobromine, and theine.</p> - -<p>Now, as will be seen later, certain compounds, containing -nitrogen and phosphorus, constitute the chief, if not the exclusive, -source of <i>uric acid</i>. These substances, long known as <i>nucleins</i> or -<i>nucleo-proteins</i>, exist in the animal tissues, and in special abundance -in those largely made up of cell nuclei, viz., thymus, lymph-glands, -etc. The important and, indeed, the distinguishing component -of the nucleins or nucleo-proteins is <i>nucleic acid</i>. This, in -that through the action of ferments, it is from the nucleic acids -that <i>uric acid</i> and the <i>purin bases</i> are derived.</p> - -<p>But, apart from this, we have to recollect that nucleic acids yield -constituents other than purin bases, viz., the <i>pyrimidine bases</i>, -phosphoric acid, and a carbohydrate group. From a study of the -structural formulæ of the pyrimidine bases it will be seen that they -are closely related to the purin bases, lacking, however, one of -the <i>urea</i> radicles. Moreover, it is believed that, though included<span class="pagenum"><a id="Page_78"></a>[78]</span> -in the makeup of nucleic acid, they are not derived from purin -but are <i>primary</i> products.</p> - -<div class="figcenter illowp100" id="formula05" style="max-width: 31.25em;"> - <img class="w100" src="images/formula05.jpg" alt=""> -</div> - -<p>To sum up, the characteristic constituents of <i>nucleic acid</i> are -the purin bases (adenine, guanine, hypoxanthine, and xanthine), -pyrimidine bases (uracil, cytosine, thymine), phosphoric acid and -a carbohydrate group.</p> - -<p>We have now discussed the <i>chemical structure</i> of uric acid and -its relationship to the <i>purin bases</i>; but before proceeding to -consider the various sources from which uric acid is derived, it will -I think be convenient to consider (1) the physical properties of -uric acid and (2) the condition in which it circulates in the blood.</p> - -<h3><span class="smcap">Properties of Uric Acid</span></h3> - -<p>When pure, uric acid is white in colour and crystallises in -rhombic form. In contrast to <i>urea</i> it is very insoluble, but much -less so in <i>blood serum</i> than in distilled water, viz., ⅟₄₀₀₀₀ of water -as opposed to ⅟₁₀₀₀ parts of plasma. It yields with alkalies two -series of salts, viz., the biurate or mono-basic, and the so-called -neutral or bi-basic urate, the latter of which is much more -soluble. In water the mono-basic urate forms a colloidal solution -from which the crystalline salt gradually precipitates.</p> - -<p>The greater solubility of uric acid in blood plasma was, by -Garrod and Haig, attributed to the <i>alkalinity</i> of the plasma. But -it must be recalled that the earlier workers in this sphere judged of -the alkalinity of the plasma by its reaction to <i>litmus</i>, a crude procedure -as compared with the use of <i>phenol-phthalein</i>, and Frankel’s -<i>electro-potential</i> measurements. Working with these as criteria, -it has been shown that blood is normally <i>alkaline</i> in only a <i>minority</i> -of cases, and indeed, according to Flack and Hill, the plasma is in -reality <i>neutral</i>.</p> - -<p>In the <i>urine</i> uric acid and the urates are held in solution by the -neutral <i>phosphates</i>. This because the decomposition of the urates -into uric acid by the acid salts of the urine is inhibited by the di-sodium -phosphate present therein. Its maintenance in solution -is possibly also reinforced through the influence of other constituents -in the urine, notably, the urinary pigments and sodium -chloride.</p> - -<h3><span class="smcap">Uric Acid in the Blood</span></h3> - -<p>As to the form in which uric acid circulates in the blood, Sir -William Roberts believed that when dissolved in blood serum it -was transformed into the relatively soluble sodium <i>quadriurate</i>.<span class="pagenum"><a id="Page_79"></a>[79]</span> -This authority held that in gout, either through deficient excretion -or over-production, the quadriurate accumulates in the blood. -Circulating therein, in a medium rich in sodium carbonate, it takes -up an additional atom of the base, and is transmuted into the -<i>biurate</i>, which is less soluble and less easily excreted by the -kidneys; consequently, the biurate is hoarded up in the blood, at -first in gelatinous, and later in an almost crystalline form, when its -precipitation is imminent or actually ensues. This, moreover, was -apt to occur at sites where the circulation was poor, the temperature -low, and more particularly in regions in which the plasma -contained a relatively high percentage of sodium chloride, <i>e.g.</i>, -synovial sheaths.</p> - -<p>But, unfortunately for the valency of this otherwise plausible -theory, it was proved by Tunnicliffe, Rosenheim, and others, that -<i>quadriurates</i> do not exist as definite chemical compounds; in -short, it is generally conceded that their existence should no -longer be accepted.</p> - -<h3><span class="smcap">Gudzent and Schade’s Theories</span></h3> - -<p>Gudzent was of opinion that uric acid can only exist in the -blood as the <i>mono-sodium-urate</i>, of which there are two isomeric -varieties, the easily soluble unstable <i>lactam</i>, and the stable relatively -insoluble <i>lactim</i> urate. It is the former, or lactam, variety -that accumulates in the blood in gout and, according to Gudzent, -it is the transmutation thereof into the lactim modification that -determines the precipitation of urates in the tissues. The lactim -urate is soluble only to the extent of 8·3 mg. per 100 cc. serum, -whereas the lactam form is soluble up to 18 mg.</p> - -<p>Others, like Bechhold, maintain that the urates are present in the -blood in a <i>colloidal</i> form, impossible of excretion by the kidneys. -Thus Schade contends that, in the presence of alkalies (hydrates), -uric acid or its salts may pass into a state in which it is far more -soluble than usual. Moreover, on its path to crystallisation from -this over-saturated solution, it passes through a <i>colloid</i> stage in -which it is relatively stable. The maintenance of this colloid -stage and consequently the retardation of precipitation is promoted -by certain substances, <i>i.e.</i>, glycerine, urea, serum, albumen, -nucleic acid, etc. But hitherto the therapeutic possibilities suggested -have not been invoked.</p> - -<h3><span class="smcap">Organic Combinations</span></h3> - -<p>It will be recalled that purin bodies cannot be detected in the -<i>blood</i> in health, though their administration by the mouth results -in an increase in the excreta. Minkowski, to account for this, -suggested that the purins in the blood were circulating in a combination<span class="pagenum"><a id="Page_80"></a>[80]</span> -which prevented them from giving the usual reactions, -typical of their presence therein. We have an analogy in the -masking of arsenic and iron in the cacodyl compounds and the -ferrocyanide ion.<a id="FNanchor_8" href="#Footnote_8" class="fnanchor">[8]</a></p> - -<p>The explanation proffered by Minkowski was elaborated by -Von Noorden. His view was that lying at the disposal of the -normal organism are a certain number of organic substances. -These latter can combine with uric acid and render it soluble. -It is then in this form passed through the blood in the kidneys, -which eliminate from it the uric acid. Now, in gout these organic -substances are deficient or wanting, and the result is that the -uric acid is passed into the blood in the form of <i>urates</i>, the elimination -of which only proceeds with difficulty; in other words, the -purins normally circulate in <i>organic</i> combination and abnormally -as <i>salts</i> of <i>sodium</i>.</p> - -<p>It is worthy of note that, from a solution containing albuminous -substances, Burian and Walker Hall found that while it was easy -to remove the bulk of the purins, a certain percentage always -remained which it was difficult to extract.</p> - -<p>The view that uric acid is probably carried in the blood in -combination with some other organic body and not, as was formerly -supposed, with sodium salts, rapidly gained adherents, -but the nature of the organic complex is still not accurately known. -Many believe that at least a moiety of the uric acid circulates in -combination with <i>nucleic</i> (thyminic) <i>acid</i>, but no such compound -has yet been isolated from the blood. Nevertheless, as MacLeod -suggests, this theory, were it proved correct, would account for the -fact that some purins at least are katabolised in the body when -they are given in a combined state, as <i>thyminic acid</i>, but are -excreted unchanged when ingested in a free state. Thus, certain -purins, <i>e.g.</i>, <i>adenine</i>, when given freely, cause inflammation and -calculous deposits in the kidneys of dogs which, however, does not -ensue when they are fed with thymic acid.</p> - -<p>But Walker Hall, discussing the good results obtained by -Schmoll and Fenner from the administration of thyminic acid,<span class="pagenum"><a id="Page_81"></a>[81]</span> -states that his experiments do not indicate that the improvement -is at all associated with any change in the <i>uric acid</i> excretion.</p> - -<p>To sum up, it is obvious, from the mere variety of the hypotheses -advanced, that we are still much in the dark as to the actual -form in which uric acid circulates in the blood. While on the one -hand the quadriurate theory appears no longer tenable,<a id="FNanchor_9" href="#Footnote_9" class="fnanchor">[9]</a> on the -other the nature of the suggested uric acid organic complex is still -unknown.</p> - -<p>Nay, more, Walker Hall, writing in 1913-14, states “there are -many who consider that the <i>sodium mono-urate</i> is the only possible -compound;” while Wells, in his “Chemical Pathology” (1918), -claims that the best evidence points to uric acid existing in the -blood “in a <i>free</i> state and not combined, as was at one time urged -by several students of gout.”</p> - -<h3><span class="smcap">Complexity of the Problem</span></h3> - -<p>How complex, indeed, the task of the bio-chemist may be -gathered from some reflections of Walker Hall. He reminds us -that the oxidation and deaminisation of the nuclein derivatives, -nucleins, nucleotides and nucleosides, is never complete. For -<i>purin bases</i> and <i>pyrimidin</i> bases run side by side in the blood-stream -together with uric acid. Also, that the unstable but -soluble biurate is constantly changing into a less soluble type, -viz., from one isomer to another. Moreover, since the red blood -corpuscles abound in potassium, urates of <i>potassium</i> must also -occur, and to these may be added, too, ammonium and calcium -compounds in small quantities.</p> - -<p>But more striking is his inference that the occurrence of -<i>isomeric forms</i> of <i>uric acid</i> suggests that <i>isomers</i> of <i>purins</i> and -<i>pyrimidins</i> also may occur. For the purin ring or pyrimidin -nucleus, with their numerous receptors for the linking up of other -substances, offer wide potentialities in the direction of isomerism.<a id="FNanchor_10" href="#Footnote_10" class="fnanchor">[10]</a> -Some of these, he hazards, may be born of one type of cell nucleus, -some of another, while it is not inherently improbable that, “In<span class="pagenum"><a id="Page_82"></a>[82]</span> -response to abnormal stimuli or excessive demand, other isomers -may be formed.”</p> - -<p>Now, though uric acid and the urates can be extracted from the -blood, it does not, as he remarks, necessarily follow that they -circulate as such <i>in vivo</i>; for, despite modern achievements, -“the best of the existing methods for the determination of uric -acid in the blood are nearly barbarous in their crudity and -intensity.” The various procedures available for such estimates -fall short of distinction between the several tautomeric forms of -uric acid, much less do they furnish any information as to the -associations or combinations of purins or pyrimidins with other -substances.</p> - -<p>For himself, recognising the generally more complex nature of -biological processes, he considers that “the circulation of the -purins as sodium mono-urate and its simple extraction by kidney -cells, seems almost too simple to be true.”</p> - -<p>As to the <i>solubilities</i> of uric acid and urates in gouty blood he -points out that the suspension capability of the blood-stream for -uric acid much transcends the highest amount of uric acid as yet -found in the gouty subject. Accordingly, to him, therefore, it -seems that “neither chemical nor physico-chemical processes -suffice to explain the problem. There must be something more, -something vital, biological.”</p> - -<p>Having ascertained as far as possible the measure of our knowledge -in regard to the foregoing points, we shall, in the succeeding -chapter, proceed to discuss the <i>sources</i> of <i>uric acid</i>, whether of -intrinsic or extrinsic origin.</p> - -<hr class="chap x-ebookmaker-drop"> - -<div class="chapter"> - -<p><span class="pagenum"><a id="Page_83"></a>[83]</span></p> - -<h2 class="nobreak" id="CHAPTER_VII">CHAPTER VII<br> -<span class="smaller">SOURCES OF URIC ACID</span></h2> - -</div> - -<p>Uric acid, like the “purin bodies” (xanthine, hypoxanthine, -guanine, and adenine), is derived from <i>nucleins</i>, <i>i.e.</i>, from the -breaking down of tissues rich in cells. The end-product of purin -or nuclein katabolism <i>uric acid</i> represents but a further stage in -the oxidation of the <i>purin</i> bodies. To the serial enzymatic -transformations that mark its derivation from <i>nucleic acid</i> we -shall allude later, but at this juncture we are concerned not with -the <i>mode</i> of <i>formation</i> of uric acid, but with the sources thereof.</p> - -<p>In this sphere we are greatly indebted to the pioneer researches -of Burian and Schur. These observers noted that on a diet rich -in <i>nucleins</i> (sweetbreads, liver, kidneys) the total daily excretion of -uric acid was considerably higher than on a milk or purin-free -diet. This difference in response to varying dietaries, in respect -of the excretion of uric acid, led Burian and Schur to the conclusion -that the purins excreted must be partly of <i>exogenous</i> and -partly of <i>endogenous</i> origin; in other words, the exogenous -purins are derived from the nucleins ingested in the food, whereas -the endogenous are the outcome of the breaking down of the -cellular tissue of the organism itself.</p> - -<p>Here it may be noted that all the ingested purins are not -excreted in the urine as uric acid, for some pass away as <i>purins</i>. -Moreover, the amount excreted will vary with the kind of purin -ingested, and also with the <i>species</i> of the animal that consumes it. -Thus, in man “only one half of the hypoxanthine administered as -such appears as uric acid in the urine, and but one fourth of the -purin in nuclein when that is fed. In the dog, compared with -man, about ten times as much purin disappears in its passage -through the organism; in the rabbit, about three times” (Flack -and Hill).<a id="FNanchor_11" href="#Footnote_11" class="fnanchor">[11]</a></p> - -<p>In amount about 0·4-0·7 gramme of uric acid is excreted in -<i>human</i> urine daily, and the purin bodies, hypoxanthine, xanthine, -and adenine, in small quantities.</p> - -<p><span class="pagenum"><a id="Page_84"></a>[84]</span></p> - -<p>Beyond exogenous and endogenous purins there is yet one other -possible source of uric acid, viz., its <i>synthetic formation</i> within the -organism. This supposition took origin in Horbaczewski’s discovery -that in the laboratory he was able to produce uric acid by -the interaction of <i>urea</i> and <i>glycocine</i>, a finding afterwards confirmed -by Latham. The theory was then advanced that a similar -synthesis might be effected by the <i>kidneys</i>; but it was found -that glycocine and urea, even when given in excess to mammals, -caused no change in the uric acid excretion.</p> - -<p>So much by way of preface to our detailed discussion <i>seriatim</i> -of the various sources of uric acid, and to which we now pass on.</p> - -<h3><span class="smcap">Exogenous Purins</span></h3> - -<p>The foodstuffs that cause an increase in purin excretion are -divisible into three groups:—</p> - -<ul> -<li>(<i>a</i>) Amino-purins.</li> -<li>(<i>b</i>) Oxy-purins.</li> -<li>(<i>c</i>) Methyl-purins.</li> -</ul> - -<p><i>Amino-purins.</i>—In man the taking of food rich in nucleated -cells and therefore in nucleo-protein and nucleins, increases the -quantity of uric acid in the urine. Thymus gland, pig’s pancreas, -and herring roe, containing the characteristic conjugated proteins -of nuclei, or Liebig’s meat extract, rich in purin bases, when -ingested, lead to a distinct increase in purin excretion.</p> - -<p>The researches of Kossel and Horbaczewski showed that such -augmentation was mainly due to the production of uric acid from -the <i>nuclein</i> substances of the food; in other words, it was due to -the katabolism of <i>nuclein</i>, the cleavage products of which comprise -<i>adenine</i> derived from thymus, and <i>guanine</i> from the pancreas, -both of these bodies being amino-purins. According to Burian -and Schur, of the amino-purins ingested, a fourth is excreted as -purin.</p> - -<p><i>Oxy-purins.</i>—To this group belong xanthine and hypoxanthine. -These substances occur in muscle, and in great abundance in meat -extract, and Minkowski noted that the ingestion of xanthine bases -markedly augmented the amount of uric acid excreted. In man, -given ingestion of hypoxanthine as such, only one half thereof -appears as uric acid in the urine. It may here be mentioned that -not all the purin bases ingested exist bound up in the nuclein -substances. An appreciable amount is present in the tissues in -a <i>free</i> state, <i>e.g.</i>, hypoxanthine in the muscles; consequently, a -moiety of the intake of purin bodies, especially in the animal -constituents of the food, is to hand ready formed, and does not -require the disruption of <i>nucleic acid</i> for its liberation.</p> - -<p><span class="pagenum"><a id="Page_85"></a>[85]</span></p> - -<p><i>Methyl-purins.</i>—The nuclei of <i>vegetable</i> cells also contain -nucleo-protein, and, therefore, can add their quota to the purin -intake. The most important are <i>caffeine</i>, <i>theobromine</i>, and -<i>theophyllin</i>, the active principles of tea, coffee, and cocoa. It may -here be recalled that of the purins administered in food, not all -are excreted as uric acid, but some as <i>purins</i>. Now it is doubtful -whether the <i>methyl-purins</i> lead to the formation of <i>uric acid</i> in -the organism, or whether they are excreted as purin bases in the -urine. According to Stewart, a fractional part of the <i>purin bases</i> -in the urine is composed of heteroxanthine, 1-methyl-xanthine, -and paraxanthine derived from the active principles of coffee, -tea, and cocoa when consumed as beverages. As stated by Burian -and Schur, one third of the methyl-purins ingested is excreted as -purin.</p> - -<p>From the foregoing data it will be obvious that the <i>exogenous</i> -urinary purins are derived from <i>nuclein</i> and certain <i>free xanthine -bases</i>, and that the influence of other nitrogenous foodstuffs in -this direction is practically negligible.</p> - -<h3><span class="smcap">Exogenous Uric Acid Excretion</span></h3> - -<p>As to the amount of exogenous purins that, when administered -orally, can be recovered from the urine, it would appear that a -certain rough parallelism obtains between the purin content of -the food and that of the urine. The amount of the exogenous -urinary purin differs for different forms of food, a variation well -illustrated by the following table, giving the results of Burian and -Schur’s researches.</p> - -<table class="borders"> - <tr> - <th>Diet.</th> - <th>Total percentage<br>of purin substances<br>in diet.</th> - <th>Percentage of<br>exogenous<br>urinary purin.</th> - </tr> - <tr> - <td>Beef</td> - <td class="tdr">0·06</td> - <td class="tdr">0·030</td> - </tr> - <tr> - <td>Coffee</td> - <td class="tdr">0·20</td> - <td class="tdr">0·075</td> - </tr> - <tr> - <td>Calf’s liver</td> - <td class="tdr">0·12</td> - <td class="tdr">0·060</td> - </tr> - <tr> - <td>Calf’s spleen</td> - <td class="tdr">0·16</td> - <td class="tdr">0·080</td> - </tr> - <tr> - <td>Calf’s thymus</td> - <td class="tdr">0·40</td> - <td class="tdr">0·100</td> - </tr> -</table> - -<p>Walker Hall, experimenting with various purin-containing -foods, found that (1) with chicken 54·4 per cent., (2) with plaice -58·7 per cent., (3) with beef 47·4 per cent., (4) with haricot beans -55 per cent. of the food purin appears in the urine as exogenous -purin. These findings of Walker Hall’s, like Burian’s and Schur’s,<span class="pagenum"><a id="Page_86"></a>[86]</span> -reveal that, roughly speaking, 50 per cent. of the purin content -in food is excreted in the urine.<a id="FNanchor_12" href="#Footnote_12" class="fnanchor">[12]</a></p> - -<p>These figures must be taken as a broad average relating only to -healthy individuals upon diets capable of perfect assimilation.</p> - -<p>More recently, Mendel and Lyman found that about 60 per cent. -of injected hypoxanthine, 50 per cent. of xanthine, 19-30 per cent. -of guanosine, and 30-37 per cent. of adenine were excreted in the -form of <i>uric acid</i>. While this is true of free purins, on the other -hand, when <i>bound</i> purins, <i>i.e.</i>, nucleins are administered, only a -small proportion thereof appears as uric acid in the urine. But -before proceeding to canvass the fate of the missing purin, it -will, we think, be helpful if we interpolate here a table (Taylor and -Rose), illustrative of the variations in uric acid excretion that -attend a <i>purin</i> as opposed to a <i>purin-free</i> diet.</p> - -<p>The subject of the experiment was, for three days, fed on a -purin-free diet of milk, eggs, starch and sugar. At the end of this -period a portion of the total nitrogen (3 grams) was administered -in the form of <i>sweetbreads</i>, thymus gland, etc., with a high percentage -content (0·482) of purin nitrogen. During the succeeding -four days still more (6 grams) of the total nitrogen was replaced -by sweetbread nitrogen. Subsequently the person was placed -on the original purin-free diet.</p> - -<table class="borders"> - <tr> - <th></th> - <th>First period.<br>Purin-free diet.</th> - <th>Second period.</th> - <th>Third period.</th> - <th>Fourth period.<br>Purin-free diet.</th> - </tr> - <tr> - <td>Total urinary N</td> - <td class="tdr"><span class="sp2">8·9</span></td> - <td class="tdr"><span class="sp2">8·7</span></td> - <td class="tdr"><span class="sp2">9·1</span></td> - <td class="tdr"><span class="sp2">8·8</span></td> - </tr> - <tr> - <td>Urea N and NH₂</td> - <td class="tdr"><span class="sp2">7·3</span></td> - <td class="tdr"><span class="sp2">7·1</span></td> - <td class="tdr"><span class="sp2">7·1</span></td> - <td class="tdr">7·05</td> - </tr> - <tr> - <td>Creatine</td> - <td class="tdr">0·58</td> - <td class="tdr">0·55</td> - <td class="tdr">0·56</td> - <td class="tdr">0·47</td> - </tr> - <tr> - <td>Purin N (total)</td> - <td class="tdr">0·11</td> - <td class="tdr">0·17</td> - <td class="tdr">0·26</td> - <td class="tdr">0·10</td> - </tr> - <tr> - <td>Uric acid N</td> - <td class="tdr">0·09</td> - <td class="tdr">0·14</td> - <td class="tdr">0·24</td> - <td class="tdr">0·07</td> - </tr> - <tr> - <td>Remainder N</td> - <td class="tdr">0·91</td> - <td class="tdr">0·88</td> - <td class="tdr">0·18</td> - <td class="tdr">1·18</td> - </tr> -</table> - -<p>From a study of the table it will be noted that, following the -introduction of sweetbreads rich in <i>nucleins</i>, the uric acid content -of the urine markedly increased, to sink again when a purin-free -diet was substituted. But it will be seen also, as MacLeod points -out, that “the increase of uric acid accounted for less than half -of the purin nitrogen ingested. This appeared as uric acid, the -excretion of purin bases being practically unchanged.” In other -words, a moiety of the bound purins, <i>i.e.</i>, nucleins ingested, appears -as uric acid in the urine.</p> - -<p><span class="pagenum"><a id="Page_87"></a>[87]</span></p> - -<h3><span class="smcap">Fate of the Unexcreted Purin</span></h3> - -<p>As to what becomes of that portion of the ingested purin that, -so to speak, disappears in the body, is largely a matter of speculation. -As MacCallum states, “the liberation of guanine and -adenine is well in the line of uric acid formation,” but “the fate -of the pyrimidin groups, thymine and cytosine, is still uncertain.” -According to this observer, Levene has hitherto been unable to -find an enzyme which will decompose the <i>nucleoside</i> in which they -occur, and that since they cannot form uric acid, they are possibly -excreted as <i>urea</i> or in other forms. He adds that only 50 per cent. -of the nucleic acid nitrogen can be counted on for the production -of <i>uric acid</i>, viz., that in the guanine and adenine groups.</p> - -<p>MacLeod, discussing this same point, suggests that some of the -unrecovered purin may undergo decomposition in the intestine, -but why so much should, after absorption of the blood, disappear -is, as he remarks, difficult of explanation; for while <i>uricase</i>, -which can decompose uric acid, exists in the tissues of the lower -animals, no such ferment is found in man, and uric acid is excreted -as such. According to MacLeod, too, “the destroyed purins -cannot be shown to influence any of the other well-known nitrogenous -metabolites of the urine.”</p> - -<p>Lastly, Stewart, discussing the ultimate destiny of the absorbed -products of <i>nucleic acid</i> digestion, suggests that, when undergoing -further cleavages, “they may be in part utilised for the synthesis -of nucleo-proteins, replacing those destroyed in the process of cell -metabolism;” or, that it is “possible that they may be wholly disrupted -into their components, and these again re-synthesised.”... -“Finally, and this fate is probably not long delayed in the case of -the surplus of purin compounds contained in ordinary dietaries, -both the purins of the food and the purins arising from the waste -of the tissues, are for the most part converted into uric acid and -excreted in the urine.”</p> - -<p>Also, it should be recollected that the purin bases normally -found in human <i>fæces</i> are in part of <i>exogenous</i> origin, and are -increased in amount after the ingestion of meat extract or thymus.</p> - -<h3><span class="smcap">Endogenous Purins</span></h3> - -<p>Even if we entirely eliminate all purin substances, by restricting -the diet to <i>purin-free</i> foodstuffs (bread, milk, cheese, eggs and -butter), purin in the form of <i>uric acid</i> is still excreted in the urine.</p> - -<p>To this moiety the term <i>endogenous</i> purin is applied; for the -continued excretion of purin on such a diet is explicable only on -the view that they are derived from the waste of the tissues, the<span class="pagenum"><a id="Page_88"></a>[88]</span> -daily “wear and tear” of cells. In other words, it is the outcome -of the katabolism of the <i>nucleo-protein</i> of the body tissues.</p> - -<h3><span class="smcap">Source of Endogenous Purins</span></h3> - -<p><i>Is the nuclear destruction of localised or generalised distribution?</i></p> - -<p>Mares (and subsequently many other observers), having noted -that, following the ingestion of <i>purin-free</i> protein food, a marked -increase in endogenous uric acid excretion ensued, suggested that -the said augmentation was the outcome of the “wear and tear” -entailed upon the nuclear material of the <i>secretory glands of the -gastro-intestinal tract</i>, following such intake.</p> - -<p>The effects yielded on uric acid excretion by those antithetic -drugs, atropine and pilocarpine, certainly seem to lend colour to -Mares’ hypothesis.</p> - -<p>Following the injection of <i>atropine</i>, the rise in uric acid output, -that normally follows the ingestion of protein, was inhibited. But -in sequence to <i>pilocarpine</i>, an <i>excitant</i> and not like <i>atropine</i>, a -depressor of secretory activity, a marked increase in uric acid -excretion followed. The contrast in response was naturally -translated as striking evidence of the important <i>rôle</i> played by the -<i>digestive glands</i> on uric acid excretion; in other words, it was -held that the major portion of the endogenous uric acid was the -reflex of such intensified glandular action.</p> - -<p>In opposition, however, Burian, as the outcome of his experimental -studies, maintained that a <i>fractional</i> portion only of the -endogenous uric acid could be derived from the <i>nucleo-protein of -the body cells</i>. This, inasmuch as it would entail a far too extensive -katabolism of nuclear substance. Accordingly he propounded -the view that the endogenous uric acid in the main was derived -from the <i>hypoxanthine</i> of the <i>inosinic</i> acid present in <i>muscular</i> -tissue. In this connection it may be noted that, on a diet approximating -to Voit’s standard, 0·5 gram of purin is excreted daily. -This, it is calculated, is equivalent to nearly 100 grams of thymus -or allied tissue, which probably far exceeds the amount that could -be gleaned from cellular katabolism.</p> - -<h3><span class="smcap">Proteins and their Derivatives</span></h3> - -<p>A comparison of the influence of <i>proteins</i> as contrasted with that -of their digested products, the <i>amino-acids</i>, it was thought, might -furnish a clue as to the extent of which the alleged activity of the -<i>digestive glands</i> was responsible for the increased uric acid output -that followed the intake of non-purin protein food.</p> - -<p>Such was the supposition entertained by H. B. Lewis, M. S. -Dunn, and E. A. Doisy. Alive, moreover, to the deficiency of<span class="pagenum"><a id="Page_89"></a>[89]</span> -the older procedure in use for the determination of small amounts -of uric acid, Lewis and his collaborators invoked the more accurate -colorimetric method of Folin and Denis (as modified by Benedict -and Hitchcock).</p> - -<p>The experiments were conducted with great care, and with as -complete control as possible of the variable factors concerned. -The investigators realised that, if any significance was to be -attached to fluctuations in uric acid excretion following the intake -of proteins and their derivatives, it was essential that accurate -information be obtained as to the extent of the <i>variations</i> to be -expected <i>normally</i> in the subjects when <i>fasting</i>. “Controls,” -therefore, in which no food was consumed throughout the experiments, -were instituted at frequent intervals so as to make sure that -the level of endogenous uric acid metabolism was not altered by -the long-continued <i>purin-free</i> diet.<a id="FNanchor_13" href="#Footnote_13" class="fnanchor">[13]</a></p> - -<p>Passing now to the results obtained, it was noted that, after the -intake of three types of <i>purin-free</i> protein food (egg white, cottage -cheese, and glidine), there ensued <i>a rise in uric acid output</i>, reaching -its maximum during the third or fourth hour after their intake. -No quantitative differences in the uric acid output after ingestion -of these three types of protein were observed; in short, the -findings did but confirm what had been repeatedly demonstrated, -viz., that the <i>excretion of the endogenous uric acid is increased by -purin-free protein food</i>.</p> - -<h3><span class="smcap">Amino-Acids and Dicarboxylic Amino-Acids</span></h3> - -<p>But the further interesting fact emerged, viz., that <i>glycocoll</i> and -<i>alanine</i>, end-products of protein digestion, also <i>augmented</i> uric -acid excretion; moreover, this even more swiftly than <i>proteins</i>, -the maximum being reached within two hours after their intake.</p> - -<p>In addition, like results followed the ingestion of the <i>dicarboxylic</i> -amino-acids (glutaminic and aspartic acids), the increase in endogenous -uric acid excretion being even more pronounced than with -glycocoll or alanine.</p> - -<p><span class="pagenum"><a id="Page_90"></a>[90]</span></p> - -<p>Now, it must be recalled that the <i>amino-acids</i> represent the <i>end-products</i> -of protein digestion. Accordingly, Lewis and his co-workers -argue that “since no digestive processes are required for -the utilisation of amino-acids, it can hardly be considered that -the <i>rises in endogenous uric acid</i> observed following the ingestion -of four different amino-acids can be attributed to the <i>work of -the digestive glands</i>.” The effect, they held, is more probably -attributable to “a direct stimulation of the body cells by amino-acids -or their katabolism products, a stimulation of nuclear metabolism,” -for it is known that amino-acids disappear very swiftly -from the <i>blood-stream</i> to be stored up temporarily in the <i>tissues</i>.</p> - -<p>The question that now confronted the observers was whether -the stimulation of nuclear metabolism was an <i>inherent</i> property of -amino-acids. If so, “<i>substituted</i> amino-acids might be expected -to exert a similar influence.” But, if on the contrary, it was due -not to the amino-acids as such but “either to the cellular work of -their katabolism or to the intermediary products of their breakdown, -a substituted amino-acid which does not follow the normal -path of amino-acid catabolism would in all probability be devoid -of the power of stimulation.”</p> - -<p>To this end, they selected <i>sarcosine</i> or <i>methyl-glycocoll</i> to elucidate -the point at issue; this, inasmuch as it has been found to -pass through the organism for the most part unchanged. The -result justified their inference, for <i>no</i> perceptible influence on uric -acid excretion was noted. Hence, on the basis of this experiment, -they inferred that the stimulation of uric acid metabolism was not -an <i>inherent</i> property of <i>amino-acids</i>; in other words, that if an -amino-acid when ingested does not undergo disruptive katabolism, -it is without effect on uric acid excretion.</p> - -<p>Now <i>deaminisation</i> is the first stage in the katabolism of <i>amino-acids</i>, -yielding as products <i>ammonia</i> and <i>a-ketonic</i> or <i>hydroxy acids</i>. -The ammonia thus formed normally undergoes conversion into -<i>urea</i> and is excreted as such. In order to ascertain whether the -<i>ammonia</i> stimulated uric acid excretion, <i>ammonium chloride</i> was -administered, but no rise in the uric acid output above the -normal level ensued. Also, the ingestion of <i>urea</i> seemed to entail -no appreciable increase in the uric acid elimination; in other -words, these katabolic products of the <i>nitrogenous</i> moiety of the -amino-acids are without effect. As to the <i>non-nitrogenous</i> intermediary -products of the katabolism of amino-acids, <i>i.e.</i>, the -<i>a-ketonic</i> or <i>hydroxy acids</i>, it was impossible to investigate the -influence of these on the endogenous uric acid elimination.<a id="FNanchor_14" href="#Footnote_14" class="fnanchor">[14]</a></p> - -<p><span class="pagenum"><a id="Page_91"></a>[91]</span></p> - -<p>Lusk also has brought forward evidence that in the presence of -amino-acids cellular activities are intensified markedly. According -to Taylor and Rose, too, not only <i>nuclear katabolism</i>, but also -<i>nuclear anabolism</i>, may be accelerated by the presence of large -amounts of amino-acids.</p> - -<p>Lewis and his collaborators consider that the results of their -researches militate against Mares’ hypothesis, viz., that the origin -of the increased amounts of endogenous uric acid that follow the -intake of purin-free protein stuffs is referable to <i>intensified activity -of the digestive glands</i>.</p> - -<p><i>They hold that “it can be accounted for equally well as the result -of a general stimulation of all cellular metabolism by the products of -digestion of proteins the amino-acids.”</i></p> - -<p>The recorded increases in endogenous urinary purin are, they -consider, far too great to be the outcome of the stimulation of so -small a proportion of the cells of the body as those of the digestive -tract. On the other hand, they do not deem it necessary to -assume that the whole of the endogenous uric acid is the outcome -of <i>nuclear</i> disruption, concurring with Burian’s view, that a moiety -thereof may be derived from the <i>hypoxanthine</i> of <i>muscular</i> tissue.</p> - -<h3><span class="smcap">Endogenous Uric Acid Excretion</span></h3> - -<p>The researches of Leathes and his collaborators permit the -deduction that endogenous uric acid excretion bears a definite -relation to the activity of cellular processes. Given unchanged -physiological conditions, <i>e.g.</i>, muscular exercise, the amount of the -endogenous uric acid excreted is, for the same individual, fairly -<i>constant</i>, and this <i>irrespective of diet</i>; but it is not the same for -<i>different</i> individuals, even those of identical body weight.</p> - -<p>According to MacLeod, the endogenous excretion in an adult -man fluctuates between 0·12 and 0·20 per cent. purin nitrogen. -The average daily endogenous uric acid output of a normal adult, -as stated by Walker Hall, is about 0·5 gram, while that of a gouty -individual is 0·45 gram.</p> - -<p>Now Burian and Schur’s original contention was that, in a given -individual on a <i>purin-free</i> diet, the endogenous purin output was -<i>constant</i>, and this despite <i>marked</i> variations in the amount of the -purin-free food digested.</p> - -<p>Recent researches, however, of Folin and of Hopkins and Hope, -indicate that this dictum must be modified to this extent, viz.,<span class="pagenum"><a id="Page_92"></a>[92]</span> -that although it is true that the endogenous excretion continues -remarkably constant, with <i>moderate</i> variations in the amount of -purin-free food, it is not so in the presence of <i>marked</i> variations.</p> - -<p>The subject (Hopkins and Hope), after a fast of six hours, was -given a meal of bread and potatoes, and at every subsequent hour -estimates were made of the amount of <i>urea</i> and <i>uric acid</i> excreted -in the urine.</p> - -<table class="borders"> - <tr> - <th>Time.</th> - <th>Urea.<br>Grams.</th> - <th>Uric acid.<br>Milligrams.</th> - <th>Amount of<br>urine. C.C.</th> - </tr> - <tr> - <td>10-11</td> - <td class="tdr">1·07</td> - <td class="tdr">26</td> - <td class="tdr">175</td> - </tr> - <tr> - <td>11-12</td> - <td class="tdr">1·13</td> - <td class="tdr">27</td> - <td class="tdr">118</td> - </tr> - <tr> - <td>12-1 p.m.</td> - <td class="tdr">1·07</td> - <td class="tdr">24</td> - <td class="tdr">164</td> - </tr> - <tr> - <td>1-2 (meal).</td> - <td class="tdr">0·64</td> - <td class="tdr">21</td> - <td class="tdr">60</td> - </tr> - <tr> - <td>2-3</td> - <td class="tdr">1·12</td> - <td class="tdr">22</td> - <td class="tdr">43</td> - </tr> - <tr> - <td>3-4</td> - <td class="tdr">1·16</td> - <td class="tdr">38</td> - <td class="tdr">41</td> - </tr> - <tr> - <td>4-5</td> - <td class="tdr">0·84</td> - <td class="tdr">40</td> - <td class="tdr">53</td> - </tr> - <tr> - <td>5-6</td> - <td class="tdr">1·16</td> - <td class="tdr">56</td> - <td class="tdr">59</td> - </tr> - <tr> - <td>6-7</td> - <td class="tdr">1·20</td> - <td class="tdr">39</td> - <td class="tdr">56</td> - </tr> - <tr> - <td>7-8</td> - <td class="tdr">1·37</td> - <td class="tdr">30</td> - <td class="tdr">95</td> - </tr> - <tr> - <td>8-9</td> - <td class="tdr">1·47</td> - <td class="tdr">33</td> - <td class="tdr">183</td> - </tr> - <tr> - <td>9-10</td> - <td class="tdr">1·33</td> - <td class="tdr">24</td> - <td class="tdr">155</td> - </tr> - <tr> - <td>10-11</td> - <td class="tdr">1·33</td> - <td class="tdr">23</td> - <td class="tdr">180</td> - </tr> -</table> - -<p>It is clear from the results obtained that a very definite increase -of endogenous purin excretion ensued, and that the said increase -occurred sooner as regards <i>uric acid</i> than urea. This bears out -what Mares demonstrated many years ago, viz., that the greatest -increase in uric acid excretion occurs in a few hours after a meal, -whereas the increase in the case of urea comes more tardily, not -reaching its maximum until some hours after.</p> - -<p>Horbaczewski referred such increase in uric acid excretion to a -digestive <i>leucocytosis</i>; in other words, that the uric acid was the -outcome of destruction of the leucocytes, and consequent formation -of purin from the released nucleic acid. Unfortunately for -this theory, the period of most marked augmentation in uric acid -excretion ensues when the leucocytes are most in evidence in the -blood-stream, not <i>after</i> they have disappeared, as would be the -case if uric acid was derived from the purin product of the nucleic -acid liberated by leucocytic destruction. We have a parallel -instance in the case of <i>pneumonia</i>, in which it has been shown that -the elimination of uric acid and other purins is at its acme when -the leucocytes are most abundant; in other words, the highest -uric acid output coincides with the period of most marked leucocytosis, -whereas during the post-critical stage, viz., when leucocytes -are being destroyed in great numbers, the output of uric<span class="pagenum"><a id="Page_93"></a>[93]</span> -acid is very markedly lowered. Discussing Horbaczewski’s theory -in light of the above criticisms, MacLeod suggests, “that the facts -appear to indicate that the purin substance is a metabolic product -of the living leucocytes,” and not, so to speak, the chemical -outcast of their disruption and death.</p> - -<p>Lastly, Walker Hall, discussing endogenous uric acid excretion, -emphasises the necessity of discriminating between the <i>uric acid</i> -output and the <i>total purin</i> output. He reminds us that the -actual cell nucleins belong chiefly to the group of amino-purins, -<i>i.e.</i>, guanine and adenine, and that the oxypurines, xanthine and -hypoxanthine, are intermediate products on their way to excretion, -another and more advanced intermediate product being uric -acid. Now, only a proportion of these intermediary products -appears in the urine, this commonly cited to be approximately -50 per cent.</p> - -<p>But this, as Walker Hall states, must be taken only as a very -broad estimate, for in the same individual the output varies -with the number of conditions, not as yet fully determined. But -the point most emphasised by him is, that though “the <i>uric acid</i> -output varies considerably, the <i>total purin</i> output does not show -similar variations; for when the uric acid excretion wanes that -of the purin bases usually rises. As a consequence, the total -purin output is more constant, less influenced by circumstances, -than the output of <i>uric acid</i>.”</p> - -<p>This being so, we shall now pass on to consider other conditions -influencing endogenous uric acid excretion.</p> - -<h3><span class="smcap">Factors Influencing Endogenous Uric Acid Excretion</span></h3> - -<p>The output of endogenous uric acid excretion is influenced by -(1) Physiological conditions, (2) Pathological states, and (3) The -ingestion of certain drugs.</p> - -<h3><span class="smcap">Physiological Conditions</span></h3> - -<p>It is now recognised that the purin bases of the body exist not -only in the bound form (nucleic acid), but also <i>free</i>, especially in -<i>muscular</i> tissue. Also, that from such free purin bases uric acid -can be readily formed as from those liberated by the disruption -of nucleic acid. Thus, <i>inosinic</i> acid, a nucleotid first isolated -from meat extract, yields phosphoric acid and the purin base, -<i>hypoxanthine</i>. In possession of these facts, we shall be better able -to appreciate the significance of the researches of Burian and -others.</p> - -<p>(<i>a</i>) <i>Muscular Exercise.</i>—According to Burian a large increase -in the excretion of uric acid was found to follow <i>muscular exercise</i>. -The same observer also noted the presence of <i>hypoxanthine</i> in<span class="pagenum"><a id="Page_94"></a>[94]</span> -defibrinated blood after its perfusion through the hind legs of a -dog whose muscles had been thrown into tetanus. Moreover, -subsequent to contraction, the muscles themselves contained an -increased amount of oxypurine. From these findings Burian concluded -that hypoxanthine was a product of <i>muscular action</i>, and -that this substance or its precursor, <i>inosinic acid</i>, was an important -source of <i>endogenous uric acid</i>. The uric acid thus formed by -oxidation was then partly destroyed in the liver and partly -excreted by the kidneys. But Burian noted also during activity -of the muscles that a certain amount of the <i>purin bases</i> failed of -oxidation, and consequently a larger amount of the same, as compared -with uric acid, passed into the circulation.</p> - -<p>Kennaway, discussing the effect of <i>muscular exercise</i> on the -excretion of endogenous purins, noted that during unaccustomed -exercise the <i>uric acid output</i> of the kidneys diminished, but that -of the purin bases is relatively augmented, but, on the whole, he -found that the total purin output (bases plus uric acid) was not -very much increased.</p> - -<p>Leathes and others, investigating the effects on uric acid excretion -of strenuous exercise, established the occurrence of a distinct -increase. Given that the same kind of exercise is practised on the -day following, the said increase is much less marked. If, however, -some different form of muscular activity is undertaken, another -increase in uric acid follows. It would appear, therefore, that, -despite conflicting evidence, the balance of opinion favours the -view that muscular activity does lead to increase in endogenous -uric acid excretion.</p> - -<p>(<i>b</i>) <i>Periodic Variations.</i>—Leathes noted <i>diurnal</i> and <i>nocturnal</i> -variations in the excretion of endogenous uric acid, the maximum -occurring within the early waking hours, and sinking to a minimum -towards the evening. His experiments, he held, indicated a variation -in the actual formation of endogenous uric acid at different -periods of the day. Rockwood also found that an increase -occurred during the daytime, and Pfeil, that there was a morning -rise in the amount of uric acid passed. The fact that doubt still -obtains as to whether muscular exercise has any effect on endogenous -uric acid excretion, renders explanation of this diurnal -variation difficult. This especially as there are no fluctuations -in the urinary functions that could in any way account for it.</p> - -<h3><span class="smcap">Pathological States</span></h3> - -<p>Endogenous uric acid is increased under -certain pathological conditions. Leathes’ recent work confirmed -the view that there is an increased production of nitrogenous waste -in <i>fevers</i>. After taking a large dose of anti-typhoid serum his -temperature rose to 103° F. Experimenting on himself, he found -his output of urea, uric acid, and creatinine all increased, but of all<span class="pagenum"><a id="Page_95"></a>[95]</span> -three <i>uric acid</i> showed the most marked alteration. The question -now arises as to whether such is due to increased production or -diminished destruction. Some further experiments conducted -by Leathes on himself may serve to elucidate this point. Subjecting -himself for a prolonged period to cold baths, a similar increase -in his <i>uric acid</i> output ensued. This would appear to indicate that, -through increased loss of heat, the bodily processes of combustion -were augmented to maintain the body temperature, with, as a -consequence, increased uric acid excretion.</p> - -<p>In <i>leukæmia</i> protein-destroying forces are at work, and the -urine contains large quantities of <i>uric acid</i>. The same is attributed -to the formation and destruction of enormous numbers of -<i>leucocytes</i>, but the urinary findings in this respect have been -extremely variable. While increased uric acid elimination has -been vouched for by many authors, some have noted increase in the -<i>purin bases</i>, sometimes with, and sometimes without increase -in the uric acid; while others again have even noted a decrease -in uric acid and <i>phosphoric acid</i> excretion.</p> - -<p>Apart from these contradictory findings, it would appear, -according to Magnus-Levy, that in <i>acute</i> leukæmias the relation -between the number of leucocytes and the uric acid output is -most variable. Lastly, the different types of leukæmia present -differences in regard of their uric acid output, the increase in the -<i>myelogenous</i> variety being much more marked than in the -<i>lymphatic</i> form.</p> - -<p>Wells, discussing these conflicting data, considers that they are -but the reflex of the “known fluctuations in the course of the -pathological processes of leukæmia; the number of leucocytes, -the size of the lymphatic organs, and the general condition of the -patient all vary greatly from time to time, often with remarkable -rapidity and the excretion of products of metabolic activity must -vary likewise.” Continuing, he observes that the enormous increase -in the amount of lymphoid tissue in the body and blood -must give rise to a greatly augmented <i>nuclein katabolism</i>, with -sequential appearance of <i>uric acid</i>, <i>purin bases</i>, and <i>phosphoric -acid</i> in the urine. This he holds to be well demonstrated by the -increased elimination of uric acid and purin bases, together with a -general increase in the nitrogen output such as has been frequently -noted in sequence to the therapeutic use of X-rays in leukæmia, -this attributable to the increased autolysis known to be induced -by X-rays.</p> - -<p>As to this question of the relationship of <i>leucocytosis</i> to <i>uric acid -excretion</i>, it must be borne in mind that the number of leucocytes -and the excretion of uric acid do not always vary directly. Parallel -studies of the blood and urine have shown that <i>leucocytosis does<span class="pagenum"><a id="Page_96"></a>[96]</span> -not invariably accompany increased uric acid excretion</i>. Indeed, -Hutchison and MacLeod have recorded cases of <i>leucopenia</i> without -any reduction in the amount of uric acid eliminated.</p> - -<p>Also, we have to recall that on a <i>purin-free</i> diet the amount of -endogenous uric acid is more than can come from <i>nuclein</i> destruction -in the body. As suggested by Burian, some may be derived -from the <i>hypoxanthine</i> in muscular tissue. In short, while -nuclein disintegration is the outstanding source of endogenous -purin, yet, for the reason cited, it cannot be regarded as the sole -source, for the exact origin of all the endogenous purin is not -as yet established.</p> - -<p>In conclusion, it would appear that some <i>drugs</i> influence more or -less markedly the excretion of endogenous uric acid, notably, -atophan; but discussion of these will, we think, be best postponed -to the section dealing with the medicinal treatment of gout. -Meanwhile we shall proceed to consider the vexed question of the -formation within the organism of uric acid by synthesis.</p> - -<h3><span class="smcap">Synthetic Formation of Uric Acid</span></h3> - -<p>Birds eliminate most of their nitrogen in the form of uric acid, -and, undoubtedly, in their instance synthetic formation of uric -acid in the liver takes place on a large scale. Thus, when blood -containing ammonium lactate is perfused through the liver of the -goose, an increase in the uric acid content of the blood occurs. -Also the ingestion of lactic, pyruvic and other organic acids leads -to augmented output of uric acid; in short, it is generally agreed -that in birds <i>synthesis</i> is the chief mode of formation of uric acid, -homologous with the formation of <i>urea</i> in the liver of mammals.</p> - -<p>If this be true of birds, on the other hand, <i>splitting</i> and <i>oxidation</i> -of <i>nucleins</i> is in <i>mammals</i> the most important source of uric acid, -but there is evidence that it cannot all be accounted for in this -way. As before remarked, the old belief that purin excretion -remains almost constant on a <i>purin-free</i> diet, despite great variations -in the amount of the ingests, is not strictly true. Thus, -using swifter and more reliable methods for the estimation of -nitrogenous metabolites, Folin noted, on an absolutely purin-free -diet, that an increase in purin excretion ensued, given -<i>marked</i> variations in the intake of food. Again, the Dalmatian -dog, as we have seen, excretes uric acid in his urine. S. R. Benedict -was therefore able to demonstrate that a very distinct increase -in his uric acid output ensued in sequence to increase in the amount -of his <i>non-purin</i> food; moreover, that even when such non-purin -foods were continued for a year, “the total amount of uric -acid excreted was at least ten times greater than could have come -from the traces unavoidably included in the food” (MacLeod).</p> - -<p><span class="pagenum"><a id="Page_97"></a>[97]</span></p> - -<p>Also Ascoli and Izar, experimenting with dog livers, noted on -incubation thereof and passage through the same of oxygen that -the uric acid disappeared; but on the substitution of carbon -dioxide an accumulation thereof ensued. Wells, however, was -unable to confirm this re-synthesis of uric acid by dog livers, and -Spiers also failed to corroborate their findings.</p> - -<p>On the other hand, there is evidence pointing to the fact that a -certain small percentage of synthetic formation does take place in -the organism. Thus certain chemical substances, and these not -purin, do cause an appreciable though slight increase in the -purin excretion of mammals, and a very marked augmentation -of the same in birds, viz., <i>lactic</i>, <i>tartronic</i> and <i>B-oxybutyric acids</i>.</p> - -<p>But, as MacLeod, discussing these experimental and clinical -findings, observes, there are to hand even more direct proofs that -<i>purin synthesis</i> occurs in mammals. Thus, as McCallum has -pointed out, we cannot escape the admission that young mammals -are able to synthetise the purins essential for their growth, and -this from food containing no purin, <i>e.g.</i>, milk. Again, prior to -incubation, a hen’s egg contains practically no nucleic acid, whereas -after development its content in the same increases by great -strides. The eggs of insects, too, with the progress of development, -amass purin very rapidly.</p> - -<p>Again, Miescher noted long since that salmon, on leaving the -sea to ascend rivers for the object of spawning, have at that time -well-developed muscles; but on arriving at the upper reaches, -marked muscular wasting ensues, while the testes undergo -enormous enlargement. MacLeod, reflecting on these observations, -argues that, “as the fish takes no food during the migration, -there must be conversion of the protein of the muscles into the -cellular tissue of the sexual glands, and <i>nucleic acid</i> must be -produced.” MacLeod’s conclusion is that “Purin synthesis -undoubtedly occurs in the mammalian body, but it is difficult to -recognise in metabolism investigation, because it is a slow continuous -process ... whether or not changes in the activity of -purin synthesis occur in conditions of disease, is a question which -awaits investigation.” Lastly, the opinion of most authorities is -that, while they concede the possibility of synthetic formation, the -amount of uric acid produced in this manner is negligible, and that -by far the most important mode of formation in mammals is by -the <i>splitting</i> and <i>oxidation</i> of <i>nucleins</i>; in other words, that uric -acid in the main is derived from the <i>amino-purins</i> by <i>deaminisation</i> -and subsequent oxidation, and from the <i>oxy-purins</i> directly -by oxidation.</p> - -<hr class="chap x-ebookmaker-drop"> - -<div class="chapter"> - -<p><span class="pagenum"><a id="Page_98"></a>[98]</span></p> - -<h2 class="nobreak" id="CHAPTER_VIII">CHAPTER VIII<br> -<span class="smaller">FORMATION AND DESTRUCTION OF URIC ACID</span></h2> - -</div> - -<p>The chemical structure and sources of uric acid having been -dealt with, we are now in a position to resume our narrative, and -to take up the thread at the point when Horbaczewski revealed -the derivation of uric acid from nucleic acid. It now devolves -upon us to scrutinise more narrowly the process by which the -formation of <i>uric acid</i> from <i>nucleic acid</i> is achieved. Incidentally, -it will not be unprofitable to note, if only briefly, the steps by which -the necessary expansion of our chemical and physiological knowledge -of nucleic acids has been acquired.</p> - -<p>As may be imagined, the primary difficulty was to prepare -nucleic acids of such purity as admitted of their elementary -chemical analysis. The necessary researches were to a large -extent confined to two types of nucleic acid, one derived from -<i>yeast</i>, and the other from the <i>thymus gland</i>; in other words, to -representatives of the only two nucleic acids in nature, one derived -from the nuclei of <i>animal</i> cells, the other from the nuclei of -<i>vegetable</i> cells.</p> - -<p>A feature common to nucleic acids of animal and vegetable -origin is that, on hydrolysis with boiling mineral acid, they yield -two purin derivatives, <i>guanine</i> and <i>adenine</i>, and a pyrimidin -derivative, <i>cytosine</i>. From thence as regards their remaining -constituent elements they display distinctions. Thus animal -nucleic acids yield <i>thymine</i>, and contain a <i>hexose</i> group in their -molecule. On the other hand, vegetable nucleic acids give forth -<i>uracil</i> and possess a <i>hexose</i> group.</p> - -<p>To sum up, <i>nucleic</i> acid is a chemical complex, made up of -phosphoric acid with purin bases, pyrimidin bases and carbohydrate -radicles. Moreover, nucleic acids, whatever their source, -show a striking similarity in structure, containing always two -amino-purins (adenine and guanine), two pyrimidines (either -cytosine and uracil, or cytosine and thymine), and a carbohydrate. -Now, while <i>purin bases</i> are always present, yet, in respect of their -<i>carbohydrate</i> group, nucleic acids display variations; this, -according as they are of animal or vegetable origin. If the former, -the carbohydrate group is a <i>hexose</i> (contains six carbon atoms) -with <i>thymine</i>. If the latter, it contains <i>pentose</i> (five carbon -atoms) with <i>uracil</i>.</p> - -<p><span class="pagenum"><a id="Page_99"></a>[99]</span></p> - -<p>The constancy in the content of the various nucleic acids is -such that Levene and Jacobs have felt justified in putting forward -the following provisional formula as to the constitution of a -<i>nucleic acid</i> of animal origin.</p> - -<div class="figcenter illowp100" id="formula06" style="max-width: 31.25em;"> - <p class="caption"><span class="smcap">Structural Formula of Nucleic Acid</span></p> - <img class="w100" src="images/formula06.jpg" alt=""> -</div> - -<h3><span class="smcap">Distribution of the Enzymes</span></h3> - -<p>The enzymes responsible for the disruption of the <i>nucleic acid</i> -complex are not to be found in all the body tissues. Moreover, -the distribution of the enzymes in the various organs and tissues -varies in different species of animals. Of the various organs the -<i>liver</i>, <i>spleen</i>, <i>thymus</i>, and <i>pancreas</i> more particularly contain -enzymes in abundance. As to their varied location in different -animals, it may be noted that the enzyme responsible for the -oxidation of <i>xanthine</i> into <i>uric acid</i>, viz., <i>xanthine-oxidase</i>, is found -in man only in the liver. In other animals, also, it is of localised -distribution, being as a rule only found in the liver or in the liver<span class="pagenum"><a id="Page_100"></a>[100]</span> -and kidney. The dog, however, appears to be an exception, -<i>xanthine-oxidase</i> being found in a variety of its tissues.</p> - -<p><i>Adenase</i>, the deaminising enzyme, is not to be found in any -organs in man. Neither does it exist in any of the tissues of the -rat. Consequently, if <i>adenine</i> be injected subcutaneously in rats, -it undergoes oxidation, without abstraction of its amino group.</p> - -<p>On the other hand, <i>guanase</i>, also a deaminising enzyme, is in -man to be detected in the <i>kidney</i>, <i>lung</i>, and <i>liver</i>, but not in the -pancreas or spleen. In the pig, however, guanase is lacking, and -its absence no doubt explains why deposits of guanine may occur -in the muscles constituting the so-called <i>guanine gout</i> met with in -swine. It is worthy of note also that in pigs’ urine the content -of purin bases exceeds that of uric acid.</p> - -<p>To sum up, in man the enzyme, <i>xanthine-oxidase</i>, which forms -uric acid from xanthine, is located chiefly or exclusively in the -<i>liver</i>. This, of course, represents the <i>final</i> stage of purin metabolism, -but the antecedent chemical processes involved in the -disruption of nucleic acids are initiated by the action of enzymes -in the <i>intestinal juices</i> and <i>wall</i>, and to a consideration <i>seriatim</i> of -these changes we now proceed.</p> - -<h3><span class="smcap">Stages in Disruption of Nucleic Acid</span></h3> - -<p>As might be expected from the complex structure of the nucleic -acid molecule, a number of ferments are concerned in its disruption. -The gastric and pancreatic juices contain not a trace of -any enzymes. Thus, when <i>nucleo-protein</i> is subjected to the -gastric juice a moiety of protein is readily split off and hydrolysed -to peptone and other products of proteolysis.</p> - -<p>But the nuclein element remains unacted upon until it comes -under the action of the pancreatic juice. Hydrolysis then ensues, -and the ingested nuclein is broken down into nucleic acid and -protein. The <i>nucleic acid</i> remains unaffected by the pancreatic -juice, but, coming in contact with the <i>succus entericus</i>, it undergoes -partial decomposition through the action of a ferment called -nuclease or <i>nucleic</i>-acidase. Under its disruptive effect the nucleic -acids or <i>poly-nucleotides</i> are further split up into groups known as -<i>nucleotides</i>. The two <i>pyrimidine</i> nucleotides split off and undergo -no further change. But, through the action of another ferment, -<i>nucleotidase</i>, the <i>purin</i> nucleotides are further decomposed to -yield <i>nucleosides</i> (substances of the glucoside class made up of a -combination of a purin base with a carbohydrate group of the -nucleic acid with which also phosphoric acid is linked).</p> - -<p>No further stage in hydrolysis of nucleic acid occurs in the -intestine, but the <i>nucleosides</i> are again in turn split up after reaching -the tissues, particularly in the <i>spleen</i>, <i>liver</i>, and <i>thymus</i>. This,<span class="pagenum"><a id="Page_101"></a>[101]</span> -under the action of specific enzymes, <i>nucleosidases</i>, which succeed -in breaking the nucleosides down into the so-called “building -stones” of the <i>nucleic acid molecule</i>, phosphoric acid group, carbohydrate -group, pyrimidine and purin bases, especially adenine and -guanine. The adenine and guanine thus formed are, by the -action of the ferments <i>adenase</i> and <i>guanase</i>, converted and, by -the removal of their amino group, transformed, adenine into -hypoxanthine, and guanine into xanthine, thus:—</p> - -<div class="figcenter illowp100" id="formula07" style="max-width: 31.25em;"> - <img class="w100" src="images/formula07.jpg" alt=""> -</div> - -<p>By the action of oxidases also present in the tissues hypoxanthine -is changed into xanthine and xanthine into uric acid -(trioxy-purine), this by a specific ferment xanthine oxidase.</p> - -<div class="figcenter illowp100" id="formula08" style="max-width: 31.25em;"> - <img class="w100" src="images/formula08.jpg" alt=""> -</div> - -<div class="figcenter illowp100" id="formula09" style="max-width: 31.25em;"> - <p class="caption"><span class="smcap">Scheme Illustrating the Probable Stages - in the Passage of Purin through the Body (Walker Hall)</span></p> - <img class="w100" src="images/formula09.jpg" alt=""> -</div> - -<p>It will be seen that the disintegration of nucleic acid involves -many stages, and its complexity is such that we make no apology -for drawing upon the masterly monograph of Walter Jones for<span class="pagenum"><a id="Page_102"></a>[102]</span> -further elucidation of this intricate question. In relating the -history of nucleic acid in the animal body Jones has found it convenient -to introduce certain terms wherewith to designate the -various elements of the <i>nucleic acid molecule</i>. Thus, the molecule -in its entirety is termed a <i>tetra-nucleotide</i>. The cleavage of this -complex is initiated by the action of two specific enzymes. -Through their agency the tetra-nucleotide is first cloven into two -<i>di-nucleotides</i>, which immediately divide up into four <i>mono-nucleotides</i>. -These ferments are:—</p> - -<p>(1) <i>Phospho-nuclease</i> (which splits off the phosphoric acid -radicle, leaving a nucleoside, guanosine or adenosine).</p> - -<div class="figcenter illowp100" id="formula10" style="max-width: 31.25em;"> - <img class="w100" src="images/formula10.jpg" alt=""> -</div> - -<p>(2) <i>Purin-nuclease</i> (which splits off the purin radicle, viz., -separates out both phosphoric acid and carbohydrate -groups, leaving free purin bases).</p> - -<div class="figcenter illowp100" id="formula11" style="max-width: 31.25em;"> - <img class="w100" src="images/formula11.jpg" alt=""> -</div> - -<p>Now, in sequence to either of the foregoing cleavages by the -phospho- or purin-nucleases another set of enzymes come into -the field. Under their <i>deaminising</i> effect the amino group is -abstracted, with the formation of either free <i>oxy-purins</i> or oxy-purins -still bound in glucoside-like combination with sugar.</p> - -<p>If the oxy-purins are free, the following is the reaction:—</p> - -<div class="figcenter illowp100" id="formula12" style="max-width: 20.3125em;"> - <img class="w100" src="images/formula12.jpg" alt=""> -</div> - -<p>Should, however, the guanine glucoside be present:—</p> - -<div class="figcenter illowp100" id="formula13" style="max-width: 31.25em;"> - <img class="w100" src="images/formula13.jpg" alt=""> -</div> - -<p>In the latter instance a hydrolysing enzyme, <i>xanthosine-hydrolase</i>, -by its action, splits off xanthine. We see, therefore, that by -either route the end-product is the same. Following a like series -of changes, the adenine radicle is transmuted into hypoxanthine. -This either directly by the action of adenase:—</p> - -<div class="figcenter illowp100" id="formula14" style="max-width: 20.3125em;"> - <img class="w100" src="images/formula14.jpg" alt=""> -</div> - -<p class="noindent">or indirectly through the agency of adenosine-deaminase, the -hypoxanthine-glucoside (inosine) is formed, and subsequently the -hypoxanthine is split off.</p> - -<p><span class="pagenum"><a id="Page_103"></a>[103]</span></p> - -<p>Xanthine and hypoxanthine are, therefore, now to hand, and -given the presence of oxygen, their oxidation to <i>uric acid</i> ensues:—</p> - -<div class="figcenter illowp100" id="formula15" style="max-width: 25em;"> - <img class="w100" src="images/formula15.jpg" alt=""> -</div> - -<p>Now, in man and the anthropoid apes, <i>uric acid</i> is the end-product -of <i>purin</i> catabolism. In contrast therewith in most mammals -only a minimal amount of the exogenous or endogenous -purins escapes in the urine as uric acid. Most of it undergoes -further oxidation into <i>allantoin</i>,<a id="FNanchor_15" href="#Footnote_15" class="fnanchor">[15]</a> this change taking place in most -mammals chiefly in the <i>liver</i>. According to Schittenhelm, if -nucleic acid be given to dogs, pigs or rabbits, from 93-95 per -cent. thereof appears in the urine as allantoin, and only 3-6 per -cent. as uric acid, and 1-2 per cent. as purin bases.</p> - -<div class="figcenter illowp100" id="formula16" style="max-width: 31.25em;"> - <p class="caption"><span class="smcap">Disruption of Nucleic Acid Molecule - (Amberg and Jones).</span></p> - <img class="w100" src="images/formula16.jpg" alt=""> -</div> - -<p><span class="pagenum"><a id="Page_104"></a>[104]</span></p> - -<p>In man, as in most mammals, uric acid is formed chiefly in the -<i>liver</i> from purins, and in the preceding table Amberg and Walter -Jones schematically represent the various steps by which disruption -of the nucleic acid molecule is attained, and uric acid -formed.</p> - -<h3><span class="smcap">Destruction of Uric Acid</span></h3> - -<p><i>Uricolysis</i>, or the destruction of uric acid, is, in most mammals, -achieved through the agency of the oxidising enzyme <i>uricase</i>, -which oxidises uric acid to <i>allantoin</i>. Consequently, in their -instance, purin bases, ingested as such or set free in the tissues, -appear in the urine, not as uric acid, but in the form of <i>allantoin</i>. -On the other hand, both in man and in the anthropoid apes, this -particular enzyme uricase is absent. In accordance therewith, -only a trace of allantoin is to be found in the urine of man and the -higher apes, while in the lower animals, <i>e.g.</i>, dogs, pigs, and rabbits, -a large proportion of the purin excretion assumes this form.</p> - -<p>Now, the absence of <i>uricase</i>, in <i>man</i>, is held to be proved by the -fact established by Wiechowski and others, viz., that uric acid, if -<i>injected subcutaneously</i>, may be almost wholly recovered in the -urine, and moreover, unchanged. On the other hand, the total -excretion of uric acid and the other purin bodies by no means -tallies exactly with the amount of the uric acid ingested as purin -bases in the food and that produced from the tissues; in other -words, it has been found that, when given by the mouth, <i>nucleic -acid</i> or <i>purins</i> are by no means <i>quantitatively</i> excreted in the -urine, even though not only <i>uric acid</i>, but also <i>allantoin</i> and the -<i>purin bases</i>, are included within the estimate. According to most -experiments, a considerable proportion of the purin-nitrogen -intake, about 50 per cent., is excreted as <i>urea</i>.</p> - -<p>The question then arises as to what becomes of that moiety of -the <i>food purins</i> which fails to appear in the urine as <i>uric acid</i>. -Now the amount of allantoin that appears in the urine is negligible. -Moreover, Ackroyd, having shown that the organism cannot -destroy allantoin, it is possible that the minimal amounts excreted -thereof in the urine are all derived from the food.</p> - -<p>Accordingly, if, as experimental feeding with <i>purins</i> or <i>nucleic -acid</i> appears to indicate, purins are destroyed in the body they<span class="pagenum"><a id="Page_105"></a>[105]</span> -“pass through some other route than allantoin, and possibly, that -part of the purin which is destroyed does not pass through the -stage of uric acid.” Such is Wells’ opinion, and he reminds us -that <i>in vitro</i> the destruction of uric acid can be attained by other -routes than through allantoin. Thus, it can be broken down into -glycocoll, ammonia, and CO₂, or by another method of disintegration -it furnishes first alloxan (C₄H₂N₂O₄), then parabanic acid -(C₃H₂N₂O₃), which in turn yields oxalic acid and urea.</p> - -<p>But while it is probable that there is more than one way in -which uric acid can be decomposed in the body, nevertheless there -is, according to Wells, no evidence that either of the alternative -routes above suggested is ever affected in the animal body. In -this <i>impasse</i> Siven suggests the further possibility, viz., that the -moiety of the food-purins which fail of recovery from the urine -undergo partial destruction in the intestine by <i>bacteria</i>.</p> - -<p>Stewart, however, in his “Physiology,” discussing <i>uricolysis</i>, -maintains that a considerable destruction of uric acid and other -purin bodies goes on in the body and mainly in the <i>liver</i>. He -reminds us that when uric acid is heated in a sealed tube with -strong hydrochloric acid, it breaks down into glycin, carbon-dioxide -and ammonia, and he maintains that “there are grounds -for believing that a similar decomposition takes place in the body, -and that the products are then transformed into urea in the -<i>liver</i>”; this, through the agency of a special ferment called the -<i>uricolytic enzyme</i>.</p> - -<p>Also, Flack and Hill, discussing the metabolism of <i>nuclein</i>, -hold that some of the uric acid thus formed may be transmuted -into urea by an uricolytic ferment present in the <i>liver</i>, muscles, -and <i>kidneys</i>. This same agent they consider “probably destroys -a considerable amount of the uric acid formed in the body. Indeed, -uric acid, even when given in the food, owing to the presence -of this enzyme, causes no increase in the uric acid output of the -body.”</p> - -<p>On the other hand, Wells, discussing the destruction of uric -acid, observes that repeated investigations show “that the -tissues of man have no power whatever to destroy uric acid <i>in -vitro</i>; the earlier reports of positive uricolysis undoubtedly being -erroneous.” His final conclusion, after weighing all available -evidence, is that it is highly probable that in man “most of the -purin absorbed from the food, and practically all the purin from -cell metabolism, is converted into uric acid and excreted as such.” -MacLeod, however, reflecting on the fact that uric acid is not -destroyed when extracts of the organs are incubated at body -temperature with uric acid or its precursors, bids us bear -in mind that, “although the uric acid is thus shown not to<span class="pagenum"><a id="Page_106"></a>[106]</span> -be destroyed <i>in vitro</i>, it may nevertheless be destroyed in the -living animal.”</p> - -<p>We see, therefore, that the question, Whether uric acid can -undergo destruction in the human body? is still a matter of dispute, -and must, pending further investigation, remain <i>sub judice</i>. Still, -despite the conflict of evidence, clinicians have felt justified in -assuming that one of the factors in the genesis of gout may be an -entire <i>absence</i> or a <i>diminution</i> in the amount or activity of this -<i>uricolytic ferment</i>.</p> - -<p>But the awkward fact remains that all researches up to date -have failed to establish the presence in the human body of any -enzyme which can decompose uric acid. Should, therefore, -future investigators place beyond the reach of cavil the claim that -no <i>uric-acid-destroying enzyme exists in the body</i>, it would seem that, -<i>ipso facto</i>, man, through lack of this capacity for rapid oxidation -of uric acid, is, by this same disability, rendered a potential victim -of <i>uric acid retention</i> and <i>deposition</i>.</p> - -<p>Elucidation of this vexed point seems more probable in view of -the striking discovery recently made by R. Benedict, viz., that in -one particular breed of dog, the Dalmatian, <i>uricase</i> is wholly -absent. In respect of this <i>lack of a uric-acid-destroying ferment</i>, -the Dalmatian breed of dog has a <i>purin</i> metabolism apparently -identical with that of man.<a id="FNanchor_16" href="#Footnote_16" class="fnanchor">[16]</a> Thus, if fed on a purin-free diet, he -passes large quantities of uric acid, and if the latter be injected -subcutaneously, elimination in quantity as such ensues; this, -in striking contrast to what obtains in all other animals in whom, -as before noted, uric acid is mostly oxidised to <i>allantoin</i> before -excretion. Now, as MacLeod observes, investigation into the -metabolism of nucleic acid has, in man, been hampered greatly, -in that the absence of uricase from his tissues, prior to Benedict’s -discovery, rendered experimental researches on the lower animals -valueless. But, in light of the above revelation later by R. -Benedict, it may reasonably be hoped that in the near future our -knowledge as to the location and nature of the intermediary -chemical processes occurring in the metabolism of nucleic acids -may be materially clarified.</p> - -<hr class="chap x-ebookmaker-drop"> - -<div class="chapter"> - -<p><span class="pagenum"><a id="Page_107"></a>[107]</span></p> - -<h2 class="nobreak" id="CHAPTER_IX">CHAPTER IX<br> -<span class="smaller">URIC ACID IN RELATION TO GOUT</span></h2> - -</div> - -<p>It will be recalled that at the close of our chapter on Pathogenesis -we referred to the growing scepticism of Garrod’s views -as to the pathogeny of gout. Still, if we except Edward Liveing’s -pertinent observation that <i>uricæmia</i> was not peculiar to gout, -naught, save alternative hypotheses, unsupported by pathological -data, was advanced. Consequently, Garrod’s facts never being -seriously called in question, his position remained unassailable, -until, in the year 1898, his original observations as to the lowered -alkalinity of the blood in acute gout, and the increased uric acid -content thereof during the same, were definitely contradicted by -Magnus Levy.</p> - -<p>Working with more modern and more reliable methods of -technique, this observer, in a series of seventeen cases of acute gout, -found no evidence of any lessening in alkalinity of the blood or of -any augmentation of its uric acid content as compared with the -inter-paroxysmal period.</p> - -<p>Again, as to Garrod’s claim that there was a diminished excretion -of uric acid during the attack, this also, while supported by -Minkowski, was called in question by Pfeiffer, Levy, and Badt, -who found the reverse to be the case, <i>i.e.</i>, a notable increase in the -excretion of uric acid during the paroxysm.</p> - -<p>These results were again in 1900 confirmed by Chalmers Watson. -An exhaustive study of a series of cases of <i>acute gouty polyarthritis</i> -convinced him that:—</p> - -<div class="blockquote"> - -<p>(1) The alkalinity of the blood is not diminished during the -attack.</p> - -<p>(2) The excretion of uric acid is not lessened during the -paroxysm, but the reverse; there is, therefore, no ground -for the supposition that there is a temporary diminution -in the capacity of the kidneys to excrete uric acid.</p> - -<p>(3) The amount of the uric acid in the blood is not greater during -the attack than in the intervening period, and if these -points be accepted, we must start <i>de novo</i> in search of the -cause of the acute paroxysm.</p> - -</div> - -<p>The iconoclastic revelations of the foregoing researches may<span class="pagenum"><a id="Page_108"></a>[108]</span> -well form a preface to our discussion of gout from the triple -aspect of:—</p> - -<ul> -<li>(1) Uric acid excretion.</li> -<li>(2) Uricæmia.</li> -<li>(3) Uratosis.</li> -</ul> - -<h3><span class="smcap">Uric Acid Excretion in Gout</span></h3> - -<p>The earlier investigations as to the behaviour of uric acid in the -organism were necessarily restricted to the noting of any variations -in the uric acid output in the urine. That the findings and, alike, -the deductions proved bewilderingly contradictory is not to be -marvelled at when we recall the many factors that govern the -amount of uric acid excreted in the urine.</p> - -<p>How fallacious, it now transpires, were the assumptions based -upon the mere uric acid output in the urine, and how little understood -even to-day the many conditions that determine its variations.<a id="FNanchor_17" href="#Footnote_17" class="fnanchor">[17]</a> -But, fortunately, we can now to some extent control and -review our urinary findings in light of the uric acid content of the -<i>blood</i>. But we anticipate, and meanwhile let us confine our discussion -to the variations in uric acid excretion that occur in <i>gout</i>, -and this as revealed by more modern students of the disease. This -will be more conveniently dealt with if we consider first the oscillations -in uric acid output in relation to <i>acute</i> attacks of the disorder, -and subsequently the same as met with in its more <i>chronic</i> -manifestations.</p> - -<h3><span class="smcap">Uric Acid Variations in Acute Gout</span></h3> - -<p>Generally speaking, there appears to be a consensus of opinion -on the following points:—</p> - -<div class="blockquote"> - -<p>(1) That in the <i>intervals</i> between <i>acute</i> attacks of gout the -elimination of uric acid lies within the normal limits, but -that</p> - -<p>(2) For one or two days <i>prior</i> to an acute attack an appreciable -<i>decline</i> in the output of uric acid occurs. This, however, -is not so marked as the subsequent</p> - -<p><span class="pagenum"><a id="Page_109"></a>[109]</span></p> - -<p>(3) <i>Increased</i> output of uric acid <i>during</i> the acute attack. -According to Magnus Levy the increase may reach from -0·3-0·5 gram, daily, and more, and may sometimes last -for a week or even two.</p> - -<p>(4) Following attack a tardy decline in uric acid output to -former level.</p> - -</div> - -<p>To sum up, during an attack of <i>acute</i> gout the uric acid output -stands at a relatively low level between the paroxysms. But -one or two days before the oncoming attack a <i>diminution</i> in uric -acid output ensues. In contrast with the outbreak of the attack, -the uric acid excretion <i>increases</i> markedly, this enduring for a -week or more, when the output again <i>declines</i>. The augmented -output <i>during</i> the paroxysm is more constant than the diminished -excretion antecedent thereto. Now, while it may be taken that -the foregoing variations in <i>uric acid output</i>, prior, during, and -subsequent to, acute attacks, obtain as a general rule, such -behaviour is not invariable; for, unfortunately, as Wells -reminds us, instances are met with in which “the uric acid excretion -shows no variation from that of normal persons.”</p> - -<h3><span class="smcap">Uric Acid Variations in Chronic Gout</span></h3> - -<p>It must never be forgotten that the <i>elimination of uric acid</i> -displays wide <i>variations</i>, this even when the subject under investigation -is on a <i>constant</i> diet. Consequently, as Folin has pointed -out, “even in the case of gout, which is distinctly associated with -uric acid, it is an extremely difficult matter to prove by means of -urine analyses that the uric acid elimination is not entirely -normal.” And he adds, “If it had not been for the fact that uric -acid, because of its insolubility, is so easily found in the joints, -it would unquestionably have been a very long time before any -definite relationship between uric acid and gout could have been -established.”</p> - -<p>None can gainsay the truth of these reflections, for, when placed -on a fixed diet, the uric acid output in the victims of <i>chronic gout</i> -differs but little from that of <i>normal</i> individuals on a similar -regime; save in this respect, that, following the intake of <i>purin-containing</i> -substances, the period of augmented uric acid excretion -that ensues is <i>prolonged</i> as compared with the normal.</p> - -<h3><span class="smcap">Retarded Exogenous Uric Acid Output</span></h3> - -<p>In 1901 Vogt showed that in gout the excretion of exogenous -purins was not only delayed but diminished. Giving simultaneously -to a <i>gouty</i> subject and a <i>healthy</i> individual a diet rich -in purins, he found that, in the former, <i>retention</i> and <i>delayed<span class="pagenum"><a id="Page_110"></a>[110]</span> -excretion</i> of <i>purins</i> ensued. Vogt’s findings were confirmed by -Reach, Soetbeer, Pollak, Mallory, and others.</p> - -<p>Brugsch and Schittenhelm also observed that, following the -intake of purin-containing substances, the exogenous uric acid -excretion was <i>retarded</i> and <i>reduced</i>; in other words, the percentage -of exogenous nitrogen excreted as uric acid nitrogen is -less than in normal individuals, although the increased elimination -extends over a longer period of time.</p> - -<p>On the other hand, Walker Hall finds that, though there is -<i>retardation</i>, there is <i>no diminution</i> in the output in gouty subjects. -Thus he states: “When an adult takes a meal consisting of half -a pound of beef and a quarter of a pound of sweetbread, containing -about 0·620 gram purins, the moiety which usually occurs in the -urine, say 0·300 gram, is not fully excreted until 6-10 hours have -elapsed. When a similar meal is taken by a gouty individual the -full 0·300 gram is eliminated, but the rate of output is delayed, -some 48-72 hours being necessary.”</p> - -<p>The same observer states that, given <i>intravenous</i> injection of -acid into a <i>normal</i> man, its elimination is spread over several days, -and the total amount injected fails to appear in the urine. But -if the injection be administered during a course of <i>atophan</i>, then -the uric acid excretion is completed within twenty-four hours, -and the whole amount injected can be recovered from the urine. -Now if in a <i>gouty</i> subject the same method of procedure be adopted, -the sequence of events is precisely similar, and like results have -been reported, following the administration of <i>sodium salicylate</i> -to vegetarians of five or more years’ standing. To sum up, the -above findings would appear to indicate that:—</p> - -<div class="blockquote"> - -<p>(1) A gouty subject can excrete exogenous purins as adequately -as a normal man, but he takes longer to do so.</p> - -<p>(2) If the extra purins be taken during a course of atophan, -even this departure from normal is obliterated, <i>i.e.</i>, the -customary delay in excretion is obviated.<a id="FNanchor_18" href="#Footnote_18" class="fnanchor">[18]</a></p> - -</div> - -<p>But, unfortunately for the diagnostic valency of this symptom<span class="pagenum"><a id="Page_111"></a>[111]</span> -in gout, viz., <i>retarded exogenous purin output</i>, it has not been -found to be <i>invariable</i>. Thus Magnus Levy has shown that, in some -instances of gout, the elimination of exogenous purin is neither -reduced nor protracted. Pratt, too, has confirmed this observer’s -findings, while, as we shall see later, this authority, also McClure, -Mallory, and others, have placed on record the still more disconcerting -fact, viz., that a diminished and retarded output of -exogenous purin is <i>not peculiar to gout</i>.</p> - -<p>The inference then would appear to be that:—</p> - -<div class="blockquote"> - -<p>(1) Reduction and retardation of the excretion of exogenous -purin, though common in gout, is not invariable.</p> - -<p>(2) The same is not peculiar to gout, but occurs in other disorders.</p> - -<p>(3) Its diagnostic valency, as a characteristic feature of gout, -is correspondingly depreciated.</p> - -</div> - -<h3><span class="smcap">Lowered Endogenous Uric Acid Output</span></h3> - -<p>As a rule, gouty subjects, on a <i>purin-free</i> diet, excrete less -endogenous uric acid than <i>normal</i> persons. Thus, according to -Walker Hall, the average daily endogenous urinary uric acid -output of a <i>normal</i> adult is about 0·5 gramme, while that of a gouty -subject is about 0·45 gramme. Brugsch and Schittenhelm hold that -in about 80 per cent. of cases the average endogenous excretion -is lower than normal.<a id="FNanchor_19" href="#Footnote_19" class="fnanchor">[19]</a></p> - -<p>According to these same observers, “the maximum fluctuation -during attack-free periods was at first believed to be less than in -the normal cases; more recent examinations, however, have -shown that in the same case of gout there may be <i>periods of high, -and periods of low, endogenous uric acid excretion</i>.” These variations, -they hold, are not to be accounted for by either mild or -severe attacks of gout, for they occur in the <i>attack-free</i> period.</p> - -<p>Again Laird, investigating the elimination of endogenous uric -acid in a case of <i>chronic</i> gout, noted that the output thereof was -<i>sub-normal</i>, and, as Brugsch and Schittenhelm observed, the same -presented marked <i>variations</i>. The leucocyte counts he found -normal, but the phosphorus output and the acidity were sub-normal. -Bloch again, while he agrees that endogenous purin -excretion is usually below the average in <i>gouty</i> subjects, found that -the output thereof is at its minimum before an acute attack of gout.</p> - -<p>The foregoing observations would suggest that the <i>retention</i><span class="pagenum"><a id="Page_112"></a>[112]</span> -or delayed excretion of uric acid applies both to <i>exogenous</i> and -<i>endogenous</i> purins. But, when we come to analyse the foregoing -findings as to the variations in uric acid output, both in acute -and chronic gout, one feels inclined to agree with O. Folin, “that -the clinically useful contributions obtained by <i>urine analysis</i> have -not been very numerous.” Thus we cannot, on the basis of the -<i>variations</i> in <i>uric acid excretion</i>, presume to diagnose gout; in -other words, if we take <i>urine analysis</i> alone, it is extremely -difficult to prove that the uric acid elimination in gout is really -and truly abnormal. Our uncertainty, moreover, is the more -pronounced when we realise that in some cases of <i>rheumatoid -arthritis</i>, etc., there is a disturbance of <i>purin</i> metabolism which -in some of its features is reminiscent of that obtaining in typical -gout. But, before proceeding to discuss this interesting resemblance, -it will, we think, be convenient here to recall that the -obliquities in metabolism found in gout are not wholly restricted -to <i>uric acid</i>.</p> - -<h3><span class="smcap">Other Anomalies in Excretion in Gout</span></h3> - -<p>As Levene and Kristeller have shown, side by side with the -delayed excretion of ingested purins, there occurs also a tardy -elimination of the other nitrogenous products of protein food. -Vogt observed that fluctuations in nitrogen retention and nitrogen -loss are quite typical of gouty subjects. As to the why and -wherefore, however, of this variability, it remains a mystery. -Nor do we know the form in which the nitrogen is retained, though -Vogt maintains that the uneliminated moiety takes the form of -purin bodies. According to Brugsch, it is during the acute -attacks of gout that the nitrogen loss reaches its zenith, and he -suggests that the nitrogen retention in the inter-paroxysmal -periods is in part compensatory. On the other hand, the gain in -weight that ensues is not adequate to account for the sum total -of the nitrogen retention; while, as before observed, in gout -there occurs, not only retarded elimination of exogenous purins, -but also of other nitrogenous products of protein food. Yet, -according to Heffter, the ratio of <i>purin bases</i> to uric acid is -unaltered in the urine of gouty subjects.</p> - -<p>Again, all <i>nucleins</i> contain a <i>phosphoric</i> acid group, and Futcher -found that the curve of the uric acid output ran in a striking -parallel with that of phosphoric acid. But the attempts of subsequent -investigators to show that the two end-products of -nuclein disintegration—uric acid and phosphoric acid—go hand-in-hand -prove contradictory. Hence Wells, in regard to phosphoric -elimination, observes that, “it seems probable that it -shows no characteristic alterations in gout.” Lastly, we will<span class="pagenum"><a id="Page_113"></a>[113]</span> -recall to the reader that in the chapter on protein metabolism it -was pointed out that the <i>amino-acids</i>, especially <i>glycocoll</i>, are found -in excess in “gouty” urines.</p> - -<p>In conclusion, it must, we fear, be admitted that the results of -<i>urinary analyses</i> have proved insufficient of themselves to unravel -the intricacies of metabolism in gout, and, after a brief digression, -we shall proceed to ascertain whether, on the other hand, chemical -analysis of the <i>blood</i> by modern methods can in any way shed -further light on this obscure problem.</p> - -<h3><span class="smcap">Purin Metabolism in other Disorders</span></h3> - -<p>Working at the Research Hospital for the Study of Special -Diseases at Cambridge, Strangeways (1910) commented on the -striking resemblance that obtained between certain cases of -so-called <i>rheumatoid arthritis</i> and gout, as evidenced by X-ray -findings and section of the joints. Their similitude in these -respects suggested that the nature of the apparent kinship of the -two disorders might be elucidated by a study of <i>purin metabolism</i> -in instances of rheumatoid arthritis.</p> - -<p>To this end Ackroyd studied the purin metabolism in eleven -persons, the victims of rheumatoid arthritis. His conclusion -was that there was no important variation from the normal. -To quote his own words, he states that “it may be (1) completely -normal, or (2) while normal as regards endogenous excretion, the -period of increased uric acid excretion which follows the administration -of hypoxanthine may be prolonged for more than four -days. It is more likely that this effect is individual, than that it -is characteristic of any particular form of the disease, excepting -those cases in which the prolongation is accompanied by active -manifestation of the disease.”</p> - -<p>W. J. Mallory, critically analysing Ackroyd’s cases, points out -that he used only <i>hypoxanthine</i> in his studies; also that, while -<i>hypoxanthine</i> has this advantage, that it is of definite and known -chemical composition, furnishing a known quantity of basic -nitrogen, it labours under this drawback: “It is by simple -oxidation converted into uric acid, and probably calls into action -only a limited part of the ferment system concerned in the formation -of uric acid.” As a consequence, therefore, the amount -of information on metabolism that can be gleaned through its -usage is more restricted than if <i>nucleinic acid</i> were invoked in -its place; for this substance, on the other hand, calls into action -all the various enzymes concerned in the disruption of nuclein -or nucleic acid.</p> - -<p>Alive to these advantages, Mallory, in addition to hypoxanthine,<span class="pagenum"><a id="Page_114"></a>[114]</span> -used <i>nucleinic acid</i> in his investigations of purin metabolism in a -series of eight “undoubted cases of so-called rheumatoid arthritis.” -The value of the inclusion of nucleinic acid is revealed by the fact -that some of the cases, when given exogenous purin in the form -of <i>hypoxanthine</i>, showed no deviation from the normal. On the -other hand, when given <i>nucleinic acid</i>, a prolongation of the period -of increased uric acid excretion ensued; this even though the -total amount of basic nitrogen in nucleinic acid is less than in -hypoxanthine. Thus 4 grams of nucleinic acid have 0·2632 gram -of basic nitrogen, while 0·75 gram hypoxanthine has 0·309 gram -of basic nitrogen.</p> - -<p>Apart from his own series of cases, Mallory analysed those of -other observers, and his conclusions are as follows: “Of nineteen -cases of rheumatoid arthritis in which the purin metabolism -has been studied by three different observers, nine cases, or -47·3 per cent., show a marked variation from the normal in their -reaction to purin-containing substances while they are on a -purin-free diet.</p> - -<p>“In these cases the period of increased uric acid excretion -which follows the administration of purin-containing substances -is much <i>prolonged</i>. Following the administration of purin-containing -substances, a considerable number of cases suffer -from attacks of <i>sub-acute arthritis</i>, accompanied in some cases -by an increased uric acid excretion.”</p> - -<p>It will be seen that in virtue of:—</p> - -<div class="blockquote"> - -<p>(1) The prolongation of the period of exogenous uric acid -excretion, and</p> - -<p>(2) Increased uric acid excretion during attacks of sub-acute -arthritis,</p> - -</div> - -<p class="noindent">certain cases of <i>rheumatoid arthritis</i> manifest a certain resemblance -to gout, though, as Mallory remarks, “other features characteristic -of that disease are lacking.”</p> - -<p>It may be observed that the attacks of <i>sub-acute arthritis</i> that -ensued in rheumatoid subjects followed the administration of -<i>hypoxanthine</i>, as shown in Ackroyd’s series. That this reaction -to exogenous purin is suggestive of a relationship between -rheumatoid arthritis and gout derives colour from the fact that -it has been repeatedly induced in <i>gouty</i> subjects by the same -means. Thus, Brugsch and Mallory (1910), after giving 0·5 gram -of hypoxanthine to a gouty patient, noted a typical outbreak of -gout. Again, Brugsch and Schittenhelm, in the same year, -reported attacks of arthritis following the administration of -<i>nucleinic</i> acid to gouty subjects.</p> - -<p>Another feature worthy of note is that, in the cases of <i>rheumatoid -arthritis</i> investigated by Ackroyd and Mallory, the percentage of<span class="pagenum"><a id="Page_115"></a>[115]</span> -exogenous purin nitrogen excreted as uric acid nitrogen largely -exceeds that observed in any case of <i>gout</i> available for comparison -by these authors.</p> - -<p>Mallory’s final conclusions were that “there seemed to be -sufficient data to show that, in certain cases of so-called rheumatoid -arthritis, the purin metabolism is not normal. Whether these -cases are real gout, or only resemble that disease in certain -features, must be determined by further studies.”</p> - -<h3><span class="smcap">Purin Metabolism in Chronic Alcoholism and Plumbism</span></h3> - -<p>Quoting from Mallory’s contribution, we note that Pollak -investigated the purin metabolism in a series of cases of <i>chronic -alcoholism</i>. In five of the examples a marked derangement of -<i>purin metabolism</i> was noted and manifested, “partly in retention, -and partly in delayed excretion, or a combination of the two.” -Having observed these variations in cases of what he considered -were <i>non-gouty</i> alcoholics, Pollak felt justified in attaching but -limited diagnostic import to the results of the examination of -uric acid metabolism in gout, this though he realises the -importance of alcoholic excess as a cause of disturbed purin -metabolism.</p> - -<p>Mallory’s observations, too, on uric acid excretion in gout -complicated by <i>lead poisoning</i> are highly interesting. In two -cases of this nature he noted that the percentage of uric acid -nitrogen excreted was relatively small—in this respect in full -accord with previous observations of Brugsch and Schittenhelm -on a gouty patient with a history of plumbism, with this -reservation, that in the latter observers’ example there were -indications of early <i>renal</i> disease, while in Mallory’s two cases -such was absent, the urine being normal, and likewise the blood -pressure.</p> - -<p>Again, Pollak in a case of <i>lead gout</i> noted an extremely <i>low -endogenous average</i>, viz., a daily average endogenous excretion of -0·06 gram uric acid in a period of five days. Eschemburg, quoted -by Pollak, has recorded an instance of gout with plumbism in -which the excretion fell as low as 0·02-0·04 grams. It may be -noted that Pollak’s was the victim also of incipient <i>renal</i> disease.</p> - -<p>Reverting to Mallory’s conclusions, this observer’s studies of -examples of <i>gout</i> with <i>lead poisoning</i> seem to indicate that -“these cases differ from normal persons to a greater degree than -do other cases of gout.” It may, he thinks, be affirmed that the -subjects of gout and plumbism, as a rule, show “some or all of the -following characteristics in a much more marked degree than do -cases unassociated with lead”:—</p> - -<p><span class="pagenum"><a id="Page_116"></a>[116]</span></p> - -<div class="blockquote"> - -<p>(1) Slight fluctuation in the endogenous excretion.</p> - -<p>(2) Low endogenous average.</p> - -<p>(3) Small percentage of exogenous purin nitrogen excreted as -uric acid nitrogen.</p> - -</div> - -<p>To sum up, then, we see that poisons, other than those responsible -for gout, may engender obliquities of general metabolism, with -disturbances of purin assimilation and output, viz., lead, alcohol, -and the <i>causa causans</i> of rheumatoid arthritis. Also, in respect of -lead poisoning and alcoholism, further affinities with gout are discernible -in that, like the latter disorder, they tend in their later -stages to be associated with arterio-sclerosis and renal inadequacy.</p> - -<h3><span class="smcap">Infantile Gout</span></h3> - -<p>Apart from the fact that gouty arthritis may occur in young -children, Comby and other observers have noted that children -born of <i>gouty</i> parents display a tendency to inflammatory -changes in the cutaneous tissues and also in the mucous -membranes.</p> - -<p>These proclivities are difficult of explanation, but some further -observations by Czerny, Paltauf, Escherich, and Pfaunder are also -worthy of note. Under the headings of “exudative diathesis” or -“neuro-lymphatismus” they have described a symptom complex -marked by lymphatism with asthma, occasional vomiting, defective -nervous equilibrium, and eosinophilia. These varied -phenomena also are common in the descendants of <i>gouty</i>, diabetic, -and arthritic subjects.</p> - -<p>The clue to the true nature of these phenomena may possibly -reside in the fact noted and emphasised by Uffenheimer, viz., that -these children exhibit a <i>purin metabolism</i> identical with that met -with in <i>gouty</i> patients.</p> - -<p>From the foregoing consideration it is clear that further -observations are called for in the sphere of purin metabolism, and -it is, perhaps, not too much to hope that extended investigations -of the uric acid content of the <i>blood</i> may clarify and illumine the -conflicting results obtained by urine analysis.</p> - -<p>As before stated, we had intended in the next chapter dealing -with the question of “Uricæmia in Gout,” but on second thoughts -it appears desirable to us to interpolate a chapter devoted to -discussion of the primary <i>renal</i> origin of gout; for we take it -that, with the phenomena of <i>uric acid excretion</i> in <i>gout</i> fresh in -our minds, it will be more easy at this juncture to attempt solution -of this very intricate problem. This achieved, we shall resume our -thread and pass to the consideration of uricæmia and subsequently -uratosis in gout.</p> - -<hr class="chap x-ebookmaker-drop"> - -<div class="chapter"> - -<p><span class="pagenum"><a id="Page_117"></a>[117]</span></p> - -<h2 class="nobreak" id="CHAPTER_X">CHAPTER X<br> -<span class="smaller">THE RENAL THEORY OF GOUT</span></h2> - -</div> - -<p>This time-worn hypothesis as to the pathogeny of gout has, -perhaps, provoked more controversy than any other etiological -problem in the sphere of clinical medicine. Nor, unfortunately, -despite the endless laborious research expended upon its solution, -the dialectic skill exercised in attempts at its elucidation, can we -claim even to-day that its complexities have been wholly unravelled. -But, perhaps it will be wiser to postpone decision, -pending detailed analysis of the several grounds upon which the -theory of the primary renal origin of gout rests.</p> - -<p>Broadly speaking, the arguments adduced tend to concern -themselves with or rather to arise out of certain apparent <i>abnormalities</i> -in <i>uric acid excretion</i>, currently held distinctive of gout, -certain resemblances also suggestive of a hidden <i>nexus</i> between -<i>gout</i> and <i>renal</i> disorders, viz.:—</p> - -<p>(1) <i>Anomalies in uric acid excretion in gout.</i></p> - -<p>(2) <i>Uricæmia, a condition common to gout and nephritis.</i></p> - -<p>(3) <i>Uratosis, a feature also common to both disorders.</i></p> - -<p>(4) <i>Occasional co-existence of gout and nephritis.</i></p> - -<h3><span class="smcap">Anomalies in Uric Acid Excretion in Gout</span></h3> - -<p>As to the variations in <i>purin</i> excretion that occur in <i>gout</i>, it must -be admitted that, notwithstanding the magnitude of the researches, -no very striking departures from normal have emerged. Such -as have been elicited occur in relation to (<i>a</i>) the acute paroxysm, -(<i>b</i>) the excretion of exogenous purin.</p> - -<p><i>The Acute Paroxysm.</i>—Garrod, it will be recalled, claimed that -during an <i>acute</i> attack of gout the excretion of uric acid was -diminished, and that coincidently therewith the uric acid blood -content rose. But these findings in the <i>blood</i> and <i>urine</i>, which -constituted the basis of his hypothesis that gout was due to <i>renal -inadequacy</i>, have, as previously noted, been categorically disproved.</p> - -<p>Turning to the more modern findings upon which such refutation -of Garrod’s view was achieved, one point emerges that appears to -favour the assumption of <i>renal block</i>. It is that, <i>one or two days -prior to an acute attack</i>, an appreciable <i>decline</i> in the output of uric -acid occurs.</p> - -<p><span class="pagenum"><a id="Page_118"></a>[118]</span></p> - -<p>But this, be it noted, is neither so marked nor so constant as the -subsequent <i>increase</i>; in short, at the zenith of an acute attack, -<i>an augmented output of uric acid</i> ensues. At the very time when -presumably the alleged functional renal impediment would be -most pronounced, the impermeability of the organs for uric acid -accentuated! Surely such behaviour seems scarcely compatible -with the supposition that there is even a temporary diminution -in the capacity of the kidney to excrete uric acid. Does it not in -truth constitute strong proof of the reverse? Moreover, the said -vagaries that herald the oncoming and that chequer the course of -the paroxysm are not <i>invariable</i>, an obvious <i>caveat</i> against -hasty <i>etiological</i> inferences therefrom. Any tendency thereto -should also be curbed by the reflection that, viewing the character -of the uric acid excretion in gout as a whole, the variations therein -are not more extensive than in <i>healthy</i> individuals, and assuredly, -<i>on the mere basis of the fluctuations in uric acid excretion</i>, no -diagnosis of gout is possible.</p> - -<p><i>Retarded Purin Elimination.</i>—The mainstay in argument, however, -as advanced by more modern advocates of the renal theory -of gout, is that a <i>retarded output of exogenous purin</i> is typical of -this disorder; but, here, again, there is no room for dogmatism. -Thus Walker Hall reminds us that “the quantity of purins -present in the food does not overstep the solubility of urates in the -blood-stream, for once the material is metabolised and ready for -removal the amount of blood, so far as solubility goes, places the -whole amount of purins within the reach of the renal cells in less -than twenty-five minutes.” We see, therefore, as far as <i>rapidity -of transport</i> to the kidneys is concerned, there is no delay in presentation -of the opportunity for the excretion of exogenous purin. -While the alleged tardiness of output is attributed to defective -action of the <i>kidneys</i>, it is at least equally possible that the delay, -as Walker Hall states, “may be due to a defective or idiosyncratic -nuclear metabolism, which results in the formation of isomeric -purins or incomplete purin combination, and which makes greater -demands upon the selective activities of the renal cells;” for it -must be recollected that as yet we are ignorant as to the exact form -in which uric acid circulates in the blood-stream, whether as -<i>sodium mono-urate</i> or in <i>organic</i> combination.</p> - -<p>Moreover, experimental <i>injections of uric acid</i> into the <i>tissues</i> or -<i>veins</i> show no impairment in the elimination capacity of the -kidneys for uric acid. Thus, Wells cites evidence that “the kidney -in gout shows no lack of ability to excrete uric acid injected into -the tissues.”</p> - -<p>Again, given <i>intravenous</i> injection of uric acid into a <i>normal</i> man, -its excretion occupies several days, and it fails to appear <i>quantitatively</i><span class="pagenum"><a id="Page_119"></a>[119]</span> -in the urine. But if administered during a course of <i>atophan</i>, -then the <i>whole</i> amount injected is excreted within twenty-four -hours. If the same procedure be followed in a <i>gouty</i> individual, -precisely the same results are obtained; in other words, both -normal and gouty kidneys react in identical fashion to atophan. -Given an inherent functional defect, <i>quâ</i> uric acid excretion, -in the <i>gouty kidney</i>, one would scarcely expect a wholly <i>normal</i> -reaction thereto. Surely some disparity would be disclosed, -some aberration in response as compared with <i>normal</i> renal -organs.</p> - -<p>Again, while McLester and others claim that atophan exerts -“a selective stimulating influence on uric acid excretion,” it is -quite possible that its <i>rôle</i> may be otherwise explained. May it -not influence the actual <i>formation</i> of uric acid, or, failing this, the -<i>form</i> in which it is presented to the kidneys for excretion? -Nicolaier and Dohrn, indeed, believe that <i>atophan</i> influences in -some way purin metabolism within the <i>muscles</i> and so leads to -<i>increased formation and excretion of uric acid</i>. At any rate, whatever -be the explanation of the action of atophan, the fact that -<i>healthy</i> and <i>gouty</i> kidneys react <i>alike</i> thereto cannot be interpreted -as proof of defective capacity for uric acid elimination in gouty -subjects, indeed the reverse.</p> - -<p>Moreover, in all our attempts to saddle the kidneys with the -responsibility for the delay in exogenous purin excretion, we are -for ever hampered in that we know not whether the alleged renal -impairment is <i>primary</i> or <i>secondary</i> to the gout. That the kidneys -are frequently functionally inefficient in the <i>later</i> stages of gout -may be conceded. But what of the <i>initial</i> phases of the disorder? -Some talk very glibly of subjects who are, they say, “potentially -gouty.” But has the rate of disposal of ingested purins been -investigated in persons suffering from so-called “goutiness,” -or, perhaps more pertinently, in those individuals, not uncommon, -who, while exhibiting <i>auricular tophi</i>, have yet experienced no -frank attack of gout?</p> - -<p>In this connection we may note that McClure has recently -emphasised the fact that the <i>kidneys</i>, in the <i>later</i> stages of gout, -are often <i>functionally</i> deficient, and that, accordingly, the faulty -elimination of exogenous uric acid by gouty persons may be -simply the result of such <i>functional renal depression</i>; in other -words, not due to gout, but to the <i>secondary</i> or <i>associated renal -deficiency</i>. Hence, having regard to the frequency with which -renal inefficiency is met with in gout of any standing, he -is inclined to discount the value of studies of <i>exogenous uric -acid elimination</i> as an aid to the diagnosis of gout. Consequently, -he holds that before the diagnostic status of retarded<span class="pagenum"><a id="Page_120"></a>[120]</span> -purin elimination, as a symptom of gout, can be established, an -investigation of the output of uric acid in the different types of -<i>nephritis</i> is essential.</p> - -<p>From the foregoing it will be seen that we stand in urgent need -of further studies of <i>early</i> or <i>oncoming</i> gout and of <i>early nephritis</i> -before we can with certitude impeach the <i>kidneys</i> as responsible -for the delay in exogenous purin output. Meanwhile, too, we -must be careful not to overlook the further disconcerting fact, -previously adverted to, that the retardation and diminution of -exogenous purin output is not <i>invariable</i> in gout. Nor, for that -matter, is it <i>peculiar</i> to gout, considerations both of which, if -confirmed, will still further discount the <i>diagnostic</i> significance -of this phenomenon.</p> - -<h3><span class="smcap">Uricæmia in Nephritis</span></h3> - -<p>Von Jaksch and Klemperer noted long since that in chronic -interstitial nephritis urates are always present in the <i>blood</i>. Now, -according to Folin and Denis, human blood contains 1·5-2·5 mg. -of uric acid per 100 c.c.; but if the eliminating powers of the -<i>kidney</i> be deficient, the uric acid content thereof rises, sometimes -to as high as from 15-20 mg. per 100 c.c.</p> - -<p>But more interesting still the fact noted by Fine, viz., that even -in <i>early</i> interstitial nephritis the same feature is well marked, <i>i.e.</i>, -the blood may contain 4-8 mg. of uric acid per 100 c.c. Indeed, -according to this authority, increase in the <i>uric acid</i> content of the -blood is the first signal of impaired renal efficiency. This, be it -noted, without any coincident proportional increase in the blood -content of <i>urea</i> or <i>creatinine</i>. The sequence would appear to -indicate that the damaged organ encounters greater difficulty in -excreting <i>uric acid</i> than these other metabolites.</p> - -<p>But, <i>pari passu</i> with the advance of the renal disease, retention -of <i>urea</i> is superadded, and still later <i>creatinine</i>. So constant, -indeed, the sequence that, by determining the percentage amount -of these three <i>metabolites in the blood</i>, the measure of the renal -mischief may be gauged.</p> - -<p>But of striking significance is the further point established by -Myers and Fine, viz., that the blood content, in respect of <i>uric -acid</i>, <i>urea</i>, and <i>creatinine</i>, in <i>early nephritis</i>, is an almost exact -replica of that met with in typical cases of <i>gout</i>. The same is well -illustrated in the following table, in which the blood content, in -respect of these three metabolites, in cases of gout and early and -late nephritis is contrasted. The percentage of the retained -metabolites in relation to the severity of the case is gauged by the -blood pressure findings.</p> - -<p><span class="pagenum"><a id="Page_121"></a>[121]</span></p> - -<h3><span class="smcap">Uric Acid, Urea N, and Creatinine of Blood in Gout -and Early and Late Nephritis</span></h3> - -<table class="borders"> - <tr> - <th>Diagnosis.</th> - <th>Uric<br>acid.</th> - <th>Urea N.<br>Mg. to<br>100 c.c. blood.</th> - <th>Creatinine.</th> - <th>Systolic<br>blood<br>pressure.</th> - </tr> - <tr class="bt"> - <td rowspan="4">Typical cases of gout.</td> - <td class="tdr">9·5</td> - <td class="tdr">13</td> - <td class="tdr">1·1</td> - <td class="tdr">230</td> - </tr> - <tr> - <td class="tdr">8·4</td> - <td class="tdr">12</td> - <td class="tdr">2·2</td> - <td class="tdr">164</td> - </tr> - <tr> - <td class="tdr">7·2</td> - <td class="tdr">17</td> - <td class="tdr">2·4</td> - <td class="tdr">200</td> - </tr> - <tr> - <td class="tdr">6·8</td> - <td class="tdr">14</td> - <td class="tdr">1·7</td> - <td class="tdr"></td> - </tr> - <tr class="bt"> - <td rowspan="10">Typical early interstitial nephritis.</td> - <td class="tdr">9·5</td> - <td class="tdr">25</td> - <td class="tdr">2·5</td> - <td class="tdr">185</td> - </tr> - <tr> - <td class="tdr">8·0</td> - <td class="tdr">37</td> - <td class="tdr">2·7</td> - <td class="tdr">150</td> - </tr> - <tr> - <td class="tdr">5·0</td> - <td class="tdr">37</td> - <td class="tdr">3·9</td> - <td class="tdr">130</td> - </tr> - <tr> - <td class="tdr">7·1</td> - <td class="tdr">16</td> - <td class="tdr">2·0</td> - <td class="tdr"></td> - </tr> - <tr> - <td class="tdr">6·6</td> - <td class="tdr">24</td> - <td class="tdr">3·3</td> - <td class="tdr">185</td> - </tr> - <tr> - <td class="tdr">6·3</td> - <td class="tdr">18</td> - <td class="tdr">2·1</td> - <td class="tdr"></td> - </tr> - <tr> - <td class="tdr">8·7</td> - <td class="tdr">20</td> - <td class="tdr">3·6</td> - <td class="tdr">100</td> - </tr> - <tr> - <td class="tdr">7·0</td> - <td class="tdr">33</td> - <td class="tdr">2·6</td> - <td class="tdr">117</td> - </tr> - <tr> - <td class="tdr">6·3</td> - <td class="tdr">31</td> - <td class="tdr">2·1</td> - <td class="tdr"></td> - </tr> - <tr> - <td class="tdr">6·3</td> - <td class="tdr">23</td> - <td class="tdr">2·4</td> - <td class="tdr">150</td> - </tr> - <tr class="bt"> - <td rowspan="10">Chronic diffuse and chronic interstitial nephritis.</td> - <td class="tdr">8·0</td> - <td class="tdr">80</td> - <td class="tdr">4·8</td> - <td class="tdr">240</td> - </tr> - <tr> - <td class="tdr">4·9</td> - <td class="tdr">17</td> - <td class="tdr">2·9</td> - <td class="tdr">170</td> - </tr> - <tr> - <td class="tdr">8·3</td> - <td class="tdr">72</td> - <td class="tdr">3·2</td> - <td class="tdr">238</td> - </tr> - <tr> - <td class="tdr">5·3</td> - <td class="tdr">21</td> - <td class="tdr">1·9</td> - <td class="tdr">145</td> - </tr> - <tr> - <td class="tdr">9·5</td> - <td class="tdr">44</td> - <td class="tdr">3·5</td> - <td class="tdr">210</td> - </tr> - <tr> - <td class="tdr">2·5</td> - <td class="tdr">19</td> - <td class="tdr">1·9</td> - <td class="tdr">120</td> - </tr> - <tr> - <td class="tdr">7·7</td> - <td class="tdr">67</td> - <td class="tdr">3·1</td> - <td class="tdr"></td> - </tr> - <tr> - <td class="tdr">6·7</td> - <td class="tdr">17</td> - <td class="tdr">1·6</td> - <td class="tdr">165</td> - </tr> - <tr> - <td class="tdr">8·3</td> - <td class="tdr">39</td> - <td class="tdr">2·9</td> - <td class="tdr"></td> - </tr> - <tr> - <td class="tdr">6·5</td> - <td class="tdr">24</td> - <td class="tdr">3·0</td> - <td class="tdr">200</td> - </tr> - <tr class="bt"> - <td rowspan="5" style="border-bottom: thin solid black;">Typical fatal chronic interstitial nephritis.</td> - <td class="tdr">22·4</td> - <td class="tdr">236</td> - <td class="tdr">16·7</td> - <td class="tdr">210</td> - </tr> - <tr> - <td class="tdr">15·0</td> - <td class="tdr">240</td> - <td class="tdr">20·5</td> - <td class="tdr">225</td> - </tr> - <tr> - <td class="tdr">14·3</td> - <td class="tdr">263</td> - <td class="tdr">22·2</td> - <td class="tdr">220</td> - </tr> - <tr> - <td class="tdr">13·0</td> - <td class="tdr">90</td> - <td class="tdr">11·1</td> - <td class="tdr">265</td> - </tr> - <tr> - <td class="tdr">8·7</td> - <td class="tdr">144</td> - <td class="tdr">11·0</td> - <td class="tdr">225</td> - </tr> -</table> - -<p class="center smaller">(Myers and Fine: “Arch. Int. Med.,” 1916.)</p> - -<p>The salient feature of the table is, however, the fact that in -<i>early interstitial nephritis</i> the retention of <i>uric acid</i> precedes that -of <i>urea</i> or <i>creatinine</i>.</p> - -<p>Its importance resides in the reflection that it lends support to -those who contend that <i>renal change</i>, leading to failure of excretion -of uric acid, <i>is the primary cause of gout</i>; in other words, it -gives colour to Magnus Levy’s contention that the phenomena of<span class="pagenum"><a id="Page_122"></a>[122]</span> -gout are referable to “a deficient and restricted secretory power -of the kidney.” The existence of such a selective excretory -incapacity, <i>i.e.</i>, for <i>uric acid</i>, does not, he considers, predicate a -genuine nephritis. He maintains that such disability on the part -of the kidney for uric acid excretion may exist without <i>morphological</i> -change; in other words, he thinks it conceivable that a -<i>single</i> function of the kidney can become almost exclusively -insufficient, though later real damage to the organ and a nephritis -frequently follow.</p> - -<p>Reflecting on the above theory, it is obvious that, if carried to its -logical conclusion, it would appear to postulate that gout is nothing -more than a form of <i>renal disorder</i>, marked simply by <i>functional -inability to excrete uric acid</i>. The postulate is no mean one, for, -as Sir Archibald Garrod says, “If the fault is in the kidneys alone, -gout must be removed once and for all from the category of -metabolic disorders, and placed among the sequelæ of renal -inadequacy, at least in so far as the uric acid phenomena of the -disease are concerned.”</p> - -<p>Furthermore, Levy’s hypothesis involves the assumption that -the excreting functions of the kidney for <i>uric acid and urea</i> are -separate and independent of each other, and to discussion of this -we now pass on.</p> - -<h3><span class="smcap">The Relationship, if any, between the Amounts of Uric -Acid and of Urea, and Total Non-Protein Nitrogen in -Human Blood</span></h3> - -<p>Taking samples of human blood from (1) <i>unselected insane</i> -subjects and (2) <i>chronic nephritics</i>, Folin and Denis determined -the amounts therein of urea, total non-protein nitrogen, and uric -acid. The figures obtained showed that “there is apparently no -relationship between the amount of uric acid and the amount of -urea or total non-protein in nitrogen, in human blood.”</p> - -<p>That such a discrepancy should obtain is doubtless of profound -though as yet imperfectly grasped significance. These authorities -rightly assume that, since the kidney is practically the sole avenue -for nitrogenous waste excretion, it follows that the <i>urea</i> and <i>total -non-protein nitrogen</i> of the <i>blood</i> must in the main be inversely -proportional to the general efficiency of the <i>renal</i> organs. Then, -obviously, the same law, too, should, in lack of some other plausible -explanation, govern the excretion of <i>uric acid</i> also. But, as the -above generalisation portends, it is apparently not so.</p> - -<p>Fortunately, Folin and Denis prosecuted their study still -further, taking in examples of <i>gout</i> (with and without clinically -recognisable <i>nephritis</i>), also instances of <i>leukæmia</i> and <i>lead -poisoning</i>.</p> - -<p><span class="pagenum"><a id="Page_123"></a>[123]</span></p> - -<p>The blood, again, in these disorders betrayed the same peculiarity, -viz., that while containing an excess of uric acid, it did not -contain correspondingly large amounts of urea or other waste -nitrogen; in other words, the findings in the blood in gout were -in full accord with the above generalisation, <i>i.e.</i>, <i>the apparent lack -of any relationship between the amount of uric acid and that of urea -or total non-protein nitrogen in the blood</i>.</p> - -<p>Now in <i>leukæmia</i> the cause of the <i>uricæmia</i> is <i>over-production</i> -of uric acid, but in this instance the same is correlated with an -increased <i>elimination</i> of uric acid by the kidneys.</p> - -<p>Turning to lead poisoning, the medicinal administration of lead -acetate results in a great <i>diminution</i> of uric acid excretion, a -response consistent with the view that lead inhibits the excretory -power of the kidney for <i>uric acid</i>, the change, at first functional, -becoming later organic; for it is held that the <i>uricæmia</i>, associated -with plumbism, proves that the action of the lead is not due -to inhibition of the formation of uric acid.</p> - -<p>Lastly, as to gout, opinion still wavers as to whether or not the -excretion of uric acid in this disorder is appreciably <i>lowered</i>. On -the other hand, it is significant that the reverse is never claimed, -viz., that in gout the uric acid output is <i>abnormally raised</i>. -Now, as we saw in <i>leukæmia</i>, the <i>high uric acid blood content</i> is -accompanied by a correspondingly <i>high uric acid output</i>; but, on -the contrary, in gout, despite the <i>accumulation of uric acid in the -blood</i>, there is <i>no parallel increase in its elimination</i>.</p> - -<p>Reflecting on the above considerations, Folin and Denis claim -that “the mere fact that the uric acid may accumulate in the blood -of the gouty without being accompanied by an increased elimination -constitutes definite proof that the gouty kidney is damaged -with reference to its ability to eliminate uric acid.”</p> - -<p>In all deference, we doubt the legitimacy of the inference, if -only for the very excellent reason that, to quote Von Noorden’s -words, even to-day “it remains uncertain whether the retention -of urate arises because the outlet is blocked, or because the uric -acid is held fast by chemical affinities.”</p> - -<p>Apart from this, there are several objections to Folin and Denis’ -assumption.</p> - -<h3><span class="smcap">Uricæmia not Necessarily Due To Renal Defect</span></h3> - -<p>Thus Pratt, in some examples of his cases of gout, found that -there was no apparent diminution or delay in the output of -exogenous purin in the urine. On the other hand, he observes -that “our study of the blood shows that <i>a marked increase in -retention of uric acid in the blood</i> may result from the ingestion of -purin bases even when <i>no evidence of retention is found on examination<span class="pagenum"><a id="Page_124"></a>[124]</span> -of the urine</i>.” This would appear to indicate that the uricæmia, -sequential to exogenous purin intake, ensues independently of and -apparently despite the absence of any delay or diminution in uric -acid elimination.</p> - -<p>Again, Walker Hall, discussing the metabolism of exogenous -purins, reminds us that a gouty subject excretes an excess thereof -as completely as a normal individual, with only this difference, -that he takes a longer time to do so; but even this disability is -removed by a simultaneous intake of atophan. His comment is -that “the gouty kidney, therefore, is not poisoned beyond compensating -for and responding to an extra load.” “Perhaps,” he -says, “the situation may be summed up in the observation that -<i>the uricæmia of the gouty is maintained in spite of a fair renal -elimination</i>.”</p> - -<h3><span class="smcap">Uricæmia not Peculiar to Nephritis</span></h3> - -<p>Again, a grave obstacle to the acceptance of Folin and Denis’ -inference is that uricæmia, though incidental to nephritis, is not -peculiar thereto.</p> - -<p>Thus Roy Upham and Higley noted its presence in 85·6 per cent. -of their cases of <i>nephritis</i>; but, on the other hand, they found -that no less than 40 per cent. of another series of clinical cases, not -<i>suffering from nephritis</i>, also showed uricæmia.</p> - -<p>This would appear to indicate that, while uricæmia is an exceedingly -common symptom of early chronic interstitial nephritis, -it is by no means <i>specific</i> for that disorder; in other words, its -diagnostic valency as a symptom of <i>nephritis</i> is distinctly limited.</p> - -<p><i>Reverting</i> now to <i>gout</i>, what evidence is there that the uricæmia -therein is due to defective eliminatory capacity on the part of the -kidney for uric acid? Certainly there is no proof that the kidney, -at any rate in the <i>initial</i> stages of gout, suffers from this particular -functional disability. Indeed, the fact that, at the very acme of -an acute attack, the output of uric acid is not only not diminished, -but actually <i>increased</i>, constitutes strong proof of the reverse.</p> - -<p>Again, as modern investigations show, the variations in the uric -acid content of the <i>blood</i>, <i>re</i> the incidence or intensity of attacks, -are most <i>erratic</i>. Far from its being essential that uricæmia be -present, acute attacks may occur with even a <i>sub-normal</i> uric acid -blood content; in short, the variations are so erratic as to seem -quite out of keeping with the assumption that the uricæmia in gout -is primarily of <i>renal</i> origin.</p> - -<p>If it were so, one would expect no such vagaries in the uric acid -content of the blood. One would rather, given the existence -<i>ab initio</i> of a <i>renal functional defect</i>, look for not only a permanent -<i>uricæmia</i>, but further, from time to time, augmentations and<span class="pagenum"><a id="Page_125"></a>[125]</span> -diminutions thereof, synchronising with the rise and wane of -gouty paroxysms; in other words, that in gout the clinical course -and crises of the disorder would be linked up with harmonious -variations in the degrees of uricæmia.</p> - -<h3><span class="smcap">Uricæmia does not Necessarily Portend Gout</span></h3> - -<p>If it were so, why does not every case of nephritis develop -gout? The researches of Myers and Fine have shown that <i>uric acid</i> -is the nitrogenous metabolite that first <i>accumulates</i> in the <i>blood</i> -in <i>early</i> interstitial nephritis. Only in its <i>later</i> stages do urea and -other waste nitrogenous products undergo like retention therein.</p> - -<p>Now let us review these findings, <i>re</i> nephritis, in light of another -statement by Folin and Denis, which runs as follows:—</p> - -<p>“In pure gout, unaccompanied by any abnormal urea retention -in the blood, the kidney is damaged (so far as we yet know) -only with its function of removing down to the normal level the -uric acid of the blood.”</p> - -<p>Is it not clear, then, that in the <i>early</i> stages of <i>nephritis</i>, viz., prior -to retention of urea and other waste nitrogen, we have precisely -that isolated functional renal disability, <i>i.e.</i>, <i>inability to excrete uric -acid</i>, that we postulate to be in operation in the <i>initial</i> stages of -<i>gout</i>?</p> - -<p>Yet, notwithstanding this similitude in the blood content of -the two disorders, cases of nephritis do not necessarily develop -gout. Indeed, as a matter of fact, examples of nephritis, of all -grades and intensities, may run to their full end without manifesting -any symptoms even remotely reminiscent of gout. Even -Magnus Levy, ardent advocate as he is of the primary renal origin -of gout, could not but admit that this salient clinical obstacle -barred the way to acceptance of his otherwise plausible view. -However, he fails to proffer any other solution of the problem.</p> - -<p>To our mind, albeit, the disparity carries with it the inevitable -postulate that in gout some other factor intrudes, some <i>tertium -quid</i>, something vital, something biological, haply an <i>infection</i>. -For even if we grant, for the sake of argument, that <i>renal retention</i>, -if it were proved, might explain such anomalies in the excretion -of uric acid and other nitrogenous metabolites as occur in -gout, yet, nevertheless, no one could possibly contend that this -factor alone could explain the nature of gout, could adequately -account for its dramatic and protean phenomena.</p> - -<h3><span class="smcap">To what may be Ascribed the Deficient Eliminating -Capacity of the Kidney for Uric Acid?</span></h3> - -<p>Naturally the advocates of the renal theory had to account in -some way for the alleged functional disability of the kidney. Thus,<span class="pagenum"><a id="Page_126"></a>[126]</span> -Sir Dyce Duckworth, recalling the occasional occurrence in -hysteria of <i>anuria</i>, held that, judging from the general phenomena -of acute gout, “the influence of the <i>nervous system</i> ... must not -be left out of account as a possible determining factor for renal -inadequacy.”</p> - -<p>Others, with whom Duckworth disagreed, propounded the view -that the deposition of urates in the renal tissues was essential for -the initiation of a nephritis in the gouty. Duckworth, on the -other hand, held that nephritis could develop in their absence.</p> - -<p>Croftan considers the renal changes in gout identical with those -of chronic plumbism. From experiments with hypodermic injections -of <i>xanthine</i> and <i>hypoxanthine</i> over a prolonged period, he -concludes that the presence of minute quantities of purin bases in -the circulation is capable of producing <i>marked renal changes</i>. On -the other hand, <i>uric acid</i>, injected into the circulation of healthy -animals for a period of over three months, produced <i>no renal -change</i> whatever.</p> - -<p>As to this possibility, viz., that the <i>circulating uric acid</i> might -lead to <i>nephritis</i> in the <i>gouty</i>, some reflections of Folin and Denis -are instructive. Normal blood, according to these observers, contains -not less than from 1-2 or 2-5 mg. per 100 grams, while -that of <i>gouty</i> blood does not, in their experience, exceed 6 mg. -Continuing, they observe, “There is, however, no reason to -suppose that a uric acid concentration of 4-6 mg. per 100 grams of -blood is very much more irritating or stimulating to the kidney -than the somewhat more dilute solution represented by normal -blood. Disregarding the insolubility of uric acid, the elevation of -its threshold of elimination from 2-4 or 6 mg. (per 100 grams of -blood) is certainly a small one. Kidneys in which the threshold -of elimination for urea has risen by 10-20 mg. (per 100 grams), -or even more, are extraordinarily common.”</p> - -<p>While they consider that such <i>urea</i> and <i>total nitrogen retention -may</i> possibly bespeak <i>latent</i> or <i>incipient nephritis</i>, they recognise -that no appreciable effects on health have as yet been determined -in connection therewith. But more pertinently to our point, they -make the further pregnant observation, “In the case of uric acid -it seems to be purely a matter of insolubility that corresponding -or even smaller degrees of kidney insufficiency with slight uric acid -accumulation should result in all the serious consequences involved -in the development of gout”!</p> - -<p>Again, some have attempted to account for the assumed renal -incapacity as being part of the <i>tissue peculiarity</i> of the gouty -subject. “Without doubt,” says Duckworth, “there are peculiarities -of tissue in the gouty, and with this may very possibly be -associated peculiarities of tissue function and metabolism.”</p> - -<p><span class="pagenum"><a id="Page_127"></a>[127]</span></p> - -<p>Naturally this suggests the further question, Are there any -distinctive <i>histological</i> changes in the <i>gouty</i> kidney? On this -point Walker Hall has some apposite reflections. Taking Folin’s -figures as a basis, it transpires that in <i>acute</i> and <i>chronic nephritis</i>, -also in <i>arterio-sclerosis</i>, there is an average content of 2·5 mg. -uric acid per 100 grams of blood. Now, notwithstanding the fact -that in these conditions an appreciable quantity of the renal -tissues is, functionally speaking, temporarily or permanently out -of action, nevertheless “the extraction of uric acid from the -blood and its subsequent excretion are practically normal.” The -inference is that a relatively small moiety of renal tissue suffices -for the excretion of the daily quantum of uric acid in the urine.</p> - -<p>Now in contrast thereto, the blood content in <i>gout</i> and <i>lead -poisoning</i> is about 4·5 mg. uric acid per 100 grams of blood, or -“an increase of about 50 mg. in the total blood-stream at any one -moment (an increase from the normal 70 up to 120 mg.).” Continuing, -Walker Hall observes that “the gouty kidney <i>per se</i>, even -when arterio-sclerotic conditions prevail, does not show anything -like the amount of cellular damage which occurs in acute or -chronic diffuse nephritis.” Thence he argues if <i>histological</i> -changes be taken as a criterion of functional efficiency, then the -<i>gouty</i> kidney should be more capable of excreting freely than the -<i>diffuse nephritic</i> organ.</p> - -<p>How does this work out in actual daily life? he asks. “0·5 gram, -in a <i>normal</i> adult, represents the <i>average daily endogenous uric acid -excretion</i> in the urine, while that of a <i>gouty</i> subject is about -0·45 gram. Now, assuming that the type and extent of the endogenous -metabolism is identical in each instance, then the balance, -<i>i.e.</i>, 0·05 gram, is distributed between the uric acid pent up in -the tissues and the uratic deposits, <i>i.e.</i>, tophi.” Walker Hall tells -us it has been stated that about 0·01 gram suffices to cover the -amount deposited as <i>tophi</i> every twenty-four hours. The residual -0·04 gram runs to swell the amount in the blood and lymph-streams. -“The increase is 0·0114 to 0·0118 gram per litre of -blood; in other words, the actual increase of uric acid circulating -through the kidneys is about 0·00047 per hour,” which, as Walker -Hall contends, “seems to be a very trifling difference, especially -as it is one of amount and not a type.” In other words, it is -<i>quantitative</i>, not qualitative. But, trivial as the disparity is, to -what may it be referred? To Walker Hall’s mind, if we are to -appreciate the standpoint of those who maintain that the gouty -<i>uricæmia</i> is referable to <i>renal inadequacy</i>, it is necessary to postulate -<i>the presence of a poison acting upon the renal tubules specifically</i>.</p> - -<p>In the gouty uric acid excretion is maintained at a “<i>low physiological -level to the very end</i>,” and it is easier, he thinks, to adopt the<span class="pagenum"><a id="Page_128"></a>[128]</span> -above hypothesis as to its cause than “to conceive of a poison -acting upon the <i>nuclear</i> processes in such a way as to induce -a persistently low uniform level” of purin excretion.</p> - -<p>This view, viz., of a <i>toxin</i> acting specifically upon the uric acid -excreting cells of the kidney, seems to be the only reasonable -assumption available. But even this is difficult of adherence -when we recall the fact that the effect of the toxin is so readily -neutralised by a few grains of <i>atophan</i>. Always we have to -recollect, too, that under <i>normal</i> conditions, even given a <i>constant</i> -diet, the elimination of uric acid displays <i>wide variations</i>. Also -the uric acid output in the subjects of <i>chronic gout</i>, when placed -on a <i>fixed</i> diet, differs but little from that of <i>normal</i> individuals -on a like dietary. At most the excretion but tends to fall to, or -slightly below, the lower normal limits of uric acid elimination.</p> - -<p>From the foregoing considerations it is but too obvious that -those who render obeisance to the primary renal origin of gout -have not only yet to prove that the functions of the kidney are -defective, but also upon them lies the <i>onus probandi why</i> gouty -subjects should exhibit, or acquire, such a disability.</p> - -<h3><span class="smcap">Uratic Deposits in Nephritis</span></h3> - -<p>Here, again, we light upon another point of contact between -gout and nephritis, for an interesting feature of the latter -disorder is that the retained uric acid, purins, and other excretory -products are deposited in <i>cartilage</i> and <i>serous membranes</i>. At -these sites they are frequently detected post mortem, though they -fail of <i>ante-mortem</i> recognition.</p> - -<p>Impressed by the fact that, at post-mortems, uratic incrustation -of the articular cartilages was frequently observed in persons who -had never suffered from overt gout, Ord and Greenfield sought to -ascertain the frequency with which such uratic deposits were -associated with <i>renal</i> disease. Out of ninety-six cases presenting -renal lesions, no less than eighteen exhibited uratic deposits in -the joints.</p> - -<p>A still more elaborate research in this sphere was undertaken -by Norman Moore. Out of forty-nine cases of chronic interstitial -nephritis, uratic deposits were present in twenty-two instances. -Again, out of nine cases of chronic parenchymatous nephritis, -deposits were found in the joints in two cases. With respect to -the first group he observes that “chronic interstitial nephritis -is not invariably accompanied by deposits in the articular cartilages, -though usually accompanied by traces of degeneration in -some of the articular cartilages.”</p> - -<p>Levison, too, an ardent supporter of the primary renal origin -of gout, noted that all the subjects dying at the Communal<span class="pagenum"><a id="Page_129"></a>[129]</span> -Hospital, Copenhagen, of granular kidney disease (during a period -of fourteen months) exhibited uratic deposits in one or other of -their joints, although they were never known to have had any -definite attack of gout.</p> - -<p>Luff, in the following table, shows the results of the examination -of the joints in seventy-seven cases of <i>granular kidney disease</i>.</p> - -<table class="borders"> - <tr> - <th></th> - <th>No. of cases.</th> - <th>Uratic deposits<br>in joint<br>or joints.</th> - </tr> - <tr> - <td>Known to have had gout</td> - <td class="tdr">10</td> - <td class="tdr">10</td> - </tr> - <tr> - <td>Never known to have had gout</td> - <td class="tdr">67</td> - <td class="tdr">31</td> - </tr> - <tr> - <td class="tdr">Totals</td> - <td class="tdr bt">77</td> - <td class="tdr bt">41</td> - </tr> -</table> - -<p>Of the ten cases known to have suffered from gout, the renal -condition was in every instance defined as “markedly granular,” -or “fairly granular.” Uratic deposits were invariably present in -one or more joints. Of the sixty-seven examples not known to -have had gout, uratic articular deposits were found in 46 per cent., -which approximates, more or less closely, to Norman Moore’s -findings. It is noteworthy that in several of the instances, -lacking uratic deposits in the joints, the kidneys were described -as “slightly granular,” or “faintly granular.”</p> - -<table class="borders"> - <tr> - <th></th> - <th>No. of cases.</th> - <th>Uratic deposits<br>in joint or<br>joints.</th> - </tr> - <tr> - <td>Marked granular kidney disease</td> - <td class="tdr">26</td> - <td class="tdr">20</td> - </tr> -</table> - -<p>If of the sixty-seven cases there be selected only those described -as “markedly granular,” or “typical granular kidneys,” the -incidence of uratic deposits in the joints, as revealed by the second -table, reaches no less a figure than 77 per cent.</p> - -<p>Another authority, discussing the frequency of incidence of -uratic deposits in the joints in cases of chronic interstitial -nephritis, states that, at post-mortem, from 50-80 per cent. show -their presence—this, moreover, in cases <i>known not to have had gout</i>.</p> - -<h3><span class="smcap">Differentiation of Uratic Deposits in Gout and Nephritis</span></h3> - -<p>Uratic deposits, it is true, occur in both these disorders. But -it is with a difference. In gout the uratic deposit assumes the<span class="pagenum"><a id="Page_130"></a>[130]</span> -form of <i>tophi</i>, whereas in nephritis it is not so. In the latter the -uratic deposit is in the nature of a passive deposition—an uratic -incrustation of the articular cartilages.</p> - -<p>Again, in gout the deposition is <i>sudden</i> and associated with an -acute paroxysm; while in nephritis it is <i>gradual</i> and unassociated -with inflammatory reaction.</p> - -<p>In gout the uratic deposits are overt, manifest as <i>tophi</i>; in -nephritis, occult and unrevealed (ante-mortem).</p> - -<p>Uratic deposits in the form of tophi occur in gout, in the absence -of clinically recognisable interstitial nephritis. But tophi do not -occur in nephritis if uncomplicated by gout.</p> - -<p>In conclusion, the mere fact that uratic deposits affect such -widely disparate forms in these two disorders is to our mind a -sure indication that their mode of origin and formation is -equally diverse—the one vital, biological; the other passive, -mechanical.</p> - -<h3><span class="smcap">Clinical Associations of Gout and Granular Kidney</span></h3> - -<p>It cannot be denied that gout and granular kidney are frequently -met with in close association. But neither can it be -disputed that in these disorders, as in many others, their outward -affinities do but hark back to inward disparities. The occasional -overlapping of the two affections, the trenching of the one upon -the clinical or pathological territory of the other, must not blind -us to the essential distinctness of the two morbid entities. -Doubtless to the earlier advocates of the renal theory their not -infrequent <i>co-existence</i> bespoke some hidden <i>nexus</i>, and at least -seemed confirmatory of their views as to the pathogeny of gout. -But, even if we allow that the connexion between the two disorders -seems superficially intimate, it cannot be gainsaid that it -is neither constant nor essential. For we have to recollect that—</p> - -<div class="blockquote"> - -<p>(1) Some gouty subjects never develop granular kidney.</p> - -<p>(2) Some individuals with granular kidney never develop -gout.</p> - -</div> - -<p>Also we have to recall that—</p> - -<div class="blockquote"> - -<p>(1) Paroxysms of gout often occur for many years before the -symptoms of interstitial nephritis develop.</p> - -<p>(2) In persons of gouty stock acute attacks may ensue at an -age at which nephritis is practically unknown.</p> - -</div> - -<p>Apart from the difficulty of reconciling these disparities, we -cannot overlook the fact that both gout and granular kidney are -very common diseases, sufficiently common, as Samuel West -pointed out, to be not infrequently associated accidentally, without -any cause or connection. Again, both affections, be it -observed, are prone to develop in the middle and later decades of<span class="pagenum"><a id="Page_131"></a>[131]</span> -life. In light of this, is it not readily conceivable that both may -arise independently, mere coincidences, both evidences of <i>pre-senilism</i>? -Hastings Gilford, indeed, classes gout with syphilis, -lead, and alcohol as amongst “the chief promoters of pre-senility.”</p> - -<p>Again, certain toxic agents which predispose to or initiate renal -mischief also favour apparently the incidence of gout, <i>e.g.</i>, <i>lead</i> -and <i>alcohol</i>. Samuel West, discussing the relationship of both -gout and lead to granular kidney, maintains that, though each -may produce chronic change in the kidney, neither of them -<i>causes</i> granular kidney. But the presence of granular kidney, he -holds, greatly enhances the liability of the victim to gout on the -one hand and plumbism on the other; also, to both together and -in each affection alike markedly increases the gravity and the risk.</p> - -<p>Sir William Roberts, too, has some wholly relevant observations -on this point. Thus all will agree with him that “it is difficult to -conceive that plumbism induces the same constitutional diathesis -as that which obtains in true gout.” He held that gout and -plumbism, though they differ in all other respects, yet have one -point in common, a tendency to uratic deposition. But such -precipitation, he contended, was the outcome of a gouty tendency, -reinforced by lead poisoning; or if, on the other hand, uratic -deposits occurred in plumbism, the same had but accentuated a -pre-existing gouty diathesis. In this connexion, too, it should be -recalled that the frequent association of gout and lead poisoning -which exists in London is not seen in the North of England or in -North America.</p> - -<p>Is it not clear, then, that reflection on the broad clinical affinities -exhibited by gout and granular kidney does but emphasise the -essential distinctness of the two morbid entities? Inferentially, -too, it lends no colour to the assumption that gout is of primary -<i>renal</i> origin.</p> - -<p>That the victim of gout, despite uricæmia and those unequivocal -tokens, <i>tophi</i>, may, notwithstanding repeated arthritic outbreaks, -be in the intervals in sound if not exuberant health, is a clinical -truism. His kidneys, too, may, as far as can be ascertained, be -normal; and his blood pressure not beyond what might be -expected at his age. His output of uric acid may but touch the -lower normal limit or a little less, and his metabolism of purin-rich -foods be but a little protracted. Thus he runs his course, more -frequently than not a strenuous one, chequered by occasional outbreaks -which not seldom he regards as salutary rather than otherwise. -Then, sooner or later, in one, two, or even three decades, -that Nemesis of age, <i>arterio-sclerosis</i> overtakes him with its -correlated <i>chronic nephritic</i> change.</p> - -<p>Is not this very reminiscent of what Walker Hall reminds us of,<span class="pagenum"><a id="Page_132"></a>[132]</span> -the sequence of events in <i>lead poisoning</i> and <i>alcoholism</i>? “These -poisons affect the general metabolism adversely and are connected -with disturbances of purin assimilation and output. At a later -stage they produce arterio-sclerosis and renal insufficiency.” And -as he shrewdly observes, “It is, therefore, of importance to exactly -appraise the stage of the disease when interpreting the results of -experiments upon gouty individuals. When this obtains widened -application, many generally accepted statements will have to be -re-written.”</p> - -<p>In conclusion, therefore, we see that the weight of clinical -evidence is against the <i>primary renal</i> origin of gout, for not only -are renal changes frequently slight, but they are often entirely -lacking in gout. Confronted with these difficulties, the question -inevitably rises as to whether there does not exist a special morbid -entity, gout, which develops independently of renal abnormalities?</p> - -<hr class="chap x-ebookmaker-drop"> - -<div class="chapter"> - -<p><span class="pagenum"><a id="Page_133"></a>[133]</span></p> - -<h2 class="nobreak" id="CHAPTER_XI">CHAPTER XI<br> -<span class="smaller">URICÆMIA IN GOUT</span></h2> - -</div> - -<p>In the summer of 1848, Garrod made his momentous announcement -that “the blood in gout always contains uric acid in the form -of urate of soda, which salt can be obtained from it in crystalline -state.” Some eleven years later in his classic work on gout, he -reiterated his affirmation, but appended thereto the words, “in -abnormal quantities.” Garrod’s analyses were mainly <i>qualitative</i>, -but, at any rate, in one instance, he obtained from a gouty patient -the equivalent of 5 mg. of uric acid per 100 gm. of blood serum, -maintaining, however, that this amount was much below that -really present.</p> - -<p>But not until 1895 was a series of <i>quantitative</i> estimates undertaken -when Klemperer in three gouty subjects passing through an -attack found the blood content of uric acid to be 6·6 mg., 8·8 mg., -and 9·5 mg. per 100 c.c. of blood. Some years later, Magnus Levy, -investigating seventeen gouty individuals, found that the amount -of uric acid in the blood ranged from 2·1-9·5 mg. per 100 c.c.</p> - -<p>Brugsch and Schittenhelm noted that, in gouty victims, uric -acid was still present in the blood even when they had been on -purin-free diet for weeks or months. They held endogenous -uricæmia to be a constant symptom in gout. Even as late as 1913 -the former investigator contended that, in a healthy person on a -purin-free diet, the presence of uric acid in the blood cannot be -satisfactorily demonstrated. But it must be recollected that the -<i>precipitation</i> (ammonical silver and cupric bisulphite) method was -beset with disadvantages. An approximate estimate only of the -blood content of uric acid was with difficulty to be achieved even -when large quantities were available.</p> - -<p>Fortunately, however, our powers of analysis in this direction -became greatly enlarged with the introduction in 1913 of the -colorimetric method of Folin and Denis.</p> - -<h3><span class="smcap">Folin and Denis’s Method</span></h3> - -<p>This colour reaction is so sensitive that one part of uric acid in a -million parts of water can be detected. Moreover, unlike the -older methods which required from 75-100 c.c. of blood or more, -determinations can be made with 20 c.c., and if the blood be rich -in uric acid only 10 c.c. Walker Hall observes that the procedure -“has many advantages and does not take up much more time than<span class="pagenum"><a id="Page_134"></a>[134]</span> -some of the qualitative methods when once the technical difficulties -are overcome.” He described it as follows:—</p> - -<p>Twenty cubic centimetres of blood are withdrawn into a wide-mouthed, -tared bottle containing 0·1 gramme of finely-powdered -potassium oxalate. The flask and contents are then weighed. -Five times the weight of <i>n</i>/100 acetic acid is heated to boiling. -The oxalated blood is poured into the boiling acetic acid solution, -and the heating continued until the solution has begun again to -boil. The mixture is filtered hot. The clear filtrate and wash -waters are acidified (0·5 c.c. of 50 per cent. acetic acid) and -evaporated to 3 c.c. Five drops of a 3 per cent. silver lactate -solution, two drops of magnesia mixture, and ten to fifteen drops -of strong ammonia hydrate are next added. The mixture is -centrifugalised. The supernatant fluid is removed. To the -residue five drops of freshly-saturated hydrogen sulphide water -and one drop of strong hydrochloric acid are added. The tube -is placed in a beaker of boiling water for ten minutes in order to -remove the hydrogen sulphide. The supernatant fluid is added -to 2 c.c. of a solution containing 100 grams of sodium tungstate -and 80 c.c. of 85 per cent. phosphoric acid in 1,000 c.c. of water -and 10 c.c. of a saturated sodium carbonate solution. The -resultant blue solution is then compared with a standard uric -acid solution, and the result obtained by the following formula:—</p> - -<p class="center">(20<i>V</i>)/(<i>RW</i>) mg. of uric acid per 100 grams blood,<a id="FNanchor_20" href="#Footnote_20" class="fnanchor">[20]</a></p> - -<p class="noindent">where 20 represents depth in millimetres of standard solution,</p> - -<ul> -<li><i>R</i>, the depth of unknown solution,</li> -<li><i>V</i>, the volume to which the unknown solution is diluted,</li> -<li><i>W</i>, the weight of blood taken for the determination.</li> -</ul> - -<p><span class="pagenum"><a id="Page_135"></a>[135]</span></p> - -<h3><span class="smcap">Uric Acid a Normal Constituent of Blood</span></h3> - -<p>Up till quite recently it was held that in normal persons the -amount of uric acid in the blood was too small to be detected; -also that uric acid was not demonstrable in the blood of normal -individuals when on a <i>purin-free</i> diet. On the other hand, if the -subject’s blood was found to contain <i>uric acid</i>, while on a purin-free -diet, it was held a characteristic feature of <i>gout</i> and of prime -diagnostic import.</p> - -<p>But, since the introduction of Folin and Denis’s method, it has -been established that uric acid is constantly present, in demonstrable -amounts, in <i>human</i> blood. These authorities, using their -<i>colorimetric</i> method, found that the uric acid content of the blood -ranged from 0·7-3·7 mg. per 100 grams. They believe that -1-2 mg. of uric acid per 100 grams of blood is well within the -normal variations, but “are not prepared to say that they -represent the full variations.”</p> - -<p>However, before applying their colorimetric method to human -subjects, Folin and Denis conducted some researches into the -uric acid blood content of a variety of animals, the results of which -appear in the following table:—</p> - -<h3><span class="smcap">Uric Acid, Total Non-Protein Nitrogen and -Urea Nitrogen in Blood</span></h3> - -<p class="center">(The Figures represent Milligrams per 100 grams of Blood.)</p> - -<table class="borders"> - <tr> - <th></th> - <th>Uric<br>acid.</th> - <th>Non-protein<br>nitrogen.</th> - <th>Urea<br>nitrogen.</th> - </tr> - <tr> - <td>Rabbit (6 cases)</td> - <td class="tdr">0·05</td> - <td class="tdr">31</td> - <td class="tdr">13</td> - </tr> - <tr> - <td>Sheep (mixed blood)</td> - <td class="tdr">0·05</td> - <td class="tdr">28</td> - <td class="tdr">13</td> - </tr> - <tr> - <td>Pig (mixed blood)</td> - <td class="tdr">0·05</td> - <td class="tdr">32</td> - <td class="tdr">14</td> - </tr> - <tr> - <td>Horse (1 case, anti-toxin animal)</td> - <td class="tdr">0·05</td> - <td class="tdr">54</td> - <td class="tdr">28</td> - </tr> - <tr> - <td>Monkey (1 case, poliomyelitis)</td> - <td class="tdr">0·05</td> - <td class="tdr">60</td> - <td class="tdr">38</td> - </tr> - <tr> - <td>Beef (mixed blood)</td> - <td class="tdr">0·2</td> - <td class="tdr">24</td> - <td class="tdr">14</td> - </tr> - <tr> - <td>Cat (2 cases, diet, liver)</td> - <td class="tdr">0·2</td> - <td class="tdr">60</td> - <td class="tdr">34</td> - </tr> - <tr> - <td>Cat (2 cases, diet, milk and eggs)</td> - <td class="tdr">0·2</td> - <td class="tdr">67</td> - <td class="tdr">37</td> - </tr> - <tr> - <td class="nw">Cat (2 cases, diet, rice and cream)</td> - <td class="tdr">0·2</td> - <td class="tdr">31</td> - <td class="tdr">20</td> - </tr> - <tr> - <td>Chicken (6 cases, mixed blood)</td> - <td class="tdr">4·9</td> - <td class="tdr">32</td> - <td class="tdr">8</td> - </tr> - <tr> - <td>Duck (4 cases, mixed blood)</td> - <td class="tdr">4·8</td> - <td class="tdr">34</td> - <td class="tdr">7</td> - </tr> - <tr> - <td>Goose (1 case)</td> - <td class="tdr">4·8</td> - <td class="tdr">26</td> - <td class="tdr">8</td> - </tr> -</table> - -<p>The most striking feature of these findings is the marked contrast -between the uric acid blood content of <i>mammals</i> as opposed -to avians. In the former the amount is minimal—0·2 mg. or less -per 100 grams of blood. On the other hand, in the blood of <i>birds</i>, -in whose instance the origin of uric acid is so different, it is present -in relatively large amounts. As Folin and Denis observe, the<span class="pagenum"><a id="Page_136"></a>[136]</span> -small amounts of <i>urea</i> in the blood of birds, as compared with -that of mammals, is also worthy of note.</p> - -<p>Reverting now to the findings in human subjects, as observed -by Folin and Denis, these have been summarised as follows by -Walker Hall:—</p> - -<h3><span class="smcap">Uric Acid, Total Non-Protein Nitrogen and -Urea Nitrogen in Blood</span></h3> - -<p class="center">(The Figures represent Milligrams per 100 grams of Blood.)</p> - -<table class="borders"> - <tr> - <th></th> - <th>Uric<br>acid.</th> - <th>Non-protein<br>nitrogen.</th> - <th>Urea<br>nitrogen.</th> - </tr> - <tr> - <td>Human, group 1</td> - <td class="tdr">0·8</td> - <td class="tdr">36</td> - <td class="tdr">19</td> - </tr> - <tr> - <td>Human, group 2</td> - <td class="tdr">1·5</td> - <td class="tdr">34</td> - <td class="tdr">18</td> - </tr> - <tr> - <td>Human, group 3</td> - <td class="tdr">2·8</td> - <td class="tdr">36</td> - <td class="tdr">19</td> - </tr> - <tr> - <td>Human, with blood pressures of 160</td> - <td class="tdr">2·9</td> - <td class="tdr">50</td> - <td class="tdr">33</td> - </tr> - <tr> - <td>Human, with blood pressures of 200</td> - <td class="tdr">1·2</td> - <td class="tdr">50</td> - <td class="tdr">22</td> - </tr> - <tr> - <td>Human, with blood pressures of 220</td> - <td class="tdr">2·7</td> - <td class="tdr">40</td> - <td class="tdr">19</td> - </tr> - <tr> - <td>Human, with blood pressures of 260</td> - <td class="tdr">3·9</td> - <td class="tdr">52</td> - <td class="tdr">20</td> - </tr> - <tr> - <td>Human, alcoholic</td> - <td class="tdr">1·0</td> - <td class="tdr">43</td> - <td class="tdr">29</td> - </tr> - <tr> - <td>Human, chronic gout</td> - <td class="tdr">3·9</td> - <td class="tdr">25</td> - <td class="tdr">13</td> - </tr> - <tr> - <td>Human, chronic gout</td> - <td class="tdr">4·4</td> - <td class="tdr">30</td> - <td class="tdr">15</td> - </tr> - <tr> - <td>Human, chronic gout</td> - <td class="tdr">5·2</td> - <td class="tdr">20</td> - <td class="tdr">13</td> - </tr> - <tr> - <td>Human, lead poisoning</td> - <td class="tdr">4·7</td> - <td class="tdr">50</td> - <td class="tdr">31</td> - </tr> - <tr> - <td>Human, lead poisoning</td> - <td class="tdr">4·8</td> - <td class="tdr">52</td> - <td class="tdr">32</td> - </tr> - <tr> - <td>Human, leukæmia</td> - <td class="tdr">3·1</td> - <td class="tdr">33</td> - <td class="tdr">14</td> - </tr> - <tr> - <td>Human, acute nephritis with arterio-sclerosis</td> - <td class="tdr">2·7</td> - <td class="tdr">40</td> - <td class="tdr">19</td> - </tr> - <tr> - <td>Human, chronic nephritis with arterio-sclerosis</td> - <td class="tdr">2·5</td> - <td class="tdr">38</td> - <td class="tdr">19</td> - </tr> -</table> - -<p>Interesting and valuable as are the above findings, Folin and -Denis are careful to point out that, even as regards the first three -groups in the above table, “the figures can scarcely be said to -represent the strictly normal variations, for no attempt was made -to select physically normal persons.” The samples of blood were -drawn from patients newly admitted to the Boston <i>Psychopathic</i> -Hospital.</p> - -<p>It may be noted that of all the <i>mammals</i> examined the blood -of <i>man</i> contains by far the greatest amount of uric acid. Also -that in humans the uric acid blood content varies in different -persons, and, moreover, as Walker Hall points out, “the figures -lend support to the view that there may be groups or families -exhibiting similar features.” It will be seen, too, that the blood -uric acid in <i>gout</i> and <i>lead poisoning</i> stands at a high level, though -not so elevated as was formerly maintained. From the figures, -too, it may be gleaned that apparently no relationship obtains<span class="pagenum"><a id="Page_137"></a>[137]</span> -between the amount of uric acid and that of the urea or total -non-protein nitrogen in the blood.</p> - -<p>At the same institution in Boston, Adler and Ragle conducted -a similar series of investigations, though on a more extended -scale. These observers, taking 156 unselected <i>psychopathic</i> -patients, found that in 107 examples the uric acid content of the -blood was from 1-2 mg., in thirty-eight more than 2 mg., and in -eleven instances less than 1 mg. To sum up, the uric acid content -varied from 0·7-4·5 mg. per 100 grams of blood, an average of -1·7 mg.</p> - -<p>As before stated, it was until recently maintained that in the -blood of <i>normal</i> individuals, on a <i>purin-free</i> diet, <i>uric acid</i> was -undemonstrable. But McLester, utilising Folin’s method, found -uric acid in the blood of fifteen <i>healthy</i> individuals, who had been -on a <i>purin-free</i> diet for at least three days, and this in amounts -ranging from 0·5-2·9 mg. per 100 grams of blood, an average -of 1·4, as contrasted with 1·7, the average amount in Adler and -Ragle’s series. Pratt, discussing these findings, considers that -the fact that the <i>average</i> amounts approximate so nearly in the -two series is worthy of emphasis. This especially as all McLester’s -examples were young healthy adults on a <i>purin-free diet</i>, while -the patients studied by Adler and Ragle were of all ages and on -a <i>mixed</i> diet.<a id="FNanchor_21" href="#Footnote_21" class="fnanchor">[21]</a></p> - -<h3><span class="smcap">Effect of Exogenous Purines</span></h3> - -<p>As we are aware, the amount of uric acid excreted in the <i>urine</i> -increases markedly on a <i>purin-rich diet</i>. But recent researches<span class="pagenum"><a id="Page_138"></a>[138]</span> -appear to raise doubts as to whether the uric acid content of the -<i>blood</i> rises correspondingly. Thus, according to Walker Hall, “a -state of <i>uricæmia</i> is said to exist if the amount of uric acid in the -blood exceeds 0·8 mg. per 100 c.c.” The figure he considers is probably -too low for, after an average meat breakfast, the blood uric -acid rises to 1 or 2 mg. per 100 c.c. <i>in normal</i> adults, or even higher -after an excessive intake of <i>purin-rich</i> foods.</p> - -<p>On the other hand, Denis, investigating the effect of ingested -purin on the uric acid content of the blood, found that in <i>normal</i> -individuals <i>no increase in the circulating uric acid</i> follows the -intake; in other words, the kidney, in <i>normal</i> persons, is quite -capable of excreting any excess of uric acid presented to it, thereby -keeping the uric acid of the blood at the same level as obtains -when only the <i>endogenous</i> moiety thereof has to be eliminated.</p> - -<p>Moreover, another factor, according to Folin and Denis, that -operates in the same direction is the <i>binding capacity of the tissues -for uric acid</i>. Pratt of Boston’s observations, too, appear to -indicate “That the uric acid derived from exogenous purin does -not accumulate in the blood unless there is a disturbance in the -uric acid metabolism.”</p> - -<p>On the other hand, given damage to the <i>kidney</i> (even when this -has not progressed to the point when nitrogen retention is apparent, -as shown by the non-protein nitrogen values), an accumulation of -uric acid takes place in the blood after a short period of purin -feeding.<a id="FNanchor_22" href="#Footnote_22" class="fnanchor">[22]</a></p> - -<p>Now, as to the second regulating factor, the <i>retention capacity</i> -of the <i>tissues</i> for <i>uric acid</i>, it may be said that the amount, in -<i>normal</i> subjects, would appear to be small. But Fine, it may be -noted, found that the uric acid content in divers tissues was -relatively proportionate to that of the blood, whether normal or -increased in amount.</p> - -<p>But, to resume, Denis also demonstrated that the uric acid content -of the blood in patients suffering from various <i>chronic diseases -other than gout</i> was also not increased on a purin-rich diet. To -sum up, the researches of Denis would appear to indicate that:—</p> - -<div class="blockquote"> - -<p>(1) In <i>normal</i> subjects <i>no increase</i> in the <i>uric</i> acid content of the -<i>blood</i> follows exogenous purin intake.</p> - -<p>(2) The uric acid content of the blood in patients suffering from -chronic diseases, other than <i>gout</i> or <i>renal</i> disease, is similarly -<i>not</i> augmented on a <i>purin-rich</i> diet.</p> - -<p>(3) The <i>uric acid content</i> of the <i>blood</i> is <i>increased</i> more or less -markedly, after a short period of purin feeding, in the -presence of defective <i>renal elimination</i>.</p> - -</div> - -<p><span class="pagenum"><a id="Page_139"></a>[139]</span></p> - -<p>In amplification of the second of the foregoing postulates some -observations by Pratt may be quoted. This authority is of -opinion that the low amount of uric acid present in the blood of -unselected <i>psychiatric</i> patients on a mixed diet (Folin and Denis, -Adler and Ragle) shows that a retention of uric acid in the blood in -any considerable amount for twenty-four to twenty-eight hours -rarely occurs. For, as he informs us, these patients at the Boston -Psychopathic Hospital, when on ordinary diet, are eating purin-containing -food daily, and they might take as much or more purin -during the forty-eight hours preceding the blood analysis as is -contained in a single sweetbread meal. Now, as Pratt argues, if -the uric acid thus derived accumulated in the blood, the amount -found would be considerably greater than that of individuals on -a <i>purin-free</i> diet. But, on the contrary, it transpires that the -average amount of uric acid found by Adler and Ragle in the -blood of patients on an ordinary diet was only 0·3 mg. more than -that found by McLester in normal individuals on a <i>purine-free</i> -diet. The diagnostic significance of these observations will be -better appreciated when we come to discuss the sequential increase -of the uric acid content of the blood in <i>gouty</i> subjects after the -ingestion of purin-rich substances.</p> - -<h3><span class="smcap">Uric Acid Content of Blood in Gout</span></h3> - -<p>Taking 1-3 mg. per 100 c.c. as the normal, the uric acid content -of the blood, in typical cases of gout, according to MacLeod, rises -to nearly 10 mg. Gudzent, from his studies, maintains that the -blood, in almost all cases of gout, contains as much or even more -<i>mono-sodium urate</i> than it can hold in solution (1-8 mg.), in other -words, it is in effect a supersaturated solution of the relatively -insoluble <i>lactim</i> urate.</p> - -<p>Pratt, working in Folin’s laboratory, investigated a series of -cases of gout, selecting only those in which (1) Tophi were found, -(2) A history of characteristic attacks of acute gout was obtained, -or (3) Typical symptoms developed while under observation.</p> - -<p>At the time of examination the average uric acid content, -irrespective of the diet or condition, was 3·7 mg. In three patients -on <i>ordinary diet</i>, who were seen during attacks, the amounts were -4·5, 4·8 and 5·7 mg. of uric acid. In two other patients, also seen -during attacks, and while on a <i>purin-free</i> diet, the uric acid in four -estimates ranged from 2·4-5·1 mg., viz., an average of 3·6 mg. -None of these patients were taking atophan.</p> - -<p>Seven patients, on a <i>mixed</i> diet, and free at the time from -symptoms of gout, contained on the average 4·3 mg. of uric acid -in their blood.</p> - -<p>On the other hand, examination of the blood in six patients on a<span class="pagenum"><a id="Page_140"></a>[140]</span> -<i>purin-free</i> diet, at the time manifesting no acute symptoms of -gout, revealed an average uric acid content of 3 mg.</p> - -<p>From the foregoing considerations it may be deduced that:—</p> - -<div class="blockquote"> - -<p>(1) In gout there is a condition not of uricæmia, but of <i>hyper-uricæmia</i>.</p> - -<p>(2) That on the average the blood in <i>gouty</i> subjects contains -twice as much uric acid as that of <i>non-gouty</i> subjects, as -evidenced by comparison of the average uric acid content -of the blood in Pratt’s series of gouty cases (4·5 mg.) with -Adler and Ragle’s non-gouty examples (1·7 mg.).</p> - -<p>(3) In contrast with non-gouty subjects, the uric acid content -of the blood in <i>gouty</i> subjects is augmented on a purin-rich -diet.</p> - -<p>(4) Both in the inter-paroxysmal periods and during attacks -the uric acid content of the blood, when on a <i>mixed</i> diet, -is higher than when on a purin-free diet.</p> - -</div> - -<h3><span class="smcap">Hyper-Uricæmia in Non-Gouty Arthritis</span></h3> - -<p>Pratt, of Boston, has found that a condition of hyper-uricæmia -is sometimes demonstrable in joint disorders other than gouty; -but he maintains that the following distinction obtains, viz., that -while in gout the hyper-uricæmia is generally <i>constant</i>, in other -forms of arthritis it appears to be <i>transient</i>.</p> - -<p>He cites a case of <i>infective</i> arthritis, not exhibiting the clinical -features of gout, in which the first analysis of the blood by Denis -revealed a uric acid content of 7·6 mg.; but on a subsequent -examination, seven months later, only 0·8 mg. was found, this, -though the patient at the time was on a <i>purin-rich</i> diet. This -difference is response to exogenous purins in gouty, as opposed to -<i>non-gouty</i> arthritics, is well illustrated in the following table.</p> - -<div class="blockquote"> - -<p>According to Walker Hall, the following example illustrates the effect of -purin-free as opposed to purin diet on the uric acid blood content in a -gouty subject:—</p> - -<table class="borders"> - <tr> - <th></th> - <th>Uric<br>acid.</th> - <th>Non-protein<br>nitrogen.</th> - <th>Urea<br>nitrogen.</th> - </tr> - <tr> - <td></td> - <td colspan="3" class="tdc smaller">Mgs. per 100 gms. of blood.</td> - </tr> - <tr> - <td>Gout with purin dietary</td> - <td class="tdr">5·5</td> - <td class="tdr">52</td> - <td class="tdr">36</td> - </tr> - <tr> - <td>Gout with purin-free food</td> - <td class="tdr">3·4</td> - <td class="tdr">40</td> - <td class="tdr">18</td> - </tr> -</table> - -<table class="borders"> - <tr> - <th colspan="4"><span class="smcap">Gouty Polyarthritis (Pratt).</span></th> - </tr> - <tr> - <th></th> - <th>Milligrams<br>of uric acid<br>in 100 gms.<br>of blood.</th> - <th></th> - <th>Milligrams<br>of uric acid<br>in 100 gms.<br>of blood.</th> - </tr> - <tr> - <td>D. N. Gout. Purin-free diet.</td> - <td class="tdr">3·1</td> - <td>52 hours after eating 280 grams haddock roe.</td> - <td class="tdr">5·8</td> - </tr> - <tr> - <td></td> - <td class="tdr"></td> - <td>3 days after eating 300 grams roast beef.</td> - <td class="tdr">6·2</td> - </tr> - <tr> - <td>K. Gout. Purin-free diet.</td> - <td class="tdr">2·4</td> - <td>24 hours after eating 270 grams roast beef.</td> - <td class="tdr">3·0</td> - </tr> - <tr> - <td>H. Gout. Purin-free diet.</td> - <td class="tdr">1·7</td> - <td>3 days after eating 150 grams thymus.</td> - <td class="tdr">3·6</td> - </tr> - <tr> - <td>P. Gout. Purin-free diet.</td> - <td class="tdr">2·1</td> - <td>3 days after eating 160 grams thymus.</td> - <td class="tdr">3·4</td> - </tr> - <tr> - <td>J. N. Gout. Purin-free diet.</td> - <td class="tdr">2·2</td> - <td>48 hours after eating 190 grams thymus.</td> - <td class="tdr">8·7</td> - </tr> - <tr> - <td class="tdr">Average</td> - <td class="tdr bt">2·2</td> - <td class="tdr">Average</td> - <td class="tdr bt">5·1</td> - </tr> - <tr> - <th colspan="4"><span class="smcap">Non-Gouty Polyarthritis (Pratt).</span></th> - </tr> - <tr> - <th></th> - <th>Milligrams<br>of uric acid<br>in 100 gms.<br>of blood.</th> - <th></th> - <th>Milligrams<br>of uric acid<br>in 100 gms.<br>of blood.</th> - </tr> - <tr> - <td>McC. Chronic polyarthritis. Purin-free diet.</td> - <td class="tdr">1·7</td> - <td>24 hours after eating 100 grams of thymus.</td> - <td class="tdr">2·2</td> - </tr> - <tr> - <td>M. Chronic polyarthritis. Ordinary diet.</td> - <td class="tdr">2·0</td> - <td>24 hours after eating 225 grams of thymus.</td> - <td class="tdr">1·8</td> - </tr> - <tr> - <td>H. Chronic polyarthritis. Ordinary diet.</td> - <td class="tdr">2·9</td> - <td>47 hours after eating 190 grams of thymus.</td> - <td class="tdr">2·5</td> - </tr> - <tr> - <td class="tdr">Average</td> - <td class="tdr bt">2·1</td> - <td class="tdr">Average</td> - <td class="tdr bt">2·2</td> - </tr> -</table> - -</div> - -<p>As Pratt points out, if the figures in the two tables be compared, -it will be seen that, prior to the sweetbread meal, the average uric -acid content of the blood in the gouty and the non-gouty patients -was identical. But twenty-four hours to three days, after the -purin intake, the average uric acid content of the blood in the -<i>gouty</i> was 5·1 mg., while in the <i>non-gouty</i> subjects it was only -2·2 mg.; in other words, in the five gouty individuals a pronounced -hyper-uricæmia was produced from one to three days after a -purin meal. On the other hand, in the <i>non-gouty</i> subjects the -uric acid content was found to be practically unaltered twenty-four -to forty-eight hours after the same purine intake.</p> - -<p>It would seem, therefore, that some <i>diagnostic</i> importance may -be attached to the <i>hyper-uricæmia</i> that is induced in <i>gouty</i> subjects<span class="pagenum"><a id="Page_141"></a>[141]</span> -after exogenous purines, as compared with its non-occurrence -in non-gouty subjects.</p> - -<p>Another interesting point elicited by Pratt was that in his -<i>gouty</i> examples, although, after a purin meal, the uric acid -content of the <i>blood</i> rose markedly, yet there was no apparent -<i>delay</i> or <i>diminution</i> in the output of <i>exogenous purin</i> in the -<i>urine</i>. Thus, in one example, after the intake of 190 grams of -thymus gland, the uric acid in the blood, in the first twenty-four -hours, rose from 2·2 mg. to 4·4 mg., reaching, on the third day, a -maximum of 8·7 mg., which, on the fourth day, sunk to 2·7 mg. -Nevertheless, 26·2 per cent. of the ingested purin nitrogen was -excreted as uric acid. Now, as pointed out in the preceding -chapter, it has been shown by many observers that in <i>gouty</i> -subjects the excretion of <i>exogenous</i> purin is <i>diminished</i> and -<i>retarded</i>. But Pratt’s study of the blood shows that a marked -increase and retention of uric acid in the <i>blood</i> may result from -the ingestion of purin bases, even when no evidence of retention -is found on the examination of the <i>urine</i>.<a id="FNanchor_23" href="#Footnote_23" class="fnanchor">[23]</a></p> - -<p>The clear inference from this is that it is desirable that our -<i>urinary</i> findings in respect of <i>uric acid</i> should be reviewed and -controlled in light of <i>blood examinations</i> to the same end.</p> - -<p><span class="pagenum"><a id="Page_142"></a>[142]</span></p> - -<h3><span class="smcap">Variations in Uric Acid Content of Blood Independently of Diet</span></h3> - -<p>Considerable variations in the uric acid content of the blood, -according to Pratt, may occur both in <i>gouty</i> and <i>non-gouty</i> subjects, -and which cannot be attributed to any <i>purin intake</i>. -Such oscillations, moreover, may ensue within a short time. -A patient of his, admitted to hospital suffering from a severe -attack of <i>gout</i>, was placed upon a <i>purin-free</i> diet. Twenty-four -hours afterwards examination revealed only 2·7 mg. of uric acid -in his blood. Subsequently, after having had no food containing -purins for fifteen days, it contained 5·1 mg.</p> - -<p>Marked variations in the uric acid content of the blood may -likewise occur in <i>non-gouty</i> subjects. After being on a <i>purin-free</i> -diet for two days, a patient of Pratt’s, with <i>recurrent iritis</i>, had -2·2 mg., while a few months after, when on a mixed diet, his blood -contained only 0·8 mg.</p> - -<p>Again, great oscillations in the blood content of uric acid, -independent of diet, are sometimes found in cases of <i>non-gouty -arthritis</i>. Thus, in one chronic case of this nature, the blood -when first examined contained 7·6 mg. of uric acid, but a few -months later, when on a purin-rich diet, only 0·8 mg. were -present. In another instance of <i>primary polyarthritis</i> the same -was strikingly exhibited. Aged twenty-two years, the subject -in October was on ordinary diet. His blood at that period -showed 2·7 mg. of uric acid per 100 mg. of blood; in December, on -a purin-free diet, 5·0; and in May, on a similar dietary, 1·6 mg.</p> - -<p>As to whether in healthy individuals, on a purin-free diet, -similar variations in the uric acid content of the blood occur, is -not sufficiently ascertained. The solitary example that may be<span class="pagenum"><a id="Page_143"></a>[143]</span> -cited is by McLester, who, as a result of four examinations of the -blood in a normal person on a purin-free diet, found that its -uric acid content was practically constant.</p> - -<p>The deductions that may be drawn from the foregoing findings -are:—</p> - -<div class="blockquote"> - -<p>(1) That in <i>gouty</i> subjects pronounced variations of the uric -acid content of the blood may occur which are not attributable -to the purin content of the food.</p> - -<p>(2) That in <i>non-gouty</i> arthritis similar fluctuations in the blood -content of uric acid, irrespective of diet, also occur.</p> - -<p>(3) That in <i>normal</i> persons, on a purin-free diet, the blood -content of uric acid, as far as is ascertained, does not -show such variations.</p> - -</div> - -<h3><span class="smcap">What Relation, if any, Exists between the Uric Acid -Content of the Blood and Attacks of Gout?</span></h3> - -<p>If uric acid be <i>causally</i> related to gout, it would seem reasonable -to expect that the blood content thereof would stand in -some clear relation to the <i>incidence</i> or <i>intensity</i> of attacks.</p> - -<p>But, according to Pratt and others, no variations indicative -of such a relationship obtain. For, independently of <i>acute</i> -attacks, and, moreover, in the absence of any pronounced <i>renal -inadequacy</i>, the blood of gouty subjects, even on a <i>purin-free</i> diet, -contains, as a rule, 4-9 mg. of uric acid.</p> - -<p>More pertinently to our point, in the experience of Daniels and -McCrudden, it transpires that, contrary to the usually accepted -teaching, typical <i>acute</i> attacks might occur without any variation -in the <i>uric acid content of the blood</i> or its <i>excretion</i>.</p> - -<p>Nor did their iconoclastic findings cease here, for, <i>mirabile -dictu</i>! attacks ensued even when the uric acid blood content was -at a <i>sub-normal</i> level; this latter, owing to the victims being at -the time on <i>atophan</i>, which increases uric acid elimination. In -this connection it is worthy of note that, according to Pratt, the -uric acid content of the blood may at times be low, even when -atophan has not been taken. In one of his cases, on a purin-free -diet, only 1·7 mg. was present, and in another case, on a mixed -diet, 1·9 mg.</p> - -<p>Daniels and McCrudden, too, note that the uric acid content -of the blood in gouty subjects may be <i>persistently</i> lowered, <i>even -under the normal average</i>. His, again, has recorded an instance -of a gouty subject, with multiple tophi, whose blood did not contain -an excess of uric acid. Bloch, also, took 200 c.c. of blood -from a man, aged twenty-five, suffering at the time from a typical -attack of gout in the big toe; but uricæmia was not present.</p> - -<p>Bass and Herzberg injected uric acid into the blood of gouty<span class="pagenum"><a id="Page_144"></a>[144]</span> -subjects until its content thereof reached 10 mg. per 100 c.c., -this without any joint symptoms supervening. The same -observers, aspirating <i>joint fluids</i> in <i>non-gouty</i> subjects, noted that -the uric acid content was approximately the same as that of the -blood. But, in contradistinction thereto, in two <i>gouty</i> subjects, -victims of <i>uræmia</i>, they found in the joint fluids 18·5 and 20·8 mg. -of uric acid, while the blood content was only 10 mg. and 8·2 mg.</p> - -<p>Furthermore, intravenous injection of uric acid engendered a -lesser degree of <i>uricæmia</i> in the gouty—this despite <i>impaired renal -excretion</i>. To their mind, therefore, the inference was that the -<i>bodily tissues</i> in gout display an enhanced capacity for taking up -uric acid.</p> - -<p>Lastly, Walker Hall, discussing the question as to whether any -relation obtains between the degree of uricæmia and the onset of -acute attacks, observes that, “the evidence is more general than -specific.” Thus he reminds us that excessive intake of purin -food has sometimes been followed by, or associated with, an acute -outbreak. Also, that the leucocytic destruction which occurs -during acute lobar pneumonia and after the use of X-rays has -occasionally coincided with an acute paroxysm. To this, again, -must be added the fact that atophan curtails the duration of acute -attacks, apparently by exciting an increased uric acid output. -Superficially regarded, these facts might appear to be conclusive; -but, as Walker Hall states, it must be recalled that overeating, -overdrinking, trauma, mental disturbances, atmospheric vicissitudes, -and bacterial infections have also preceded acute outbreaks.</p> - -<p>To sum up, the main conclusions deducible from the foregoing -clinical and experimental findings would appear to be that:—</p> - -<div class="blockquote"> - -<p>(1) No constant relation has as yet been established between -the uric acid content of the blood and acute attacks of gout.</p> - -<p>(2) No variations in the same apparently herald or accompany -typical acute paroxysms.</p> - -<p>(3) Attacks may occur with a <i>sub-normal</i> uric acid blood content.</p> - -<p>(4) The tissues of gouty subjects apparently possess an enhanced -binding capacity in respect of uric acid.</p> - -<p>(5) <i>Given impaired renal excretion in gouty subjects</i>, the uric acid -content of the <i>joint fluid</i> rises markedly, exceeding that -of the blood.</p> - -</div> - -<h3><span class="smcap">Discussion of the Foregoing Data</span></h3> - -<p>While the researches of the past decade have proved distinctly -encouraging, yet we must not blind ourselves to the fact that the -foregoing findings, and alike our deductions therefrom, are largely -provisional; for we stand in grave danger of over-emphasising the<span class="pagenum"><a id="Page_145"></a>[145]</span> -significance of the results forthcoming from the investigation of -isolated samples of blood from different individuals. The recorded -estimates of the uric acid content of the blood in <i>strictly normal -persons</i> are all too few, the findings in <i>diseased</i> subjects too conflicting, -to warrant dogmatic inferences, wide generalisations. In -truth, the problem is by no means as simple as may at first sight -appear, and this but a slight digression will suffice to make clear.</p> - -<p><i>The Significance of Uricæmia.</i>—It is generally maintained that -the blood content of uric acid in gout is above normal. Yet the -<i>excretion</i> of <i>uric acid</i>, save during acute attacks, rests within physiological -limits. Again, <i>à propos</i> of our claim that the <i>blood</i> is -<i>surcharged</i> therewith, we have the awkward fact, as yet inexplicable -on chemical or physico-chemical grounds, that the blood-stream -can hold in suspension far more uric acid than has ever yet -been met with in gout, according to Bechhold and Ziegler no -less than 50 mg. of <i>uric acid</i> per 100 c.c. of blood serum before -deposition tends to occur. On the other hand, <i>urates</i> are less -soluble therein, not exceeding 2·5 mg. per 100 c.c. How remote -from the limit of saturation the highest figures observed in gout! -What a large margin of solubility is still available!</p> - -<p>Again, the uric acid blood content in gout is far less than was -formerly thought. Only by a few milligrams does it transcend -that found in normal individuals. Can this slight disparity have -such profound potentialities as to determine the incidence or not -of <i>gout</i>? and this with the saturation point still so remote. The -urates, too, being practically non-toxic, how difficult to conceive -that the almost trivial excess of the uric acid blood content over -the normal is adequate to produce the fulminant and dramatic -phenomena of acute gout.</p> - -<p>Again, though we speak of uricæmia as a dominant characteristic -of gout, we are uncertain whether the alleged increase in the -uric acid content of the blood is <i>real</i> or merely <i>apparent</i>. We can, -it is true, extract <i>uric acid</i> and <i>urates</i> from the blood-stream, but -it does not necessarily follow that it is as such that they circulate -<i>in vivo</i>. We need walk circumspectly here for, despite the most -modern methods of blood analysis, we are still ignorant as to the -exact form in which uric acid exists in the blood-stream; whether -the purins of the food appear in the blood-stream as <i>sodium monourate</i>, -or in <i>organic fusion</i>. Accordingly, in the interests of progress, -it were well to bear in mind the pitfalls that beset uric acid -estimation, the insufficiently eclectic capacity of even the most -modern tests, and to consideration of these more chastening -aspects we now proceed.</p> - -<p><i>Sources of Fallacy in Uric Acid Estimation.</i>—With Folin’s -findings as his basis, Walker Hall estimates that, excluding the<span class="pagenum"><a id="Page_146"></a>[146]</span> -lymphatics and lymph spaces, the entire blood-stream contains -normally 70 mg. of uric acid, <i>i.e.</i>, 2 mg. of uric acid per 100 grams -of blood, 3,500 c.c. (total quantity of blood).</p> - -<p>Thence he argues that, inasmuch as about 1 litre of blood -traverses the kidney per minute, the total content thereof of <i>uric -acid</i> would gain access to the renal organs in three and a half -minutes. Now the average total output of the kidneys is 500 mg. -per twenty-four hours. Accordingly, assuming that the blood -arriving at the kidneys contains as a constant the above 70 mg. -uric acid, the total daily output would pass through these organs -in twenty-five minutes.</p> - -<p>Now, given immediate extraction of all the uric acid by the renal -cells, then the blood in the renal veins will become <i>free of uric acid</i>. -If so, the estimates of the uric acid content of the blood will reflect -exactly the measure of the <i>endogenous</i> or <i>exogenous</i> nuclein metabolism. -But, “if the renal vein blood is not <i>purin-free</i>, then the -<i>estimations will fail to yield a true picture of the activities of nuclein -exchange</i>.”</p> - -<p>Again, as to the precise import of isolated estimates of the uric -acid blood content, we must recollect that the <i>excretion of purins</i> -is not distributed evenly over the twenty-four hours, varying as -it does under the influence of food, exercise, sleep, and other -factors. <i>A propos</i> of this, Pratt’s observations clearly show that -both in <i>gouty</i> and <i>non-gouty subjects fluctuations in the uric acid -blood content</i> also occur, and this independently of <i>diet</i>. To what, -then, may these variations be referred? Obviously a question of -great moment, especially when we recall the eccentric behaviour of -the <i>blood uric acid</i> in relation to the incidence of <i>acute gouty -attacks</i>. For, until the inward meaning of these vagaries is -revealed, the value of recorded estimates must necessarily be -discounted considerably.</p> - -<p>We must recall, too, that a certain moiety of the purins derived -from nuclein metabolism lags in the <i>lymph</i> spaces and <i>lymphatics</i>, -and this, as Walker Hall reminds us, must reduce the quantity -present in the blood-stream at any one time. Also, as the same -authority reflects, the lymph stream being probably richer in -<i>sodium ions</i> than the blood, the entry of the nucleins therein -may be retarded and so lead to a still further reduction of the -blood content.</p> - -<p>There is yet another possibility, he reminds us, viz., “that the -purin content of the blood varies in the peripheral pulmonary -hepatic and osseous streams, and that, while in some parts the -purins are being carried to the kidneys for excretion, in others -they are being transported from one organ to another for further -metabolism.”</p> - -<p><span class="pagenum"><a id="Page_147"></a>[147]</span></p> - -<p>For, as before pointed out, the enzymes responsible for the ultimate -disruption of the <i>nucleosides</i> are scattered in different organs, -and Walker Hall suggests that “a transport of half metabolised -nucleotides from one organ to another may form a part of the -normal processes of nuclein metabolism.” This may well lead us -on to consider the limitations that beset even the most modern -tests in use for uric acid determination.</p> - -<p><i>Disabilities of Modern Tests.</i>—With all its outstanding advantages, -even the Folin method of uric acid estimation has its drawbacks. -As Curtman and Lehrman have pointed out, different -workers have, even on <i>identical blood samples</i>, arrived at results -which vary widely. Nor, disconcerting though it be, do the -limitations of this mode of hæmo-analysis cease here.</p> - -<p>Thus we know from Gudzent and Apolant that the soluble but -unstable biurate is constantly being transmuted into an insoluble -stable type, in other words, metamorphosis from one <i>isomer</i> into -another. But, unhappily, the tests to hand fail of differentiation -of the several <i>tautomeric</i> forms of uric acid. Also, as isomers of -uric acid actually exist, then <i>quâ</i> Walker Hall, why not isomers -of <i>purins</i> and <i>pyrimidins</i> also? But here again our tests are -insufficiently eclectic. They give us no clue as to the affinities -or blends of purins or pyrimidins for or with other substances.</p> - -<p>Again, as our criteria fall short of identifying the exact form of -the “purin combinations” it follows, therefore, that they tell us -nothing as to whether “the increase is due to a more active -transport of purins from one organ to another for further metabolism -or simply to a transport to the kidneys for elimination.”</p> - -<p>In other words, hampered by the above disabilities in our tests, -it is beyond our power to determine whether “the increases denote -a supernormal nuclein metabolism or an unusual type of nuclein -cleavage.” Should it ultimately transpire that the increase in the -purin blood content is a <i>real</i> one, viz., made up of “an excess of -normally formed and normally bound purins,” a great step -forward will have been achieved. For, to account for the -same it will, as Walker Hall observed, be necessary to postulate -a <i>supernormal nuclear activity</i> of <i>generalised or</i> localised -distribution.</p> - -<p><i>Need for Further Investigations.</i>—While none can doubt that, by -means of chemical investigation of the <i>blood</i>, the clinical problem -of gout will be elucidated to a much greater extent than has -been possible by means of <i>urine analysis</i>, still much remains to be -done before recent findings can be applied to the solution of the -etiology of <i>gout</i>.</p> - -<p>The results of <i>blood analyses</i> up to now have afforded us no clue -as to the intimate nature of the warp in <i>nuclein metabolism</i>. At<span class="pagenum"><a id="Page_148"></a>[148]</span> -the most, the researches in this sphere do but make it increasingly -clear that uricæmia is <i>not the cause but the result</i> of gout.</p> - -<p>Albeit, this conclusion does not justify us in putting out of -court all thought of <i>uric acid</i> in connection with gout. Any -tendency thereto will be immediately checked when we recall that -uratic deposits, <i>i.e.</i>, <i>tophi</i> constitute the solitary unequivocal token -of gout, and to this aspect of the question the ensuing chapter -will be devoted.</p> - -<p>Meanwhile, systematic investigations of the purin content of -the blood, not only in gouty but in <i>normal</i> subjects, would surely -dissipate much of the obscurity that envelops this complex -question. It were well, too, that <i>blood</i> and <i>urine</i> analyses go hand -in hand in our investigations. How illumining these have been -in connection with <i>atophan</i>, the increased urinary output of uric -acid having been found to be correlated with a simultaneous -sinking in the level of the uric acid of the blood.</p> - -<p>Again, the <i>excretion of urinary purin</i> ebbs and flows with the -intake of food and the degree of muscular activity, while sleep also -exerts an influence, not to mention constitutional disturbances, -<i>e.g.</i>, fever infections, etc.</p> - -<p>Can it be doubted that the <i>blood</i> content of uric acid varies with -these same vicissitudes? Walker Hall tells us that the data to -hand, “as to the rapidity of the appearance of purins in the blood-stream -after food, infections, fever, etc.,” though few in number, yet -suggest that “the excretion by the kidney is <i>tidal</i> in character, and -that the blood uric acid has similar characteristics.” In light of -these possibilities, we may well pause before attempting to appraise -exactly the significance of isolated blood examinations.</p> - -<p>What, too, as the above authority observes, of the influence on -the <i>gouty uricæmia</i> of infancy, puberty, the menopause, and for -that matter the pre-senile and senile periods of life with their -associated vascular lesions? The researches of Uffenheimer prove -that even in young children the disorders of purin metabolism -distinctive of gout are to be met with, <i>i.e.</i>, “infantile gout.”</p> - -<p>We stand also in urgent need of knowledge as to the uric acid -blood content in the <i>early</i> as opposed to the late stages of gout; in -need, too, of further examinations of the blood to this end, not only -during the passage of <i>acute</i> attacks, but even more under those -conditions which are presumed to determine their incidence.</p> - -<p>But, despite these gaps in knowledge, these disabilities of -technique, there is no need for despair. “It is a slow progress -along the zigzag which leads to the centre of the ‘gouty maze,’ -but the researches of the last decade have opened up many new -and possible pathways thereto.”</p> - -<hr class="chap x-ebookmaker-drop"> - -<div class="chapter"> - -<p><span class="pagenum"><a id="Page_149"></a>[149]</span></p> - -<h2 class="nobreak" id="CHAPTER_XII">CHAPTER XII<br> -<span class="smaller">URATOSIS IN RELATION TO GOUT</span></h2> - -</div> - -<p>The two salient features of the gouty diathesis are:—</p> - -<div class="blockquote"> - -<p>(<i>a</i>) The tendency to excess of uric acid in the blood, <i>i.e.</i>, <i>hyper-uricæmia</i>, -and</p> - -<p>(<i>b</i>) The tendency to uratic deposition, <i>i.e.</i>, <i>uratosis</i>.</p> - -</div> - -<p>With the former we have dealt, but before passing to discuss the -latter, it will, we think, be advisable to review both these morbid -tendencies in relation to gout.</p> - -<p>Hyper-uricæmia and uratosis, though they both occur in gout, -are by no means of identical pathological valency or significance. -In hyper-uricæmia the uric acid, either in a free state or combined, -circulates in the blood and lymph. In uratosis the uric acid is -anchored in solid form in the substance of the tissues. In the -former, then, the uric acid, if it be noxious, acts as a chemical -poison, in the latter as a mechanical irritant.</p> - -<p>But the more striking contrast is that while hyper-uricæmia is -not restricted to gout, but occurs in many other disorders; on the -other hand, uratosis is absolutely confined to the gouty state, -constituting its pathognomonic stigma.</p> - -<p>Again, hyper-uricæmia may exist for prolonged periods without -producing uratosis. But uratosis cannot, as far as is ascertained, -occur without a co-existing hyper-uricæmia. From these disparities -it may legitimately be inferred that the factors responsible -for the genesis of hyper-uricæmia and of uratosis, are not identical; -in other words, that in uratosis some other agency or agencies -are at work over and beyond those that beget hyper-uricæmia.</p> - -<p>Lastly, inasmuch as uratosis stamps the seal of specificity upon -gout, it follows, from this and the above considerations, that there -is a more intimate relation between gout and uratosis than between -gout and hyper-uricæmia, and that the factors which make for -uratosis have a more intimate bearing upon the pathogeny of -gout than those which lead to hyper-uricæmia.</p> - -<h3><span class="smcap">Constitution of Tophi</span></h3> - -<div class="poetry-container"> -<div class="poetry"> - <div class="stanza"> - <div class="verse indent0">“Et tophus scaber, et nigris exesa chelydris Creta.”</div> - </div> - <div class="stanza"> - <div class="verse right"><i>Virgil, Georg.</i>, ii., 214.</div> - </div> -</div> -</div> - -<p>The view that tophi were composed of chalk prevailed for -centuries. As we see such was the conception of Virgil, and in our<span class="pagenum"><a id="Page_150"></a>[150]</span> -own country John Hunter entertained the same erroneous notion, -while amongst the laity this view as to their nature is held widely -even to-day as it was in the time of Dryden.</p> - -<div class="poetry-container"> -<div class="poetry"> - <div class="stanza"> - <div class="verse indent0">“Knots upon his gouty joints appear,</div> - <div class="verse indent0">And chalk is in his crippled fingers found.”</div> - </div> - <div class="stanza"> - <div class="verse right"><i>Dryden, Pers.</i></div> - </div> -</div> -</div> - -<p>Albeit, the term “chalk-stones” is a misnomer, as tophi, when -pure, may be wholly devoid of lime. Modern analyses, too, have -failed to demonstrate the presence of calcium carbonate, the -essential ingredient being <i>urate of soda</i>.</p> - -<p>On the authority of Rendu, we have it that Tennant and Pierson -were the first to demonstrate the presence of uric acid in gouty -deposits, which discovery was later confirmed by Fourcroy and -Wollaston (1797), these latter observers showing that they consisted -almost exclusively of urate of soda.</p> - -<p>Subsequently to Wollaston’s day, many analyses have been -conducted, by Marchand, Lehmann, Wurzer, and Langier, -L’Heretier, Ebstein and Sprague. Of the various findings we -append those by Marchand, Lehmann and one of later date by -Ebstein and Sprague.</p> - -<h3><span class="smcap">Marchand’s Analysis</span></h3> - -<table> - <tr> - <td>Urate of soda</td> - <td class="tdr">34·20</td> - </tr> - <tr> - <td>Urate of lime</td> - <td class="tdr">2·12</td> - </tr> - <tr> - <td>Carbonate of ammonia</td> - <td class="tdr">7·86</td> - </tr> - <tr> - <td>Chloride of sodium</td> - <td class="tdr">14·12</td> - </tr> - <tr> - <td>Animal matter</td> - <td class="tdr">32·53</td> - </tr> - <tr> - <td>Water</td> - <td class="tdr">6·80</td> - </tr> - <tr> - <td>Loss</td> - <td class="tdr">2·37</td> - </tr> - <tr> - <td></td> - <td class="tdr bt">100·00</td> - </tr> -</table> - -<h3><span class="smcap">Lehmann’s Analysis</span></h3> - -<table> - <tr> - <td>Urate of soda</td> - <td class="tdr">52·12</td> - </tr> - <tr> - <td>Urate of lime</td> - <td class="tdr">1·25</td> - </tr> - <tr> - <td>Chloride of sodium</td> - <td class="tdr">9·84</td> - </tr> - <tr> - <td>Phosphate of lime</td> - <td class="tdr">4·32</td> - </tr> - <tr> - <td>Cellular tissue</td> - <td class="tdr">28·49</td> - </tr> - <tr> - <td>Water, loss, etc.</td> - <td class="tdr">3·98</td> - </tr> - <tr> - <td></td> - <td class="tdr bt">100·00</td> - </tr> -</table> - -<h3><span class="smcap">Ebstein and Sprague’s Analysis</span></h3> - -<table> - <tr> - <td>Uric acid</td> - <td class="tdr">59·70</td> - </tr> - <tr> - <td>Tissue, organic matter</td> - <td class="tdr">27·88</td> - </tr> - <tr> - <td>Sodium oxide</td> - <td class="tdr">9·30</td> - </tr> - <tr> - <td>Potassium oxide</td> - <td class="tdr">2·95</td> - </tr> - <tr> - <td>Calcium oxide</td> - <td class="tdr">0·17</td> - </tr> - <tr> - <td>MgO, Fe, P₂O₅, S</td> - <td class="tdr">Traces.</td> - </tr> -</table> - -<p><span class="pagenum"><a id="Page_151"></a>[151]</span></p> - -<p>It will be seen that all of them agree more or less closely as to -the essential ingredients being uric acid and soda. According to -Ebstein and Sprague they consist usually of almost pure <i>biurate</i> -of <i>sodium</i> and <i>potassium</i>. But, as a rule, after a time <i>calcium</i> -salts are deposited. Dunin, it may be noted, has found deposits -resembling gouty tophi, which contained only calcium salts. -Kahn, again, claims that tophi do not always consist solely or even -largely of urates, but that these may be replaced by <i>calcium</i> salts. -It may be added, too, that M. B. Schmidt has recorded, under the -designation of “Calcium gout,” a case in which there existed a -generalised deposition of calcium, and this in tissues other than -those usually involved in “metastatic calcification.” But, to -sum up, although there may be admixture of lime salts and -organic matter, the salient chemical constituent of tophi is -<i>biurate of sodium</i>.</p> - -<h3><span class="smcap">Mode of Formation</span></h3> - -<p>Gouty tophi, like all pathological concretions, are laid down in -accordance with a definite law. In the first instance, a central -nucleus is essential. To this must be added a “binding substance” -or structural framework of different nature from the main mass of -the concretion.</p> - -<p>Garrod, discussing the intimate structure of “chalk-stones,” -observes that, “the large amount of phosphate of lime occasionally -met with is probably derived not only from the tissue in which -the chalk-stones have been developed, but likewise from secondary -deposition, the result of ordinary inflammation around the original -nucleus (urate of soda) which acts as a foreign body.”</p> - -<p>It is, however, quite possible that some substance other than -<i>urate of soda</i> constitutes the primary nucleus, for, as we now know, -concretions most frequently gather around masses of mucin, -clumped bacteria, desquamated cells, precipitated proteins, etc. -Thus, the renal <i>uric acid infarcts</i>, supposed to result from disruption -of the nucleo-proteins of the <i>fœtal nucleated red corpuscles</i>, -take origin around injured <i>epithelial</i> cells, which latter form the -nucleus.</p> - -<p>As to <i>gouty tophi</i>, too, it has been suggested that they form in -response to any <i>toxin</i>, resistance to which may involve death of -the tissue cells with consequent disruption of their <i>nucleins</i> and -formation of <i>urates</i>. Such was the view held by Woods. -Hutchinson, who also thought that the calcareous accretions might -be regarded as “protective,” analogous to the formation of shells -in the invertebrates, the process here consisting in the deposition -of lime salts in cells already saturated with uric acid and urates.</p> - -<p>In any case, whatever be the exact nature of the nucleus, the<span class="pagenum"><a id="Page_152"></a>[152]</span> -urate of soda collects thereupon, the acicular crystals tending to -assume the form of radiating needles. But the successive depositions -not being of regular incidence, the surface of the crystals, -in the intervals of quiescence, becomes covered by <i>mucin</i>, animal -or earthy matter. Hence, the concretions display not only a -<i>radiating</i>, but a <i>concentric</i> or <i>laminated</i> structure.</p> - -<p>The mucin acts as the “binding substance,” the crystals -lying in its meshes, and, moreover, remaining as the framework -of the concretion even after the crystals are dissolved -out; in other words, the gouty tophus is made up of a blend -of <i>crystalloids</i> and <i>colloids</i>, evolved from solutions of the same -character.</p> - -<p>The importance of recognising the true nature of this binding -substance, <i>i.e.</i>, mucin, merits a brief digression, in light of Ebstein’s -view that local tissue <i>necrosis</i> is a necessary antecedent to uratic -deposition. Now, exhaustive studies of the histology of uratic -deposits, both those experimentally induced and of spontaneous -gouty origin, have been conducted by Freudweiler, His, Krause, -and Rosenbach.</p> - -<p>All their results, according to Gideon Wells, “indicate that uric -acid and urates excite some slight inflammatory reaction, cause a -slight local necrosis, and seem to act as a weak tissue poison.” -According to Rosenbach, however, this sequence is not invariable, -inasmuch as he noted that such deposits may occur without -inducing necrosis. More pertinently to our contention, however, -is it that Krause’s experience seems to indicate that errors of -interpretation were possible. Thus, he suggests that part of the -material in the areas of uratic deposits merely constituted the -<i>framework</i> of a crystalline deposit, though such were currently -regarded as <i>strands</i> of <i>necrotic tissue</i>.</p> - -<p>But, to resume, tophi being blends of <i>crystalloids</i> and <i>colloids</i>, we -must recollect that the suspension capacity of <i>colloidal</i> solutions -for crystalloids is much superior to that of simple solutions, by -reason of the fact that at the surface of each colloidal particle -there exists a zone in which the crystalloids are much more closely -aggregated than elsewhere, thus permitting more crystalloids to be -dissolved in the solvent between the colloidal particles. But, be -it noted, this same tendency to concentration of the crystalloids -at the surface of the colloidal elements leads to the colloids acting -as determinants of <i>precipitation</i> when <i>crystalloids</i> are in excess. -Accordingly, when the crystalloids pass out of solution, they form -crystals or precipitates intimately blended with the colloids. -Thus, for example, when uric acid crystallises out of urine it -carries with it the colloidal pigments. On the other hand, if the -colloids are precipitated, the solvent capacity of the solution being<span class="pagenum"><a id="Page_153"></a>[153]</span> -consequently depreciated, the crystalloids are deposited in -intimate relation with the colloids.</p> - -<p>Again, Schade has pointed out that colloids may precipitate in -reversible form or not. If in irreversible (<i>e.g.</i>, fibrin) form, the -concretion will remain permanent. But if the colloidal precipitate -is reversible, it may be redissolved, as happens with the uric <i>acid -infarcts</i> of the infant’s kidney. In conclusion, we see, therefore, -<i>re</i> crystalloids and colloids in animal juices, that the conditions of -their solubility are most complex, and though they do not explain -the nature of gout, the variations doubtless stand in intimate -relation to the <i>formation of tophi</i>.</p> - -<h3><span class="smcap">Localisation of Uratic Deposits</span></h3> - -<p>Uratic deposits evince a decided predilection for <i>cartilages</i>, -tendons, muscles, and skin. This localised distribution of the -depositions would seem to suggest their dependence on <i>local tissue -peculiarities</i>. Now the presence of <i>sodium</i> salts in a solution -diminishes the solubility of urates therein. Consequently, in -seeking to explain the incidence of <i>tophi</i>, it was suggested that -<i>cartilage</i> and <i>tendons</i>, being richer in <i>sodium ions</i> than the <i>blood</i>, -this might account for the fact that urates tend to be precipitated -in these particular structures.</p> - -<p>Again, Almagia, working in Hofmeister’s laboratory, noted -that thin sections of <i>cartilage</i>, if left for some hours in a solution of -sodium urate, will take up <i>uric acid</i>. Direct inspection readily -reveals the presence of white foci and diffuse opacities due to -uratic deposits. The marked affinity of normal cartilage for -uric acid is again attested by the fact that, given injection thereof -in quantity into the peritoneal cavity of rabbits, the uric acid -may often be detected by the murexide reaction in <i>joint cartilage</i>, -though apparently not in other tissues.</p> - -<p>This behaviour would appear to justify the conclusion that the -observed accumulation of uric acid in the cartilages in the presence -of states of <i>uricæmia</i>, may be explicable on this same basis. -In any case, this marked affinity of even <i>normal</i> cartilage for uric -acid seems to disprove the necessity of Ebstein’s postulate, -viz., that the dissolved uric acid sets up inflammation, and that -an <i>antecedent necrosis</i> precedes the <i>deposition of urates</i>. Still, -even if we concede the fact that <i>normal cartilage</i> has a marked -affinity for <i>uric acid</i>, how is it that in <i>leukæmics</i>, despite their -high blood content of <i>uric acid</i>, no <i>uratic deposits</i> ensue? Does -not such disparity seem to indicate that in gout some other factor -intrudes? in other words, that the excess of <i>sodium ions</i> in -particular tissues, while it may favour deposition therein, is<span class="pagenum"><a id="Page_154"></a>[154]</span> -inadequate of itself to actually determine the formation of -tophi.</p> - -<h3><span class="smcap">The Causation of Tophi</span></h3> - -<p>Many and divers are the theories that have been propounded -to account for the genesis of tophi. For some their incidence -would appear to predicate something abnormal in the conditions -of uric acid solution and circulation. Others have pinned their -faith to some affinity on the part of the bodily tissues for uric -acid—an enhanced retention capacity on their part for this -substance. Some again, impressed by the objective changes that -mark the clinical evolution of tophi, have been led to regard them -as <i>concomitants</i> or <i>sequels</i> of <i>gouty inflammation</i>. But, be the -true explanation what it may, we may well preface our discussion -of the various theories by the obvious comment, viz., that the -origin of tophi must doubtless depend in the ultimate upon -<i>constitutional</i> or <i>systemic</i>, as well as <i>local</i>, factors.</p> - -<h3><span class="smcap">Solubilities of Uric Acid</span></h3> - -<p>In the older conceptions of the pathology of gout the hypothesis -that found most vogue was that the separation of uric acid from -the blood into the tissues was due to <i>diminished alkalinity</i> of the -blood and tissue juices; but, as before pointed out, it has been -established that the alkalinity of the blood is <i>not</i> reduced, and the -theory has consequently been abandoned.</p> - -<p>But, with the advent of Gudzent’s findings, viz., that uric -acid existed in two forms—one soluble and unstable, and the other -insoluble and stable, and that the former is constantly changing -into the latter—another conception of the origin of tophi arose. -It was supposed that, by reason of the disparity in solubility of -these <i>tautomeric</i> types of <i>uric acid</i>, the blood in gouty subjects -must at times be in a state of <i>super-saturation</i> with uric acid; -and, moreover, that equilibrium could only be restored through -abstraction of the urates by crystallisation.</p> - -<p>Unfortunately for this theory, it has been shown that the blood -of gouty subjects is not <i>super-saturated</i> therewith; indeed, -over and above the highest increments hitherto met with in gouty -blood, a considerable margin of solubility for uric acid is still -available. In truth, the problem is by no means so simple; for -the conditions governing the solvency of uric acid in the blood -are bewilderingly complex, subject as they are to the manifold -variations in solubility exhibited by crystalloids in the presence -of the many divers colloids.</p> - -<p>But, to resume, Minkowski, it will be recalled, noted that<span class="pagenum"><a id="Page_155"></a>[155]</span> -from a mixed solution of <i>uric</i> and <i>nucleinic acids</i> the former -cannot be precipitated by either acetic acid or alkaline ammonio-silver-magnesia -mixture. Accordingly he advanced the view -that uric acid “primarily exists in the blood and the tissue juices -in combination with nucleinic acid, and that, not only the conversion -of the purin bases into uric acid, but also the solubility -and transportation, as well as the further changes of the uric acid -in the living body, is regulated by this linking with a nucleinic -acid rest.”</p> - -<p>But, unfortunately for the value of this hypothesis, there is -no proof that <i>nucleinic acid</i> is actually present in the blood; -for, as Fürth remarks, is this inhibition of the precipitation of -uric acid, in the presence of nucleinic acid, “necessarily indicative -of a true acid combination with nucleinic acid,” -“but such inhibition of precipitation is rather to be referred -to the general group of variations of solubility which are manifested -by crystalloid substances in the presence of all sorts of -colloids.”</p> - -<p>Complex phenomena of solubility of this nature must be considered -in connection with the circulating uric acid. Nucleinic -acid is not the only important substance, but “the general mass -of the blood proteins must be particularly thought of.”</p> - -<p>Continuing, Fürth reminds us that uric acid is much more -soluble in <i>blood serum</i> than in water, and forthwith envisages this -disparity in light of the factors that affect solubility of uric acid -in the <i>urine</i>. The latter is markedly influenced by the presence -of urea and di-sodium phosphate, and the relation of this to -mono-sodium phosphate. Nor, he reflects, is there any doubt -“of the importance of such inter-relations, too, in the formation -of <i>uric acid deposits in the tissues</i>.” But he adds, “Although -the importance of these complex conditions of solubility as they -prevail among colloid and crystalloid substances in the animal -juices may be accepted in relation to the formation of uric acid -concretions, there is no real reason for seeking the explanation of -gout in this sphere.”</p> - -<h3><span class="smcap">Tophi in Relation To Uricæmia</span></h3> - -<p>It might be thought that some relationship might be established -between uratic deposits and the degrees of uricæmia, but the -data to hand give no countenance to the assumption. Thus, His -has recorded the case of a gouty subject with multiple tophi whose -blood did not yield an excess of uric acid. Pratt, again, could trace -no relation between the amount of uric acid in the blood and the -severity or character of the disease. Two of his patients had<span class="pagenum"><a id="Page_156"></a>[156]</span> -numerous and widely distributed large deposits of sodium urate -beneath the skin, yet the <i>blood content</i> of <i>uric acid</i> in both was -less than the average amount found in gout. Thus, on a purin-free -diet, one had 2·4, the other 2·2 mg. These findings, he considers, -show that the presence of <i>multiple tophi</i> is no indication -that a state of <i>hyper-uricæmia</i> exists.</p> - -<p>Walker Hall, discussing this same question, holds that there is -but little evidence “as to the relation of uricæmia to the formation -of tophi.” He asks the question whether the deposition is the -outcome of abnormal purin combination in the blood and lymph -stream? which latter at present, he states, are regarded as passive -carriers of the urates. For, he says, the small purin increase in -gouty blood cannot surely make all the difference, seeing the large -volume of solubility still available. The physico-chemical -hypothesis, he claims, is inadequate to explain the relationship -between uricæmia and the tophi, and hazards the suggestion that -after all it may be that “the uricæmia plays little or no part in the -depositions, and that these are due to the defective removal of -substances resultant from local nuclear activities.” He asks, -moreover, whether such substances differ in type from those of -normal nuclein metabolism and so fail to be suspended in the -surrounding lymph in such a way as to ensure their entrance into -the blood-stream? Like others, he notes that atophan brings about -a removal of some of the deposited urates. But such diminution -of the tophi may, of course, he says, be due to increased flow of -serum to the inflamed part; though, on the other hand, the more -massive deposits “are surrounded by layers of young granulation -tissue and phagocytes and peritophal fibrous tissue, and -these in turn offer some hindrance to the permeation of serum or -drugs.”</p> - -<p>In reviewing the foregoing views as to the formation of tophi, -it is obvious we stand in urgent need of more knowledge. Neither -the chemical nor the physical theory or a combination of the twain -seems adequate. This for the salient reason that, as far as the -existing evidence permits us to draw conclusions, it would seem -probable that not only local but constitutional or systemic conditions -play an important <i>rôle</i> in tophi formation.</p> - -<p>But as far as our discussion has advanced, we may, we think, be -justified in the following deductions:—</p> - -<div class="blockquote"> - -<p>(1) That tophi are blends of crystalloids and colloids and subject -to the complex conditions of solubility attaching to -such combinations.</p> - -<p>(2) That the relatively high sodium content of certain tissues, -<i>e.g.</i>, cartilage, favours the incidence of uratic deposits -therein.</p> - -<p><span class="pagenum"><a id="Page_157"></a>[157]</span></p> - -<p>(3) That tissue necrosis is not necessarily an antecedent to -uratic deposits.</p> - -<p>(4) That no relationship can be established between the incidence -or multiplicity of tophi and uricæmia.</p> - -</div> - -<p>It will be seen from these conclusions that the proximate cause -responsible for the genesis of tophi is yet to seek, and in pursuance -of our quest we turn to another aspect of this complex subject.</p> - -<h3><span class="smcap">Tissue Affinities for Uric Acid</span></h3> - -<p>Injecting uric acid intravenously into <i>gouty</i> subjects, Umber -noted that at times the whole was retained, but on some occasions -was excreted in fractional portions. On the other hand, a <i>normal</i> -individual under similar circumstances eliminates it completely. -In explanation thereof, he proffered the opinion that this failure -on the part of gouty persons to excrete exogenous uric acid was -due to a <i>special affinity of their tissues for uric acid</i>.</p> - -<p>As to intravenous injection of uric acid, however, modern -investigation has established that, both in normal as well as gouty -subjects, its excretion is spread over several days, and the <i>whole</i> -is <i>not</i> recoverable from the urine. Now this incomplete excretion -or <i>retention</i> of uric acid was attributed to <i>defective elimination by -the renal cells</i>; but, as shown in a previous chapter, this conception -fails of demonstration. Nor, for that matter is there any proof -either that the retention is due to <i>fixation of the uric acid in the -blood serum</i>. Accordingly, to our minds, it is permissible then to -canvass the further possibility adumbrated by Umber, viz., that -an <i>increased affinity of the tissues for uric acid</i> may haply account -for the diminished purin excretion, the excess of uric acid in the -blood, lymph, and tissues, and that these same may lead to -<i>uratic deposition</i>.</p> - -<p>This last hypothesis derives colour from the findings of Schmoll, -Magnus Levy, Vogt, Reach and Bloch, who noted that, after -giving thymus to <i>gouty</i> persons, they found far less uric acid in -the urine than in the case of normal subjects. Also, that the -ingestion of thymus by the victims of <i>chronic</i> gout repeatedly -resulted in acute outbursts of the disease. Moreover, as we saw -when discussing the <i>sources</i> of uric acid, there are cogent -reasons for avoiding a too restricted conception which would make -the leucocytes, the muscles, or the digestive glands alone -responsible for the <i>endogenous production of uric acid</i>; in other -words, that a more catholic attitude on our part is indicated, one -which would envisage it as the outcome of continuous and -<i>general cellular</i> wear and tear. That an <i>increased cellular destruction</i>, -as induced experimentally, <i>e.g.</i>, by exposure to Röntgen<span class="pagenum"><a id="Page_158"></a>[158]</span> -rays, is capable of raising the <i>blood content</i> of <i>uric acid</i> in a <i>gouty</i> -subject, and of precipitating a gouty paroxysm, may be inferred -from the researches of P. Linsen.</p> - -<h3><span class="smcap">Retention Capacity of Tissues for Uric Acid</span></h3> - -<p>It may be recalled that Wiechowski and others observed that -in man, of <i>parenterally</i> introduced uric acid, 80-90 per cent. -reappears in the urine. Accordingly, Schittenhelm and Wiener -argued that, if uric acid is indestructible in the human body, then, -given <i>retarded elimination</i>, the <i>tissues</i> should contain considerable -quantities thereof. Subsequently, in 1914, they sought to investigate -human tissues as to their content of uric acid. Their -studies were conducted on three examples, a case of anuria, one -of pernicious anæmia, and one of gout.</p> - -<p>The case of <i>anuria</i> occurred in a male, aged sixty-two, in -sequence to thrombosis of both renal veins following operation. -Two-hundred gram samples of the following tissues, lung, heart, -spleen and liver, were examined for uric acid with wholly negative -results. The residue of the organ was worked up together, but -only 0·01 gram of uric acid was isolated.</p> - -<p>In the case of <i>pernicious anæmia</i> no uric acid was demonstrable. -The <i>gouty</i> subject had for twenty-five years suffered from typical -attacks and exhibited many auricular tophi. The following -organs, in their entirety, were analysed, the <i>liver</i> (1,550 gram), no -uric acid; <i>spleen</i> (290 gm.), 10 mg. uric acid (3·5 mg. per 100 gm.); -<i>kidney</i> (270 gm.), no uric acid; <i>lung</i> (930 gm.), 15 mg. uric acid -(1·6 mg. per 100 gm.); <i>muscle</i> (440 gram), no uric acid; and -<i>intestine</i> (420 gram), no uric acid.</p> - -<p>It will be seen that <i>uric acid was either absent or present in -minimal amounts</i>, and these results Schittenhelm and Wiener interpreted -as confirming their long advocated contention as to the -<i>destructibility of uric acid</i> in the human organism.</p> - -<p>Morris S. Fine, from the results of similar investigations, considered -the failure of these observers to isolate <i>uric acid</i> in these -cases of <i>anuria</i> and <i>gout</i> as most remarkable. He considers “their -results may in part be ascribed to the use of hot sodium hydroxide -previous to the precipitation of the proteins in the extraction of -the tissues, as the instability of uric acid in alkaline solutions is a -well-known property.”</p> - -<p>In this criticism Fine would appear to be fully justified, in -view of the marked contrast between the findings of Schittenhelm -and Wiener, and his own data is recorded in the tables on -p. 159.</p> - -<p>While it is unfortunate that Fine’s theory contained no instances<span class="pagenum"><a id="Page_159"></a>[159]</span> -of <i>gout</i>, his findings are a definite proof that, to quote his own -words, <i>uric acid can be demonstrated in considerable concentrations -in human tissues</i>. Incidentally, also, his tissue analyses are flatly -contradictory to Schittenhelm and Weiner’s persistent contention, -viz., that the human organism <i>can decompose uric acid</i>.</p> - -<p>Gideon Wells states that in normal individuals the tissues contain -but little uric acid, and this not in quantities sufficient to -permit readily of its isolation in a pure state. Albeit, Wells found -considerable amounts of uric acid in the tissues of a young woman -who, in sequence to poisoning with HgCl₂, died after complete -suppression of urine for nine days.</p> - -<h3><span class="smcap">Table I.—Concentration of Uric Acid in Human Tissues -and Fluids per 100 Grams of Material</span></h3> - -<table class="borders"> - <tr> - <th>Case.</th> - <th>E. E. Uremia.</th> - <th>T. D. Uremia.</th> - <th>S. H. Uremia.</th> - <th>M. F. Diabetes.</th> - <th>C. M. Diabetes.</th> - <th>S. T. Amputation.</th> - <th>H. J. Pneumonia.</th> - </tr> - <tr> - <td></td> - <td class="tdc smaller">mg.</td> - <td class="tdc smaller">mg.</td> - <td class="tdc smaller">mg.</td> - <td class="tdc smaller">mg.</td> - <td class="tdc smaller">mg.</td> - <td class="tdc smaller">mg.</td> - <td class="tdc smaller">mg.</td> - </tr> - <tr> - <td>Blood</td> - <td class="tdr">15·4</td> - <td class="tdr">14·3</td> - <td class="tdr">17·0</td> - <td class="tdr">0·7</td> - <td class="tdr">0·7</td> - <td class="tdr">0·7</td> - <td class="tdr"></td> - </tr> - <tr> - <td>Pleural fluid</td> - <td class="tdr">16·7</td> - <td class="tdr">15·9</td> - <td class="tdr"></td> - <td class="tdr"></td> - <td class="tdr"></td> - <td class="tdr"></td> - <td class="tdr"></td> - </tr> - <tr> - <td>Ascitic fluid</td> - <td class="tdr">18·0</td> - <td class="tdr"></td> - <td class="tdr"></td> - <td class="tdr"></td> - <td class="tdr"></td> - <td class="tdr"></td> - <td class="tdr"></td> - </tr> - <tr> - <td>Pericardial fluid</td> - <td class="tdr"></td> - <td class="tdr">14·3</td> - <td class="tdr">18·0</td> - <td class="tdr"></td> - <td class="tdr"></td> - <td class="tdr"></td> - <td class="tdr"></td> - </tr> - <tr> - <td>Subcutaneous fluid</td> - <td class="tdr">18·0</td> - <td class="tdr"></td> - <td class="tdr"></td> - <td class="tdr"></td> - <td class="tdr"></td> - <td class="tdr"></td> - <td class="tdr"></td> - </tr> - <tr> - <td>Spinal fluid</td> - <td class="tdr">2·8</td> - <td class="tdr">2·0</td> - <td class="tdr">4·7</td> - <td class="tdr"></td> - <td class="tdr"></td> - <td class="tdr"></td> - <td class="tdr"></td> - </tr> - <tr> - <td class="nw">Skeletal muscle</td> - <td class="tdr">8·0</td> - <td class="tdr">3·9</td> - <td class="tdr">5·8</td> - <td class="tdr">0·7</td> - <td class="tdr">2·6</td> - <td class="tdr">2·0</td> - <td class="tdr"></td> - </tr> - <tr> - <td>Heart muscle</td> - <td class="tdr">10·0</td> - <td class="tdr">7·3</td> - <td class="tdr">8·8</td> - <td class="tdr"></td> - <td class="tdr">1·2</td> - <td class="tdr"></td> - <td class="tdr"></td> - </tr> - <tr> - <td>Liver</td> - <td class="tdr">18·0</td> - <td class="tdr">15·6</td> - <td class="tdr">11·5</td> - <td class="tdr"></td> - <td class="tdr">5·0</td> - <td class="tdr"></td> - <td class="tdr">4·0</td> - </tr> - <tr> - <td>Spleen</td> - <td class="tdr">12·6</td> - <td class="tdr">14·3</td> - <td class="tdr">9·1</td> - <td class="tdr"></td> - <td class="tdr">1·2</td> - <td class="tdr"></td> - <td class="tdr">Trace</td> - </tr> - <tr> - <td>Skin</td> - <td class="tdr"></td> - <td class="tdr">13·0</td> - <td class="tdr"></td> - <td class="tdr"></td> - <td class="tdr"></td> - <td class="tdr"></td> - <td class="tdr"></td> - </tr> -</table> - -<h3><span class="smcap">Table II.—Concentration of Uric Acid -in Miscellaneous Human Tissues per -100 Grams of Material</span></h3> - -<table class="borders"> - <tr> - <th>Tissue.</th> - <th>Uric<br>acid.</th> - </tr> - <tr> - <td></td> - <td class="tdc smaller">mg.</td> - </tr> - <tr> - <td>Pectoral muscle</td> - <td class="tdr">2·5</td> - </tr> - <tr> - <td>Uterine muscle</td> - <td class="tdr">2·0</td> - </tr> - <tr> - <td>Uterine muscle</td> - <td class="tdr">2·5</td> - </tr> - <tr> - <td>Uterine muscle</td> - <td class="tdr">1·2</td> - </tr> - <tr> - <td>Mixed tonsils</td> - <td class="tdr">1·7</td> - </tr> - <tr> - <td>Thyroid</td> - <td class="tdr">0·0</td> - </tr> -</table> - -<p>Again, as before alluded to, Bass and Herzberg found that<span class="pagenum"><a id="Page_160"></a>[160]</span> -intravenous injection of uric acid caused less <i>uricæmia</i> in the <i>gouty</i>, -despite diminished renal excretion. Hence, they concluded that -<i>in gout the retention capacity of the tissues for uric acid is -augmented</i>.</p> - -<p>Fürth, an ardent advocate of Umber’s hypothesis, emphasises -the fact that Wiechowski was never able to detect any evidence of -<i>uricolysis</i> in the human body. Continuing, he observes, if we -reject all idea of <i>uric acid retention in the tissues</i>, “It would be a -particularly difficult thing to understand why gouty patients do -not simply expel by a compensatory hyper-excretion the uric acid -which is accumulated from a supposed failure of uricolysis; precisely -as in leukæmia the patient compensates simply by an -exaggerated excretion of the excessive uric acid which is mobilised -in the body from the excessive purin decomposition.” His conclusion, -therefore, is that, “<i>In the gouty individual there must exist -some cause which makes a compensatory uric acid excretion impossible; -and that is plainly a retention affinity of the tissues, because of which -the uric acid is actually held in the tissues.</i>”</p> - -<p>In light of Fine’s revelations the retention capacity of the bodily -tissue for uric acid may, we take it, be considered as fairly well -established. But, in view of the <i>precipitation or anchoring of -urates in the tissues in gout</i> it is most desirable that further investigations -be made to discover whether in <i>gouty</i> subjects the <i>tissue -retention capacity</i> for <i>uric acid</i> is <i>enhanced</i>.</p> - -<p>“The impression,” says Fürth, “grows on one that this hitherto -little considered factor, of an increased affinity of the tissues for -uric acid in the gouty subject is very much closer to the real -kernel of the gout problem than, for example, the question of the -fixation of uric acid in the blood about which there has been so -much contention, and with which of necessity we are compelled, -at least, to some little extent to concern ourselves.” The results -of modern researches tend to support this more catholic conception. -We would recall that Lewis and his co-workers, seeking the -source of the <i>increased endogenous purin excretion</i> that follows -ingestion of <i>purin-free</i> food, were forced to reject the view that -it was solely derived from katabolism of the <i>nuclear</i> substance of -the <i>digestive glands</i>, and to refer it instead to “wear and tear” -of the <i>body cells as a whole</i>. Precisely the same change in attitude, -we may remind our readers, has overtaken us in regard to the site -of <i>urea</i> formation, viz., that not only the <i>liver</i> cells, but those of -the muscles also participate in its production.</p> - -<p>While admitting that dogmatism is out of place, still to our -mind this theory of <i>tissue retention</i> makes strong appeal. In light -of it the nebulous “gouty diathesis” seems on its way to become -incarnate in some <i>inborn peculiarity</i> of <i>tissue-function</i>, a falling<span class="pagenum"><a id="Page_161"></a>[161]</span> -short of full physiological activity, or, as M. Rendu termed it, a -“<i>primordial vice of nutrition</i>.”</p> - -<p>In other words, in gout there is no rift nor lack of finish in the -orderly sequence of enzymatic reactions that eventuate in <i>uric -acid</i>. Uric acid is formed and, as far as we know, after a normal -fashion. But, here comes the flaw, viz., the uric acid, when -formed, fails of transport and elimination. It is <i>precipitated</i> and -<i>anchored</i> in the <i>tissues</i>, from whose grip it fails to detach itself. In -short, it is not the formation of uric acid, or its failure of further -metamorphosis, but the <i>retention</i> of uric acid, and more pertinently, -its <i>fixation in the tissues</i> that constitutes the salient feature of -gout.</p> - -<p>Now, all modern research tends to indicate that uric acid is not -an intermediary, but a <i>terminal</i> product of metabolism, and, moreover, -that there are no <i>uricolytic</i> ferments within the body whereby -its destruction can be accomplished.</p> - -<p>If we grant that—</p> - -<div class="blockquote"> - -<p>(1) Uric acid is not an intermediate but an end-product of -metabolism; and</p> - -<p>(2) That the human body is devoid of uric acid-destroying -enzymes,</p> - -</div> - -<p class="noindent">then it follows that man, <i>ipso facto</i>, is <i>potentially liable to uric acid -retention and deposition</i>, the same objectivated as <i>tophi</i>. In this -innate potentiality of and to <i>uratosis</i> resides the “gouty” -diathesis.</p> - -<p>If the postulates (1) and (2) be established, then, though it -sound rank heresy, it follows that gout is not, chemically speaking, -an “error of metabolism.” Not, at any rate, in the ordinary -acceptation, viz., not a failure in the transmutation of uric acid -into urea and intermediate products. If uric acid be an <i>end-product</i>, -then no further cleavage into <i>urea</i>, etc., occurs, and -in this connection the failure to discover <i>uricolytic enzymes</i> is -significant.</p> - -<p>We have before proffered the suggestion that not only local, but -<i>constitutional</i>, or systemic influences also play a part in the origin -of tophi. Provisionally, therefore, we would infer that—</p> - -<div class="blockquote"> - -<p>(1) The tissues of gouty subjects display an abnormal affinity -for uric acid, <i>i.e.</i>, an increased retention capacity for the -same;</p> - -<p>(2) That certain chemico-physical factors, previously alluded to -(content of sodium ions, etc.), favour the incidence of -uratic deposits in particular tissues.</p> - -</div> - -<p>In other words, we have in these two elements haply the constitutional -and local factors that we postulate as essential to the -formation of tophi. Albeit, they represent but <i>latent tissue<span class="pagenum"><a id="Page_162"></a>[162]</span> -potentialities</i>, inadequate of themselves to determine the eruption -of <i>tophi</i>.</p> - -<p>Moreover, be it recalled that the <i>causa causans</i> of gout must be -responsible not only for the incidence of <i>tophi</i>, but also for the -more dramatic features of gout, its <i>arthritic</i> outbreaks, etc. To -dissociate the cause or causes of the uratic deposits from that of -the joint inflammations would indeed appear impermissible.</p> - -<p>But, taking this view, it is clear that, apart from the constitutional -and local factors above postulated, tophi and, alike, the -arthritic phenomena of gout, demand for their production the -intrusion of some further element, some <i>tertium quid</i>, vital and -biological. To this end, therefore, we purpose reviewing tophi in -their <i>clinical</i> aspects, as herein possibly we may find some further -clue to their exact mode of genesis.</p> - -<h3><span class="smcap">Clinical Evolution of Tophi</span></h3> - -<p>As to the clinical characters that mark the genesis and maturation -of tophi not a little conflict of opinion seems to obtain. Do -tophi arise painlessly or not? Do the uratic depositions occasion -any local inflammatory reaction? Or, are they merely concomitants -or sequels thereof?</p> - -<p>With what wearisome iteration has the same question been propounded -in regard of <i>gouty arthritis</i>. Are the attacks of pain and -inflammation due to deposits, or do the deposits take place at the -site of inflammation?</p> - -<p>But, restricting our enquiries to tophi, we may remind the -reader that Aretæus, writing in the second century, A.D., made -the following observations: “Callosities also form in the joints; -at first they resemble abscesses, but afterwards they get more condensed, -and the humour being condensed is difficult to dissolve; at -last they are converted into hard white tophi (Πῶροι στερροὶ λευκοὶ), -and over the whole there are small tumours like <i>vari</i> and larger, -but the humour is thick white and like hailstones” (Περὶ Αρθριτιδος). -To our mind, it would be difficult to emulate, much less to surpass, -the succinct and, as we believe, accurate picture here drawn of the -various stages that mark the life history of tophi. It will be noted -that Aretæus says that in their initial stages they “resemble -abscesses,” and, turning to the writings of the elder Garrod and -others, we find abundant evidence that it is so.</p> - -<p>Discussing the more frequent incidence of tophi in the hands -than in the feet, Garrod describes the physical characters presented -by tophi in the making as seen in one of his examples of -gout. “On the dorsal surface of the second phalangeal joints -of three fingers, small rounded protuberances were observed, the<span class="pagenum"><a id="Page_163"></a>[163]</span> -skin over them being red; these bulgings appeared soft, as if -containing a thick fluid, but not the slightest indication of white -matter could be seen through the skin; they might have been -either gouty concretions in their early stage of formation or some -other form of swelling; from a simple inspection I could form no -opinion as to their true nature, but their history convinced me -that they arose from a deposit of urate of soda. Upon puncturing -one of the little swellings, full light was thrown upon the case, as -a thick white fluid immediately exuded, a drop of which placed, -under the microscope, with the use of polarised light, gave the -appearance represented in Fig. 1; the crystals were proved by -analysis to consist of urate of soda.”</p> - -<p>We see, therefore, that Aretæus and Garrod were at one in their -observation that tophi in their initial stages are betokened by -<i>small red swellings</i>; in other words, as Aretæus says, they “resemble -abscesses.” Garrod also held that uratic deposits probably -form during an attack of gout, but occasionally they appear -shortly afterwards. Thus, in one of his cases no auricular tophi -were found when the subject left hospital, but within ten days, on -re-examination, a deposit was detected. “Perhaps,” he reflects, -“some fluid was effused during the fit, but being at first transparent, -could not easily be distinguished.”</p> - -<p>That Garrod held the swellings to be <i>inflammatory</i> in nature is -clear from his writings. Thus, he says, “When tissues little liable -to take on inflammatory action become infiltrated (with urate -of soda), but slight vascular disturbance is produced. This is -especially the case with the fibro-cartilage of the ear, and although -we now and then meet with patients aware of the formation of -these little nodules, who experience in fact a gouty fit in the ear, -yet in the majority of cases attention has never been directed to -the part, so slight has been the inflammation caused by the -effusion.”</p> - -<p>Again, James Moore, whose graphic description of tophi formation -is quoted by Garrod, also held that “this process is usually -preceded and accompanied by inflammation.” Hilton Fagge, too, -says, “it appears probable that the deposition of lithate of soda -causes inflammation in other tissues besides the joints. It does, -as we have seen, in the ear and occasionally in the skin.” But, he -also states, “in the pinna of the ear, in fact, gouty concretions -commonly form without any indications of previous inflammatory -action. In some instances the patient experiences sensations of -heat and pricking, and the part is tender, but more often he is -quite unconscious of the fact that such concretions in the pinna -are present.”</p> - -<p>Duckworth also noted that uratic deposits are <i>not always painless</i><span class="pagenum"><a id="Page_164"></a>[164]</span> -during their formation, and he noted that not only may -auricular tophi be painful at this stage, but that, following the -subsidence of acute gout in a joint, painful swellings may develop -in its vicinity, which subsequently proved to have been tophi in -process of formation.</p> - -<p>For myself, I am of opinion that each and every process of -tophus formation is preceded by local inflammatory reaction of -varying grades of severity. In a matter of this sort, positive is -more valuable than negative evidence. We see that all the -authorities quoted admit that <i>tophi</i> are associated with <i>inflammation</i> -and some measure of <i>pain</i>, though they add the reservation -that in many instances, if not the majority, these phenomena -have apparently been absent. Apparently, we say advisedly, -for conceding that the pain attending the formation of auricular -tophi is but slight, how all too easy for the subject to have -wholly forgotten it when he comes later under notice. By this -time the tophi, from being latent, have become overt. The -initial soft red swellings, their nature probably misinterpreted at -their initiation, are now transmuted into pearly concretions of -hard or semi-solid consistence. Small wonder, then, that attempts -to elicit the history of slight pain and pricking or tenderness often -prove barren; for, be it noted, tophi take months to mature, as -Garrod long since pointed out.</p> - -<p>Moreover, we would emphasise the fact that <i>tophi</i>, more often -than is thought, occasionally precede by some years the outbreak -of <i>arthritic</i> attacks. Both Duckworth and Garrod are -quite definite on this, and we can confirm them.</p> - -<p>In such instances, then, even granted that our attention be drawn -to them in their initial stages, how easy to misinterpret their true -nature! Thus, we have known tophi in their early stages of -formation confused with <i>chilblains</i>. In this connection we might -remind the reader that, according to Duckworth, amongst the -peculiarities of tissue in those goutily disposed is feebleness of -the peripheral capillary circulation, “a condition leading to disorders -of chilblain-type, the vessels filling slowly after being -emptied.”</p> - -<p>We repeat that the cause or causes of tophi and, alike, of the -arthritic phenomena of gout are, and must be, one and indivisible, -for the process of tophus formation is but an attack in miniature -of gout. Although he may never have had an arthritic outbreak, -the individual who exhibits a tophus undeniably has gout. More -certainly so than if he had had an inflammatory outbreak in his -great toe; for this, at any rate, may be of <i>non-gouty</i> origin, but -the tophus, never!</p> - -<p>Reflecting on the foregoing considerations, we would submit—</p> - -<p><span class="pagenum"><a id="Page_165"></a>[165]</span></p> - -<div class="blockquote"> - -<p>(1) That tophi are always preceded by local inflammatory -reaction of varying grades of severity, and that the uratic -deposits are sequels thereto;</p> - -<p>(2) That in their early stages their presence is betokened by -soft red swellings associated often with sensations of -pricking and tenderness;</p> - -<p>(3) That their transmutation into white pearly concretions is a -process that takes months to mature;</p> - -<p>(4) That tophi and arthritic outbreaks have a common causal -origin.</p> - -</div> - -<p>The question that now thrusts itself upon us is,—What, then, is -the cause of the inflammatory phenomena which determines the -eruption of tophi, and alike of the arthritic outbreaks?</p> - -<h3><span class="smcap">The Cause of the Inflammatory Phenomena</span></h3> - -<p>Garrod’s discovery that uric acid was present in the blood in -gout not unnaturally led to the assumption that herein lay the -origin of its symptomatology, and what else than confirmatory -could be the deposition of uratic deposits here and there in the -body. The corollary seemed obvious that, given the presence -of a certain proportion of uric acid in the blood, then gout must -result. But, unfortunately, it was not so; for, lo! and behold, -an excess of uric acid in the blood is in no sense pathognomonic of -gout.</p> - -<p>Thus, the blood in <i>leukæmia</i> contains a high percentage of uric -acid, in some cases exceeding that found in gout, and enduring, -moreover, for a longer period. Yet no symptoms distinctive of -gout appear, nothing that can be referred to <i>uric acid</i>. But it was -contended the reason why gout does not ensue is because simultaneously -with increased formation there is increased elimination -of uric acid. But, unfortunately, despite augmented excretion, -the percentage of uric acid in the blood is still maintained at a -high level, and still no gout occurs.</p> - -<p>Moreover, it is met with also in nephritis, simple and pernicious -anæmia, intestinal inflammation, certain fevers, notably in malaria -between attacks, and in typhus after the febrile stage, pneumonia, -plumbism, etc. Indeed, the ubiquitousness with which uric acid -is found in the blood, and this in conditions wholly distinct from -gout, would of itself seem sufficient to dissipate any lingering -doubts as to its being anything more than a symptom of gout and -not its proximate cause.</p> - -<p>Obviously, with these revelations the uric acid theory was within -measurable distance of being uprooted. Deposed from its high<span class="pagenum"><a id="Page_166"></a>[166]</span> -estate as a causal agent, and accredited with only a symptomatic -value, the question arose whether indeed this bogey, “uric acid,” -was even capable of fulfilling a minor <i>rôle</i>, of originating any -symptoms, much less gout, in its entirety. In other words, is -uric acid toxic or non-toxic?</p> - -<h3><span class="smcap">Non-Toxicity of Uric Acid</span></h3> - -<p>The adherents of the uric acid theory did not hesitate to attribute -to its toxic action, not only the severe phenomena of acute -attacks, but even all the functional disorders of so-called <i>irregular</i> -or <i>visceral</i> gout. By the more ardent advocates, such as Haig, we -were treated to a word picture of how solid crystals of uric acid -erupted out of the blood-stream, and anchoring themselves in -nerve sheathes, the renal substance and the mucous membrane, -gave birth to chronic neuralgias, nephritis, rhinitis, and so forth. -But, alas, there is very serious doubt as to whether uric acid or the -urates are capable of acting even as mechanical, much less as true -<i>toxic</i> irritants.</p> - -<p>Perhaps the most cogent evidence of the slight toxic effects of -uric acid or urates is that derived from a study of the <i>uric acid -infarcts</i> so frequently noted in infants dying within the first two -weeks of birth. According to Gideon Wells, “little or no change -occurs in the renal tubule as a result of these depositions, except -such as can be attributed to their mechanical effect.” This same -observer, discussing this question of the toxicity of uric acid, -observes, “It may be safely stated that at the present time there -exists no good evidence which makes it probable that uric acid -is responsible for any pathological conditions whatever, except -uric acid calculi, uric acid infarcts in the kidneys, and certain -manifestations of gout.” His further conclusion is that uric acid -possesses but a very slight degree of toxicity, and that an actual -intoxication of the organism with this substance probably never -occurs.</p> - -<p>Again, we have the fact that in instances of <i>malnutrition in -children</i> excess of uric acid may occasionally be found in the blood. -Yet no symptoms comparable to <i>gout</i> occur, even though uric -acid <i>calculi</i> form. Also, as has been pointed out, showers of uric -acid may be present in their urine, and yet no symptoms arise, -save those referable to <i>mechanical</i> irritation of the renal or vesical -tissues.</p> - -<p>Turning to experimental researches, the evidence is cumulative -as to the <i>non-toxicity</i> of uric acid. Rabbits and dogs seem quite -irresponsive, either to its ingestion in large quantities in their -food, or to repeated intravenous injections of 1 or 2 grammes<span class="pagenum"><a id="Page_167"></a>[167]</span> -thereof, save only that the urine showed a large increase in uric -acid.</p> - -<p>Again, Ransom, of New York, found that no systemic disturbance -ensued in two cases of <i>chronic nephritis</i>, following the taking -by the mouth of 3 grammes of uric acid per diem for three days in -succession. All that resulted was a notable increase in the uric -acid output. In one case, he went further, and on the fourth -day administered 6 grammes, but nothing happened.</p> - -<p>Walker Hall, with commendable devotion, took large doses of -uric acid with resultant headache and malaise, which endured for -some hours. But as Luff shrewdly observes, “almost any substance, -however (common salt for example), will produce toxic -effects if taken in very excessive quantities.” Despite his brief -indisposition, Walker Hall maintains that uric acid is rather a -symptom of, than the precise <i>materies morbi</i> in gout.</p> - -<p>Nor, apparently, even in gouty subjects can aggravation of the -condition be induced by intravenous injection of uric acid. Bass -and Herzberg did so until the blood content of uric acid reached -the high level of 10 mg., and yet no joint attack supervened. -Neither, for that matter, has it been possible to establish any -relationship between degrees of uricæmia and the incidence or -severity of gouty paroxysms.</p> - -<p>Again, taking a typical instance of acute gout in the big toe, how -difficult to conceive that the same owes its origin to uric acid -circulating in the blood especially when we realise that the -blood content of uric acid in gout exceeds but by a few milligrammes -that in <i>normal</i> blood. Moreover, if it does so, then why -does it fail to ensue in leukæmia and in other states associated -with uricæmia. Also, we like to think that the penchant of acute -gout for the toe is that the circulation is inefficient at this peripheral -site. But how often is the circulation all too vigorous in -gout, and for that matter frequently feeble in leukæmia and in ill-nourished -children. But, notwithstanding that in the two latter -conditions, <i>uricæmia</i> exists yet, despite favouring circulatory -conditions, they develop no gout.</p> - -<p>Garrod contended that the violent pain, intense inflammation, -and profound constitutional disturbance of acute gout were due -to <i>mechanical</i> irritation occasioned by the sudden deposition of -biurate crystals in the delicate interior of the implicated joint. -Also, that the absence of constitutional disturbance in the inter-paroxysmal -periods was because the deposition of urates, being -gradual, the tissues acquired tolerance, and yet, forsooth, this -same substance is held responsible for the fulminant outbreak -that ensues anon.</p> - -<p>But it is, as Ringrose Gore shrewdly observed, “against the<span class="pagenum"><a id="Page_168"></a>[168]</span> -usual laws of nature that, if an irritant foreign body remains in any -organ the symptoms should quickly subside, while the irritant -actually increases, for after each attack, and during the intervals -between the attacks, the deposits of such biurate enlarge.” In -conclusion, is it not infinitely more probable, as Gore states, that -the inflammatory reaction <i>precedes</i> the deposition of urates and -that these latter, in short, are the <i>consequence</i> and not the cause -of the gouty arthritis?</p> - -<p>Reverting to tophi, their experimental production, it is claimed, -has been achieved by His.<a id="FNanchor_24" href="#Footnote_24" class="fnanchor">[24]</a> Administering alcohol to dogs and -simultaneously injecting them locally with sodium mono-urate, -he produced deposits which seemed identical with tophi produced -spontaneously in gout. But, unfortunately, up to the present, it -has been found impossible to induce their formation by flooding -the circulation with urates. The utmost, indeed, that His and -other workers in this sphere feel able to postulate is that uric acid -is a “weak tissue poison.”<a id="FNanchor_25" href="#Footnote_25" class="fnanchor">[25]</a> Scarcely the words in which to -describe the poison responsible for gout! for, as we have before -stated, the agent that is responsible for <i>tophi</i> must also be capable -of inducing the arthritic phenomena and other features of the -disorder.</p> - -<p>The sum of our reflections is that the <i>toxicity</i> of uric acid has been -grossly over-estimated, and that, like its relative <i>urea</i>, it is practically -<i>non-irritating</i> and <i>inert</i>; in other words, it cannot any -longer be regarded as the <i>essential cause</i> of the <i>acute</i> or <i>chronic</i> -forms of <i>gout</i>, whether of <i>articular</i> or <i>ab-articular</i> site. Moreover, -far from its presence in excess in the blood being pathognomonic -of gout, it must, as Walker Hall contends, be held merely “as -symptomatic of conditions which help or prevent its solubility -and excretion and does not itself cause lesions which accompany -uricacidæmia.”</p> - -<h3><span class="smcap">Are the Precursors of Uric Acid Toxic?</span></h3> - -<p>Naturally the upholders of the uric acid theory were loth to find -their fetish uric acid was allotted a meaningless <i>rôle</i>. That -it should be deemed inert was to dislodge the very corner-stone of -the imposing superstructure they had been at such pains to raise. -Uric acid not responsible for the genesis of gout! But, haply, -maybe their position was still unassailable; for what of the -purin <i>bases</i>, the forerunners of uric acid? Might not the blame -lie with these?</p> - -<p><span class="pagenum"><a id="Page_169"></a>[169]</span></p> - -<p>Straightway <i>xanthin</i>, <i>hypoxanthin</i>, <i>adenin</i>, etc., were credited -with pernicious potencies.<a id="FNanchor_26" href="#Footnote_26" class="fnanchor">[26]</a> Nor did they lack apparent support -from the experimental side. Thus, Mandel affirmed that purin -bases, apart from infection, might originate pyrexia. Others, -again, noted that in dogs and rabbits fed on adenin, degenerative -changes in the <i>kidneys</i> ensued, with deposits resembling uric acid -and urates in their substance. The fact, too, that <i>guanin-gout</i> -was occasionally met with in swine, also lent colour to their -views.</p> - -<p>Moreover, that ingestion of these congeners of uric acid led in -animals to renal lesions, seemed to support the contention of many, -that renal disorder might be the primary cause of gout. But, -unfortunately, Kolisch and Weintrand’s assertion that the -alloxur bases were found in increased quantities in the urine of -gouty patients was contradicted by Schmoll, His, Laquer, and -others.</p> - -<p>Still more cogent, apparently, the announcement in 1910, by -Brugsch and Mallory, that they had seen a typical attack of gout -ensue in a gouty patient in sequence to a dose of 0·5 gram of -<i>hypoxanthin</i>. Nor did this reaction of gouty persons fail of -confirmation, as in the same year, Brugsch and Schittenhelm, in -gouty patients, noted attacks of arthritis, after the administration -of <i>nucleinic acid</i>.</p> - -<p>Nevertheless, we must beware of laying too much stress on -isolated experiments of this nature, so hypersensitive are some -of the victims to any strange or unaccustomed ingesta. Were all -the myriad other determinants of gouty attacks eliminated, over-drinking, -trauma, mental disturbances, etc.? for be it recollected, -all the victims of these experiments with <i>hypoxanthin</i> and -<i>nucleinic acid</i> were <i>gouty</i> subjects, <i>i.e.</i>, potentially liable to attacks -at any moment.</p> - -<p>Even admitting the ingestion of, <i>e.g.</i>, hypoxanthin was followed -by a gouty outbreak, it must be insisted that mere sequence does -not establish causation. Clinically, on the whole, there is little or -nothing to support the contention that the <i>purin bases</i> have much -to do with the pathogeny of gout. “The proof of the pudding -is in the eating,” and contrary to the view, at one time so prevalent, -that purin foodstuffs were most deleterious, it has been -found that, for the average gouty person, a purin-free dietary is -not only not essential, but prejudicial. Those, therefore, who may -be inclined to see in the above sequence proof of a <i>causal</i> connection, -would do well to recall Bacon’s dictum that “there is in the<span class="pagenum"><a id="Page_170"></a>[170]</span> -human mind a peculiar tendency to dwell on affirmative and -to overlook negative instances.”</p> - -<p>In conclusion, we must affirm our belief that <i>neither uric acid nor -its precursors</i> is responsible for the fever, local inflammation, and -general constitutional disturbance in gout, for uric acid and the -urates are themselves practically non-toxic. Albeit, though -holding this view, I do not for one moment suggest that <i>uric acid</i> -has nothing whatever to do with gout. The fact that <i>tophi</i>, its -pathognomonic stigmata, are compounded of biurate of soda, would -<i>per se</i> stamp such an attitude as untenable. On the other hand, -<i>uric acid</i> must be viewed in its proper perspective as a concomitant -or sequel of gout, the essential <i>cause</i> of which must be sought -elsewhere.</p> - -<hr class="chap x-ebookmaker-drop"> - -<div class="chapter"> - -<p><span class="pagenum"><a id="Page_171"></a>[171]</span></p> - -<h2 class="nobreak" id="CHAPTER_XIII">CHAPTER XIII<br> -<span class="smaller">THE RISE OF THE INFECTIVE THEORY</span></h2> - -</div> - -<p>With the abandonment of the uric acid theory of the causation -of gout we see a reversion, curiously enough, to the hypothesis held -by the ancient physicians as to its pathogeny. Like Cælius -Aurelianus and Paulus Ægineta, we now incline to refer the -origin of the disorder to some derangement of the <i>gastro-intestinal</i> -tract. This conception indeed endured up to the latter half of -the eighteenth century, and was definitely maintained by Van -Swieten in his commentary on the aphorisms of his great preceptor, -Boerhaave. For him the <i>fons et origo mali</i> in gout was -disturbance of the functions of the alimentary tract.</p> - -<div class="blockquote"> - -<p>“Indigestio viscorum pro origine proxima hujus morbi habitur.”</p> - -</div> - -<p>The English Hippocrates, too, Sydenham, in his classic treatise -observes: “The more closely I have thought upon gout, the -more I have referred it to <i>indigestion, or to the impaired concoction -of matters both in the parts and juices of the body</i>.”</p> - -<p>Not only in regard of the initial site are we reverting to the -views of old-time physicians, but the tenor of our reflections upon -the <i>nature</i> of the disorder exhibits a like trend. Thus the older -physiologists, doubtless impressed by its fulminant onset and -clinical features, ranked gout amongst the fevers, describing it -indeed as a “tertian fever terminating in fourteen days.”</p> - -<p>Indeed, the great Boerhaave avowed his belief that gout was -<i>contagious</i>—a forecast, we may take it, of the modern theory of -<i>infection</i>. Subsequently his pupil, Van Swieten, went a step -further, maintaining that sometimes wives, while nursing husbands -afflicted with gout, contracted the malady!</p> - -<p>Passing now to relatively modern times, it will be noted that in -1864 Laycock classed acute gout with rheumatic fever as an -“excretory fever,” while Parkes even prior to this, in 1860, wrote: -“I define gout after Garrod as a febrile infection with inflammation -about the joints leading to a deposition of urate of soda.”</p> - -<p>But it must be freely acknowledged that, subsequent to -Garrod’s discovery of <i>uric acid</i> in the blood in gout, the spell -exercised by the <i>uric acid theory</i> was such that it dominated -medical thought almost to the exclusion of all other possibilities.<span class="pagenum"><a id="Page_172"></a>[172]</span> -All energies were forthwith centred upon endless laborious -researches into possible modes of uric acid formation, but which, -alas, did little to purge men’s minds of their obsession that <i>uric -acid</i> was the <i>proximate cause</i> of gout.</p> - -<p>Still it would be unfair to infer that the disabilities attaching to -the uric acid hypothesis were wholly unrealised. Indeed, it may -be fairly said of Duckworth’s reflections on the pathogeny of gout -that they definitely foreshadowed the <i>infective</i> theory. His views -postulated what may be termed a <i>toxic tropho-neurosis</i>, wherewith -to explain the paroxysmal nature, the periodicity and protean -symptomatology of the disorder.</p> - -<p>But in the early part of 1900 we may, I think, discern in some -words of Chalmers Watson a change coming over our thoughts -as to the pathology of gout, this as the result of some studies of -a series of examples of <i>acute gouty polyarthritis</i>. The results of -his researches were such that he challenged the accuracy of -Garrod’s original observations as to the lowered alkalinity of the -blood during acute attacks, also his claim that the uric acid -content of the blood was increased and the uric acid excretion -diminished during the paroxysm. If these points be accepted, he -says we must start <i>de novo</i> in search of the cause of the acute -paroxysm.</p> - -<p>He noted also the interesting fact that during acute attacks of -gout a very marked <i>leucocytosis</i> was present. Another outstanding -feature was the presence in large numbers of peculiar -myelocyte-like cells, half as many in number as the ordinary -finely granular oxyphil leucocytes. Reflecting on these findings, -he observes: “It would, I think, be well if much less attention were -centred on the excretion of uric acid alone as the all-important -factor in the disease, whether in its acute or chronic form. The -results obtained by the line of investigation here followed suggest -the advisability of more attention being devoted to the histo-chemical -characters of the blood, the ratios of uric acid to other -important products of metabolism, and, if opportunity be afforded, -an examination of the bone marrow.”</p> - -<p>To other interesting features of these researches of Watson’s we -shall allude later, but, concerned here more with tracing the -evolution of the infective theory of gout, we would hasten to add -that in September of the same year Ringrose Gore, discussing the -inadequacy of the uric acid theory, boldly avowed and ably propounded -his belief in the <i>infective</i> origin of the disorder.</p> - -<p>Thus he writes: “I consider a toxin to be the cause of this -disease. If so, such toxin must be formed in the intestine. As -the symptoms of gout are constant, it must be a definite toxin, the -product of a definite bacillus acting upon the intestinal secretion.<span class="pagenum"><a id="Page_173"></a>[173]</span> -As gout is capable of being caused in any subject, it must be one -of the bacilli normally found in the intestinal canal.”</p> - -<p>Nor did Gore lack supporters in his suggestion that the alimentary -tract was the primary source of the changes in the metabolism -of gout. For in the same year Minkowski, Le Gendre, and in this -country Watson, hazarded the view that intestinal derangements, -through the medium of their resultant toxins, initiate disturbances -in the liver, and these in turn determine those obliquities -of metabolism typical of gout.</p> - -<p>At the same time their contentions derive colour from the -researches of Grübe, who, despite traditional views, maintained -that in gout the hydrochloric acid of the gastric juice, far from -being increased, was in most cases <i>diminished or wholly lacking</i>, -while, on the other hand, lactic acid was present in some instances.</p> - -<p>In 1903 Woods-Hutchinson ably contended that “gout and -lithæmia are mere symptom names for a miscellaneous group of -<i>chronic toxæmic processes</i> of widely varied origin, characterised by -the production of uric acid and the urates.” He held that the -uric acid in gout as well as the associated phosphoric acid are -merely a criterion of the measure to which the nucleins of the body -cells (chiefly probably of leucocytes) have undergone destruction -in consequence of their invasion by a toxin or toxins of organic or -inorganic nature. He furthermore contended that the <i>rôle</i> of -the <i>liver</i> in gout was purely negative, consisting in its inability -“to absorb or transform into harmless excretory substances the -excess of toxins brought to it by the portal vein.”</p> - -<p>In 1904 Falkenstein furnished collateral evidence that the -starting point of gout lay in a diseased condition of the <i>gastric -glands</i>, those responsible for the secretion of <i>hydrochloric acid</i>. -The supply of hydrochloric acid being deficient in the gouty, their -digestive capacity is distinctly lowered. Abnormal fermentation -ensues with insufficient oxidation, and “the substances containing -quantities of nuclein are partly prevented from being further split -up, and partly favour the synthetic formation of uric acid.” He -would thus refer the excessive formation of this latter directly to -the diseased glands. He further observes that, despite the deficiency -of hydrochloric acid, the gastric juice is often hyperacid, -this being due to the presence therein of organic acids, such as -butyric, lactic, and acetic acids.</p> - -<p>In the same year Chalmers Watson, as the outcome of investigations -into gout as it occurs in the <i>fowl</i>, held that:—</p> - -<div class="blockquote"> - -<p>(<i>a</i>) There is ample evidence to prove that the uric acid in the -blood is not the primary factor in gout, and</p> - -<p>(<i>b</i>) Uric acid can be deposited in cartilages and other tissues,<span class="pagenum"><a id="Page_174"></a>[174]</span> -even in considerable amount, without the association of -any inflammatory phenomena.</p> - -</div> - -<p>He concludes that the last-mentioned point clearly proves -that:—</p> - -<div class="blockquote"> - -<p>(<i>c</i>) Uric acid is not the factor which causes the inflammatory -phenomena characteristic of the acute attack.</p> - -</div> - -<p>He then proceeds to inquire as to the nature of the toxic principles -in the blood, and the factors that influence their passage -thence into the tissues. In connection with these queries he -emphasises the necessity of envisaging the all-important part -played by the <i>alimentary canal</i>, holding that herein doubtless -resides the clue to the solution of the problem.</p> - -<p><i>Post-mortem</i> examination of the fowl revealed marked catarrh -of <i>ileum</i>, <i>duodenum</i> and <i>large intestine</i>, while the pancreatic duct -was filled with catarrhal products. The congested <i>spleen</i>, apart -from proliferation of its endothelial elements, exhibited a marked -increase in the number of <i>granular leucocytes</i> in the capillaries and -sinuses as compared with the features of the control sections, -which, as Chalmers Watson observes, is the characteristic -reaction of this organ to invasion by bacteria or their products. -The kidneys on examination revealed here and there uratic -deposits surrounded by inflammatory tissue. The relationship -of these to the inter-lobular arteries was such as to suggest an -<i>infection</i> by the <i>blood stream</i>.</p> - -<p>The collecting tubules in the deeper part of the cortex and -medulla were markedly dilated and choked with granular leucocytes. -Sections of the organs were examined bacteriologically -by Muir, the necrosed areas revealing the presence of “rod-like -bodies of the size of large bacilli massed together in dense clusters; -the appearance suggested that these rods were either degenerated -cell products of an unusual character, degenerated bacteria, or -crystalline in nature.” Examination of the same by polariscope -by Marshall disposed of the possibility that they were crystalline. -Finally it was thought that the appearances generally favoured the -view that the rods in question were bacteria which had lost their -reaction to bacterial stains owing to bacteriolytic or other changes.</p> - -<p>As to the inference that the defunct fowl fell a victim to acute -gout, Watson based it on the existence of the <i>uratic deposits</i> in the -tissues, the changes in the synovia, the widespread thromboses, -and the renal necroses. As to the other lesions, the chief interest -centres in those located in the intestine, pancreas and kidney. -The state of the <i>pancreatic duct</i> raises the question as to whether -it points to any connection between these changes and the common -occurrence of <i>glycosuria</i> in gouty subjects. The alteration -in the <i>leucocytes</i> merits notice in that similar changes were found<span class="pagenum"><a id="Page_175"></a>[175]</span> -by Watson in the blood in <i>acute gouty polyarthritis</i>, the same, -moreover, being subsequently confirmed by Bain.</p> - -<p>Chalmers Watson’s final conclusion was that “the clinical -features of gout—regular or irregular, acute or chronic—are more -adequately explained by the light of our present knowledge of -infections, relapses, and immunity than by any other theory. -The distinctive feature of this infection in gout is that the toxin -or toxins have a special property of disturbing nitrogenous metabolism -in a manner favourable to the deposit of uric acid in certain -tissues.”</p> - -<h3><span class="smcap">Suggestion of a Specific Infection</span></h3> - -<p>It will have been noted that, despite the growing number of -adherents to the infective theory, no attempt had been made to -saddle any particular organism with the responsibility of initiating -gout. But in 1905 Trautner, holding <i>mucous colitis</i> to be one of -the initial manifestations of gout, affirmed his belief that the -<i>bacillus coli communis</i> was the responsible microbic agent.</p> - -<p>He claimed that this particular organism, during its passage -through the system, gives rise to a reducing agent which is subsequently -transmuted into <i>xanthin</i> and <i>uric acid</i>. This is, of -course, but a variant of Gore’s original view that the toxin of -gout is a product of certain bacteria normally present in the -intestine, but which under certain conditions take on a pathogenic -action.</p> - -<p>The microbic theory fast gained ground. Thus Luff, who in -the first edition of his work advocated the renal origin of gout, -subsequently renounced the same in favour of its infective origin. -To sum up, the opinion generally was that it was more than -probable that <i>gastro-intestinal derangements</i>, with their altered -secretions, exert an influence on the intestinal flora with resultant -formation of toxins, and that these same, acting chiefly on the -liver, put in motion those obliquities of metabolism which eventuate -in gout.</p> - -<p>Sikes, however, in 1907, discussing the <i>rôle</i> of gastro-intestinal -disorders, expressed a doubt as to whether the same are primarily -or secondarily related “to the actual chemical processes at the -base of the disease.”</p> - -<p>He thinks it at least as probable that the gastro-intestinal -disorders are due to an alteration in the intestinal secretions from -an internal cause as that they are due to bacteria in the formation -of toxins, or, he suggests, to some alteration in the epithelial -cells, so that they take up chemical compounds of different -nature from the ordinary. To him it does not seem at all probable<span class="pagenum"><a id="Page_176"></a>[176]</span> -that gout will ever be found affiliable to any specific micro-organism, -inclining rather to the belief that a solution of the -riddle will only be found in a closer and more extended study of -that most difficult subject, the actual <i>chemistry of the cell -protoplasm</i>.</p> - -<hr class="chap x-ebookmaker-drop"> - -<div class="chapter"> - -<p><span class="pagenum"><a id="Page_177"></a>[177]</span></p> - -<h2 class="nobreak" id="CHAPTER_XIV">CHAPTER XIV<br> -<span class="smaller">GOUT AS AN INFECTION</span></h2> - -</div> - -<p>“The old order changeth, giving place to new,” and the uric -acid theory having failed us, it is essential that we cast round for -some other solution of the problem, carrying with us, however, -this guiding principle, that <i>uric acid</i>, having lost its <i>etiological</i> -status, be viewed in its right perspective as not the cause, but -the <i>consequence</i>, of gout.</p> - -<p>Happily, with the advent of bacteriology our views, or rather -our hazards, as to the nature of joint diseases underwent profound -modification. But, strange to say, though quick to apprehend -the significance of infection, its causal relation to other joint -disorders, we still seem unaccountably loth to discard our time-worn -conception of “gouty” arthritis as of purely <i>metabolic</i> -origin. This, to my mind, is the more remarkable in that the onset, -clinical phenomena, and course of acute gout, and no less the -life history of the disorder as a whole, are emphatically indicative -of the intrusion of an <i>infective</i> element in its genesis.</p> - -<p>In developing this hypothesis I purpose devoting the present -chapter to consideration of the frequency with which local foci -of infection are met with in gout, the frequency, too, with -which exacerbations of the disorder are presaged by acute glandular -affections of undeniably infective source. The latter part -of the text will concern itself with the rival claims of <i>auto-toxæmia</i> -and <i>infection</i> or <i>sub-infection</i>. In the subsequent chapter -we shall analyse critically the component elements of the acute -paroxysm of gout, their compatibility or not with an infective -origin. The affinities between gouty arthritis and the specific -infective arthritides will then be noted, and, finally, an endeavour -made to link up the specific stigmata of gout—its uratic deposits—with -the postulated infective element.</p> - -<h3><span class="smcap">Local Foci of Infection</span></h3> - -<p>The extreme frequency with which <i>infective foci</i> are met with -in the victims of gout is by no means adequately realised. Moreover, -we are only now beginning to appreciate the grave significance -of such “nests” of infection and how devious are the ways -in which they work their malign influence. For our forefathers -gout began, and, forsooth, often ended, in the “stomach,” or it<span class="pagenum"><a id="Page_178"></a>[178]</span> -was the “liver” that was impeached. But the portal to the -alimentary canal was for them only a cavity, the contained -structures of which, albeit, to their mind often betrayed evidences -of a “gouty diathesis.” They distinguished “gouty” teeth, -“gouty” tonsillitis, “gouty” pharyngitis, even “gouty” -parotitis; but all these they classed as tokens or sequelæ of gout—not -possible causes or excitants thereof.</p> - -<p>Nevertheless, their observations on “gouty” teeth are of -deep interest, though their significance was misinterpreted.</p> - -<p>Thus, Duckworth, for example, wrote: “The tendency to -shed sound teeth has been noted with some frequency in middle -or later life in goutily disposed persons, and they are more than -others liable to occasional and fugitive attacks of pain in several -sound teeth at a time, with a sensation as if these were starting -from their sockets, being tender to bite upon.” In truth, a -succinct picture of <i>pyorrhœa alveolaris</i>, of unprejudiced source, -hence the more valuable.</p> - -<p>Garrod again tells us that he saw an initial attack of gout -supervene after extraction of a tooth, a sequence attributed by -him to loss of blood. How interesting this, in light of the fact -that exacerbations of joint disease have frequently been seen to -follow the removal of septic teeth. The same authority also -noted the incidence of a primary attack of gout following <i>epistaxis</i>, -and the same after copious <i>hæmatemesis</i>, and Todd several times -observed such articular outbreaks after <i>venesection</i>.</p> - -<p>Lastly, says Garrod, “cases illustrative of the effects of the -suppression of an habitual hæmorrhoidal discharge are by no -means uncommon, and ... numerous instances arising from -<i>boils and carbuncles</i> have come under my notice.” By Garrod -and his contemporaries all these various determinants of gouty -paroxysms, <i>i.e.</i>, loss of blood, etc., were believed to exert their -influence <i>viâ</i> the <i>nervous</i> system, with consequent disturbed -equilibrium of nutritive processes throughout the body. But -while it may be admitted that depression of the <i>vis resistantiæ</i> -plays a part, it does so, I believe, by favouring the occurrence of -<i>infection</i>.</p> - -<p>Let us turn now to modern findings, and we shall see that they -do but confirm those of the older clinicians. Lambert in 125 cases -of gout found the teeth unsound in 82 per cent. of males and -1 per cent. of females, while in 9 per cent. of the former and -17 per cent. of the latter there was associated <i>chronic dyspepsia</i>. -Two years after (1909) Wynn, Wirgman and Turner noted the -invariable correlation of gout with local foci of infection. In -the majority, <i>pyorrhœa alveolaris</i> was present. <i>Tonsillar sepsis</i>, -too, was not uncommon, and much more rarely <i>nasal</i> disorders.<span class="pagenum"><a id="Page_179"></a>[179]</span> -Again, out of fifty-two examples of so-called “gouty” throat -Edward McCracken found <i>pyorrhœa alveolaris</i> to be present in -thirty-nine, and Fenner also tells us that this affection is common -in the subjects of gout.</p> - -<p>In truth, the victims of <i>gouty</i> arthritis are no more immune -from <i>dental</i> lesions than those of other types of joint disease. -Thus, Mr. Macdonald, dental surgeon to the Royal Mineral Water -Hospital, Bath, informs me that this form of <i>oral sepsis</i> is extremely -common in <i>gouty</i> individuals, and in my experience it -is but rarely that evidences of its presence are not forthcoming -in these subjects. The desirability of early recognition of such -foci—in light of their highly probable <i>etiological</i> significance—can -scarcely be overestimated. For their consequences, both -local and remote, are of paramount importance.</p> - -<p>Thus, G. I. Stewart’s recent observations have conclusively -demonstrated that “bad teeth” are causally related to <i>tonsillar</i> -affections. How illumining this, in view of McCracken’s experiences -in “gouty throats.” As we saw, <i>pyorrhœa alveolaris</i> -was present in more than half the examples. But, more pertinently -to the point at issue, he comments on the frequency with which -the victims of gout develop <i>acute tonsillitis</i>, of lacunar or parenchymatous -type, also that such attacks frequently precede -outbreaks of <i>arthritic</i> gout. Duckworth again noted the same -liability of the gouty to unsound teeth and tonsillitis, and that -the latter was often followed by articular outbreaks. Luff also -observed that “gouty” tonsillitis was occasionally a precursor -of articular gout, always subsiding on the appearance of the -latter complication.</p> - -<p>Again, acute and chronic <i>pharyngitis</i> are proverbially common -in “gouty” subjects. Moreover, in both types the subsidence of -the throat affection has frequently been signalised by an articular -outbreak of classic site. <i>Parotitis</i>, too, has been repeatedly met -with in gout, and, according to Luff, “rapidly subsides on the -appearance of regular gout in one or more joints.”</p> - -<p>In truth, whether we peruse recent or older works on gout, -we cannot fail to remark the unanimity of opinion as to the -frequency of incidence of these <i>glandular</i> affections—these states -of <i>oral sepsis</i>—in the subjects of <i>gout</i>. Equally noteworthy is -their insistence on the constancy with which such local affections -have proved harbingers of oncoming <i>articular</i> outbreaks. Lastly, -the mere fact that our forefathers dignified these local disorders -with special appellations, “gouty” tonsillitis, pharyngitis, etc., -is cogent proof that they regarded them as among the integral -features of gout.</p> - -<p>Now, as to the true significance of these acute <i>glandular</i> affections,<span class="pagenum"><a id="Page_180"></a>[180]</span> -held by clinicians of repute to be of “gouty” origin. What -of “gouty” tonsillitis, pharyngitis, etc.? Still more, what of our -deductions regarding the relationship of these same when met -with in association with other joint disorders? Do we not hold -them each and all as evidences of <i>infection</i>—“acute rheumatism,” -“gonorrhœal arthritis,” etc.?—and we may well ask, Why not in -<i>gout</i>?</p> - -<p>Says Duckworth, “Angina tonsillaris—very painful but not -suppurating—may in the gouty suddenly yield to an acute -articular attack.” Is it not here more than likely that the tonsil -was the initial site or portal of <i>infection</i>, and the arthritis <i>secondary</i> -thereto? Is not this same interpretation in all probability true -also of all forms of “gouty” throats when followed by <i>arthritic</i> -outbreaks?</p> - -<p>The marvel, then, is that not only have we held, but apparently -many still hold, that the tonsillitis, pharyngitis, even the gingivitis—like -the subsequent articular lesions—are one and all -attributable to the underlying <i>gout</i>. We certainly would not do -so in the case of any arthritis other than “gouty,” and to my -mind the time is ripe for a change of attitude. The “gouty” -throats, like the “gouty” teeth, should be regarded not as -symptomatic of gout, but <i>etiologically</i> related thereto. We -should cease to talk of “gouty” throats, teeth, etc., should -renounce the prefix, for there is nothing <i>specific</i> of <i>gout</i> either in -the tonsillar, pharyngeal, or dental lesions. We should instead -view these various local disorders in their true perspective as -<i>foci of infection</i>, <i>causally</i> related to the subsequent and <i>secondary</i> -“gouty” arthritis.</p> - -<p><i>Gastro-Intestinal Disorders.</i>—It is a matter of common -experience that acute attacks of gout are often preceded by or -associated with flatulence, heartburn, acidity, loss of appetite, -confined bowels, scanty, high-coloured urine, and a feeling of -lassitude. In short, nothing is more certain than that exacerbations -or relapses very commonly follow symptoms referable to -gastro-intestinal and hepatic disorders.</p> - -<p>How well established is it that these subjects after unusual, -though not necessarily excessive, indulgence at the table, almost -inevitably, and sometimes almost immediately, suffer twinges -in the big toe, if not frank outbreaks of gout. Such reaction seems -to indicate clearly that the functional disturbances in the alimentary -tract stand in some causal relation to the subsequent -arthritic phenomena. The assumption gains colour, too, from -the very certainty with which freedom from such gouty manifestations -is attained by abstinence from, or more moderate indulgence -in, articles of diet predisposing to such ebullitions.</p> - -<p><span class="pagenum"><a id="Page_181"></a>[181]</span></p> - -<p>So much by way of prelude as to the probability—attested by -clinical observation and the results of treatment—that the -<i>intestinal canal</i> is often the source of the responsible microbe or -toxin. Let us now pass to consider what factors other than an -<i>oral sepsis</i> may favour the incidence of <i>functional</i> disorders of the -<i>alimentary</i> tract.</p> - -<p><i>Variations in Free HCL.</i>—Some years ago Grübe and Falkenstein -found that in gout the hydrochloric acid of the gastric juice, -far from being increased, was in most cases <i>diminished or wholly -wanting</i>.</p> - -<p>Now, as we know, the gastric juice when of normal acidity is -quite capable of dealing with moderate quantities of pathogenic -bacteria. But in the presence of <i>oral sepsis</i> it is probable that a -greater number are swallowed than can be satisfactorily coped with.</p> - -<p>Given therefore excess of pathogenic organisms and <i>relative -insufficiency of free HCL</i>, conditions favourable to the growth of -bacteria ensue, while incidentally the chance of such reaching the -intestine is materially enhanced.</p> - -<p>When, however, the defensive barrier is wholly withdrawn, viz. -when there is an absence of free HCL, then of course the necessary -inhibition of microbic growth fails of achievement. Moreover, -also owing to diminished acidity, ill-digested protein substances -gain access to the intestine, and their subsequent putrefaction is -favoured.</p> - -<p>In opposition to the foregoing, many hold that an <i>excess of free -HCL</i> in gout is not uncommon, and unquestionably some are thus -troubled. The pernicious effects of the hyperchlorhydria are -accentuated by the fact that intestinal indigestion ensues secondarily, -owing to the acid chyme completely antagonising pancreatic -secretion and thus impairing digestive capacity.</p> - -<p><i>Intestinal</i> rather than gastric indigestion is, I think, more -typical of the gouty subject. It will be recalled that the food -nucleins are unaffected by the gastric juice, and though the -protein moiety is split off from the nucleinic acid by the pancreatic -ferments, yet neither the poly- nor the mono-nucleotides are -thereby acted upon. It is in truth the <i>succus entericus</i> with its -nucleotidase that plays the most important digestive <i>rôle</i> as -regards nucleins, breaking them up into nucleosides which are, -to a large extent, absorbed as such.</p> - -<p>To resume, this condition of <i>intestinal indigestion</i> may arise -from a variety of causes: excess or deficiency of gastric juice, -defective motility, and diminished secretion of intestinal juices, -and in all cases improper food may determine such <i>intestinal -derangement</i>.</p> - -<p>The clinical features presented are very variable. It is often<span class="pagenum"><a id="Page_182"></a>[182]</span> -difficult, if not impossible, on the basis purely of the subjective -symptoms, to decide in any given instance how far the symptoms -are referable to <i>intestinal stasis</i>, or to a <i>chronic infection</i>, with a -resultant catarrhal state of the mucosa, or to both causes combined -in varying proportions.</p> - -<p>But, be the explanation what it may, in our experience the most -common antecedent or concomitant of gout is <i>intestinal dyspepsia</i>. -Its secondary consequences are far reaching, especially if the small -bowel be involved, catarrh of which may lead to <i>reduction</i> in the -secretion of <i>bile</i> and <i>pancreatic juice</i>.</p> - -<p>How commonly in these cases do we meet with symptoms -indicative of sluggishness of the hepatic functions, such as turbidity -of the urine, a pale or abnormally dark colour of the alvine -evacuations. Also, whatever be its true etiology, they exhibit -not so uncommonly <i>sugar</i> in the urine, the so-called “gouty” -<i>glycosuria</i>.</p> - -<p>Now, as a mere glance will show, diminution and impairment of -the biliary and pancreatic secretions have far-reaching consequences. -Foodstuffs undergo abnormal changes, are less easily -absorbed, and simultaneously chemical products are formed which -irritate the intestinal mucosa. Nor do the baneful effects cease -here, for, owing to the unusual nature and reaction of the intestinal -content, the <i>bacterial flora</i> in the bowel undergo modifications.</p> - -<p>Thus, organisms normally present only in small numbers in the -small intestine find the altered medium more suitable for their -growth and multiplication; while others, whose usual habitat is -the large bowel, migrate upwards, and infect the ileum and duodenum, -and ultimately the biliary and pancreatic passages.</p> - -<p>In the presence of such deficiency in the intestinal juices, proteins -are imperfectly digested, and putrefaction under microbic -action favoured. At the same time the digestion of carbohydrates -is impaired, organic acids are formed, and gases in larger -amounts liberated. Ultimately, owing to absorption of these -irritating products, a condition of <i>chronic toxæmia</i> results.</p> - -<h3><span class="smcap">Summary</span></h3> - -<p>It now devolves upon us to decide whether the phenomena -of gout are best explicable as the outcome of <i>auto-intoxication</i>, -or of <i>infection</i> or <i>sub-infection</i>. The uric acid theory was in -truth one of <i>auto-toxæmia</i>, the varied manifestations of gout -being attributed to mechanical or toxic irritation by <i>uric acid</i>, the -end-product of purin metabolism. But, as we hope to have -shown conclusively, uric acid is <i>not toxic</i>, and <i>per se</i> is apparently -as innocuous as those other and intermediary products of metabolism -which give rise to cystinuria and alkaptonuria.</p> - -<p><span class="pagenum"><a id="Page_183"></a>[183]</span></p> - -<p>The question then arises, Is gout haply due to a retention of -other metabolites? That outbreaks of gout follow fast on the -heels of dietetic irregularities is proverbially true. But there is -no certain evidence that the symptoms generally ascribed to auto-toxæmia -are referable to substances derived from the foodstuffs -under the action of the digestive juices. Toxic as are peptones -and primary proteoses when they gain direct access to the tissues, -the symptoms produced in no way resemble those affiliated to -alimentary toxæmia, much less those of <i>gout</i>. Rather, according to -Adami, do they approximate to those typical of <i>anaphylactic shock</i>.</p> - -<p>Normally, too, the mucous membrane proves an efficient -barrier, these poisonous bodies during their passage through it -being transmuted into harmless substances. Nor can we refer -the symptoms of gout to a toxæmia secondary to <i>intestinal stasis</i> -or other causes. In other words, it cannot be attributed to -assumed toxic action on the part of the intermediary and terminal -products of protein disintegration. For seemingly these chemical -outcasts of the economy become progressively less toxic on their -downward path to effete matter.</p> - -<p>The diamines, too, produced by bacterial action on foodstuffs, -are so minimal as to be negligible, while the toxicity of cholin and -neurin is unestablished; and as for indol and skatol, they are -with difficulty absorbed from the healthy colon. Experimental -researches on carbohydrate and fatty disintegration have likewise -proved sterile, while there is no evidence that the anaerobes -present in the digestive tract produce ecto-toxins, or undergo lysis -with release and absorption of their endo-toxins.</p> - -<p>In short, it is but too clear from the foregoing brief <i>résumé</i> of -recent experimental findings that, if <i>uric acid</i> cannot be held -responsible for the causation of <i>gout</i>, there is no evidence likewise -that the disorder owes its genesis to any other of the as yet -isolated <i>chemical</i> products of gastro-intestinal digestive activities. -Having dealt with this aspect of the question, we shall now -pass on to consider whether the phenomena of gout can be more -adequately explained on a basis of <i>infection</i> or <i>sub-infection</i>.</p> - -<p><i>Infection or Sub-infection.</i>—Our knowledge as to the exact -manner in which <i>local foci of infection</i> work their malign effects -almost daily undergoes expansion. It will be recalled that Stewart -has shown that “bad teeth” are often etiologically responsible -for tonsillar inflammation. It further is well established that -<i>streptococci</i> are of common incidence in the <i>tonsils</i>, and Rosenow -and Brown from experimental observation have established that -these hemolysing organisms, migrating <i>viâ</i> the blood stream, -exhibit a marked predilection for forming a fresh nidus in the <i>gall -bladder</i>. Here they may initiate a <i>cholecystitis</i>, and secondly<span class="pagenum"><a id="Page_184"></a>[184]</span> -gallstones, and in sequence thereto the symptoms associated with -<i>gall-bladder-dyspepsia</i>. The same formidable list of sequels may -follow infection of the gall bladder from the <i>teeth</i>, <i>stomach</i>, or <i>intestines</i>, -notably from the vermiform appendix.</p> - -<p>In like fashion the origin of <i>appendicitis</i> may be traced back to -<i>septic foci</i> in the <i>mouth</i>, <i>tonsils</i>, <i>naso-pharynx</i>, or to the <i>gastro-intestinal -tract</i>. Here again there ensue the symptoms of so-called -<i>appendix-dyspepsia</i>. As in the case of the gall-bladder variety, -the <i>primary lesion</i> in the <i>appendix</i> may be <i>latent</i>, and the exact -diagnosis may be a matter of great difficulty, often indeed only to -be achieved <i>retrospectively</i>, viz., when abatement of the symptoms -follows ablation of the appendix.</p> - -<p>We see, therefore, how far-reaching are the consequences of <i>local -foci of infection</i> in the <i>mouth</i> or elsewhere. Now, the <i>gouty</i> subject -enjoys no immunity from the remote sequels of local sepsis. But -as a rule, unfortunately, whatever be the nature of his <i>dyspeptic</i> -symptoms, they are, like his <i>dental anomalies</i>, his <i>tonsillar inflammations</i>, -forthwith dismissed as <i>symptomatic</i> of gout, not etiologically -related thereto.</p> - -<p>Now, I have seen pyorrhœa and chronic appendix-dyspepsia -running side by side in the same subject with recurring classical -attacks of gout in the big toe. The faulty teeth were extracted, -and later the chronically inflamed appendix removed; and -though he had an attack of gout shortly after the operation, there -has as yet been no recurrence thereof.</p> - -<p>Again, by the older writers “gout in the liver” was most -firmly believed in—as one authority puts it, “a subacute catarrh -of the intrahepatic biliary system which may lead to a subacute -parenchymatous hepatitis”! But more pertinent to my point -is the insistence of older authors upon the frequent association -of gout and <i>gall-stones</i>. Senac, of Vichy, claimed indeed that -out of 166 cases of <i>biliary lithiasis</i> 95 had gout or an hereditary -predisposition thereto. Judging by modern experience, this -is probably a gross over-estimate. In contrast, our own -countryman Murchison dwelt upon the frequency of jaundice -in gout independently of biliary colic. And, as we shall see -later, Brinton held that many of the dramatic phenomena -accredited to “retrocedent gout” were unrecognised examples -of <i>biliary colic</i>.</p> - -<p>But, controversy aside, the point I would lay stress on is, that -we should refrain from labelling offhand “dyspeptic” symptoms -in a “gouty” subject as <i>gouty</i>, this when we are so constantly -confronted with <i>local foci of infection</i> in the <i>mouth</i>, or elsewhere, -which afford us an explanation of the gastro-intestinal symptoms -at once more obvious and more rational. This also the more<span class="pagenum"><a id="Page_185"></a>[185]</span> -especially in that—as far as subjective symptoms go—those -deemed typical of so-called “gouty” dyspepsia are indistinguishable -from those met with in <i>appendix-</i> or <i>gall-bladder-dyspepsia</i>. -Indeed, I might go further and point out that the -<i>variations in free HCL</i> in the gastric juice—as observed in <i>gout</i>—conform -to those met with in the above disorders. Thus, in -“gouty” dyspepsia, the free HCL may be normal, in excess, -or wholly absent, as in gall-bladder or appendix-dyspepsia. I -would therefore plead that in any “dyspepsia” arising in a -genuinely <i>gouty</i> subject we endeavour to elucidate the exact -nature of the <i>underlying lesion</i>, but to this we shall return again -when discussing diagnosis.</p> - -<p>Again, the fact that gall-bladder or appendix lesions may be the -outcome of septic foci in the mouth enables us the more easily to -explain the not infrequent co-existence of gout and <i>glycosuria</i>. -For an infected gall-bladder may by extension determine a chronic -<i>pancreatitis</i>.</p> - -<p>Lastly, what of the relationship of local foci of infection to -<i>“gouty” synovitis</i> and <i>arthritis</i>? Is one focal infection more -than another particularly related to arthritides? Whatever -be the true inference, if we take <i>arthritides</i> as a whole, nothing -seems so efficient a cause of their production as <i>oral sepsis</i>. Accordingly, -some are inclined to think that organisms, <i>e.g.</i>, <i>streptococcus -viridans</i>, at the roots of the teeth or others in the tonsillar crypts, -pass, <i>viâ</i> the blood-stream, <i>direct</i> to the <i>joints</i>. Others, again, hold -that, given oral sepsis, infection of the stomach and lower levels of -the alimentary tract and its accessory cavities ensues. And in -sequence thereto infection of the joints may take place from local -foci throughout gastro-intestinal tracts.</p> - -<p>Those who favour the view that <i>direct infection viâ</i> the -blood from foci of oral sepsis is the more probable <i>modus -operandi</i> are wont to produce the following points in support -of their view. Arthritis, they say, is relatively rare in -<i>enteric fever</i>. In yet another disorder, <i>dysentery</i>, which gives -every chance of absorption from the intestine, arthritis when it -occurs is seldom very acute, while in <i>appendicitis</i> it is distinctly -uncommon.</p> - -<p>On the other hand, we must recall that even in normal animals -the alimentary and respiratory tracts, and alike the liver and -kidneys, constantly afford cultures of pathogenic and non-pathogenic -bacteria. Such was established by Adami and his -co-workers, who moreover found that such organisms, through -the agency of leucocytes, continually pass into the system, where -subsequently in the healthy animal they as constantly undergo -destruction.</p> - -<p><span class="pagenum"><a id="Page_186"></a>[186]</span></p> - -<p>If, however, inflammatory processes are at work, their migration -into the tissues is favoured. For under such conditions -leucocytes aggregate at the reactive focus, and concurrently, -their migration being more active, larger numbers of bacteria -achieve entry into the system. The subsequent course of events -is determined by the number and virulence of the organisms that -effect a lodgment in the tissues, where under favourable conditions -they originate other foci of infection or sub-infection.</p> - -<p>By <i>sub-infection</i> is understood the fact that microbes carried -into the system undergo slight, if any, numerical increase, and do -not set up <i>foci of suppuration</i>. Here we may note that “gouty” -inflammation, however intense, never ends in <i>pus formation</i>. -But, to resume, the bacteria, instead of multiplying, undergo lysis, -and, their endo-toxins being released, the more highly specialised -tissue cells in the vicinity are destroyed. Coincidently the -lower grade connective tissue elements are by the self-same -poisons stimulated to proliferate, and an area of <i>chronic interstitial -fibrosis</i> is formed.</p> - -<p>Incidentally this is interesting, inasmuch as the <i>visceral</i> organs -in gout evince a tendency to <i>fibrosis</i>. But, as Gideon Wells -observes, “the actual increase of uric acid in the blood and -tissues in gout is so slight that we are not warranted in saying -that the usual tendency to sclerosis in all the organs in gout is due -to the action of uric acid rather than to some other unknown -agent or agents.” In view of these revelations, is it not infinitely -more likely that the chronic interstitial fibroses in gout are the -outcome of such <i>sub-infection</i>?</p> - -<p>The assumption gathers weight in light of the experimental -proof adduced by Adami that not only tubercle bacilli, but -<i>streptococci</i> and other organisms, <i>taken orally</i>, can gain an entrance -into the system. Upon this basis we get a clear conception of the -possible relationship of gout to <i>local foci of infection</i>. Thus, -whether it be a condition of oral sepsis—pyorrhœa alveolaris, -tonsillar sepsis, sinus disease, intestinal disorders, constipation, -and so forth—we see that it is highly probable that organisms -at any one of such infective foci may gain access to the blood-stream -with subsequent installation of local lesions in <i>joints</i> or -other structures.</p> - -<p>Now, as pointed out, inflammatory states or <i>functional</i> derangements -of the <i>alimentary</i> tract, whether focal or diffuse, favour the -ingress into the tissues of organisms. Is it not reasonable, therefore, -we ask, to suppose that the functional derangements which so -commonly precede or accompany gout may modify the character -of the <i>intestinal flora</i>, and promote their migration inwards in -greater numbers? The inevitable swiftness with which relapses<span class="pagenum"><a id="Page_187"></a>[187]</span> -or exacerbations of this disorder follow even venial dietetic indiscretions -distinctly favours this assumption, one, moreover, -substantiated by the amelioration or immunity which follows -abstention from the offending foodstuffs. The often prolonged -course, too, of gout, and its marked liability to periodic recurrence, -would be explicable as the outcome of a continued or intermittent -series of sub-infections.</p> - -<p>My conclusions then are that:—</p> - -<div class="blockquote"> - -<p>(1) The majority of cases of gout are marked by the presence -of <i>local foci of infection</i>, pyorrhœa alveolaris, tonsillar, -pharyngeal or nasal sepsis, etc., or by gastro-intestinal -derangements, constipation, etc.</p> - -<p>(2) The said local foci should be regarded not as symptomatic of, -but <i>etiologically</i> related to, gouty arthritis, and that the -same is strongly indicated by the fact that</p> - -<p>(3) Acute <i>glandular</i> affections of undeniably <i>infective</i> source—tonsillitis, -pharyngitis, etc.—frequently and immediately -<i>precede</i> acute paroxysms of <i>articular</i> gout, and, lastly,</p> - -<p>(4) The gastro-intestinal defects, secretory or motor, which -chequer the course of gout, enhance the pathological -activities of the intestinal flora, and incidentally the -liability to infection, at various sites of the alimentary -tract.</p> - -</div> - -<hr class="chap x-ebookmaker-drop"> - -<div class="chapter"> - -<p><span class="pagenum"><a id="Page_188"></a>[188]</span></p> - -<h2 class="nobreak" id="CHAPTER_XV">CHAPTER XV<br> -<span class="smaller">GOUT AS AN INFECTION (<i>continued</i>)</span></h2> - -</div> - -<h3><span class="smcap">Analysis of the Acute Paroxysm</span></h3> - -<p>If we reflect on the general features and local characters of -an initial outbreak of gout they are precisely such as would, did -they occur anywhere but at the classic site, <i>the big toe</i>, suggest -an <i>infection</i>. The abrupt onset, the local signs, the crisis, and no -less the subsequent swift restoration to health, how strikingly -reminiscent of an <i>exanthematous</i> fever! Moreover, does not this -outward clinical resemblance seem to predicate an inward pathological -similarity? And now to scrutinise more narrowly the -component elements that make up the content of a paroxysm of -gout.</p> - -<p>Its fulminant <i>onset</i>, with shivering, if not a definite rigor, in a -person in sound and sometimes exuberant health, irresistibly -reminds one of the sudden onfall of an infective disorder. Doubtless, -as Duckworth says, “the conditions leading up to the attack -have been some time previously in operation.” But, as he -rightly contends, “some determining factor must now be invoked -to explain how, as it were, the train is fired.” Quite so, and -what more likely to call into the open these latent morbid potentialities -than an <i>infection</i>?</p> - -<p><i>The constitutional disturbance</i> is often profound, certainly out -of all proportion to the severity and extent of the local phenomena. -Especially prominent are the <i>nervous</i> concomitants—the -excruciating pain, the irascibility, etc. Viewing these in -light of the paroxysmal nature and periodicity of gout, Duckworth -postulated a kinship between the disorder and the <i>paroxysmal -neuroses</i>. But, given an infective element, what more plausible -than to attribute the nervous phenomena of gout to the simultaneous -action of its <i>toxins</i> on the higher centres?</p> - -<p>The <i>temperature</i> curve, again, is obviously compatible with -this conception. It begins abruptly, its course punctuated by -daily remissions. No specific peculiarities apparently differentiate -it from other arthritides of established or assumed infective origin, -but its relatively low grade pyrexia recalls that typical of <i>gonococcal</i><span class="pagenum"><a id="Page_189"></a>[189]</span> -arthritis. Its most striking feature, however, is the disproportion -between the level of the pyrexia and the intensity of -the general and local phenomena. Moreover, the temperature is -not only low, but relatively ephemeral in duration, while the -inflammatory reaction in its violence emulates that of the most -sthenic forms of arthritis.</p> - -<p>Albeit both the febrile disturbance and the local reaction display -infinite grades of severity. Thus, <i>acute gouty polyarthritis</i> -may be <i>afebrile</i> and the <i>asthenic</i> varieties of the affection marked -by little inflammatory reaction. All these vagaries, however, are -quite compatible with infection—the reflex, as it were, of varying -degrees of <i>toxæmia</i>.</p> - -<p>Says Duckworth, “The pyrexia proper to acute gout is paroxysmal -with remission, and the pain of gout is likewise paroxysmal. -One is reminded of the influence of marsh poison upon the nervous -centres. This paroxysmal no less than periodic element in gout -stamps a nervous character upon the malady and binds it in -alliance with other well-recognised neuroses.”</p> - -<p>How interesting these reflections by this distinguished physician -in light of latter-day revelations! For, in so far as these -features in gout are reminiscent of <i>malaria</i>, they disclose an -affinity, not for a malady of nervous, but one of established -<i>infective</i>, origin.</p> - -<p>Simultaneously with the onset of <i>pyrexia</i> the pulse quickens. -The blood shows that increase in fibrin characteristic of inflammation, -a fact noted by Gulland, Cabot, Buchanan and others. -But more significant is the presence of <i>leucocytosis</i>. It may be of -high grade. In a case of acute gouty <i>polyarthritis</i> recently under -my care the leucocyte count reached 27,000. Even in a <i>subacute</i> -example of the classic <i>monarticular</i> type the leucocyte count -attained 25,920. It was of <i>leucoid</i> type and attended by moderate -anæmia due to deficiency of red corpuscles.</p> - -<p>Nor is leucocytosis restricted to the periods of exacerbation, -but it may be met with in the <i>inter-paroxysmal</i> stages. In my -experience, even in cases of definitely <i>chronic</i> type it may reach -14,000. The higher grades of leucocytosis are obviously very -suggestive of an <i>infection</i>, and that lesser degrees should be -encountered in examples of definitely chronic type seems to -point to gout being of the nature of a <i>chronic</i> or <i>serial</i> infection.</p> - -<p>I would here add also that the converse of leucocytosis, viz., -<i>leucopenia</i>, is sometimes met with in chronic cases. Dr. Munro -and I have met with two instances of such in chronic gout in -the intervals between paroxysms. This decrease in the number of -leucocytes (leucopenia) is, of course, deeply interesting and, -needless to say, quite compatible with infections, <i>e.g.</i>, enteric,<span class="pagenum"><a id="Page_190"></a>[190]</span> -malaria, tuberculosis. In fact, it suggests that gout may be the -outcome of divers infections, and not due to any specific organism.</p> - -<p><i>Enlargement of the lymphatic glands</i> was, by older authors, -believed not to occur in gout. But obviously the lack of -macroscopic evidence does not exclude the possibility of -microscopic changes in these structures. The likelihood of such, -moreover, is enhanced by the occasional occurrence of <i>lymphangitis</i> -in connection with the inflammatory articular lesions. -Buzzard, indeed, long since claimed that there was “clinical -evidence of subacute gouty inflammation of lymph spaces in -certain regions due to uratic deposit and influence.”</p> - -<p>As a matter of fact, enlargement of the lymphatic glands does -occur. Thus, my colleague James Lindsay cites an instance -thereof. The subject, a painter, fifty-three years of age, had -gout of some three years’ standing. During an acute paroxysm -thereof “there was a mass of glands in the right groin, synchronous -with an acute inflammation affecting the right knee and -periarticular tissues. On the subsidence of the gouty inflammation -the glands became smaller, but never entirely disappeared -during the four weeks he was subsequently under observation.”</p> - -<p><i>Splenic enlargement</i>, states Duckworth, has been met with in -many cases of gout, and occasionally infarcts. But such splenic -enlargement is, he thinks, <i>not specifically</i> related to gout, but is -due to associated conditions. Personally, I have not as yet met -with splenic enlargement in gout.</p> - -<p>This aside, is it not palpably significant of infection that -Paget, Garrod, and others, repeatedly noted the incidence of -acute <i>phlebitis</i> in a limb the seat of acute articular gout? Did -we observe such a complication in any arthritis other than -gouty, should we not inevitably regard it as indicative of the -spread of an <i>infection</i> from the joint to the related veins?</p> - -<p>Reverting to the <i>local articular phenomena</i>, they are not only -compatible with, but emphatically suggestive of, an <i>infective -source</i>. The typical signs of inflammatory reaction are swiftly -installed in acute classical gout, and this with an intensity -unrivalled save by the most sthenic types of acute arthritis. -Witness how insistent were our forefathers, <i>e.g.</i>, Scudamore, on -the differentiation of acute gout, not so much from acute rheumatism -as from <i>erysipelas</i> or <i>phlegmon</i>. Garrod, indeed, held -that “if a medical man, by chance entirely ignorant of the -nature of gout, were to see a toe affected by this disease in -its full intensity, swollen, hot, red, and tender, he would -probably think that the affection must of necessity terminate -in suppuration, yet I believe this never happens as the result of -simple gouty inflammation.” This leads us to note a salient<span class="pagenum"><a id="Page_191"></a>[191]</span> -feature of gouty inflammation, viz., it never results in <i>pus formation</i>. -Now, allowing for the increased powers of discrimination -that happily to-day are ours, is it not, I ask, significant that the -disorders deemed most likely of confusion with acute gout belong -to the frankly <i>infective</i> category?</p> - -<p>That Garrod’s <i>caveat</i> was not uncalled for I feel sure, having -myself known an acute gouty arthritis incised in the hope of -evacuating pus. Sometimes the error in judgment is reversed -and <i>pyæmic</i> or <i>septic</i> conditions in or near the great toe joint -confounded with gout. Thus, Sir James Paget tells of an instance -in which a pyæmic abscess forming near the great toe and consequent -upon ligaturing of piles was thus confused. I recall, too, -another example in which the supposed gouty arthritis of a great -toe was of pyæmic nature, the outcome of a suppurating otitis -media. Garrod, it may be recollected, ranked <i>pyæmia</i> as one of -the disorders to which gouty subjects were especially liable.</p> - -<p>Gouty inflammation resembles most other forms of the same -morbid change, but some, however, contend that the association -of <i>œdema</i> therewith is pathognomonic. Indeed, by some of the -older authors this concomitant feature of gouty inflammation -ranked as a criterion differentiating it from “true rheumatic -inflammation.” Œdema, of course, is not distinctive of gouty -as opposed to other forms of inflammation. But its occurrence -therein is, we would submit, but another token of its affinity -with the <i>infective</i> arthritides. We need but recall the constancy -with which local œdema is met with in, <i>e.g.</i>, <i>gonococcal</i> arthritis. -More typical of gout, however, is the <i>desquamation of the cuticule</i> -that follows the subsidence of the acute arthritis. Here we are -reminded of the similar peeling of the skin that occurs in another -<i>infective</i> disorder associated with arthritis, <i>i.e.</i>, <i>scarlatina</i>.</p> - -<p>Acute gout is <i>definitely paroxysmal</i>. The attack, at any rate -when primary, is relatively ephemeral, lasts but a few days, and -after it has passed, as Cullen says, “leaves the person in very -perfect health, enjoying greater ease and alacrity in the functions -of both body and mind than that for a long time before experienced.”</p> - -<p>In short, acute gout would appear to be a self-delimited disease, -its fleeting duration predicating that if an organism be responsible, -the same is short-lived. Even in <i>chronic</i> gout, though it -never quite loses its grip of those it has made its prey, yet nevertheless -there are intervals of respite between the attacks, however -long the latter may be. In other words, the disease never loses -its paroxysmal character, which to my mind is very suggestive -of a serial infection.</p> - -<p>The <i>periodicity</i> of gout was, as we have seen, well known to the<span class="pagenum"><a id="Page_192"></a>[192]</span> -ancients. Its recurrence in early spring and late autumn has -even been celebrated in verse:—</p> - -<div class="poetry-container"> -<div class="poetry"> - <div class="stanza"> - <div class="verse indent0">“On whose sacred internodial Altars I</div> - <div class="verse indent0">Each Spring and Fall at least will sacrifice</div> - <div class="verse indent0">Morbifick, painful loads of Matter tartarous,</div> - <div class="verse indent0">With recrements of nervous juice impregnate.”</div> - </div> - <div class="stanza"> - <div class="verse right">“The Honour of the Gout,” by <i>Philander Misaurus</i>.</div> - </div> -</div> -</div> - -<p>Scudamore referred its prevalence at these particular seasons -to their attendant vicissitudes of heat and cold (the strongest of -all the exciting causes of gout). Trousseau states that “gout -with successive paroxysms shows itself early or late in the year, -at the beginning of spring or late autumn, the wherefore I know -not.”</p> - -<p>This tendency on the part of acute gout to seasonal rhythm -is ultimately lost. For, once the disorder is established, no period -of the year confers absolute immunity. Whatever be the explanation -of the vernal and autumnal incidence of gout in its early -stages, this peculiarity is at any rate not incompatible with its -<i>infective</i> origin. In this connection it may be recalled that it -was once described as “a tertian fever terminating in fourteen -days.”</p> - -<p>Again, further evidence may be obtained from the action of -colchicum, our sheet-anchor in the treatment of gout. Thus, -Dixon and Malden have shown that <i>colchicine</i> has no action on the -metabolism of <i>purins</i> or on the <i>kidney</i>. On the other hand, it -causes a primary diminution followed by a <i>marked increase</i> in -the number of <i>leucocytes</i>, which suggests the possibility that it -exerts its beneficial effects by combating <i>infection</i>.</p> - -<p>Lastly, turning our attention to the anatomical changes as -disclosed after death during an acute articular paroxysm, these -present appearances quite compatible with their infective origin. -Dr. Munro, in one of my examples of <i>acute gouty polyarthritis</i>, -aspirated the knee joint. The results of <i>cytological</i> examination -were precisely such as are deemed characteristic of arthritides -of infective source.</p> - -<p>The results of our analysis of the component elements of an -acute paroxysm of gout are, for the following reasons, strongly -indicative of the intrusion of an <i>infective</i> element:—</p> - -<div class="blockquote"> - -<p>(1) The onset, temperature curve, the character of the local -phenomena, and course of the disorder.</p> - -<p>(2) The presence of <i>leucocytosis</i> with secondary anæmia, and -exceptionally of <i>leucopenia</i>.</p> - -<p>(3) Enlargement of the lymphatic glands, and possibly of the -spleen.</p> - -<p><span class="pagenum"><a id="Page_193"></a>[193]</span></p> - -<p>(4) Occasional complication of the acute articular disorder by -<i>lymphangitis</i> and <i>phlebitis</i>.</p> - -<p>(5) The paroxysmal nature and periodicity of the disorder.</p> - -<p>(6) The compatibility of the morbid anatomical changes and -the cytological content of aspirated joint fluid with their -genesis by infection.</p> - -</div> - -<h3><span class="smcap">The Evolution and Life History of Gout</span></h3> - -<p>If the onset, phenomena, and course of acute gout are reminiscent -of infection, so, also, does a review of the life history -of the disease, as a whole, carry with it the same inference.</p> - -<p>For the course of gout, like other arthritides of chronic type, -is not one of steady, uninterrupted progress, but one marked -rather by <i>periodic</i> or <i>intermittent</i> advances, as if seemingly due to -a series of successive <i>infections</i> or <i>sub-infections</i>. One is reminded -of <i>gonococcal</i> arthritis in its more severe forms, the acute exacerbations -which chequer its course being generally referred to -intermittent absorption of fresh doses of the toxin from some -smouldering infection in the prostatic urethra.</p> - -<p>Now, if the general course or evolution of <i>gouty</i> arthritis is -notably similar to that of the specific infective arthritides, so, also, -do the clinical features approximate. Thus its <i>onset</i>, more often -than not, is <i>abrupt</i> and attended by pyrexia of <i>irregular</i> or <i>septic</i> -type, with an occasional <i>leucocytosis</i>.</p> - -<p>Again, that not all cases of gout are of <i>acute fulminant</i> type -may be admitted. We know that it may assume the guise of a -fleeting <i>arthralgia</i> or “flying gout,” a transient <i>synovitis</i>, as well -as an acute <i>arthritis</i> of <i>mono-</i>, <i>oligo-</i>, or <i>poly-articular</i> extent. -This same <i>polymorphism</i> in respect of the joint lesions in gout -is a replica of that met with in the <i>specific infective arthritides</i>. -The milder varieties betokened by arthralgia or synovitis tend -commonly to disappear, as it were, spontaneously in precisely -the same manner as the arthralgias or synovites that follow the -exanthemata, and we presume that, comparably with these latter, -the source of infection dries up and <i>restitutio ad integrum</i> of more -or less completeness follows.</p> - -<p>But with repeated attacks, as in the specific infective arthritides, -progressive infiltration and thickening of ligaments, capsule, and -related tendinous and aponeurotic structures ensue. As far as -these anatomical changes are concerned, gouty arthritis and the -specific arthritides are at one, but with this outstanding difference, -the associated <i>uratic deposition</i>. Save in respect of this last, the -analogy is complete, and herein resides the specificity of gouty -arthritis.</p> - -<p><span class="pagenum"><a id="Page_194"></a>[194]</span></p> - -<p>Chalmers Watson, from his observations of “gouty deposits” -in human subjects in their relation to <i>tendons</i>, <i>cartilage</i>, and <i>bone</i>, -came to the conclusion that the <i>tout ensemble</i> of the pathological -lesions was very reminiscent of that typical of the more chronic -types of <i>infective</i> disorders. Thus necrotic areas in gouty tendons -stood in such clear relationship to the vascular supply as to -suggest some infection <i>viâ</i> the blood-stream. Again, areas of -erosion in the cartilage were found to be due, not to uric acid, -but to the disintegrating action of small round cells of the nature -of granulation tissue.</p> - -<p>As to uratic deposits located in the <i>bones</i>, it was noted that -their vicinity was characterised by marked vascularity, the -existence of giant cells, and an accumulation of the small round -cells so commonly correlated with the action of bacterial toxins.</p> - -<p>In reviewing the foregoing clinical and pathological data and, -alike, the inferences as to their significance, it cannot, we think, -be gainsaid that, collectively, they are more readily explicable as -being due to an infection than to any other morbid source.</p> - -<h3><span class="smcap">Analogies between Gout and the Specific Infective Arthritides</span></h3> - -<p>A striking parallel can be drawn between the varied manifestations -of gout and those met with in <i>specific infections</i>. But, to -begin with, we must recall that our attitude towards infective disorders, -<i>e.g.</i>, acute rheumatism, gonorrhœa, etc., is altered in that -we regard them now, not as local, but <i>general</i>, systemic infections.</p> - -<p>Thus, following the revelations of bacteriologists, we now, for -example, recognise that in <i>gonococcal</i> infection not only may -there be <i>articular</i> involvement, but that <i>muscular</i> and <i>nervous</i> -lesions may be associated therewith. This same, also, in <i>acute -articular rheumatism</i>. True, its causal organism is still <i>sub -judice</i>, but data accumulate as to the frequency with which the -<i>muscles</i> are involved, and, to a less extent, the sheaths of <i>nerves</i>.</p> - -<p>Take <i>dysentery</i>, again; it, too, as Sydenham pointed out, may -be complicated, not only by <i>arthritis</i>, but by <i>myalgias</i>, while more -recent experience emphasises the frequency with which <i>neuralgias</i> -are associated therewith. In <i>syphilis</i>, also, the association of -<i>articular</i>, <i>muscular</i>, and <i>nerve</i> lesions is well attested; and by -French physicians it is insisted that, in <i>tubercle</i>, myalgias and -neuralgias, as well as joint disorders, are infinitely more common -than is generally realised.</p> - -<p>To sum up, this <i>triad</i> of <i>arthritic</i>, <i>muscular</i>, and <i>nerve</i> lesions, -either serially or simultaneously, is the most common complication<span class="pagenum"><a id="Page_195"></a>[195]</span> -of <i>specific infections</i>. Now, is not this same congeries of articular, -muscular, and nerve disorders precisely the clinical content of -<i>gout</i>?</p> - -<p>Thus its <i>articular manifestations</i> constitute the most striking -feature of the disease. As to the <i>muscular</i> troubles, there is a -consensus of opinion as to their relative frequency. Inflammatory -foci with associated uratic deposit have been found in muscles -and tendons. We may here recall that the purin bases of the -body exist, not only in the bound form (nucleic acid), but also -<i>free</i>, especially in <i>muscular</i> tissue, also that from such free purin -bases <i>uric acid</i> can be as readily formed as from those liberated by -disruption of nucleic acid.</p> - -<p>Clinically, one meets with all forms of fibrositis in actual -association with acute articular gout. Such may affect either the -neck, shoulder, loin, or sciatic nerve. In their work on “Fibrositis,” -Bassett Jones and Llewellyn have shown that the disorder -develops with significant frequency in the victims of gout. This -but confirms the conviction held by Gowers, Garrod, Hilton Fagge, -and others, viz., that the muscular and nervous types of fibrositis -are frequently and obviously related to gout.</p> - -<p>How noteworthy the well-established proclivity of gout to -involve bursæ, tendon sheaths, and fasciæ, especially the plantar! -Is not this exactly paralleled in certain <i>infections</i>? Note the -predilection of post-scarlatinal rheumatism for bursæ and tendon -sheaths; that of the gonococcus for these structures as well as -fasciæ, not to mention the frequency with which bursal enlargements -are traceable to syphilitic, tuberculous, and other -infections.</p> - -<p>We see, therefore, that in virtue of its tendency, not only to -<i>arthritic</i>, but also to <i>muscular</i> and <i>nerve</i> disorders, gout falls into line -with the <i>specific infections</i>. Its predilection for bursal and fascial -structures is but another evidence of affinity with this group of -disorders. In view of these similitudes, one may well ask, Are -not these <i>gouty</i> manifestations, all of them, susceptible of a like -explanation, viz., that they are the outcome of an <i>infection</i>?</p> - -<p>For, in reviewing the foregoing analogies, it cannot, we think, -be denied that in the aggregate they are emphatically suggestive -of an infective origin.</p> - -<h3><span class="smcap">Correlation of the Metabolic Phenomena of Gout -with the Postulated Infective Element</span></h3> - -<p>In essaying this difficult task, we must recall to the mind of -the reader our findings or deductions from the data disclosed -in preceding chapters.</p> - -<p><span class="pagenum"><a id="Page_196"></a>[196]</span></p> - -<p>The outstanding conclusions that we felt justified in formulating -were that:—</p> - -<div class="blockquote"> - -<p>(<i>a</i>) Uric acid is not the cause but the <i>consequence</i> of gout.</p> - -<p>(<i>b</i>) <i>Inflammatory reaction</i> is, we believe, an invariable precursor -in all gouty processes.</p> - -</div> - -<p>In other words, we suggest that, although abnormalities of -metabolism form an integral part of gout, they are of themselves -inadequate to achieve its efflorescence. Thus, when we came to -consider the elemental manifestations of gout, <i>i.e.</i>, uratic deposits -or <i>tophi</i>, we saw that neither the purely physical nor the purely -chemical theory of their origin would suffice, nor, for that matter, -could any solution of this complex problem be gleaned from -even a blend of the twain. In short, such hypotheses are too -<i>mechanical</i>. The intrusion of some other factor, “some vital -something biological,” seems essential for the elucidation of -<i>uratosis</i>, <i>i.e.</i>, uratic deposition. For this, <i>not uricæmia</i>, is the -specific characteristic phenomenon of gout. If we cannot explain -uratosis on physical or chemical grounds, then how much less, -in view of the <i>non-toxicity</i> of <i>uric acid</i>, can we, on this basis, -account for the <i>inflammatory</i> phenomena of the disorder?</p> - -<p><i>Inflammatory reaction</i> is, we hold, an invariable <i>antecedent</i> in -all gouty processes, whether of <i>articular</i> or <i>ab-articular</i> site. -Granted that inflammatory reaction is a necessary prelude, the -specificity of gout is attested by the fact that this same is followed -by the deposition of urates. But while the sequential uratic -deposition invests all forms of “gouty” inflammation with a -specific character, unshared by any other disease, it follows that -the cause of the said inflammation must, if possible, be ascertained.</p> - -<p>For Walker Hall “the contention that gout lowers the general -tissue resistance, and so opens the way to bacterial infections, is -so obvious that it need hardly be formulated.” In light of -this, we need have the less diffidence in hazarding our opinion -that the morbific agent responsible for “gouty” inflammation -is an <i>infection</i> or <i>sub-infection</i>. Now, in all forms of arthritis -other than gouty, the intrusion of a germ is held to be self-explanatory -and final; in short, all the local morbid changes -and constitutional disturbances are held satisfactorily accounted -for by the organism or its toxins.</p> - -<p>The problem of gout, however, is not so simple. Its arthritis -is peculiar in that it is always accompanied or followed by <i>uratic -deposition</i>, which, be it noted, is not an ordinary sequel of inflammation. -It is, in short, the outcome of inflammation supervening -in an individual of <i>gouty diathesis</i>. What do we know of this -latter?</p> - -<p>The researches of the bio-chemists reveal that <i>uric acid</i> is the<span class="pagenum"><a id="Page_197"></a>[197]</span> -end-product of nuclein metabolism—the summation of a long chain -of enzymatic reactions. Some indeed have thought to find an -adequate explanation of gout in <i>enzymatic abnormalities</i>. Thus, -Adami and McCrae suggest that gout is the outcome of <i>insufficient -oxidation</i>, whereby the precursors of uric acid and similar bodies -are not fully oxidised, and, by their accumulation and toxicity, -set up morbid changes, and the uric acid formed is, in its turn, -imperfectly oxidised and accumulates. This diminished oxidation -is due to a constitutional deficiency of <i>oxydases</i>, inherited or -acquired.</p> - -<p>This opens up the old problem as to whether uric acid is an -intermediary or a terminal product of metabolism. But, from -evidence cited in preceding chapters, it appears probable, if not -certain, that uric acid is an end-product. Moreover, as Gideon -Wells observes, “the failure of recent studies on the enzymatic -transformation of purins to locate anywhere in the human body -an enzyme-destroying uric acid makes hazardous the attempt to -explain gouty metabolism as a result of enzymatic abnormalities.”</p> - -<p>Indeed, in view of this, as hitherto ascertained, <i>absence of -uricolytic enzymes</i>, there can, as Wells says, “be little doubt that -the fundamental reason for the existence of uric acid gout in man -lies in the inability of the human organism to destroy uric acid. -Consequently, inasmuch as man, unlike other mammals, cannot -destroy uric acid rapidly by oxidation, he is always a potential -victim of uric acid retention and deposition.”</p> - -<p>Now we have, we hope, shown that there is no evidence that the -<i>uric acid retention</i> in gout is due to functional inability on the -part of the <i>kidney</i> to excrete uric acid. This being so, we have, -as Von Noorden rightly says, no right to do violence to the facts -by assuming that, in a case lacking any other evidence of <i>nephritis</i>, -a condition of “latent nephritis” is the cause of the uric acid -retention and deposition.</p> - -<p>Similarly, there is at present no evidence forthcoming that -the retention of uric acid is due to <i>abnormal purin combinations</i> -in the <i>blood</i>. Nay, according to Wells, on the best evidence -obtainable, uric acid exists in a <i>free</i> state in the blood, and not -combined, as has been urged by many workers in this sphere.</p> - -<p>But if the cause of <i>uric acid retention</i> lies neither in the <i>kidneys</i> -nor in the <i>blood</i>, there must exist something abnormal in the gouty -individual which renders impossible what may be termed a -<i>compensatory uric acid excretion</i>. Now, as disclosed in the previous -chapter, experimental research, in diseases other than gout, has -shown that the <i>bodily tissues have an appreciable capacity for -retention of uric acid</i> (Fine). This, moreover, gains probability -from the fact that Wiechowski, in his prolonged studies as to the<span class="pagenum"><a id="Page_198"></a>[198]</span> -possibility of uric acid decomposition in the human body, was -never able to detect any evidence of <i>uricolysis</i>. Furthermore, -on the clinical side, the fact that <i>intravenous injection of uric acid</i> -does not produce a corresponding degree of <i>uricæmia</i> seems, as -Bass and Herzberg suggest, to indicate that in gout the <i>retention -capacity of the tissues for uric acid is augmented</i>. Lastly, in the -precipitation and anchoring of urates in the tissues in gout, we -have objective proof, <i>i.e.</i>, tophi, that the uric acid is actually -held in the tissues.</p> - -<p>Does not this seem to indicate that there are <i>peculiarities of -tissue in the gouty</i>? What, then, the subtle change that determines -the <i>retention and deposition</i> of urates in the tissues in -gout?</p> - -<p>May we not, with Walker Hall, hazard the reflection that there -may be differences between the <i>nucleotides</i> of normal and gouty -tissues? For, doubtless, if there be peculiarities of tissue in the -gouty, these will be reflected in abnormalities of <i>tissue function and -metamorphosis</i>.</p> - -<p>Gowlland Hopkins, discussing the metabolism of purins, holds -that in gout there is some disturbance or defect in the <i>fermentative -functions of the tissues</i>. Of a verity the range of <i>intranuclear</i> -activities offers scope enough when we recollect that the cells -of all tissues contain not only <i>nucleinase</i>, but also <i>nucleotidase</i> and -<i>nucleosidase</i>. Even so, the resultant nucleins, the nucleotides, and -nucleosides, have still further changes of deaminisation and oxidation -to undergo, these carried out in the liver and elsewhere!</p> - -<p>We may talk of defects in the enzymatic functions of the -tissues, but, viewing gout clinically, and more particularly the -hypersensitiveness of its victims to the most varied stimuli, -dietetic and other, one inclines rather to predicate in their instance -an inherent <i>instability</i> of <i>nuclein metabolism</i>. For in the gouty, -as Walker Hall observes, “a slight injury or indiscretion of diet, -an overloaded intestine, or increased toxicity of the intestinal -flora, may be followed by a disturbance of the general nuclein -metabolism, and a local reaction in certain tissues.”</p> - -<p>With this pronouncement all clinicians will be in accord, and -herein, too, we may, I think, discern how the latent tissue idiosyncrasies -of the gouty are evoked, <i>i.e.</i>, by <i>infection</i>; in other words, -that, under the influence of these morbific agents, the innate -morbid potentialities of the gouty become overt and manifest.</p> - -<p>The exact <i>modus operandi</i> whereby the assumed organisms -or their toxins determine the <i>efflorescence</i> of gout is uncertain. -We know that, following the intake even of <i>non-purin-containing -foodstuffs</i>, an <i>increase in uric acid excretion</i> ensues, and that the -same is the outcome of the stimulation of <i>general</i> nuclein metabolism.<span class="pagenum"><a id="Page_199"></a>[199]</span> -Is it not conceivable that the responsible toxin acts in -like fashion, and haply by disturbing the orderly sequence of -those exquisitely delicate enzymatic reactions which culminate in -the formation of uric acid, and with which potentialities every -living cell in the organism is dowered? Further than this we, -pending future researches by the bio-chemists, may not go, for -“the positive material is much too insufficient, and much too -ambiguous.”</p> - -<p>In conclusion, I would postulate that in <i>gouty</i> subjects:—</p> - -<div class="blockquote"> - -<p>(1) There is an inherent abnormality or instability of <i>nuclein</i> -metabolism, and conjoined therewith an enhanced tissue -affinity or augmented retention capacity for uric acid.</p> - -<p>(2) These latent tissue peculiarities, through the agency of -<i>infections</i> or sub-infections, become manifest as gout.</p> - -<p>(3) The said organism or organisms excite inflammatory -reaction with sequential uratic deposition, either of articular -or ab-articular site.</p> - -<p>(4) The predilection of such uratic deposition for certain -particular tissues is determined by their greater content -of sodium ions as compared with the blood.</p> - -<p>(5) The local and general phenomena of gout, its paroxysmal -nature and tendency to periodicity, are most readily -explicable on the basis of a <i>chronic infection</i> supervening -in a subject the victim of those innate peculiarities of -tissue with their correlated obliquities of function which -connote what we term the “gouty diathesis.”</p> - -</div> - -<hr class="chap x-ebookmaker-drop"> - -<div class="chapter"> - -<p><span class="pagenum"><a id="Page_200"></a>[200]</span></p> - -<h2 class="nobreak" id="CHAPTER_XVI">CHAPTER XVI<br> -<span class="smaller">CLINICAL ACCOUNT</span></h2> - -</div> - -<h3><span class="smcap">Acute Localised Gout</span></h3> - -<p>If we would clarify somewhat the obscurity that enshrouds -the genesis of disease, our watchword must here, as in other -spheres, be “Despise not the day of small things.” We know not -the proximate cause of gout, it is true, nor the exact <i>modus -operandi</i> of those agents, infective or other, which bring to fruition -the latent morbid potentialities of its victims. But, even if so -handicapped, we should be quick to descry those portents of the -coming storm, those minor backslidings from physiological -righteousness, that doubtless foreshadow the outbreak of the -disorder.</p> - -<p>For it cannot be doubted that the evil potentialities which -make for gout are for long in operation before their definite -installation in its chosen seat, the joints, ensues. As Trousseau -puts it, “The diathesis is in action before there is time for the local -affection to show itself in a precise form.” In short, given -imminence of an attack, the whole system is charged with gout, -or, as Sydenham laconically expressed it, “Totum corpus est -podagra.”</p> - -<h3><span class="smcap">Prodromal Symptoms</span></h3> - -<p>While we recognise that local inflammatory reaction in the -joints is more particularly characteristic of gout, it is no less -necessary that we take cognisance of the general precursory -symptoms that often, if not always, usher in its onfall. Gout -begins in a disorder of <i>function</i>.</p> - -<p>Uncomfortable sensations may obtain days and weeks before -the incidence of the fit. To old time sufferers they are sufficiently -alarming. But their significance, as heralds of an initial attack, -by victim and too often by physician also, is usually only appreciated -when the threatened fit becomes an actuality. Speaking -of premonitory phenomena in gout, Sydenham remarked, “Its -only forerunner is indigestion and crudity of the stomach, of -which the patient labours some weeks before,” and doubtless -this is in the main true.</p> - -<p><span class="pagenum"><a id="Page_201"></a>[201]</span></p> - -<p>As Trousseau long since observed, the patient’s appetite often -becomes capricious. He likes his meat strongly spiced, and craves -for acids. But his satisfaction is short-lived. For eating is -followed by drowsiness, feelings of oppression and fulness, with -unpleasant eructations, or more rarely definite retching. -The bowels are generally costive, but in exceptional instances -diarrhœa has been noted. The state of the urine is variable. -Generally scanty and high-coloured, it may in some be copious -and pale.</p> - -<p>Uneasiness in the right hypochondrium and even slight swelling -of the liver was noted by Trousseau and also by Scudamore. Such -congestion of the portal system and hepatic enlargement may be -only fugacious, but often the same is permanent, a penalty of -the same cause—free living—which leads to the production of gout. -For in many instances but too true is it that “for years together,” -as Sydenham said, “a man has drunk and feasted, has omitted his -usual exercise, has grown slow and sluggish, has been over-studious -or anxious, in short, has gone wrong in some important point of -life.”</p> - -<p>But more palpable to his friends than to himself are the concomitant -changes in his disposition and character. From being -good-natured and easy-going he becomes morose and irritable. -The irascibility of the gouty is proverbial, and the explosive -mental outbursts to Duckworth appeared at times to be “a -metamorphic substitution for a more overt and regular attack,” -or, as Sydenham expressed it, “Non rectius podagræ quam iracundiæ -paroxysmus omnis dici potest.”</p> - -<p>Sometimes his mental vagaries are exchanged for or accompanied -by neuralgia, painful cramps in the limbs, etc. In truth, the -premonitory phenomena of gout are protean, inasmuch as, given -any prior weakness or functional derangement of any viscus, the -symptoms of oncoming gout are masked by aggravation of the -same, it may be by cardiac irregularities, vesical irritability, or in -an old bronchial subject by increase of cough, etc.</p> - -<p>But it may be objected, there is nothing <i>specific</i> about these -various <i>functional</i> disturbances. They are not more common in -the <i>gouty</i> than in others. Moreover, the habits of life productive -of gout favour the development of gastric and hepatic derangements. -The mental irritability, the gastric disturbances, etc., -may be quite as well accounted for by overeating and overdrinking -as by gout.</p> - -<p>Now, if there be nothing <i>specific</i> of gout in these so-called prodromata—“heartburn, -acidity, flatulence, etc.”—then what is -their true significance? For, obviously recognition of their true -import is most essential. Now to my mind the said “dyspeptic”<span class="pagenum"><a id="Page_202"></a>[202]</span> -symptoms should be regarded not as symptomatic of gout, but as -<i>etiologically</i> related thereto.</p> - -<p>For, though the etiology of gout is still much debated, the same -obscurity will certainly not be clarified, if we merely content ourselves -with dubbing such “dyspeptic” symptoms as “gouty.” -On the other hand, if we, at this early stage, endeavour to elucidate -the <i>true origin</i> of the “dyspeptic” symptoms, who will deny -that this is the more rational and scientific mode of procedure? -The timely elimination of <i>septic foci</i> in the mouth, tonsils, and naso-pharynx -conjoined with modification or restriction of food intake -and recognition betimes of the signs of intestinal infection and -constipation would perhaps stave off or avert the threatened -articular outbreak.</p> - -<p>It has been suggested that there is some statistical evidence -that “acute rheumatism” has declined in frequency since the -introduction of <i>tonsillectomy</i>. In the same way, I cannot help -thinking that the growing infrequency and attenuation of gout is -in part due to increasing appreciation by the laity and the profession -of the vital importance of <i>oral hygiene</i> and timely and -radical treatment of <i>local foci of infection</i>. The fact that in -<i>children</i>, victims of so-called <i>infantile gout</i>, the <i>purin metabolism</i> -may show those same derangements held typical of the subjects -of gout, is surely an indication that the disorder begins betimes, -and that we too must not tarry if we would prevent these evil -potentialities coming later to fruition.</p> - -<p>Now, if there be nothing <i>specific</i> of gout in the “dyspeptic” -derangements held <i>prodromal</i> thereof, the reader may well ask the -pregnant question, Are there any symptoms or signs that will -enable one to identify the victim of these minor discomforts as -being “actually” or “potentially” a “gouty” subject? In -attempting to answer this reasonable query one would emphasise -the fact that <i>tophi in the ears or at other sites sometimes -antedate articular outbreaks</i>.</p> - -<p>Now given that an individual exhibits <i>auricular tophi</i>, one or -many, can anyone deny that he is “gouty,” nay more, that he -has <i>gout</i>, this even though he never has had, or may never -have, an <i>articular</i> outbreak? In truth, the eruption of a <i>tophus</i> in -the <i>ear</i> is as essentially a “fit of gout” as if it had occurred at the -classic site, the <i>big toe</i>.</p> - -<p>How vivid the light then thrown upon the import, the <i>etiological</i> -significance, of otherwise inexplicable <i>functional</i> derangements! -How grim the potentialities of, <i>e.g.</i>, “dyspeptic” symptoms as -revealed by detection in the subject of a <i>tophus</i>! Whether viewed -from the <i>diagnostic</i> or <i>prognostic</i> aspect, its importance cannot be -overestimated. For let us not forget that the <i>tophus</i> is the one<span class="pagenum"><a id="Page_203"></a>[203]</span> -incontrovertible token of the “gouty diathesis.” This morbid -localisation is the sole outward expression of the inward and -dominant pathological trend.</p> - -<p>The great Charcot did not despise its aid. He narrates the case -of a man thirty-five years of age, a sufferer for some months from -“acid dyspepsia,” in whom he predicted a fit of <i>gout</i> from noting -an <i>uratic concretion</i> in one <i>ear</i>. Is not the moral obvious that in -an individual complaining of gastric or hepatic disturbances, etc., -we should, at any rate, examine the ears for <i>tophi</i>?</p> - -<p>For, far more often than is currently realised, their eruption -<i>antedates</i> the <i>articular</i> outbreaks.<a id="FNanchor_27" href="#Footnote_27" class="fnanchor">[27]</a> Moreover, they may not be -solitary, but numerous, the <i>cutaneous gravel</i> of older authors. In -truth, these cases of tophi, <i>uncomplicated</i> by <i>articular</i> lesions, seem -to merit some distinguishing term, representing as they do a -purely <i>ab-articular</i> form of gout.<a id="FNanchor_28" href="#Footnote_28" class="fnanchor">[28]</a> They constitute what might be -termed primitive elemental gout, of which the subsequent <i>articular</i> -outbreaks are but an extension, a further manifestation of the -“gouty diathesis.” For it is just this same tendency to <i>uratosis</i> -or deposition of sodium biurate, and this alone, that to our mind -constitutes <i>gout</i>, this “primordial vice of nutrition,” not the -congeries of distempers that with the passing ages have clustered -around the primitive gout, well-nigh submerging its identity.</p> - -<p><i>Premonitory Symptoms of Tophus Formation.</i>—While tophi may -<i>antedate</i> articular attacks, we do not always meet with them as -<i>mature</i> concretions easily recognisable as such. We must have -regard therefore to the symptoms and signs indicative of their -impending eruption. Consequently in a patient complaining -of the various functional disturbances that so frequently anticipate -gout we should never dismiss as trivial any complaints of <i>pricking</i> -or <i>tenderness</i> in the <i>ears</i>.</p> - -<p>Sometimes the pain in the ears is <i>acute</i>, the tenderness such as -forbids their pressure on a pillow. Graves, of Dublin, not only -noted that the pain in some instances was agonising, lasting a -few hours, but he himself suffered also from such attacks of -auricular pain, which only disappeared when gout supervened in -his <i>fingers</i>. I have myself frequently known the pain and soreness -referred to chilblains, though later their tophaceous nature -was disclosed.</p> - -<p><span class="pagenum"><a id="Page_204"></a>[204]</span></p> - -<p>Given such auricular pain and tenderness, we should examine the -<i>pinna for small red swellings</i>.<a id="FNanchor_29" href="#Footnote_29" class="fnanchor">[29]</a> These, when definitely localised, -should be punctured and the thick white fluid which exudes -examined microscopically for <i>urate of soda</i> crystals. In some -instances the creamy-like exudate does not yield a crystalline -deposit, and Dr. Munro and I are inclined to believe that there -is a <i>pre-uratic</i> stage in the evolution of tophi. We have observed -this absence of crystalline deposits in apparently unmistakable -tophi, as evidenced by the usual pearly white concretions in the -rim of the ear. I recollect that the late Sir William Osler, when -visiting our laboratory, was deeply interested in this possibility, -as suggested by Dr. Munro, of a <i>pre-uratic</i> stage. Needless to say, -all local sources of fallacy—Woolner’s tip, fibroid nodules, sebaceous -cysts—were excluded, while, in the lack of <i>crystalline</i> proof, the -evidence in favour of the associated <i>arthritis</i> being gouty rested on -its being at the classical site, the <i>great toe</i>. Moreover, as an -alternative explanation we have the possibility of <i>reabsorption</i>. -We may recall Duckworth’s well-known example where a man had -two attacks of gout in the right great toe joint, yet autopsy -revealed no speck of uratic deposit. We know, too, that, following -an <i>acute</i> attack, tophi may diminish in size or even disappear, while -coincidently fresh tophi form at other sites.</p> - -<p><i>Premonitory Articular Pains.</i>—Again, when, in association with -indigestion or other premonitory symptoms, twinges in the toe -recur from time to time, especially after consuming wines or -certain articles of food, these same are very suggestive of impending -gout. Garrod is very definite on this point: “I have no doubt -that many persons experience extremely slight attacks of gout -before the development of the affection in an acute form, and -several of my patients have assured me that for years before their -first severe attack in the great toe they have felt slight periodic -twinges. I am of opinion that when such twinges occur deposition -has already taken place.”</p> - -<p>In conclusion, we would urge that, given <i>gastric</i> or <i>hepatic</i> disturbances, -etc., in a subject predisposed by <i>heredity</i> or <i>habits</i> to -gout, we should note the presence or absence of the following:—</p> - -<div class="blockquote"> - -<p>(1) Pain, pricking, or tenderness in the ears, with or without -small red swellings.</p> - -<p>(2) Similar sensations at site of finger joints, with dorsal -swellings over which the skin may be red or unchanged.</p> - -<p><span class="pagenum"><a id="Page_205"></a>[205]</span></p> - -<p>(3) The existence or not of pearly white concretions, <i>i.e.</i> mature -tophi (as tested microscopically), at the above sites or -elsewhere.</p> - -</div> - -<p>Further signs that may be sought for in cases of doubtful nature, -<i>i.e.</i> <i>unevidenced by tophi</i>, would be:—</p> - -<div class="blockquote"> - -<p>(4) The presence of <i>uricæmia</i>.</p> - -<p>(5) A lowered or sub-normal output of uric acid in the urine.</p> - -<p>(6) Diminution or retardation of the output of exogenous purin.</p> - -</div> - -<p>To take up the thread of our narrative regarding the <i>prodromal</i> -symptoms which at any moment may give place to an <i>articular</i> -outbreak. The <i>determinants</i> or <i>exciting</i> causes having been already -dealt with in the section on etiology, we shall here only note those -symptoms or signs that portend the <i>imminence</i> of the paroxysm. -These are very variable. But it is suggestive if without any -change in the habits the “dyspeptic” symptoms abate somewhat -or disappear.</p> - -<p>Indeed, it is well recognised that, whatever the nature of the -prodromal phenomena, they all tend to cease just before the -oncoming attack. Occasionally a pre-existing depression gives -way to a feeling of exuberant health or well-being. We recall the -instance of a celebrated physician whose lectures always just -prior to an attack took on an added brilliance.</p> - -<p>Reverting to more definite harbingers, it has been noted that -the <i>urine</i> becomes <i>scanty</i>, and its content of <i>uric acid</i> much -<i>diminished</i>, some three or four days before the paroxysm, though -such is not invariable. Easier of note and widely recognised is the -fact that in those exhibiting tophi <i>pricking pains or tenderness</i> -are experienced at their site. Scudamore, Garrod, and Duckworth -are all agreed on this point. Another sign noted by -Sydenham was that the <i>veins</i> of the <i>part</i> about to be affected -become <i>engorged</i>—a feature confirmed by Trousseau and others.<a id="FNanchor_30" href="#Footnote_30" class="fnanchor">[30]</a></p> - -<h3><span class="smcap">The Acute Paroxysm</span></h3> - -<p>A brief interlude, lasting a few hours or a day, frequently intervenes -between cessation of the prodromal discomforts and the -onset of the attack. This delusive sense of well-being deceives -none but the uninitiated, for to the old time sufferer it is but the -truce before the threatened assault.<a id="FNanchor_31" href="#Footnote_31" class="fnanchor">[31]</a></p> - -<p>Still the subject feels better and more placid than his wont, -seeks his bed, and sinks to sleep (“sanus lecto somnoque committur”).<span class="pagenum"><a id="Page_206"></a>[206]</span> -But suddenly, more commonly an hour or two after -midnight, he awakes to a pain in the foot, usually in the ball of -the great toe, though more rarely in the heel, instep, or ankle. -Simultaneously he becomes chilly, shivers, or has a rigor. But -as the pain, at first bearable, grows in intensity, these feelings -lapse, giving way to feverish restlessness. Posture after posture -is renounced, but, toss as he will, he strives in vain to find a place<span class="pagenum"><a id="Page_207"></a>[207]</span> -of ease for the tortured limb. Even the pressure of the bedclothes -is intolerable. But towards morning (“sub galli cantu”) the pain -remits as suddenly as it began. Anon the sufferer breaks into a -gentle sweat, falls asleep, and wakes to find the painful part red, -swollen, tense, and shiny, surrounded with œdema and turgid veins.</p> - -<p>The same series of events recurs, though often in mitigated -form, for some days and nights. During the day his pain is -lulled, but towards evening it gathers in intensity to cease or -diminish towards morning. The cycle continues from eight to ten -days; then pain ceases, redness fades, œdema subsides, and the -inflamed cuticle peels, with itching. The temperature meanwhile -has sunk to normal, the local tenderness and stiffness gradually -pass off, and health is restored. “Gout is the cure of the gout,” -said Mead long since, and certainly recovery from the first attack -of gout is usually speedy and complete. A renewed sense of <i>bien-être</i> -ensues, free from the discomforts that led up to the outbreak. -Indeed, in exceptionally rare instances the disease seemingly -exhausts itself in a single paroxysm, or decades may pass before -another visitation. Sir William Roberts tells of a Yorkshire -squire who sustained a classical attack in his twenty-seventh year, -the next in his eighty-ninth year. Frequently a second attack -may not occur for one, two, or even three years. But the tendency -to recurrence usually becomes more and more pronounced as the -years roll on, and eventually the gouty man resigns himself to -the doleful expectation of an attack once or twice a year, during -spring or fall, with some approach to periodic regularity.</p> - -<p>Initial attacks of gout are usually <i>monarticular</i>, but consideration -of the polyarticular variety will best be postponed until we come to -consider <i>acute gouty polyarthritis</i>. Also we think it will be more -convenient for us to defer discussion of <i>retrocedent</i> gout to the -chapter dealing with the irregular or anomalous types of the disorder. -Meanwhile we will now proceed to detailed description of -the individual phenomena that make up the clinical content of -acute gout.</p> - -<h3><span class="smcap">Detailed Consideration of Phenomena</span></h3> - -<p><i>Onset.</i>—From Sydenham’s classical account it might be inferred -that the onfall of gout is always fulminant. But this is far from -being the case. For I find myself in agreement with Hilton Fagge -that in many, if not the majority of instances, even the <i>initial</i> -outbreak of the disorder is installed in a far less dramatic manner. -Certainly in not a few cases its manner of approach is insidious, -not to say stealthy. At onset then the nature of the case is therefore -frequently misinterpreted both by victim and physician. -The free liver, fearing that Nemesis has overtaken him, is fertile<span class="pagenum"><a id="Page_208"></a>[208]</span> -in suggestion. He has overwalked, his boot pinched him, or it is -a sprain. Local appearances may be non-committal. There may -be no swelling nor redness, and no access of pain at night. Still -there is discomfort when he walks. The so-called sprain lingers, -and one morning the great toe, instep, or ankle, is swollen, tender, -flushed, and the victim’s fears and the physician’s suspicions are -converted into certainty: it is gout!</p> - -<p>Still in this matter of the onset I must not overlook the findings -of my colleague James Lindsay. In 569 cases, the onset was -sudden in 458, and in the remaining 111 examples gradual. It -was noted that only 14·5 per cent. of the male cases were of gradual -onset. But no less than 47·1 per cent. of the female cases developed -after this fashion.</p> - -<p>Again to resume, it is by no means invariably the case that the -onset is <i>nocturnal</i>. For, as Duckworth has pointed out, many -attacks begin during the day, and this is perhaps more often the -case after the disorder is fully established.</p> - -<p><i>Locality.</i>—Gout in its classical form is <i>monarticular</i> in distribution. -In 375 out of 512 <i>initial</i> seizures, Sir Charles Scudamore -found that the metatarso-phalangeal joint of the great toe -of one or other foot was the joint affected. Garrod, too, noted -that, excluding the great toe, in not more than 5 per cent. were -other joints implicated. As to the frequency of incidence in joints -other than the big toe, opinions differ. For Scudamore it is the -ankle, for Garrod the instep, and afterwards the outer side of the -foot and the knee. In contrast, Hilton Fagge holds that next -to the great toe gout vents its initial fury with greatest frequency -upon the <i>metacarpo-phalangeal</i> joint of the index finger, adding, -“certainly not the thumb.” Most authorities however agree that -gout in its early stages rarely attacks the joints of the <i>upper</i> limb, -and even in its most inveterate form the <i>shoulder</i> and <i>hip</i> joints -are immune. Personally, I have never seen a case of gout in the -shoulder or hip; such cases are usually examples of <i>osteo-arthritis</i>.</p> - -<p>Exceptionally, even in first seizures, more than one joint may -be affected. Thus it may migrate from one big toe to its fellow, or -travelling further afield, may invade ankle, knee, wrist, or elbow, -or small joints of hand. W. Gairdner held that in gout the joints -of the <i>left</i> were more commonly attacked than those of the right -limb. But James Lindsay’s figures would appear to indicate precisely -the reverse, viz. a predilection for the <i>right</i> side of the body.</p> - -<p><i>Pain.</i>—If we may accept the lurid imagery of its victims, even -the tortures of the Inquisition failed to transcend in agony the—</p> - -<div class="poetry-container"> -<div class="poetry"> - <div class="stanza"> - <div class="verse indent12">“... pangs arthritic</div> - <div class="verse indent0">that infest the toe of libertine excess.”</div> - </div> - <div class="stanza"> - <div class="verse right"><i>Cowper.</i></div> - </div> -</div> -</div> - -<p><span class="pagenum"><a id="Page_209"></a>[209]</span></p> - -<p>Sydenham said that at its onset the pain was as that of a dislocation -(<i>ossium dislocatio</i>). At its zenith it was as if the flesh -was being gnawed, squeezed in a bootscrew, or scalded by molten -lead or boiling water. Sensory perversions are superadded, and, -as Ambrose Paré said, “some patients say they burn, while -others complain of icy coldness.”</p> - -<p>Its peculiarly exasperating nature is well illustrated by Hosack, -an old time Professor of Medicine of New York, who thus delivered -himself: “Some compare it with the gnawing of a dog, the -pressure of a vice, or the pain of the actual cautery; this probably -is not far from the truth, judging from the anecdote I have heard -of a man subject to gout. This man falling asleep barefooted -before a large fire, the fire fell, and a large coal found its way to -his foot; half awake and half asleep, he cried out: ‘There’s that -d——d gout again!’ He at length awoke, when he found a -large coal frying his great toe. The sensation of the two evils -was probably the same.”</p> - -<p>The pain is aggravated in that frequent “startings” of the limb -prevent the victim keeping the foot at rest. The slamming of a -door, or the incautious shaking of the bed, so quickens its throbbing -intensity as provokes a literal frenzy of rage. But fortunately -it is not always so. For though the pain of gout is unquestionably -severe, at times excruciating, yet it presents infinite grades of -severity. Also one must recollect that but too many of its victims -are already in a high state of irritability before the outbreak. -Moreover, their powers of self-control are too often sapped by -unbridled self-indulgence, and they have but slight reserves of -patience and fortitude to draw upon.<a id="FNanchor_32" href="#Footnote_32" class="fnanchor">[32]</a></p> - -<p>Apart from the personal factor, in <i>subacute</i> cases the pain is -notably less severe than in the <i>acute sthenic</i> form. The pain of gout, -as a rule, is more intense than that of <i>acute rheumatism</i>, and, I fancy, -than that of all other varieties of acute arthritis.<a id="FNanchor_33" href="#Footnote_33" class="fnanchor">[33]</a> Sir Thomas -Watson in his fascinating lectures tells of a witty Frenchman who, -comparing acute gout and acute rheumatism in respect of pain -intensity, remarked: “Screw up the vice as tightly as possible, -you have rheumatism; give it another turn, and that is gout.”</p> - -<p>Lastly, in respect of the duration of the pain, it is not always -true that it wholly <i>intermits</i> at the approach of dawn. It does so -frequently, it is true, but in some instances pain, more or less -severe, continues during the day as well as the night. Occasionally,<span class="pagenum"><a id="Page_210"></a>[210]</span> -on a <i>crescendo</i> scale, it continues increasing almost up to the -crisis. Generally speaking, too, the shorter the duration of the -paroxysm the more intense the pain, and the more prolonged the -less the degree of suffering.</p> - -<p>Following the crisis, the pain gradually becomes less and less, -giving place to a feeling of numbness of the toe, which in older -subjects may endure for some days.</p> - -<p><i>General Phenomena.</i>—Symptoms, other than those referable to -the affected part, vary widely in different cases. In this respect -the acute <i>sthenic</i> forms contrast with the acute <i>asthenic</i> types. In -the former the pulse quickens; the temperature rises, but rarely -exceeds 101°-102°, though Garrod saw it reach 104°. The tongue -is furred, the breath foul, with anorexia and thirst. Though the -appetite is frequently impaired or lost, yet in some instances it is -retained. Dyspeptic symptoms, hiccough, eructations, etc., are -sometimes prominent, but often wholly lacking. The bowels are -constipated, as a rule, the stools pale, or dark and extremely -offensive. The urine is generally scanty, high-coloured, with a -lateritious sediment on cooling. It may contain a trace of -albumen. Severe <i>cramps</i> affecting muscles of the leg, thigh, and -upper parts of the body, are more or less prominent symptoms in -a considerable number of instances.</p> - -<p>The <i>pyrexia</i> appears to be <i>symptomatic</i>, more or less in proportion -to the acuteness of the local phenomena. Comparably the -highest temperatures are usually met with in <i>sthenic</i> forms in -relatively young or robust middle-aged subjects. Duckworth -noted the interesting point that “a preliminary rise is commonly -noted for one, two, three or four days before a joint is actively -involved.” With the articular outbreak the febrile movement -becomes more active. The temperature runs up to 100° or over, -but with the morning abatement sinks to normal or nearly so. -The following evening it rises again frequently to a higher level, -102° with a morning remission, and so it continues for a variable -number of days, it may be only two or eight to ten. It then -subsides, and frequently for a few days remains sub-normal. -Lastly, the <i>acute asthenic</i> forms, that occur often in women -(Garrod), may be wholly <i>afebrile</i>.</p> - -<p><i>Changes in the Blood.</i>—Apart from its increased content of -uric acid, further morbid changes take place in the blood in gout.</p> - -<p>Neusser in 1894 described what he termed “perinuclear basophilic -granules” over and about the nuclei of the leucocytes in -the blood of gouty patients. He held that the dark granules constituted -the mother substance from which uric acid was derived, -and that their presence in the blood was distinctive of the “gouty -diathesis.” Subsequent researches, however, by Futcher and<span class="pagenum"><a id="Page_211"></a>[211]</span> -others appear to have shown the absence of any interrelationship -between the amount of these granules and uric acid elimination, -though Neusser claimed that cases showing them excreted -uric acid in excess.</p> - -<p>More significant, however, is it that the blood in acute gout -may show a high grade <i>leucocytosis</i> with <i>secondary anæmia</i>.</p> - -<p>In a case under my care of <i>acute gout</i> at classic site, though by -no means of unusual severity, the following was the content of the -blood picture:—</p> - -<div class="blockquote"> - -<p class="center"><span class="smcap">Blood Count.</span></p> - -<table> - <tr> - <td>Red corpuscles, per c. mm.</td> - <td class="tdr">3,692,000</td> - <td class="tdc">=</td> - <td class="tdr"><span class="sp2">73·8</span></td> - <td>per cent.</td> - </tr> - <tr> - <td>Hæmoglobin</td> - <td class="tdr"></td> - <td class="tdc"></td> - <td class="tdr"><span class="sp5">80</span></td> - <td class="tdc">”</td> - </tr> - <tr> - <td>Colour index</td> - <td class="tdr"></td> - <td class="tdc"></td> - <td class="tdr">1·08</td> - <td class="tdc">”</td> - </tr> - <tr> - <td>Leucocytes, per c. mm.</td> - <td class="tdr">25,920</td> - <td class="tdc"></td> - <td class="tdr"></td> - <td class="tdc"></td> - </tr> -</table> - -<p class="center"><span class="smcap">Differential Count.</span></p> - -<table> - <tr> - <td>Lymphocytes</td> - <td class="tdr">8·0</td> - <td>per cent.</td> - <td class="tdc">=</td> - <td class="tdr">2,074</td> - <td>per c. mm.</td> - </tr> - <tr> - <td>Large mononuclears</td> - <td class="tdr">3·5</td> - <td class="tdc">”</td> - <td class="tdc">=</td> - <td class="tdr">907</td> - <td class="tdc">”</td> - </tr> - <tr> - <td>Polymorphonuclears</td> - <td class="tdr">87·0</td> - <td class="tdc">”</td> - <td class="tdc">=</td> - <td class="tdr">22,550</td> - <td class="tdc">”</td> - </tr> - <tr> - <td>Eosinophiles</td> - <td class="tdr">0·5</td> - <td class="tdc">”</td> - <td class="tdc">=</td> - <td class="tdr">130</td> - <td class="tdc">”</td> - </tr> - <tr> - <td>Mast cells</td> - <td class="tdr">1·0</td> - <td class="tdc">”</td> - <td class="tdc">=</td> - <td class="tdr">260</td> - <td class="tdc">”</td> - </tr> - <tr> - <td></td> - <td class="tdr bt">100·0</td> - <td></td> - <td></td> - <td></td> - <td></td> - </tr> -</table> - -<p>The salient feature of the blood picture is the high grade <i>leucocytosis</i> of -leucoid type with moderate anæmia—appearances quite compatible with, -and suggestive of, an <i>infective</i> arthritis. To these interesting blood changes -we shall again refer when dealing with the acute polyarticular variety, the -above case being of monarticular type, <i>i.e.</i>, the big toe.</p> - -</div> - -<p><i>Uric Acid Excretion.</i>—If when on a <i>purin-free</i> diet a gouty -subject develops a paroxysm, the curve of uric acid excretion in -the urine is so characteristic as to be almost pathognomonic of -the disorder. As His pointed out, immediately before the onset of -the paroxysm the endogenous uric acid sinks to a lower level -(termed by Umber the <i>anacritical stage of depression</i>). With the -onset of the attack the uric acid content of the urine quickly -increases, to reach its zenith on the second or third day. -F. Pfeiffer, who first noted this point, termed it an <i>uric acid wave</i>. -Subsequently, with the gradual subsidence of the paroxysm, it -again drops into what Umber termed the <i>post-critical stage of -depression</i>. While this curve of endogenous purin excretion may -be modified by oft recurring exacerbations, still Umber holds that -nevertheless it is of decided value in differential diagnosis.</p> - -<p><i>Local Phenomena.</i>—The site and character of the pain having -been dealt with, we now pass on to consider the objective changes -in the affected part. The local <i>engorgement</i> of veins that <i>precedes</i> -the <i>articular</i> outbreak becomes more pronounced, extending -from the vicinity of the painful joint as far as the leg. The overlying<span class="pagenum"><a id="Page_212"></a>[212]</span> -skin of the joint quickly becomes red and tumid. It is not -a bright, but a dark red, the superjacent skin taking on a shining -smoothness that has been compared to the peel of an onion. -Indeed, in its more violent form it resembles but too closely the -ordinary appearance of an <i>abscess</i>, over which the skin is becoming -thin. The redness is not strictly confined to the surface of the -joint, but spreads a little beyond, and where it ceases <i>œdema</i> is -perceptible.</p> - -<p>The redness in its intensity attains its zenith in from twenty-four -to forty-eight hours, and then in hue becomes more violaceous. -On the other hand, the <i>œdema</i> may go on increasing for some -days. At first, owing to tension, the presence of œdema may not -readily be elicited. But with the subsidence of inflammation the -swollen parts readily pit on pressure. It is scarcely possible to -detect <i>intra-articular effusion</i> unless it be the ankle joint that is -involved.</p> - -<p>According to Duckworth, in the more <i>sthenic</i> forms there may -be local <i>ecchymoses</i>. With the crisis the redness, œdema, and -venous turgescence die down. The previously distended skin -becomes wrinkled, and with complete subsidence of inflammation -<i>desquamation</i> ensues. This process is generally attended with -troublesome <i>itching</i>. It is most noticeable about the <i>feet</i> and -<i>hands</i>, but more rare at other sites. Scudamore said that in -seventy-eight out of 234 cases no peeling occurred, but, as Garrod -observed, it may readily be overlooked unless especially sought for.</p> - -<p>The exquisite sensitiveness of the parts, as before noted, gives -way to <i>numbness</i>. The diminished sensibility, coupled with -<i>stiffness</i> of the joint, renders walking difficult for some days, and, -indeed, a month or more may elapse before the joint, even in -favourable cases, recovers its customary mobility.</p> - -<p>In acute <i>asthenic</i> forms great contrasts appear. Pain and -tenderness in the toe may be moderate, but there may be little -local heat or redness and no <i>pyrexia</i>. But <i>œdema</i> is generally in -evidence, and the usual <i>desquamation</i> of skin follows.</p> - -<p><i>Tophus Formation.</i>—To the local changes that mark their -eruption at ab-articular sites we have already alluded. Here we -would only reiterate that their formation <i>follows</i> the local joint -inflammation. Consequently if a few days after the attack local -pain or tenderness, with or without swelling in the vicinity of the -joint, should be complained of, it should not be dismissed as of -no account, but the affected parts should be scrutinised carefully -and, where possible, at short intervals. This in the interests of -diagnosis of a joint affection which may at the time have been of -doubtful nature, more especially if the primary attack occur -elsewhere than at the classical site. Some observations of<span class="pagenum"><a id="Page_213"></a>[213]</span> -Trousseau are well worth quotation: “Physicians who have -watched the progress of the evolution of tophus believe that it is -formed during the paroxysm of gout. They are mistaken: the -deposit appears during the interval between attacks, or at least -when the attacks have not been of long duration, and when they -do not recur in such rapid succession as to run into one another, -in which cases their secretion has commenced during the preceding -and continued during the succeeding attack.”</p> - -<hr class="chap x-ebookmaker-drop"> - -<div class="chapter"> - -<p><span class="pagenum"><a id="Page_214"></a>[214]</span></p> - -<h2 class="nobreak" id="CHAPTER_XVII">CHAPTER XVII<br> -<span class="smaller">CLINICAL ACCOUNT (<i>continued</i>)</span></h2> - -</div> - -<h3><span class="smcap">Acute Generalised Gout</span></h3> - -<p>While gout may throughout its life history confine its ravages -to the <i>foot</i>, if not solely to the <i>toe joints</i>, it may, even in the <i>initial</i> -attack, involve many articulations. Such cases usually, if not -always, occur in persons of marked <i>gouty heredity</i>. In its simplest -forms the orthodox <i>monarticular</i> seizure is simply exchanged for -a sequential implication of each big toe joint. If so, as Trousseau -pointed out, the joint that is the last to be involved is least -affected, and the soonest to get well again, while the accompanying -œdema is of shorter duration. But in more severe cases not -only the big toe, but the <i>tarsal</i> joints, the <i>knee</i> and the <i>hand</i>, -may be invaded in the <i>first</i> attack. Occasionally, too, the disorder -displays concomitantly its tendency to involve other structures, -<i>tendons</i> and <i>aponeuroses</i>, <i>e.g.</i>, the <i>tendo Achillis</i>, <i>plantar fascia</i>. -Such <i>widespread initial involvement</i> is usually preceded by <i>prodromal</i> -phenomena of unusual severity and prolonged duration. -These <i>initial</i> attacks of <i>polyarticular</i> distribution are extremely -rare.</p> - -<p>Far more commonly acute gouty polyarthritis supervenes -after several attacks of classic location have been suffered. The -gouty inflammation in these cases invades the joints after a -serial fashion. But each joint as it becomes involved goes -through the same painful cycle. Thus, for five or six days the -pain goes on increasing, then abates, and finally the wished-for -crisis comes. So it happens that the gout may be raging simultaneously -in several articulations, though in each at different -stages of evolution. Consequently the symptoms do not pursue -an even tenor, but are made up rather of a series of little -attacks—<i>series et catena paroxysmulorum</i>, to invoke Sydenham’s -expression.</p> - -<p>Frequently periods of apparent recovery take place. The -temperature remains normal for some days, and welcome convalescence -seems established, when, to the victim’s despair, the -temperature again rises, and the same weary cycle, though -perhaps shorter, is yet to be endured. Running this chequered -career, the disorder may last for six weeks or two or three months.</p> - -<p><span class="pagenum"><a id="Page_215"></a>[215]</span></p> - -<p>In such attacks not only the <i>feet</i>, <i>knees</i>, <i>hands</i>, and <i>elbows</i>, -may be promiscuously involved, but often also the <i>ligaments</i>, -<i>bursæ</i>, <i>tendon sheaths</i>, and <i>aponeuroses</i>. The suddenness with -which the disorder shifts its seat from one joint to another, or -from joints to bursæ or muscles, often leads to its confusion with -<i>acute rheumatism</i>. In other words, that <i>fixity</i> distinctive of gout -in its monarticular forms is here exchanged for <i>mobility</i>, that -specific quality of acute rheumatism.</p> - -<p>Naturally, the implication of so many varied structures casts -its impress on the clinical picture, inasmuch as the physical -characters vary with the different textures involved, their capacity -for inflammatory distension, etc. On the <i>dorsum</i> of the <i>hand</i> and -<i>foot redness</i> and <i>œdema</i> will be prominent, and Scudamore noted -that the flush might be widely diffused, simulating <i>erysipelas</i>, -with here and there small <i>ecchymoses</i>.</p> - -<p>When structures more deeply placed, <i>i.e.</i>, <i>tendon sheaths</i> at -ankle, knee, and wrist, are singled out for attack, swelling is less -marked and redness of the skin more patchy in distribution. The -<i>bursæ</i> at the elbow or back of the knee may swell with extraordinary -rapidity. The parts become exquisitely tender and -painful, while the overlying skin takes on an angry blush. They -may subside, but more often continue permanently enlarged, -defiant of reduction.</p> - -<p>Involvement of the <i>olecranon bursa</i> is very typical of gout. -Pratt, of Boston (1916), tells of a case in which the subject had -during twenty-seven years suffered from recurring attacks of -<i>acute gouty polyarthritis</i>. The eight or ten physicians who had -treated him had all regarded the disease as <i>rheumatic fever</i>. -Pratt himself observes: “I did not feel sure of the diagnosis until -I saw the swelling on his elbow, which presented the typical -picture of a chronic <i>gouty olecranon bursitis</i>.”<a id="FNanchor_34" href="#Footnote_34" class="fnanchor">[34]</a> Occasionally -the bursæ when filled with uratic deposit undergo <i>suppuration</i> -following injuries. The bursa in connection with the great toe -frequently becomes acutely inflamed, and Scudamore in a gouty -hand saw an old ganglion take on the same inflammatory reaction.</p> - -<p>The tendon sheaths when involved lead to great disablement, -as even the most tentative attempts at movement give rise to -sudden and agonising cramp. The <i>tendo Achillis</i> is a favourite -site, or the tendons of the wrist, or the ligament of the patella. -The same is true of the <i>aponeuroses</i>, the predilection being for -the lumbar or gluteal fascia, in which instance it may extend -to the sheath of the sciatic nerve. These extensions of gout to<span class="pagenum"><a id="Page_216"></a>[216]</span> -tendon and nerve sheaths frequently outlast the articular lesions, -and may become the dominant element in the clinical picture.</p> - -<p>Naturally, when not only joints, but <i>bursæ</i> and other structures, -are involved and implicate both upper and lower limbs, the -victim presents a pitiful spectacle, one of almost complete helplessness. -Œdema and general venous turgescence may be very -pronounced in one or more members, giving a subjective sensation -of almost overwhelming weight in the limb.</p> - -<p>Reverting to the <i>constitutional</i> symptoms, the outstanding -feature is that, notwithstanding the widespread involvement of -joints with manifest local inflammatory reaction, the <i>pyrexia</i> is of -<i>moderate</i> grade, and so frequently, indeed, is it <i>afebrile</i> that this -peculiarity is of diagnostic significance.</p> - -<p><i>Changes in the Blood.</i>—The findings are extremely interesting in -view of the high grades of <i>leucocytosis</i> to be met with both in -<i>pyrexial</i> and <i>apyrexial</i> examples.</p> - -<p>In a case of <i>acute gouty polyarthritis</i> under my care the blood -picture was a very striking one. The patient had suffered from -gout for some eleven years, with recurrent acute exacerbations. -There was widespread involvement of the joints both in upper -and lower limbs. On the dorsum of the mid-phalangeal joints -small semi-solid swellings were present, the exact nature of which -was somewhat puzzling. But inasmuch as the pinna in both ears -was studded with <i>tophi</i>, this seemed to provide a clue. The -auricular tophi were verified microscopically. The extra-articular -phalangeal swellings were then aspirated with a hypodermic -syringe. A turbid straw-coloured fluid issued, which -microscopically was found to contain <i>biurate</i> crystals. His -temperature rose nightly from 101° up to 102° F., with morning -remissions. The left knee and wrist were the seat of <i>effusion</i>, -and some of the small finger joints were inflamed.</p> - -<p class="center"><span class="smcap">Blood Count.</span></p> - -<table> - <tr> - <td>Red corpuscles, per c. mm.</td> - <td class="tdr">4,432,000</td> - <td class="tdc">=</td> - <td class="tdr"><span class="sp2">88·6</span></td> - <td>per cent.</td> - </tr> - <tr> - <td>Hæmoglobin</td> - <td class="tdr"></td> - <td class="tdc"></td> - <td class="tdr"><span class="sp5">60</span></td> - <td class="tdc">”</td> - </tr> - <tr> - <td>Colour index</td> - <td class="tdr"></td> - <td class="tdc"></td> - <td class="tdr">·68</td> - <td class="tdc">”</td> - </tr> - <tr> - <td>Leucocytes, per c. mm.</td> - <td class="tdr">27,200</td> - <td class="tdc"></td> - <td class="tdr"></td> - <td class="tdc"></td> - </tr> -</table> - -<p class="center"><span class="smcap">Differential Count.</span></p> - -<table> - <tr> - <td>Lymphocytes</td> - <td class="tdr">9</td> - <td class="tdc">=</td> - <td class="tdr">2,450</td> - </tr> - <tr> - <td>Large mononuclears</td> - <td class="tdr">13</td> - <td class="tdc">=</td> - <td class="tdr">3,540</td> - </tr> - <tr> - <td>Polymorphonuclears</td> - <td class="tdr">78</td> - <td class="tdc">=</td> - <td class="tdr">21,220</td> - </tr> - <tr> - <td>Eosinophiles</td> - <td class="tdr">0</td> - <td class="tdc">=</td> - <td class="tdr">0</td> - </tr> - <tr> - <td>Mast cells</td> - <td class="tdr">0</td> - <td class="tdc">=</td> - <td class="tdr">0</td> - </tr> - <tr> - <td></td> - <td class="tdr bt">100·0</td> - <td class="tdc"></td> - <td class="tdr"></td> - </tr> -</table> - -<p><span class="pagenum"><a id="Page_217"></a>[217]</span></p> - -<p>The left knee joint was aspirated by Dr. Munro. A clear fluid -of straw yellow tint was withdrawn, which yielded some fibrin on -standing. The cytological examination gave the following -results:—</p> - -<p class="center"><span class="smcap">Total Count.</span></p> - -<table> - <tr> - <td>44,800 per c. mm. (nearly all leucocytes).</td> - </tr> -</table> - -<p class="center"><span class="smcap">Differential Count.</span></p> - -<table> - <tr> - <td>Polymorphonuclears</td> - <td class="tdr">92</td> - </tr> - <tr> - <td>Lymphocytes</td> - <td class="tdr">7</td> - </tr> - <tr> - <td>Large mononuclears</td> - <td class="tdr">1</td> - </tr> - <tr> - <td>Eosinophiles</td> - <td class="tdr">0</td> - </tr> - <tr> - <td>Basophiles</td> - <td class="tdr">0</td> - </tr> - <tr> - <td></td> - <td class="tdr bt">100</td> - </tr> -</table> - -<p>Attempts at culture on broth and agar proved <i>sterile</i>. In -addition three separate blood cultures, taken at intervals of a few -days, on agar slopes and broth, all gave <i>negative</i> results.</p> - -<p>In another instance of <i>polyarticular</i> distribution the subject -was seen during the <i>inter-paroxysmal</i> period. He displayed -auricular <i>tophi</i>, the crystalline content of which was verified -microscopically.</p> - -<p class="center"><span class="smcap">Blood Count.</span></p> - -<table> - <tr> - <td>Red corpuscles, per c. mm.</td> - <td class="tdr">5,732,000</td> - <td class="tdc">=</td> - <td class="tdr"><span class="sp2">194·6</span></td> - <td class="tdr">per cent.</td> - </tr> - <tr> - <td>Hæmoglobin</td> - <td class="tdr"></td> - <td class="tdc"></td> - <td class="tdr"><span class="sp5">65</span></td> - <td class="tdc">”</td> - </tr> - <tr> - <td>Colour index</td> - <td class="tdr"></td> - <td class="tdc"></td> - <td class="tdr">·57</td> - <td class="tdc">”</td> - </tr> - <tr> - <td>Leucocytes, per c. mm.</td> - <td class="tdr">13,200</td> - <td class="tdc"></td> - <td class="tdr"></td> - <td class="tdc"></td> - </tr> -</table> - -<p class="center"><span class="smcap">Differential Count.</span></p> - -<table> - <tr> - <td>Lymphocytes</td> - <td class="tdr"><span class="sp3">34</span></td> - <td class="tdc">=</td> - <td class="tdr">4,490</td> - </tr> - <tr> - <td>Large mononuclears</td> - <td class="tdr"><span class="sp3">3</span></td> - <td class="tdc">=</td> - <td class="tdr">400</td> - </tr> - <tr> - <td>Polymorphonuclears</td> - <td class="tdr">61·5</td> - <td class="tdc">=</td> - <td class="tdr">8,120</td> - </tr> - <tr> - <td>Eosinophiles</td> - <td class="tdr">·1</td> - <td class="tdc">=</td> - <td class="tdr">130</td> - </tr> - <tr> - <td>Mast cells</td> - <td class="tdr">·5</td> - <td class="tdc">=</td> - <td class="tdr">66</td> - </tr> -</table> - -<p>Chalmers Watson some years previously investigated the blood -in cases of <i>acute gouty polyarthritis</i> both during an exacerbation and -in the <i>inter-paroxysmal</i> period. His findings were as follows:—</p> - -<p>During the <i>attack</i> the films showed very marked <i>leucocytosis</i>. -Also there was present a large number of peculiar myelocyte-like -cells, these more than half as numerous as the ordinary finely -granular oxyphil leucocytes.</p> - -<div class="blockquote"> - -<p>“Each of these cells contained a large oval or horse-shaped nucleus, -poor in chromatin. The nucleus occupied about half of the total area of -the cell. It did not stain uniformly, and it was usually situated to one -side, coming right up to the cell outline, and occupying from a third to a -half of the total circumference. In many of these cells the nucleus was -almost round, with but one slight indentation; in others the indentation -was pronounced. The whole cell stained a pale blue, presented a degenerated -appearance, and contrasted markedly with the ordinary leucocyte<span class="pagenum"><a id="Page_218"></a>[218]</span> -seen in the same film, with its brilliant blue nucleus and bright red eosinophil -granules. The special cells under description were also remarkable for -their size, measuring about 15 m. in diameter, a few being smaller, -about 10 m. Some of them contained vacuoles in the cytoplasm. The -general appearance of these cells suggested exhaustion in so far as the -cytoplasm did not contain the typical fine oxyphil granules characteristic -of the myelocyte. From the character of the nucleus and cytoplasm, they -were undoubtedly distinct from lymphocytes. The large lymphocytes -were scarce; small lymphocytes were numerous. True eosinophil cells -were also scarce. The main bulk of the leucocytes consisted of the ordinary -finely granular oxyphil leucocytes and the peculiar myelocyte cells -described.</p> - -<p>“<i>Blood plates.</i>—Some of the blood-plates were large (4 m. in diameter), -and often formed very irregular torn-looking masses. The red cells were -apparently normal.”</p> - -</div> - -<p>Shortly after Chalmers Watson, Bain published his results of -blood examination in <i>acute gouty polyarthritis</i>. He also noted -the presence of a distinct <i>leucocytosis</i>. A differential count disclosed -a marked increase of the eosinophil cells, and he adds: -“There was present a moderate number of the peculiar myelocyte-like -cells originally described by Chalmers Watson.”</p> - -<p>Dr. Munro, though he carefully examined the gouty blood -films to this end, was unable to identify the myelocyte-like cells -noted by these observers.</p> - -<p>Recently, through the kindness of my colleague Dr. Waterhouse, -Dr. Munro and I had again an opportunity of examining -the blood in a case of this kind during the <i>inter-paroxysmal</i> period. -The subject, a male, had had repeated attacks at the classic site, -with subsequent extension to other joints. Multiple tophi were -present in both ears, and the crystals of uric acid were demonstrated -microscopically.</p> - -<p class="center"><span class="smcap">Blood Count.</span></p> - -<table> - <tr> - <td>Red corpuscles</td> - <td class="tdr">7,364,000</td> - <td class="tdc">=</td> - <td class="tdr"><span class="sp3">147</span></td> - <td>per cent.</td> - </tr> - <tr> - <td>Hæmoglobin</td> - <td class="tdr"></td> - <td class="tdc"></td> - <td class="tdr"><span class="sp3">74</span></td> - <td class="tdc">”</td> - </tr> - <tr> - <td>Coloured index</td> - <td class="tdr"></td> - <td class="tdc"></td> - <td class="tdr">0·5</td> - <td class="tdc">”</td> - </tr> - <tr> - <td>Leucocytes</td> - <td class="tdr">21,400</td> - <td class="tdc"></td> - <td class="tdr"></td> - <td class="tdc"></td> - </tr> -</table> - -<p class="center"><span class="smcap">Differential Count.</span></p> - -<table> - <tr> - <td>Lymphocytes</td> - <td class="tdr">28·5</td> - <td>per cent.</td> - <td class="tdc">=</td> - <td class="tdr">6,099</td> - <td>per c. mm.</td> - </tr> - <tr> - <td>Large mononuclears</td> - <td class="tdr">2·5</td> - <td class="tdc">”</td> - <td class="tdc">=</td> - <td class="tdr">535</td> - <td class="tdc">”</td> - </tr> - <tr> - <td>Polymorphonuclears</td> - <td class="tdr"><span class="sp3">64</span></td> - <td class="tdc">”</td> - <td class="tdc">=</td> - <td class="tdr">13,696</td> - <td class="tdc">”</td> - </tr> - <tr> - <td>Eosinophiles</td> - <td class="tdr">3·5</td> - <td class="tdc">”</td> - <td class="tdc">=</td> - <td class="tdr">749</td> - <td class="tdc">”</td> - </tr> - <tr> - <td>Basophiles</td> - <td class="tdr">1·5</td> - <td class="tdc">”</td> - <td class="tdc">=</td> - <td class="tdr">321</td> - <td class="tdc">”</td> - </tr> -</table> - -<p>The blood picture, it will be seen, is one of erythræmia—a -marked leucocytosis, a normal differential percentage count, -pronounced secondary anæmia.</p> - -<p>Da Costa also notes, in a case of gout, erythræmia (7,125,000) -with a leucocyte count of 14,000. Ewing, too, records an instance<span class="pagenum"><a id="Page_219"></a>[219]</span> -of chronic gout with huge tophi, seen in an acute exacerbation, in -which the blood gave a leucocyte count of 21,000 with 70 per cent. -hæmoglobin. In another severe instance of subacute type the -same observer again met with leucocytosis (15,000).</p> - -<p>In regard to these interesting blood findings, it is to be cordially -hoped that as the somewhat rare opportunities occur they will be -taken full advantage of.</p> - -<p>As to the other general clinical features the <i>nervous</i> system, -as might be expected, is often greatly perturbed, and the mental -distress and anxiety in some instances appear to cause even more -irritation than the bodily pain. Febrile movement when present -accords with that observed in <i>monarticular</i> sites, save only in the -tendency to <i>relapses</i>. Sweating is not a common feature, as in -<i>acute rheumatism</i>. Neither does acute <i>endocarditis</i> occur in gout. -On the other hand, as this acute polyarticular form may recur -throughout years, it may in its later stages be complicated by -<i>nephritis</i>.</p> - -<p>Furthermore, in its differentiation from acute rheumatism the -more advanced age of the sufferer, always over thirty-five and -more often nearer fifty or over, will be of help. The presence of -an hereditary taint, the nature of the occupation and personal -habits, and more pertinently the history of a classical attack in the -great toe, may give a clue.</p> - -<p>But in this, as in all other varieties of gouty arthritis, the one -and only unequivocal objective proof of the nature of the disorder -is the <i>presence of tophi</i>. Lamentable indeed is the frequency -with which this fact is forgotten, to our confounding and the -patient’s detriment. As Hilton Fagge, discussing the diagnosis of -gout, long since observed: “All those parts which are apt to be -the seat of tophi should be examined. If a single deposit of urate -of soda can be found it settles the question.”</p> - -<p>In conclusion, before passing to consideration of <i>chronic articular -gout</i>, it will be convenient here to discuss certain <i>concomitant -phenomena</i> of the acute types. We refer to the muscular and -nerve forms of fibrositis, which, we hasten to add, are of common -occurrence also in the chronic types of articular gout.</p> - -<h3><span class="smcap">Collateral Phenomena of Gout</span></h3> - -<p>The liability of acute articular gout to be complicated by -<i>muscular</i> and <i>nerve</i> disorders has already been briefly alluded to. -Also it was pointed out that in respect of this tendency gout -displayed an analogy with the <i>specific</i> infections, viz., in that these -latter too are prone not only to arthritic, but to muscular and -nerve, lesions also.</p> - -<p>Our forefathers, greatly exercised by this apparent overlapping<span class="pagenum"><a id="Page_220"></a>[220]</span> -of “gout” and “rheumatism,” in their efforts at discrimination -drew fanciful contrasts between the subjective sensations produced -by gout and rheumatism, but all to no end, for said -Heberden, “It must be owned that there are cases in which the -criteria of both are so blended together that it is not easy to -determine whether the pain be gout or rheumatism.”</p> - -<p>Gradually, however, a change in attitude made itself felt. It -became no longer customary to regard such examples as blends of -gout and “rheumatism,” but to hold the <i>muscular</i> and <i>nerve</i> -disorders as also attributable to the underlying gout. Thus, so -impressed was Garrod with the frequency of the incidence of -<i>lumbago</i> and <i>sciatica</i> in <i>gouty</i> subjects that he was doubtful as to -whether they ought to have been classed by him as among the -“diseases to which gouty persons are particularly liable.” He -thought “they might perhaps have been properly classed among -the forms of <i>irregular</i> gout.”</p> - -<p>Duckworth, again, felt sure “that much so-called ‘muscular’ -rheumatism is really gouty,” and forthwith ranked its manifestations -among the <i>irregular</i> forms of gout. Hilton Fagge was likewise -convinced that the muscular types of fibrositis are frequently -and obviously related to gout; while Sir William Gowers, discussing -this same muscular fibrositis, is even more explicit: “It -is currently associated with gout, and the truth of the belief is soon -impressed upon the practitioner. But it is gout with a difference: -it may occur in those who are gouty in the common sense of the -word, but some of the most severe cases I have seen, especially -the brachial form, have been in those who have inherited a tendency -to gout, but have not merited its development.”</p> - -<p>Turning to the <i>nerve</i> manifestations, Charcot long since pointed -out that gout and sciatica might co-exist, while Gowers is insistent -that “underlying most cases of sciatica is either the state -of definite gout, or that ‘rheumatic diathesis’ in which the -fibrous tissues suffer, especially those that are connected with the -muscles, a form closely connected with common gout by co-existence -or descent.”</p> - -<p>As to my own opinion, I have, in collaboration with Bassett -Jones, discussed in detail this relationship of gout to fibrositis in -our monograph on the latter disorder, and I shall largely transcribe -our remarks therein on this vexed point.</p> - -<p>Of all the conditions reputed to be etiologically related to -fibrositis, in none of them is the connection more obvious or more -easily traceable than between this affection and <i>gout</i>. Whether -or no the hyperplasia of the connective tissues be directly due to -the gouty toxin must perforce for the present remain uncertain. -But there is no doubt as to the relatively frequent incidence of<span class="pagenum"><a id="Page_221"></a>[221]</span> -fibrositis in “gouty” subjects. It is as true to-day as when -Scudamore wrote it that occasionally “a patient when he has gout -in the regular situations suffers, in consequence of some partial -exposure to cold, a rheumatism in other parts, as in the muscles -of the neck, or in the shoulder joints; and a seizure of lumbago -at the time of the invasion of the gout is also not uncommon.”</p> - -<p>Apart from the <i>simultaneous</i> incidence of gout and <i>fibrositis</i> -in the same subject, it is equally certain that the victims of a -“gouty” heritage are unusually prone to develop fibrositis.</p> - -<p>Thus, in a series of 1,000 cases hereditary or acquired gout was -present in no less than 281—viz., a percentage incidence of 28·1. -While this taint was more in evidence in fibrositis of the joints, -it obtained appreciably in regard to all muscular types of the -affection, more especially <i>lumbago</i>, its influence also being very -obvious in the case of <i>sciatica</i> and other types of nerve sheath -involvement.</p> - -<p>In light of this, we must admit being somewhat nonplussed -by those who confidently affirm that “gout” plays little or no -part in the production of “fibrositis.” Speaking from an extensive -experience, we confidently believe the reverse is the case, and -that the <i>gouty</i> element is but too frequently overlooked in examples -of this affection.</p> - -<p>Approaching another aspect of this vexed question of the -relationship of gout, what of the ambiguous attitude of those -who, while denying it any share in the causation of <i>lumbago</i> and -other types of <i>muscular</i> fibrositis, yet at the same time attribute -to gout an important etiological <i>rôle</i> in the allied conditions -<i>sciatica</i> and <i>brachialgia</i>?</p> - -<p>Thus, they maintain that the fleeting attacks of lumbar fibrositis -or lumbago which ensue after dietetic indiscretions have no -relation to gout, but are simply indicative of some digestive -disability on the part of the individual for certain articles of diet. -Hardly to our mind a satisfactory mode of differentiation; -much less can it be held to put out of court the influence of <i>gout</i>. -For are not the gouty precisely the very persons who display this -inability to cope satisfactorily with unusual or excessive meals? -Hence the frequency with which in their instance attacks of -lumbar fibrositis, often transient, almost invariably ensue when -any unwonted excess of purin-containing food has to be disposed -of, and especially when at the same time katabolic changes have -been stimulated in the body by the ingestion of alcohol, not -necessarily excessive in amount.</p> - -<p>That the <i>lumbar</i> regions should have been singled out is the more -remarkable, for, if there be one form of fibrositis more than -another prone to be associated with gout, it is precisely <i>lumbago</i>.</p> - -<p><span class="pagenum"><a id="Page_222"></a>[222]</span></p> - -<p>Our difficulty, moreover, in appreciating the cogency of this -plea for excluding the influence of gout in muscular fibrositis -is the more accentuated in that those who advocate it claim that -this very gout is the salient etiological factor in <i>sciatica</i> and -<i>brachialgia</i>.</p> - -<p>This position is untenable, and for the following reasons: the -pathological lesion in both instances is the same—viz., <i>fibrositis</i>; -in lumbago and deltoid rheumatism it implicates the sheaths -and interstitial tissues of the <i>muscles</i>, in sciatica and brachialgia -the similar investments of the <i>nerves</i>.</p> - -<p>Strictly speaking, therefore, any differentiation that we can -effect between muscular and neuralgic types of fibrositis is -perforce merely <i>topographical</i>. To draw <i>etiological</i> distinctions -is well-nigh impossible, for the very continuity of the fibrous -tissues favours the passage of one type into the other. Hence -clinically we find that the bulk of our cases of sciatica are preceded -by lumbago, and similarly many cases of brachial neuralgia or -neuritis develop by extension out of a pre-existing deltoid -fibrositis.</p> - -<p>In light of such transitions of <i>muscular</i> into <i>neuralgic</i> types of -fibrositis, it seems inconsistent to postulate a gouty origin for -the latter and at the same time to deny it any share in the -production of the former. For ourselves, we fully recognise gout -as the most potent predisposing factor in sciatica and brachialgia, -and <i>ergo</i> in the closely associated and often antecedent muscular -types of fibrositis.</p> - -<p>While insisting on the importance of gout as a <i>predisposing</i> -factor in <i>fibrositis</i>, we feel called upon to emphasise the fact that -we are not sheltering ourselves under that nebulous term “latent” -gout, for our contention is based on the ground that in the vast -majority of the cases for which we claim a gouty origin -unequivocal proofs of gout, such as <i>tophi</i>, etc., were present.</p> - -<h3><span class="smcap">Incidence of Gouty Stigmata in Various Types of Fibrositis</span></h3> - -<p>Out of 343 instances of fibrositis of the <i>joints</i> such stigmata -of gout were present in 118 males and nine females. Of <i>muscular</i> -types, taking as our example <i>lumbago</i>, we find that out of -twenty-seven examples no less than ten displayed definite -evidences of a gouty taint. Similarly, out of thirty-eight cases -of lumbago complicated by other manifestations of fibrositis -eleven males and one female were of gouty habit. Also in -twenty-three cases of lumbago associated with arthritic -fibrositis six males, but no females, displayed the same<span class="pagenum"><a id="Page_223"></a>[223]</span> -proclivity. Lastly, out of thirty-eight cases of lumbago -complicated by right or left sciatica ten were of the same -diathesis.</p> - -<p>Passing in turn to consider this same factor in relation to -<i>sciatica</i>, we note that out of 142 examples twenty-four men and -three women were gouty. Occasionally, too, apart from <i>glycosuria</i>, -it appears to be responsible for bilateral sciatic pains, for -in three examples of this nature gout was present.</p> - -<p>James Taylor is also very definite on this point, that, glycosuria -aside, affections of individual peripheral nerves occur frequently -in the gouty. There is little doubt, he says, that sciatica is -“frequently present in the gouty and is sometimes directly due -to that state.” While admitting that in many, if not most, cases -of sciatica there are associated arthritic changes in the <i>hip joint</i>, -he yet affirms his belief that “there are some in which the neuritis -is a primary condition.”</p> - -<p>With this statement my own experience accords, but with a -reservation, viz., that the <i>sciatic neuritis</i> is apparently <i>secondary</i> -to a lumbar or <i>gluteal fibrositis</i>, with sequential involvement of -the <i>sciatic nerve sheath</i> and extension to the nerve trunk.</p> - -<p>Taylor holds also that <i>anterior crural</i> and <i>brachial neuritis</i> -may be directly due to <i>gout</i>. As to brachial neuritis, he says: -“I have known it occur apart from any recognisable arthritic -change in a patient who was the subject of gout.”</p> - -<p>Having regard to the flippant manner in which the term -“neuritis” is but too frequently bandied about, it is refreshing -to note that in all Dr. Taylor’s cases “the existence of the -neuritis” was shown “by the tenderness of the nerve trunks, -the spontaneous, often severe, pain, and atrophic changes both -in the skin and the muscles—the glossy skin and atrophied -muscles.”</p> - -<p>As for the involvement of other nerves, trigeminal neuralgia -is held to be the most common; but, for myself, I have never felt -justified in claiming any such example as gouty. Nor am I -satisfied that persons of gouty habit are more prone than others -to attacks of migraine.</p> - -<p>Lastly, I cannot confirm out of my own experience -Duckworth’s statement that “<i>herpetic</i> attacks in all varieties of -‘gout’ are common.” Nor have I seen <i>shingles</i> co-exist with -acute gout, neither have I come across any examples of so-called -<i>gouty spinal meningitis</i>!</p> - -<p>In conclusion, I would submit that:—</p> - -<div class="blockquote"> - -<p>(1) Acute articular gout is not infrequently complicated by -fibrositis.</p> - -<p>(2) The same infection that determines the articular outbreak<span class="pagenum"><a id="Page_224"></a>[224]</span> -is responsible for the concomitant muscular and nerve -phenomena.</p> - -<p>(3) Persons of gouty heritage are especially liable to fibrositis, -notably <i>lumbago</i> and <i>sciatica</i>.</p> - -<p>(4) Gout predisposes to fibrositis in that the inherent pathological -attributes of gouty tissues favour the incidence of -<i>infection</i>.</p> - -</div> - -<p>In regard of this last postulate, it is well known that <i>gouty</i> -persons who contract <i>gonorrhœa</i> are more prone than the <i>non-gouty</i> -to develop <i>gonorrhœal rheumatism</i>, in other words, to -sustain a widespread infection involving the fibrous tissues, not -only of the joints, but of the muscles and even of the nerve -sheaths. With this concrete example to hand, is it not reasonable -to suppose that such a constitutional taint will favour the -incidence also of other infections or sub-infections, and that -this may explain the relative frequency of fibrositis, not only -in the actually gouty, but in those of gouty heritage, this the -more cogently having regard to the fact that so much exact -evidence is forthcoming in favour of local infection as the cause -of all types of fibrositis?</p> - -<hr class="chap x-ebookmaker-drop"> - -<div class="chapter"> - -<p><span class="pagenum"><a id="Page_225"></a>[225]</span></p> - -<h2 class="nobreak" id="CHAPTER_XVIII">CHAPTER XVIII<br> -<span class="smaller">CLINICAL ACCOUNT (<i>continued</i>)</span></h2> - -</div> - -<h3><span class="smcap">Chronic Articular Gout</span></h3> - -<p>In delineating the features of the <i>acute polyarticular</i> variety, -we have to a certain extent trenched on the clinical territory of -the <i>chronic</i> form; this is scarcely avoidable, inasmuch as the line -drawn between acute and chronic gout is purely arbitrary. Thus -one authority remarks of acute gout: “If the disease continue -beyond three or four weeks, it is to be considered as persistent -or chronic” (Flint). Trousseau, again, discussing the acute -variety, more particularly the acute polyarticular type, states -that it “may last for some weeks, or even for three months,” -adding: “Should it extend beyond that period, it is no longer -acute gout; it is chronic gout.”</p> - -<p>The truth is that articular gout in this respect is very prone -to vagaries. Thus, in rare instances an attack of <i>acute</i> or <i>sub-acute</i> -gout, more particularly the latter, may merge without break -into the <i>chronic</i> form of the disease.<a id="FNanchor_35" href="#Footnote_35" class="fnanchor">[35]</a> Far more commonly the -tragedy is more slowly played out. The unfortunate victim, after -passing through several more or less classical attacks, finds that -the intervals become shorter and shorter until they merge, as it -were, one into the other. Fortunately its course is not one of -continuous uniform severity. <i>Remissions</i>, but not complete -<i>intermissions</i>, occur, and every now and again intercurrent acute -attacks take place.</p> - -<p>But, the reader may observe, surely this is very reminiscent -of <i>acute gouty polyarthritis</i>, with its serial content of acute -paroxysms?<a id="FNanchor_36" href="#Footnote_36" class="fnanchor">[36]</a> Quite so; but there is this difference, that, -although such may last six weeks or three months, still there is a -period put to the sufferings. A respite of months or years of -immunity, and relative health may then supervene.</p> - -<p>Not so, unfortunately, when such paroxysmal waves sweep over -the subject of long-standing or <i>chronic gout</i>. Not only do the<span class="pagenum"><a id="Page_226"></a>[226]</span> -recurrent acute outbreaks occur with <i>increasing frequency</i>, but also -with <i>increasing length of duration</i>. It is here no longer a question -of the intercurrent acute attack lasting days, but <i>weeks</i>. Also -during such exacerbations either four, five, or six joints are -simultaneously attacked, or in such rapid sequence that before -one joint is free another is involved.</p> - -<p>But a word here as to the variations in <i>distribution</i> of the -<i>articular lesions</i> in <i>chronic gout</i>. The well-marked <i>penchant</i> of -<i>acute</i> gout for the <i>great toe</i> continues throughout the life history -of the disorder, the predilection for this site being equally a -characteristic of the <i>chronic</i> type. As to the subsequent articular -involvement, Garrod held the sequence to be as follows: <i>heels</i>; -<i>ankles</i>; <i>knees</i>; the smaller articulations of the <i>hands</i>; lastly, the -<i>shoulders</i> and <i>hips</i>. It has never been my lot to see either the -shoulders or hips involved; but I have seen <i>osteo-arthritis</i> of the -<i>hip</i> in <i>men</i> displaying <i>auricular tophi</i>, and I am inclined to think -that, in the presence of the latter, it has sometimes been assumed -that the hip mischief was of <i>gouty</i> nature—the “hip gout” of the -older authors.</p> - -<p>Moreover, the <i>order of sequence</i> is by no means invariable, for -oftentimes a local circumstance, <i>i.e.</i>, <i>injury</i> or <i>sprain</i>, determines -the location. Again, chronic gout is very erratic in respect of the -<i>number</i> of joints implicated. In some almost all the joints may -be affected, while in others, no matter how ancient the disorder -and how oft its recurrence, it remains localised to but a few joints; -or it may progress after a leisurely fashion, with each attack -invading different joints in succession.</p> - -<p>Naturally, if the disorder confine itself to a few joints, and -these, and these alone, are the seat of the oft-recurring attacks, -permanent changes sooner or later make their appearance. Nor -are the morbid effects limited to the joints, but they invade the -continuity of the limb, for the oft-repeated inflammatory reactions -lead to engorgements of persistent nature. The contour of the -affected members is distorted by the œdematous tumefaction, -which, more pronounced at the level of the joints, extends in -lesser degree beyond their confines. The skin, too, especially over -the fingers, undergoes a change in texture, often becomes smooth -and glossy, and through its dusky pink subjacent uratic deposits -may be discerned.</p> - -<p>Old gouty subjects are often of sallow or parchment-like -complexion. The <i>blood</i> in these cases of polyarticular gout conforms -in attenuated degree, in the matter of leucocytosis and -secondary anæmia, to that observed in the more <i>acute</i> types, as -witness the following blood pictures.</p> - -<p>All were males, the subjects of chronic articular gout of many<span class="pagenum"><a id="Page_227"></a>[227]</span> -years’ standing. They all exhibited <i>tophi</i>, which were verified -microscopically. The examinations were conducted during the -inter-paroxysmal periods.</p> - -<p class="center">(1) <span class="smcap">Blood Count.</span></p> - -<table> - <tr> - <td>Red corpuscles, per c. mm.</td> - <td class="tdr">4,832,000</td> - <td class="tdc">=</td> - <td class="tdr"><span class="sp2">96·6</span></td> - <td>per cent.</td> - </tr> - <tr> - <td>Hæmoglobin</td> - <td class="tdr"></td> - <td class="tdc">=</td> - <td class="tdr"><span class="sp5">64</span></td> - <td class="tdc">”</td> - </tr> - <tr> - <td>Colour index</td> - <td class="tdr"></td> - <td class="tdc">=</td> - <td class="tdr">·66</td> - <td class="tdc">”</td> - </tr> - <tr> - <td>Leucocytes, per c. mm.</td> - <td class="tdr">11,000</td> - <td class="tdc"></td> - <td class="tdr"></td> - <td class="tdc"></td> - </tr> -</table> - -<p class="center"><span class="smcap">Differential Count.</span></p> - -<table> - <tr> - <td>Lymphocytes</td> - <td class="tdr"><span class="sp3">42</span></td> - <td class="tdc">=</td> - <td class="tdr">4,620</td> - </tr> - <tr> - <td>Large mononuclears</td> - <td class="tdr"><span class="sp3">4</span></td> - <td class="tdc">=</td> - <td class="tdr">440</td> - </tr> - <tr> - <td>Polymorphonuclears</td> - <td class="tdr">52·5</td> - <td class="tdc">=</td> - <td class="tdr">5,775</td> - </tr> - <tr> - <td>Eosinophils</td> - <td class="tdr"><span class="sp3">0</span></td> - <td class="tdc">=</td> - <td class="tdr">0</td> - </tr> - <tr> - <td>Mast cells</td> - <td class="tdr">1·5</td> - <td class="tdc">=</td> - <td class="tdr">165</td> - </tr> -</table> - -<p class="center">(2) <span class="smcap">Blood Count.</span></p> - -<table> - <tr> - <td>Red corpuscles, per c. mm.</td> - <td class="tdr">5,040,000</td> - <td class="tdc">=</td> - <td class="tdr"><span class="sp2">100·8</span></td> - <td>per cent.</td> - </tr> - <tr> - <td>Hæmoglobin</td> - <td class="tdr"></td> - <td class="tdc">=</td> - <td class="tdr"><span class="sp5">72</span></td> - <td class="tdc">”</td> - </tr> - <tr> - <td>Colour index</td> - <td class="tdr"></td> - <td class="tdc">=</td> - <td class="tdr">0·72</td> - <td class="tdc">”</td> - </tr> - <tr> - <td>Leucocytes, per c. mm.</td> - <td class="tdr">13,400</td> - <td class="tdc"></td> - <td class="tdr"></td> - <td class="tdc"></td> - </tr> -</table> - -<p class="center"><span class="smcap">Differential Count.</span></p> - -<table> - <tr> - <td>Lymphocytes</td> - <td class="tdr"><span class="sp2">15</span></td> - <td class="tdc">=</td> - <td class="tdr">2,010</td> - </tr> - <tr> - <td>Large mononuclears</td> - <td class="tdr">2·5</td> - <td class="tdc">=</td> - <td class="tdr">335</td> - </tr> - <tr> - <td>Polymorphonuclears</td> - <td class="tdr"><span class="sp2">78</span></td> - <td class="tdc">=</td> - <td class="tdr">10,452</td> - </tr> - <tr> - <td>Eosinophils</td> - <td class="tdr"><span class="sp2">1</span></td> - <td class="tdc">=</td> - <td class="tdr">134</td> - </tr> - <tr> - <td>Mast cells</td> - <td class="tdr">3·5</td> - <td class="tdc">=</td> - <td class="tdr">469</td> - </tr> -</table> - -<p class="center">(3) <span class="smcap">Blood Count.</span></p> - -<table> - <tr> - <td>Red corpuscles, per c. mm.</td> - <td class="tdr">4,280,000</td> - <td class="tdc">=</td> - <td class="tdr"><span class="sp2">85·6</span></td> - <td>per cent.</td> - </tr> - <tr> - <td>Hæmoglobin</td> - <td class="tdr"></td> - <td class="tdc">=</td> - <td class="tdr"><span class="sp5">66</span></td> - <td class="tdc">”</td> - </tr> - <tr> - <td>Colour index</td> - <td class="tdr"></td> - <td class="tdc">=</td> - <td class="tdr">0·77</td> - <td class="tdc">”</td> - </tr> - <tr> - <td>Leucocytes, per c. mm.</td> - <td class="tdr">12,000</td> - <td class="tdc"></td> - <td class="tdr"></td> - <td class="tdc"></td> - </tr> -</table> - -<p class="center"><span class="smcap">Differential Count.</span></p> - -<table> - <tr> - <td>Lymphocytes</td> - <td class="tdr">23</td> - <td class="tdc">=</td> - <td class="tdr">2,760</td> - </tr> - <tr> - <td>Large mononuclears</td> - <td class="tdr">3</td> - <td class="tdc">=</td> - <td class="tdr">360</td> - </tr> - <tr> - <td>Polymorphonuclears</td> - <td class="tdr">74</td> - <td class="tdc">=</td> - <td class="tdr">8,880</td> - </tr> - <tr> - <td>Eosinophils</td> - <td class="tdr">0</td> - <td class="tdc">=</td> - <td class="tdr">0</td> - </tr> - <tr> - <td>Mast cells</td> - <td class="tdr">0</td> - <td class="tdc">=</td> - <td class="tdr">0</td> - </tr> -</table> - -<p>In these chronic forms, save during exacerbations, there may -be little or no febrile movement, and local pain, heat, and redness -may be slight or wholly lacking. But the articular swellings never -wholly disappear, and the mobility of the joints is never entirely -regained. The articulations, few or many, become stiff, ankylosed, -and deformed, by the growth of <i>tophaceous deposits</i>. But -to detailed description of these latter we shall return later.</p> - -<p>In inveterate cases of this nature the victim grows more and -more crippled and infirm, the inroads of the disease upon the -constitution more and more palpable. Pelion is heaped upon<span class="pagenum"><a id="Page_228"></a>[228]</span> -Ossa, as one ailment sets in after another, now of the digestive -organs, now of the heart, or of the kidneys. These subjects of -chronic gout are more often than not dyspeptic, show signs of -<i>arterio-sclerosis</i>. Their <i>blood pressure</i> is <i>raised</i>, their vessels -tortuous and thickened, and the left ventricle enlarged.</p> - -<p>As to the <i>variations in uric acid excretion</i>, these, as before -remarked, show no appreciable deviation from normal. Occasionally, -however, there is a tendency to <i>uric acid gravel</i>. Of more -sinister significance, albeit, is the fact that in many of these cases -the urine is copious, of low density, paler than normal, and shows -a trace of <i>albumen</i> with hyaline casts.</p> - -<p>As the disease marches to its fell end the appetite becomes -impaired, gastric catarrh and diarrhœa may sap the waning -strength, or palpitations, fits of dyspnœa, or angina-like attacks, -sometimes fleeting, but often of organic source, may portend a -fatal issue. Ripe for the sickle, a kindly “stroke” perchance -puts an end to his protracted misery. Or symptoms, long since -manifest, of progressive <i>renal</i> failure may usher in the closing -scene, and happy the victim if he pass muttering, half conscious, -into that dream-like stupor drifting by insensible graduations to -death.</p> - -<div class="poetry-container"> -<div class="poetry"> - <div class="stanza"> - <div class="verse indent20">“The life of all his blood</div> - <div class="verse indent0">Is touched corruptibly, and his pure brain</div> - <div class="verse indent0">(Which some suppose the soul’s frail dwelling-house)</div> - <div class="verse indent0">Doth by the idle comments that it makes</div> - <div class="verse indent0">Foretell the ending of mortality.”</div> - </div> - <div class="stanza"> - <div class="verse right"><i>Shakespeare.</i></div> - </div> -</div> -</div> - -<p>So much in attempted portraiture of the long-drawn-out -tragedy of inveterate chronic gout. But, fortunately, it is not -always thus, and nowadays, at any rate, the evils wrought on the -constitution by the malady are seldom so malignant. For not -only, as before stated, has gout become less frequent, but its -virulence also much attenuated. States of so-called “gouty -cachexia” were, however, more familiar to our forefathers. It -more commonly ensues in subjects of strongly <i>hereditary</i> tendency, -and particularly in those in whom the <i>initial</i> attacks ensue before -thirty years of age. I recall the instance of a colonel who sustained -his first attack of gout when a subaltern of but eighteen, -brought on, as he thought, through exposure while shooting -snipe in Peshawur. It is in such cases that this so-called “gouty -cachexia” may overtake a man while yet in his prime, and vest -him untimely “with all the characters of age.”</p> - -<p>As to the milder types of regular chronic gout, such usually -arise, not in youth, but in men past the meridian of life. In their -instance the recurrence of gouty paroxysms is often erratic. -Periodicity becomes less pronounced or wholly lost. The life<span class="pagenum"><a id="Page_229"></a>[229]</span> -history of the disease may be summed up in a few sporadic outbreaks, -occurring irregularly throughout a long life. Even when -at first the attacks occurred regularly in the spring and fall the -rhythm of incidence becomes broken. An attack comes before -its time, is belated, fails of appearance wholly, or an intermediate -paroxysm comes as a surprise. Moreover, in many such the gouty -manifestations with the passing years tend to become more -and more attenuated, maybe even to extinction. Thus, a man -who in the middle decades was a martyr to gout in old age -gains freedom from its visitations, the disease having apparently -exhausted its vicious potentialities.</p> - -<p>Reviewing articular gout as a whole, one cannot but realise -that it does in respect of the recurrence of gouty paroxysms -exhibit inexplicable vagaries, inexplicable in that, as Sir William -Roberts long since said, “in many instances they are dependent -neither upon medical treatment nor upon altered dietetic habits, -but are due to spontaneous changes in the constitution. They -form part of the natural history of gout; and it is important to -bear their existence in mind when we seek to estimate the value -of therapeutic means in order to prevent ourselves from becoming -the dupes of misinterpreted sequences.”</p> - -<p>Albeit, we would not end on too sombre a note. For, in respect -of the graver consequences of gout, it is unquestionable that -right living, aided by efficient therapy, may arrest the course or -mitigate the severity of the disorder. Moreover, as long as the -attacks do not follow quick upon each other, but are separated -by long intervals, there is little fear of a cachectic condition supervening. -Life may not be appreciably shortened, and such textural -degenerations as may ensue, though frequently attributed -to gout, may often with at least equal plausibility be assigned to -advancing years, but this with reservation, for, as Duckworth -says, “the wilful libertine is likely soon to become cachectic, -while the prudent man may altogether avoid this state or avert -its evils for many years or decades of years.”</p> - -<h3><span class="smcap">The Joint Deformities of Chronic Gout</span></h3> - -<p>The palpable changes in the affected joints differ widely in -different cases, and why is not apparent. Thus, the first attack, -if of prolonged duration, may bequeath a legacy of crippledom -comparable to that met with after repeated paroxysms. On the -other hand, some, although they have suffered from the disorder -off and on throughout their lives, yet escape those consecutive -deformities which in others deform and cripple the hands and -feet, though the disease may be of relatively brief duration.</p> - -<p><span class="pagenum"><a id="Page_230"></a>[230]</span></p> - -<p>But in the less fortunate cases the continued ravages of gout -lead to a pitiful disablement of the affected limbs, reaching its -acme in the <i>hands</i> and <i>individual fingers</i>, flail-like and semi-paralytic -as they so frequently become.</p> - -<p>Not only are the digits variously distorted, their joints more or -less ankylosed, but the overlying skin, distended by the ever -increasing subjacent uratic deposits, becomes thinned and purplish -red in hue, and occasionally ulcerates. Similarly at ankle, knee, -wrist and elbow thickening and deformity ensue as the concretions -accumulate in and around the affected joints, these -further accentuated by the correlated inflammatory and degenerative -processes. Coincident deposits in the tendon sheaths and -related bursæ contribute their quota, and at knee and elbow the -bursal masses may reach extraordinary dimensions. Not only -do the joints become deformed, but distorted also, through reflex -muscular spasm and instinctive adoption of unnatural attitudes -for the avoidance of pain.</p> - -<p>So much for the broad outline of the picture presented, but a -still closer scrutiny is called for. The deformities produced are -the outcome of uratic deposits, which, as Charcot long since -pointed out, take on the shape of “irregularly rounded or ovoid -swellings, bunched, and either large at the base or just the -opposite, <i>i.e.</i>, provided with a pedicle.”</p> - -<p>As shown in the coloured plate, the favourite site for their -development is the <i>dorsum</i> of the <i>hand</i> or the vicinity of the -<i>metacarpo-phalangeal</i> or <i>mid-phalangeal</i> joint. The resultant -disfigurement of the hand is very characteristic. Irregular -tuberous swellings surmount the knuckles, and spreading laterally, -obliterate the fossæ between them and their fellows. The same -extend forward over the first phalanges, from nigh the distal end -of which again arise similar bossy excrescences over the mid-phalangeal -joints. Encroaching thus upon the length of the first -phalanx from either end, but little of its shaft is ultimately left -exposed. In like fashion the mid-phalanx may be buried in -uratic deposits, its contour wholly lost; and, the terminal phalanx -participating, the digits become almost pedunculated, the nails -projecting from the ends thereof—the “parsnip hand” of Sydenham. -Such is the appearance presented in inveterate chronic gout.</p> - -<p>Fortunately such examples are relatively rare, and a study of -the condition in its earlier stages reveals some interesting features. -The uratic deposits, it is important to note, <i>are not located exactly -at the level of the articulation</i>. Unattached as they are to the -<i>articular ends</i>, they are not compelled to, nor do they in any way, -adapt themselves, as it were, to the contour or shape thereof. -In short, the tophaceous formations are <i>erratic</i>, are not like<span class="pagenum"><a id="Page_231"></a>[231]</span> -<i>osteo-arthritic</i> nodules, erupted from and continuous with the -articular bone ends. Again, relatively independent of the contiguous -tissues, they, unlike osseous outgrowths, are slightly -<i>movable</i> in lateral directions.</p> - -<p>When of <i>recent</i> incidence, their consistence is <i>soft</i>, and, be they -never so ancient, they do not attain the <i>density</i> and <i>hardness</i> of -<i>bony outgrowths</i>. The overlying skin, to which they are sometimes -adherent, takes on a peculiar glossy and satin-like texture, its -dusky pink blotched with spots of dead white colour, <i>i.e.</i>, subjacent -uratic deposits.</p> - -<p>In other particulars also they differ from bony outgrowths. -The tophaceous masses may <i>soften</i> and <i>disappear</i> after exacerbations -of <i>arthritis</i>, and others may form at different sites. Following -such absorption or difference in their location, some increase in -joint <i>mobility</i> may happily ensue. This same fortunate occurrence -may follow discharge of the uratic masses through <i>ulceration</i> and -<i>perforation</i> of the skin.</p> - -<h3><span class="smcap">Tophi: Their Evolution and Distribution</span></h3> - -<p>In our chapter on <i>Uratosis</i> we dealt with the chemical nature -and mode of formation of tophi. Also we affirmed our belief that -tophi, whether <i>articular</i> or <i>ab-articular</i> in site, were always -<i>preceded by local inflammatory reaction</i>, and to the clinical tokens -of their impending eruption we need not recur. Albeit this -point, <i>i.e.</i>, <i>antecedent</i> inflammation, is of such prime importance -that we have not hesitated to append to our text a lengthy footnote,<a id="FNanchor_37" href="#Footnote_37" class="fnanchor">[37]</a> -this because, as Garrod, who quotes the same <i>in extenso</i>,<span class="pagenum"><a id="Page_232"></a>[232]</span> -rightly claims, the genesis and evolution of tophi has never been -so graphically depicted as in Moore’s description.</p> - -<p>It will be seen that this observer holds that tophus formation -“is usually preceded and accompanied by inflammation.” Garrod, -as we know, believed uric acid to be the <i>cause</i>, and not the consequence, -of gouty inflammation. But he emphasises the fact that -the phenomena attendant on the eruption of auricular tophi are -“exactly the same as when a joint is affected, and constitute, in -fact, a true gouty paroxysm, commencing with infiltration of the -tissue and subsequent inflammation.” Still, though venturing -to differ as to the sequence of events, we gladly invoke this -authority’s observations in proof of the fact that the <i>inflammation</i> -even in the <i>ear</i> is not always of negligible grade: “I have seen -many cases in which the ear symptoms have proved very annoying, -so that patients have been unable to rest their ears on the pillow.”<span class="pagenum"><a id="Page_233"></a>[233]</span> -<i>Subacute gout</i> sometimes occurs in the ears, says Duckworth, -who furthermore believed that the <i>indurations</i> in the <i>cartilage</i> -observed by him in <i>gouty</i> subjects were the outcome of such -attacks. Laycock, too, long before noted that the ears of gouty -subjects often appeared to be “soldered.”</p> - -<p><i>Pain or discomfort in auricular tophi often presages an oncoming -articular paroxysm.</i> “Those gouty persons,” said Scudamore, -“who are affected with concretions (chalk-stones), experience for -a short time before the fit pricking pains in the parts where they -are situated. This is described even by those who have minute -points of concretions in the lobes of the ears and in no other parts -of the body.” Hence tophi have a <i>prognostic</i> as well as diagnostic -valency in that the incidence of pain at their site may foretell -the oncoming of <i>articular</i> outbreaks.</p> - -<p>While, as before emphasised, the eruption of tophi may <i>antedate</i> -the occurrence of <i>articular</i> gout, on the other hand tophi -may be present at the joints, but lacking in the ears and all other -<i>ab-articular</i> sites. Auricular tophi, extracted occasionally by -patients, are sometimes shed <i>spontaneously</i>. According to -Duckworth’s statistics, in one-third of all well-marked cases of -gout the ears present tophi in the <i>helix</i>, the <i>anti-helix</i> and its -<i>fossa</i> and the <i>lobule</i>, and in some cases they may be situated on -the <i>posterior</i> surface of the <i>pinna</i>.</p> - -<h3><span class="smcap">Other Sites of Tophi</span></h3> - -<p>Apart from the external ears, tophi are apt to form in various -localities. Most frequently they are situated in the vicinity of -the <i>joints</i> and <i>bursæ</i>, especially that over the <i>olecranon</i>. As -attack follows attack at short intervals the tophaceous matter is -heaped up around the joint, and in this way many articulations -may be involved, even all of them, says Trousseau, “as happened -to Gordius, who composed on himself the following jocular -epitaph:—</p> - -<div class="poetry-container"> -<div class="poetry"> - <div class="stanza"> - <div class="verse indent0">“‘Nomine reque duplex ut nodus Gordius essem.’”</div> - </div> -</div> -</div> - -<p>Uratic deposits sometimes attain a prodigious size. I have -seen them the equivalent of a small hen’s egg. The largest tophi -are invariably found in the neighbourhood of some joint, and the -upper extremities furnish the most marked examples. But even -when of considerable magnitude they may be non-adherent, the -skin gliding freely over their surface. As John Hunter wrote: -“The chalk shall remain for years without producing inflammation, -and seldom produces it at all but from quantity.”</p> - -<p>Often, however, their presence at length induces irritation of the<span class="pagenum"><a id="Page_234"></a>[234]</span> -overlying integument. As they approach the surface the skin -assumes a purple hue, becomes thin, and ulcerates. The uratic -ulcers thus formed have generally an indolent fungous base. As -the deposits extrude or are removed they are continually redeposited, -and in this manner ounces of urates may be discharged. -The same is followed by great relief and diminution of deformity.</p> - -<p>Discussing such lesions, John Hunter tells us that “when the -interior surfaces are exposed they hardly take on common -inflammation and suppuration, healing more readily than a sore of -the same magnitude from any other cause; even a joint shall be -exposed, yet common inflammation shall not come on, nor shall -it suppurate: only a watery fluid shall come out, bringing the -chalk with it occasionally, and it shall heal up kindly.”</p> - -<p>A glance, too, at the preceding footnote shows that Moore also -agreed with Hunter as to the absence of common inflammation -and suppuration. Moreover, even of recent years it has been -suggested that, because gouty tophi do not suppurate even when -ulcerated through the skin, the <i>urates</i> have <i>antiseptic</i> properties. -But Bendix (<i>Zeit. klin. Med.</i>, 1902) failed to demonstrate such -qualities experimentally. The truth would appear to be that, -though gouty inflammation never ends in <i>suppuration</i>, yet <i>abscess -formation</i> very commonly occurs in the <i>peri-tophal</i> tissues. Such -more often ensues in subjects of frail health or of definitely -cachectic type. Garrod saw as many as five or six open at one -time in each hand, and others on the feet. In his experience they -give rise to but little constitutional disturbance. Scudamore, -speaking of the same, says the sores produced are “unusually -tender, aching, and sometimes very painful as the fit is making its -approach.”</p> - -<p>Ultimately the gouty ulcers thus formed dry up, and this -indifferently whether or not the uratic deposits are wholly extruded -in the discharging pus. The wound then closes, leaving a -small scar, which, however, given a fresh attack of gout, is but too -likely to break down, and this process may occur repeatedly. -Bursal sacs containing tophi not infrequently suppurate, constituting -abscesses containing urates.</p> - -<p>An interesting fact noted by Garrod was that so long as such -abscesses were discharging freely the subjects enjoyed comparative -immunity from overt gout. But, given healing of the same, -in several instances he had seen it the signal for a sharp outbreak. -Duckworth, too, states that “whenever ulceration and flow of -tophaceous matter occurs it is rare to meet with paroxysmal -attacks anywhere in the body. With the cessation of the discharge -renewed fits may intervene.”</p> - -<p>While they tend to aggregate themselves round the joints, yet<span class="pagenum"><a id="Page_235"></a>[235]</span> -tophi sometimes invade the <i>integument</i> of the <i>limbs</i>. They have -been seen in the skin over the <i>ulna</i> and <i>tibia</i>, and commonly over -the <i>olecranon</i> and <i>patella</i>. Pye Smith recalls the instance of a -man in whom a number of small ulcers, discharging urate of soda, -formed in the middle of his <i>thighs</i> and <i>legs</i>. The case is not an -isolated one, but the incidence of subcutaneous uratic deposits -in the limbs, save over <i>articulations</i>, is exceptional.</p> - -<p>In the <i>palms</i> of the <i>hands</i> and the <i>pulps</i> of the <i>fingers</i>, the -knuckles and phalanges, tophi are found not infrequently; and -Trousseau tells of a lady of sixty in whom the cutaneous <i>palmar -folds</i> of both hands were “marked with radiating white lines -such as are seen in those who have long been employed in tempering -plaster.”<a id="FNanchor_38" href="#Footnote_38" class="fnanchor">[38]</a> Similar deposits have been noted in the <i>plantar -surface</i> of the <i>feet</i>.</p> - -<p>Reverting to the <i>trunk</i>, uratic deposits have been found in the -<i>scapular</i> region, also in the <i>perineum</i>. I have twice seen tophi in -the <i>corpora cavernosa</i> of the penis. In the face, apart from the -ears, they have been found in the <i>alæ</i> of the nose. In the <i>eyelids</i> -Duckworth noted uratic deposits in streaks resembling xanthoma; -they were chemically tested, and proved to be of this nature. -Speaking of “gout in the eye,” Garrod states: “I have witnessed -many cases in which conjunctivitis and sclerotitis appear to be -distinctly connected with the gouty diathesis, and in two cases -there existed <i>deposits</i> of <i>urates</i> on the surface.”</p> - -<p>As before stated, we recognise only one type of gout, viz., the -tophaceous variety. But even so it must be noted that in some -instances the process of tophus formation is greatly accentuated. -In other words, the tophi may not only be of prominent size, but -of unusually widespread distribution. Indeed, poetic exaggeration -has it that one Baylas and one Acragas were entombed -while alive in their own uratic deposits. But, apart from such -imaginative flights, there are unquestionably some cases in which -tophi are most widely diffused. Thus Plater tells of a patient whose -whole body, even the eyelids, was studded with them: “ex toto -corpore, per poros, adeo ut etiam palpebræ oculorum non -exemptæ fuerint, ejusmodi materia gypsœa, circa poros cutis -mox in tophos mutata, prodisset.”</p> - -<p>These cases of multiple tophi are far more common in men. -Duckworth met with some well-marked cases in women. They -may occur also in persons who have been lifelong abstainers. -Sometimes trauma seems to have played a part in determining -their localisation. Garrod held that, given prodigious uratic<span class="pagenum"><a id="Page_236"></a>[236]</span> -deposition, the kidneys might be held as unsound and undergoing -sclerosis; and, according to Duckworth, the rule commonly holds -good.</p> - -<h3><span class="smcap">Affinities Between Gout and Other Diseases</span></h3> - -<p>Whatever be the explanation, no fact in practical medicine is -better established than this, viz., that certain disorders are -peculiarly liable to arise in gouty subjects. Of these the more -noteworthy are glycosuria, phlebitis, certain cutaneous disorders, -and nephritis. While, for myself, I prefer to regard these -affections as merely diseases to which the gouty are especially -subject, nevertheless each and all of them, by one authority or -other, have been classed as among the <i>irregular</i> manifestations -of gout.</p> - -<p>This, on the assumption that these several morbid entities may -precede, alternate with, or follow arthritic seizures, frequently -also on the basis of their alternation in hereditary transmission -with arthritic gout. Thus, in a family of marked gouty proclivity, -while one son, despite a temperate life, may have severe -articular gout, on the other hand his brother may suffer only with -<i>irregular</i> manifestations, <i>i.e.</i>, phlebitis, eczema, etc.</p> - -<p>As to whether these particular disorders, phlebitis, glycosuria, -etc., are directly caused by the toxin of gout, or whether their not -infrequent association with gout is merely accidental, is a moot -point. But to the sources of fallacy in this connection we shall -allude more in detail when dealing later with irregular gout. -Meanwhile extended knowledge of the intimate etiology of phlebitis, -glycosuria, etc., tends to an attitude more critical than that -of our forefathers, who, <i>faute de mieux</i>, relegated a large number -of conditions whose pathology was inexplicable to the nebulous -domains of irregular gout.</p> - -<h3><span class="smcap">Gout in Relation to Glycosuria</span></h3> - -<p>That some obscure link existed between glycosuria and gout was -long since suspected. Prout noted it as far back as 1843, and -Bence Jones discussed the subject under the title “Intermitting -Diabetes” (1853), while in the following year Gairdner announced -that he had long surmised the kinship between the two disorders. -About the same time Claud Bernard remarked that gout and -glycosuria might alternate, and so did Trousseau, and many since -that day have ranked glycosuria as one of the forms of <i>irregular</i> -gout, whether legitimately or not is an open question, but at -any rate it does not affect the established clinical fact that glycosuria -occurs with significant frequency in gouty individuals.</p> - -<p><span class="pagenum"><a id="Page_237"></a>[237]</span></p> - -<p>Gouty glycosuria is more common in males than females. The -subjects are usually robust, middle-aged, and of full habit. Sugar -is found intermittently in their urine in small amounts, but no -acetone bodies. It is as a rule unaccompanied by thirst or wasting. -It quickly responds to dietetic restrictions. As Gull long since -observed, gouty glycosuria does not “discover itself,” but is -“not uncommonly discovered.” This tersely sums up the clinical -difference between this affection and true diabetes, albeit, as in -all glycosurias, there is always the risk that carbohydrate excess, -mental strain, or other adverse circumstances may aggravate the -disorder and the case merge into one of true <i>diabetes</i>.</p> - -<p>Following the installation of glycosuria, the tendency to paroxysmal -<i>articular</i> outbreaks often ceases. The converse also has -been observed, viz., that when, in sequence to dietetic restrictions, -the sugar disappears, the articular pains may reappear. The fact -that attacks of glycosuria may alternate with attacks of gout led -to the assumption that a positive antagonism existed between the -two disorders. Hence the phrase “the more sugar the less gout,” -and <i>vice versâ</i>. This, however, with reservations, for a fugitive -glycosuria has been seen during an acute articular paroxysm, and -a classical outbreak in the toe has been known to supervene in the -course of a well-established glycosuria.</p> - -<p>It is generally held that glycosuria is most commonly associated -with <i>irregular</i> forms of gout. But, in view of our ignorance of the -intimate nature of even <i>regular</i> gout, I should myself deprecate -affixing the prefix “gouty” to any glycosuria other than one -that has supervened in sequence to, or alternates with, gouty -<i>arthritic</i> seizures. Moreover, the glycosuria of gout is usually the -alimentary glycosuria of fat elderly people, in whom the sugar -excreted represents the unconsumed surplus of carbohydrate food. -But fat elderly people are not necessarily “gouty,” neither is -every so-called benign glycosuria inevitably linked on to a gouty -diathesis. In fact, the relegation of glycosuria to the gouty -category is but too often not a matter of diagnostic certainty, but -rather an inference. Hence my plea that the prefix “gouty” -would best be restricted to glycosurias occurring in individuals -who suffer <i>regular</i> attacks of gout, or those displaying those -objective tokens pathognomonic of the disorder, <i>i.e.</i>, <i>tophi</i>.</p> - -<p>Again, James Taylor has recently reminded us that, if nerve -affections are relatively common in true <i>diabetes</i>, the same may be -met with in <i>gouty glycosuria</i>, even when of temporary duration. -Thus symptoms indicative of <i>peripheral neuritis</i> may occur, <i>i.e.</i>, -lost knee jerks, paræsthesiæ, and paresis of the lower limbs. Now, -as this authority pertinently observes, the subjects of <i>gouty glycosuria</i> -are frequently given to <i>alcohol</i>. Consequently the question<span class="pagenum"><a id="Page_238"></a>[238]</span> -whether or not the symptoms are due, not to sugar, but to <i>alcohol</i>, -arises forthwith.</p> - -<p>In some undoubtedly the alcoholic factor plays a <i>rôle</i>, but such -symptoms may, on the contrary, arise in very abstemious individuals. -This notwithstanding, James Taylor holds that the -clinical complex differs substantially from that met with in true -<i>alcoholic neuritis</i>. It is slighter in degree, the paresis usually -restricted to lower limbs, while the exquisite tenderness to pressure -on nerve trunks so typical of alcoholic neuritis is little or not -at all in evidence. Nor is there the same tendency to contractures -in muscles as met with in the alcoholic variety, and withal there -is an absence usually of the mental changes—loss of memory—associated -therewith. Accordingly Taylor holds that we must -recognise the existence in the <i>gouty</i> of a true <i>glycosuric peripheral -neuritis</i> quite independent of <i>alcoholic peripheral neuritis</i>.</p> - -<p>Other concomitant nerve troubles noted in this association are -<i>severe intercostal neuralgia</i> and, even more commonly, <i>neuralgia</i> of -the <i>fifth nerve</i>, and to this may be added <i>migraine</i> and that other -neurosis <i>asthma</i>. Intense mental irritability and depression is not -an infrequent sequel in gouty glycosuria. According to James -Taylor, melancholia even may result, especially if the glycosuria -have merged into true diabetes—a sequel, he says, especially -prone to occur in Jewish subjects.</p> - -<p>Having seen and suffered many painful disillusionments through -too flippant relegation of neuralgias or neuritides to diatheses -“gouty” or “rheumatic,” I would emphasise the necessity for -great caution. In other words, before labelling a neuralgia or -neuritis as “gouty,” all possible causes, <i>infective</i> or <i>other</i>, should -be excluded, this always, but pre-eminently so in <i>brachialgia</i>, -<i>sciatica</i>, and <i>trigeminal neuralgias</i>. Nor even, should there be a -history of classic <i>outbreaks</i> or blatant <i>tophi</i> present, should we be -less vigilant.</p> - -<p>By all means recognise the <i>gouty diathesis</i>. It often avails much -in treatment, but not if, <i>e.g.</i>, <i>dental caries</i>, <i>antral disease</i>, <i>cervical -rib</i>, or <i>pelvic growth</i> be overlooked, not to speak of recent or concurrent -sources of <i>infection</i> or <i>toxic absorption</i>.</p> - -<p>Lastly, we should always recollect that gouty glycosuria, as Gull -said, “does not discover itself”; it is not writ large on the subject -like true diabetes. But given the incidence of <i>nerve</i> troubles in a -<i>gouty</i> person, <i>i.e.</i>, a paræsthesia, itching, neuralgia, etc., we should -always suspect its presence.<a id="FNanchor_39" href="#Footnote_39" class="fnanchor">[39]</a> Incidentally our search may reveal -not only sugar, but also <i>albumen</i>, and the latter may explain much -that appeared inexplicable.</p> - -<p><span class="pagenum"><a id="Page_239"></a>[239]</span></p> - -<h3><span class="smcap">Gout in Relation to Phlebitis</span></h3> - -<p>It is to Sir James Paget that we are indebted for recognition of -the fact that phlebitis occurs with significant frequency in gouty -subjects. This great surgeon held that the disorder was the outcome -of a modification or transformation of gout, the result of -“morbid conditions changing and combining in transmission from -parents to offspring.” At the present time some regard it merely -as a complication of gout, others as one of the <i>irregular</i> manifestations -of the disease.</p> - -<p>It occurs most commonly in men, women being rarely the subjects -of gouty phlebitis. It may install itself insidiously with but -mild local discomfort, and yet on examination a cord-like hardness -is detected. In others it announces itself with pain, in rare -instances intense, this more commonly if the deep veins of the -calf are its seat.</p> - -<p>Its predilection is for the veins of the lower extremity, the -superficial rather than the deep vessels. If the former, a faint -blush over the affected veins may be seen, but if the deep veins, -then œdema and tenderness may be the sole token of its presence.</p> - -<p>Frequently the phlebitis is patchy in distribution and migratory. -Thus, as Paget says, it may on one day be located in a short -length of the saphenous vein, flitting the next day to some other -portion thereof, or, it may be, to the corresponding vein of the -opposite limb. This tendency on its part to metastasis and symmetry -led Paget to the conclusion that “the essential and primary -disease is not a coagulation of the blood, but an inflammation of -portions of the venous walls.”</p> - -<p>Its duration is not uncommonly prolonged, and it displays a -marked tendency to recurrences, the latter determined by blows, -unusual exertion, or, according to some, exposure to cold. Most -cases end favourably, but death from embolism sometimes occurs. -Occasionally, given occlusion of the large veins, some degree of -swelling lingers permanently.</p> - -<p>The instances most indicative of a <i>gouty</i> origin are those in -which the veins of a limb, the seat of <i>acute gout</i>, are simultaneously -attacked by phlebitis. In three cases of this nature recorded by -Garrod, the subjects, despite their suffering from acute articular -gout, persisted in leaving their beds to record their votes in the -parliamentary election of 1884. This type of case, according to -Garrod, is usually confined to men, and, with the exception of the -cases above noted, a <i>varicose</i> condition of the veins of the legs of -long standing existed in his series of examples.</p> - -<p>Garrod recognises in addition a second type, in which phlebitis,<span class="pagenum"><a id="Page_240"></a>[240]</span> -“usually of a much less acute character, ensues without the -previous development of gouty inflammation in the neighbourhood -of the part.” Here we may recall that, according to Paget, the -incidence of phlebitis in an elderly person without any external -cause warrants the suspicion of gout. Perhaps the chief justification -for such an assumption rests on the fact that phlebitis -appears sometimes to be <i>hereditary</i>. Paget cites the instance of a -man who suffered from phlebitis of both saphenous veins during -an attack of acute gout. On the maternal side his mother, -two uncles, a grandmother, and two cousins had been the subjects -of phlebitis.</p> - -<p>In conclusion, for myself, I would suggest that the term “gouty” -phlebitis be restricted to those instances in which a limb, the seat -of <i>acute articular gout</i>, is complicated by <i>phlebitis</i> of the veins of -the affected part. Here we are dealing with what is palpably an -extension of the gouty inflammation from the affected <i>joint</i> to the -<i>veins</i>, and which, I venture to assert, is strongly confirmatory of -the view that an <i>infective</i> element intrudes in “gouty” arthritis. -We may recall that, <i>e.g.</i>, <i>gonorrhœal phlebitis</i> of the lesser saphenous -veins is not so uncommon, while the frequency with which phlebitis -complicates <i>infections</i> calls for no emphasis.</p> - -<p>Leaving aside these rare instances of <i>acute gout complicated by -acute phlebitis</i>, I think there is a too flippant tendency to regard -any phlebitis occurring in middle-aged or elderly subjects as -being of this nature, this often in the absence of any evidence, -hereditary or other, of a gouty element in the case. Frequently, -too, the subjects are women with <i>varicose veins</i> of long standing, -and <i>ipso facto</i> potentially liable to phlebitis. But why, in the -absence of ancestral or acquired gout, dub such cases forthwith -as “gouty”? We may, it is true, as in Paget’s classical instance, -elicit a <i>familial</i> tendency to phlebitis, but even so I doubt the legitimacy -of the inference that the phlebitis is necessarily “gouty.” -Is it not equally true that the tendency to <i>varicose veins</i> is -hereditary, and <i>ergo</i> predicates an enhanced liability to phlebitis?</p> - -<h3><span class="smcap">Cutaneous Disorders</span></h3> - -<p>The incidence of tophi in the skin naturally engendered the conception -that gout was responsible for many and diverse types of -cutaneous affections. In accordance with this, every effort was -made to prove that they were the outcome of uratic infiltrations, -but in vain.</p> - -<p>Objective proof of this nature being lacking, the older clinicians -found their justification in the alternation of arthritic attacks with -cutaneous disorders, and their alternation in inheritance was laid -great stress upon, this especially by French dermatologists,<span class="pagenum"><a id="Page_241"></a>[241]</span> -notably Bazin, but at the present day Jacquet’s non-committal -pronouncement is probably representative of the attitude of the -French school as a whole towards “arthritic” affections of the -skin: “Le lien admis entre le groupe de maladies dites <i>arthritiques</i> -est très mal connu dans son essence, mais il serait tout -aussi contraire à l’esprit scientifique de le nier avec rigueur que -de l’affirmer avec presomption.”</p> - -<p>As to the skin disorders associated with <i>acute</i> types of gout, -perhaps the most interesting and well ascertained is <i>herpes</i>. It -may precede an acute attack, may alternate with it, or be a sequel -thereof. Rendu noted that acne, boils, and carbuncles also might -occur prior to, in alternation with, or in sequence to acute attacks, -and Scudamore noted the same in respect of erysipelas.</p> - -<p>The noteworthy liability of the gouty to these disorders is but -another proof that gout predisposes its victims to <i>infections</i>. The -fact that acute gouty arthritis might follow acne, boils, etc., lends -colour to our contention that the same may be of infective origin. -But unfortunately the suspicion also intrudes that some of the -arthritides occurring in such association may, on insufficient -grounds, have been diagnosed as “gouty,” this especially if the -joint disorder were located anywhere save at its classic site, the -<i>big toe</i>.</p> - -<p>Passing to skin affections associated with <i>chronic</i> gout, it must -be admitted that as a whole the contention that they are “gouty” -in origin is, to say the least of it, doubtful. French dermatologists -claimed that the cutaneous eruptions of the “gouty” might be -recognised by their polymorphism, circumscribed location, etc., -but these are no more distinctive peculiarities than the concomitant -pricking, hyperæsthesia, and hyperalgesia upon which Bazin laid -such emphasis in their diagnosis.</p> - -<p>In short, sequences, coincidences, and alternations are the basis -of much that has been written upon so-called “gouty” cutaneous -affections, criteria all of them fruitful sources of fallacy.</p> - -<p>As to <i>psoriasis</i>, I have met with it so frequently in association -with non-gouty arthritides that I have never felt justified in -claiming any example as “gouty.” So-called “gouty” <i>pruritis</i> -and <i>prurigo</i>, these when they occur in the “gouty” are frequently -referable to an associated glycosuria, and when this is not -the case, it is frequently a senile prurigo. The claim that urticaria -is “gouty” may be dismissed without comment.</p> - -<p>As to frequency of incidence in the “gouty,” <i>eczema</i> undoubtedly -must be awarded the palm. But whether the scaliness of skin on -extensor surfaces of arms and legs and back of neck, which ultimately, -under the influence of skin infection through scratching, -develops into a dermatitis which assumes the character of eczema,<span class="pagenum"><a id="Page_242"></a>[242]</span> -can be, strictly speaking, held as of “gouty” origin, is questionable. -Certainly, whatever be the origin of the pruriginous -scaliness of the skin, there can be no doubt that the later dermatitis -is the outcome of infection by skin organisms. Frequently -the presumption that the eczema is “gouty” rests upon general -rather than specific grounds, on “goutiness” rather than “gout.” -Accordingly I think it would be wiser to regard eczema as an -occasional complication of gout rather than an integral element -thereof.</p> - -<p>Lastly, there can be no doubt that many of the so-called -“gouty” cutaneous disorders ensue at what may be called the -arterio-sclerotic stage of life. It is when renal and cardio-vascular -changes are present that we meet with exudative -erythema, pityriasis, exfoliative dermatitis, and purpuric eruptions. -All these have at one time or another been foisted upon -gout, whereas they are far more closely related to the cardio-vascular -and renal changes with which the disorder is so frequently -associated.</p> - -<h3><span class="smcap">Gout and Nephritis</span></h3> - -<p>The association between gout and renal disease is admittedly -intimate, in so far as gouty subjects often have granular kidneys, -while gout is a frequent complication of this type of renal disorder. -Nevertheless, the clinical relation between the two diseases is -ill defined and, moreover, somewhat erratic. In most instances -the renal defect is engrafted upon the antecedent gout, or the -sequence is reversed; and, again, the two conditions may arise -contemporaneously. Lastly, in sharp and disconcerting contrast -to this mutual overlapping of the two disorders, we have the -awkward fact that more commonly <i>gout</i> and <i>granular kidney</i> -run to their fell end quite <i>independently</i> of each other.</p> - -<p>Thus, Sir William Roberts observed: “It is quite common -to see articular gout, even of chronic and inveterate character, -run its entire course without any accompanying signs of structural -disease of the kidneys.” The same, to be sure, is equally true -of <i>granular kidney</i>, which may pass to its close without any -suspicion of gout.</p> - -<p>Now, as we have seen, the primary <i>renal</i> origin of gout fails -of demonstration. Is <i>gout</i>, then, <i>causally</i> related to <i>granular -kidney</i>, or is there some less direct relation between them?</p> - -<p>As to this, to begin with, it is extremely rare that a “gouty” -subject develops <i>acute</i> nephritis. In the exceptional instances -when it does occur it is either purely accidental or else the outcome -of an <i>exacerbation</i> of a <i>previously existing interstitial nephritis</i>.</p> - -<p><span class="pagenum"><a id="Page_243"></a>[243]</span></p> - -<p>The question then arises, Can gout when long continued -originate <i>per se</i> the condition we are pleased to term “gouty -kidneys”? As seen above, such renal lesions are by no means -an inevitable sequel or concomitant of long-standing gout. Moreover, -there is nothing <i>specific</i> of <i>gout</i> in the so-called “gouty” -kidney. It is an <i>interstitial nephritis</i>, which may assume the -appearances of the ordinary “contracted kidney” or the “arterio-sclerotic” -type. There may be <i>uratic</i> deposits at the apex of the -pyramids, or even an <i>uric acid calculus</i>; but even so that of -itself constitutes no proof of the renal changes being “gouty” in -origin. In short, the prefix “gouty” as applied to these types -of renal lesion is just as unscientific and unwarrantable as used -in regard of “phlebitis,” “eczema,” and so forth.</p> - -<p>Nor, <i>quâ</i> <i>gout</i> as a <i>causal</i> factor, are we in better case if the -renal disorder be of the “arterio-sclerotic” type. No direct -relationship is established between gout and arterio-sclerosis -beyond the fact that both are usually met with in middle-aged or -elderly people. Moreover, a man may develop arterio-sclerosis -and arterio-sclerotic kidneys, yet never have any vestige of -gout.</p> - -<p>There being nothing <i>specific</i> of <i>gout</i> in the lesions of so-called -“gouty” kidneys, we must revert to the clinical findings to -refute or establish any <i>causal</i> connection between gout and the -renal disorder. Now, gout is a disease of middle and late life, -and rarely of itself proves mortal. On the other hand, it appears -increasingly probable that the seeds of granular kidney are laid -in earlier life, and, on the average, its course is shorter than that -of gout. Also the two disorders have clinical <i>facies</i> absolutely -distinct the one from the other.</p> - -<p>From the above considerations it is, I think, clear that, whatever -the hidden nexus between gout and “granular kidney,” it is -neither essential nor constant. It is rather, I believe, of the -nature of a coincidence. Furthermore, as applies to so many -problems pertaining to gout, and, for that matter, to “granular -kidney” also, we labour under the grave disability that both -terms are, especially “gout,” very vaguely applied and when used -are often a matter of personal opinion. Consequently, as Samuel -West shrewdly observes, “it is difficult to discuss satisfactorily -the relation of two conditions to each other when neither condition -admits of precise definition, for some authorities are more -easily satisfied in the diagnosis of gout than others; and, while -some place all forms of chronic interstitial nephritis in one and the -same category, others are not so comprehensive, and regard -granular kidney as a definite clinical disease, of which the interstitial -nephritis is only a part.” Under these circumstances, the<span class="pagenum"><a id="Page_244"></a>[244]</span> -need for further and more exact researches in this sphere is but -too obvious.</p> - -<p>Meanwhile, accepting the general opinion as to the frequency -of the co-existence of gout and granular kidney, is there any -explanation thereof? For myself, I am inclined to believe that -the common overlapping of the two disorders is in large measure -due to this, that the factors, <i>i.e.</i>, excess in alcohol, overeating, -etc., that make for the eruption of gout, are largely identical with -those that promote the development of <i>granular kidney</i>. Hastings -Gilford holds “there is very little doubt that syphilis, lead, and -gout do not so much originate Bright’s disease as excite it into -activity when it already exists in a smouldering or latent -condition.”</p> - -<p>With this view I feel much in accord, and if to the malign -effects of gout be superadded the effects of alcohol or, haply, lead -also, how incalculably greater the chances of fanning into flame -any latent tendency to nephritis—a legacy, perhaps, of some long -bygone infection.</p> - -<h3><span class="smcap">Prognosis in Gout</span></h3> - -<p>Gout <i>per se</i> rarely, if ever, proves fatal. Certainly, as Sir -Thomas Watson long since said, “<i>gout in the extremities</i> is not -a mortal disease.” When death did occur during or in close -relation to an <i>acute</i> paroxysm, it was by our forefathers attributed -either to its <i>retrocession</i> or to some <i>misplaced</i> or <i>irregular</i> manifestation. -Indeed, their attitude was very much that of the -French physician who observed: “La goutte articulaire est celle -dont on est <i>malade</i>, et la goutte interne est celle dont on <i>meurt</i>.”</p> - -<p>But, as we shall see later in our chapter on <i>Irregular</i> Gout, -most, if not all, of their instances of the assumed translation of -the <i>materies morbi</i> of gout to some vital organ are without -foundation. The demise, often dramatically sudden, was not -due to <i>gout</i>, but to some insidious, unguessed-at organic degeneration, -or to one of the accidental intercurrent maladies to which -these subjects seem especially liable. To sum up, the immediate -danger to life from regular gout when uncomplicated is slight.</p> - -<p>Not that gout is salutary, lessens the liability to other diseases, -or promotes longevity. Very much the reverse—“a tendency -to <i>recurrence</i> is a law of the disease.” Broadly speaking, the more -pronounced the tendency to recurrence of articular outbreaks, -the more protracted the isolated paroxysms, the worse the outlook, -the more sombre, too, the greater the number of joints involved. -Conversely, if the disease, though it recur, restrict itself to the -classic site, the big toe, the longer, as a rule, the intervals of<span class="pagenum"><a id="Page_245"></a>[245]</span> -freedom, the brighter the prospects of long life. Lastly, the more -the subject is crippled, the more pronounced the tendency to -tophaceous deposits, the more likely is the disease to pursue a -downward course, the greater the risk of associated degenerations -in renal and vascular tissues.</p> - -<p>While these reflections are in the main, we think, justifiable, -we must recollect that in gout, as in other maladies, the elements -of <i>prognosis</i> reside in the <i>individual</i>, not the disease. Does he -come of a long-lived stock?—not uncommonly a feature of gouty -families. If so, the outlook is favourable. If he come of a short-lived -breed, then in all probability, no matter how carefully he -lives, he will not likely make “old bones,” this, certainly, if the -gout makes its appearance early in life, say under thirty.</p> - -<p>As to the axiom, generally accepted, that the earlier in life gout -makes its <i>début</i>, the more unfavourable the outlook, there are -exceptions. Where <i>longevity</i> marks the stock, they usually are -true to type. Thus, even if the first outbreak occurs in the -twenties, I have known them reach the allotted span and over. -Nor if their urine show traces of <i>albumen</i> is this necessarily of -grave import, for these gouty veterans may for many years, -even to old age, exhibit traces of albumen without apparently -developing genuine Bright’s disease.</p> - -<p>“There dies not above one of a thousand of the gout, although -I believe that more die <i>gouty</i>,” wrote Graunt long years since; -and this contains a kernel of truth, for the <i>prognosis of gout</i> rests -in the main not on the <i>gout</i>, but the <i>conditions correlated therewith</i>—the -absence or not of <i>complications</i>. For, be it always remembered, -gout, though it may appear in youth, is chiefly an appanage of -the middle and later decades, in short of the <i>regressive</i> period of -life.</p> - -<p>This last is, I think, apt to be forgotten, and gout vicariously -saddled with all the infirmities of age. Thus, out of 2,680 -examples of <i>arterio-sclerosis</i> Huchard held <i>gout</i> and lithiasis -responsible for no less than 693. An appalling indictment, but -what of the long arm of <i>coincidence</i>? For <i>age</i> unquestionably is -the chief factor in the production of arterio-sclerosis, though -many allot gout a dominant <i>rôle</i> in its genesis. This certainly is -by no means proven. Still, whatever be the relationship, <i>gout</i> and -<i>arterio-sclerosis</i> are very often found <i>in association</i>. If so, the -prognosis will obviously rest, not on the gout, but on the <i>vascular</i> -disease—the pulse tension. If therewith be correlated -<i>albuminuria</i> and a displaced apex beat, the outlook is unfavourable.</p> - -<p>Again, is the subject lean or obese? If the former, so much -the better, for <i>corpulency</i> and <i>gout</i> are a sinister combination.<span class="pagenum"><a id="Page_246"></a>[246]</span> -Gout in itself, as previously observed, favours microbic invasion, -and obesity accentuates the liability. Moreover, the gouty -obese are prone to <i>arterio-sclerosis</i> and <i>granular kidneys</i>, with -sometimes a superadded <i>glycosuria</i>, or even true diabetes. In -such subjects also the presence or absence of signs of cardiac -mural degeneration must enter into our forecast, which at best -is but gloomy.</p> - -<p>Apart from arterial degeneration, we have to recollect the -tendency to <i>phlebitis</i> of <i>recurrent</i> type. This when present -always carries with it the risk of <i>embolism</i> and sudden death. -Cases therefore displaying this proclivity to phlebitis must be -judged accordingly. The gouty <i>glycosuric</i>, too, is always subject -to the risk that the condition may develop into one of true -diabetes. The absence of response to dietetic restrictions, viz., -persistent sugar in the urine, the onset of thirst, polyuria, or other -concomitants of diabetes, will darken the prognosis.</p> - -<p>Also I myself believe that the presence of local foci of infection -gravely prejudices the course of gout, accentuates any tendency -to recurrence of the attacks, and incidentally reinforces any -latent proclivity to vascular and visceral degenerations.</p> - -<p>Last, but not least, what of the subject’s habits? The -“internal environment” of the tissue cells of the gouty is -presumably of itself none too good; but if to this be added the -poison of <i>alcohol</i>, lead, or the toxic products of gluttony, it is -incalculably worse. The painter or the plumber, if he can, would -be wise to change his calling. If the alcoholic be deaf to remonstrance -or the glutton continue to gorge, their chances of life -dwindle proportionately, and if given to both vices, still more -so.</p> - -<p>In conclusion, the prospects of long life in gout depend in the -main on the presence or absence of associated morbid states. -If there be no complications such as I have indicated, the disease, -in my experience, is not likely to shorten life materially, always -provided that the victim is amenable to what should be the -watchword of the gouty,—</p> - -<div class="poetry-container"> -<div class="poetry"> - <div class="stanza"> - <div class="verse indent0">“The rule of not too much, by temperance taught</div> - <div class="verse indent0">In what thou eat’st and drink’st, seeking from thence</div> - <div class="verse indent2">Due nourishment, not gluttonous delight.”</div> - </div> - <div class="stanza"> - <div class="verse right"><i>Milton.</i></div> - </div> -</div> -</div> - -<hr class="chap x-ebookmaker-drop"> - -<div class="chapter"> - -<p><span class="pagenum"><a id="Page_247"></a>[247]</span></p> - -<h2 class="nobreak" id="CHAPTER_XIX">CHAPTER XIX<br> -<span class="smaller">ETIOLOGICAL AND CLINICAL DIAGNOSIS</span></h2> - -</div> - -<h3><span class="smcap">Articular Gout</span></h3> - -<p>The intimate cause of gout is unknown—a humiliating -reflection, albeit salutary, if it but engender a more catholic -attitude on our part when seeking to unravel the nature of this -obscure joint affection. For, to secure ideal ends, diagnosis must -be, not only clinical, but <i>etiological</i>. This is the more likely to -be attained if we shed all preconceived ideas and prejudices.</p> - -<h3><span class="smcap">Etiological Diagnosis</span></h3> - -<p>Confronted, then, with a suspected case of gout, whether acute -or chronic, what shall be our way of approach? Not the easy -and hazardous path of lightning diagnosis affected by those who -plume themselves on their so-called clinical “instinct,” but the -slow, laborious route of clinical “observation,” that leads more -surely to the vantage ground of truth, this assuredly in all -diseases, but in none more so than in <i>joint</i> disorders, whose -outward resemblances so oft hark back to inward disparities.</p> - -<p>First, as to the manner of man, while one would not decry the -hints obtainable from <i>physiognomical</i> peculiarities, it is often -hard, if not impossible, to fit the subject to the so-called “gouty -diathesis.” They are not all of the John Bull type; not a few -are spare in build. Hence the danger of too ready inference from -so-called “gouty” traits, to be regarded rather as ancillary to, -but not substitutes for, more exact criteria.</p> - -<p>Now, as to heritage, for, despite the fallacies that surround -inquiries into family predispositions, they often furnish valuable -hints as to the metabolic trend of the stock. True, ancestral -stories often prove indefinite, but fortunately less so in the -“gouty” than in those of “rheumatic” tendency. For, as Sir -Dyce Duckworth points out, even the laity are quick to recognise -what they term “chalky” gout, and so “if a history be given -of ancestors or relatives thus affected, there need be no hesitation -in pronouncing for true gout amongst them, and for the probably -gouty nature of such arthritic ailments as may be complained of -by the patients under examination.”</p> - -<p><span class="pagenum"><a id="Page_248"></a>[248]</span></p> - -<p>Turning to the individual himself—for the subjects of regular -gout are rarely women—what is his age? If he is over thirty-five -and has never previously had an arthritic disorder, it is much -more likely to be <i>gout</i> than rheumatism, this only as a broad -generalisation.</p> - -<p>What occupation does he follow? What are his habits? Is he -of the “idle rich” who “fare sumptuously every day”? Is he -a plumber, a painter, or a butler, coachman, or club waiter, -these last being men who, as Sir Thomas Watson observes, -“often live more luxuriously and more idly a great deal than their -masters”? In short, we must search for any evidence of overeating, -overdrinking, and indolence. For of this triad of vices is -gout too oft begotten.</p> - -<p>As to illnesses, his past may tell of classic outbreaks, one or -more in the great toe, and if to this be added a visible <i>tophus</i>, we -stand face to face with a “gouty diathesis.” More eloquent this -than a “cloud of witnesses” as to previous attacks of migraine, -asthma, eczema, etc. All these and more may emerge during -the subject’s recital, and by all means let them be ascertained. -But forget not that they often arise in the <i>non</i>-gouty. Above all, -though, miss not the significance of heightened blood pressure, a -cardiac lesion of degenerative type, sugar or albumen in the -urine. For these are of the things that will out, but let it not be -to our discomfiture!</p> - -<p>Even presuming that all facts and observations up to now -point to a “gouty” origin of the arthritis, the end is not yet. -What has evoked the arthritis? We seek a cause. For to call an -arthritis “gouty” is but to restate the problem. How clear the -need then for a meticulously careful investigation, in the hope of -achieving not a merely nosological, but an <i>etiological</i>, diagnosis.</p> - -<p>To narrow our field, we should, in the first place, exclude <i>gonococcal</i> -infection, and failing this, influenza, syphilis, or any of -the zymotic or other disorders prone to be followed by or associated -with <i>joint</i> affections.</p> - -<p>If none of such be forthcoming, we should search for <i>local foci -of infection</i>. The mouth and its accessory cavities first claim -attention. It should be closely scanned for the presence of oral -sepsis, the most fruitful source of which is <i>pyorrhœa alveolaris</i>. -If <i>dentures</i> are worn it is wise not to take the subject’s word that -all his teeth have been extracted. Like others, I have in such -found the broken-off stumps still <i>in situ</i>. The condition of -“bridges” should be noted, fruitful sources of sepsis as they are. -Clinical examination of the mouth may prove inadequate, as -<i>buried roots</i>, <i>cysts</i>, or <i>abscesses</i>, not to mention <i>alveolar rarefaction</i>, -etc., demand for their detection <i>radiographs</i>.</p> - -<p><span class="pagenum"><a id="Page_249"></a>[249]</span></p> - -<p>The <i>pharynx</i> and <i>tonsils</i> should be thoroughly investigated, for -disorders of these same are by no means uncommon in “gouty” -subjects. Any history of <i>aural</i> or <i>nasal</i> discharges demands the -same careful local examination; and, needless to say, the same -course must be pursued in regard of any <i>local infections</i> of the -<i>genito-urinary passages</i>. In short, in <i>gouty</i>, as in <i>non-gouty</i>, forms -of <i>arthritis</i>, thorough and routine examination of every patient by -modern <i>bacteriological</i> methods is imperative.</p> - -<p>Ignorant of the precise <i>etiology</i> of <i>gouty</i> arthritis, we can ill -afford to overlook any associated <i>infective</i> foci which may prejudice -the well-being of the victim, as, for aught we know to the -contrary, we may be overlooking the very <i>fons et origo mali</i>. -Compare our attitude towards other arthritides of cryptic origin, -how systematic our search for <i>infective</i> foci, and what a light has -thereby been shed on their intimate etiology!</p> - -<p>Here may we lodge a plea for routine examination of the blood -in all cases of <i>gout</i>? For, as shown, the findings, <i>leucocytosis</i>, etc., -have doubtless some profound significance. Apart from this, the -routine employment of <i>complement-fixation</i> tests for the organisms -responsible for local infections might illumine the obscurity that -overhangs this complex problem of their relationship to remote -pathological lesions.</p> - -<p>If up to now our search for local foci prove futile, it remains -for us to note the presence or absence of <i>functional derangements</i> of -the <i>alimentary tract</i>, or its <i>accessory glands</i>. We must not, -because we think perhaps that the patient “looks gouty,” assume -that his <i>dyspeptic</i> symptoms are of like origin. It is our duty to -ascertain, if possible, the precise nature and origin of the dyspepsia.</p> - -<p>We know that, given <i>oral sepsis</i>, sequential infections of the -<i>appendix</i> and <i>gall bladder</i> are not uncommon. Recently it has -been remarked that many <i>gouty</i> patients suffer with attacks of -pain in the region of the appendix, and simultaneously tenderness -over the gall bladder. That the subjects of gout enjoy no -immunity from appendix or gall bladder disorders is certain, and -at this we need not be surprised, seeing the frequency with which -they suffer from alleged causes thereof, <i>i.e.</i>, dental sepsis, etc.</p> - -<p>But what we would insist upon is that we should not be content -merely with dubbing these symptoms “gouty,” as they are much -more likely to be, not symptomatic of gout, but <i>etiologically</i> related -thereto. If then we are to arrive at the exact nature of the underlying -lesion, the probable site of infection or toxic absorption, -we must invoke all modern methods of investigation. Thus, how -valuable the existence of an X-ray barium or bismuth meal in -furnishing positive evidence of gastric or duodenal ulcer on the one -hand or of <i>gall bladder</i> or <i>appendix</i> disease on the other. What<span class="pagenum"><a id="Page_250"></a>[250]</span> -an aid to the location of adhesions the demonstration of <i>ileal</i> -and <i>cæcal</i> stasis, etc.!</p> - -<p>In obscure cases the <i>fæces</i> may have to be scrutinised for -evidences of <i>pancreatic</i> inefficiency, viz., bulky pale stools, undigested -meat fibres, and excess of neutral fat. Their <i>bacterial</i> -content, too, if abnormally high, should be noted. As in other -arthritides of unknown origin, the results following the administration -of <i>vaccines</i> prepared from the predominant organisms have -been such as to suggest a causal connection.</p> - -<p>The urine should be subjected to <i>chemical</i> and <i>bacteriological</i> -examination. As to <i>uric acid</i>, the delusion still widely prevails -that gouty subjects excrete large amounts thereof. How frequently -is “the degree of acidity” of the urine or “its content of -uric acid” held to justify a diagnosis of gout. The deduction is -quite unjustifiable. Equally so the assumption that the reverse, -a defective excretion of uric acid, is an invariable feature of the -gouty diathesis. For though when on a <i>purin-free</i> diet the output -of uric acid in the gouty is low, it rarely, if ever, falls below the -level of normal. The truth is that we cannot <i>on the mere basis of -the variations in uric acid excretion in the urine</i> presume to diagnose -gout.</p> - -<p>To have any semblance of diagnostic value, the patient should -be on a <i>purin-free</i> diet, and a long series of exact quantitative -examinations made. C. v. Noorden, to gauge the limit of tolerance -of his patients, gives them increasing amounts of purin, and -so determines the quantity the subject can deal with without -showing retention. But, as Von Fürth satirically observes, -“when a physician allows a quantitative analysis to be made of -any arbitrarily collected specimen of urine of his patient and then -makes a diagnosis of the presence or absence of a ‘gouty diathesis’ -after a glance at the list of data of the analysis, he is really not -proving by his actions his possession of diagnostic acumen as -much as he is laying bare his total ignorance of bio-chemical -matters.”</p> - -<p>So much for the diagnostic valency of uric acid estimates in -chronic gout, but if the patient be on purin-free diet, and an acute -attack ensue, the curve of uric acid excretion is fairly characteristic. -In other words, for a day or two preceding the outbreak, the uric -acid output falls below the usual level, but early in the attack -rises markedly, to be followed by a secondary fall.</p> - -<p>Some aid in diagnosis has been afforded by the fact that after -ingestion of purin-containing food the gouty individual does not, -like a normal person, eliminate the excess of uric acid, but the -excretion is “spread out over a number of days.” But this -retardation and diminution in the excretion of exogenous purins<span class="pagenum"><a id="Page_251"></a>[251]</span> -has been seen in non-gouty forms of arthritis, not to mention some -cases of nephritis and chronic alcoholism. Hence delayed nuclein -exchange, though highly suggestive of gout, is not infallibly -diagnostic thereof.</p> - -<p><i>As to uric acid in the blood</i>, it will, I fear, not for long, if ever, -be easy to prevail on patients to submit to withdrawal of the -amount of blood necessary, even by modern methods, for its -estimation. Fortunately, our American <i>confrères</i> appear to be -more successful in securing such opportunities. Pratt states that -in his twenty-one cases of genuine gout the uric acid content of -the blood, irrespective of diet, was 3·7 mg. per 100 grams, as -opposed to 1·7 mg., the average amount in 156 non-gouty cases -studied by Adler and Ragle. Still Pratt noted that in a few cases -of undoubted gout the uric acid content of the blood was within -normal limits, though it never fell, even on a purin-free diet, below -1·4 mg. Nevertheless he holds that there is conclusive evidence -that the uric acid content of the blood is in gouty individuals -notably increased both in the intervals and during attacks.</p> - -<p>He has found the sweetbread meal an aid in diagnosis, and the -following is his method of procedure: “The patient is placed on -a purin-free diet, and the daily output of uric acid in the urine -determined. After having been on this diet for at least four days -the blood is analysed for uric acid, and 150 to 300 grams of sweetbread -(weighed raw) are fed. The purin-free diet is then resumed. -The blood of gouty subjects forty-eight to seventy-two hours -after the sweetbread meal has shown in every case examined an -abnormally high amount of uric acid, while in control subjects this -was not found. It is not improbable that this rise in the uric acid -content of the blood may occur in certain cases of nephritis and -other pathological conditions.”</p> - -<p>A <i>bacteriological</i> examination of the <i>urine</i> should be undertaken. -Trautner held <i>mucous colitis</i> as one of the initial manifestations of -gout, and believes that the <i>bacillus coli communis</i> is the primary -agent in gouty affections. He suggests that it produces a reducing -substance which during its passage through the body is transmuted -into xanthin and uric acid. Be this as it may, there is -increasing evidence that an etiological potency may attach to -coliform bacilli, streptococci, and other organisms. Dr. Munro -in his researches at the Royal Mineral Water Hospital, Bath, noted -that the blood serum in one of my cases of acute gout agglutinated -<i>B. coli</i>. He has also found streptococci in the urine in acute gout, -and these subjects certainly enjoy no immunity from other forms -of bacteriuria.</p> - -<p>It is beyond the scope of this volume to outline the methods of -differentiating and determining the exact organisms which may<span class="pagenum"><a id="Page_252"></a>[252]</span> -be responsible for gouty arthritis. But if we aim at rational as -opposed to purely haphazard serum or vaccine therapy, we must -effect a differential specific diagnosis in a bacteriological sense. -How searching our investigations must be in these cases we -learn from Adami’s brilliant address on <i>sub-infection</i> when he laid -down the axiom that in all cases “there ought to be routine blood -cultures, routine examination and reports on the stools and their -predominant bacterial types, blood counts, hæmoglobin examination, -in fact the full clinical study of each case, so that nothing -is neglected.”</p> - -<p>No apology is needed for our insistence on the imperative -necessity of routine systematic investigation from all sides of -these cases of gouty arthritis. For its origin still remains hidden, -and who can doubt that, to remove this long-standing reproach, we -must approach our study of these cases in a more catholic attitude -of mind, one bent on <i>etiological</i>, not merely nosological, diagnosis?</p> - -<h3><span class="smcap">Clinical Diagnosis</span></h3> - -<h4><i>Introductory Remarks</i></h4> - -<p>The word gout itself is void of offence, innocent of scientific -pretensions, neither expressing nor violating any article of pathological -belief. But let us not forget that the term is neither self-explanatory -nor final. Derived through the French <i>goutte</i> from the -Latin <i>gutta</i>, it but expresses laconically the fanciful doctrine of -those who so christened it.</p> - -<p>What the old humoralists saw was the <i>tophus</i>, and would that -they had clung more steadfastly to this as their sheet anchor in -diagnosis! but casting their moorings, they launched forth on the -uncharted seas of abstract philosophy. Even in the writings of -the nineteenth century physicians we trace the influence of their -disquisitions, and we are tempted to think that some even of our -day still bide beneath their thrall.</p> - -<p>But, with the advance of pathology to the dignity of a natural -science, we must assert our independence of misty hypotheses, -rendering obeisance only to facts. What then, may we ask, is the -outstanding fact of the “gouty diathesis”? It is, in a word, -the <i>tophus</i>! Even as the vague and shadowy constitutional warp -known as the “rheumatic diathesis” finds expression, or rather -becomes incarnate, in fibrous <i>nodule</i> and <i>induration</i>, so also does -the equally nebulous “gouty diathesis” become objective, crystallised -in the <i>tophus</i>.</p> - -<h3><span class="smcap">The Diagnostic Status of Tophi</span></h3> - -<p>This problem calls for more critical consideration than is -usually accorded thereto. The tophus is, in truth, the touchstone<span class="pagenum"><a id="Page_253"></a>[253]</span> -of gout, yet not a little controversy obtains as to the -frequency of its incidence in “gouty” subjects.</p> - -<p>At one extreme we find Sir Charles Scudamore maintaining -that tophi have occurred in only a few individuals “of particular -‘gouty’ idiosyncrasy,” in, according to him, less than 10 per -cent. of the victims. At the other Sir Alfred Garrod, discussing -these figures, observes: “From my own experience I consider these -numbers far below the real proportion, from their being deposited -in parts of the body scarcely to be expected.”</p> - -<p>Now as to these distinguished physicians, who shall doubt that -of the twain Garrod stood on firmer ground than his predecessor? -In arriving at their diagnoses of gout, Scudamore rested on -clinical “instinct,” Garrod on clinical “observation.” To the -more scientific mind of the latter the tophus appealed with all -the insistence of a fact, while the former was yet in bondage to -abstract philosophy, dominated too much by crude and unproven -hypotheses.</p> - -<p><i>Given the presence of tophi, the diagnosis of a “gouty diathesis” -is assured; in their absence it is but speculative.</i></p> - -<p>It is upon this dictum that we would take our stand, and this -without depreciating in any way the pioneer researches of Garrod. -For it must be recognised that the increasing differentiation of -joint diseases has proceeded apace. How many are now affiliated -to specific germs, not to mention the undreamt-of light thrown -on their inward characters by X-rays! Scudamore’s work -appeared exactly a century ago, Garrod’s in 1876. The conclusion -then seems inevitable that many of their alleged cases of <i>gout</i>—at -any rate, those <i>unattested by tophi</i>—would now be relegated to -widely different categories.</p> - -<p>But this zeal for infinite cleavage and subdivision, so characteristic -of the modern school, far from diminishing, does but -<i>accentuate</i>, the <i>diagnostic</i> valency of the tophus. It still remains -<i>the</i> infallible criterion of diagnosis, and, for myself, I feel convinced -that infinitely more good than harm would ensue if we -refuse to recognise any individual as being of the “gouty diathesis” -unless he exhibit these objective stigmata thereof.</p> - -<p>Of course to some such a rigid attitude will spell anathema. -I hear them say in oracular tones: “Never forget gout, or awful -indeed will be your awakening.” More harm, say they, is wrought -by failure to recognise gout than by diagnosing gout where none -is. Doubtless they are right in counselling us not to forget gout, -but not to the exclusion of all else. For, at issue with them, I -hold it better to miss gout than to miss <i>syphilitic</i>, <i>gonorrhœal</i>, -and other forms of arthritis.</p> - -<p>“A name being so readily found for an obscure disease, the<span class="pagenum"><a id="Page_254"></a>[254]</span> -practitioner considers himself as excused from the difficult task -of nicer discrimination.” Thus wrote Scudamore a century since, -a rebuke and a warning for all time.</p> - -<h3><span class="smcap">Tophi in Relation to Arthritis</span></h3> - -<p>How elated we are, and rightly, when in an obscure form of -arthritis we pounce on these objective criteria of gout, how apt -to deem our diagnostic quest as ended, and with what fatal glibness -the time-worn “gout” slips from our lips, sure, alas, of -ready and almost complaisant acceptance. Fallacious inference, -all too prevalent, that the presence of <i>tophi</i> stamps any <i>concomitant -arthritis</i> as “gouty.”</p> - -<p>True, tophi are pathognomonic of gout, but their existence does -not confer on their host <i>immunity from all other forms of arthritis</i>. -In view of the increasing light shed upon joint disorders, who can -doubt that (and this not only for our forefathers) the <i>tophus</i> -has too often proved a veritable snare, allaying all diagnostic -doubts, lulling us into false security? For an individual may, for -example, exhibit <i>auricular tophi</i> and be the victim also of an -<i>arthritis</i>, but the latter is not inevitably “gouty.” All that can -be assumed at sight is merely that the joint disorder, whatever -its nature, has ensued in a subject of “gouty diathesis.”</p> - -<p>For it may be of specific infective origin, <i>gonococcal</i>, syphilitic, -pneumococcal, etc. <i>Quâ</i> a concomitant arthritis, then, the diagnostic -significance of tophi, at any rate when of <i>ab-articular</i> site, -must not be overrated. It is at once a beacon and a warning. -In other words, the diagnosis of a co-existent arthritis as “gouty” -should not be entertained pending the exclusion of all other -forms of arthritis.</p> - -<p><i>Conversely, in the absence of tophi, the diagnosis of an arthritis -as “gouty” is not absolute, but presumptive.</i></p> - -<p>For in the lack of these objective stigmata how can the authenticity -of our diagnosis be established? Is it not when achieved -a <i>nosological</i> rather than a diagnostic feat? Put otherwise, is not -our diagnosis, especially in <i>initial</i> attacks, largely <i>topographical</i>? -Not that we would for one moment decry the advantage of -realising the predilection of certain organisms for this or that -particular joint: of the gonococcus for the sterno-clavicular, of -typhoid for the hip, post-scarlatinal rheumatism for the phalangeal -joints, etc. But we would drive home the fact that our diagnosis -in <i>initial</i> attacks of “gout” is very largely <i>topographical</i>. Let -but inflammatory trouble ensue in the <i>big toe</i>, and forthwith we -assume it gout, as if, forsooth, this particular joint were immune -from all other forms of disease, this, too, while in the same<span class="pagenum"><a id="Page_255"></a>[255]</span> -breath we comment on its extreme liability to injury. So, indeed, -we maintain, is the marked predilection of gout for the toe joint -explained. Is not this a little crude? Does not the same circumstance -increase its liability to <i>infection</i> and, we may add, not -less important, its proneness to <i>static deformities</i>? But to this -we shall recur when discussing <i>differential</i> diagnosis.</p> - -<p>To return, how often, apart from the above pitfalls, is the -diagnosis “gout” arrived at without any search for tophi wherewith -to support the assumption. Our contention is that even -in primary attacks of gout our search for <i>tophi</i> should be exhaustive. -If undiscoverable, why not be honest with ourselves and -recognise that our diagnosis is <i>presumptive</i> pending their -development?</p> - -<p>Sir William Roberts on this point observes: “As a rule, diagnosis -of acute articular gout is easy, but exceptional cases of difficulty -occur. The <i>gouty</i> character of the inflammation is <i>affirmed by the -discovery of uratic concretions</i> in the rim of the ear or elsewhere.”</p> - -<p>Again, Sir William Osier, discussing the diagnosis of acute -gouty polyarthritis, remarks: “We have had of late years several -cases admitted for the third or fourth time with involvement of -three or four of the larger joints. The <i>presence of tophi</i> has settled -the nature of a trouble which in previous attacks has been regarded -as ‘rheumatic.’”</p> - -<p>One may, we think, gather from these two statements the inference -that both these distinguished authorities hold <i>tophi</i> to be the -<i>only infallible criterion</i> upon which to base a diagnosis of <i>gouty -arthritis</i>. In my own practice I must affirm that I never feel -justified in christening any arthritis as <i>gouty</i> unless I have discovered -<i>tophi</i>, and then only when to the best of my ability <i>all -other known causes of arthritis</i> have been excluded.</p> - -<h3><span class="smcap">Frequency of Tophi in True Gouty Arthritis Underestimated</span></h3> - -<p>In reviewing the statistics of authors as to the frequency of -the incidence of tophi in their cases of assumed gouty arthritis -I am inclined to think their relative infrequency is apparent -rather than real, in other words that many of their cases of -alleged “gouty” arthritis which <i>lack tophi</i> would, if investigated -by modern methods, have been shown to be due to other causes of -arthritis, this especially as regards their assumed cases of -<i>chronic</i> gout. For who can doubt that prior to the discovery of -X-rays many cases of <i>osteoarthritis</i>, etc., were thus erroneously -labelled? Nor indeed, as we hope to show later, is it improbable<span class="pagenum"><a id="Page_256"></a>[256]</span> -that similar fallacies obtained even in regard to <i>acute</i> types of -gout, particularly when of <i>polyarticular</i> distribution.</p> - -<p>It will be noted that we confine our criticisms to those examples -of “gouty” arthritis <i>unassociated with tophi</i>. But if, as we -maintain, our scepticism be justifiable, then it follows that it -<i>diminishes</i> to an unknown extent the <i>percentage of cases of -genuine “gouty” or uratic arthritis which lack tophi</i>.</p> - -<h3><span class="smcap">Difficulty of detecting Tophi</span></h3> - -<p>Apart from the probability of such erroneous relegation to the -“gouty” category of <i>non-gouty</i> arthritides, there remains this -further consideration, the ease with which tophi, even when -superficial, may be overlooked. We look for pearly white concretions, -and if none are seen we straightway assume that <i>tophi</i> -are <i>absent</i>. This, I am sure, is a very common pitfall. At their -inception tophi are neither white nor hard. They are largely -fluid and soft to touch. The skin over them may be unchanged in -colour or reddened. Only when mature, and the overlying skin -is thin, do they assume the ordinary aspects of a tophus. These -observations apply not only to tophi in the ears, but to those in -the vicinity of the small joints of the hands and feet or elsewhere. -I would urge that in the case of all soft localised swellings of -dubious nature in the neighbourhood of the phalangeal joints -aspiration with a hypodermic syringe will often prove very helpful. -If fluid can be withdrawn and the same microscopically examined, -it will more often than is supposed reveal the presence of biurate -crystals.</p> - -<p>More information is badly needed as to the relationship of -their formation to acute attacks of gout. Garrod on this point -remarks: “The deposits are probably formed during an attack -of gout, but occasionally they appear shortly afterwards. In one -case, of which I have notes, the ears were carefully examined -without result when the patient left the hospital, but within -ten days, on re-examination, a deposit was found. Perhaps some -fluid was effused during the fit, but being at first transparent, -could not be easily distinguished.” Sir Dyce Duckworth, too, -observes: “After acute attacks of gout have passed off there may -follow renewed pain in the neighbourhood of the joint, and later -there is discovered a nodular or soft swelling. In the latter case -there may be fluctuation, indicating a liquid collection of urates. -This should never be opened. In a few weeks this tumour tends -to indurate, grow more compact, and a so-called ‘chalky’ -concretion is established.”</p> - -<p>Reflection upon the foregoing considerations leads me to the<span class="pagenum"><a id="Page_257"></a>[257]</span> -conclusion that not only was Garrod right in his affirmation -that “<i>gouty inflammation is invariably attended with the deposition -of urate of soda</i>,” but more that <i>examples of true uratic -arthritis which lack tophi are exceptional</i>, and that <i>in their absence -their diagnosis as such cannot be with certitude established</i>.</p> - -<p>We have now, we trust, sufficiently defined our attitude towards -the tophus, the salient objective stigma of a “gouty diathesis,” -and the indispensable <i>rôle</i> it plays in enabling us to establish the -diagnosis of articular gout.</p> - -<hr class="chap x-ebookmaker-drop"> - -<div class="chapter"> - -<p><span class="pagenum"><a id="Page_258"></a>[258]</span></p> - -<h2 class="nobreak" id="CHAPTER_XX">CHAPTER XX<br> -<span class="smaller">CLINICAL DIAGNOSIS (<i>continued</i>)</span></h2> - -</div> - -<h3><span class="smcap">Acute Articular Gout—Localised Variety</span></h3> - -<p>The nonchalance with which not a few writers dismiss the -diagnosis of <i>acute gout</i> when located in the <i>great toe</i> or elsewhere -in the foot is, to say the least of it, somewhat remarkable. “It -is a very easy matter,” say they, and as an earnest of their good -faith are silent as to the many pitfalls that await the unwary. -Should they deign to <i>differential</i> diagnosis, they are at pains to -discriminate between it and <i>acute articular rheumatism</i>, which -<i>re</i> classical outbreaks in the <i>toe</i> seems a little superfluous! But -not a word of <i>traumatic</i> lesions, <i>infective</i> processes and <i>static</i> -deformities, all infinitely more likely stumbling-blocks.</p> - -<p>Did all cases conform to the classic type, <i>acute sthenic gout</i>, -it might be held relatively easy. But such are not, to say the -least of it, common nowadays. More often than not our examples -are, as Garrod terms them, of acute <i>asthenic</i> character. As he -observes: “There may be indeed pain and tenderness in the toe, -and some amount of swelling, but accompanied with little heat -or redness, and all febrile disturbance may be absent; still œdema -is generally observed and itching and desquamation follow.”</p> - -<p>That diseases, like their victims, alter with environment is -but too clear. Who can doubt that the gout of the Regency has -to-day assumed a milder clinical <i>facies</i>? Physicians of those days -were haunted with the fear of confounding it with <i>erysipelas</i> -and <i>phlegmon</i>. Still, while no such fears apparently beset us -to-day, it were well to walk circumspectly.</p> - -<p>Thus, recently a friend of mine came across an instance of -what he deemed <i>acute gout</i> in a <i>metacarpo-phalangeal</i> joint. Its -failure to respond to colchicum and the growing intensity and -extent of the local inflammation suggested incision, when, lo, -pus issued, to the subject’s comfort, but to his own chastening!</p> - -<p>There are, however, many more likely sources of fallacy, these, -too, of the most diverse type, inasmuch as they differ according -to the exact location in the foot of the assumed gouty process. -For while the <i>big toe</i> is the <i>site of predilection</i> for the <i>initial</i> manifestation, -it is not always so. The <i>primary</i> outbreak may be -located in any of the smaller joints of the foot, or outside them in -related structures: in the <i>heel</i>, the <i>sole</i>, or the <i>tendo Achillis</i>.<span class="pagenum"><a id="Page_259"></a>[259]</span> -These vagaries greatly enhance the difficulties of diagnosis. For -the process of differentiation will vary according to the particular -joint or structure involved, the predilections of certain infective -processes, not to mention the marked liability of the foot to painful -disturbances of static origin.</p> - -<h3><span class="smcap">Differential Diagnosis</span></h3> - -<p>Inasmuch as the primary outbreak may be located in any part -of the foot, we purpose, for reasons just cited, dealing <i>seriatim</i> -with gout in (1) the big toe; (2) the instep; (3) the heel; (4) the -sole.</p> - -<h3><span class="smcap">Gout in the Big Toe</span></h3> - -<p><i>Infections.</i>—There is no <i>â priori</i> reason why any of the infections -may not find a nidus in the <i>first metatarso-phalangeal</i> joint. Thus, -Garrod, as we know, held gouty subjects specially liable to <i>pyæmia</i>. -In rare instances, the primary focus has been in or near the -<i>great toe</i>, and has consequently been mistaken for <i>gout</i>. The -rapid progress of the disease would of course soon clear up the -nature of the case. But if the subject has previously suffered -from gout, such a diagnostic error at first sight is quite excusable. -Accordingly, as a safeguard in all doubtful cases, inquiry should -be made as to the existence of <i>bladder</i> troubles, <i>piles</i>, etc., -especially <i>any recent operation</i> in this or other regions.</p> - -<p>Again, while gout in its <i>articular</i> form is rarely, if ever, met -with in children, it must be recalled, on the authority of Sir James -Goodhart, that <i>rheumatism</i> in their instance is occasionally -limited to <i>one</i> joint. Moreover, this distinguished physician -actually saw it localised in the <i>great toe</i>, “in a case in which the -subsequent course of the disease showed that it was acute -rheumatism.”</p> - -<p><i>Acute Gonococcal Arthritis.</i>—We may recall that Van Swieten, -a disciple of Boerhaave, held that sometimes a wife while nursing -her gouty husband had contracted the same disorder. A tribute, -we fear, to Van Swieten’s diplomacy rather than to his clinical -acumen—an euphemism for gonorrhœal rheumatism!</p> - -<p>Of course in adolescents or in young adults <i>monarticular</i> pain, -with or without swelling, heat, or redness, should not suggest -“gout,” but an <i>infective</i> disorder either in the <i>joint</i> or the -related <i>bone-ends</i>. At the same time middle-aged men enjoy -no immunity from gonorrhœa, and we may add that <i>gonococcal -infection</i> of the <i>metatarso-phalangeal</i> joints is not so uncommon. -When located in that of the great toe, it is easy to see how readily -the acute arthritis may be confused with gout. But, unlike the -latter, its duration is measured by months or weeks rather than<span class="pagenum"><a id="Page_260"></a>[260]</span> -by days. It is well to recollect, too, that “gouty” persons are -more prone to develop arthritis following gonococcal infection. -Given therefore a history even remote, we should in doubtful -cases recall the longevity of the organism, its persistence in the -prostatic recesses, and the need for bacteriological investigation.</p> - -<p><i>Traumatic Lesions.</i>—Its exposed situation renders the big toe -very liable to trauma. Often, too, the injury being slight, and not -followed by any immediate consequences, the connection may -easily be overlooked. A blow or a fall may readily bruise the -synovial membrane without at first any external sign. But -given trivial hæmorrhage into the cavity or subjacent tissues, an -acute synovitis with effusion is induced.</p> - -<p>Again, joint disorder following <i>injury</i> is usually <i>monarticular</i>, -whereas the same when the outcome of so-called “constitutional” -causes is generally <i>oligo</i>- or <i>poly</i>-articular. The relevancy of this -is obvious when we recall that <i>initial</i> attacks of <i>gout</i> are <i>monarticular</i>. -Accordingly, given a history of definite injury to the -toe joint, the question arises, Is it <i>acute gout</i> or <i>acute traumatic -arthritis</i>? this especially if the subject has not had a previous -attack of gout at this site.</p> - -<p>Here I would lay stress on the fact that <i>indirect</i> rather than -direct traumatisms are more common antecedents or determinants -of gout, viz., sprains or strains. Moreover, in reviewing the -writings of the older physicians one is driven to the conclusion -that frequently a septic cellulitis, synovitis, or a frankly traumatic -arthritis was confused with acute gout.</p> - -<p>The following examples cited by Scudamore are, we contend, -susceptible of such an explanation: “A gentleman much -subject to gout, when considering himself unusually well, underwent -the slight operation of having the nail of the great toe cut -on account of its improper growth. The toe was much pressed, -and gouty inflammation was the immediate consequence.” In -another case “the patient, never before having suffered the gout, -tore off a broken portion of the thumb-nail, so as to make the part -tender. Very soon the thumb and part of the hand put on a -swollen and shiny appearance, and was exquisitely painful. A -poultice was applied. Suddenly on the third evening the pain -quitted the thumb and seized the toe, next the ankle, then the -knee, and lastly the great toe of the other foot. Throughout he -secured ease and sleep till the first light of the morning appeared, -and hence facetiously observed that the gout in this respect -assumed all the behaviour of a ghost.” Was not this probably a -case of <i>septic absorption</i> with <i>cellulitis</i> and a mild degree of -sapræmia, evoking <i>arthralgic</i> pains?</p> - -<p>In conclusion, without denying the potentialities of trauma,<span class="pagenum"><a id="Page_261"></a>[261]</span> -whether direct or indirect, in determining an outbreak of gout, we -would submit that its diagnosis under such circumstances should -not be hastily arrived at, but by the slower process of elimination, -this especially if the trauma has involved slight abrasions with -the possibility of sepsis. A quick response to <i>colchicum</i> would of -course be highly suggestive of <i>gout</i>.</p> - -<p><i>Acute Osteoarthritis.</i>—It is perhaps not so widely recognised -as it should be that osteoarthritis not uncommonly attacks the -metatarso-phalangeal joint of the great toe. It becomes enlarged -owing to the hypertrophy of the articular ends. Like similar -lesions in the small joints of the hand, the big toe joint from -time to time undergoes exacerbation, with increased vascularity -and local heat, which, though of minor degree, may by a superficial -examiner be readily misinterpreted as <i>gout</i>. The parts are -painful, somewhat swollen, hot, and tender, but the local symptoms -are never intense, and constitutional disturbance is lacking. -The presence of osteoarthritic lesions elsewhere and the revelations -of <i>skiagraphy</i> will suffice for differentiation of such cases from -<i>asthenic articular gout</i>.</p> - -<h3><span class="smcap">Static Foot Deformities</span></h3> - -<p><i>Hallux Valgus with Inflamed Bunion.</i>—Scudamore in his -“Treatise on Gout” observes that “the bursal disease over the -first joint of the great toe, which is familiarly known as <i>bunion</i>, is -a very common complaint with gouty persons.” In view of the -fact that no reference is made in the context to the absence or -presence in such cases of a condition of hallux valgus, one is led -to believe that Scudamore overlooked the deformity and regarded -the local bursitis as the outcome of a gouty inflammation of this -structure.</p> - -<p>Bradford and Lovatt, discussing hallux valgus, observe: “There -may be pain and irritability in the great toe joint, and in severe -cases extreme pain and difficulty in walking, which is usually -attributed by the patient to <i>gout</i>.” We would only qualify this -statement by the fact that the local heat, redness, and swelling -that in this condition so often follow slight injuries or excessive -walking is not only so interpreted by the patient, but far too -frequently also by his <i>medical attendant</i>.</p> - -<p>Routine examination of the bare foot will minimise the chance -of such a fallacy, though of course it must be borne in mind that -a <i>gouty</i> subject may present this deformity. But when we recollect -that <i>hallux valgus</i> of <i>slight degree</i> “is almost universally -present after middle childhood,” we see that, given the presence -of this static foot deformity, any inflammatory process in the<span class="pagenum"><a id="Page_262"></a>[262]</span> -superjacent structures is infinitely more likely to be due to an -<i>inflammatory bursitis</i> than to a <i>gouty arthritis</i>.</p> - -<p>Given an inflamed bursa with cellulitis spreading over the -dorsum of the foot, confusion with <i>acute sthenic gout</i> is all too easy. -But in our experience, <i>mirabile dictu</i>, the ordinary more or less -chronic circumscribed redness over the bunion is but too commonly -misinterpreted as gout, this particularly in women, -despite the rarity with which gout attacks their <i>toe</i> and the -frequency with which their footgear is precisely adapted to produce -<i>hallux valgus</i>. Given therefore the presence of this static -foot deformity, we should in the absence of objective stigmata of -gout, viz., <i>tophi</i>, suspend our diagnosis pending observation of -the results obtained by local treatment of the displaced toe.</p> - -<p><i>Hallux Rigidus.</i>—This deformity is but too often overlooked, -and if marked by pain and more or less rigidity of the first <i>metatarso-phalangeal</i> -joint, it may, in lack of adequate examination, -be flippantly dismissed as “gout,” this more particularly in its -later stages, when, in addition to pain and stiffness therein, the -joint is swollen, tender to the touch, and the bony ends actually -enlarged. Here again local examination, if carefully carried out, -will suffice to obviate such errors, while the quick response to rest -and appropriate applications, with correction of the frequently -associated sunken arch, will sufficiently attest its true nature.</p> - -<p><i>Metatarsalgia.</i>—As pointed out in our previous work on Fibrositis, -“this painful condition is more often than not confused with -rheumatism or gout.” We have known subjects wander to -nearly every spa on the Continent under such a misconception. -Not to mention the financial expense, the dietetic penances -imposed, the consequences of such faulty diagnosis, are by no -means trivial, for the intensity of the suffering may reduce the -walking capacity to a minimum.</p> - -<p>The neuralgic pain radiates into the toes and often upwards -into the leg, usually comes on while walking, and is relieved by -the removal of the boot. For its detection any altered relationship -in the position of the third, fourth, and fifth metatarsals, -especially their displacement to a lower level than normal, should -be noted, and any limitation of the power of dorsal flexion of the -foot likewise estimated. The presence of <i>callosities</i> under the -<i>heads</i> of the <i>metatarsals</i> is very suggestive of this painful condition.</p> - -<h3><span class="smcap">Gout in the Instep</span></h3> - -<p>Next to the metatarso-phalangeal joints, the <i>tarsal</i> articulations -are the most frequent site of <i>initial</i> attacks of gout. Here -again we would insist on the necessity of excluding <i>infections</i> of<span class="pagenum"><a id="Page_263"></a>[263]</span> -the <i>tarsal joints</i> or <i>shafts</i> and even more important, <i>static foot -deformities</i>.</p> - -<p><i>Gonococcal Arthritis.</i>—In a table compiled by Garrod from those -of Foucart, Brandes, Rollet, and Fournier, the relative frequency -of the implication of individual joints in gonorrhœal arthritis -shows that out of a total of 119 the <i>tarsus</i> and <i>metatarsus</i> were -attacked in five instances. In the more acute cases the periarticular -swelling, local heat, and pink blush may be confused -with <i>acute gout</i>. The resemblance is enhanced in that, as in gout, -the overlying <i>tendon sheaths</i> are liable to become inflamed and -distended with fluid.</p> - -<p><i>Tuberculous and Syphilitic Disease of the Tarsal Joints or the -Related Joints.</i>—In cases of obscure pain and inflammatory trouble -in the instep the possibility of arthritic and bony lesions of this -nature should not be overlooked, especially if there be suggestive -lesions elsewhere, or if the history afford evidence of the possibility -of such contingencies.</p> - -<p><i>Pes Planus.</i>—In all cases of pain and swelling, with or without -redness, in the instep, it is well to recollect that, though flatfoot -may for a long time exist without giving rise to symptoms, it -frequently happens that, in sequence to some unusual strain on -the plantar arch, the static disturbance in the foot enters quite -<i>abruptly</i> on a <i>painful</i> phase. Congestion and swelling of the foot -is common, and actual teno-synovitis of the tibial and peroneal -muscles is not infrequent. Tenderness, too, at points of ligamentary -strain is almost always present, and more or less constant -pain.<a id="FNanchor_40" href="#Footnote_40" class="fnanchor">[40]</a></p> - -<p>The frequency with which the <i>local</i> and <i>referred</i> pains of <i>flatfoot</i> -are misinterpreted as “gout” and dietetic restrictions and other -useless and uncalled-for methods of therapy enjoined is well -exemplified by a case which has just left our consulting room.</p> - -<p>The subject, a middle-aged spinster of lean kind, came to Bath -for treatment of her supposed gout, and for which indeed she had -previously received spa therapy. Her feet when bared showed -a condition of double <i>hallux valgus</i> with related <i>bursal thickenings</i>.<span class="pagenum"><a id="Page_264"></a>[264]</span> -The occasional inflammation of these latter structures and the -recital of doubtful ancestral proclivities were the sole evidence on -which was based the diagnosis of <i>gout</i>. In addition, as is so -frequent in hallux valgus, there was associated therewith a -<i>bilateral flatfoot</i>, and it may be added that in the left foot a <i>hammer-toe</i> -had been removed some years since. Unfortunately the -neglected symmetrical flatfoot had, as so frequently happens, -initiated, through the erroneous deflection of a body weight, a -condition of <i>chronic villous synovitis</i> in both knees. This again -was misinterpreted as but another proof of her assumed “gouty” -diathesis. Reflecting upon human nature, how curious the -reluctance with which such subjects elect to part with their -“gout.” Women especially hold tenaciously thereto, even those -of austere type, clinging to the taint handed down to them from -some far-off ancestor whose “superfluity of naughtiness” was a -by-word among his generation. To exchange gout, <i>morbus -dominorum</i>, for “flatfoot” and inflamed “bunions,” savours of -degradation, and to couple it with aspersions on their footgear -is well-nigh insupportable. Nor are the “lords of creation,” we -fear, exempt from this failing. We recall during the War being -consulted by a highly placed officer who complained of gout. A -well-preserved man of nigh sixty years of age, he obviously prided -himself on being immaculately booted. As such patients frequently -do, he brought his own diagnosis of “gout.” Removing -his footgear, manifestly too small, his crucified toes stood out -with bunions in a state of hot resentment. But impeachment of -his boots was too much for him. Persuasion and argument were -futile, and I doubt not he walks to-day stiff, a martyr to his -vanity. “Il faut souffrir pour être belle.”</p> - -<h3><span class="smcap">Gout in the Heel</span></h3> - -<p>In some instances the first manifestations of gout occur in the -heel, while in others the sheath of the neighbouring tendo Achillis -is the part first invaded. Probably there is no region of the foot -in which there exist more pitfalls, and doubly careful should we -be before concluding that any painful or inflammatory condition -thereof is one of “gout.”</p> - -<p><i>Referred Pain.</i>—Pain in the heel affords many loopholes for -misinterpretation. It may, as Sir James Paget pointed out many -years ago, be symptomatic of a <i>renal calculus</i>. In my own experience -it is sometimes complained of by the subjects of <i>internal -hæmorrhoids</i>, the pain waxing and waning with the variations -in the rectal trouble, and only disappearing permanently -when the piles have been radically treated. It is, again, a<span class="pagenum"><a id="Page_265"></a>[265]</span> -symptom sometimes complained of by the victims of <i>enlarged -prostate</i>.</p> - -<h3><span class="smcap">Local Sources of Fallacy</span></h3> - -<p>If the pain and tenderness be located on the <i>under</i>-surface of -the os calcis, there are several misconceptions possible.</p> - -<div class="blockquote"> - -<p>(1) Careful examination may reveal a tendency to flatfoot, the -pain being referable to strain on the posterior insertion of -the plantar fascia.</p> - -<p>(2) The root of the trouble may be a gonococcal inflammation -of the plantar fascia, or of the periosteum covering the os -calcis.</p> - -<p>(3) A skiagram may show the existence of a bony spur on the -inferior surface of the os calcis.</p> - -<p>(4) The bursa under the os calcis may be inflamed.</p> - -<p>(5) Also, as Tubby has pointed out, pain in the heel may be -referable to shortening of one leg or constant standing, -and more rarely to tuberculous disease of the os calcis.</p> - -</div> - -<p>If the pain and tenderness be located on the <i>posterior</i> surface of -the os calcis, or in the tendo Achillis, the following should be -excluded before assigning the trouble to “gout”:—</p> - -<div class="blockquote"> - -<p>(1) <i>Post-calcaneal Bursitis.</i>—Inflammation of the bursa lying -between the os calcis and the tendo Achillis is not uncommon. -It may be uni- or bi-lateral, and in the majority -of instances is attributable to violent exercise, or chafing -of the heel by ill-fitting boots. The local swelling and -tenderness at the site of the inflamed bursa and its -aggravation by plantar flexion of the foot will afford a -clue to its true nature. (An exostosis projecting from the -hinder surface is sometimes a cause of post-calcaneal -bursitis.)</p> - -<p>(2) <i>Synovitis of the Tendo Achillis.</i>—Symptoms very similar to -those above described have been met with in a teno-synovitis -of the tendo Achillis, as evidenced by swelling -of the sheath, tenderness, and silky crepitus.</p> - -</div> - -<h3><span class="smcap">Gout in the Sole</span></h3> - -<p>There is a wide disposition to regard all painful or unpleasant -sensations in the sole of the foot as evidences of “goutiness.” It -may be recalled that Strabo, according to Plutarch, apostrophised -heat or itching of the feet at night as “the lisping of the gout.” -Duckworth, too, emphasised the frequency of this symptom in -the gouty, and Sir Charles Scudamore also held heat and dryness -of the sole as frequent harbingers of acute attacks. Now, did we<span class="pagenum"><a id="Page_266"></a>[266]</span> -but confine our hazards as to gout only to cases marked by heat -or itching in the sole, possibly little harm might result; but -unfortunately there is a flippant readiness to relegate all obscure -pains or abnormal sensations in the sole to the “gouty” category. -Needless to say, this is quite unjustifiable. We need not reiterate -the bounden necessity of excluding all static foot deformities, but -we should in addition recall the various types of <i>plantar neuralgia</i>.</p> - -<p><i>Plantar Neuralgia.</i>—Occasionally, as we have pointed out -elsewhere, the pain is of almost unendurable severity. It constitutes -one of the types of so-called <i>partial sciatica</i>, the pain and -paræsthesia being confined to the plantar nerves. Indeed, pain, -numbness, hyperæsthesia, or sweating of the sole are often -symptomatic of a definite neuritis. Such may follow typhoid -fever or caisson disease, and in this latter be of aggravated type. -When we realise that the pain in these cases may be limited to -the tips of the toes or the <i>ball of the great toe</i>, we see how readily it -may be confused with “gout.” Fortunately plantar neuralgia -is exceptionally rare; but even after exclusion of the foregoing -causes we should, before pronouncing any such neuralgia to be -“gouty,” recollect that plantar neuralgia or hyperæsthesia is -very common in <i>alcoholism</i> and <i>hysteria</i>.</p> - -<p><i>Erythromelalgia.</i>—Among the exceptional cases that find their -way to spas are examples of this rare disorder. Almost invariably -they come under the diagnosis of “gout” or “rheumatism.” -When we reflect that in the majority of instances the initial -burning pain typical of the disease is located in some part of the -sole of one foot, and that the associated redness and vascularity -may be delimited to the <i>ball of the great toe</i>, the heel, or outer or -inner side of the foot, we see the danger of its being too easily -referred to “gout.”</p> - -<p>If seen at the zenith of an attack, the severe pain, the local -heat, the intense purplish redness, the distension of the veins, -and in some instances œdema, how close the resemblance to -gout! Precisely also, as in gout, the simulation of a deep-seated -inflammatory process is very pronounced. Indeed, in not -a few examples of erythromelalgia fruitless incisions have been -made. Accordingly in all cases of pain, redness, and swelling -in the sole of the foot, we should canvass the possibility that we -may be face to face with an instance of erythromelalgia, a disorder -which, like gout, is most frequently met with in men of middle age.</p> - -<p>In drawing to a close our remarks on the diagnosis of <i>acute -gout</i> in the <i>foot</i>, we would emphasise the fact that in all such cases -the bare feet should be thoroughly examined. For, apart from -<i>infective</i> and <i>traumatic</i> lesions, the frequency with which the -various <i>static foot deformities</i> are confused with “gout” is<span class="pagenum"><a id="Page_267"></a>[267]</span> -incredibly common. That <i>gout may co-exist with hallux valgus</i> -or other distortion we readily admit, but this does not absolve -us of our responsibility—correction of the static deformity. -Combine this, if you will, with constitutional treatment if there -be evidence, <i>i.e.</i>, tophi, of a “gouty” diathesis, but, we repeat, -correct the mechanical defect. For gout may come and go, but -static errors remain. In so doing, the victim will be saved much -preventable suffering, and, for aught known to the contrary, the -removal of irritation and local congestion may haply minimise -the chances of subsequent gouty outbreaks.</p> - -<h3><span class="smcap">Anomalous Sites for Initial Outbreaks</span></h3> - -<p>While <i>primary</i> attacks are in the vast majority of instances -localised to the <i>foot</i>, if not actually to the <i>toe</i>, it is well to recollect -that very rarely the <i>knee</i>, the <i>wrist</i>, <i>elbow</i>, or <i>ankle</i> may be the -chosen spot. In such cases there is need for exceptional caution -before committing oneself to a diagnosis of <i>gout</i>. Certainly not -until all other known causes of <i>acute arthritis</i> of <i>monarticular</i> type -have been excluded.</p> - -<p>If in the <i>knee</i> or <i>wrist</i>, any possibility of <i>injury</i> or <i>strain</i> should -be thoroughly canvassed. To make assurance doubly sure, a -radiograph should always be taken. Specific infective forms of -arthritis then call for careful elimination—<i>i.e.</i>, gonococcal, etc. -If there be no history of such, a painstaking search should be made -for any local foci of infection, <i>e.g.</i>, mouth and accessory cavities. -If any be found, they should be radically treated, as it is much -more likely that the arthritis is due thereto than to gout.</p> - -<p>If, notwithstanding a meticulously careful investigation, no -cause can be assigned, we may entertain the possibility of its -being <i>gout</i>, the more legitimately if the subject be a middle-aged -man coming of gouty ancestry and exhibiting himself tokens of -this diathesis, <i>i.e.</i>, <i>tophi</i>. It would be confirmatory, too, if, apart -from its exceptional localisation, the joint disorder in its course -conformed to that typical of gout in the toe, in other words if it -was of sudden nocturnal onset, showed marked daily remissions -in temperature and pain, responded swiftly to the action of colchicum, -and was not protracted beyond the usual week or ten days.</p> - -<p>Sir Hale White, discussing the diagnosis of acute gout of -unusual localisation, remarks: “The real difficulty in acute -cases comes when it is suggested that an acute arthritis with -pyrexia and swelling and redness of a joint other than that of the -great toe is caused by gout. I have recently seen the difficulty -in one patient in the wrist, in another in the knee. Such cases, -if they are not gout, are some bacterial arthritis.”</p> - -<hr class="chap x-ebookmaker-drop"> - -<div class="chapter"> - -<p><span class="pagenum"><a id="Page_268"></a>[268]</span></p> - -<h2 class="nobreak" id="CHAPTER_XXI">CHAPTER XXI<br> -<span class="smaller">CLINICAL DIAGNOSIS (<i>continued</i>)</span></h2> - -</div> - -<h3><span class="smcap">Acute Gouty Polyarthritis</span></h3> - -<p>In the pathways of medicine, as in other walks in life, we are -apt to become stereotyped, to fall into grooves, and sooner or -later the inevitable rude awakening comes. Thus, so prone are -we to think of gout as belonging, so to speak, to the foot, that -when it erupts elsewhere it is often the last contingency to dawn -upon us. If we diagnose it too often and too readily in the foot, -we do so too seldom when it appears in joints remote.</p> - -<p>Now, while in <i>initial</i> outbreaks of gout it is exceptional for -more than <i>one</i> joint to be affected, it is not always so. For -sometimes in those strongly predisposed by <i>heredity</i> not one, but -<i>many</i> joints, may be implicated in the <i>primary</i> attack. Such -cases, however, are extremely rare.</p> - -<p>As a rule, this <i>acute gouty polyarthritis</i> occurs in individuals who -have already experienced articular paroxysms at the classic site; -but in the subsequent polyarticular attacks the <i>toe</i> joints are -often unimplicated, and the disease is located in the larger -articulations—the knees, ankles, wrists, or elbows. Herein -resides the difficulty of diagnosis in these cases: the likelihood of -confusion with other polyarthritides.</p> - -<p>Confronted then with an <i>acute polyarthritis</i> of obscure nature -marked by pain, redness, swelling, and pyrexia, what are the -points necessary to establish it as being of gouty origin?</p> - -<p>The sex and age should be noted, also the heritage, habits, and -occupation. A history of <i>previous attacks located in the big toe</i> -would be of prime value. The presence of a cardiac <i>valvular</i> -lesion, while it would suggest a previous attack of <i>acute rheumatism</i>, -would in no wise negative the possibility of the subject -developing <i>gout</i> in later life. Here I may say that if the subject -is over thirty-five and has never had acute rheumatism or acute -gout, it is much more likely at his time of life that his <i>acute -polyarthritis</i> is of <i>gouty</i> than of rheumatic origin.</p> - -<p>As to the character of the pyrexia, it is usually of <i>low</i> grade; -but if the condition be <i>afebrile</i>, it is even more suggestive of a -<i>gouty</i> arthritis. But recollect, too, that the pyrexia in <i>gonococcal</i> -arthritis is also of low grade or absent.</p> - -<p><span class="pagenum"><a id="Page_269"></a>[269]</span></p> - -<p>There is nothing distinctive of <i>gout</i> either in the character or -distribution of the articular lesions. The ankles, knees, hands, -wrists, are most commonly involved, much more rarely the -elbows, shoulders, or hips. Naturally the local changes will -differ according to the joint involved and the structures implicated; -but these local variations in appearance, including -œdema, may all be met with in any form of <i>infective</i> arthritis.</p> - -<p>As to <i>uric acid excretion</i>, Osler, who was deeply interested in -this type of arthritis, held that any <i>lowering</i> of the ratio of the -<i>uric acid</i> to the <i>urea excretion</i> would be significant of gout. Also -we should, as these cases of acute gouty polyarthritis are -of the nature of successive paroxysms (“series et catena paroxysmulorum,” -to use Sydenham’s expression), note <i>any variations -in the uric acid output</i> ensuing <i>pari passu</i> with their rise and -wane.</p> - -<p>Last, but most important of all, a thorough search must be -instituted for <i>tophi</i>, not only in the ears, but elsewhere. If -anything could emphasise the indispensable <i>rôle</i> played by <i>tophi</i> -in the diagnosis of gout, it would be our utter inability to effect -in their absence a diagnosis of these <i>acute</i> types of <i>gouty polyarthritis</i>. -The establishment of the existence <i>in situ</i> of such -<i>articular uratic deposits</i> disposes forthwith of all possible doubts -as to the true nature of the case; but if, as so frequently happens, -the tophi when present are of <i>ab-articular</i> site, then we must -withhold our decision pending the exclusion of certain other -joint disorders, to the differentiation of which we now proceed.</p> - -<h3><span class="smcap">Differential Diagnosis</span></h3> - -<p>The class of disorders that call for discrimination are those of -infective origin. In the first place, <i>acute articular rheumatism</i> -must be excluded; nor is it less necessary that we should eliminate -<i>gonorrhœal</i> and <i>syphilitic</i> types; while, last, but not least, that -vast group, the <i>undifferentiated infective arthritides</i>, is but too -often a source of confusion.</p> - -<h3><span class="smcap">Acute Articular Rheumatism</span></h3> - -<p>Unquestionably many cases of <i>acute gouty polyarthritis</i> have -been confounded with <i>acute articular rheumatism</i>, and <i>vice versâ</i>. -Garrod on this point remarks: “That many cases of acute gout -have been mistaken for acute rheumatism I do not doubt, and, -on the other hand, that some few cases of acute rheumatism have -been regarded as of a gouty nature I am no less certain. I may -refer to the oft-quoted case related by Dr. Haygarth in which<span class="pagenum"><a id="Page_270"></a>[270]</span> -gout was supposed to have been transferred from the extremities -to the heart as an example of the latter error.”</p> - -<p>It is only, of course, with that type of acute gouty polyarthritis -accompanied by <i>pyrexia</i>, and not the <i>afebrile</i> variety, that confusion -with acute articular rheumatism is possible. What then -are the points of discrimination?</p> - -<table> - <tr> - <th></th> - <th><span class="smcap">Acute Articular Rheumatism.</span></th> - <th><span class="smcap">Acute Gouty Polyarthritis.</span></th> - </tr> - <tr> - <td>Age and sex</td> - <td>Most common between ages of fourteen and thirty. Predominance - of males after twenty.</td> - <td>Maturity and old age. Males. Females markedly exempt.</td> - </tr> - <tr> - <td>Heredity</td> - <td>Very disputable.</td> - <td>Very pronounced.</td> - </tr> - <tr> - <td>Onset</td> - <td>Usually abrupt and often with tonsillitis.</td> - <td>Insidious, with premonitory gastro-intestinal symptoms.</td> - </tr> - <tr> - <td>General symptoms</td> - <td>High fever, sometimes hyperpyrexia. Profuse acid sweats.</td> - <td>Moderate pyrexia. Marked daily remissions.</td> - </tr> - <tr> - <td>Distribution of lesions</td> - <td>Preference for large joints and markedly mobile.</td> - <td>Small joints, hand or foot often involved. Fixity typical.</td> - </tr> - <tr> - <td>Local characters</td> - <td>Joints exhibit slight reddish flush. No subsequent desquamation. - No residual change.</td> - <td>Scarlet hue and œdema with later peeling of cuticle and itching. - Tendency to involvement of bursæ and tendons.</td> - </tr> - <tr> - <td>Pain</td> - <td>Chiefly evoked by movement.</td> - <td>Spontaneous, more intense.</td> - </tr> - <tr> - <td>Duration</td> - <td>Twenty to thirty days, sometimes longer.</td> - <td>Six weeks to three months.</td> - </tr> - <tr> - <td class="nw">Associated phenomena</td> - <td>Cardiac lesions common.</td> - <td>Tophi. Occasionally glycosuria and albuminuria.</td> - </tr> - <tr> - <td>Therapeutic test</td> - <td>Salicylates a specific.</td> - <td>Not so in gout, but colchicum takes this <i>rôle</i>.</td> - </tr> -</table> - -<h3><span class="smcap">Acute Gonococcal Arthritis</span></h3> - -<p>This disorder, as we know, is sometimes of oligo- or poly-articular -distribution. Moreover, as the attendant pyrexia may -be slight or absent, it may readily be confounded with the <i>afebrile</i> -variety of acute <i>gouty</i> polyarthritis. Osier, discussing diagnosis -of the latter condition, observes: “A patient with three or four -joints red, swollen, and painful in acute rheumatism has fever,<span class="pagenum"><a id="Page_271"></a>[271]</span> -and while <i>pyrexia</i> may be present, and often is, in gout, its absence -is, I think, a valuable diagnostic sign.”</p> - -<p>This is of course true, but it still remains necessary, for reasons -above cited, to eliminate <i>acute gonorrhœal arthritis</i>. The tendency -to such confusion has been emphasised by Sir Rose Bradford and -Sir William Roberts, and I would urge the necessity of being -alive to this possibility even in middle-aged men. One thing is -certain, viz., we should be extremely chary of pronouncing any -coincident urethral discharge to be a so-called “gouty -urethritis”; nor should we translate any coincident <i>conjunctivitis</i> -or <i>iritis</i> as further evidence of the articular affection being -“gouty.” It is far more likely to be <i>gonococcal</i>. Apart from -these inflammatory ocular affections, the relics also of previous -attacks—viz., irregularity in contour or inequality in size of the -pupils—have before now put me on the right track in obscure -types of polyarthritis.</p> - -<p>To sum up, the following are distinctive characters of <i>generalised</i> -gonorrhœal arthritis:—</p> - -<p><i>Etiology.</i>—History or presence of urethral discharge and -isolation of the gonococcus.</p> - -<p><i>Onset.</i>—Insidious, seldom acute.</p> - -<p><i>General Symptoms.</i>—Absent or slight relatively to extent and -severity of joint mischief. Pyrexia, low grade or absent.</p> - -<p><i>Distribution of Lesions.</i>—Preference for large joints. Special -liability of sacro-iliac, chondro-costal synchondroses, sterno-clavicular, -tibio-fibular, and temporo-maxillary joints.</p> - -<p><i>Local Characters.</i>—Persistent passive effusion or peri-articular -boggy swelling, with redness and local heat. No tendency to -migrancy. Joint swelling very persistent.</p> - -<p><i>Associated Phenomena.</i>—Involvement of fasciæ, especially -plantar, and of tendon sheaths, very distinctive, while coincident -iritis or conjunctivitis is almost diagnostic.</p> - -<h3><span class="smcap">Secondary Syphilitic Arthritis</span></h3> - -<p>The ease with which a subacute arthritis of this nature may be -confounded with “gout” or “rheumatism” calls for comment. -We have met with cases despatched to spas under this impression. -The customary <i>intermittent fever</i> of <i>secondary syphilis</i> is usually -present. The detection of periosteal nodes in addition to the joint -swellings should arouse suspicion, while the presence of <i>secondary -syphilides</i> and the rapid response to <i>specific</i> treatment will be confirmatory.</p> - -<p>I well recollect some years ago a young farmer being sent to me -by a medical man as suffering from <i>gouty arthritis with gouty<span class="pagenum"><a id="Page_272"></a>[272]</span> -eczema</i>. The eruption was a typical <i>roseola</i>, and the condition -promptly cleared up under <i>anti-syphilitic</i> treatment.</p> - -<h3><span class="smcap">Acute Rheumatoid or Atrophic Arthritis</span></h3> - -<p>While the old term “rheumatic gout” still clings to this affection, -it has now achieved its isolation from gout on the one hand -and rheumatism on the other. The fact that it occurs in young -women in whom gout never occurs, and has a very marked -clinical <i>facies</i> of its own, should almost preclude the possibility -of its being a source of confusion. Still, for the sake of completeness, -we append its chief characteristics.</p> - -<p><i>Age and Sex.</i>—Most common in young women.</p> - -<p><i>Onset.</i>—More or less acute.</p> - -<p><i>General Symptoms.</i>—Continuous low grade pyrexia, quick pulse, -and rapid emaciation, and commonly concomitant gastro-intestinal -derangements.</p> - -<p><i>Distribution of Lesions.</i>—Polyarticular. Beginning in the small -joints, it spreads centripetally, with a tendency to symmetry. No -migrant trend, but a steady, progressive involvement of joint after -joint, including temporo-maxillary and cervical articulations.</p> - -<p><i>Local Characters.</i>—Overlying skin of affected joint white or -semi-asphyxial in tint. Contour spindle-shaped, but in terminal -stages shrinkage from atrophy of articular structures sets in. -Muscular wasting and contracture conspicuous features.</p> - -<p><i>Associated Phenomena.</i>—Trophic and vasomotor changes -prominent, but <i>no tendency to cardiac lesions</i>.</p> - -<h3><span class="smcap">Infective Arthritis of Undifferentiated Type</span></h3> - -<p>It were well in approaching any acute polyarthritis of obscure -nature to bear in mind the axiom that <i>any or all infections may be -complicated by arthropathies</i>, also that if the said polyarthritis -does not respond quickly to colchicum or salicylate of soda we are -almost certainly dealing with an infective arthritis either of -specific or undifferentiated type. The <i>specific</i> forms of infective -arthritis, as far as seems necessary, have been dealt with, but -those rarer forms not referred to, viz., <i>influenzal</i>, <i>pneumococcal</i>, -<i>dysenteric</i>, <i>meningococcal</i>, etc., have also to be borne in mind, if the -history reveal any recent occurrence of these disorders.</p> - -<p>Still far more common than any of these are the <i>acute infective -arthritides</i> of <i>undifferentiated</i> type. As we before remarked, an -extraordinary general clinical resemblance obtains between these -types of joint disorder and <i>acute gouty polyarthritis</i>. Indeed, <i>in -the absence of tophi</i>, their differentiation is well-nigh impossible.<span class="pagenum"><a id="Page_273"></a>[273]</span> -Even the blood picture in both types of the disorder is strikingly -similar in the matter of <i>leucocytosis</i> and <i>secondary anæmia</i>.</p> - -<p>Recently Dr. Henry A. Christian, lecturing at a clinic of the -Harvard Medical School, emphasised this clinical similarity and -the difficulty of discriminating between these two types of joint -disorder. As he rightly says, “while there is a definite <i>acute gouty -polyarthritis</i> (as evidenced by external tophi or deposits in bone or -cartilage with variations in uric acid output) and also an equally -definite <i>infective arthritis</i>, yet between those two there is a very -considerable number of cases that present some of the factors -suggestive of <i>gout</i> and other factors suggestive of an <i>infectious -arthritis</i>, and there is where the difficulty comes.”</p> - -<p>This is precisely the state of affairs, and one may well ask -where <i>gout</i> ends and <i>infection</i> begins. Let us take an example. -A man exhibiting <i>tophi</i>, the subject also of <i>pyorrhœa alveolaris</i>, -develops an <i>acute polyarthritis</i>. What then is the nature of the -joint disorder? There is a gouty element in his case, as attested -by <i>tophi</i>, also an infective element, as evidenced by <i>oral sepsis</i>.</p> - -<p>Now are we to regard such a case as one of <i>infective arthritis</i> of -<i>undifferentiated</i> type occurring in a <i>gouty</i> subject, or are we -to proceed on the assumption that the presence of <i>tophi</i> negatives -the possibility of infection and forthwith to class it as a case of -<i>acute gouty polyarthritis</i> of so-called <i>metabolic</i> origin?</p> - -<p>This is no theoretical quibble. In the Royal Mineral Water -Hospital, Bath, one constantly meets with cases in which the very -elect would be puzzled as to whether they should be placed in the -category of <i>gouty</i> or in that of <i>infective</i> arthritis. I have at -present in my wards a middle-aged man, stout of body, rubicund -of face, with well-marked auricular tophi and widespread arthritis. -There are no tophi round his joints. On X-ray examination his -phalanges show Bruce’s nodes, and his phalangeal joints show -changes indistinguishable from those constantly met with in infective -arthritides occurring in <i>non-gouty</i> subjects.</p> - -<p>Indeed, this overlapping may proceed still further, the gouty -and the infective characters neighbouring in such proximity as to -suggest actual fusion, a community of origin. What else in truth -can be the inference, when one meets with examples in which the -<i>peri-articular</i> tissues are the seat of demonstrable <i>uratic deposits</i>, -while the X-ray changes within the joint proper, the bone and -cartilage, are typically those met with in <i>infective</i> arthritis?</p> - -<p>Now, who will deny that if tophi were absent in such a case -we should without hesitation hold the case to be one of infective -arthritis? My own contention is that even in the presence of -tophi the same appellation is indicated. In other words, I submit -that <i>acute gouty polyarthritis</i> is itself but a form of <i>infective<span class="pagenum"><a id="Page_274"></a>[274]</span> -arthritis</i> which derives its <i>specific</i> character from the associated -<i>uratic deposits</i>.</p> - -<p>As to differentiation of the latter from these cryptic infective -arthritides, this will rest mainly on—</p> - -<p>(1) The presence of tophi;</p> - -<p>(2) A history of previous attacks in the great toe;</p> - -<p>(3) A swift response to colchicum.</p> - -<p>In addition, acute gouty polyarthritis is confined to <i>middle-aged -males</i>, while no period of life is immune from infective arthritis, -and both sexes are equally liable.</p> - -<p>Again, acute gouty polyarthritis may be <i>afebrile</i>. Pyrexia -when present is moderate in grade, its curve undulating as the -paroxysms rise and wane. In infective arthritis the temperature -curve is irregular and erratic.</p> - -<p>Lastly, the <i>uric acid output</i> in acute gouty polyarthritis drops a -day or two before the paroxysm, rises markedly after its inception, -then sinks again. Also we may add that occasionally glycosuria -or albuminuria is present.</p> - -<p>In conclusion, I would allow myself a brief digression regarding -these infective arthritides of undifferentiated type. They constitute -the bulk of the cases of arthritis that find their way to the -Royal Mineral Water Hospital, Bath, under one or other of the -appellations “gout,” “rheumatism,” and “rheumatic gout.” -It is within this category that most of the cripples met with at -spas fall, and their obduracy to “drug” treatment accounts for -their belated despatch thereto.</p> - -<p>I would that I could sufficiently emphasise the imperative -necessity of early recognition of the true nature of these cases. -Colchicum is a most valuable drug, and so is salicylate of soda. -But they have their limitations. They act swiftly or not at all. -Persistence with them in the absence of any response is worse -than futile: it is definitely prejudicial. Because of our unreasoning -devotion, our almost fetishistic addiction, to these drugs, I often -feel that these agents, especially salicylate of soda, have made -more cripples than they have saved. For, unfortunately, -unqualified reliance on these drugs is apt to blind us to the surgical -necessities of these cases. Foci of infection pass unnoticed, joints -stiffen at unfavourable angles, and not infrequently a potential -bread-winner is lost.</p> - -<p>I make no apology for this digression, for it is, strictly speaking, -wholly apposite, this in view of the fact that failure of quick -response to the action of colchicum or salicylate of soda, say -within a week, speaks in favour of the infection having ensued in a -<i>non-gouty</i> as opposed to a gouty subject.</p> - -<hr class="chap x-ebookmaker-drop"> - -<div class="chapter"> - -<p><span class="pagenum"><a id="Page_275"></a>[275]</span></p> - -<h2 class="nobreak" id="CHAPTER_XXII">CHAPTER XXII<br> -<span class="smaller">CLINICAL DIAGNOSIS (<i>continued</i>)</span></h2> - -</div> - -<h3><span class="smcap">Chronic Articular Gout</span></h3> - -<p>If the diagnosis of acute types of articular gout often presents -difficulties, these same are, if anything, accentuated when we -approach its chronic manifestations. For, <i>apart from uratic -deposits</i>, the anatomical lesions that ensue in joints the seat of -long-continued gout have no <i>specific</i> character. In short, there is -nothing pathognomonic of gout in the changes produced, and which, -as a matter of fact, we know to be capable of production, by many -different morbid agencies. Surely this lack of specificity in its -structural lesions should make us very chary of admitting to the -category of chronic articular gout any examples of arthritis -<i>destitute of uratic deposits</i>.</p> - -<p>In our chapter on <i>classification</i> we emphasised the desirability -of restricting the usage of the term chronic articular gout to that -type long since known as <i>tophaceous</i> gout, this because there is -little, if any, doubt that that variety known as chronic deforming -gout (syn. arthritis deformans uratica) is largely made up of -examples of rheumatoid or atrophic arthritis and hypertrophic -arthritis or osteoarthritis.<a id="FNanchor_41" href="#Footnote_41" class="fnanchor">[41]</a></p> - -<p>As to <i>osteoarthritis</i>, I do not for a moment deny that <i>uratic<span class="pagenum"><a id="Page_276"></a>[276]</span> -deposits</i> may be met with in its victims. One frequently meets -with patients, the subjects of osteoarthritis of the hip, who at the -same time exhibit tophi in the ears.</p> - -<p>But such to our mind are to be regarded as merely instances -of <i>osteoarthritis</i> occurring in subjects of “gouty -diathesis.” This apparent blending of the two disorders must -not be allowed to impair the clarity of our conception as -to the essential distinctness of gouty arthritis and osteoarthritis.</p> - -<p>Sir W. Hale White has some pregnant observations on this point. -Many patients, he says, “with chronic arthritis are quite wrongly -said to have gout; usually they have osteoarthritis. The -presence of bony outgrowths is strongly against gout, though it -is not conclusive, for such may occur in true gout either more or -less all round the joint or in the form of little nodules, but they -never attain the considerable size common in arthritis,” and he -adds: “If no urate of soda is visible anywhere the diagnosis may -be very difficult.”</p> - -<p>To proceed, the general and local phenomena of chronic articular -gout are such as scarcely lend themselves to succinct definition, -and for their description we would refer the reader to the chapter -dealing with its clinical aspects. As that careful observer Sir -Alfred Garrod states: “Chronic gout is at times confined to one or -two joints, but sometimes numerous articulations are involved.” -In other words, chronic articular gout may be mono-, oligo-, or -poly-articular in distribution; and naturally the process of -differentiation is modified accordingly.</p> - -<p>This being so, I purpose dealing in the first instance with chronic -monarticular gout, and in succession with the types of oligo- and -poly-articular location.</p> - -<h3><span class="smcap">Chronic Monarticular Gout</span></h3> - -<p>Occasionally gout in its recurrences clings obstinately to the -great <i>toe</i> and <i>tarsal</i> joints. But since the advent of <i>radiography</i> -there should be little or no difficulty in differentiating a chronic -gouty arthritis of the great toe from the only other arthritic lesion -with which it is likely at this stage to be confounded, viz., <i>osteoarthritis</i>. -But at the same time we would refer the reader back -to the chapter dealing with the differential diagnosis of the localised -variety of acute gout, as therein we dealt fully with other possible -sources of fallacy, <i>i.e.</i>, <i>static deformities</i>, etc. We shall therefore -now proceed to discuss those exceptional cases in which chronic -gout is located not in one of the small, but in one of the <i>larger</i>, -articulations.</p> - -<p><span class="pagenum"><a id="Page_277"></a>[277]</span></p> - -<h3><span class="smcap">Monarticular Gout in Large Articulation a Rarity</span></h3> - -<p>Given a chronic arthritis of one of the larger joints, say the ankle, -knee, or elbow, we should be careful not to jump too readily to -the conclusion that it is of “gouty” nature. The more obscure -it appears the more need for caution. Needless to say, if the objective -changes be but minimal and the condition be, so to speak, -practically a mere arthralgia, there rests upon us the paramount -necessity of careful discrimination before labelling it as “gouty” -in kind.</p> - -<p>Thus, if it be the knee, it may be a referred pain due to hip -disorder, <i>e.g.</i>, <i>osteoarthritis</i> or <i>tuberculous</i> disease, or it may be -symptomatic of an inflammatory process, or, having regard to the -usually mature or advanced age of the subject, it may be a -<i>neoplasm</i> in the bones.</p> - -<p>On the other hand, suppose the subject come complaining not -much of pain in his joint, but more troubled because of its <i>enlargements</i>. -If now on examination we find also that there is little -or no tenderness, but simply a condition of <i>peri-articular thickening</i> -or <i>intra-articular effusion</i>, what shall be our method of procedure? -Certainly not to leap forthwith to the conclusion that it is gouty. -No, not even if he exhibit <i>tophi</i> in his ears.</p> - -<p>Now, as to pain and tenderness, it is a blessed feature of gouty -arthritis that, generally speaking, in the chronic forms pain -becomes much attenuated. But let us at the same time recollect -that <i>syphilitic</i> arthritis, both secondary and tertiary, is relatively -<i>painless</i>. But it is the much rarer <i>tertiary</i> form, be it remembered, -which is usually <i>monarticular</i>. By the bye, too, we should never -forget that a <i>Charcot’s joint</i> is also painless.</p> - -<p>Coming now to the <i>objective</i> phenomena, is the case predominantly -one of peri-articular infiltration or intra-articular effusion? -As to the former, while you never know, still <i>tuberculous</i> joint -disease is exceptionally rare at the age at which we usually meet -gout. On the other hand, <i>gummatous synovitis</i>, with or without -osteoperiostitis, is occasionally met with. It is just such a case -as this that may be confounded with gout, the irregular lumpy -thickening of the sub-synovial tissues with effusion being wrongly -attributed to a gouty process with uratic deposits. Do not be -misled if a history of injury be forthcoming in such cases, for it is -not uncommon and may be given in good faith.</p> - -<p>Now what if synovial effusion of chronic or recurring form be -the striking objective feature of the case under review? In this -event always recollect that of all the causes of <i>monarticular</i> -disorder <i>injury</i> is far and away the most frequent. Not a few -cases of monarticular joint disease come annually to the Royal<span class="pagenum"><a id="Page_278"></a>[278]</span> -Mineral Water Hospital, Bath, under the diagnosis of “gout” -and “rheumatism.” But in all too many the symptoms are -referable in truth to ligamentary strain, displaced cartilage, or -foreign bodies, lesions always to be sought for and excluded in -monarticular joint affection. Duckworth has it that <i>hydrarthrosis</i> -is met with in chronic articular gout, in his deforming -variety. He states that “hydrarthrosis is less commonly due to -gout than to rheumatism,” but, we would remark, apart from -traumatic lesions, more commonly due to <i>gonorrhœa</i> or <i>syphilis</i> -than to either of them.</p> - -<p>But the reader may say, this dissertation notwithstanding, -Where does <i>gout</i> come in? Precisely so, and if his experience -tallies with mine, he will find that chronic articular gout localised -in <i>one</i> of the <i>larger</i> joints, and one only, is exceptionally rare. -Personally, I should never feel justified in making the diagnosis -unless I had elicited a history of (1) recurring classic outbreaks in -the great toe with (2) an absence of traumatic infective and nerve -arthropathies and, on the other hand, (3) demonstrable existence -of <i>uratic deposits in situ</i> in the peri-articular tissues, the cartilage or -bones as revealed by <i>skiagraphy</i>, or in the related bursæ.</p> - -<p>In conclusion, if all these various pitfalls have been avoided, it -will almost without exception be found that the final differentiation -in doubtful cases will rest between gout and <i>osteoarthritis</i>; -and in the vast majority, I had almost said all, it is the latter -morbid process that will be found responsible.</p> - -<p>This all too lengthy disquisition will not have been in vain -if it instil caution. For it is in the monarticular types of joint -affection that errors of catastrophic proportion occur more commonly -than in any other form of joint disorder.</p> - -<h3><span class="smcap">Chronic Gout of Oligo-articular Distribution</span></h3> - -<p>The course of chronic articular gout, as has been observed, may -be chequered by acute outbreaks involving three, four, or more -of the larger joints. But, apart from this, there are those so-called -<i>asthenic</i> and <i>afebrile</i> types of gout in which two or more joints may -be the seat of a chronic gouty arthritis. In my experience it is -the <i>knees</i> that are most frequently attacked. The joints are -enlarged, the seat of more or less effusion, but the distinctive -feature is the presence of deformity due to the irregularly rounded -or ovoid swellings produced by <i>uratic deposits</i>. Enlargement of -the patellæ is also present, and they lose their sharp edges, and -sometimes they as well as the neighbouring articular ends are -studded with small bony outgrowths, but of minimal size compared -with those met with in <i>osteoarthritis</i>. The related <i>bursæ</i>, too,<span class="pagenum"><a id="Page_279"></a>[279]</span> -are often the seat of <i>deposits</i>, a valuable clue to diagnosis. Needless -to say, such marked cases are nearly always the outcome of -oft-repeated attacks, the ultimate deformity being the result of -successive accretions of urate of soda laid down in the trail of the -exacerbations.</p> - -<h3><span class="smcap">Its Confusion with Chronic Villous Synovitis</span></h3> - -<p>The frequency with which this misconception occurs is very -noticeable. If a <i>middle-aged</i> woman of florid complexion and -<i>corpulent</i> habit begins to complain of pain and stiffness in her -knees with more or less swelling thereof, there is a very prevalent -tendency to attribute not only her joint disorder to <i>gout</i>, but any -gastric or nervous symptoms that she may simultaneously complain -of are translated as being confirmatory of the assumption. -It gathers weight too from the traditional and widespread belief -that “the change of life” is the period <i>par excellence</i> at which -women develop the morbid vagaries associated with “irregular -gout.”</p> - -<p>Now, as Bassett Jones and I have pointed out in a previous -work, this condition, <i>symmetrical villous synovitis</i> of the <i>knees</i>, is -a very common joint disorder in <i>women</i> at or near the <i>menopause</i>. -Frequently they give a history of numerous <i>pregnancies</i>, or of -<i>rapidly increasing obesity</i>, while with or without this latter they -display a <i>faulty postural attitude</i>, indicative of lowered muscular -and ligamentary tone. Following in the wake of these, the -subject develops a <i>symmetrical flatfoot</i>, which, according to the -stage at which it is seen, may be of flexible or rigid type.</p> - -<p>Now, such is the mutual <i>static interdependence</i> of the component -parts of the lower limb that this condition of flatfoot promotes or -favours the incidence of <i>villous overgrowths</i> in the proximal joints, -the <i>knees</i>. As to the <i>modus operandi</i> we have put forward the -following explanation: “The everted foot, with its sunken arch, as -before stated, determines an alteration in the normal coaptation -of the articular surfaces in the knee, and this incongruence is -revealed in skiagraphs by the marked prominence laterally of the -external tibial tuberosity beneath the external femoral condyle. -Coincidently, and for the same reason, additional strain is thrown -upon the internal lateral ligament. This in turn favours a state of -passive congestion or hyperæmia of the synovial membrane, which -becomes relaxed and thrown into folds, especially at its reflexions -near the edges of the cartilages. If, as often happens, the individual -is the subject of <i>varicose veins</i> or suffers from a <i>general lack -of tone in her muscular or ligamentary structures</i>, this tendency to -venous engorgement of the knees is much enhanced.”</p> - -<p><span class="pagenum"><a id="Page_280"></a>[280]</span></p> - -<p>“Under the influence of these mechanical factors and their -associated circulatory disturbances, <i>thickening and enlargement -of the synovial fringes ensue</i>. The inflammatory condition thus -produced tends to increase automatically, as, owing to the -articular incongruence, the enlarged fringes are very prone to -become caught between the joint surfaces; in other words, a -vicious circle is produced, as with the increasing villous hypertrophy -the liability to internal traumatisms increases <i>pari passu</i>.”</p> - -<h3><span class="smcap">Villous Synovitis Static and Non-gouty in Origin</span></h3> - -<p>In short, the joint disorder is fundamentally of <i>static or mechanical</i> -origin, and, this being so, the results of <i>anti-gouty</i> treatment -are open to a further misinterpretation. The victims, as we have -said, exhibit very generally a tendency to <i>obesity</i>. Now, Ebstein -and many others hold the view that <i>obesity and gout have affinities</i>. -Ebstein, moreover, believes that treatment directed to the reduction -of body weight will check the appearance of gouty arthritis -or ameliorate the same when avowed. What happens is this: -these corpulent subjects are placed on a special dietary. Hydrocarbon -foodstuffs are limited, bread, amylaceous food and liquids -being also restricted. Naturally, <i>pari passu</i> with reduction in -their body weight, their overburdened joints become more equal -to their office. But those who assume that the chronic arthritis -is of <i>gouty</i> origin attribute, and, we think, wrongly, the beneficial -results attained to correction of the underlying “gouty” habit.</p> - -<p>We prefer to subscribe to the simpler or mechanical theory, and -in view of the widespread and, as we believe, erroneous belief in -the gouty nature of this arthritis, we take the liberty of appending -the salient features of these cases, while adding further a few -remarks on the differential diagnosis of other symmetrical affections -of the knees which may also be wrongly attributed to gout.</p> - -<h3><span class="smcap">Clinical Symptoms of Villous Synovitis</span></h3> - -<p>The onset is gradual and insidious. Stiffness is the salient -symptom, but sometimes the subject is more distressed by a sense -of weakness, distension and unreliability. Pain is slight or absent, -save when during walking pseudo-locking occurs. The mobility -of the joints is usually unimpaired, and if any limitation exist it is -the power of full extension that is usually restricted.</p> - -<p>Objectively the joint shows either general enlargement or -swelling localised to the <i>supra</i>- or <i>infra-patellar</i> regions. Intra-articular -effusion which comes and goes is a very characteristic -feature. On palpation a peculiar soft silken crepitus will be heard<span class="pagenum"><a id="Page_281"></a>[281]</span> -and felt as the patient alternately flexes and extends the limb. -The enlarged fringes are also easily to be felt as knots or nodules -which can be moved up or down on the underlying bone. The -ease with which they can be appreciated depends upon the degree -of effusion present at the time. Judging from their symptomatology, -it seems probable that some of the cases included in Sir Dyce -Duckworth’s category, chronic deforming gout, are of this -description.</p> - -<p>The diagnosis of villous synovitis should not be considered -complete without <i>skiagraphy</i> being undertaken to reveal or exclude -osteophytic outgrowths. For the subjective symptoms and signs -of <i>early</i> osteoarthritis are practically identical with those of -villous arthritis, and although the presence of osteoarthritic -lesions elsewhere would be suggestive, skiagraphy alone will -enable us to effect a differentiation with certainty. Indeed, -Bassett Jones and myself are strongly of the opinion that the life -history of osteoarthritis involves two stages: (1) a <i>primary</i> or -<i>pre-osteophytic</i> phase, often of prolonged duration, whose clinical -characteristics are those of villous hypertrophy; (2) a <i>secondary</i> -or <i>terminal</i> stage, in which bony and cartilaginous outgrowths -make their appearance.</p> - -<p>Other symmetrical disorders of the knees that may be -wrongly ascribed to gout are hydrarthrosis and gummatous -synovitis.</p> - -<p><i>Bilateral Hydrarthrosis.</i>—Given effusion into both knees which -is <i>passive</i>, <i>copious</i>, and <i>persistent</i> rather than recurrent, then its -possible <i>infective</i> origin must be carefully canvassed. The common -sources are <i>gonorrhœa</i>, <i>syphilis</i>, and <i>tubercle</i>. The history or -presence of an urethral discharge and detection of the gonococcus -will identify the first named. In syphilis the existence of -other lesions, the response to Wassermann’s test and specific -treatment are the points on which to rely, and in tubercle, -the detection of visceral foci and the sero-reaction will give -the clue.</p> - -<p>As to the <i>intermittent</i> type of hydrarthrosis, the remarkable -<i>periodicity</i> in incidence of the effusion will suffice to obviate any -possibility of confusion.</p> - -<p><i>Peri-synovial and Peri-bursal Gummata.</i>—Affecting as they do -commonly the knee joints of adults, these may, in the absence of a -history of infection, be a source of error. The uneven and -nodular swelling may quite easily be confounded with uratic -deposits. Pain is slight and mobility but little impaired. The -presence of neighbouring scars, a positive Wassermann reaction, -and a favourable response to anti-syphilitic therapy will clear up -the diagnosis.</p> - -<p><span class="pagenum"><a id="Page_282"></a>[282]</span></p> - -<h3><span class="smcap">Chronic Gout of Polyarticular Distribution</span></h3> - -<p>The clinical portrait of tophaceous gout when of widespread -distribution is one of the most striking to be met with in the -whole domain of medicine, but for the broad outlines of the -picture presented we would refer the reader to the chapter -dealing with the clinical description of chronic articular gout.</p> - -<p>In these polyarticular forms the most distinctive joint -deformities are those met with in the <i>hands</i> or feet, more particularly -the former. The excrescences produced are the outcome -of successive <i>uratic deposits</i>. These latter when massive can -scarcely be confused with any other disorder, for the superjacent -skin, distended by the ever-increasing underlying uratic deposits, -becomes thinned and purplish red in hue, and occasionally -ulcerates. I have at present in my wards a case of this nature, -and the subject hoards up the exuding “chalk” in a small -bottle.</p> - -<p>Fortunately such marked examples are relatively rare, though -easily recognised; but it is the less marked types that occasion -difficulty in diagnosis. The point at issue of course is the -differentiation of moderate-sized or small tophaceous swellings -from bony outgrowths. Frequently the task is impossible of -achievement without resorting to puncture, when, if anything can -be withdrawn, microscopic examination may reveal the presence -of <i>biurate</i> crystals.</p> - -<p>For the rest, attention to the following points will prove helpful -in enabling us to differentiate clinically between gouty arthritis -and other chronic joint disorders attended by deformities:—</p> - -<div class="blockquote"> - -<p>(1) Tophi when of recent incidence are <i>soft</i>, and when of long -standing are never so dense or so hard as bony outgrowths.</p> - -<p>(2) The overlying skin is thin, and through its substance the -subjacent white concretions may sometimes be discerned. -It may be adherent, or the seat of ulcers.</p> - -<p>(3) Uratic deposits are <i>not located exactly at the level of the -articulation</i>. They do not adapt themselves to the -contour or shape of the bone-ends.</p> - -<p>(4) Unlike osseous growths, they may be slightly movable in -lateral directions.</p> - -<p>(5) Tophi may <i>soften</i> or <i>disappear</i> after exacerbations of -arthritis.</p> - -</div> - -<h3><span class="smcap">Differential Diagnosis</span></h3> - -<p>The conditions likely to be confused with chronic polyarticular -gout are osteoarthritis, rheumatoid arthritis, and the multiple<span class="pagenum"><a id="Page_283"></a>[283]</span> -arthropathies met with in affections of the central nervous -system.</p> - -<h3><span class="smcap">Osteoarthritis</span></h3> - -<p>Its chief characteristics may be summarised as follows:—It is a -disease rarely met with under forty years of age. The mode of -onset is generally insidious, never really acute. In this respect -it contrasts with gout, the initial outbreak of which is invariably -acute. Osteoarthritis attacks both sexes equally. Although it -may be polyarticular, its specific tendency is towards a mono- -or, more accurately speaking, oligo-articular distribution, with -no marked leaning to symmetry. It has a pronounced predilection -for attacking the <i>hip</i>, the <i>shoulder</i>, and the <i>spine</i>—sites rarely, if -ever, attacked by gout.</p> - -<p>Unlike gout, constitutional symptoms, pyrexia and so forth, are -generally absent; muscular atrophy is slight, hardly ever pronounced, -likewise muscular spasm and contracture.</p> - -<h3><span class="smcap">Local Characters of Joint Swellings</span></h3> - -<p>These are best appreciated in the small joints of the hand. -Osteoarthritis has an affinity for <i>terminal</i> joints—the so-called -Heberden’s nodes. Another favourite site is the carpo-metacarpal -joint of the thumb, while the preference of gout is -for the metacarpo-phalangeal joint thereof and for the same -articulation in the other digits.</p> - -<p>The overlying skin, as a rule, is unchanged, and never assumes, -as in gout, a dusky red or purplish hue. The margin of the -articular surfaces, instead of being smooth and rounded, is broken -and irregular, its nodular contour being due to osseous outgrowths -studding the line of junction of the bones entering the -articulation.<a id="FNanchor_42" href="#Footnote_42" class="fnanchor">[42]</a></p> - -<p>In this respect they contrast with tophi, which are located -near to, but not at, the level of the joint fissure. Again, unlike -tophi, bony outgrowths are fixed, immutable, undergoing no -change save in the direction of progressive enlargement. While -the tendency of an osteoarthritic joint is to expand and increase, -still the enlarged and gnarled joints never attain the colossal -bulbous appearance presented by inveterate examples of -tophaceous gout.</p> - -<p><span class="pagenum"><a id="Page_284"></a>[284]</span></p> - -<h3><span class="smcap">Rheumatoid Arthritis</span></h3> - -<p>This affection differs from the foregoing disorder as well as -gout in that it is most commonly met with in persons under forty -years of age. Moreover, it attacks women much more frequently -than men. Of polyarticular distribution, it evinces a marked -tendency to symmetrical invasion. Like gout, it has a pronounced -preference for the smaller joints, while, similarly, it avoids the hip -and shoulder.</p> - -<p>Constitutional symptoms are conspicuous: pulse quickened, -temperature raised, extreme wasting not uncommon. Intense -and widespread muscular atrophy with contracture is a prominent -feature, also trophic disturbances of varied nature and degree.</p> - -<h3><span class="smcap">Local Characters of Joint Swellings</span></h3> - -<p>In early stages the skin over the joint is waxy white or semi-asphyxial -in tint, outline of joint smooth, rounded, and spindle -in shape, with, as a rule, no irregular bony projection at the level -of the articulation. If seen at a later stage, the swollen joint -will be found shrunken from atrophy of all the articular structures -as well as the skin. Ultimately it becomes reduced even below -its normal size, the small “end-joint” of atrophic or rheumatoid -arthritis. The deformities due to muscular spasm are usually -in the direction of luxation and hyperextension, and differ from -those of gout and osteoarthritis, in which there is more generally -lateral displacement.</p> - -<h3><span class="smcap">Nerve Arthropathies</span></h3> - -<p>The joint disorders incidental to tabes and syringomyelia do -occasionally find their way to spas for treatment under the -mistaken conception that they are instances of “gout,” “rheumatism,” -or “rheumatic gout.” In the case of tabes the mistake -is often referable to the confounding of its lightning pains with -“gout” or “rheumatism,” with subsequent relegation of the -swollen joints, whether single or multiple, to one or other of these -categories. In the syringomyelic it is, I think, the close -resemblance that obtains between the joint lesions and those of -osteoarthritis or so-called “rheumatic gout” that accounts for -their uncalled-for and utterly useless transference to spas. I -have known a case of syringomyelia with multiple arthropathies -in the hands sent to Bath under the mistaken idea that they were -of “gouty” origin.</p> - -<p>These remarkable joint affections will be distinguished by their<span class="pagenum"><a id="Page_285"></a>[285]</span> -fulminant onset with marked effusion and absence of <i>pain</i>, -tenderness, and heat. In addition, associated phenomena will be -present, viz., ataxic pupillary changes and lost knee-jerks in -tabes, while syringomyelia is characterised by dissociated -anæsthesia, trophic disturbances of bones, progressive muscular -atrophy with paralysis.</p> - -<h3><span class="smcap">Hæmophilic Arthritis</span></h3> - -<p>It will be recalled that Rieken held the view that so-called -“bleeders” were prone to attacks of gout, and that sometimes -these alternated with intra-articular hæmorrhages. Nor was he -devoid of supporters, for Sir Dyce Duckworth maintained that a -definite hereditary relationship obtained between gout and -hæmophilia, while that astute observer Jonathan Hutchinson -also contended that the vascular weakness was the outcome of -gout and aggravated by serial hereditary transmission. Wickham -Legg, however, in his masterly contribution questioned the -correctness of Rieken’s proposition.</p> - -<p>Personally, I cannot out of my own experience confirm or -rebut the view that “bleeders” come of gouty stock, nor have I -ever met an avowed gouty subject who was likewise the victim -of hæmophilia. <i>Quâ</i> its joint complications, hæmophilia to our -mind would appear to display closer affinities with peliosis -rheumatica than with gout; but, in view of Duckworth and -Hutchinson’s claims, it were wiser on our part to withhold -judgment, while paying them the deference of being alive to the -possibility of there being some obscure connection, though not -proven, between the two disorders. Again, as emphasising the -necessity for discrimination, we would draw attention to the fact -that Konig recognised three stages in hæmophilic arthritis: -(1) hæmarthrosis; (2) an inflammatory process, with pyrexia and -spindle-shaped swellings apt to be confused with tuberculosis; -(3) extensive arthritic changes reminiscent of arthritis deformans. -Confusion with gouty arthritis clearly is only likely in the second -or third stages, and in the matter of diagnosis the <i>personal and -family tendency</i> to hæmorrhages is the most important clue.</p> - -<hr class="chap x-ebookmaker-drop"> - -<div class="chapter"> - -<p><span class="pagenum"><a id="Page_286"></a>[286]</span></p> - -<h2 class="nobreak" id="CHAPTER_XXIII">CHAPTER XXIII<br> -<span class="smaller">CLINICAL DIAGNOSIS (<i>continued</i>)</span></h2> - -</div> - -<h3><span class="smcap">Skiagraphy</span></h3> - -<p>As an aid to the differentiation of <i>gouty</i> from <i>non-gouty</i> forms -of <i>arthritis</i> skiagraphy has scarcely fulfilled the somewhat -optimistic claims at one time made on its behalf. As to <i>acute</i> -gout, radiography reveals nothing abnormal in the bones, though -Tousey holds that this of itself at once enables us to exclude -<i>osteomyelitis</i>, which, he says, “these cases sometimes resemble.”</p> - -<p>Turning now to <i>chronic articular gout</i>, Huber in 1896 drew -attention to certain <i>focal areas of rarefaction</i>, or diminished -density, in the distal extremities of the phalanges. These localised -transparent areas in the bone-ends are discrete, circular, or oval -in shape. When located near the edges of the bones, they are of -segmental contour, and, viewed in profile, give the appearance of -small punched-out holes, simulating syphilitic dactylitis. Despite -their proximity to the diseased joints, they apparently do not -communicate with the articular cavities.</p> - -<p>These bony changes Huber held distinctive of gout, and -Koehler, Drinberg, and Jacobsohn and other subsequent writers -confirmed Huber’s findings, and, like him, held these areas of -rarefaction to be the result of <i>uratic deposits</i> at their sites. -Strangeways has dissected bones in which these transparent -areas were demonstrated by X-rays. The examination revealed -that the bone was definitely excavated, filled with a gelatinous-looking -substance, and in advanced cases of gout, moreover, a -characteristic deposit of urates clung, as it were, to the margins -of the cavities.</p> - -<p>Similar focal areas of decreased density were noted by Strangeways -in certain cases of <i>rheumatoid arthritis</i>, and both he and -Burt found it impossible on the X-ray findings to differentiate -between these and gout, <i>i.e.</i>, without invoking the aid of clinical -data.</p> - -<div class="figcenter illowp100" id="illus-286" style="max-width: 43.75em;"> - <p class="caption">Radiographs of the Foot and Hand, showing extensive bony - and other changes in long-standing Gout.</p> - <img class="w100" src="images/illus-286.jpg" alt=""> -</div> - -<p>Apart from these transparent areas, Wynne many years ago -pointed out that small <i>nodes</i> or <i>bony deposits</i> are sometimes met -with flanking the sides of the phalanges. More recently Ironside -Bruce by <i>radiography</i> has again drawn attention to these bony -outgrowths near the extremities of the phalanges (Bruce’s nodes).<span class="pagenum"><a id="Page_287"></a>[287]</span> -At first these were thought by Bruce to be composed of <i>urates</i>, -but Strangeways from a study of macerated specimens has -demonstrated their true <i>bony</i> nature, and also that <i>uratic -deposits are not opaque to X-rays</i>, as was formerly thought.</p> - -<p>In skiagrams of chronic gout all stages of <i>ankylosis</i> may be -seen in the interphalangeal joints. In some it is merely fibrous, -in others merging therefrom into bony, and not infrequently -true synostosis is observed. Deflections or subluxations are -frequent features, due either to the thrust of tophi or small bony -outgrowths or to peri-articular contractures.</p> - -<p>So much for the skiagraphic findings in chronic gout, and now -to discuss their valency as aids to diagnosis of this arthritic -disorder. The chief controversy centres around the significance -of the <i>focal areas of rarefaction</i> which have been found in the bones -of the wrists, hands, ankles, and feet of gouty subjects. Here we -may comment on one grave handicap, viz., the lack of certainty -as to whether the cases radiographed by different observers were -true instances of <i>gouty</i> arthritis.</p> - -<p>To justify our expression of doubt we may take, for example, -the series reported by Drinberg and Jacobsohn. The said “transparent -areas” were present in all the eighteen cases, but the -presence of <i>tophi</i> was only established in three. Now, as McClure -and McCarty rightly contend, “since the tophus is the only -universally accepted pathognomonic sign of gout, for studies of -that disease only those patients should be chosen in whom tophi -are found, and sodium urate crystals from them microscopically -demonstrated.” No one can, I think, gainsay the legitimacy of -this stipulation.</p> - -<p>In accordance with their contention, McClure and McCarty -record their radiographic findings in a series of cases all of which -exhibited <i>tophi</i>, and from which sodium urate crystals were -isolated. Now, in all these cases the <i>focal areas of diminished -density</i>, generally held to be peculiar to gout, were present; but -they add that “similar changes were present in two other cases -which were clinically gout, but in which no tophi were demonstrated.” -Also “in another case without tophi, but which was -clinically gout, the focal areas of decreased bony density were not -found.”</p> - -<p>In addition, they examined the skiagrams of 100 cases of -<i>chronic arthritis</i> which “had not been diagnosed clinically as -<i>gout</i>.” In thirteen of the examples “the focal areas of decreased -density, the so-called gouty bony changes, were found, and were -fully as well defined as in the cases of true gout.”</p> - -<p>Judging from the skiagraphic appearances, there seemed no -reason to suppose that the factors responsible for the production<span class="pagenum"><a id="Page_288"></a>[288]</span> -of these rarefied areas were in any way different from those -at work in true gout. Now, most authorities have claimed -that the bony changes were due to <i>uratic deposits</i> in the bones; -but it is at least possible that their origin may be otherwise -explained.</p> - -<p>Thus Nichols and Richardson have shown that, given <i>focal -absorption of lime salts</i>, changes apparently identical with those -currently attributed to the presence of <i>tophi</i> may result. These -same, though they may not be demonstrable either macroscopically -or microscopically, are detectable by X-rays.</p> - -<p>Such foci of absorption, viz., areas of decreased density, frequently -are located in regions subjected to <i>pressure</i>. Thus they -may occur at the inner surfaces of the heads of the first metatarsal -bones, or they may form underneath large tophaceous deposits -in the soft tissues.</p> - -<p>Now, Strangeways has shown that it is impossible by radiography -to detect <i>tophi in bones</i>. Accordingly we have at present -no means of deciding in any given case whether the localised -<i>transparent areas</i> in the bones are due to <i>tophi</i> or to <i>focal absorption</i> -of lime salts. If we are to cling to the conception that they are -due to <i>tophi</i>, then it is clear that <i>tophi in the bones</i> are more common -than is currently suspected, and that, <i>ergo</i>, the frequency of -gouty arthritis is underestimated. For these transparent foci in -bones, according to McClure and McCarty, occur in from 10 to 12 -per cent. of cases of chronic arthritis “which clinically are not -gout.”</p> - -<p>Yet these authorities hold that, despite the fact that they occur -in cases of <i>non-gouty</i> arthritides, they have some diagnostic -significance. For, taking the work of other observers in conjunction -with their own observations, they come to the following -conclusions:—</p> - -<div class="blockquote"> - -<p>(1) The focal areas of decreased density, heretofore considered -as peculiar to gout, are rarely absent in that disease.</p> - -<p>(2) Their absence would be some evidence against the existence -of gout in a given case.</p> - -<p>(3) On the other hand, their presence is no more than suggestive -of gout, since they are found in from 10 to 12 per cent. of -cases which clinically are not gout.</p> - -<p>(4) The focal areas of decreased density, usually held due to -tophi, are probably very often merely focal areas of -absorption of lime salts.</p> - -</div> - -<p>In continuation these authorities have endeavoured to identify -the nature of the <i>arthritis</i> that occurs in <i>gout</i>. Like other workers -in this sphere, the study of the radiographs obtained of gouty -joints reveals that a variety of changes occur in the bones and<span class="pagenum"><a id="Page_289"></a>[289]</span> -joints of the hands and feet in gouty subjects. These, they consider, -may be classified conveniently as follows:—</p> - -<div class="blockquote"> - -<p>(1) Cases marked by <i>focal areas of rarefaction</i>, without any other -perceptible change;</p> - -<p>(2) Cases presenting, in addition to these translucent areas, -minor degrees of lipping at the articular margins;</p> - -<p>(3) Cases in which the changes in (1) and (2) are conjoined -with either localised atrophy of the bones entering into -an affected joint, or with generalised atrophy of all the -bones in the affected limb;</p> - -<p>(4) In addition to all the above changes, narrowing of certain -joint spaces with marked proliferative and atrophic -changes occurs.</p> - -</div> - -<p>In reviewing these findings of McCarty and McClure, it is important -to recollect that they were found in a series of cases all -of which exhibited <i>tophi</i>. Moreover, it will be seen that the radiographic -changes in some are reminiscent of <i>atrophic</i> or rheumatoid -arthritis, in others of <i>hypertrophic</i> arthritis or osteoarthritis, while, -lastly, the appearances typical of <i>infective</i> arthritis are also represented. -In addition, if we recall that <i>focal areas of rarefaction</i>, -indistinguishable from those met with in <i>gout</i>, also occur in all -types of <i>non-gouty</i> arthritis, we at once see how impossible it is to -detect anything in the <i>radiographic</i> findings distinctive of <i>gouty</i> -as opposed to <i>non-gouty</i> arthritides.</p> - -<p>McClure and McCarty, comparing the radiographic changes in -gouty as opposed to <i>non-gouty</i> arthritis, observe that, though -<i>rarefactive foci</i> occur in all varieties of <i>non-gouty</i> arthritis, they are -conjoined with <i>other bony or joint changes</i>. On the other hand, -<i>translucent</i> areas <i>unassociated with any bone or joint alterations</i> -have been found only in <i>gout</i>. But whether this can be claimed as -distinctive of <i>gouty arthritis</i> is, they think, uncertain, since -relatively few opportunities for X-ray examination of <i>non-gouty</i> -arthritis in its <i>early</i> stages have been forthcoming.</p> - -<p>Continuing, of their four radiographic types of gouty arthritis -the second resembles osteoarthritis; but the third and especially -the fourth group, they consider, “fall into a peculiar class,” this -inasmuch as their characters resemble the <i>infective</i> type of <i>non-gouty</i> -arthritis. They claim, however, that a differentiation, -radiographically speaking, can be effected, this because of the -“sharply localised” extreme degree of bony atrophy which occurs -in the infective type of non-gouty arthritis. However, as they -admit that radiographs of the latter (infective non-gouty arthritis) -have been noted which “closely resemble” the “atrophic and -proliferative changes occurring in gout,” their final conclusion is -that in the skiagrams even of typical gouty arthritis there is<span class="pagenum"><a id="Page_290"></a>[290]</span> -nothing in the bony or arthritic changes that is <i>diagnostic</i> of -gout.</p> - -<p>For myself, I must admit that I have come to the same conclusion -as McClure and McCarty, viz., that the skiagraphic findings -in <i>gouty</i> and <i>non-gouty</i> arthritis trench so much the one upon the -characters of the other that I should be loth indeed to base a -diagnosis of gout simply on the revelations of <i>skiagraphy</i>. The -chief interest to my mind, as I have previously observed, centres -round those examples in which <i>peri-articular tophi</i> are associated -with underlying bony and arthritic changes (as revealed by X-rays) -indistinguishable from those typical of <i>infective</i> arthritis of <i>non-gouty</i> -type.</p> - -<p>We have seen also that <i>local foci of rarefaction</i> may be met with -in <i>infective</i> arthritis of <i>non-gouty</i> type. Moreover, the <i>proliferative</i> -and marked <i>atrophic</i> bony changes found in some instances of -gouty arthritis are quite compatible with their <i>infective</i> origin. -Witness how impossible it is to differentiate skiagraphically -between <i>atrophic</i> arthritis and <i>gouty</i> arthritis, and at the same time -let it not be forgotten, on the other hand, that the dividing line -between the <i>infective</i> arthritides and the more acute forms of -<i>atrophic</i> or rheumatoid arthritis is by no means sharply defined. -Review this also in light of the fact of the close resemblance that -obtains between <i>acute articular gout</i>, especially the polyarthritic -variety, and types of arthritis of avowedly <i>infective</i> origin, and we -see at once how close is the clinical similitude. We turn to <i>radiography</i>, -and here again we are met with the same family resemblance, -suggestive of a probable community of origin. How clear -then the inference that it is on <i>tophi</i>, and tophi alone, that we must -base an absolute diagnosis of <i>gouty</i> arthritis. Moreover, since -tophi are not detectable by <i>skiagraphy</i>, our mainstay must be -physical examination directed to their detection. As for those -cases of so-called “clinical gout,” viz., unattested by tophi, it is -probable that their absolute identification, as such, will never be -attainable on purely clinical, but on <i>bacteriological</i>, data, which, -it is to be hoped, will before long be forthcoming.</p> - -<h3><span class="smcap">Differential Diagnosis</span></h3> - -<p><i>Infective Arthritis.</i>—According to Goldthwait, of Boston, no -changes can be detected by skiagraphy in bone or cartilage in -infective arthritis. The density of the former is in no way -diminished, while the cartilage retains its normal thickness. If, -however, the infective arthritis is of destructive character, new -bone may be thrown out in the process of repair. If then in such -cases sole reliance be placed on the X-ray appearances without -any reference to the clinical history and course of the disorder,<span class="pagenum"><a id="Page_291"></a>[291]</span> -then, as Goldthwait says, this irregular formation of bone is likely -to be confused with the X-ray findings in osteoarthritis. It is, -however, possible, according to him, to distinguish the nature of -the case by careful scrutiny of the skiagraphs.</p> - -<p>The new formation of bone in these destructive forms of arthritis -conforms in every way to that seen as a result of <i>septic osteitis</i> or -periostitis. In other words, the osteophytic outgrowths take -origin at the <i>focus of infection</i>, wherever that may be, and not, as -in <i>gout</i> and <i>osteoarthritis</i>, at the <i>margin of the cartilage</i>. Still one -must recollect that in gout <i>exostoses</i> (Bruce’s nodes) develop sometimes -at the <i>sides</i> of the phalanges. These outgrowths are not -peculiar to gout, but may be met with in <i>infective</i> forms of arthritis. -I am inclined therefore to refer their origin to a local osteitis or -periostitis of infective source. That Bruce’s nodes, though not -diagnostic of gout, are frequently met with therein, is, I submit, -but further evidence of the intrusion of an <i>infective</i> element in the -genesis of <i>gouty arthritis</i>.</p> - -<p><i>Hypertrophic or Osteo-arthritis.</i>—This is marked by proliferative -changes at the margins of the articular ends of the bones. With -the advance of the disease the shafts of the related bones become -increasingly dense. In <i>chronic gout</i>, too, the margins of the -cartilages may be studded with little nodules. Radiographically -speaking, they cannot be distinguished from those met with in -osteoarthritis, save only that they never attain the massive size -met with in the latter disorder. The diagnosis in doubtful cases -will practically always rest on the clinical history, and more -pertinently on the presence of <i>tophi</i>.</p> - -<p><i>Rheumatoid or Atrophic Arthritis.</i>—If the changes in the cartilage -and bone in osteoarthritis are active and proliferative, these same -in rheumatoid arthritis are retrograde and passive in character. -In short, hypertrophy of these structures in the former, atrophy -in the latter, constitute the distinguishing features.</p> - -<p>The morbid process in the articular ends in rheumatoid arthritis -is one of rarefaction and softening. The cartilage may undergo -total or partial absorption, a change to be detected in the very -early stages. The bones participate in the pathological change, -the first evidence of which is an abnormal translucency to the rays, -usually, but not always, confined to that portion of the shaft -entering into the joint. Eventually the articular ends of the -phalangeal and metacarpal bones may undergo erosion, in some -cases to a very marked degree, the bones more or less telescoping -into each other.</p> - -<p>Now, owing to the fact that in <i>gout</i> also considerable disintegration -of the bone may result, the appearances in some instances -may resemble those found in the skiagraphs of <i>rheumatoid</i><span class="pagenum"><a id="Page_292"></a>[292]</span> -joints. Stress has been laid on this similarity by Strangeways, -and it was also previously remarked by Goldthwait. The latter, -however, claims that while in <i>atrophic</i> or <i>rheumatoid</i> arthritis the -bone, though thin, maintains its outline, on the other hand in -<i>gout</i> the outline of the bone is not distinguishable owing to its -more complete destruction by the morbid process. Goldthwait -holds that the resemblance of chronic articular gout to rheumatoid -arthritis is most noticeable when the <i>articular ends</i> of the bone in -both instances are the seat of the disease. In other examples, -however, the <i>shafts</i> of the bones being affected by the gouty disorder, -they may show punched-out areas. These latter, however, -are but <i>focal areas of rarefaction</i> seen in profile, and inasmuch as -they may be met with in infective arthritides of non-gouty type, -too much reliance cannot be placed on their presence as distinctive -of gout, much less as a criterion of differentiation from other -arthritides.</p> - -<p>We have to remember, too, that marginal proliferative changes -may occur in rheumatoid arthritis. They are, like those met with -in gout, miniature replicas of the bony outgrowths of osteoarthritis.</p> - -<p>In conclusion, the resemblance between the skiagrams of chronic -gout and rheumatoid arthritis is so close as absolutely to forbid -our sole reliance on skiagraphy to effect a differential diagnosis. -In short, skiagraphy, though of great and probably increasing -value, cannot for one moment be allowed to usurp the place of -careful clinical observation, to which it must be held always -subsidiary. Last, but not least, pending fresh radiographic -revelations, our diagnosis of chronic articular gout and alike its -differentiation from rheumatoid arthritis and other arthritides -must rest on the one unimpugnable criterion, the presence of <i>tophi</i>.</p> - -<hr class="chap x-ebookmaker-drop"> - -<div class="chapter"> - -<p><span class="pagenum"><a id="Page_293"></a>[293]</span></p> - -<h2 class="nobreak" id="CHAPTER_XXIV">CHAPTER XXIV<br> -<span class="smaller">IRREGULAR GOUT</span></h2> - -</div> - -<p>“It is not a sacred disease. There will therefore be no profaneness -in handling it freely,” affirmed Benjamin Rush of gout -some hundred years since.</p> - -<p>Nevertheless one approaches with diffidence this debatable -ground, so hedged in by high sanction and tradition. Albeit -reverence for authority must, in the interests of progress, be -tempered by that spirit of inquiring scepticism which would sift -the chaff from the grain, this the more emphatically in that of -all morbid conditions “irregular” gout, by the very vagueness -of its clinical content, lends itself the more easily to unbridled -inference, hazardous conjecture, and fanciful surmise.</p> - -<p>As for the unlicensed freedom too often exercised in relegating -disorders to this category, Rush would appear to have out-heroded -Herod, <i>pace</i> the following rhetorical reflections, for -they could scarcely rank as clinical observations. “The great -toe and the joints of the hands and feet are no more its exclusive -seats,” said Rush, “than the stomach is the throne of yellow -fever. In short, gout may be compared to a monarch whose -empire is unlimited. The whole body crouches before it.... -The gout affects the glands and lymphatics. It produced a -salivation of a profuse nature in Major Pearce Buller, which continued -for two days. It produced a bubo in the groin in a citizen -of Philadelphia. He had never been infected with the venereal -disease. Of course no suspicion was entertained by me of its being -derived from that cause.... Scrofula and all the forms of -dropsy are the effects in many cases of a disposition of the -gout to attack the lymphatic system.... A distressing collection -of air in the rectum, which renders frequent retirement -from company necessary to discharge it, is likewise a symptom -of gout.”</p> - -<p>It is difficult to conceive that any such pronouncement could -have emanated from a physician of Rush’s standing and repute, -a contemporary, be it noted, of Heberden, to whose masterly -commentaries on the history and cure of gout all posterity is -indebted. Nevertheless as recently as 1854 Sir Spencer Wells -claimed that “any attempt to describe the nervous diseases of<span class="pagenum"><a id="Page_294"></a>[294]</span> -females caused by gout would lead to an enumeration of almost -all forms of their diseases, especially those usually considered as -hysteric. The intestinal derangements with tympanitis, neuralgia, -or colic, the hysteric pain in the right epigastrium, the -cardialgia and gastrodynia, the hysteric vomiting and epigastric -spasms, the morbid sensibility of the pharynx and fauces, hysterical -palpitation, asthma or bronchitis, loss or alteration of the voice, -some forms of hysteric paraplegia or hemiplegia more or less -complete, chorea or tetanus, some of the curious paroxysmal -affections observed in hysteria, and all the varieties of neuralgia -and simulated inflammation, commonly called hysteric, frequently -arise from the presence in the blood of the impurities which are -the true characteristics of gout.”<a id="FNanchor_43" href="#Footnote_43" class="fnanchor">[43]</a></p> - -<p>Truly, in light of this heavy indictment, one scarcely wonders -that Rush classed the domain of gout as limitless. But one must -recollect that, <i>nosologically</i> speaking, our forefathers were sadly -hampered. Anomalous symptoms and disorders had to be -referred to one or other of the available titles of disease, and -what term more elastic than the timeworn “gout,” so easy to -saddle with vicarious responsibilities?</p> - -<p>But <i>pari passu</i> with advancing knowledge of the pathology -of the <i>nervous</i> system and the rise of <i>hysteria</i> to the status of a -clinical entity gout was shorn of the excrescences heaped on -it by Laycock, Wells, and others.</p> - -<p>But nevertheless the emancipation of gout from nervous -and other alien disorders was slow of achievement, and largely, -I think, through the wide acceptation of Murchison’s theory of a -pathological state allied to gout and termed by him “lithæmia,” -or the “uric acid diathesis.”</p> - -<p>According to this authority, the deposit of <i>lithates in the urine</i> -is a “manifestation of a morbid condition of the blood and of the -entire system,” the outcome of a <i>functional derangement of the -liver</i>. Such hepatic disturbance might endure for years without -manifesting any other symptom than a frequent <i>deposition of -urates</i> and occasionally <i>uric acid in the urine</i>. But, added -Murchison, the same if neglected “may ultimately be the means -of developing gout.”</p> - -<p>Clinically it manifested itself by a variety of symptoms—depression<span class="pagenum"><a id="Page_295"></a>[295]</span> -of spirits, irritability, lethargy, headache, pains and -aches in the limbs, vertigo, insomnia, dyspepsia, palpitation, -raised blood pressure. Such were the motley group of disorders -affiliated by Murchison to <i>lithæmia</i>. But his disciples, more -ardent, set no limit to the manifestations of <i>uric-acidæmia</i>.</p> - -<p>Not only gout, but <i>rheumatism</i> and allied disorders, were -amongst its progeny, and Osler tells us that one writer enumerates -not fewer than thirty-nine separate morbid conditions associated -with <i>lithæmia</i>. But leaving aside the extravagant claims of -Haig and his followers, the impression even now is but too -prevalent that <i>gout</i> and <i>lithæmia</i> are convertible terms. There is -little or nothing to justify the assumption that an increased output -of uric acid in the urine or deposition of urates therein is -diagnostic of gout. Such, moreover, presupposes the further -assumption that <i>uric acid</i> is the <i>cause</i> of gout.</p> - -<p>We may affirm that certain symptoms betoken malassimilation -of food or defective tissue metabolism. But it is by no means -certain, as Murchison held, that a <i>functional disorder of the liver</i> -is the <i>fons et origo mali</i>, much less that <i>uric acid</i> is the sole noxious -substance. Yet in a masterly discussion of the subject Pratt, -of Boston, tells us that as recently as 1895 a “leading clinical -teacher” affirmed that “headache, migraine, depression of -spirits, shooting pains, cramps, palpitation, vertigo, are a part of -the symptomatology of lithæmia.”</p> - -<p>Surely, if we are to make any pretence of reducing the phenomena -of <i>lithæmia or irregular gout</i> to a scientific precision -worthy of the present status of medicine, we should fight shy of -such sweeping assertions. The <i>caveat</i>, we fear, is not superfluous. -For as that judicial physician, Austin Flint, once satirically -observed, “the designation ‘uric acid diathesis’ is used by some -physicians in a rather indefinite way to describe various morbid -states which may not at any time be accompanied by deposits -of urates, and in which there is no proof of an excess of uric acid -in the blood.”</p> - -<p>Caustic as was this stricture, it was no less prophetic than -apposite. For recent <i>blood analyses</i> have, as Pratt states, demonstrated -that there is <i>no increase of uric acid in the blood</i> in that -medley of disorders attributed by Murchison and his followers to -“lithæmia,” or “the uric acid diathesis.” Here we would inveigh -strongly against the too prevalent habit of stigmatising as -“gouty” such symptoms as headache, vertigo, palpitation, etc., -not only without any evidence of their being of this nature, but -frequently when no attempt has been made to eliminate “errors -of refraction,” aural disorder, etc. Moreover, granted that such -possible sources have been excluded, we have no justification<span class="pagenum"><a id="Page_296"></a>[296]</span> -in invoking “gout.” For, as noted, all modern observations fail -to demonstrate the presence of <i>uricæmia</i>. Under such circumstances, -given that the anomalous symptoms are inexplicable, -would it not be wiser to content ourselves with the assumption -that their presence postulates, not lithæmia, but a <i>toxic condition -of the blood plasma</i>? This at least carries with it the inference -that a search should be made for the focus of toxic absorption, -whereas for but too many the term <i>lithæmia</i>, even when undemonstrated, -is held to be self-explanatory and final.</p> - -<p>Turning to another aspect of this subject, we are reminded by -Duckworth that Hutchinson “directed attention to various -maladies affiliated with what he terms rheumatic gout and gout, -but differing somewhat from both, and these include various eye -troubles, such as iritis, hæmorrhagic retinitis, and some forms of -glaucoma, lumbago, sciatica, chronic rheumatoid arthritis, -Heberden’s nodes, and possibly hæmophilia.”</p> - -<p>As to the so-called “gouty” origin of the various eye troubles, -these will be dealt with separately by Mr. Beaumont in his -section. For the rest, hæmophilia may, we think, be safely -discarded, Heberden’s nodes relegated to osteoarthritis, while -rheumatoid arthritis has long since vindicated its claim to clinical -individuality.</p> - -<p>But as to lumbago and sciatica, these cannot be so easily disposed -of, as a reflection of Heberden’s brings home to us. “It -must be owned,” says he, “that there are cases in which the -criteria of both are so blended together that it is not easy to -determine whether the pain be gout or rheumatism.” Our own -attitude towards this vexed point was precisely defined in a -previous chapter in which we dealt with the affinities between -gout and other diseases.</p> - -<p>Having dealt with the broader and more extravagant claims -made on behalf of the clinical content of <i>irregular gout</i>, we now -restrict our purview to those disorders, chiefly <i>visceral</i> in site, -which even to-day are referred by some to this category. We -shall in the first instance deal with that variety known as -retrocedent gout, and shall subsequently proceed to discuss -other so-called irregular manifestations of the disorder.</p> - -<h3><span class="smcap">Retrocedent Gout</span></h3> - -<p>The term retrocedent or suppressed gout still lingers in medical -nomenclature, largely, we think, as a tribute to tradition, for -rarely indeed is it invoked in current literature. Known since -the days of Galen and Aretæus, it originally signified a condition -in which sudden <i>inhibition</i> of the <i>acute joint affection</i> is followed<span class="pagenum"><a id="Page_297"></a>[297]</span> -by or coincides with the development of serious <i>internal</i> symptoms -referable either to the gastro-intestinal, cardio-vascular, -or nervous system. Thus, there may be, <i>e.g.</i>, vomiting, diarrhœa, -dyspnœa, cardiac arrhythmia, cerebral hæmorrhage, delirium or -coma.</p> - -<p>Naturally for our forefathers the abrupt subsidence of the -joint disorder with the incidence, as fulminant, of severe and -alarming <i>visceral</i> symptoms appeared to be an example of true -<i>metastasis</i>. That death, tragically sudden, so often ensued, but -rendered more imperious the necessity for explanation; and, in -the then state of knowledge, the proffered assumption could hardly -be regarded as anything other than a perfectly legitimate and -useful hypothesis.</p> - -<p>The retrocession of the articular affection in <i>acute</i> examples of -gout ensues <i>abruptly</i>, but in chronic types it usually transpires -more gradually. Often no cause is assignable, but frequently the -so-called metastasis has followed exposure, chill, or the imprudent -application of cold to the inflamed joints. The late Dr. Parry, of -Bath, in one winter saw two instances of apoplexy follow “the -removing of gout in the extremities by immersing the feet affected -in cold water.” In some, following the same revulsive procedures, -severe <i>cardiac</i> pain has ensued with syncopal attacks, -sometimes fatal, while in others <i>gastro-enteric</i> symptoms of like -gravity have developed.</p> - -<p>It is the <i>asthenic</i> types of gout that, according to Duckworth, -are most prone to <i>metastasis</i>. When the phenomena occur -rapidly, flitting from place to place, they have been designated -“flying gout.” Nevertheless, as before said, the most dramatic -examples arise in <i>acute sthenic gout</i>, though in their instance less -likely to occur spontaneously than in sequence to depressing -external agents, <i>e.g.</i>, cold lotions, etc.</p> - -<p>Reviewing the recorded examples of <i>retrocedent gout</i> in the -light of latter day experience, it is, we think, most significant -that no such dramatic examples apparently occur nowadays, -at least none to which the term “<i>retrocedent gout</i>” appears -applicable. The designation, indeed, bids fair to become obsolete. -What then is the explanation? That even to-day cases of acute -articular gout yield to, or are replaced by, functional <i>visceral</i> -disturbances, of varying degrees of gravity, is certainly true. -But, partly through increase of knowledge and partly through -the growth of a more critical attitude, we seldom, if ever, feel -justified in ascribing them to <i>gouty metastasis</i>.</p> - -<p>Take “gout in the stomach,” to which organ, in the days of the -Regency, it appeared to fly on the slightest pretext, a “vulgar -belly-ache taking rank by courtesy” as such, before Sir Thomas<span class="pagenum"><a id="Page_298"></a>[298]</span> -Watson pricked the bubble of these pretentious ailments by his -suggestion that “gout” (so called) in the stomach sometimes -turned out, under the test of an emetic, to be nothing more than -<i>pork</i> in the stomach. A caustic stricture, but doubtless well -merited. For the symptoms held typical of “gout in the -stomach” are but those of <i>gastric irritation</i>, with nothing to -suggest that they are of “gouty” origin.</p> - -<p>Again, as Brinton in his classic exposure of this clinical myth -observes, some of the recorded instances doubtless derive their -melodramatic aspects from unrecognised <i>biliary colic</i>. As he -rightly says, some of the cases instanced by Scudamore were -jaundiced <i>usque ad unguem</i>. Gallstones, too, are among the -many derivatives of the so-called “gouty” habit. The age -incidence of both disorders is identical, whence doubtless the -conception of the relationship. But what of the abdominal -catastrophes attached to <i>gallstones</i>, all wholly unguessed at in -those days? What, too, of the unrecognised and doubtless -frequently coincident <i>renal</i> disease, with its menace of <i>uræmia</i>—pain, -vomiting and prostration, not to mention Buzzard’s -reflection that some cases of gout in the stomach were probably -referable to gastric “crises,” <i>i.e.</i>, <i>tabes dorsalis</i>?</p> - -<p>If we recall that none of these sources of fallacy—and we have -named but the more common—were eliminated, and also the -absence of any <i>anatomical</i> proof <i>post mortem</i> of gastric lesions, -one may well ask with Brinton, “Is there any ‘gout in the -stomach’ left after the subtraction of these various affections?” -Personally, I can say with Brinton that “I know of no such -case; have never seen one; have never been able to get trustworthy -evidence of one from some of the most accomplished -physicians living, or from the best records.”</p> - -<p>Reverting to the <i>cardiac</i> and <i>cerebral</i> phenomena that have -sometimes followed the <i>retrocession</i> of acute gout, the same -difficulties confront us. The conclusion that they are examples -of <i>retrocedent gout</i> is drawn from premises which really do not -support it. Strictly speaking, there is nought but the <i>time -relation</i> to go upon, and the laconic comment “Non sequitur” is -obvious.</p> - -<p>To continue, the more we know of the causes and effects of -disease, the less relevant becomes the time relation, and the -nearer do our conceptions of cause and effect approximate to the -more truly valid conception of ground and consequence. But -what <i>grounds</i> have we for assuming that the anginal, the syncopal -attack, or the apoplexy is the <i>consequence</i> of gout, that it is -exclusively due to the <i>materies morbi</i> of gout?</p> - -<p>The very disparity between the local lesions seems to exclude<span class="pagenum"><a id="Page_299"></a>[299]</span> -the possibility of their being due to one and the same cause: in -the joint, acute <i>inflammation</i>; in the heart and brain, <i>degenerative</i> -changes. Where then the nexus? Surely it is but a <i>time relation</i>, -a coincidence, the outcome of, <i>concurrent</i> though <i>unrelated -cardiac</i> and <i>vascular</i> lesions. In short, the cases of so-called -retrocedent “cardiac” and “cerebral” gout usually resolve -themselves into <i>cardio-mural degeneration</i>, <i>arterio-sclerosis</i>, or -<i>renal disease</i>.</p> - -<h3><span class="smcap">Other Irregular Manifestations</span></h3> - -<p>The more dramatic examples of retrocedent gout, as before -stated, occur mainly in the <i>acute</i> varieties of the disorder. But -the same visceral metastases are occasionally linked up with the -less severe articular manifestations, or with that vague clinical -entity known as “goutiness,” the same being frequently known -as “wandering” or “flying” gout. Most of the examples met -with in the present day belong to the last category. This may -possibly find its explanation in the growing infrequency of the -more acute or sthenic types of gout.</p> - -<p>Both of the mild and of the severe forms of metastasis the same -pathological interpretation is hazarded. The gout is described as -“suppressed” or “retrocedent.” According to the former conception, -the gouty process itself suffers <i>inhibition</i>, while the latter -term signifies <i>deflection</i> of the <i>materia peccans</i> of gout from the -joint into the viscera. Of the twain the former hypothesis seems -to me the more plausible. Thus, given an acute gout at its -inflammatory zenith, it is conceivable that, if <i>abruptly checked</i>, the -same might <i>reflexly</i> precipitate the occurrence of internal lesions -in structures undermined by insidious and <i>pre-existing degenerative</i> -changes. In other words, the aborted attack is not the cause, -but the <i>occasion</i>, of the cardiac failure, the apoplectic stroke, the -uræmia, etc.</p> - -<p>On the other hand, given that such were due to actual <i>transference</i> -of the gouty poison, one would expect that it would induce -the same <i>inflammatory</i> phenomena in the viscera as in the joint. -But there is no <i>anatomical</i> proof that such occurs, no evidence of -an actual invasion of the impeached viscus by the <i>gouty inflammation</i>. -<i>Uratic deposits</i> have, it is true, been found <i>post mortem</i> -at the site of visceral lesions, but, be it noted, generally in -<i>degenerating</i> tissue altered by other morbid processes. Some, -however, affirm that in such the gouty process has <i>quâ</i> the uratic -deposits left, so to speak, its attestation behind it.</p> - -<p>But any <i>degenerative</i> focus may in a <i>gouty</i> subject become the -seat of such a <i>deposition</i>. Yet it would be presumptuous to infer<span class="pagenum"><a id="Page_300"></a>[300]</span> -its gouty origin from this fact alone. Such are common in -<i>chronic nephritis</i>, and this apart from gout. What need for wonder -then that the same should occur in gouty subjects, with their -blood surcharged with uric acid?</p> - -<p>Were such uratic deposits located at the site of <i>inflammatory</i> as -opposed to degenerative visceral foci, it would to our mind give -more colour to the assumption that they were the outcome of a -true gouty process; in other words, that, as in the joints, they -were the <i>sequel</i> or concomitant of <i>acute gouty inflammation</i>. But -it is not so.</p> - -<p>As for the structural or organic degenerations met with in gouty -subjects, very many, if not all, as Longstreth rightly says, “belong -to some one of the great general classes of tissue changes, some of -which are due to special causes, but the most of them own many -causes. One of these many causes can be under certain circumstances -gout, but there is really nothing special in the appearances -by which we can unequivocally pronounce them of gouty origin.” -With this view few would join issue, save only the reservation -that the <i>scleroses</i> so commonly met with in <i>gout</i>, if due -thereto, must owe their origin to some more vital agent than -<i>uric acid</i>, a few milligrammes more or less in the blood content -thereof.</p> - -<p>It will be seen then that the <i>anatomical</i> evidence that gout can -affect the <i>internal</i> organs is wholly lacking. The criteria then -upon which the assumption is based that this or that functional -disturbance is a manifestation of irregular or <i>visceral</i> gout are -wholly <i>clinical</i>.</p> - -<p>Doubtless the conception of irregular gout was derived from -“the unaided operation of custom.” Thus, when one clinical -event, A, was noticed frequently to precede another, B, the idea of -an association between A and B was generated, and by virtue of -this association A was said to be the cause of B. But obviously -the fact that B has followed A does not establish any necessary -connection between the two clinical events. In other words, the -idea of a causal relation is in a sense a purely intellectual feat, a -clinical inference <i>presumptive</i> and <i>retrospective</i>.</p> - -<p>The evidence that a relationship exists between <i>irregular</i> and -<i>regular</i> manifestations of gout rests upon the following sequences -and alternations of clinical events:—</p> - -<div class="blockquote"> - -<p>(1) The subsidence or disappearance of functional visceral -derangements following the development of articular gout;</p> - -<p>(2) Their occurrence directly after an articular paroxysm has -been apparently suppressed;</p> - -<p>(3) Their recurrence and alternation with arthritic outbreaks, -this in some instances repeatedly;</p> - -<p><span class="pagenum"><a id="Page_301"></a>[301]</span></p> - -<p>(4) Lack of any appreciable cause for the functional derangements -and their indefinite anomalous character;</p> - -<p>(5) Their favourable response to specific gouty therapy.</p> - -</div> - -<p>As before noted, <i>digestive</i> troubles frequently precede the initial -outbreak of articular gout. The same likewise are frequent in -chronic cases between the intervals of arthritic seizures.</p> - -<p>Now it has been customary to regard the <i>alimentary</i> or other -disturbances that precede an initial <i>articular</i> attack as “gouty,” -and likewise those that intervene between the gouty paroxysms -in long-standing cases. In other words, in light of the subsequent -<i>articular</i> outburst, what was mysterious ceases to be a mystery. -All the vague “acidities, flatulencies, megrims, and biliousnesses, -of whatever occult kind,” are forthwith hailed as “gouty,” this -merely upon the ground of the <i>sequence</i> of clinical events, because -the symptoms have disappeared from, <i>e.g.</i>, the stomach to reveal -themselves in the joint or joints, or <i>vice versâ</i>.</p> - -<p>Now my own view is that the antecedent hepatic or digestive -disturbances that so frequently precede initial attacks of gout are -in all probability, nay assuredly, <i>not</i> gout. They should rather -be regarded as the <i>cause</i>, the foundation, of the malady than -its effect, a cause inoperative save in the presence of individuals -victimised by inherent morbid tissue potentialities. For -similar symptoms are but too common in the <i>non-gouty</i>. They -are very common <i>antecedents</i> of, <i>e.g.</i>, <i>rheumatoid or atrophic -arthritis</i>. Nevertheless we do not when the <i>arthritic</i> disorder -<i>subsequently</i> manifests itself talk of the preceding digestive disturbances -as “rheumatoid” dyspepsia. Then why this presumptive -and retrospective diagnosis of similar prodromal phenomena -as “gouty” dyspepsia? For there is pending the articular outbreak -nothing distinctive in the digestive derangements, nothing -that would enable us to diagnose them as “gouty.” They -might, for aught we know, be significant of oncoming <i>rheumatoid -arthritis</i>.</p> - -<p>Now in the case of the latter we regard the <i>prodromal</i> digestive -phenomena as probably indicative of some <i>infection</i> located somewhere -in the <i>alimentary tract</i>. It would be wiser, I think, to adopt -the same attitude in regard to our “gouty” examples. Moreover, -as we know, such dyspeptic symptoms recur from time -to time throughout the life history of both rheumatoid and gouty -arthritis. In the former disorder we regard them as indicative of -<i>recurring infection</i>, followed as they so uniformly are by <i>exacerbations</i> -of the <i>joint</i> trouble. Is it not time we adopted the same -attitude towards the <i>gastric</i> or <i>hepatic functional</i> disorders that -punctuate the course of <i>chronic gout</i> with a periodicity that rivals -that of the articular paroxysms?</p> - -<p><span class="pagenum"><a id="Page_302"></a>[302]</span></p> - -<p>Unquestionably to my mind when we have regard to the -extreme frequency with which <i>local foci of infection</i>, <i>e.g.</i>, oral -sepsis, etc., are found in gouty subjects, this would be the more -rational attitude, the one more in conformity with modern medical -thought.</p> - -<p>But if we would condemn those who, in the presence of unequivocal -tokens of gout, label <i>antecedent</i> or <i>intercurrent dyspepsias</i>, -etc., as “gouty,” what are we to say of those that even in patients -who have never had <i>regular gout</i> or exhibited <i>tophi</i> yet presume to -classify their associated digestive troubles as “gouty”? This, I -contend, is wholly unjustifiable. I would say more, that such -conjectures are hazardous in the extreme, this both in the -overtly gouty as well as in the non-gouty. I recall the instance -of an individual who suffered from classical articular gout which -palpably alternated with attacks of abdominal pain, but the -clue to the true nature of the latter symptoms, as revealed at -operation, was a <i>chronically inflamed appendix</i>. If so in this case, -how many so-called “gouty” acidities have resolved themselves -into <i>appendicular or gall-bladder dyspepsia</i>!</p> - -<p>My conclusion then is that the <i>gastro-intestinal</i> disorders attributed -to gout cannot legitimately be regarded as examples of -<i>irregular gout</i>. They should not be held “symptomatic” of, but -<i>etiologically</i> related to, <i>gout</i>, a view more calculated to lead to exact -diagnosis and rational therapy, and incidentally to elucidate the -true nature of gout.</p> - -<p>In respect of other organs and the symptoms connected with -them in “gouty” persons the case is very much the same. -Always and ever are we confronted with the same difficulty, inability -to determine whether <i>antecedent</i>, <i>co-existing</i>, or <i>consecutive</i> -affections in certain examples of gout, are not associated merely -by <i>coincidence</i>.</p> - -<p>Disturbed <i>cardiac</i> action is not uncommon in gouty subjects, -<i>palpitation</i> and <i>arrhythmia</i> and <i>syncopal</i> threatenings, and frequently -symptoms difficult of differentiation from true <i>angina -pectoris</i>.</p> - -<p>I am reminded of an old physician whom I saw in consultation -some years ago, who suffered from alarming attacks of <i>precordial</i> -anxiety. He was well on in the sixties, and very obese. He was -convinced that his cardiac irregularities, etc., were of <i>gouty</i> origin, -and often exclaimed regretfully: “If I only dared to take two -bottles of port, and got it in my toe, all would be well.” He had -never had an articular outbreak, and based the diagnosis of his -case on the fact that from time to time his <i>urine</i> for long since contained -<i>excess of urates</i>. Having suffered much of many physicians, -he at last grew restive, took the bit between his teeth, rushed to a<span class="pagenum"><a id="Page_303"></a>[303]</span> -spa, and forthwith embarked on a very strenuous course of -“waters and baths.” At once he got a severe attack of acute -polyarthritic gout, and <i>mirabile dictu</i>, all his cardiac troubles -straightway ceased.</p> - -<p>Retrospectively viewed, many would regard the preceding -cardiac condition as of “gouty” source. That the old gentleman, -of florid countenance, plethoric build, and lethargic habit, was -potentially “gouty,” there is no doubt. But he was also abnormally -fond, not of alcohol, but, curiously enough, of sweetmeats -and cakes of all sorts, hence “dyspeptic.” He had a feebly -acting heart, but no detectable <i>valvular</i> lesion, though <i>mural -degeneration</i> seemed likely. My own diagnosis was <i>flatulent -dyspepsia with secondary cardiac disturbance</i>, and finally <i>acute -gout</i>, the exciting cause of which, as I have so frequently seen, -was a course of <i>hydrotherapy</i>. The patient never regretted his -venture, and, I am glad to say, lived for some years.</p> - -<p>Such cardiac paroxysms are not uncommon in the “gouty,” -and, alarming though they are, I question if purely <i>functional</i> -disturbances of this nature ever prove fatal. As to the <i>valvular -lesions</i> and <i>mural degenerations</i> observed in the “gouty,” there is -little or no evidence that they are dependent on gout. Indeed, the -lack of a tendency to <i>endocarditis</i> is one of the criteria distinguishing -gout from acute rheumatism. I note that in one textbook -<i>pericarditis</i> is classed among the cardiac manifestations of -irregular gout. But it must not be forgotten that <i>renal</i> disease, -a frequent concomitant of gout, predisposes to <i>pericarditis</i>, which, -indeed, occurs in granular kidney even when unassociated with -gout.</p> - -<p>As to the <i>respiratory organs</i>, such chronic maladies as <i>bronchitis</i> -and <i>asthma</i> are very frequent in the “gouty,” but I question if -they are more so than in non-gouty subjects. In any case their -symptomatology and course are the same whether gout be present -or not. Much, too, has been made of the fact that <i>asthmatic</i> -and <i>arthritic</i> manifestations may <i>alternate</i>. But we must recollect -that <i>asthma per se</i> has a <i>paroxysmal</i> tendency; it has a tendency -to <i>periodicity</i> and a liability to be excited or aggravated by much -the same factors as favour outbreaks of gout. It is said, too, -that there is a “gouty” <i>pneumonia</i>, and that the same has been -replaced by an acute articular paroxysm. But, in respect of all -these alleged “gouty” respiratory disorders, would it not be -more scientific to cease talking of them as “gouty” and instead -to speak of them as bronchitis and asthma occurring in “gouty” -subjects? This, I may remark, is not to say that we should take -no count of the reigning diathesis in our <i>treatment</i> of all associated -affections.</p> - -<p><span class="pagenum"><a id="Page_304"></a>[304]</span></p> - -<p>Of the <i>nervous</i> phenomena relegated to gout we hear nowadays -less and less. “Gouty” headaches are almost a thing of the past. -The acute “gouty” delirium of older writers in many cases was -but an euphemism for <i>alcoholism</i>, and likewise the <i>spinal paralyses</i>; -while the <i>convulsions</i> and <i>comas</i> were certainly almost always -attributable to <i>uræmia</i>. It would be held rash to-day to speak, -like our forefathers, of “gouty” <i>cystitis</i>, <i>urethritis</i>, or <i>orchitis</i>, -for there is no evidence of any pathological connection between -them; and the same stricture is also applicable to the many -<i>cutaneous</i> affections affiliated without sound pretext to the -<i>materies morbi</i> of gout.</p> - -<p>In the early part of the nineteenth century the French school -were most insistent on the prevalence and variety of the cutaneous -manifestations of <i>l’arthritisme</i>; but even by them the all-pervading -influence of gout in the etiology of skin disorders is no -longer held even as a working hypothesis.</p> - -<p><i>Conclusions.</i>—The sum of my experience and reflections on -so-called “irregular” gout leads me to regard it as an “abstraction” -rather than as a proven clinical fact. Moreover, if I may -judge by the “admission certificates” to the Royal Mineral Water -Hospital, Bath—a fair test, as I maintain—many are of the same -mind as myself, for during the past ten years I do not recall a -single instance in which a patient sought admission thereto as -suffering from “irregular” gout.</p> - -<p>But some writers on gout—indeed, I think I may say all—whatever -doubts they entertain as to the propriety of retaining -the term, yet qualify their pronouncement in favour of -some particular variety of anomalous gout, <i>visceral</i>, <i>cutaneous</i>, -or other. Still, in justification of my own uncompromising -attitude, I must say that dispassionate analysis of their -eclectic claims, in light of present day knowledge, to my mind -fails to show any adequate reason for the faith that is in them. -Of some of them I feel sure that sub-consciously they have -been influenced by a respect for tradition, forgetful of Pliny’s -sentiment,—</p> - -<div class="blockquote"> - -<p>“Quamvis enim cedere auctoritati debeam, rectius tamen arbitror, -in tanta re, ratione quam auctoritate superari.”—<i>Lib. i., Ep. 20.</i></p> - -</div> - -<p>But, to resume, this much at any rate may be affirmed, viz., -that there is no proof that visceral disturbances or cutaneous -disorders are due to <i>uric acid</i>. On the other hand, in view of my -contention that the inherent morbid potentialities of the “gouty” -demand for their fruition the intervention of an <i>infection</i>, the -reader may rightly ask whether the same agent may not be -capable of evoking the <i>visceral</i> or <i>cutaneous</i>, as opposed to the -arthritic, manifestations of gout.</p> - -<p><span class="pagenum"><a id="Page_305"></a>[305]</span></p> - -<p>Trousseau, a whole-hearted advocate of irregular gout, drew -an analogy between gout and syphilis. Somewhat contemptuously -he observes: “To those physicians in whose eyes localisation -constitutes the particular disease the differences in appearances -are so many different diseases, while to those who consider that -the disease consists much more in the aggregate of the general -phenomena, in their evolution, in their progress (and that, thank -Heaven! is the direction in which sound observation leads), -these affections, differing in appearance, are only multiplied -expressions of the same species of morbid action. To the real -physician exostosis, alopecia, psoriasis, roseola, bubo, and -chancre are always syphilis—syphilis in different garbs.” In the -same way he held that the infinitely varied manifestations of -<i>irregular</i> gout were all affiliable to one and the same morbid agent. -He claimed, too, that visceral gout was “the result of a sort of -imperfect inflammation analogous to that which manifests itself -in the joints.”</p> - -<p>Unfortunately for the cogency of the argument, there is no -proof that such visceral inflammations as do occur in the “gouty” -are of gouty origin. Unfortunately, too, the microbic agent -that we postulate as responsible for “gouty” <i>arthritis</i> is as yet -unisolated. If this disability be removed, it might be found that -the said organism was capable of originating, not only the arthritic, -but the alleged visceral, forms of gout. But pending such -discovery I am of opinion that the term “visceral” gout should -be abandoned, in other words that we should cease to talk -of, <i>e.g.</i>, bronchitis, dyspepsia, etc., as “gouty,” and should talk of -them as bronchitis or dyspepsia occurring in the gouty. In this -way we may escape, or, better, render uncalled for, the scathing -criticism of Pye Smith:—“It has become common to ascribe -bronchitis, dyspepsia, gastralgia, iritis, gravel, cystitis, and even -psoriasis to the ‘gouty’ diathesis; but the evidence is very slight, -and the ‘gout’ to which such evidence as there is applies is the -distillation of morbid humours which belong to a bygone -pathology.... There is no reason to believe that gout ever -flies to the stomach, but over-indulgence at the table may produce -acute dyspepsia as well as inflammation of the great toe. -Elderly people are liable to gravel, gout and cough; and while -lead and drink may lead to gout and chronic Bright’s disease, -cirrhotic kidneys favour an attack of gout.”</p> - -<h3><span class="smcap">Infantile Gout</span></h3> - -<p>While subjects of gout have told me that they had had an attack -in their teens, I have never myself seen an instance. Still less<span class="pagenum"><a id="Page_306"></a>[306]</span> -can I claim to have seen what I felt justified in calling “gout” in -children. On the other hand, if, as one authority states, -“tonsillitis (quinsy), enlarged tonsils, granular states of the -pharynx, and catarrhal conditions of the throat and respiratory -mucous membranes are not infrequent expressions of gouty -inheritance in children,” then, of course, all of us must be quite -familiar with “infantile gout.”</p> - -<p>But even this formidable list of legacies from gouty parents is -eclipsed by a more recent writer, J. Comby (1902), who, discussing -“infantile arthritism,” divides children coming of gouty stock -into two types: the “lymphatic” and “nervous.” The -children of the former class suffer from fleeting swelling of the -lymphatic glands, rhino-pharyngitis, tonsillitis, and, if they be -girls, from chlorosis. Also they are given markedly to tachycardia, -bradycardia, and vasomotor ataxia. They are also -especially liable to asthma and the crises of dyspnœa, and -pulmonary congestion may alternate with urticarial and eczematous -eruptions. Truly, their lot is hard, for they fall a ready -prey to colic, constipation, all varieties of dyspepsia, not to -mention nocturnal and diurnal enuresis!</p> - -<p>Comby also claims that these gouty children are especially -liable to recurrent or <i>cyclical vomiting</i>. In this matter he is -confirmed by J. Thomson, who noted that these children not -infrequently give a history of having had asthma, urticaria, -eczema, stammering, and other nervous complaints, also that -in many instances <i>uric acid crystals</i> or a copious deposit of <i>urates</i> -have been noted in their urine.</p> - -<p>As to the “nervous” type, they labour with insomnia, night -terrors, convulsions, and when older with migraine. To these -liabilities must be added undue proneness to acne, seborrhœa, -psoriasis, chilblains, angio-neurotic œdema, urticaria, etc., not -to mention muscular and joint aches and pains.</p> - -<p>Whether this medley of distempers can with any pretensions -to scientific reason be affiliated to a gouty heritage, or whether they -can be regarded as expressions of a budding “gouty diathesis,” is, -I submit, of the nature of pure speculation. That the child who -suffers with cyclical vomiting may show uric acid crystals or -urates in his urine is certainly no proof that he has inherited gout, -much less that he is actually “gouty.” In uro-lithiasis the uric -acid is precipitated in the urinary passages, viz., strictly speaking, -<i>outside</i> the body, whereas in <i>gout</i> the pathological error originates -<i>within</i> the organism. More apposite is Uffenheimer’s observation, -previously noted, that children of this type suffer the same -disturbances of <i>purin</i> metabolism as are met with in adult gouty -subjects.</p> - -<p><span class="pagenum"><a id="Page_307"></a>[307]</span></p> - -<p>If the fact is confirmed that the <i>output of exogenous purin</i> in -such children is <i>diminished</i> or <i>retarded</i>, it would certainly be a -most interesting finding, possibly with a now unguessed-at -significance. But we should recall that even in the subjects of -<i>regular</i> gout such is <i>not invariable</i>, and, moreover, occurs in -diseases other than gout. Pending further exact investigations -I think it would be wiser not to indulge in such vast generalisations, -mindful of the sentiments expressed by the illustrious -Sydenham in his letter to Dr. Gould:—</p> - -<div class="blockquote"> - -<p>“I have bin very careful to write nothing but what was the product of -careful observation. So when the scandall of my person shall be layd -aside in my grave it will appear that I neither suffered myselfe to be -deceived by indulging in idle speculations nor have deceived others by -obtruding anything to them but downright matter of fact.”</p> - -</div> - -<hr class="chap x-ebookmaker-drop"> - -<div class="chapter"> - -<p><span class="pagenum"><a id="Page_308"></a>[308]</span></p> - -<h2 class="nobreak" id="CHAPTER_XXV">CHAPTER XXV<br> -<span class="smaller">OCULAR DISEASE IN THE GOUTY</span></h2> - -<p class="center larger"><span class="smcap">By W. M. Beaumont</span></p> - -</div> - -<p>With the passing of Jonathan Hutchinson disappeared the -premier British exponent of <i>l’arthritisme</i>, that generic term so -attractive to our French <i>confrères</i>. Whether gout and rheumatism -are branches of one common stem need not detain us, for -it is an abstraction more suitable to the philosophic age of -medicine before pathology emerged as an exact science. Be -this as it may, there has been in the past, and there still remains in -the present, as a bond of union, a universal belief that both are -subtle causes of disease of the eye. But the age of hypothesis is -giving place to the era of facts, and we find in recent writings a -more cautious expression of individual opinion, a less dogmatic -positivism regarding the relationship of gout and rheumatism to -ocular disease.</p> - -<p>In referring to modern text-books we find Parsons<a id="FNanchor_44" href="#Footnote_44" class="fnanchor">[44]</a> describes -gout as one of the “alleged causes” of iritis. In rheumatic -iritis he states that the patients “are often gouty.” The gouty -nature of iritis is indicated by the similarity of onset of some -cases of iritis with that of gout. “Iritis in an elderly patient is -likely to be gouty, often starting suddenly in the night and sometimes -ushering in an attack of gouty arthritis.” In episcleritis -“rheumatism and gout are commonly indicated as the chief -causes.”</p> - -<p>Werner<a id="FNanchor_45" href="#Footnote_45" class="fnanchor">[45]</a> includes gout in a list of disorders of metabolism -which produce iritis “by means of toxins of a chemical nature.”</p> - -<p>Sim<a id="FNanchor_46" href="#Footnote_46" class="fnanchor">[46]</a> considers that iritis occurs in gout “as the result of some -toxic influence”; and in addition he says, “Iritis is to be met -with in gout.”</p> - -<p>These authors express accurately, I think, the present views -with regard to gout as it affects the eye; with each there is a -tone of restraint and suggestion rather than of boldness and -assertion, and the contrast to Hutchinson’s emphasis is noteworthy: -“I believe,” he tells us, “that iritis due to the arthritic -diathesis is a common malady.”</p> - -<p><span class="pagenum"><a id="Page_309"></a>[309]</span></p> - -<p>Among the many and indiscriminate diseases of the eye which -have been considered to be due to gout are included blepharitis, -conjunctivitis, episcleritis, scleritis, orbital cellulitis, neuro-retinitis, -retro-bulbar neuritis, optic neuritis, optic atrophy, -iritis, cyclitis, choroiditis, glaucoma and retinal hæmorrhage. -Truly an all-embracing rather than an eclectic list, a medley -of diseases without any melody.</p> - -<p><i>Evidence of Gout in the Eye.</i>—When we inquire what is the -evidence which justifies the belief that gout causes ocular disease -we find little more than a traditional hypothesis inherited in a -long line of succession from the Fathers of Medicine. Nevertheless -the opinion that there is a connection is widespread, not only -in Europe, but also in America.</p> - -<p>In considering this relationship we cannot overlook the effects -of the diathesis on other viscera. How in these is a diagnosis of -gouty origin arrived at? It would appear that the assumption -of an irregular form of gout is based upon the following observations:—</p> - -<div class="blockquote"> - -<p>(i.) That it sometimes happens that an undoubted attack -of articular gout aborts and is followed by symptoms -referable to a grave visceral disorder, <i>e.g.</i>, gout in the -stomach (retrocedent gout);</p> - -<p>(ii.) That sometimes the converse occurs, viz., that an attack -of visceral disorder may suddenly be replaced by an -acute articular manifestation;</p> - -<p>(iii.) That such visceral derangements may alternate, not only -with articular, but also with other, such as cutaneous, -outbreaks;</p> - -<p>(iv.) That eye disease has been known to wax and wane in -unison with concurrent arthritic gouty manifestations;</p> - -<p>(v.) That occasionally in gouty people an attack of iritis of -sudden onset in the night has been followed by remission -of the symptoms in the day<a id="FNanchor_47" href="#Footnote_47" class="fnanchor">[47]</a>;</p> - -<p>(vi.) That visceral symptoms in the gouty are anomalous and -inexplicable on any other basis;</p> - -<p>(vii.) That the treatment usually advocated for gout has a -favourable influence.</p> - -</div> - -<p><i>Deposition of Urates.</i>—Two cases are recorded by Garrod in -which there was a deposit of urates in the sclera. These instances -do not appear to have been confirmed by other observers, and -they may be regarded as exceptional cases, occurring, it should -be noted, in the outer envelope of the eye. But though these<span class="pagenum"><a id="Page_310"></a>[310]</span> -tophaceous deposits may occur in the sclera and in the eyelid, -they have never been known to invade the intrinsic structures, -such as the iris or ocular media. The eye, in fact, is on all fours -with the sites of urates elsewhere—deposition occurs in parts of -relatively low vitality.</p> - -<p>Although urates are not found within the eye, there is in other -morbid ocular conditions quite frequently a deposition of foreign -matter, such as alien crystals, of varied description. For -instance:—</p> - -<p>In the <i>sclera</i> on rare occasions we find osteomatous degeneration.</p> - -<p>In the <i>choroid</i> there may be true bone which forms a cup so -extensive that it can be felt by the finger, or, again, there may be -calcareous plaques.</p> - -<p>The <i>retina</i> may undergo colloidal changes or be the site of -carbonate of lime or of cholesterin.</p> - -<p>The <i>vitreous</i> may sparkle with showers of cholesterin.</p> - -<p>The <i>lens</i> may contain both tyrosine and cholesterin.</p> - -<p>The <i>aqueous</i> shows similar crystals.</p> - -<p>In the <i>iris</i> degenerative calcareous or osseous deposits are -occasionally seen.</p> - -<p>The <i>cornea</i> may be affected by hyaline degeneration with -deposition of lime salts.</p> - -<p>The <i>conjunctiva</i> may be calcareous.</p> - -<p>In all these cases the foreign particles, whether crystals or -otherwise, are usually the retrogressive changes of senescence -proclaiming that the forces which make for degeneration are -more potent than those which make for regeneration.</p> - -<p>But <i>urates</i> are not found <i>in</i> the eye, even though the patient -is gouty. On the other hand, both in gouty joints and in other -similarly affected parts of the body we find a deposition of urate -of soda.</p> - -<p><i>Gouty Diathesis.</i>—From the days of Sydenham—himself a -martyr to gout—diathesis has been a name to conjure with, and -an all-sufficient diagnosis. In the podagrous patient any intercurrent -disorder, any inexplicable ache or pain, was ascribed to -gout, and patient and doctor were alike satisfied. “Tempora -mutantur,” but still we are prone to call morbid conditions -gouty when they occur in gouty people.</p> - -<p>If we accept the theory that gout is due to an excess of uric -acid in the blood, the view which I have expressed elsewhere<a id="FNanchor_48" href="#Footnote_48" class="fnanchor">[48]</a> that -gout does not cause iritis is directly challenged. For if it be -granted that a sudden outpouring of so non-toxic an acid <i>causes</i> -an acute inflammation—for instance, in the synovia of the great<span class="pagenum"><a id="Page_311"></a>[311]</span> -toe—why should not our faith incline us to go further and find in -this malevolent, though bland, acid a source of inflammation -affecting the fibro-muscular meshwork of the iris?</p> - -<p>If, however, we adopt the infective theory, then the association -of the uratic deposits no longer dominates our creed—we -view them as mere clinkers and by-products erupted from the -furnace.</p> - -<p>The infective theory of gout also lends plausibility to an association -with iritis, for this latter is a disease of infective origin. For -the intimate relationship of all forms of asthenic arthritis with -iritis is of very frequent occurrence, but is practically never seen -in the more sthenic arthritides: rheumatic fever, acute gout and -traumatic arthritis.</p> - -<p>Nearly fifty years ago Jonathan Hutchinson drew up a “Report -on the Forms of Eye Disease which occur in connection with -Rheumatism and Gout.”<a id="FNanchor_49" href="#Footnote_49" class="fnanchor">[49]</a></p> - -<p>At the present day it is not easy to differentiate his 117 cases -according to modern classification, but he includes gout, rheumatism, -rheumatic arthritis, etc. The differential diagnosis between -gout and rheumatism was simplified by the creation of a mule—“rheumatic -gout”—and upon its back were packed the doubtful -cases.</p> - -<p>Hutchinson’s views regarding the essential difference between -gout and rheumatism are crystallised in his statement that in -rheumatism there is an arthritic susceptibility to weather, in gout -an arthritic susceptibility to diet.</p> - -<p>Osteoarthritis also seems to have been included as one of the -gouty diseases, probably because <i>post-mortem</i> examination revealed -uratic deposits in the disorganised cartilage. This, however, -would appear to be an epi-phenomenon, and must not be allowed -to obscure the essential distinction between true gout and osteoarthritis. -It is a sign of articular disorganisation of <i>long standing</i>, -and is the homologue of the similar deposition of crystals, etc., -already referred to as occurring in the eye as the result of chronic -disease therein.</p> - -<p><i>The significance of tophi</i>, as the touch-marks of gout, is undoubted, -but even if they are detected in the eyelids or elsewhere, -we are skating on thin ice if we rashly declare that a -coexisting intra-ocular disorder is gouty. Most forms of iritis -betray the same clinical <i>facies</i>, although the etiological causes -are diverse. But in none do we find any appearances pathognomonic -of gout.</p> - -<p>The argument that because a patient has tophi therefore the<span class="pagenum"><a id="Page_312"></a>[312]</span> -iritis is also gouty does not hold good, for gout does not confer -immunity from other diseases, and even though we cannot prove -an alibi for the diathesis, we can often in these cases also indict -gonorrhœa, pyorrhœa or some other pathogenic agent.</p> - -<p>The favourite site for tophi is one in which blood-vessels are -sparse; but, although the cornea is void, imbibition of blood from -the marginal looped plexus of capillaries and an abundant lymph -supply provide amply for nutrition, and tophi are not found in -this locality. The sclerotic, however, has a meagre supply of -vessels, and for some unexplained reason tophi rarely invade it. -In the eyelids, on the other hand, possibly from the cartilage -being rich in sodium, tophi are occasionally seen. If we accept -the tophus as the one unequivocal criterion of gout, we are not -justified in labelling an iritis as gouty in its absence. If we do, -our diagnosis is presumptuous and not absolute. Strictly -speaking, the diagnosis cannot be made. We may the more -readily admit our limitations, inasmuch as they are a blessing -in disguise, and suggest a further etiological search.</p> - -<p>In Hutchinson’s list of eye diseases which occur in association -with rheumatism and gout there is a history of gonorrhœa in -twenty-six cases, syphilis in seventeen, of both gonorrhœa and -syphilis in six. Herpes occurred in two, pustular acne in one, -eczema in one, albuminuria in one, ague in one. Bad teeth are -reported in two. In all the total was fifty-seven cases out of 117 -(48·7 per cent.) in which there was a possible source of infection. -It is probable that this percentage would have been materially -increased if at that time it had been recognised how great is the -influence of pyorrhœa and other sources of infection in the etiology -of irido-cyclitis.</p> - -<p>With regard to all infections it is only in the present day that -full advantage is taken of bio-chemical and bacteriological -methods of differentiation. How frequently the true origin of -disease must have been overlooked when the pallid spirochæte -was unknown, when the Wassermann test was not applied, and -when the complement fixation test for gonorrhœa was not -recognised.</p> - -<p>With regard to a combined cause it has been maintained that -gonorrhœa is always more severe in the gouty than in other people, -and it may be that the more intense the gonorrhœa the more -likely may it be to produce constitutional symptoms, of which -iritis is one. In all such the combination of gout and iritis -would indelibly impress upon the mind of the surgeon the intimate -association of joint and eye. It was long ago recognised that -many forms of joint disorder were associated with iritis, and, as -the cause of the arthritis was not always gout, Mackenzie introduced<span class="pagenum"><a id="Page_313"></a>[313]</span> -the generalisation “arthritic iritis.” “Not being able,” -he tells us,<a id="FNanchor_50" href="#Footnote_50" class="fnanchor">[50]</a> “to determine the diathesis which predisposes to -this ophthalmia” (iritis), “I use <i>arthritic</i> as a conventional term, -without adopting it in the strict sense of gouty.” The expression -is well worthy of retention for the reason that it warns us to be -prepared for an attack of iritis in many forms of arthritis and -arthralgia.</p> - -<p>In the following articular diseases the triad joint, muscle and -nerve disorders is not uncommonly linked with iritis:—</p> - -<ul> -<li>Tuberculous arthritis;</li> -<li>Syphilitic arthritis;</li> -<li>Gonococcal arthritis;</li> -<li>Certain forms of specific arthritis: malarial, dysenteric, etc.;</li> -<li>Infective arthritis of undifferentiated type, as yet unaffiliated to specific germs.</li> -</ul> - -<p>In the following forms of arthritis iritis is less common:—</p> - -<ul> -<li>Acute articular rheumatism;</li> -<li>Acute gout;</li> -<li>Osteoarthritis (hypertrophic);</li> -<li>Rheumatoid arthritis (atrophic).</li> -</ul> - -<p>Iritis occurring in these last suggests the possibility of error -in the diagnosis of the putative parent disease. Especially is the -clinical similarity of gonorrhœal (polyarticular) rheumatism to -rheumatoid arthritis to be borne in mind.</p> - -<p><i>The Relative Incidence of Iritis.</i>—In the text-books it is often -stated that the syphilitic form of iritis is the one most frequently -met with, and that gouty iritis, if it is met with at all, is much -more rare. But in these comparative statements we have no -clue to the frequency of iritis with syphilis, nor of iritis with -gout. For a true analogy we do not want the syphilographer to -tell us the aggregate number of cases of iritis that he has seen, -but what is the percentage of cases of syphilis in which iritis -occurs, and we want the gout physician to state his percentage -of iritides in gout, or, negatively, what is the percentage of -cases in which iritis does not occur.</p> - -<p>If gout is a more prevalent disease than syphilis, it does not -follow that “gouty” cases of iritis will be more numerous than -those due to syphilis. Let us suppose, for the sake of clearness, -that 1 per cent. of people suffering from gout get iritis, and that -also 1 per cent. of people infected by syphilis get iritis, and that -in a certain town there are two hundred people who are gouty -and one hundred people who are syphilitic. It is probable that -there will be two persons suffering from gouty iritis (always<span class="pagenum"><a id="Page_314"></a>[314]</span> -supposing there is such a disease), but only one from syphilitic -iritis. The absolute totals will differ, but the relative will be -identical. It is clear, then, that infectivity cannot be gauged -by the statistical enumeration of the consulting-room. Gout -is a rarer disease than our patients would have us believe, -but accepting their views, even then we should expect to -see more cases of iritis caused by it, if such existed; we -should expect to find more definite proof of a causal connection, -and less frequently a history of gonorrhœa, of pyorrhœa, and of -syphilis.</p> - -<p><i>No Uratosis, no Gout.</i>—If we pin our faith to the equation</p> - -<p class="center">Hyperuricæmia + Uratosis = Gout,</p> - -<p class="noindent">we can at once exclude all cases of ocular disease as gouty in the -absence of either factor. According to Garrod, “true gouty -inflammation is <i>always</i> accompanied with a deposit of urate of -soda in the inflamed part.” We should therefore expect that -uratosis would occur <i>in situ</i> if an iritis were gouty. But it does -not: the touch-mark is absent, and there are no chemical, -pathological or clinical signs of urates in the iris after the inflammation -has subsided. What then is the alternative? Either -Garrod’s aphorism is inaccurate or iritis is never gouty. In -other words, we must postulate that an iritis may be regarded -as gouty without uratic deposits. If this be the case, the so-called -gouty iritis may well rank with the occult migraines, -flatulencies and acidities which are termed irregular, suppressed -or latent gout. Strictly then it would be a latent gouty iritis fit -to rank with that last refuge of the uric acid enthusiasts, the -“latent nephritis” which they worship as the <i>fons et origo mali</i> of -gout.</p> - -<p><i>Metastasis.</i>—The predilection of the gonococcus for synovial -membranes is seen not only secondarily to urethral infections, but -also in ophthalmia neonatorum, in which the joints of infants -are affected sequentially to the eyes.<a id="FNanchor_51" href="#Footnote_51" class="fnanchor">[51]</a></p> - -<p>The gonococcus also has been found in cases of peritonitis, -pleurisy, pericarditis, etc., but it is said to have only once been -isolated in the eye in iritis.<a id="FNanchor_52" href="#Footnote_52" class="fnanchor">[52]</a></p> - -<p>It is not only the gonococcus which can initiate a metastasis -from the eye to the joints, to the peritoneum, or elsewhere. The -same process may be started by the <i>bacillus typhosus</i>, by -the streptococcus of erysipelas, and by that of puerperal septicæmia.</p> - -<p><span class="pagenum"><a id="Page_315"></a>[315]</span></p> - -<p>De Grandmont<a id="FNanchor_53" href="#Footnote_53" class="fnanchor">[53]</a> records the case of a young man recovering -from typhoid, complicated with jaundice and nephritis, who was -attacked by iritis with posterior synechiæ and hypopyon. Paracentesis -was done, and the pus of the anterior chamber was transferred -to agar-agar. Two days later a pure culture was obtained -presenting all the reactions and characteristics of the bacillus of -Eberth. Of this culture a small quantity was injected into the -vitreous of a rabbit. A month later the rabbit was killed, when -the liver and intestines were found to be infiltrated with the same -bacillus of Eberth.</p> - -<p><i>In erysipelas</i> de Grandmont has seen a hyalitis from which a -culture was grown on gelatine that presented all the morphological -characteristics of erysipelas.</p> - -<p>He has also met with a case of hyalitis associated with puerperal -septicæmia, and he has no doubt that it was the result of a similar -microbic invasion of the vitreous.</p> - -<p>Gout does not render patients immune from tuberculous, -syphilitic or gonococcal disease, and when in such so-called -diathetic stocks an iritis occurs, especially in gonorrhœa, years -after the primary disease, it is probable that gout, rather than -lues, will be assigned as the cause.</p> - -<p>The local appearances of iritis are identical in gonococcal and -other infective iritides; they resemble clinically those seen in -syphilis and tubercle except that in these there are sometimes -condylomata of the iris in the one and tuberculous nodules in the -other. To be comparable a gouty iritis should be characterised -by iritic tophi.</p> - -<p><i>“Arthritic” Iritis.</i>—Forty-eight is a large percentage in Hutchinson’s -cases of ocular disease associated with gout and rheumatism, -and it is justifiable to assume that there was something more than -coincidence in the triple <i>entente</i> of diathesis, arthritis and iritis. -But the fact that the poisons of syphilis and gonorrhœa, etc., are -potent causes of iritis is indisputable, and therefore the patients -might have suffered from it even if they had never had either gout -or “rheumatism.” Consequently these articular diseases are -both superabundant and superfluous, and they may have no -etiological status. A patient afflicted with arthritis is very -susceptible to an associated attack of iritis provided that there -is a septic focus anywhere in the body.</p> - -<p>A practical point to remember, especially in gonorrhœa, is that -the onset of joint trouble should warn us to anticipate the possibility -of an associated iritis and should prompt us to instil atropine -at an early stage. We should forestall the disease by treating<span class="pagenum"><a id="Page_316"></a>[316]</span> -the suspicion. The frequency with which gonorrhœa is followed -sooner or later by iritis entitles this ocular phenomenon to be -considered a secondary symptom of gonorrhœa, as it is of syphilis.</p> - -<p>Before the potency of distant infective foci (for example, in -nasal disorders, pyorrhœa, sinusitis, etc.) to produce ocular -disease was recognised, there was justification for the inclusion of -a so-called idiopathic iritis, but it is seldom now that we have to -be satisfied with this negative diagnosis. Nevertheless the -assignment of a toxæmic etiology must be based on a definitely -ascertained focus of toxic absorption, or failing this, at least on -symptoms of general malaise which render such a focus highly -probable.</p> - -<p><i>Frequency a Factor in Diagnosis.</i>—It was known a century -before the birth of bacteriology that gonorrhœa caused iritis. It -was also noted that certain constitutional symptoms occurred in -syphilis, and that among them not infrequently iritis was one. -Observation and deduction was the process with our forefathers, -and it seldom led them astray.</p> - -<p>If in any sequence of events cause and effect are to be established -when there is no obvious proof of connection, we may have -to be content with an empirical diagnosis, and this was the position -before the discoveries of bacteriology enabled us to place the -etiology of iritis on a firm basis. How then did our ancestors -know that syphilis and gonorrhœa caused iritis? Was it not—</p> - -<div class="blockquote"> - -<p>(1) <i>That the frequency of the association was the essence of the -diagnosis</i>,</p> - -<p>(2) <i>That there was absence of any other recognised cause</i>, and</p> - -<p>(3) <i>In the former disease the effect of anti-syphilitic therapy</i>?</p> - -</div> - -<p>Applying these rules to gout, we find—</p> - -<div class="blockquote"> - -<p>(1) <i>No marked frequency of association of ocular disease and -gout</i>,</p> - -<p>(2) <i>That when iritis does occur there is often some other possible -source of origin</i>, and</p> - -<p>(3) <i>That anti-gout treatment has only a doubtfully beneficial -effect</i>.</p> - -</div> - -<p><i>“Gouty” Iritis is not a Clinical Entity.</i>—Before a symptom or -affection can be classed as secondary to a primary disease there -must be evidence of a connection stronger than <i>post hoc, ergo -propter hoc</i>. For instance, in syphilis an iritis <i>frequently</i> follows -which may be of the specific condylomatous type, and a laboratory -examination of the inflamed iris may demonstrate the presence of -the spirochæte. On the other hand, an iritis occurring in a gouty -patient is indistinguishable from that form which results from -infections of undifferentiated type. Moreover, iritis so <i>seldom</i> -occurs associated with gout, and when it does there are so often<span class="pagenum"><a id="Page_317"></a>[317]</span> -present other well-recognised possible causes, such as pyorrhœa -or gonorrhœa, that the doubt about the paternal relationship of -gout to the iritis is overwhelmingly strong.</p> - -<p>In the following table a comparison is made between types of -iritis:—</p> - -<h3><span class="smcap">Iritis</span>.</h3> - -<table class="borders"> - <tr> - <th></th> - <th>Gout.</th> - <th>Syphilis.</th> - <th>Tubercle.</th> - <th>Toxæmia.</th> - </tr> - <tr> - <td>Pathognomonic symptoms.</td> - <td class="tdc">0</td> - <td>Gumma of iris.</td> - <td>Tubercles of iris.</td> - <td class="tdc">0</td> - </tr> -</table> - -<p>If pathognomonic symptoms were always present the differentiation -of the various causes of iritis would be less difficult. -But this is not the case, and consequently, whatever the primary -cause, the appearances of the iritis, in spite of the pathogenesis, -objectively resemble each other in very many instances.<a id="FNanchor_54" href="#Footnote_54" class="fnanchor">[54]</a></p> - -<p>Medical authorities call certain cases (not varieties) of iritis -gouty; they are content to rest the diagnosis on the ground that -they occur in gouty people. Yet there is not a single <i>ocular</i> -symptom which differentiates the disease from a similar one in -<i>non-gouty</i> subjects. Before the dogma can be accepted that -because a gouty man has iritis it is therefore a gouty iritis and, -like the poet’s primrose, nothing more, it must be shown that -irido-cyclitis is proportionately more frequent in people who are -gouty than in those who are not. Even then it is suggestive, -but not conclusive, for it is conceivable that, although gout -is not strictly the cause, yet it may so reduce the resisting -power of the iris that it becomes a readier prey to some lurking -organism.</p> - -<p>It is commonly reported that the existence of a gouty diathesis -gives to any inflammatory condition of traumatic origin—synovitis, -for instance—a special tendency to chronicity, and I would not -deny that it may have the same influence in the case of iritis of -traumatic endogenous origin.</p> - -<p>If then a gouty man is not immune from other possible causes -of iritis, one of these, and not gout, may be responsible for it. -Especially is a gouty diagnosis doubtful when there is a focus of -suppuration in the tonsils, teeth or elsewhere. Also the prolonged -hibernation of the gonococcus, for many years after the attack<span class="pagenum"><a id="Page_318"></a>[318]</span> -of gonorrhœa, is apt to be overlooked. The presence of excess -of uric acid in the blood, which sometimes occurs in these patients, -may mislead us into the belief that we have a true gouty iritis -to deal with. But even although it is ascertained that a -hyperuricæmia of 4-8 mg. of uric acid is present, it is no proof -that the co-existing iritis is necessarily gouty. We might have -an even higher content of uric acid in the blood in leukæmia, and -yet no iritis be present. It may be admitted that on rare occasions -iritis occurs in leukæmia, but no one suggests that the leukæmia -or the associated iritis is due to uric acid toxæmia. We should be -on infinitely surer ground if not uricæmia, but uratosis, were -present. We could then, at any rate, confidently assert that, -whatever the origin of the iritis, it had supervened in a subject -of gouty habit. I do not think that we, as clinical observers of -iritis, should go further than to say: “The man is gouty; his -iris is inflamed.” Here in Bath, among hecatombs of gouty -people, irido-cyclitis is one of the rarer associated diseases -requiring treatment. When it does occur it is usually of obviously -septic genesis rather than of gouty origin.</p> - -<p>Contrasting gonorrhœa with gout, we find in the former when -there is systemic infection, as shown by arthritic complications, -there may be also iritis, so often, in fact, that it is legitimate to -bracket it as a related symptom. It is a toxæmic condition in -which we rely on the <i>frequency</i> of the combination to diagnose -the cause.</p> - -<p>In writing on iritis in 1908,<a id="FNanchor_55" href="#Footnote_55" class="fnanchor">[55]</a> I referred to the rarity of the -association of gout and iritis. In an analysis of 17,197 cases of -“rheumatism” and rheumatoid arthritis occurring at the Royal -Mineral Water Hospital, Bath, in twenty years, there were twenty -patients who suffered from acute or subacute iritis. During the -same period there were 2,159 gouty patients not one of whom -had iritis. In a special hospital it is possible that the diagnosis -of gout might be limited by a stricter nosological differentiation -than occurs in private practice. It is, moreover, not uncommon -for ophthalmic surgeons to see patients who call themselves -gouty, or who say that their doctors have told them that they -are, and yet on examination no corroboration is found, no -clinical outbreak, or, more pertinent, no tophi. They come to -us with an attribution of iritis to gout without the filmiest shadow -of evidence.</p> - -<p>In considering the correlation of cause and effect it not infrequently -happens that we find no obvious connection between the -one and the other. In syphilis, for instance, alopecia is a usual -secondary symptom, and we rely on the frequency of the sequence<span class="pagenum"><a id="Page_319"></a>[319]</span> -to satisfy ourselves that it is no mere coincidence. If it could be -shown that alopecia did not occur more frequently in syphilitic -people than in non-syphilitic we might justly doubt the connection. -The same reasoning may be applied to iritis and gout: the -association is so rare that it is negligible. To justify a causal -connection between diseases the possibility of a fortuitous concurrence -must be excluded, for when the double event occurs only -very exceptionally, it is difficult to exclude the long arm of -coincidence.</p> - -<p>A man has iritis and tophi; <i>ergo</i> we say he has gouty iritis. -But why? They co-exist, it is true, but where is the link of -attachment of cause and effect? How different is our attitude -if we know in another case that our tophaceous iritic patient has -gonorrhœa. We then say, gonorrhœal iritis in a gouty subject. -Would it not also in the first case be more scientific if we frankly -confessed that it was an infective iritis of undifferentiated type -occurring in a person of gouty diathesis?</p> - -<p>In considering the iritides in relation to gout there are two -types which demand our attention. With the possible exception -of traumatic iritis, this grouping embraces all the etiological -varieties of the affection. In the first are those cases which are -due to specific infection, such as syphilis, gonorrhœa and tuberculosis. -In the second are those infections of undifferentiated -type in which the causal germ has not yet been isolated. Now -clearly we must read the latter in the light of their analogues, -the specific iritides. In them the modes of onset, the clinical -course, are duplicated, presenting similar variations, and they -are doubtless the reflexes of the varying grades of intensity of -the causal organism.</p> - -<p>Concussion iritis would fall into line, for it is possible in this -case that the iris is rendered a <i>pars minoris resistentiæ</i> by the -blow, and that the iritis which follows is due to a cryptic focus, it -may be in the gastro-intestinal tract or elsewhere. The chief -sources of iritis are syphilis, gonorrhœa, tubercle and infections -from undifferentiated organisms of low grade. If these said -iritides occur in a person of gouty diathesis they are unmodified -by it clinically or pathologically, macroscopically or microscopically, -save possibly in the direction of chronicity—a result, -it may be, of those inherent peculiarities of tissue metabolism -ingrained in a gouty subject, and in which presumably the iris -shares.</p> - -<p>And that which has been said of iritis in the gouty applies -equally to other forms of so-called gouty ocular manifestations. -There are no statistics available to show that there is any differential -frequency in those who are gouty compared with those who<span class="pagenum"><a id="Page_320"></a>[320]</span> -are not. Authors have laboriously recorded cases of eye diseases -which have waxed and waned in unison with podagrous toes, -but the publication of these cases is in itself a confession of the -rarity of the coincidence, a rarity which destroys the authenticity -of any communal kinship. Coincidence is merely another name -for the rigid and immutable law of chance, for a cycle of events -which occurs with irregular regularity. If it could be shown that -a diet rich in purins brought on an attack of ocular disease in -gouty people, and if the experiment could be repeated with a -similar result and sufficiently often to exclude all probability -of coincidence, scepticism would no longer be justified. But -until more definite evidence is forthcoming “gout” in the eye is -nebulous.</p> - -<p>In attempting to define the relationship of gout to ocular -disease, there is one author to whose opinion we turn with the -respect due to a master. Garrod’s judicial summing up supports -the view that there is a connection between gout and ocular disease, -but his cautious statement seems to imply that the affection of -the eye is modified by rather than due to gout. His statement -is as follows<a id="FNanchor_56" href="#Footnote_56" class="fnanchor">[56]</a>:—</p> - -<div class="blockquote"> - -<p>“<i>Gout of the Eye.</i>—A form of ophthalmia connected with -gout has long been recognised, and appears to be tolerably -well established, but as rheumatic inflammation of the eyes is -equally allowed to exist, difficulties may at once arise in the -diagnosis. I have witnessed many cases in which conjunctivitis -and sclerotitis appeared to be distinctly connected -with the gouty diathesis, and in two cases there existed -deposits of urates on the surface; gouty iritis also occasionally -occurs. I once saw a case of acute inflammation of -the sclerotic coat and iris which supervened a few days after -the operation for cataract in a gouty subject. By active -treatment the disease was arrested, but distinct articular gout -soon manifested itself.</p> - -<p>“Our information on this subject may be thus summed -up: patients having a well-marked gouty diathesis now and -then experience attacks of inflammation of the different -structures of the eye; and it is important to bear in mind -the fact that the state of the habit considerably modifies and -keeps up such affections, and also that treatment directed -to the gouty condition of the system proves very effectual in -curing the local mischief.”</p> - -</div> - -<p>It will be observed that Garrod tells us that his two important -cases of sclerotitis “appeared to be distinctly connected with the -gouty diathesis.” With the reticence of the careful and accurate<span class="pagenum"><a id="Page_321"></a>[321]</span> -observer, he does not say they were due to it even though there -were deposits of urates on the surface. He would seem to recognise -that cases of sclerotitis with uratic deposits were unusual -events, and that generalisations cannot be based upon exceptional -cases. A gouty man is gouty to his innermost cells, and the eye, -like every other part of the body, is a potential uratic site. We -must grant therefore that the course of an iritis, however caused, -may be influenced, though not necessarily dominated, by the -diathesis. Consequently it may be necessary that cases of iritis -of undoubted gonococcal or other infective source occurring in -gouty people should be treated by iodides, salicylates, atophan or -colchicum.</p> - -<p>From the academic point of view ocular gout may exist, but -from the practical point we should invariably seek, and we shall -probably find, some still more important source of infection -requiring treatment.</p> - -<p><i>Ocular Symptoms in Hyperuricæmia.</i>—The popular view that -gout depends upon uricæmia is so generally accepted that the expressions -“uric acid diathesis” and “gouty diathesis” are tantamount -to tautology. Nevertheless they are different, the first postulating -the supposed cause, the second the inferred result. There -is a commingling of cause and effect. Uricæmia is a normal -condition of the blood, but in certain diseases—gout, leukæmia, -plumbism, pneumonia, etc.—a considerable excess of urates is -found. No form of ocular disease is included as an associate of -hyperuricæmia unless one or other of the ancillary diseases is also -present.</p> - -<p><i>In leukæmia</i> when severe there is an extremely pale fundus, -with a yellowish tint; hæmorrhages, when they occur, are often -pale; the choroidal vessels also, if they can be seen, are pallid; -the veins in the retina are full and tortuous. There may also be -yellow foci, and occasionally retinitis with white spots. In a word, -the leaking vessels tell of vascular disease.</p> - -<p><i>In lead-poisoning</i> we find paralysis of ocular muscles, amblyopia, -contracted fields of vision, papillitis and retro-bulbar neuritis. -It is the nervous system upon which the stress principally -falls.</p> - -<p><i>In pneumonia</i> we do not expect to find any ocular complications; -in spite of the uricæmia, the eyes are scatheless.</p> - -<p>It seems unlikely that hyperuricæmia can produce such widely -different signs in the eyes. Rather, on the other hand, the ocular -symptoms conform to the type we should expect to find associated -with leukæmic blood in the first and with lead-poisoned nerves in -the second.</p> - -<p>In this congeries of ocular symptoms, marked by hyperuricæmia,<span class="pagenum"><a id="Page_322"></a>[322]</span> -we do not find iritis included, and yet this is a commonly accepted -<i>gouty</i> affection of the eye.</p> - -<p><i>False Gout.</i>—It often happens that patients tell us that they -are gouty although they do not claim to suffer from attacks in the -old-fashioned way. With them there is a wide difference between -the substantive “gout” and the adjective “gouty,” the latter -apparently implying an attenuated form of the former. Such -patients are seen at health resorts and are very frequently those -in whom obesity and plethora are present to a marked extent. -The full-blooded appearance involves the head, body and limbs, -but the eyelids, for some unexplained reason, may escape. The -patients have lived not wisely, but too well. On examination an -increased quantity of uric acid in the urine is found, and is -supposed to justify the diagnosis of gout. Sometimes the malassimilation, -is associated with arterio-sclerosis, with diabetes, or -with albuminuria. But the patient is almost invariably convinced -that he has gout, that it is hereditary, that it has been handed -down to him through a long line of ancestry from primeval days, -and that an ascetic life would not have prevented it in his case.</p> - -<p>Should such a one be attacked by iritis, the circularity of the -argument is complete: he has iritis, therefore he is gouty; he is -gouty, therefore he has iritis. But usually in the early days of -this so-called gout we see no ocular changes; the time for organic -disease (inflammatory and hæmorrhagic) has not yet arrived; -auto-intoxication has not yet begun. But sooner or later with -the maturation of disease come ocular degenerative signs, retinal -hæmorrhages, and so on. The sequence is malassimilation, -“goutiness,” sub-infection, ocular disease. Thus in diabetes -melitus (omitting toxic and traumatic forms) we find pancreatic -disease, nutritional changes, and not usually until late retinitis, -cataract, iritis, etc. In renal disease retinitis is also late and often -ushers in the final scene.</p> - -<p>If in these cases of so-called gout we implicitly accept the -patient’s nomenclature of disease, we shall find plenty of gouty -iritis, but we may overlook the fundamental condition of his -arteries, of his kidneys, and of other organs.</p> - -<p>The sins of repletion in such patients may be relieved by the -virtue of abstinence, not by colchicum.</p> - -<p><i>Retinal Hæmorrhage.</i>—That retinal hæmorrhage may be caused -by gout was firmly maintained by Jonathan Hutchinson.<a id="FNanchor_57" href="#Footnote_57" class="fnanchor">[57]</a> This -opinion was shared by Gowers, who states that the “influence -seems well-established.”<a id="FNanchor_58" href="#Footnote_58" class="fnanchor">[58]</a></p> - -<p>Hutchinson pointed out that in cases of retinal hæmorrhage of<span class="pagenum"><a id="Page_323"></a>[323]</span> -renal origin, stellate white deposits occurred, whereas in gouty cases -they were absent. By this criterion he classified his cases. In -his first patient Hutchinson relates that he can only state from -memory that there was no albumen, but that “he seemed in -good health and that there was reason to suspect gout, although -he had not had a definite attack.” In his second case, a woman -who had suffered from rheumatic gout and true gout, there were -numerous hyaline casts in the urine, but no albumen. In both -cases the hæmorrhages were flame-shaped, and Hutchinson lays -stress on the shape in gouty retinitis hæmorrhagica. The group -consisted of fifteen patients, eleven men and four women. -“Gout had been positively present in six, and was strongly probable -in four or five others. In one the gout was complicated, and -probably in part produced, by lead poisoning, and this is the only -instance in which the urine contained much albumen. In another -in which no history of gout was obtained, the patient, a man <i>æt.</i> 67, -had diabetes, which was the probable cause of the retinitis.... -In about a third of the cases albumen was found in the urine, -but it was usually a mere trace and only present occasionally.... -In four, including the case of diabetes, white deposits characteristic -of renal retinitis were present in small quantity, and in all these -albumen was found in the urine.”</p> - -<p>Hutchinson sums up his cases with the catholic observation -that retinitis hæmorrhagica is a malady the boundaries of which -are very indefinite. And when we bear in mind the changes of -modern medical opinion with regard to the influence of arterio-sclerosis -on the retinal circulation and the effects of vascular -hypertension the etiological difficulties regarding retinal hæmorrhages -are hardly less illimitable than they were when Hutchinson -penned his valuable contribution. In all his cases (as in those -which we see now forty-two years later) there are many factors -which may have been responsible for the hæmorrhages apart from -gout.</p> - -<p>In renal disease gout is widely recognised as a possible precursor. -So we are again in the same quandary that we experience in -considering the relationship of gout to iritis. Are the retinal -hæmorrhages due to gout or to the resulting renal disease? The -claim of gout to be the <i>deus ex machina</i> once more seems to be -superfluous, for retinal hæmorrhages are an end result which -may be reached by a variety of pathological routes. Gout may -be one, but if so it acts <i>viâ</i> interstitial nephritis. In other words, -hæmorrhagic retinitis is the apanage of nephritis and the appendix -of gout.</p> - -<p>It is impossible to affirm that a retinitis is gouty, for there are -no distinctive features, but it occurs in gout when vascular<span class="pagenum"><a id="Page_324"></a>[324]</span> -disease has supervened, not gouty retinitis, therefore, but -retinitis in the gouty. This is all that can be affirmed when we -find albumen in the urine and tophi in the ears, eyelids, etc. -Moreover, it is wiser in the interest of the patient to take this -broad view. There may be a link between the kidney and the -diathesis, but it is invisible.</p> - -<p>Neither are we absolved from searching for some other cause -of renal disease. The case may be fundamentally one of arterio-sclerosis -with a secondarily induced sclerotic kidney, or, on the -other hand, the hæmorrhages may be symptomatic of pernicious -anæmia and due to toxins. With regard to prognosis it is helpful -to remember that retinal hæmorrhages, especially when they are -isolated, suggest the possibility of death ensuing suddenly from -cerebral hæmorrhage; but albuminuric retinitis is itself frequently -a terminal stage of chronic renal disease. We have not sufficient -proof to call retinitis gouty, and we should adhere to the more -catholic appellation “nephritic retinitis.”</p> - -<p>James Taylor, writing on neuro-retinitis in the gouty,<a id="FNanchor_59" href="#Footnote_59" class="fnanchor">[59]</a> states -that—</p> - -<div class="blockquote"> - -<p>“Commonly, of course, it occurs in association with albuminuria, -yet it is met with apart from this even in cases -where no very obvious cardio-vascular changes can be -demonstrated in other regions. And thromboses in retinal -veins, apart from cardiac hypertrophy and demonstrable -changes in the arteries or in the blood pressure, are of frequent -occurrence. In such cases gout is possibly—in many cases -demonstrably—a very important factor in the etiology.”</p> - -</div> - -<p>The opinion that cases of neuro-retinitis may be gouty is -based upon (<i>a</i>) the fact of the apparent absence of cardio-vascular -disease elsewhere, (<i>b</i>) the lack of any other ostensible -cause. Doubtless many cases of retinal hæmorrhage are seen -for which we are unable to assign a cause; in some of these there -is no suggestion of gout and nothing to support a postulation of -a latent form of that diathesis. Taylor’s statement that gout -in many cases is demonstrably a very important factor in the -etiology cannot be lightly set aside, but as the appearances of -neuro-retinitis are similar whether gout is present or absent, it is -legitimate to question if the diathesis is really necessary.</p> - -<p><i>Glaucoma.</i>—Brudenell Carter, Hutchinson and Nettleship -have claimed that gouty people are more apt than others to -suffer from glaucoma, but no convincing argument has been -brought forward in proof of any definite nexus.</p> - -<p><i>The conclusion</i> I would arrive at is that it is unwarrantable -to speak of “gouty” ocular disease, for there is nothing in the<span class="pagenum"><a id="Page_325"></a>[325]</span> -character of the inflammation specific of gout. We renounce the -prefix in order—</p> - -<div class="blockquote"> - -<p>(1) That we may not be lulled into false etiological security, and</p> - -<p>(2) That we may approach the elucidation of the case and the -treatment thereof free from preconceptions. The mouth -and its accessory cavities are the primary sphere of our -investigation. This is no mean task, including as it does -the radiography of the teeth, even though these are -apparently healthy. In the tortuous route of elimination -we look for concealed dental roots, rarefying osteitis, -buried tonsils, post-nasal infections, antral disorders.</p> - -</div> - -<p>The view that non-traumatic iritis is only a symptom imposes -upon us a wide outlook in our search for a diagnosis. In this no -viscus can be overlooked, no organ forgotten. All are members -one of another, and the wise physician takes cognisance of their -interdependence. The recognition of an inflamed iris is only the -first stage in the diagnosis, for iritis is the sequel of a story written -elsewhere. It is a question, not an answer.</p> - -<p>But we know not what the future has in store, and though, with -our present knowledge, I affirm that I can find no evidence that -the eye is a <i>locus signi</i> for gout, the day may come when, either -from bacteriological or other sources of progress, it may be shown -that there is a mystic source of intercommunity. In other words, -it may yet happen that the mysterious <i>materies morbi</i> of gout, -whether microbic or chemical, may be demonstrated experimentally -as capable of inducing, not only the arthritic phenomena, -but also those inflammatory lesions in the eyes which provisionally -are sometimes called “gouty.”</p> - -<p>Lastly, I would enter a plea for more systematic, more scientific, -investigation of the true link, if any, between iritis and arthritis. -The war has taught us the value of “team-work”; it has taught -us that the clinician must be reinforced by the bio-chemist, the -bacteriologist and the pathologist. The work and the workers -must be co-ordinated in our daily struggle with disease as we meet -with it in our individual patients. The realm of medicine, with -ever widening borders, is too vast for single control. In the -foregoing pages I have said much about iritis, and it is a good -example of what I mean. In justice to our patient, we may -call for a Wassermann or a complement fixation test; we may -require the teeth-roots made visible by an X-ray expert, or, it may -be, the passage of a bismuth meal radiographed, hidden tonsils -explored by the laryngologist, or the antrum illuminated; the -fæces may need bacteriological examination. A gynæcologist -may help us regarding a leucorrhœa or a possible ovarian -abscess.</p> - -<p><span class="pagenum"><a id="Page_326"></a>[326]</span></p> - -<p>With many of our patients, alas! considerations of expense -compel us to forego our aspirations.</p> - -<p>What is the remedy? Is it not State help, central clinics -staffed by highly trained experts engaged in research work? -Here the poor could be examined and reports supplied to the -attendant doctors free, and less impecunious patients at an inclusive -fee. Centres such as these would do much to advance the -science of medicine and thereby raise the standard of health and -make the sick and ailing healthy citizens of a great empire.</p> - -<p><i>Salus populi suprema lex.</i></p> - -<hr class="chap x-ebookmaker-drop"> - -<div class="chapter"> - -<p><span class="pagenum"><a id="Page_327"></a>[327]</span></p> - -<h2 class="nobreak" id="CHAPTER_XXVI">CHAPTER XXVI<br> -<span class="smaller">TREATMENT OF GOUT</span></h2> - -</div> - -<p>Adaptation is the keynote to progress in therapy—adaptation -of our therapeutic measures to the ceaseless advances of pathology. -In the history of gout it has ever been so, the changing, oftentimes -contradictory, vogues in treatment, always the reflex of equally -mutable and conflicting views as to its pathogeny. For who can -doubt that the facts of pathology supply the indices of rational as -opposed to empirical methods of therapy?</p> - -<p>Albeit, much remains to be done before we can claim to fulfil -the demands of ideal treatment of gout. For we are still ignorant -of its exact etiology, cannot yet boast of our control of the morbid -potentialities that constitute the pathological groundwork of the -malady. We cannot obliterate the diathesis, and must still -deplore with Sydenham that “as for a radical cure, one altogether -perfect, and one whereby the patient might be freed from even -the disposition to the disease, this lies, like truth, at the <i>bottom of -a well</i>; and so deep is it in the innermost recesses of nature that -I know not when or by whom it will be brought forward into light -of day.”</p> - -<p>But although we cannot dissipate the inherent proclivities to -the disorder, we can, I think, claim to fulfil the humbler <i>rôle</i>, viz., -obviate their coming to fruition. Haply in the fulness of time -we may be able to influence the <i>endogenous</i> factors that make for -gout, may through the labours of the bio-chemist be able to -translate or assess them in terms of <i>functional inefficiency</i> of this -or that particular viscus. But meanwhile we must perforce -content ourselves with the eradication or control of the <i>exogenous</i> -factors of gout—the <i>excitants</i> whereby or through whose agency -the malady from being <i>latent</i> becomes manifest and overt.</p> - -<h3><span class="smcap">Radical Treatment of Local Foci of Infection or Toxic Absorption</span></h3> - -<p>When discussing the etiology of gout we emphasised the probability -of the intrusion of an <i>infective</i> element in its genesis. -We commented, too, on the extreme frequency with which local -infective foci are encountered in <i>gouty</i> subjects and the imperative -necessity of their early recognition and radical treatment. In<span class="pagenum"><a id="Page_328"></a>[328]</span> -doing so, we but conform to what should be regarded as the -salient canon in the treatment of any form of <i>arthritis</i>, viz., a -diligent search for a <i>focus of infection</i>. A <i>monarticular</i> arthritis, -such as gout in its initial outbreaks almost invariably is, calls for -the same painstaking investigation as a polyarticular, for one -never knows when the former may merge into the latter. Nor, -if we find one focus, should we rest content, assuming that this -is the only one of significance. For in many instances there are -probably several foci. Thus, how frequently are septic teeth -conjoined with tonsillar and aural troubles, and, as modern investigation -shows, these, again, may be associated with remote foci in -gall bladder, appendix, etc.</p> - -<p>To begin with, a thorough examination of the mouth and nasopharynx -is essential. During the inspection any artificial dentures -must be removed, lest we overlook concealed and septic stumps. -“Bridges,” again, are a notable source of sepsis. The roots upon -which they are fixed or the related gums may be infected. <i>Phlebitis</i>, -as we know, is a common associate of gout, and C. A. Clark, -emphasising the septic potentialities of bridges, cites an obstinate -case of phlebitis which only cleared up after removal of a filthy -device of this nature.</p> - -<p>Again, <i>devitalised teeth</i> that have been “crowned” should -always be suspect. Infection at the root is common, with abscess -formation. Such are not necessarily painful, and may give no -indication of their presence until they find an exit of discharge, -maybe by a gumboil or <i>viâ</i> the antrum, etc. These abscesses -around the apices of non-vital teeth are difficult of diagnosis in -their early stages. Even the X-rays may fail to detect them -when minute, this owing to the small amount of pus, or because -abstraction of the lime salts from the bone has not proceeded to -an extent that may be appreciable by skiagraphy. The first -indication of their presence is a small area of rarefaction in the -bone around the apex of the root.</p> - -<p>It is important to recognise that teeth that appear sound upon -external examination are not necessarily so. In short, ordinary -clinical examination may be quite inadequate. Not only must -the condition of the “crowns” of the teeth, but that of their -<i>roots</i> also, be ascertained. For when we reflect that, in addition -to <i>abscesses</i>, <i>cysts</i>, <i>buried roots</i>, <i>inflamed</i> and <i>impacted molars</i> may -be present, we see, if we are to achieve a full and accurate diagnosis, -<i>radiographs of the jaws</i> are essential. A single-plate negative is -practically of no value. A <i>series of films taken all round the mouth</i> -is the only satisfactory procedure. Such give finer detail, and -show up the interstices of the teeth—the sites of predilection for -<i>periodontal disease</i> or <i>pyorrhœa alveolaris</i>.</p> - -<p><span class="pagenum"><a id="Page_329"></a>[329]</span></p> - -<p>Passing to pyorrhœa alveolaris, which has been defined as the -twentieth century scourge, it cannot be denied that if all the -evils attributed thereto are to be nipped in the bud, then <i>X-ray -examination</i> of the <i>teeth</i> must be resorted to at a much earlier -stage than it commonly is. Clean as well as unclean mouths fall -a prey thereto, and, as a rule, investigation of the teeth is an -after-thought, this particularly in the subjects of <i>gouty arthritis</i>. -Usually the gout has been in full swing for years. The patient’s -<i>dyspeptic</i> symptoms have been dismissed as “gouty,” and -“alkaline stomachics,” etc., have been his lot, though his teeth -may be in a foul condition—one which would not have been -tolerated probably in any form of arthritis other than “gouty.”</p> - -<p>But if to diagnose pyorrhœa alveolaris in its early stages we -must needs invoke radiography, on the other hand we should be -careful not to overlook its presence when advanced. The gums -may be pale and shrunken, at other times red and swollen and -very prone to bleed. When pockets form round the teeth, pus -and blood may be expressed. Probing may not reveal their -true depth, whereas X-rays do.</p> - -<p>Sometimes only one or two teeth are affected, at other times -many, and these not necessarily adjacent to each other. Thus it -happens that the disease is more advanced at one part of the mouth -than at another. Exacerbations frequently occur—a blessing in -disguise. The affected teeth become tender to bite on and loose -in their sockets, but often pain lessens, and the tooth again -tightens up, and the all-necessary visit to the dentist is again -and again postponed. Sometimes abscesses form, which discharge -into the peridental pockets. Eventually the teeth may -drop out almost painlessly. Herein resides the danger of the -condition, its relative <i>painlessness</i>. Hence the ease with which -<i>secondary infections</i> may ensue, <i>e.g.</i>, in the <i>tonsils</i>, the <i>gastrointestinal -tract</i>, etc., while the original source may be altogether -overlooked.</p> - -<p>The subjects of gout are often middle-aged or old. We should -recollect then that chronic <i>periodontitis</i> may in their instance -ensue in sequence to <i>senile atrophy of the alveolus</i>. Recently in a -patient of mine nearly eighty, a sufferer from gout and sciatica, -a persistent <i>pyrexia</i>, of apparently cryptic origin, forthwith ceased -after extraction of his teeth. He lived some considerable time -afterwards, but I often regret that his septic teeth had not been -drawn long before.</p> - -<p>Unfortunately no specific germ can as yet be saddled with the -responsibility for <i>pyorrhœa alveolaris</i>, though some would convict -the <i>endamœba buccalis</i>. <i>Spirillæ</i> and <i>staphylococci</i> form a -large proportion of the bacterial flora met with in <i>oral sepsis</i>, but<span class="pagenum"><a id="Page_330"></a>[330]</span> -the results of <i>vaccine</i> treatment would seem to indicate that -<i>streptococci</i>, <i>diplococci</i>, and <i>staphylococci</i> are the most frequent -causes of complications. Still it must not be forgotten that the -<i>streptococcus viridans</i> is by some held to be specially related to -<i>arthritis</i>. Hartzell (1915) invariably found it in the teeth and -peridental tissues in 220 patients suffering from arthritis. This -<i>streptococcus hæmolyticus</i> frequently leads to <i>secondary tonsillar -sepsis</i>, and, as previously noticed, to subsequent <i>gall bladder -infection</i>, etc.</p> - -<p>Passing to <i>local treatment</i>, if oral sepsis or pyorrhœa alveolaris -exists, carious teeth when present should be extracted, or their -cavities cleansed and filled. Accumulations of tartar should be -removed, and unhealthy gums attended to. Thus “pockets” -should be swabbed, syringed, or subjected to ionisation. Exacerbations -frequently follow the extraction of teeth. Acute -paroxysms of gout have followed this simple operation. In cases -where the extraction of many teeth is called for, it should be -preceded by as thorough a cleansing of the mouth as can be -assured. It is a matter of common experience that severe -exacerbations of arthritis follow neglect of this precaution, owing -to the enhanced toxic absorption from the extensive raw surface.</p> - -<p>Unquestionably, whether it be a matter of <i>curettage</i>, of “<i>pockets</i>,” -<i>alveolar abscesses</i>, or <i>extraction of teeth</i>, it is wiser to proceed -<i>gradatim</i>. Hartzell, when many septic foci exist in the gums -and teeth, allows three to six days to intervene between “treatments,” -this in order to gain full advantage of what may be -called <i>surgical auto-inoculation</i>. For, as he contends, any local -measures, curettage, etc., necessarily involve inoculation of -the subject with a large number of organisms, thus producing an -effect similar to that of an efficient vaccine, “with the added -advantage that the constant supply is shut off from the focus -disturbed.”</p> - -<p>Recurring attacks of <i>tonsillitis</i>—well-recognised determinants -of gouty outbreaks—demand thorough local treatment. If this -fail, the propriety of removing the tonsils will call for consideration. -But, as tonsils may be very misleading in appearance, -the aid of an expert is often indispensable. Thus the worst types -of tonsillar sepsis may exist in the small “buried” tonsil. In -such cases the indications for <i>enucleation</i> are the more emphatic -when we note the increasing evidence that <i>tonsillar sepsis</i> may -be etiologically related to <i>appendicitis</i> or <i>cholecystitis</i>.</p> - -<p>Again, as before pointed out, Wynn Wirgman noted that some -cases of gout are associated with <i>nasal</i> disorder, and certainly -in non-gouty forms of arthritis expert treatment has reacted -very beneficially on the joint condition. Watson Williams has<span class="pagenum"><a id="Page_331"></a>[331]</span> -recently drawn attention to “<i>latent sinusitis</i>” as a cause of -<i>systemic infections</i>. He cites two cases of chronic <i>rheumatoid -arthritis</i> which, previously resistant to treatment, were greatly -improved by operation on the <i>sphenoidal sinuses</i>. The washings -from the sinuses were free from pus, but on culture showed -growths, in the one case of <i>streptococcus albus</i> and in the other of -<i>streptococcus aureus</i> and <i>streptococcus brevis</i>.</p> - -<p>Needless to say, the genito-urinary tract should be carefully -investigated, especially in polyarticular gout, or monarticular -when located in unusual articular sites, this if only to eliminate -the possibility of a latent <i>gonococcal</i> infection. Apart from this, -we should recollect that <i>cystitis</i> is common in gouty subjects, and, -according to older authors, might occur as a result of “<i>metastasis</i>,” -not to mention the cases of so-called “gouty” <i>urethritis</i>, -which, it is claimed, not uncommonly supervenes at the end of -an articular attack of gout. Nor should we forget the <i>rectum</i>, -for hæmorrhoids are not uncommon in these subjects. Years -ago Garrod noted that the cessation of a habitual hæmorrhoidal -discharge frequently proved the signal for an outbreak of gout. -Moreover, there is increasing evidence that <i>rectal ulcerations</i> may -be causally related to some forms of arthritis.</p> - -<p>When all the foregoing regions have been thoroughly investigated -the lower levels of the gastro-intestinal tract must be -thoroughly examined by all modern methods. Diminution, -absence, or excess of free HCL may call for determination, while -X-ray studies may afford us an explanation of dyspeptic symptoms. -Lastly, the urine and fæces may call for exhaustive investigation.</p> - -<p>In conclusion, however, if there be any local focus of infection -so situated as to admit of radical measures, these should be undertaken -prior to resorting to vaccine therapy.</p> - -<p>But, obviously for the success of vaccine therapy, it is essential -that an accurate <i>bacteriological</i> diagnosis of the case under consideration -be accomplished, which of course is comparatively easy -if we are able to isolate the particular organism by direct cultural -experiment. To this end cultures should be made from the roots -of extracted teeth, the gums, tonsils, or nasal or other discharges. -Albeit, we must never be content to select haphazard any organism -that we may isolate from the patient’s mouth, nose, urine, fæces, -or elsewhere. Doubtless the true clue will lie in the institution of -<i>complement fixation tests</i> for the organisms responsible for local -infections. Research to this end is now in course of progress at -the Royal Mineral Water Hospital, Bath, for it is becoming -increasingly clear that nothing short of “team-” work will suffice -for the full elucidation of the “gouty” and the non-gouty -arthritides.</p> - -<p><span class="pagenum"><a id="Page_332"></a>[332]</span></p> - -<h3><span class="smcap">Diet</span></h3> - -<p>Truly in respect of diet the gouty have “suffered much of -many physicians,” have been the butt, so to speak, of all the fads -and frailties of medical opinion. Should that chemical outcast -“uric acid” but appear in excess in the urine, it was, and still is -for many, an infallible index, not only of gout, but of gout maintained -and nurtured by improper feeding. The inference seemed -obvious: the ideal diet for the gouty was a diet free from any uric -acid-forming material. This achieved, the gouty “will be free -from his leprosy, and henceforward, if he abide by the prescribed -regime, all will be well with him.” But, as Sir James Goodhart, -from whom we take this last passage, pertinently asks, “is this -so?” The answer is, I fear, in the negative. For who has not -met with gouty veterans who, having run the gamut of endless -dietetic experiments, still remain “gouty,” though, <i>mirabile dictu</i>, -still avid for fresh ventures?</p> - -<p>For myself, I know of no stereotyped diet for the “gouty,” for -in this respect every man is a law unto himself. “Get the acid -out of your system,” is the watchword of many, and, I fear, often -to the undoing of their victims. Bent on the annihilation of the -disease, they overlook the <i>individual</i>. But, weary of futile chasing -of uric acid out of the economy, most students of gout now agree -that the aim of all dietetic measures should be to secure, as far as -possible, <i>gastro-intestinal asepsis</i>. For, as experimental studies -have shown, it is possible, by means of a judiciously selected and -varied diet, to modify the character and even to inhibit the growth -of the intestinal flora. The far-reaching nature of such an influence -is clear when we reflect that all abnormal fermentative and putrefactive -processes in the alimentary canal appear to be referable to -the action of microbial agents.</p> - -<p><i>Diet in Acute Paroxysms.</i>—The initial outbreak of gout may -occur at any age, and respect must be had to this as well as to -other individual peculiarities. If the subject be young, say in -the forties, and a free liver, he may at the onset experience distaste -for food, if not actual nausea. If so, let him follow his bent, -and confine himself to hot water, barley-water, or hot weak tea. -Such a modified process of starvation is beneficial rather than -harmful. Drinking freely of bland diluents promotes the elimination -of toxic or waste materials, while the intake of hot water -stimulates the hepatic cells and promotes the excretion of bile.</p> - -<p>Milk, easy of digestion and rapid absorption by a febrile patient, -is the ideal form of nourishment. Moreover, a milk diet constitutes -the most effectual means of attaining a comparative degree of intestinal -asepsis. From two and a half to three pints may be taken in<span class="pagenum"><a id="Page_333"></a>[333]</span> -the twenty-four hours. While some will find no difficulty in -assimilating it, others soon experience nausea, vomiting, and even -diarrhœa, from the passage of undigested curds. It is therefore -advisable to begin with small amounts given at regular intervals. -If ill digested, it may be diluted with some alkaline water, or -three to five grains of citrate of soda added to each tumblerful.</p> - -<p>To obviate monotony the intake may be varied by oatmeal or -barley gruel, veal, mutton, chicken, or vegetable broth, but strong -soups and animal extracts must be avoided. There is no objection, -however, to bread and milk, tapioca, semolina, or sago puddings.</p> - -<p>With the disappearance of fever and the decline of acute -symptoms fish may be introduced into the dietary, with later on -a little white meat or chicken. This may be safely done when -local pain and tenderness decline, and alike the tension of the parts, -as shown by pitting. Moreover, at this stage the appetite usually -asserts itself. Still the return to regular diet must be made slowly -and cautiously, if we wish to combat the very common tendency -in these patients to functional <i>gastro-intestinal</i> and <i>hepatic</i> derangements. -Lastly, in acute <i>sthenic</i> gout occurring in a robust subject -there is no need whatever for <i>alcohol</i> in the <i>febrile</i> stage. Also, it -may be added, the younger and the stronger the patient, the -better will he thrive on a pure milk or a lacto-farinaceous diet, -and the less urgent the necessity for relinquishing the same until -all fear of a relapse has passed.</p> - -<p>On the other hand, in acute <i>asthenic</i> gout in an <i>elderly</i> and -perhaps somewhat <i>debilitated</i> subject one must more than ever -have regard to the individual, especially if he be an old time -sufferer, perhaps with multiple joint involvement. Such a man -“has not so much the gout as the gout has him.” He has to be -helped to support his burden. In short, the diet for the <i>young</i> -and <i>plethoric</i> differs from that suitable for the <i>old</i> and <i>asthenic</i>.</p> - -<p>Restriction of such to a milk diet is sometimes positively harmful. -The mischief is, that, once begun, every attempt at a more -varied diet immediately provokes a relapse.<a id="FNanchor_60" href="#Footnote_60" class="fnanchor">[60]</a> As Sir Thomas -Watson wisely observed: “They must be allowed a certain -quantity of their accustomed good cheer, or they become an -easier prey to the disease. In such cases you must ‘trim’ as well -as you can between opposite dangers, between the Scylla of -excess and the Charybdis of debility.” In short, you must maintain -their vigour and their strength. For this a pure milk diet -will not suffice. In addition thereto, pounded or minced chicken, -a little fish, sole or whiting, may be given. When also, as often<span class="pagenum"><a id="Page_334"></a>[334]</span> -happens, they have been wont to take alcohol, two ounces of -mature brandy or whisky, well diluted with Salutaris or other -mineral water, may be allowed them every twenty-four hours.</p> - -<p>Indeed, if the subject be old and broken down, it may be -necessary to increase the amount of stimulant. In such cases to -go on treating the <i>disease</i>, heedless of long-established habits, -is bad policy. Wholly to withhold alcohol may well precipitate -disaster. Homilies on abstinence or temperance are best postponed -pending convalescence.</p> - -<p>Moreover, these cases of <i>acute gouty polyarthritis</i>, whether in the -middle-aged or old, very commonly run an <i>afebrile</i> course. If -then, as not infrequently happens in these distressing cases, the -patient’s progress is slow and unsatisfactory, there need be no -hesitation in renouncing a strictly lacto-farinaceous regimen in -favour of a more mixed diet: clear vegetable soups, well-made -Julienne, mutton, veal, and chicken broths, lightly boiled fish of -the digestible kinds, pounded and minced chicken, etc.</p> - -<p>Even when in these cases <i>pyrexia</i> is present, it is rarely continuous, -but is diversified by <i>afebrile</i> intervals. If then, while -the paroxysm is in full flare, it be deemed advantageous to adopt a -milk diet, it is all the more important that in the <i>inter-paroxysmal</i> -stages we take full advantage of these periods of enhanced -digestive capacity.</p> - -<p><i>Diet in Chronic Gout.</i>—Sydney Smith, writing to the Countess -of Carlisle in his seventy-first year, humorously apostrophises his -gout: “What a very singular disease it is! It seems as if the -stomach fell down into the feet. The smallest deviation from -right diet is immediately punished by limping and lameness, -and the innocent ankle and blameless instep are tortured for the -vices of the nobler organs.”</p> - -<p>Precisely so, but what constitutes the “right” diet? We are -told that this is good and that is bad for gout. Some would have -us eschew red meat and cleave unto white; for others common -salt is the devil that must be cast out. Some speak ill of all -the fruits of the earth. Strawberries especially, they say, are -the bane of gout, yet in these same Linnæus found salvation. -For many, again, sugar is anathema, tea and coffee but uric acid -solutions, and alcohol in all forms rank poison!</p> - -<p>What a trial the gouty subject who, obsessed by his “acidity,” -has passed through the furnace of many spas! “Everything -I eat turns to acid” is his plaint. He has been all things by -turns—a fruitarian, a vegetarian, no meat or all meat, etc. -Such persons, in truth, are “uric acid” maniacs. But—forget -it not—they are of our making, and often in their multitude of -counsellors have found, not wisdom, but <i>starvation</i>! Well would<span class="pagenum"><a id="Page_335"></a>[335]</span> -it be if the evil done ceased with themselves, but unfortunately -they seek converts to whatever cult they affect.</p> - -<p><i>The Fallacy of Fixed Dietaries.</i>—As Bacon in his “Regimen of -Health” (1597) wisely observes: “Some physicians are so regular -in proceeding according to art for the disease as they respect not -sufficiently the condition of the patient.” The wisdom of this -has, I fear, been overlooked by those who hold that the ideal -diet for the “gouty” is one destitute of the <i>precursors of uric acid</i>. -Its acceptance makes not for flexibility in dieting, but rigid, -undiscriminating routine.</p> - -<p>Apart from the violation of principle, the direct result is, that -the victim runs amok among the <i>carbohydrates</i>, with as a frequent -penalty an <i>acute</i> outbreak, this although uric acid is not a -direct product of carbohydrate metabolism; nor, as far as is -known, does the carbohydrate intake influence the rate of -formation of uric acid. Thus do theory and practice come into -conflict, and, as usual, the patient pays. How pernicious this -obsession that uric acid is a morbid agent! Uric acid is not an -etiological entity, and, as Walker Hall rightly observes, “it is -high time that every practitioner made a point of fully educating -the public in this respect.”</p> - -<p>Any attempt to formulate a set dietary proves but a snare and -a delusion. No regime is applicable to the “gouty” as a class, -nor even to the individual “gouty” subject at all periods of -his life history. His disease persists for an indefinite period, and, -like most chronic maladies, undergoes variations. <i>Pari passu</i> his -digestive capacity rises and wanes. The regime therefore must -be adapted and readapted to his varying necessities. For it is -the <i>patient</i>, and not the “gout,” dictates the diet. But only too -commonly the <i>disease</i> is dieted, the victim ignored—<i>hinc illæ -lachrymæ!</i></p> - -<p>Our dietetic ventures must obviously rest on a sounder basis. -This we do know, viz., that <i>functional disturbances of digestion</i> -generally precede a “gouty” paroxysm, and that their amelioration -is followed by relief of symptoms. The aim of our dietetic -measures then is the <i>prevention of digestive disturbances</i>, not the -routine withdrawal or reduction of uric acid precursors.</p> - -<p>The dietetic treatment of the “gouty” is that of the “dyspeptic,” -with, if anything, an added discrimination, for an -unknown factor intrudes—the “gouty diathesis”—which has -also to be reckoned with, but of this later. Now “dyspeptics” -cannot be dieted by rule of thumb. Whether they be “gouty” -or “non-gouty” matters not. A careful study of the phenomena -of digestion, if not essential in every case, is certainly called -for in the more obstinate and obscure forms. In short, an attempt<span class="pagenum"><a id="Page_336"></a>[336]</span> -should be made to determine the special form of “indigestion.” -Is the derangement of function a disorder of motility or secretion? -Is it catarrhal or nervous in origin?</p> - -<p>That such is the proper mode of procedure is undeniable. For -are we not too prone to assume that the “dyspepsias” of the -“gouty” are <i>sui generis</i>, all due to <i>one</i> cause, the <i>materies -morbi</i> of <i>gout</i>, instead of being merely “<i>excitants</i>” of gout and -due to a variety of digestive functional disabilities, and these of -equally diverse origin?</p> - -<p><i>Thorough Physical Examination a Necessary Prelude to Dieting.</i>—When -we recall that the “dyspepsias” of the “gouty” endure -through long years, the suggestion that every effort should be -made to localise and establish the exact nature of the underlying -derangement seems almost superfluous. Yet how often is the -question dealt with offhand, though, ideally speaking, I cannot -help thinking that the <i>primary</i> outbreak of <i>gout</i> should be the -signal for an exhaustive examination by all modern methods. -The consequences of dyspepsia in the “non-gouty” are bad enough, -but infinitely more so in the “gouty” subject. But it is the -former group, not the latter, that has been the favoured object -of study by experts, which is, I think, somewhat unfair.</p> - -<p>There is need of a searching investigation, a more common -invoking of the tests whereby the functional efficiency of the -stomach may be gauged. We know that there may exist on the -one hand hyperchlorhydria and on the other hypochlorhydria. -But we need to know more as to disturbances in gastric motility, -delay or hurry in digestion, not to mention abnormalities in -shape, position, size, tone, pyloric end rhythm, etc. In view of -the almost general admission that <i>gastro-intestinal</i> derangements -are causally related to outbreaks of <i>gouty arthritis</i>, surely our -remissness in this matter is somewhat surprising, the more so -in light of the heroic procedures, viz., <i>ileocolostomy</i> and <i>colectomy</i>, -advocated in <i>rheumatoid arthritis</i>, a condition by many deemed -related to gout.</p> - -<p>Leaving such aside, none will, I think, deny not only the value of -<i>test meals</i> for <i>free HCL variations</i> and experimentation with all -kinds of foodstuffs, but also of X-ray examination of the <i>alimentary -tract</i>. How subversive of all preconceptions the revelations of -radiography in <i>gastric</i> and <i>intestinal</i> conditions, of what infinite -value in disentangling the ambiguous significance of purely subjective -sensations! Thus, alterations in <i>gastric</i> tone, motility, -and peristalsis may hark back to remote lesions in <i>gall bladder</i> or -<i>appendix</i>, and these also account for variations in free HCL.</p> - -<p>“Great eaters,” said Sydenham, “are liable to gout, and of these -the costive more especially”—an observation the truth of which<span class="pagenum"><a id="Page_337"></a>[337]</span> -all will confirm. It may be taken as a maxim that nothing for -the gouty is more prejudicial than <i>constipation</i>. Here it is -obviously of importance that we know the site of delay, whether -in the lower coils of the ileum, the colon, or merely the rectum, -<i>i.e.</i>, dyschezia. How else obtain this information, save through -X-ray examination?</p> - -<p>Any departure from normal in consistency, colour or content of -the fæces should be noted so as to identify <i>hepatic</i> or <i>pancreatic</i> -derangements. An analysis of the urine should always be undertaken, -its reaction noted, the presence of albumen or casts ascertained. -It is important, too, that we do not overlook <i>glycosuria</i> -or <i>oxaluria</i>, or substances indicative of excessive intestinal -putrefaction. All these bear far more pertinently on <i>diet</i> than -estimates of <i>uric acid</i>.</p> - -<p>The behaviour of the <i>skin</i>, whether inactive or not, must also -be taken into consideration. Moreover, as the subjects of gout -are usually middle-aged or old, it is highly important to note the -general drift of metabolism, whether in the direction of <i>obesity</i> -or undue <i>leanness</i>. Herewith we must take an inventory, as it -were, of the subject’s general mode of living. What are his -habits in respect of food and drink? Is his diet excessive or -improper in quality? Are his meals taken at irregular times? -Does he masticate his food properly?</p> - -<p>In the matter of <i>exercise</i>, his occupation or pursuits require -thought. Do they involve excessive exertion or favour a -sedentary habit? For both these factors bear narrowly on -his power or not of disposing of ingested material. Indeed, all -the foregoing reflections stand in close relationship to the complex -processes of digestion and metabolism, and the efficacy of -our prescribed regime will depend on how far our suggested -innovations meet the particular needs of the subject under review.</p> - -<p><i>Need for Collaboration of Clinician and Bio-chemist.</i>—Before we -shall be able to lay down a diet for the “gouty” on truly -scientific grounds much remains to be done. Our clinical examinations, -in no way to be despised, must nevertheless be supplemented -by the more subtle tests of the bio-chemist. Consider the -complexity of the problem. We have to diet not only the “gouty,” -but the “potentially” gouty.</p> - -<p>They shade the one into the other. Even the man who has had -gout has his periods of respite, of apparent unblemished health. -If seen at such a juncture, he may display the relics of his gouty -attacks, <i>i.e.</i>, <i>tophi</i>. But can we say of him that he actually <i>now</i> -has gout? He has crossed the Rubicon, disclosed his morbid -trend, but meanwhile he has apparently recrossed to the vantage -ground of normal metabolism. He stands again with those who<span class="pagenum"><a id="Page_338"></a>[338]</span> -are about to, but have not yet developed the disorder, <i>i.e.</i>, the -“potentially” gouty.</p> - -<p>Who will deny that it is when a man is, so to speak, gravid with, -but not yet delivered of, gout that dietetic measures will avail -him most? But this, alas! carries with it as its postulate the -diagnosis of <i>latent</i> gout. Now, Walker Hall suggests that “the -nuclein metabolism of the gouty patient is run at high pressure or -full capacity, instead of the usual normal quarter or at half-pressure -capacity, in order to cope with the ordinary processes of -assimilation, and that there is very little reserve energy.” Does -not this seem to indicate that a fruitful sphere of research might -be the invoking of “endurance” tests and other methods of determining -the <i>functional capacity</i> or <i>efficiency</i> of the various <i>viscera</i>?</p> - -<p>At present we content ourselves with blaming the stomach, the -liver, the kidneys, etc., and often on very inadequate grounds. -It would be a great step forward if we could determine betimes -which particular <i>viscus</i> is <i>functionally deficient</i>. There are signs -that this boon will not be long withheld, signs that not only can -the functional efficiency of the <i>stomach</i> be tested, but also of the -liver, kidneys, and even the spleen.</p> - -<p>Thus Labbe and Daughin study the colloidal nitrogen in the -urine, and find the ratio to the total nitrogen much augmented -when the <i>functional efficiency of the liver is depressed</i>. Again, -Bauer and Spiegel use the <i>bilirubin content</i> of the <i>blood</i> to the same -end. They maintain that there is a bilirubin threshold, the -assessment of which denotes the <i>functional capacity</i> of the <i>liver</i>. -In health the <i>blood content</i> thereof is surprisingly <i>uniform</i>. But -in passive congestion of the liver it rises very markedly, and the -same after administration of <i>cholagogues</i>.</p> - -<p>In like fashion the value of <i>blood urea</i> concentration is extolled -by Kast and Wardell as a satisfactory index of the <i>functional -power</i> of the <i>kidney</i>. The <i>uric acid</i> content of the blood is by -Baumann, Hansmann, Davis, and Stevens regarded as a very -delicate index of <i>renal</i> function, though unreliable in the presence -of œdema, cardiac decompensation, or when the urine is highly -concentrated in hot weather. These are but a few of the methods -available, and in the same way Frey has devised tests for the -functional efficiency of the <i>spleen</i>, while Barton invokes the -administration of urea, chlorides, adrenalin, creatine, etc., to -assess the functional capacity of the <i>liver</i>, <i>kidney</i> or <i>spleen</i>.</p> - -<p>Such is the trend of modern medicine—to link up clinical with -laboratory findings—and in gout perhaps more than in any other -disease is this collaboration urgently called for. For who can -doubt that gout is a malady of mixed intrinsic (endogenetic) and -extrinsic (ectogenetic) origin?</p> - -<p><span class="pagenum"><a id="Page_339"></a>[339]</span></p> - -<p>We need to know more about the <i>endogenous</i> factor, the basal -perversion of cell structure or function, that differentiates the -tissues of the “gouty” from those of their fellows. For it is these -inherent peculiarities—structural, physical, or chemical—that -give to the disease its <i>sui generis</i> character. How then in the -“living” subject shall these hidden morbid potentialities be -identified? How save through the medium of <i>function</i>, the -outward expression of metabolic activities, in other words by -appraisement of the <i>functional capacity</i> of the various <i>viscera</i>? -For gout primarily is a disorder of function, or, as Rendu phrased -it, a primordial “vice of nutrition.” Hence our insistence on the -invoking of the various laboratory methods for elucidating the -<i>functional</i> powers, the efficiency or not of the <i>liver</i>, <i>kidneys</i>, etc.</p> - -<p>This satisfactorily achieved, we may, through their reflected -functional disability or disabilities, divine somewhat the nature -of the innate tissue peculiarities of the “gouty,” may hope at long -last to translate the misty “gouty diathesis” in terms of <i>functional -deficiency</i>, deficiency of the working capacities of the -<i>stomach</i>, <i>liver</i>, or <i>kidneys</i>, and perhaps find that the basal flaw in -some lies in the <i>liver</i>, in others in the <i>kidney</i>, and thus the older -clinicians be justified of their claims for “hepatic” or “renal” -varieties of gout.</p> - -<p>That <i>exogenous</i> factors, <i>i.e.</i>, <i>infections</i>, bring to fruition these -latent morbid tissue potentialities of the gouty, is my belief. -Hence my contention that dietaries for the “gouty” should be -such as promote <i>gastro-intestinal asepsis</i>. Albeit, <i>infections</i> are -but the “seeds,” and who can doubt that the ideal diet for the -“gouty” should also take cognisance of the “soil”—the pathological -groundwork of gout?</p> - -<p>The “soil” in gout is, I believe, one peculiarly favourable to -microbic invasion, and here again recent studies of the <i>cytology</i> -of the blood bid fair to yield us some criterion whereby the “degree -of body resistance” to infections may be gauged.</p> - -<p>But until the bio-chemist reveals to us the why and the wherefore -of their peculiar tissue vulnerability our dieting of the “gouty” -must perforce consist largely in diminishing the <i>exogenous</i> excitants -of the malady. Ultimately, when researches now in progress have -fructified, we may be able to influence the <i>endogenous</i> factors, -may correct the functional defect of this or that viscus, stabilise -the nuclein exchanges, and heighten the resistance of the tissues. -In short, as Sir Archibald Garrod puts it, “we must consider the -soil as well as the seed which falls upon it, and that he is the best -exponent of the healing art who treats the individual patient -rather than his disease.”</p> - -<p>“<i>The Accessory Food Factors.</i>”—“Due nourishment, not<span class="pagenum"><a id="Page_340"></a>[340]</span> -gluttonous delight,” is the true clue to the rational dietetic treatment -of the “gouty.” But this question of “due nourishment,” -how complex it grows in light of recent revelations. Thus, it is -now generally agreed that to satisfy the animal needs for growth -and the maintenance of nutrition something more than a due -admixture of proteins, fats, carbohydrates, and inorganic salts is -essential.</p> - -<p>We must, of course, ensure that the caloric value of the food -intake be adequate, and the supply of protein sufficient to maintain -the nitrogen balance, also that the intake of protein suffice for -the exigencies of tissue waste, not forgetting that for this is -required a sufficient quota of the individual primary fractions of -the protein molecule.</p> - -<p>But this, we now know, is not all, for there are other and indispensable -dietetic components. In the food we eat are substances -of hitherto unguessed-at potency—the “vitamines,” or, as they -are now more properly termed, “accessory factors of diet.”</p> - -<p>Of these elusive bodies but three as yet have been isolated: -<i>fat-soluble A</i>, <i>water-soluble B</i>, and <i>water-soluble C</i>. In infancy -absence of the first-named “vitamine” leads to <i>rickets</i>. Lack of -the second engenders <i>scurvy</i>, of the third <i>beri-beri</i>.</p> - -<p>But, apart from these well-defined “deficiency diseases,” -McCarrison has pointed out that the absence of these “accessory -food factors” leads to grave <i>functional</i> derangements, especially -of the organs of digestion and assimilation and those subserving -endocrine functions, not to mention malnutrition of the nervous -system and the induction of hyperadrenalinæmia and chronic -inanition.</p> - -<p>A heavy indictment, but, more pertinently to our subject, -McCarrison inclines to think that <i>bilious vomiting</i>, <i>cyclical acidosis</i>, -<i>mucous disease</i>, and other <i>metabolic</i> disorders met with in <i>children</i> -are very probably due to deficiency of certain “accessory food -factors.” In light of this it is interesting to recall that these -same symptom complexes are by Comby and others regarded as -manifestations of <i>infantile gout</i>.</p> - -<p>More arresting still is McCarrison’s observation that all the -clinical phenomena distinctive of “deficiency diseases” as a -whole are apparently the result of <i>nuclear</i> starvation of all tissue -cells. In short, these “accessory food factors” are essential to -<i>due nutrition of the nuclear substance</i>. How interesting this in -light of the generally accepted view that “gouty” individuals -are victimised by some inherent defect or alteration of <i>nuclein</i> -metabolism. Does not this seem to indicate that one of the -clues to successful dieting of the “gouty” must be adaptation of -the nuclein intake to the needs of the individual, in short that<span class="pagenum"><a id="Page_341"></a>[341]</span> -we must strive for the stable maintenance or conservation of -nuclein metabolism?</p> - -<p>Again, as before stated, one of the results attaching to deficiency -of “vitamines” is <i>functional derangement of the organs of digestion -and assimilation</i>. Such disturbances are prominent in <i>gout</i>, and -that “errors of diet” play an important <i>rôle</i> in the genesis of the -disorder can scarcely be denied. At the same time there is no -proof as yet that the absence of some mysterious “accessory -factor” makes for the development of the disorder.</p> - -<p>Nevertheless reflection on these findings is, I think, wholly -apposite. It should, at any rate, chasten those who affect -extreme dietaries on insufficient grounds. They are not justified -of results, for, with Sir Archibald Garrod, I venture to doubt -“whether by dieting our ‘gouty’ patients we achieve nearly as -much as we think we do.”</p> - -<p>Such good, moreover, as we do compass, is, I think, exerted -<i>indirectly</i>. Even in the <i>inter-paroxysmal</i> periods of the disorder, -despite good or perhaps exuberant health, gout is there. Its -morbid tissue potentialities are <i>latent</i>, though <i>functionally inactive</i>. -To maintain this state of <i>passivity</i> is the aim of all dietetic -measures, viz., to diminish or withdraw the dietetic factors that -are <i>provocative</i> of gout.</p> - -<p>The diet most void of offence is one the least calculated to excite -<i>digestive disturbance</i>—one that makes more surely for <i>gastro-intestinal -asepsis</i>. At this juncture it is interesting to note -McCarrison’s observation that although the absence of certain -“accessory food factors” is the essential etiological agent in the -genesis of “deficiency diseases,” yet he holds that <i>infections</i> and -parasitic agencies are often important causes in determining the -<i>onset of symptoms</i>.</p> - -<p>Similarly in the causation of gout, “errors of diet” are not -the only agencies at work. They are in truth but contributory -factors in that such indiscretions favour the incidence of catarrhal -states. These again promote increased toxicity of the intestinal -flora with sequential disturbance of general <i>nuclein</i> metabolism -and associated specific local reactions in certain tissues.</p> - -<p>I make no apology for this somewhat lengthy digression. In -the sphere of dietetics, as elsewhere, “a little knowledge is a -dangerous thing.” We need to walk more circumspectly in this -matter of dieting; and to this end reflection on the disabilities that -still beset us cannot fail to be salutary, and will form, I think, a -fitting prelude to our suggested mode of procedure.</p> - -<hr class="chap x-ebookmaker-drop"> - -<div class="chapter"> - -<p><span class="pagenum"><a id="Page_342"></a>[342]</span></p> - -<h2 class="nobreak" id="CHAPTER_XXVII">CHAPTER XXVII<br> -<span class="smaller">TREATMENT OF GOUT (<i>continued</i>)</span></h2> - -</div> - -<h3><span class="smcap">Regulation of Diet in the Gouty</span></h3> - -<p>The victim of gout is easier led than driven. Show no “bowels -of compassion” for his failings, talk to him in the spirit of a -dehumanised disciplinarian, and your tenure of his confidence -will likely be short. You deal with a man more often wise than -foolish, not merely a digestive tube.</p> - -<p>The physician must be authoritative and yet tactful. Thus if -the victim be a hearty eater, and you think he eats too much, try -and get him to eat less. But do not bid him straightway live -as an anchorite. Be a little more diplomatic. A good appetite -is not a sin. An appetite over-stimulated by condiments or -endless varieties of courses is. He should eat to satisfy his -hunger, not to gratify his palate.</p> - -<p>Do not irritate the patient with a strict dietary if avoidable. -Far more often than not it is the <i>quantity</i>, not the quality, of the -food that is at fault. Frequently mere reduction in bulk of the -pabulum of all kinds taken will suffice. In short, <i>restriction</i>, not -elimination, is the wiser maxim, especially so in indolent or -sedentary persons in whom we may with advantage limit the food -intake to the minimum consistent with the due maintenance of -nutrition.</p> - -<p>On the other hand, there is a widely prevalent idea among -“gouty” subjects that if they take enough exercise they can eat -and drink what they please and as much as they please. That -active habits do counteract to some extent the evil effects of -overeating and overdrinking is certainly true. Nevertheless, -as Sir Thomas Watson reminds us, gout was extremely common -in the old time squire, who not only “rode hard,” but “lived -hard” also. It is so, though to a less extent, even to-day, -and often such subjects prove very refractory. Often a reference -to their “weight” will appeal more than any hygienic considerations. -Make use, therefore, of their sensitiveness on this -point, and so by diplomacy attain your end.</p> - -<p>Overeating often goes with overdrinking at meals. I well -recall a gouty old sportsman of bucolic type who was accustomed -to swill his food down with several whiskies and sodas. Very<span class="pagenum"><a id="Page_343"></a>[343]</span> -conservative in all ways, it was not easy to break him of the habit. -Fortunately it occurred to me to ask him, “Did you ever see a -horse eat and drink at the same time?” Reflecting solemnly, -with obvious reluctance came the reply, “Damme, I never did, -now that I come to think of it.” That settled the question. I -had no more trouble, neither had he. Not often is one so lucky. -But “Eat your meals dry” is not a bad rule in cases of sheer -overeating. The appetite is sooner blunted.</p> - -<p>As to the <i>quality</i> of the food, always recollect that “gouty” -people are very prone to <i>idiosyncrasies</i>; but the idiosyncrasy is -purely <i>personal</i>, not applicable to the “gouty” as a class. With -them it is very much a case of “What’s one man’s meat is another -man’s poison.” The physician who rides rough-shod over idiosyncrasies -in the matter of foods rides for a fall. Let him rely on -his own experience and knowledge in the matter of general -dietetic principles; but when it comes to details—the eschewing -or not of this or that—let him trust, not in his own, but in his -patient’s, experience.</p> - -<p>Many of these subjects know perfectly well what suits them -and what does not. Their experience is your best guide. Having -elicited this information, an appeal to their common sense rarely -fails. Of the “gouty” it is especially true that “every man at -forty is either a fool or his own physician.” For the fool there is -but one corrective—<i>dolor acerrimum naturæ pharmacum</i>. The -wise has only to be reminded of his own experience, viz., that -certain articles of diet infallibly disagree with him—<i>verbum -sapienti satis</i>.</p> - -<p>In dieting the “gouty” we should never forget that the <i>main -groups of foodstuffs must be duly represented</i>. We may reduce -this or that, but never for long will they do well if one or other of -the essential ingredients of human food be wholly eliminated. -It is, as Sir Archibald Garrod remarks, doubtful whether even a -minor constituent, such as the purins, can be continuously -withheld with impunity.</p> - -<p>Still, even from the more extreme dietaries advocated by some -one may glean this useful lesson, that the temporary benefit that -often accrues points the moral that <i>simplicity</i> of meals is best for -these subjects. If they crowd soup, fish, meat, game, sweets, -etc., all into one meal, they always pay the penalty. As Burney -Yeo wisely says: “We should not mix up albuminates, fats, -and carbohydrates, or flesh, vegetables, fat, and fruit in the same -meal. One meal should be composed almost exclusively of -nitrogenous food, another of fats and carbohydrates, and -another of fruit, at proper intervals, and they will all agree and -be suitable, but the contrary will be the case if they are mixed<span class="pagenum"><a id="Page_344"></a>[344]</span> -together in the same meal, one hindering the digestion of the -other.”</p> - -<p>I have often found the old rule, “One meal of meat, one meal -of fish, and one of neither,” an excellent way of impressing on -these patients the importance in their instance of simple, as -opposed to elaborate, meals. Arrangement of their daily bill of -fare along these or similar lines is well worth the trouble.</p> - -<p>If the food of the “gouty” needs to be carefully selected, it is -no less necessary that the cooking be simple and appropriate. -For the manner of the cooking is, I am sure, in many instances, -more responsible for “gouty” outbreaks than the nature or the -quantity of protein or other intake. Twice-cooked food, made-up -dishes rich in extractives, are unquestionably pernicious. Nor -are pickled or salted meats desirable. Similarly, strong meat -<i>consommés</i>, hare soup, and beef extracts are best avoided. The -same applies to rich gravies, sauces, spices, etc., all obviously -likely to upset the digestion. Again, as to fish, it is better boiled -or grilled than fried, and still better not fried in fat. In short, -it is the “trimmings” more often than not that do the mischief, -these strongly abetted by “second helpings.”</p> - -<p>The physician may well insist upon a sufficient interval elapsing -between meals. To attain due space between lunch and dinner, -I invariably forbid “gouty” subjects to eat anything with their -<i>tea</i>. The repasts should be taken in a leisurely fashion, if possible -in a cheerful atmosphere. “Unquiet meals make ill digestions.” -The nerve element in these cases is so pronounced that caution -is anything but superfluous, viewing the inhibitory effects of -worry and mental excitement on the secretory mechanisms of -the alimentary tract.</p> - -<p>The importance, too, of thorough mastication and regularity -in meal-times should be impressed upon them. The desirability, -too, of postponing the drinking of fluids to the end of the meal, -and then only in small amounts, should be emphasised.</p> - -<p>Strenuous exercise, mental or bodily, immediately after a meal -is undesirable, and if, as is so often the case, there be any gastric -disorder, the subject should rest both before and after meals. -This is best taken lying down, especially if there be any tendency -to <i>gastric dilatation</i> or <i>visceroptosis</i>. The same in <i>hyperacidity</i>, -but in this latter sleep is contra-indicated. For it has been -shown experimentally that the acidity of the stomach content is -greater during rest than movement. But this is just one of those -points on which authorities differ, and decision may have to be -left to the patient’s own experience.</p> - -<p>Lastly, we should always endeavour to ascertain as nearly as -possible the actual amount of the food intake per diem. This<span class="pagenum"><a id="Page_345"></a>[345]</span> -then must be weighed in light of the subject’s age, body weight, -and mode of life. The middle-aged “gouty” person tends more -often than not to obesity, and it will fall to the physician to decide -whether the food intake be excessive or his habits too sedentary. -Far more often than not it will be found that it is not that he -walks too little, but that he eats too much. The appetite of -youth goes ill with the inactivity of middle age. With these -general considerations we will now pass to a discussion of the -main elements of diet.</p> - -<h3><span class="smcap">The Individual Foodstuffs</span></h3> - -<p><i>Proteins.</i>—Ruthless cutting off of <i>protein</i> foods, though not so -usual as of yore, is still far too commonly practised. The number -of unfortunate wretches who are docked of their red meats is still -astonishing. The “uric acid” bugbear dies hard. Unless red -meat is known to disagree, I never advise a “gouty” subject to -abstain wholly therefrom. I feel sure that it is rarely, if ever, -called for, and when enjoined has frequently wrought much harm. -As far as I know, there is no scientific reason for the very prevalent -idea that for the “gouty” white meat is preferable to red. It is -certain that both contain an equal quantity of extractives, and -equally certain that for some, <i>mirabile dictu</i>, white meat, <i>e.g.</i>, -rabbit, is more indigestible than red.</p> - -<p>Accordingly let your “gouty” patient eat animal food, at any -rate at <i>one</i> meal, but let it be of <i>one</i> sort only. Let his appetite -be his only sauce, his meat plainly cooked and well masticated. -It matters not if it be red or white. What does matter is whether -for <i>him</i> it be <i>digestible</i>. Mutton or lamb are more likely to prove -so than beef or pork, and chicken, turkey, or fresh game more -easily assimilable than duck or goose.</p> - -<p>From Walker Hall’s experiments Luff thinks “it would appear -reasonable to administer sweetbread to gouty patients, since its -nuclein portion is only slightly absorbed, for thymus sweetbread -contains principally adenin, which is rapidly excreted, and pancreas -sweetbread contains mainly guanin, an amino-purin incapable -of increasing the urinary purin output and of exerting any injurious -effects upon the tissues.”</p> - -<p>Nevertheless I still think that “gouty” subjects are better -without thymus, pancreas, and other highly nucleated substances. -Despite our ignorance of the true nature of gout, we do know -that there is generally <i>an excess of uric acid in the blood</i>, and that -to increase the content thereof is undesirable. Again, we know -that in <i>normal</i> men, after ingestion of pancreas and thymus -gland, the <i>uric acid</i> output in the urine is <i>markedly increased</i>.<span class="pagenum"><a id="Page_346"></a>[346]</span> -But, on the other hand, many observers—Magnus-Levy, Vogt, -etc.—have noted that after the eating of thymus by gouty individuals -they found far less uric acid in the urine than in the case of -normal persons. In short, such purin-rich foods in their instance -is followed by <i>uric acid retention</i>.</p> - -<p>More pointed still is the fact that <i>acute</i> outbreaks of gout have -been repeatedly brought on by administering <i>thymus</i> to the subjects -of <i>chronic</i> gout. Surely, in light of this, it is impolitic to approve -of <i>sweetbreads</i> as desirable ingredients of a “gouty” dietary, this -even if only on empirical as opposed to scientific grounds. That -some “gouty” persons eat sweetbreads with impunity is undeniable. -But certainly if on inquiry a subject overtly gouty -admits a <i>penchant</i> for these foods, we should at any rate advise -their restriction or elimination.</p> - -<p><i>Fish.</i>—This pre-eminently, with certain exceptions, is very -desirable food for the “gouty,” especially those whose digestive -powers seem unequal to coping with the stronger kinds of animal -food. The white-flesh fishes, <i>i.e.</i>, sole, whiting, turbot, brill, cod, -plaice, flounder, are the preferable. On the other hand, the red-flesh -fish, <i>i.e.</i>, salmon, mackerel, herring, sprat, pilchard, eel, etc., -contain much fat, and are more likely to upset the “queasy” -stomachs of the “gouty.”</p> - -<p>But fish, it must be recollected, is less stimulating and satisfying -than the flesh of birds and mammals. If wholly denied butcher’s -meat and restricted to white fish, the subjects soon tire of it. It -is best to prescribe fish for one meal, say lunch, and in addition -one type of meat for dinner. Also it is important even in white -fish to choose those most easy of digestion, viz., sole, whiting, or -flounder, in preference to cod and haddock. Above all, let the -fish be fresh, and not “out of season.” Again, fish which is -dried, salted, smoked or pickled, is much less digestible than when -fresh. If, even when taken in moderation and only occasionally, -it has been found to upset digestion, then abstinence is the better -course. Caviare is, I think, best abstained from, and hard or soft -roes generally only taken in strict moderation.</p> - -<p>As to shell-fish, they have the reputation of being most unfriendly -to the “gouty.” Toxic symptoms after lobster and crab are held -to be more common in their instance than others. But many are, -I fear, ready to extend a personal idiosyncrasy on the part of some -particular “gouty” subject into a law for <i>all</i> “gouty” subjects. -I myself have seen no harm follow them when taken in moderation, -this as regards the fleshy parts, more digestible in the -lobster than the crab. It is, I think, wise to abstain from the -spawn of the female lobster, still more from the sauces for which -it is so largely used. As to oysters, I do not think there is any<span class="pagenum"><a id="Page_347"></a>[347]</span> -objection to a “gouty” individual eating them raw, and when -“in season,” but in moderation.</p> - -<p>In conclusion, there is, in the matter of flesh or fish, no rule -applicable to all “gouty” persons. Far from being harmful, it -is both necessary and beneficial if taken in moderation. No small -part of the objections raised to red meat is referable to the other -rich foods that often accompany it rather than to the meat -itself.</p> - -<p><i>Carbohydrates.</i>—If it be wrong to withdraw recklessly all proteins, -it is no less inadvisable, in the absence of special indications, -wholly to eliminate sugar or starchy foods. Nevertheless far -more often than not “gouty” subjects get the impression -that if they wholly eschew <i>sugar</i> all will be well. Latterly, -too, I have noticed that the ban is being extended to <i>starchy</i> -foods also.</p> - -<p>Surely this as a routine procedure is wrong, the more so if, -as too often happens, the unhappy subject is left without any -guidance as to how long he is to suffer this deprivation. As a -<i>temporary</i> measure it is often beneficial. But “gouty” subjects -form no exception to the ordinary law that if nutrition is to be -maintained, their diet must contain a due proportion of the main -groups of foodstuffs. A “due” proportion, not excess, for -though <i>quâ</i> <i>uric acid</i> carbohydrates may appear ideally suitable, -yet the “gouty” are unfortunately no more immune than others -from the <i>dyspeptic</i> disturbances that almost infallibly ensue -when sweet foods are taken immoderately.</p> - -<p>It is this tendency in some “gouty” subjects to amylaceous -dyspepsia that has been wrongly extended into a law for <i>all</i> gouty -subjects, whether they exhibit any carbohydrate intolerance or -not. The only law is that for the “gouty,” as well as for the -non-gouty, carbohydrates, whether taken as starch or sugar, are -harmful if eaten to excess.</p> - -<p>With this reservation, bread may be given as crisp toast, or -rusks, or in the form of <i>Zwiebach</i>. Nor is there any objection to -milk puddings—sago, tapioca, etc.—always provided that they -are found digestible when taken in moderate quantity. Similarly -in regard to sugar there is, as Sir Archibald Garrod says, “no -reason to believe that to a gouty man a lump of sugar is poison, -and provided that it is digestible it must surely be immaterial -whether the allowance of carbohydrates be taken in the form of -sugar or starch.”</p> - -<p><i>Fats.</i>—Apart from <i>obesity</i>, there does not seem to be any scientific -reason why fats should be denied to the “gouty.” All depends -on their <i>digestibility</i>, and in this they display variations. The fat -of ducks and geese is well dispensed with in favour of bacon fat and<span class="pagenum"><a id="Page_348"></a>[348]</span> -pork fat, which are much more digestible. The fats of meat, -when roasted or browned, are best avoided.</p> - -<p>Similarly there is no harm in a moderate amount of butter or -cream, but fatty sauces and soups are, I think, best refrained from. -Ebstein considered the best form of fat for the gouty was good -fresh butter. As to cream, Sir James Goodhart, discussing the -treatment of uric acid, observes: “In strict moderation it is -seldom hurtful, for there is very little in the common objection that -it makes one bilious. Those who avoid it are commonly ‘bilious’ -because all their organs are starved.” But he makes this further -observation for our guidance, that “after middle age cream taken -in any excess may associate itself in some with the output of -uric acid.”</p> - -<p><i>Vegetables.</i>—The various green vegetables are eminently suitable -for the “gout,” not so much on account of their -nutritious qualities, but because of the important inorganic -salts they supply, notably salts of potash. They give a wholesome -variety and relish to food, render the urine more alkaline, -and do not favour the deposit of fat. Their indigestible -residue, too, stimulates the intestinal coat, and so promotes -regular action of the bowels.</p> - -<p>Cabbages, greens, savoys, Brussels sprouts, cauliflower and -broccoli are familiar examples. These, provided they are fresh -and well cooked, are preferable to root vegetables, with the exception -of potatoes. Nor must we overlook the fact that green -leaves are rich in fat-soluble vitamine. Fortunately, too, in the -case of this particular vitamine, the loss involved by ordinary -cooking is not serious. Spinach, too, is rich in vitamines, and is -laxative, but, being rich in oxalates, is contra-indicated in -oxaluria. Sorrel, by reason of its acid oxalates, is also undesirable -under such conditions, and the same is true of rhubarb. Tomatoes -also in former days were forbidden in gout under the erroneous -idea that their content of oxalic acid was high. Cucumbers, I -think, when eaten raw, are apt to upset “gouty” people. -Asparagus and onions should be taken sparingly, as they are rich -in purins.</p> - -<p>For “gouty” subjects, of all vegetables, the cruciferous or -cabbage tribe is the most suitable, provided they are young, -fresh, well cooked, and taken in moderation. In addition to -its rich vitamine content, cabbage, like cauliflower and lettuce, -is almost <i>purin-free</i>. The excessive intake of meat may often to -some extent be counteracted by encouraging such gluttons to -eat freely of green vegetables. In this way we obviate that -sinking sensation which habitual overeaters suffer on limitation -of their pabulum. Lastly, vegetable soups are most suitable,<span class="pagenum"><a id="Page_349"></a>[349]</span> -preferably those easily digestible, relatively poor in purins, or -rich in potassium salts.</p> - -<p>Of the roots and tubers even of potatoes the “gouty,” I -think, should eat sparingly. The large percentage of starch in -potatoes is apt to upset those of feeble digestion. Much depends -on whether they are “mealy” or “floury,” and not “waxy” and -“watery.” Steaming is the best method of cooking them. -Turnips are best abstained from, and also carrots, parsnips, -beetroot and radishes, save at any rate in minimal quantities.</p> - -<p>Lastly, the legumes—peas, beans, lentils—because of their -high purin content, should always be partaken of sparingly, -though perhaps it may yet be found that their purin content -may be more than compensated for by their contained vitamines. -The edible fungi, mushrooms and truffles are best dispensed -with.</p> - -<p><i>Fruits</i> are a valuable food for the “gouty.” They impart -alkalinity to the urine, and promote intestinal action, always -provided they are not partaken of immoderately or when unripe -or overripe, when they are apt to set up gastro-intestinal irritation.</p> - -<p>Most fresh ripe fruits are wholesome. Their content, too, of -vitamines cannot be overlooked, especially that of oranges. -Moreover, the fact that vitamines, as a rule, are destroyed at -cooking temperatures seems to indicate that some uncooked food -should on principle be taken daily by the “gouty” as well as -others. Raw ripe fruits in this respect, like salads, have an -advantage over cooked fruits or vegetables.</p> - -<p>In my own experience I do not know that there is any fruit, -even strawberries, that will infallibly disagree with the “gouty.” -One meets now and again with gouty subjects who are unable to -eat certain fruits with impunity, but one meets with quite as -many of the same idiosyncrasies in the <i>non-gouty</i>. The objections -to certain fruits, <i>e.g.</i>, strawberries, as to certain vegetables, <i>e.g.</i>, -asparagus, are largely theoretical rather than practical. Let -the subject’s own experience be your guide in this matter, or if -he be unobservant, teach him to observe for himself what fruits, -if any, disagree with him.</p> - -<p>With this reservation I am of opinion that, taken in moderate -quantity, fruits are most useful constituents of diet for the -“gouty.” In some cases it will be found that they cannot take -fruit when mixed up with other food, but both enjoy and derive -benefit from it when taken by itself. It is well, again, in others -to restrain their immoderate indulgence in lemons, as these -frequently, as Sir James Goodhart pointed out, upset gastric or -intestinal digestion. It is advisable also to warn them that -plums, currants, gooseberries, and other fruits containing large<span class="pagenum"><a id="Page_350"></a>[350]</span> -quantities of free acids are apt to have the same effect, while -the melon, too, is prone to give rise to gastric disturbance. -Peaches and nectarines, on the other hand, are eminently -suitable for the “gouty,” also apples, pears, oranges, grapes, -cherries, etc.</p> - -<p><i>Condiments.</i>—These substances give a flavour and relish to -food, while their carminative properties stimulate appetite and -favour digestion. On the other hand, their excessive use is a -potent source of gastric irritation. Thus, for example, they are -valuable in atonic dyspepsia, though liable to aggravate a condition -of chronic gastritis.</p> - -<p>The most important and most extensively used is common -salt. Some incline to think that its use by persons of the “uric -acid diathesis” is prejudicial. But unquestionably it is a necessary -and wholesome article for the “gouty” when taken in -moderation. In cases of gout complicated by <i>hyperchlorhydria</i> -strict moderation in or abstinence from salt seems indicated, this -because, the HCL of the gastric juice being wholly derived from -the chlorides of the blood, it seems irrational to increase the supply. -Some therefore forbid its use both as a condiment or in the cooking -of food, making the subject depend on the salts naturally present -in foodstuffs.</p> - -<p>Vinegar, I am sure, upsets some “gouty” persons’ digestion, -and I think Sir Dyce Duckworth is right when he counsels -abstinence therefrom. Thus some “gouty” subjects can digest -raw cucumber, but not with vinegar. Others find salmon if -combined with the same condiment upsets them, but not without. -As to the various other condiments—mustard, pepper, horseradish, -etc.—there is no objection whatever to their use by the -“gouty” in moderation and in the absence of any definite -gastric disorder.</p> - -<p>So much for our consideration of the individual foodstuffs—their -suitability or not—for the subjects of gout. That such a -general survey is advisable may perhaps be conceded, but in so -far as it may approximate to <i>fixed rules</i> it savours of evil, this -at any rate as far as the dieting of <i>dyspeptic</i> derangements of -the “gouty” is concerned. To bring into prominence my -point, I would lay down the postulate that there is <i>no specific -form of “gouty” dyspepsia</i>.</p> - -<p>The gastric derangements met with in gout are in no sense -peculiar thereto. In other words, they present no symptoms -specific of gout, despite the term “gouty dyspepsia.” The term -“hyperacidity” as commonly invoked is far too laxly used in -regard to “gouty dyspepsia.” The “acid risings” of the “gouty” -are of two kinds. Hyperacidity may be due to <i>organic acids</i>,<span class="pagenum"><a id="Page_351"></a>[351]</span> -butyric, lactic, or acetic, the outcome of fermentation, or the -condition may be one of hyperchlorhydria, or excessive secretion -of HCL.</p> - -<p><i>Hyperacidity</i> due to <i>organic acids</i> is met with in some cases of -<i>atonic dyspepsia</i>, <i>chronic gastritis</i>, and <i>dilatation of the stomach</i>. -The free HCL is either diminished or absent. Differentiation of -this type from <i>hyperchlorhydria</i> may be impossible without -examination of the stomach contents.</p> - -<p>Hyperchlorhydria <i>per se</i> sometimes occasions pyloric spasm, and -minor degrees of dilatation follow, this the more commonly as -the subjects of gout are middle-aged or elderly. In others the -dilatation is part of a general <i>neurasthenia</i> from which the “gouty” -no more than others are immune.</p> - -<p>Again, gout of long standing is often associated with <i>chronic -gastric catarrh</i>. Such is very common in beer-drinkers or men -employed in breweries. A state of <i>atonic dilatation of the stomach</i> -is a common sequel. In these cases of chronic gastritis in the -“gouty” the free HCL may be normal, diminished or absent. -Eventually, as the result of oft-repeated gastritis, the parts -involved undergo widespread <i>fibrotic degeneration</i>. Also we have -to recollect that the “gouty” are very subject to obstinate -<i>gastralgias</i>.</p> - -<p>We see therefore that the “dyspepsias” of the “gouty” may -be not only of varied nature, but may also demand differential -dieting at different phases of their evolution. The subject in the -early stages of his gout may suffer from hyperchlorhydria, while -later chronic gastritis may ensue, with the reverse condition, -<i>hypochlorhydria</i>. The <i>protein</i> dietary suitable for the former has -in the presence of the latter to be replaced by <i>carbohydrates</i>, -despite their tendency to fermentation. Again, if either condition -be complicated by <i>dilatation</i> other exigencies must be met. The -meal content must be light, not bulky, and the fluid intake -restricted.</p> - -<p>Again, the foregoing gastric disorders may be complicated by -<i>glycosuria</i> or <i>albuminuria</i>, each with separate dietetic indications. -How inevitably futile then must be any attempt at stereotyped -diet for the “gouty.” In short, the dyspepsias and other -morbid states of the “gouty” call for eclectic, not routine, -dieting, and to this end I append a few suggestions.</p> - -<h3><span class="smcap">Special Dietaries</span></h3> - -<p><i>Amylaceous Dyspepsia.</i>—Not a few “gouty” subjects suffer -from atonic dyspepsia, with <i>acidity</i> due to <i>organic acids</i> arising -from fermentation. Frequently it appears to be the outcome of<span class="pagenum"><a id="Page_352"></a>[352]</span> -some previously prescribed regimen forbidding all flesh food, -or of too frequent or irregular meals or habitual overfeeding, -food-bolting, excessive smoking, etc. Correction of such faulty -habits is an essential prelude to any dietetic rules.</p> - -<p>In such cases it is advisable to reduce the intake of starchy and -saccharine foodstuffs, such as bread, potatoes, pastry, sugar, milk -puddings, and the like. Bread should be stale, or dextrinised by -dry heat, as in thin toast and rusks. Potatoes, if taken, should -be in the form of purées. Sweet dishes should be partaken of -sparingly, if at all. They should be encouraged to take the more -digestible forms of meat and the lighter kinds of fish. Green -vegetables and fresh ripe fruit, raw or cooked, are valuable. <i>Fats</i> -of the more digestible sorts are also desirable. Grilled but not -fried fat bacon is easily digested.</p> - -<p>As to beverages, light China tea is more suitable than strong -Indian kinds. Frequently I have found substitution of cocoa most -beneficial. But in any case the amount of fluid at meal-times -should be restricted.</p> - -<p>As a guide to the formulation of a dietary in such cases the -following may be suggested:—</p> - -<p>On awaking in the morning a tumbler of hot water should be -slowly sipped. A squeeze of lemon may be added if liked.</p> - -<p><i>Breakfast.</i>—Boiled or plainly grilled sole, whiting, or flounder, -or a slice of crisp grilled bacon or lean cold tongue, or a soft-boiled -egg. A slice or two of crisp dry toast or stale bread and a -little butter. At close of meal sip slowly one cup of weak China -tea, or the same of cocoa or milk and water.</p> - -<p><i>Lunch.</i>—Chicken or game, or lamb, mutton, or beef, hot or cold, -roast or boiled. Gravy to be free from fat. One only of the former -kinds of meat to be taken with a reasonable quantity of tender, -well-boiled vegetables. Spinach, kidney or French beans, sea or -Scotch kale, vegetable marrow, or salad may be taken, but without -oil, vinegar, or beetroot. Dry toast or rusks. Half a tumbler of -water sipped <i>after</i> eating.</p> - -<p><i>Afternoon Tea.</i>—One or two cups of weak tea with milk or one -cup of cocoa.</p> - -<p><i>Dinner</i> (two courses only).—Fish of the kinds allowed for -breakfast without potatoes, or a slice of any tender meat, <i>e.g.</i>, -saddle or loin of mutton or thick part of an underdone chop, or -small portion of fresh game, without bread sauce or crumbs. -One or two slices of stale bread or dry toast. A little well-stewed -fruit or custard, junket, or jelly. Half a tumbler of water with -from one to two tablespoonfuls of spirit if desired.</p> - -<p>If there be any suspicion of chronic gastritis, condiments and -stimulants must be renounced, but not in purely atonic dyspepsia,<span class="pagenum"><a id="Page_353"></a>[353]</span> -in which they are of value. In either disorder the patient should -abstain from salted and cured meats, tinned foods, pastry, sweets, -raw vegetables, and cheese. Before retiring a tumbler of hot -water with a squeeze of lemon may be sipped slowly.</p> - -<p><i>Hyperchlorhydria.</i>—This, the true “acid gouty dyspepsia,” -is the most troublesome type of dyspepsia met with in the -“gouty.” Regulation of the diet is the best means whereby to -combat the excess of HCL in the stomach. All irritating spices -or condiments, mustard, vinegar, etc., should be avoided. Salt -especially should be used sparingly or wholly abstained from. As a -rule, alcoholic stimulants are not well borne, and may, in the -absence of special indications, be prohibited. In a limited number -of instances a light wine may be allowed as a stomachic. To -avoid irritation, hard substances, such as nuts, should be interdicted, -and food thoroughly masticated, and taken neither too -hot nor too cold. Bolting large morsels of food may readily -excite pyloric spasm.</p> - -<p>In these cases of superacidity the most suitable foods are -<i>proteins</i>, which combine and neutralise the excess of acid. A -liberal meat diet consisting in the main of chicken, beef, mutton or -ham, is indicated. Also fish, eggs, hard or soft boiled, are permissible. -<i>Farinaceous</i> foods are not well tolerated, and if given -must be of the most digestible kind. Vegetables should be mashed -and strained to rid them of cellulose, and only the more digestible -kinds taken, and in the form of purées. Fats tend to lessen acidity, -and are therefore indicated in the form of butter, cream, olive oil, -and such like. Of beverages alkaline and mineral waters, -Apollinaris, Seltzer, and Vichy, prove very beneficial. Their -contained carbonic acid exerts a sedative effect and diminishes -the secretion of acid. Milk or stimulants may be profitably -diluted therewith.</p> - -<p>Coffee is best abstained from, and cocoa and tea freshly made -with half milk substituted. Soups are best avoided. If with the -<i>hyperacidity</i> there be associated any degree of <i>atonic dilatation</i>, -the fluid taken at meals should be restricted. Also in this instance -the food should be taken in small quantities and at frequent -intervals. Otherwise these cases of <i>hyperacidity</i> do well on three -meals per diem provided they are separated by an adequate -interval.</p> - -<p>If the foregoing measures prove ineffectual the <i>carbohydrate</i> -content of the food should be withdrawn, and the patient limited -to a strictly <i>meat</i> diet, taken either raw or very slightly cooked. -It goes best when finely minced or grated on stale bread. According -to Osler, an ample dietary is afforded if three and a quarter -ounces of meat and two medium slices of stale bread be taken<span class="pagenum"><a id="Page_354"></a>[354]</span> -three times a day, with a glass of Apollinaris water or soda-water, -or what in this authority’s opinion is just as satisfactory—spring -water. For the bread a little dry toast or twice baked (<i>Zwiebach</i>) -bread may be substituted. Some advocate the meals being taken -wholly dry, or with two ounces of fluid only; but two hours later -a half to two pints of hot water should be slowly sipped. A -month or six weeks of such a diet will usually suffice, after which a -gradual return may be made to a mixed dietary.</p> - -<p>Apart from the binding of excess of acid by the protein substances -and consequent relief of discomfort, the so-called Salisbury -diet has other advantages. Abstraction of the carbohydrates -obviates intestinal fermentation and flatulence. Also, the food -administered being small in bulk, and taken more or less dry, a -dilated or atonic stomach tends to revert to its normal size.</p> - -<p>In conclusion, in regard to these cases of hyperchlorhydria it -must be realised that not only their diet and the manner of their -eating, but their general habits of living, must also be revised. -They must be warned of the great tendency to recurrence and the -necessity of orderly and regular habits and of strict abstemiousness -in regard to not only alcohol, but tobacco. The nerve element -in some of these cases is very pronounced, and sometimes nothing -short of a rest cure will suffice.</p> - -<p><i>Hypochlorhydria.</i>—Chronic gastric catarrh due to overeating -and overdrinking is not an infrequent complication of gout in -its later stages. Such subjects suffer with daily or periodical -vomiting of stringy mucus. In such cases the HCL of the gastric -juice is deficient or absent. Consequently protein foods are -digested with difficulty, and carbohydrates are more easily -disposed of. The lighter forms of meat, such as chicken or fish -or raw scraped beef, are indicated. Nor, in view of the chronic -nature of the derangement and the necessity of maintaining -nutrition, should we hesitate to allow such “gouty” subjects -other digestible forms of meat, such as sweetbreads, brains, etc. -Fats also and carbohydrates up to the limit of tolerance should -be allowed. Ingestion, however, of fluid at meals should be reduced -as far as possible. Of beverages milk, and especially buttermilk, -is particularly suitable.</p> - -<p>Despite the deficiency of HCL, they may suffer much with acid -eructations or flatulency owing to organic acids arising through -fermentation. If so, farinaceous foods must be restricted, particularly -potatoes and the coarser vegetables, while of course -pastry and sweet foods should be prohibited. Bread should be -taken in the form of dry toast or rusks.</p> - -<p><i>Hyperuricæmia.</i>—As far as is known, the endogenous moiety -of urinary uric acid is uninfluenced by diet. On the other hand,<span class="pagenum"><a id="Page_355"></a>[355]</span> -as has been shown in previous chapters, the exogenous fraction -can be reduced by suitable dieting. To this end, in order to -prevent the intake of food containing uric acid precursors, the -purin-free dietary was devised. Under such a regime both red -and white meats must be proscribed, also fish and the legumes—peas, -beans, lentils, asparagus, onions and oats—as these last are -all rich in purins. Tea, coffee, and chocolate must also be -eschewed.</p> - -<p>In lieu of these substances more or less poor in purin bodies -must be exclusively taken: milk sour or curdled, buttermilk and -whey, white bread, butter, cheese, eggs, rice, tapioca, macaroni, -sago, cereal foods, nuts and fruit. Even strawberries are permissible, -for Weiss noted that the addition to an ordinary diet -of 1 lb. of strawberries, 1½ lb. cherries, or 2 lb. of grapes, diminishes -the amount of uric acid excreted by almost 50 per cent. -With the exception of those interdicted above, all vegetables -are allowable, cabbage, cauliflower and lettuce being almost -purin-free.</p> - -<p>Personally I am not enamoured of purin-free diets for the -“gouty,” any more than I am of the purely vegetarian regime, -so extolled by some as the means of averting gout. The purin-free -diet, if I may say so, smacks too much of the laboratory, -its <i>raison d’être</i> the baseless assumption that <i>uric acid</i> is the <i>fons -et origo mali</i>.</p> - -<p>I am very doubtful of the intrinsic merits claimed for it. I do -not think it exerts a direct or <i>specific anti-gouty</i> influence. Such -advantages as do accrue are referable, in my opinion, to the -greater measure of <i>intestinal asepsis</i> that such a regimen promotes. -It is suitable, therefore, in cases in which there are evidences of -<i>intestinal putrefaction</i>. Distinctly unappetising, it is useful, too, -as a disciplinary measure for those prone to overeating.</p> - -<p>Its advocates claim that it tends to diminish the <i>excess of uric -acid in the blood</i>. But, as was pointed out when dealing with -uricæmia, <i>variations</i> may occur in the <i>uric acid content of the blood -independently of diet</i>. Moreover, acute attacks have been observed -even when the uric acid blood content was at a <i>sub-normal</i> level.</p> - -<p>To place all “gouty” subjects on a <i>purin-free</i> diet as a routine -procedure is to my mind wholly impermissible. The fact that -prolonged adherence thereto is usually found impracticable is -surely an indication that we are violating nature’s laws. It may -prove beneficial in a few isolated cases, and then only for a time; -but in the vast majority of instances it is frankly prejudicial. -Given a carefully revised mixed diet, it will, in my experience, -be rarely, if ever, necessary to subject “gouty” individuals to -this dietetic penance.</p> - -<p><span class="pagenum"><a id="Page_356"></a>[356]</span></p> - -<p><i>The Reduction of Obesity.</i>—Unfortunately obesity is a common -associate of gout, and with it not infrequently comes <i>glycosuria</i>. -Middle-aged “gouty” subjects have in their youth often been -given to strenuous exercise. But notwithstanding that with -advancing years their capacity and disposition for exercise -lessens, they nevertheless take the same amount of food as of -yore.</p> - -<p>It is most difficult to make them realise that, with the alteration -of their habits, the amount of food which at one time was -but adequate is now excessive. I have found it useful to remind -such of Ebstein’s dictum, “The gouty who have grown old in -spite of their disease are almost always those who have been able -to avoid obesity.” Still it is only fair to add that in some of the -gouty obese no accusation of overeating or overdrinking can be -lodged, and their aptitude for fattening seems often hereditary.</p> - -<p>Reduction of the body weight when excessive in gouty -subjects is hardly, I think, sufficiently emphasised. The victim -himself is but too often convinced, however, that he ought not to -be “lowered,” and sometimes, I think, infects the physician with -his apprehensiveness on this score. But, as Harry Campbell -rightly observes, “people do not die of starvation so easily as is -generally thought, and it is very difficult for the physician to -kill his patients in this way.” Yes, and, on the contrary, how -often do gouty people “dig their graves with their teeth.”</p> - -<p>Again, there is the <i>static</i> element to be considered in these -cases. The articular manifestations of gout are by preference -located in the lower extremities. It is clear then that excessive -stoutness, particularly if of recent development, must inevitably -throw increased strain on the already-hampered articulations. -The feet of the “gouty” are their most vulnerable point, and the -number who are flat-footed is noteworthy. In the presence of -this static fault, “strains” or “sprains”—those fertile excitants -of gouty outbreaks—are much more liable to occur, and I myself -feel sure that in this way the frequency of attacks in the feet and, -for that matter, in the knees also, is favoured.</p> - -<p>Lastly, the gouty obese is frequently elderly, his vessels somewhat -the worse for wear. Also he may show signs of cardiac -weakness or a trace of albumen or sugar in his urine. Even so -his weight should be reduced if possible. His watchword should, -like Falstaff’s, be:—</p> - -<div class="poetry-container"> -<div class="poetry"> - <div class="stanza"> - <div class="verse indent0">“Make less thy body hence, and more thy grace;</div> - <div class="verse indent0">Leave gormandising; know the grave doth gape</div> - <div class="verse indent0">For thee thrice wider than for other men.”</div> - </div> -</div> -</div> - -<p>There are so many dietetic methods of treating obesity that<span class="pagenum"><a id="Page_357"></a>[357]</span> -they cannot all be outlined here. The Banting method, like the -Salisbury, is too severe for the average patient, while the Weir-Mitchell -method has one cogent objection to general adoption, -viz., the expense entailed. Nevertheless as regards the last-named, -or skim milk, method, it certainly achieves marvellous -results in those cases in which there is a mere accumulation of fat -without any other complication.</p> - -<p>Generally speaking, however, one has to be content with the -following suggestions: All varieties of lean meat may be taken, -as well as poultry, game, and fish, subject to idiosyncrasies and -digestibility. Meat may be taken twice daily, not exceeding six -ounces at one time. All starchy and farinaceous food is to be -reduced to a minimum or wholly forbidden. Leaf vegetables -may be taken freely, but the roots and tubers, such as potatoes, -abstained from. Bread should be largely reduced in quantity and -thoroughly torrified. Sugar must be prohibited, and saccharine -or saxin substituted. Fresh fruits may be eaten, but milk should -be avoided, also cream, or very strictly limited. Where feasible, -it is often a good plan if the subject can for one day a week content -himself with a diet of skim milk.</p> - -<p>Alcohol, as far as possible, should be rigidly excluded, or only a -very moderate quantity of good whisky or a light wine, such as -hock or Moselle, permitted. As a rule, only a little hot water -should be sipped at meals. But I think in these subjects of -so-called “uric acid diathesis” it is well not to restrict their fluid -too markedly. A pint of hot water may be drunk one and a half -hours before each of the three meals, and one pint more half an -hour before bedtime. Weak hot tea may be substituted, as many -subjects find a difficulty in drinking so much plain hot water at -one time. If while on this regime the subject lose weight and -<i>pari passu</i> gain strength, all is well. If he lose weight and therewith -lose strength, further reduction or its continuance is contra-indicated. -It should be recollected that the reducing effects of -dieting may be markedly enforced by an open-air life, with riding -or other outdoor exercise.</p> - -<p><i>Glycosuria.</i>—This condition conjoined with obesity is not -uncommon in middle-aged “gouty” subjects. It is of benign -type, and the amount of sugar excreted is usually reduced to a -mere trace by extraction of the carbohydrates in the food. Thus, -we should forbid, <i>e.g.</i>, sugar, pastry, sweet wines, and dishes made -with flour, rice, or sugar. In these cases von Noorden considers -that it is better after reduction of the amount of sugar by dieting -to a mere trace to be content rather than to get rid of it wholly -by a rigid elimination of all carbohydrates. To this end the -patient may be allowed to eat a limited amount of bread, potatoes,<span class="pagenum"><a id="Page_358"></a>[358]</span> -and other vegetables, while he may eat freely of butter, bacon, -and other fats.</p> - -<p>One should recollect also that these “gouty” glycosurics have -periods of enhanced carbohydrate tolerance, this, as Burney -Yeo pointed out, quite “independently of any therapeutic interference.” -In short, at times they can take quite a considerable -amount of carbohydrates without passing sugar in their water.</p> - -<p>Needless to say, the regime must be adapted to each individual -case. The urine should be examined frequently, and the influence -on the sugar content of different articles of food noted; also the -weight should be frequently taken. It is certainly unnecessary -in gouty glycosurics to wholly banish the carbohydrates. By -such a plan we are more likely to do material injury than by -exceeding by a little their limits of tolerance. Our remarks of -course apply strictly to <i>alimentary</i> glycosuria. But we should -also remember that exceptionally a case of gouty glycosuria may -emerge into one of true <i>diabetes</i>.</p> - -<p><i>Albuminuria.</i>—In the so-called “gouty” contracted kidney, if -the amount of albumen in the urine be very large, or when there -are symptoms of nephritis, a milk diet for a few days or a week at -a time may be given. More often it is unnecessary, or it is -frequently badly borne or rejected. Consequently a modified -milk diet has to be adopted, and a gradual return to a mixed diet -permitted, provided no increase in the quantity of albumen ensues.</p> - -<p>But at the same time it must be realised that no rigid rule can -be laid down for “gouty” albuminurics. As a guide to the -suitability of a diet it is better to rely on the <i>general condition</i> -than on variations in the amount of albumen. For, as Professor -H. Andrew Smith, of New York, long since said, “if on changing -from a non-nitrogenous diet to a nitrogenous one we find a -general improvement in the patient’s condition, it is an evidence -that the change is beneficial, no matter if the albumen fills a larger -portion of the test tube. On the other hand, if we cut off a large -proportion of animal food from the diet, and our patient grows -more dyspeptic, weaker, more anæmic, more dropsical, it is nothing -to the point that only one half or one-third of the former quantity -of albumen is found in the urine; the change has done harm, and -the sooner we change back again the better. We should, above -all things, seek that diet for the patient which he can best digest -and assimilate, for we may rest assured that the products of faulty -digestion and assimilation will irritate the kidneys more than any -amount of normal material they may be called upon to eliminate, -while, at the same time, the general system will suffer from lack of -support.”</p> - -<p>Lastly, up to this juncture all our suggested dietetic modifications<span class="pagenum"><a id="Page_359"></a>[359]</span> -have been in the direction of reduction or abstinence. But -we must recollect that in practice we find that not a few gouty -persons are most careful and prudent in diet. They commit no -indiscretions, but nevertheless their gout is still with them. -They are of the asthenic type, thin, pale, sallow, and given to -neuralgic forms of fibrositis. They do not want “lowering”; to -curtail their food is harmful. In their instance, with due respect -to digestive idiosyncrasies, a more or less generous diet should be -prescribed. Let them forsake dietetic schedules and follow their -instincts. Let your advice be that of Sir William Temple: -“Simple diet, limited by every man’s experience to his own easy -digestion, and thereby proportioning as near as can be the daily -repairs to the daily decays of our wasting system.”</p> - -<h3><span class="smcap">Beverages in Gout</span></h3> - -<p>It cannot be gainsaid that the beneficial effects of so-called -“water cures” are in great measure referable to the increased -amount of <i>water</i> ingested during their progress. Absorbed in the -main in the small intestine, it passes into the general blood stream, -whence it is excreted <i>viâ</i> the skin, kidneys, lungs, and fæces. Its -elimination through these various channels sufficiently accounts -for its value as a means of flushing the bodily tissues and hastening -the excretion of retrograde and toxic products. Indeed, its -efficiency as a depurative agent cannot be over-estimated, and -nothing is more beneficial for the subjects of a “gouty” diathesis -than regular consumption of an adequate quantity of this -admirable solvent.</p> - -<p>By general consent, the water ingested should be preferably -<i>hot</i>. Water of a higher temperature than that of the blood -stimulates the hepatic cells, and promotes biliary excretion. It -has been shown, moreover, by Glax that while draughts of cold -water raise vascular tension and diminish pulse frequency, on the -other hand hot water diminishes arterial tension and accelerates -the pulse rate.</p> - -<p>It is also claimed that the increased elimination of water <i>viâ</i> the -kidneys is correlated with an augmented output of the solid -constituents of the urine; that the phosphates, sulphates, -sodium chloride, and likewise urea are for the time excreted in -greater amounts.</p> - -<p>The point at issue, however, is whether or no this increase in -the amount of <i>urea</i> excreted can be held to indicate enhanced -tissue change in the nitrogenous elements in the body fabric.</p> - -<p>Winternitz claims that it does, in contrast to Von Noorden, who -holds that nitrogenous tissue change and the formation of <i>urea</i><span class="pagenum"><a id="Page_360"></a>[360]</span> -and <i>uric acid</i> are <i>uninfluenced</i> by the amount of water imbibed. -In further contradistinction some contend that following the -ingestion of water the <i>excretion of uric acid</i> is <i>diminished</i>.</p> - -<p>Fortunately for “gouty” subjects, the beneficial effects of -water flushing of their systems occur independently of any <i>coincident -increase in their uric acid output</i>. This is true even of -mineral waters. Thus Bain and Edgecombe noted that following -the ingestion of the old sulphur water of Harrogate the excretion of -uric acid was diminished. Nevertheless cases of “gout, especially -of the <i>asthenic</i> type, derived the most marked benefit from its -use.” “This fact is mentioned,” they say, “because some writers -attach the greatest importance to an augmented excretion of uric -acid in the urine as a necessary concomitant of successful treatment. -This we firmly believe to be an erroneous view.”</p> - -<p>Indeed, ignorant as we are of the exact etiology of gout, we must -at any rate provisionally attribute the proved efficacy of water-drinking -in gout to its flushing action on the tissues, its furtherance -of the excretion of waste products. Nor can we doubt that the -ingestion of hot water, involving as it does equalisation of its -temperature with that of the body, must exert a profound and -intimate effect upon processes of cell nutrition. Moreover, -through its solvent and penetrative quality, its mineral or chemical -constituents are enabled to penetrate freely the interstices of the -tissues throughout the economy.</p> - -<p>It is, therefore, well to advise “gouty” subjects to drink -daily on rising from eight to ten ounces of hot water, repeating -the same half an hour before lunch and dinner, and finally the -last thing at night. For in my experience “gouty” subjects on -the whole do better if they drink some time before their meals -than during their progress. It is an old belief that hard waters -are unsuitable for the “gouty.” Sir Dyce Duckworth believed -so, and Sir Charles Scudamore in 1823 delivered himself as follows: -“The kind of water denominated hard has always been considered -as unfriendly to health, and especially injurious to persons -afflicted with gravel or stone. Many probably imagine that the -earthy salts which it contains assist in making up the mass of -the calcareous concretion.”</p> - -<p>But more probably, as Sir Archibald Garrod suggests, the old -view that tophi were composed of chalk had probably something -to do with the origin of the tradition. That hard waters may be -noxious in so far as they favour constipation may be granted. -But, on the other hand, we have to reconcile with this the awkward -fact that earthy or calcareous waters, <i>e.g.</i>, those of Bath, etc., -are among those whose efficacy in gout is beyond question.</p> - -<p>Again, how can we reconcile with this view the prevalent<span class="pagenum"><a id="Page_361"></a>[361]</span> -practice of placing “gouty” subjects, temporarily at any rate, -on a <i>milk</i> diet, this although milk is especially rich in lime? -That a regime of milk in the young and robust “gouty” subject -is often extremely beneficial is beyond question. On the other -hand, it is equally certain that others do not thrive thereon. In -prescribing it, therefore, we must be guided largely by <i>personal -idiosyncrasy</i>.</p> - -<p>Lastly, as to <i>tea</i> and <i>coffee</i>, there is a theoretical objection that -both contain methyl purins. Albeit, it must be seldom indeed -that gout is met with in pure tea-drinkers who at the same time -abstain wholly from alcohol. Either tea or coffee, if taken apart -from food, usually agrees well with the “gouty,” always -provided that they be well made and not over-strong. Of the -twain tea is, I think, more generally suitable than coffee, and -where both disagree cocoa is an excellent substitute.</p> - -<h3><span class="smcap">Alcohol in Gout</span></h3> - -<p>Said Sir Thomas Watson: “I am sure it is worth any <i>young</i> -man’s while who has had the gout to become a teetotaler.” Few -will gainsay the wisdom of this advice. But I would fain go -further and impress on <i>gouty parents</i> the incumbent duty of -bringing up their children as <i>total abstainers</i>. For gout, once -avowed, has a vicious tendency to recurrence. The illustrious -Sydenham, I think, would have approved of such advice: -“Water alone is bad and dangerous, as I know from personal -experience. When taken as the regular drink from youth upwards -it is beneficial.”</p> - -<p>When, however, gout attacks a man for the first time in middle -or late life, most authorities agree that an abrupt change of habit -in respect of stimulants is of questionable wisdom. In saying -this, I do not for one moment mean that excess should be approved, -but that I do not believe that the enforcement of total abstinence -is prudent. In such cases restriction, not total elimination, is the -better course. One must recollect, too, that total abstainers are -by no means exempt from gout, while, on the other hand, many, -if not the majority, of drunkards are. The latter have their -penalties, cirrhosis, etc., but not inevitably gout.</p> - -<p>I agree that gout is infinitely more common in those who take -alcohol than in those who abstain therefrom. But nowadays, -at any rate, the “gouty” as a class cannot with fairness be ranked -as among the confessedly intemperate. With relatively few -exceptions, they belong rather to those given to what may be -termed the legitimate use of alcoholic beverages. My conclusions -then are that:—</p> - -<p><span class="pagenum"><a id="Page_362"></a>[362]</span></p> - -<div class="blockquote"> - -<p>(1) The children of “gouty” parents should be brought up as -total abstainers.</p> - -<p>(2) The incidence of a first attack in a young man should be the -signal for abstinence from alcohol in all forms.</p> - -<p>(3) Given its occurrence in an older subject who has used -alcohol but sparingly and stands in no need of it as a -stimulant, the same total abstinence should be inculcated.</p> - -<p>(4) In middle-aged or old subjects habituated to the use or -abuse of alcohol <i>abstemiousness</i>, not abstinence, is the -safer course.</p> - -</div> - -<h3><span class="smcap">The Various Alcoholic Beverages</span></h3> - -<p><i>Malt Liquors.</i>—I think we should distinguish between the -“strong” and the “mild” varieties, even as we do between -“heavy” and “light” wines. “Strong” malt liquors unquestionably -are most provocative of gout, and it is not without -significance that most “gouty” subjects have, frequently on -their own initiative, abandoned their use. So much importance, -indeed, do I attach to this, that if I were called to -formulate any rule in the matter of alcohol for “gouty” subjects -it would be the unsuitability of “strong” malt liquors, which -not only increase the tendency to recurrence of the paroxysms, -but appreciably lengthen their duration.</p> - -<p>The prefix “strong” I use advisedly, as the volume of alcohol -contained in different beers may vary by as much as from 1 to -10 per cent. Thus Scotch ale contains as much as 8·5 per cent., -and, generally speaking, all “old” ales are usually “strong” -ales. Albeit, to condemn malt liquors unreservedly is, I am sure, -inadvisable. The truth is that in respect of their <i>gout-inducing -power</i> malt liquors, like wines, display great variations.</p> - -<p>Thus “strong” malt liquors, like “heavy” wines, are markedly -provocative of gout, whereas the “milder” ales, like the -“lighter” wines, are relatively impotent in this respect. Said -the elder Garrod on this point: “The lighter wines, as claret, -hock, and Moselle, although capable of acting as the exciting -cause of an attack in gouty subjects, have when taken in moderation -but comparatively little inducing power, and in this respect -rank with the weaker kinds of malt liquors.” In this connection -is it not significant that gout is extremely rare among agricultural -labourers, who drink freely of that popular and ancient beverage -mild beer? Sydenham on this point is very definite: “This is a -rule for the gouty: they may take those liquors which neither -chill the stomach nor intoxicate in any moderate quantity. Such<span class="pagenum"><a id="Page_363"></a>[363]</span> -is the small beer in our own country, which in foreign countries -may be replaced by weak wine-and-water.”</p> - -<p>I hold no brief for alcohol, but of the twain I am sure it is wiser -to advise a poor man, even though “gouty,” to stick to “mild -beer” rather than urge him to betake himself instead to “ardent -spirits.” For the rich man, too, while in his prime and still capable -of vigorous exercise, I am firmly of opinion that, with due deference -to <i>idiosyncrasy</i>, a <i>mild</i> beer not containing more than from -3 to 6 per cent. of alcohol will do him not more, but less, harm -than <i>whisky</i>.</p> - -<p>I have yet to learn that the working man who has gout and sticks -to mild, sound beer in moderation gets attacks more often or -more severely than the rich man who affects whisky. “It must,” -as Sir Archibald Garrod observes, “be confessed that among -hospital patients who could not, if they would, follow out any -strict rules of dietary, who seldom pay heed to our advice that -they should give up beer, and who, as soon as an acute attack is -over, revert to their previous habits of life, the course of gout does -not seem to differ materially as regards the character, frequency, -and severity of the attacks from that followed in people who are -able to adjust their living according to the best advice to be -obtained.”</p> - -<p>I think then in this matter of <i>malt liquors</i>, their suitability or -not for “gouty” subjects, we should be well advised to reconsider -our attitude. In other words, I would urge that we draw a -distinction between “strong” and “mild” malt liquors. By all -means let us continue to condemn the “heavy” varieties, while -not extending the ban to the “lighter” forms. I would, however, -make the following reservations: that—</p> - -<div class="blockquote"> - -<p>(1) It be a “light” beer, in which the “bitter” principles -predominate, and the extractives are small in amount<a id="FNanchor_61" href="#Footnote_61" class="fnanchor">[61]</a>;</p> - -<p>(2) It be “sound” and not “turned” beer, and of course free -from any possibility of <i>lead</i> impregnation;</p> - -<p>(3) It be taken in moderation, not exceeding one to two pints -per diem;</p> - -<p>(4) The “gouty” subjects by whom it is taken be physically -active;</p> - -<p>(5) Due respect be paid to <i>personal idiosyncrasy</i>, reserving its -use for those in whom its effects are definitely <i>stomachic</i> -and <i>tonic</i>, while discountenancing its use when followed -by <i>heaviness</i>, <i>drowsiness</i>, and <i>biliousness</i>.</p> - -</div> - -<p>As to <i>cider</i>, there is no doubt that the partially fermented or<span class="pagenum"><a id="Page_364"></a>[364]</span> -sweet variety is more harmful than “dry” or “rough” cider. -Still there is no room for dogmatism even here, for a “gouty” -man, if he be unaccustomed to cider, may find that, whether “dry” -or not, it may provoke an attack. Sir Archibald Garrod tells us -that he has known not a few gouty patients who alleged that cider -suited them admirably, but he adds: “An experience of some -months has usually modified their opinion on this point.”</p> - -<p><i>Wines.</i>—When we come to consider <i>wines</i>, we are on very -uncertain ground, this especially if we base our opinion too -much on the <i>chemical</i> analysis of this or that variety. The current -belief is that the most unsuitable wines are those that contain -large amounts of <i>alcohol</i>, <i>sugar</i>, or <i>free acid</i>. Then we discover it -is not the amount of <i>alcohol</i> in the fluid that determines the -incidence of gout and, in witness to our perspicuity, call to note -the rarity of gout in Scotland, where <i>whisky</i> is the favourite -beverage; <i>ergo</i> whisky <i>par excellence</i> is <i>the</i> drink for the “gouty,” -and so we find ourselves in this <i>impasse</i>: we fulminate against -<i>alcohol</i> as <i>the</i> cause of gout, and in the same breath advise our -“gouty” patients to drink precisely those fluids containing the -highest percentage thereof.</p> - -<p>True, when we turn to <i>wines</i> we find that it is precisely -those that are richest in <i>alcohol</i> that most potently predispose -to gout, <i>e.g.</i>, port. But seeing that <i>whisky</i> contains infinitely -more <i>alcohol</i> than port, and yet is little gout-provoking, we -search round for some other constituent in wine on which -to lay the blame. So we decline on the varying degrees -of <i>acidity</i> in different wines. But this again on reflection, it -is decided, is of little moment. For, on the one hand, port -and sherry are among the least acid wines, and yet, like -the even less acid malt liquors, most productive of gout, -while, on the other hand, the more acid clarets and hocks -are deemed relatively harmless. Then the varying quantities -of <i>sugar</i> in the different wines come under the ban. But -here again no definite line can be drawn. For some wines most -provocative of gout have a high sugar content, while others -equally potent in this direction contain but small amounts.</p> - -<p>Now the most salient deduction from the foregoing considerations -is our inability at present on <i>chemical grounds</i> to determine -why certain <i>wines</i> are productive, and others are relatively nonproductive, -of gout. We can impeach neither the alcohol content, -the acidity, nor the sweetness. For on all these points startling -exceptions preclude dogmatism. Does not the clue to these varying -reactions <i>quâ</i> gout reside in the <i>individual</i>, not in the character -of the wine? We are far too prone to say that this or that <i>wine</i> -is “gouty,” to say that this wine gives you gout, and that not.</p> - -<p><span class="pagenum"><a id="Page_365"></a>[365]</span></p> - -<p>The evil potentialities that make for gout reside not in this or -that particular wine, but in the <i>individual</i>. This or that wine -does not give him gout, but evokes or brings to fruition a morbid -tendency already <i>latent</i> in him. In the absence of this inherent -proclivity, it would not have elicited those specific local reactions -typical of gout. But for those who would interpret this statement -as approval on my part of alcohol or an absolving thereof from -any part in the genesis of gout I would issue this <i>caveat</i>: Alcohol -will not originate gout in a <i>non-gouty</i> subject, but it will almost -infallibly in those in whom there exists by heredity an inborn -tendency to gout. In short, the “gouty” are <i>hypersensitive</i> to -the evils of alcohol; the greater the need then for <i>abstemiousness</i> -and self-restraint.</p> - -<p>But, to resume the thread, in the absence of any absolute -chemical criterion as to the relative suitability of this or that wine -for the “gouty,” what shall be our advice to the <i>“gouty” individual</i> -on this point? In a word, his “palate” and his “stomach” -are the best criteria of the wholesomeness of this or that particular -wine in his particular instance. If he is in the habit of taking -wine do not forthwith, as is so often done, forbid him wine -in all forms and order him <i>whisky</i>. This is done so light-heartedly -that I do not wonder that the subject goes away frequently -with the idea that <i>whisky</i> is not only innocuous, but -desirable.</p> - -<p><i>The whisky-drinker is not immune from gout</i>, and I have no -hesitation in affirming that “light” <i>wines</i> when fine, mature, and -of a <i>good</i> quality are, subject to individual idiosyncrasy, quite as -suitable for the “gouty” as whisky. Of the many wise warnings -given us by Sir James Goodhart none is more apt for the present -day than the following. Discussing the “treatment of uric -acid,” he observes: “I am as much as ever an opponent of the -prevalent dictum, ‘You must not touch wine; you must drink -whisky,’ which too often means to the patient, ‘A glass of good -wine is poison; I may take as much whisky as I like, and it is -harmless,’ one of the most mistaken and mischievous beliefs that -ever plagued a world.”</p> - -<p>Again, if a “gouty” man takes wine, there is always one -special variety that agrees with him, and as certainly one other or -more that infallibly upset him. Putting aside all preconceived -ideas, find out his <i>personal idiosyncrasies</i> in this respect. In this -way you elicit and utilise for your ends the <i>individual’s</i> own -experience, the only experience that counts.</p> - -<p>A man of a certain age, he generally by the time he develops -overt gout has arrived at definite conclusions as to what does and -what does not suit him. He will frequently tell you he has had<span class="pagenum"><a id="Page_366"></a>[366]</span> -to give up malt liquors, perhaps port and champagne, and now -finds that whisky, gin, or the lighter wines agree with him better. -Or, as like as not, he may upset all your preconceived ideas. He -may be of those gouty subjects—and they are not so few—who can -drink champagne in moderation, or even a glass or two of port, -daily with apparent impunity. On the other hand, a glass of -claret or hock plays the mischief with him. He may, like some -individuals cited by Burney Yeo, be one of those exceptional -gouty subjects in whom even stout is well borne, Yeo thought -largely because they habitually took daily large quantities of -alkaline salts.</p> - -<p>The sum of these erratic findings is that you must respect -<i>idiosyncrasy</i>. It is said that the best wine for a “gouty” subject -is the one that causes most <i>diuresis</i>. For myself, I am equally -positive that the worst wine for a gouty man is that which upsets -his <i>stomach</i>, which gives him some hours afterwards “acidity” -or a feeling of “liver.” Often, too, it is not the wine, but the -<i>stomach</i> into which it is put, that is to blame. Thus the “gouty” -subject with <i>atonic dyspepsia</i> finds a glass of sound wine helps -digestion. On the other hand, if he suffers from <i>hyperacidity</i> or -<i>chronic gastritis</i>, the reverse will probably be the case.</p> - -<p>Again, it is not the name, but the <i>quality</i>, of the wine that counts. -It makes all the difference whether the wine taken is fine, mature, -and of good quality, or some factitious, mixed, or adulterated -product, passing muster, say, as claret. Fine mature clarets or -red Bordeaux wines are most suitable for the gouty. But, as -Burney Yeo rightly says, “a more injurious beverage than bad -claret or imperfectly matured claret—and, speaking generally, all -but the more expensive or most carefully selected clarets are -bad—was never drunk.”</p> - -<p>It seems opportune here to lodge a protest against <i>fashions</i> in -wines for the “gouty.” At one time it was claret, then light -white wines, Moselle, etc., and anon whisky, and even cider had its -vogue. Fashions in wines, as in other spheres, postulate uniformity -and lack of discrimination. Any one of the foregoing beverages -may suit some particular “gouty” individual, but not <i>all</i> -“gouty” subjects.</p> - -<p>We have said that in some instances the wine, in others the -stomach, is at fault. But intrinsically it may lie in neither, -but simply in the <i>quantity</i> of the wine drunk. It may not, as -judged by ordinary standards, be an excessive amount, but it -may be excessive for that particular man. It is here that a medical -man may often intervene with advantage. For a man may, -quite unbeknown to himself, be really a heavy drinker, one of -those unfortunates who are peculiarly tolerant of alcohol. A<span class="pagenum"><a id="Page_367"></a>[367]</span> -tactful reminder of the amount he is consuming per diem will -frequently come as a shock, often a very beneficial one.</p> - -<p>Apart from this, it is, I am sure, wise to fix the <i>daily amount</i>. -The daily habit in the “gouty” is all-important. If accustomed -to take one or two glasses, and they stick to it, all may be well; -but it is on the occasions when the glass grows into a half-bottle -that the trouble comes. Metabolically speaking, the “gouty” -subject is most unstable, and disturbance of what one may call -his daily alcoholic rhythm is always perilous. Unfortunately it -works either way, too, both in the matter of “too little” as well -as “too much.” Here experience and sound judgment will -alone enable the physician to decide how far he may tamper with -long-established habits.</p> - -<p>At other times the amount, though, strictly speaking, not -excessive, is so when judged in light of the victim’s <i>habits</i>. He -may be an intellectual worker, but <i>sedentary</i>, and he must either -lessen his drink or increase his exercise, or he may <i>overeat</i> as -well as overdrink—a victim of the prevalent idea that the one -evil counteracts the other. Between the Scylla of overeating -and the Charybdis of overdrinking there is no safe course save -by way of <i>reduction</i> of both.</p> - -<p>We see therefore that in the matter of the choice of a wine for -a “gouty” subject there are many points to be considered. Of -these <i>personal idiosyncrasy</i> stands first. By this criterion, and -none other, can the <i>suitability</i> of the wine be decided. Then the -state of the <i>digestive</i> functions, if deranged, has to be considered. -Is the gastric disorder such as will be benefited or, on the other -hand, impaired by wine of any sort? Again, <i>glycosuria</i>, <i>albuminuria</i>, -<i>raised blood pressure</i>, or <i>cardiac degeneration</i> may intervene -to complicate the issue, and so our policy in regard to alcohol -has constantly to be adapted and readapted to the varying -requirements of the organism.</p> - -<p>It will be seen that I have largely refrained from specifying the -wines <i>suitable</i> or <i>unsuitable</i> for the “gouty.” To have done so -would have been alien to the general tenor of my remarks, -convinced as I am that our trend in the matter of alcohol for the -“gouty” should be more in the direction of “individualisation” -than of “standardisation.” Subject to the reservations -that such an attitude portends, I would proffer the following -suggestions:—</p> - -<p>As a general rule, wines which are “dry” are much more -suitable for the “gouty” than those which are “sweet.” Wines -are termed “dry” when nearly all the sugar of the grape is -transmuted into alcohol, as in “dry” sherries. They are termed -saccharine or “sweet” when the process of fermentation is<span class="pagenum"><a id="Page_368"></a>[368]</span> -arrested before all the sugar has been exhausted, as in Malaga. -Again, wines which are both “strong” and “sweet,” <i>e.g.</i>, Malaga, -sweet champagne, Tokay, etc., are more pernicious than those -which are “strong” yet “dry,” <i>e.g.</i>, port, sherry, Madeira.</p> - -<p>Sir James Goodhart, discussing wines suitable for the “gouty,” -confesses to a “personal leaning in favour of the wholesomeness -of a glass of good old sherry in those cases where a little wine -seems a judicious prescription.” With this I fully agree, and -would suggest that of sherries the “gouty” should favour the -“Manzanilla” rather than the “Amontillado” class. The former, -save for the addition of a small quantity of spirit, are mostly -shipped in the natural state; also they are light and “dry” as -compared with the latter, which are generally “sweet” and full-bodied.</p> - -<p>It is interesting to recall, too, that Sydenham regarded <i>sherry</i> -as preferable either to Rhenish or French wines. He himself in -his own person found “sack” or Canary the most helpful. “I -have during the fits of the last years tried many things to lessen -the symptoms. Nothing, however, effected my purpose so much -as a small draught of Canary wine, taken now and then, when the -faintness or sickness were most oppressive.” Here one may note -that sherry was the first wine to be known as “sack” in this -country, and that the wine shipped in Sydenham’s time was -of the “dry” variety. Chemically the “sweet” sherry differs -from the natural “dry” light wine through its relatively high -content of alcohol and sugar.</p> - -<p>Turning to <i>port</i>, Sir Alfred Garrod absolutely tabooed its usage -by the gouty. But this appears too sweeping, and nowadays, -at any rate, it is well recognised that, especially in <i>asthenic</i> -types of gout, a glass or two of old port is well borne. Consequently -in such cases we should not, in the absence of any adverse -symptoms, forbid its continuance. The bad reputation achieved -by port is, I am sure, a relic of the Regency. But “three-bottle” -men are no longer with us, and, allowing for personal -idiosyncrasy, I very much question if sound port taken in -moderation wholly merits the aspersions cast upon it. I do not -by that for one moment suggest its general adoption by “gouty” -people, but that where an old or elderly gouty subject takes -port and can be trusted not to extend his glass to half a bottle -his inclination may be respected. The sugar content of port varies -according to the vintage, ranging from 7 to 15 per cent., and the -“gouty” man should favour the “drier” varieties.</p> - -<p>As for champagne—a manufactured article rather than a -natural wine—there is no question that, if taken at all, it should -be a “dry” brand. Such contains from 9 to 12 per cent.<span class="pagenum"><a id="Page_369"></a>[369]</span> -of alcohol and from 1 to 4 per cent. of sugar, whereas the -“sweet” brands may hold as much as 16 per cent. All -depends on the <i>quality</i> of the champagne, and, as Ewart wisely -remarks, “it is wiser for the ‘gouty’ patient not to incur considerable -risks by trying brands with which he is not familiar, -though he may sometimes with impunity, and occasionally with -benefit, enjoy a glass of champagne which he can trust from -personal experience.”</p> - -<p>If, on the whole, the most unsuitable wines for the “gouty” -are the strong sweet <i>spirituous</i> or <i>liqueur</i> wines, on the other -hand the <i>red</i> or astringent and <i>white</i> wines are the most esteemed. -As to the <i>red</i> wines, there is no doubt that the delicate Gironde -(Bordeaux) wines are <i>par excellence</i> the most suitable. They -have sufficient body and alcohol without being heavy or fiery, -while their acidity and sugar content are very low. But of -course the quality of the wines varies considerably with the -vintage. Subject to this, sound, well-made clarets taken in -moderation and somewhat diluted with water are the most -wholesome wines we can prescribe for the “gouty.”</p> - -<p>The more full, though still not coarse, wines of the Burgundy -district are by some denounced. One authority, I note, states -that in elderly gouty subjects he had often found that two or -three glasses of claret or Burgundy were in the course of a few -hours followed by eczema. While such idiosyncrasies may obtain, -it is not true of the “gouty” as a class. I should consider a -“gouty” subject in any case unwise to take two or three glasses -of Burgundy. But I do not hesitate to order <i>one</i> or perhaps two -glasses somewhat diluted with water. Being a stronger and more -tonic wine than Bordeaux, it is useful in the more <i>asthenic</i> types -of gout. The pity is, of course, that the cheaper Bordeaux and -Burgundy wines are so largely adulterated, while the more mature -clarets are available only for the rich. As good substitutes for -French wines Burney Yeo commends the red Hungarian wines, -such as Carlovitz, while we may add that some of the Dalmatian -wines are of fair quality and somewhat resemble Burgundy.</p> - -<p>Reverting to <i>white</i> wines, these, as compared with the red wines -of the Gironde, contain less tannin and more free acid. According -to Burney Yeo, they exert, too, a more diuretic effect, and to -remove their excessive acidity he advises their dilution with some -alkaline table water. Most of the white wines come from the -Rhine or Moselle districts. The Rhenish are relatively full-bodied -and of marked vinosity, while the Moselle wines are mostly light -and of a somewhat delicate nature. Light hocks and still Moselles -are quite permissible, also the white wines of France, such as -<i>vin de Grave</i>, all varieties of the latter being fairly “dry” and<span class="pagenum"><a id="Page_370"></a>[370]</span> -light in character. On the other hand, the <i>white</i> wines of Sauterne, -like some of the Hungarian wines—<i>i.e.</i>, Ruster—are rich in saccharine -constituents. In this respect they contrast with the -Rhenish and Moselle wines. Of these last Johannisberg contains -only 0·42 per cent. of sugar, Rudisheimer 0·39, Zeltinger 0·13, -and Stein-Reisling 0·01, while Ruster contains no less than -21·74 per cent. of sugar.</p> - -<p>In conclusion, I would re-emphasise the fact that, if wine be -taken, the patient’s own experience is the best test as to which -particular wine is the most suitable in his case. This elicited, the -subject should be counselled to adhere to it, taking it only at <i>meal-times</i>, -and establishing a rigid rule as to <i>quantity</i>. The least -excess is harmful, and breaking of the ordinary routine in the -matter of the amount drunk is a fertile source of “gouty” outbreaks. -In any case the <i>quality</i> of the wine should be above -suspicion, and if the expense is prohibitive, he had best eschew -wine altogether in favour of mature spirits.</p> - -<p><i>Spirits.</i>—Brandy, whisky, and gin are the spirits most in vogue -in Great Britain, and it has become an axiom with some that, if -alcohol in any form be requisite for the “gouty,” the least harmful -is one or other of these beverages when adequately diluted. Of -the three whisky undoubtedly has found most favour, and the -pernicious and far too prevalent idea is that whisky not only does -not beget gout, but is actually <i>beneficial</i> for gout. The consequence -is that many “gouty” people take far more whisky than -is desirable, seemingly oblivious of the fact that, if whisky in -<i>moderation</i> be suitable for the “gouty,” whisky in <i>excess</i> is -as deleterious for them as for the non-gouty. In short, like any -other form of alcohol, if taken immoderately, it will bring to -fruition a latent gout, this, as suggested by Ford Robertson, not -by the direct action of the alcohol, but by the “indigestion -toxæmia” it sets up.</p> - -<p>In advising therefore a “gouty” subject to take whisky we -should insist that (1) it should be taken only at <i>meal-times</i> and -(2) only in <i>moderation</i>. The habit of occasional “nips” at all -times of the day should be unreservedly condemned. As to what -constitutes a <i>moderate</i> quantity is often a difficult question to -decide.</p> - -<p>When feasible, I endeavour to limit the <i>daily allowance</i> to <i>a wine-glassful</i>, -distributed over lunch and dinner. But it is quite -impossible to lay down hard and fast rules in a matter in which -<i>personal idiosyncrasy</i> plays such a strong <i>rôle</i>. Frequently, in -addition to the above amount, one has to relent to the extent of a -“nightcap,” or but too commonly one has to be content if one -can compass reduction to an amount which for the particular<span class="pagenum"><a id="Page_371"></a>[371]</span> -individual under review seems apparently compatible with no -appreciable damage to health.</p> - -<p>Sometimes one of the frequent accompaniments of gout comes -to our assistance. It may be <i>raised blood pressure</i>, <i>glycosuria</i>, -<i>albuminuria</i>, <i>obesity</i>, etc. In such cases a word in season may -reduce an otherwise recalcitrant subject to reason.</p> - -<p>Needless to say, in regard to “ardent spirits,” as to wines or -malt liquors, we must, when determining the quantity to be taken -per diem, review the same in light of the person’s <i>habits</i>, whether -<i>active</i> or <i>sedentary</i>, whether associated with overeating or not. -For manifestly all these bear on the point at issue.</p> - -<p>Lastly, as to whether the subject should take brandy or gin in -preference to whisky is a matter for himself to decide. Whichever -suits him best is the best for him. Albeit, I confess to a -leaning in favour of “dry Plymouth” gin, this being more diuretic -than other spirits by reason of the juniper contained therein. -But, in whatever form “ardent spirits” be taken, it is most -essential that it be sound. Brandy should be of the finest quality, -the whisky mature, and inferior kinds of both wholly eschewed.</p> - -<hr class="chap x-ebookmaker-drop"> - -<div class="chapter"> - -<p><span class="pagenum"><a id="Page_372"></a>[372]</span></p> - -<h2 class="nobreak" id="CHAPTER_XXVIII">CHAPTER XXVIII<br> -<span class="smaller">MEDICINAL AND OTHER MODES OF THERAPY—ACUTE GOUT</span></h2> - -</div> - -<h3><span class="smcap">Medicinal Therapy</span></h3> - -<p>The illustrious Sydenham, for more than thirty years a sufferer -from gout, was clearly in doubt as to whether a cure of the malady -was to be attempted or even desired. It was Nature’s prerogative, -he contended, to dispose of the peccant matter after her own -fashion by depositing it in the joints, whence it might be dissipated -by insensible transpiration. Evacuant measures were, he thought, -frankly prejudicial in that they occasioned reabsorption into the -blood of morbid substances already cast forth from the system -into the joints, with haply deflection of the same upon the -viscera, with all its added perils.</p> - -<p>In view of these conceptions, Sydenham naturally discountenanced -any attempt to arrest or control the course of -acute gout. “Nay, more,” said he, “I can confidently affirm -that the greater part of those who are supposed to have died of -the gout have died of the medicine rather than the disease.” -Not only were purging, blood-letting, and alike the use of -diaphoretics by him condemned, but, more, a policy of “inert -expectancy” enjoined. The true <i>rôle</i> of the physician was that -of the bystander viewing the workings of the <i>vis medicatrix -Naturæ</i>, while for the tortured victim remained the pithy -consolation that his gout was to be regarded as a minister of -health, whose presence and stay ought by all means to be -courted. Long years after Sydenham’s death his <i>laisser faire</i> -attitude survived in Meade’s epigram, “the gout is the only -cure of the gout,” and in Cullen’s depressing axiom that “in -patience and flannel alone” lay salvation. Can we wonder that -this policy of masterly inactivity made gout the happy hunting -ground of the charlatan?</p> - -<p>It may be admitted that an <i>initial</i> attack of gout often leaves -the subject better than before, but the deep remedial forces of -Nature, at first apparently all-sufficing, later prove unequal to -their task. Secondary evils follow the attacks, and “the racking -pains, unfitness of motion and other disorders which afflicted him -during the greatest part of his life” are at once a proof of Nature’s -limitations and the fallaciousness of Sydenham’s doctrines.</p> - -<p><span class="pagenum"><a id="Page_373"></a>[373]</span></p> - -<p>So much by way of prelude, but perhaps, as Heberden surmised, -the chief reason why Sydenham and his disciples found it advisable -to do nothing to curb the violence of gout was that they knew -nothing wherewith to achieve such control. Thus, though -<i>colchicum</i> had been used from time immemorial by the ancient -physicians, it had in Sydenham’s time almost been abandoned -as a remedy in gout, when, long after, according to Scudamore, a -Mr. Want (“Essays in the Medical and Physical Journals,” -No. 185, etc.) drew attention to its specific value in gout, and -restored the drug to its pristine status.</p> - -<h3><span class="smcap">Acute Gout</span></h3> - -<p>In the main the general principles of treatment conform to -those adopted for other inflammatory ailments, with, of course, -the important reservation that our mode of procedure be adapted -to the individual case; viz., due regard must be had to age, the -intensity of the attack, and the presence of complications. For -obviously the treatment suitable for a robust plethoric subject -might prove the very reverse of salutary for a broken-down -victim more or less worn out by previous attacks and haply -the subject also of <i>arterial</i> and <i>renal</i> changes.</p> - -<p>The medicinal treatment of acute gout necessarily divides -itself into <i>constitutional</i> and <i>local</i> measures. In pursuance of the -first, we seek to control the inflammation and febrile disturbance -while assisting the organism to eliminate those toxic substances -in the blood that have determined the incidence of the paroxysm.</p> - -<p>The attack usually supervenes while the subject is in bed, and, -generally speaking, keeps him there. Indeed, rest is imperative, -and as far as possible sources of worry should be excluded. The -nature of the diet suitable for the acute stages has already been -adverted to, and, practically speaking, the first point that calls -for investigation is the state of the bowels. Were they prior to -the attack open regularly, loose, or confined? Constipation is -the usual forerunner, and if so, a swiftly acting purge must be -given. Indeed, even if previously the action of the bowels has -been free, they usually, with the onset of the attack, become -bound, the intensity of the local pain presumably exerting an -inhibitory effect.</p> - -<p>As to the advisability of initial purgation in acute gout, -Sydenham was definitely opposed thereto. In contrast, others, -who held with Scudamore that portal congestion was an etiological -factor, highly eulogised free catharsis. The truth, as usual, lay -between the opposing views. In other words, we must strike the -happy mean between adequate evacuation and excessive purgation, -for there is good reason to believe that the latter often<span class="pagenum"><a id="Page_374"></a>[374]</span> -so to speak, defeats its own end. It may determine more rapid -recurrence of the disorder or its perpetuation in a chronic and -asthenic form.</p> - -<p>Incidentally one may recall that the objections unfairly -launched against <i>colchicum</i> took origin in the misconception that -its good offices were referable to its <i>cathartic</i> action. Hence by -our forefathers the drug was pushed until the characteristic -“colchicum stools” appeared, with their attendant nausea and -prostration. This of course led to this valuable drug being -looked at askance, whereas the error lay, not in the drug, but -in the method of its administration, for, fortunately, its specific -effect in <i>gouty arthritis</i> may be secured without the induction of -depression, nausea, or purgation. Indeed, as Sir Alfred Garrod -long since pointed out, it “frequently proves of most benefit -when its operation is unattended with increased alvine -evacuation.”</p> - -<p>Albeit, from the tenor of our digression it must not be inferred -that purgation is inadvisable in gout, but only that this salutary -purpose must not be effected by <i>colchicum</i>. At the same time we -must not think that mere <i>purgation</i> will of itself allay the articular -inflammation, for it has been repeatedly shown that it exercises -little or no control in this direction; but, on the other hand, it -sweeps out irritating matter, promotes the return to a healthy -state of the alimentary canal, and in this way reinforces the -beneficial effect of colchicum.</p> - -<p>My own opinion is that, if seen just <i>before</i> or just <i>after</i> the acute -attack begins, it is wiser to secure a free action of the bowels -before placing the subject on colchicum, this the more imperatively -if it be a case of acute sthenic type supervening in a -robust subject evidently labouring under constipation. If there -be no palpable derangement of the liver, we may content ourselves -with ordering at bedtime a full dose of Gregory’s powder, or -Pil. rhei co. gr. 5-8, or Pil. colocynth co. gr. 5-8, followed in -the morning by a saline aperient. French physicians, especially -Robin, in such circumstances rely solely on sodium sulphate. The -salt has the advantage of not lessening the secretion of urine, and -the dose advocated is 1 ounce.</p> - -<p>If the conjunctivæ show an icteric tinge or the character of the -stools suggests that the liver is at fault, small doses of a mercurial -preparation, such as calomel (gr. 4) or blue pill, may be given at -night, either Pil. hydrarg. gr. 5 or Pil. hydrarg. gr. 1, in combination -with Pil. coloc. cum hyoscy. gr. 4, and the same followed in -the morning by 1-2 ounces of Mist. sennæ co. The nauseating -flavour of the latter is best disguised by 1-2 drachms of Glyl. -vanillæ, or for the “black draught” we may substitute 4-6<span class="pagenum"><a id="Page_375"></a>[375]</span> -drachms of sodium sulphate, a Seidlitz powder, or a full dose of -Carlsbad or Condal water.</p> - -<p>When mercurials are contra-indicated or from experience -known by the subject to disagree, podophyllin may be prescribed -in some such form as the following: Podophyllin gr. ¼ c̄, Pil. -coloc. hyoscy. gr. 4.</p> - -<p>In other instances the cholagogue effect of the mercurial is -procured by substitution for it of a small dose of the Ext. colchici -in combination with the compound colocynth pill. Our forefathers, -too, frequently prescribed colchicum and mercury -conjoined with aloes or colocynth, and the following is an excellent -and well-tried formula:—</p> - -<table class="rx"> - <tr> - <td>℞</td> - <td>Ext. colchici acet.</td> - <td>gr. ½</td> - </tr> - <tr> - <td></td> - <td>Ext. aloes barb.</td> - <td>gr. 1</td> - </tr> - <tr> - <td></td> - <td>Ext. hyoscy. vir.</td> - <td>gr. 1</td> - </tr> - <tr> - <td></td> - <td>Pil. hydrarg.</td> - <td>gr. 1½</td> - </tr> - <tr> - <td colspan="3">Fiat pil., 1.</td> - </tr> -</table> - -<p>In short, in the matter of the initial purgation the drug chosen -must be suited to the individual and the degree of purgation also -graded. The old rule was that if the belly is hard, the subject -can stand purging, but not otherwise; and it is, I think, a fairly -sound index. Mercurials in aged subjects are best avoided, and -likewise in those with defective kidneys. Salivation in their -instance is easily provoked, and Sir Alfred Garrod held that -mercury “in advanced forms of gout should be altogether avoided.” -French physicians think saline aperients preferable to the English -method of giving calomel, and unquestionably they are eminently -suitable for robust and plethoric subjects.</p> - -<h4><i>Colchicum in Acute Gout.</i></h4> - -<p>Whatever be its mode of action, colchicum still remains <i>par -excellence the</i> remedy for acute gout. As before noted, Dixon -and Maiden hold that <i>colchicine</i> has no action on the <i>metabolism</i> -or <i>excretion</i> of <i>purins</i>, nor on the <i>kidneys</i>. On the other hand, it -influences markedly the <i>leucocytes</i>, their number in the circulation -undergoing a primary decrease and a secondary increase. Bain, -it is true, found that under colchicum a slight <i>increase in uric acid -excretion</i> occurred, but thinks it extremely doubtful if its influence -in this direction is invariable.</p> - -<p>That colchicine should exert such a marked effect in gout and -yet apparently be destitute of any influence on <i>uric acid excretion</i> -is of course very striking. It calls, moreover, for more reflection -on the part of those who seem to contend that because a drug<span class="pagenum"><a id="Page_376"></a>[376]</span> -<i>increases uric acid elimination</i> it must necessarily be beneficial -both for the gout as well as for the victim.</p> - -<p><i>Method of Administration.</i>—In <i>initial</i> attacks the drug must be -exhibited with caution. Some persons are idiosyncratically -sensitive thereto. Attacks of faintness may ensue, or even -ordinary doses occasion purging or nausea and vomiting. Their -incidence shows either that the subject is abnormally sensitive -or the dose too large. Such untoward phenomena indicate its -abandonment or drastic reduction. With these reservations, -colchicum may be administered in every primary attack and most, -if not all, of the succeeding paroxysms.</p> - -<p>Albeit, the older the subject and the more ancient the gout, the -more warily should we proceed, especially if there is marked -irritability of the digestive system, renal disorder, or cardiac -degeneration. Robin holds that if <i>visceral</i> gout is present, or the -urine contains much <i>albumen</i>, no colchicum should be given.</p> - -<p>It is notorious that <i>old</i> persons stand colchicum badly. In -their instance we need be the less ready to resort to heroic doses -when we recall that acute gout is a self-delimited disease, and -while it would be improper to do nothing in elderly subjects -exhibiting visceral lesions, etc., it is well that we proceed -cautiously, so as to avoid the induction of circulatory depression -or the excitation of nausea or a diarrhœa which may be, and often -is, difficult of control. Moreover, if these untoward symptoms -are allowed to ensue, there is a tendency for the gout to recur as -soon as the effects of the colchicum have worn off.</p> - -<p><i>Preparations of Colchicum and Dosage.</i>—Those most commonly -in use are the <i>tincture</i> and <i>wine</i> of colchicum, and of these the -latter is most in favour. As to dosage, most authorities -agree that a full dose—30-40 minims of the vinum colchici—should -be given at the inception of treatment and followed -by smaller amounts, from 10-20 minims two or three times a -day.</p> - -<p>By French physicians the tincture of colchicum is preferred, -and by Robin that extracted from the <i>flowers</i> rather than the -seeds. The dose of our own official <i>Tinct. colchici seminum</i> -ranges from 5-15 minims, and by the French Codex the maximum -single dose is placed at 25 minims, and the maximum intake -during twenty-four hours at 100 minims approximately. It -may be noted that preparations from the <i>seeds</i> are more purgative -than those derived from the corn. Lastly, we have the official -extract of colchicum and the acetic extract. The dose of the -former ranges from ¼-1 grain, and it is frequently given in the -form of a pill with ipecacuanha and mercury. The addition of -a small dose of atropine is often advisable, to obviate the vomiting<span class="pagenum"><a id="Page_377"></a>[377]</span> -and diarrhœa often primarily induced by increase of peristalsis. -By many the acetic extract is preferred, J. S. Matthews holding -that the effective dose ranges from 2-6 grains.</p> - -<p>Turning now to discuss the most opportune juncture at which -to administer colchicum, certainly in the <i>initial</i> and the earlier -paroxysms we may with advantage postpone the giving of -colchicum pending <i>free clearance of the bowels</i>. No harm will -follow its being withheld until the <i>second</i> day. Indeed, many -physicians, both British and Continental, counsel delay in its -exhibition until the fit is well established.</p> - -<p>Again, in <i>primary</i> paroxysms—viz., while ignorant of the -personal equation in respect of <i>colchicum</i>—it is well that our -maximum dose should not exceed 20 minims, and when the bowels -have not been previously purged, the drug should be combined -with sulphate and carbonate of magnesia, as in the following -prescription:—</p> - -<table class="rx"> - <tr> - <td>℞</td> - <td>Magnesii sulphatis</td> - <td>gr. 60</td> - </tr> - <tr> - <td></td> - <td>Magnesii carbonatis</td> - <td>gr. 10</td> - </tr> - <tr> - <td></td> - <td>Potassii citratis</td> - <td>gr. 30</td> - </tr> - <tr> - <td></td> - <td>Vini colchici</td> - <td>♏︎ 20</td> - </tr> - <tr> - <td></td> - <td>Aquæ menthæ viridis</td> - <td>ad unciam.</td> - </tr> - <tr> - <td colspan="3">Misce. fiat mistura. Two tablespoonfuls with two of - hot water every three hours until bowels have been freely opened.</td> - </tr> -</table> - -<p>This achieved, the sulphate of magnesia may be omitted, and -the mixture taken every six instead of every three hours; but it -is a good plan to keep the original mixture at hand, giving a dose -every morning while the acute stage lasts. Then during the day -the colchicum should be persisted with either in the form of the -wine or the tincture.</p> - -<p>Moreover, there are often special indications to be met. Thus -the skin in acute gout is often hot and dry, and the urine unusually -scanty and high-coloured. In this event the colchicum may -with advantage be given with the citrate, bicarbonate or nitrate of -potash, so as to produce a diaphoretic and diuretic effect. In -other instances acidity is a prominent symptom, and here the -combination of colchicum with the citrate of potash and magnesia -will be found useful.</p> - -<p>As the intensity of the inflammation wanes and the local pain -and tension subside the dose of the colchicum should be gradually -diminished; but even after convalescence is established it may -advantageously be continued for a few days in small doses, say, -5 minims of the vinum colchici three times a day. The condition -of the tongue will usually furnish a safe index, as rarely will it -clean up prior to abatement of the gouty fit.</p> - -<p><span class="pagenum"><a id="Page_378"></a>[378]</span></p> - -<p>In <i>subsequent</i> paroxysms and alike in the <i>acute exacerbations</i> -that chequer the course of <i>chronic</i> gout we may, in the absence of -<i>idiosyncrasy</i> or other contra-indication, proceed more boldly. -Thus, if the bowels have not previously been briskly purged, we -may at once prescribe the following formula:—</p> - -<table class="rx"> - <tr> - <td>℞</td> - <td>Vini colchici</td> - <td>♏︎ 15-20</td> - </tr> - <tr> - <td></td> - <td>Magnesii carbonatis</td> - <td>gr. 15</td> - </tr> - <tr> - <td></td> - <td>Magnesii sulphatis</td> - <td>gr. 60</td> - </tr> - <tr> - <td></td> - <td colspan="2">Aquæ cinnamomi ad ℥j.</td> - </tr> - <tr> - <td colspan="3">Fiat mistura, ℥ij. statim sumenda et ℥j. quartis horis p.p.a.</td> - </tr> -</table> - -<p>The primary dose, as will be noted, will contain either 30 or 40 -minims of the wine, and, though Sir Alfred Garrod prescribed up -to a drachm, it will scarcely, if ever, be necessary to exceed -30-40 minims. The subsequent dose of from 15-20 minims -may after a day or two be reduced, and instead the mixture -given in ½-ounce doses three or four times a day. Or, if preferred, -the mixture in its reduced dosage may be renounced in favour -of a pill containing either the extract of colchicum or, what -many consider even better, the acetic extract thereof. Thus -the following pill may be taken every night for a few days, -and then on alternate nights:—</p> - -<table class="rx"> - <tr> - <td>℞</td> - <td>Ext. colchici</td> - <td>gr. ¼</td> - </tr> - <tr> - <td></td> - <td>Aloin</td> - <td>gr. ⅛</td> - </tr> - <tr> - <td></td> - <td>Ext. bellad. alcoh.</td> - <td>gr. ⅛</td> - </tr> - <tr> - <td></td> - <td>Capsicin</td> - <td>gr. ⅟₂₀</td> - </tr> - <tr> - <td></td> - <td>Ext. rhei</td> - <td>gr. 1</td> - </tr> - <tr> - <td colspan="3">Fiat pil., 1.</td> - </tr> -</table> - -<p>The acetic extract may be given in larger doses, and was in -great favour as the chief constituent of many so-called “gout -pills” in combination with ipecacuanha and mercury:—</p> - -<table class="rx"> - <tr> - <td>℞</td> - <td>Ext. colchici acet.</td> - <td>gr. 1½</td> - </tr> - <tr> - <td></td> - <td>Pulv. ipecac. co.</td> - <td>gr. 1½</td> - </tr> - <tr> - <td></td> - <td>Ext. colocynth co.</td> - <td>gr. 1½</td> - </tr> - <tr> - <td colspan="3">Fiat pil., 1 nocte sumenda.</td> - </tr> -</table> - -<p>An excellent formula, in which the colchicum is combined with -mercury, has already been furnished on a preceding page. Needless -to say, it should, like the above pill, be followed in the morning, -if necessary, by a mild saline purgative.</p> - -<p><i>Colchicine.</i>—This, the active principle of colchicum, has of -recent years been widely and successfully employed in acute gout, -as well as in exacerbations of the chronic type. By some subjects, -especially the old, it is often better borne than colchicum preparations. -The dose ranges from ⅟₁₀₀-⅟₃₂ grain in a pill. By the -French Codex the maximum single dose is fixed at ⅟₃₂ grain, and<span class="pagenum"><a id="Page_379"></a>[379]</span> -the maximum administered during twenty-four hours should not -exceed ⅟₁₆ grain approximately.</p> - -<p>The following is a suitable combination in an elderly subject, -and it may be noted that the drug has been found of use, too, in -cerebral congestion and uræmia:—</p> - -<table class="rx"> - <tr> - <td>℞</td> - <td>Colchicine</td> - <td>gr. ⅟₁₀₀</td> - </tr> - <tr> - <td></td> - <td>Ext. belladon. alcoh.</td> - <td>gr. ⅛</td> - </tr> - <tr> - <td></td> - <td>Ext. nucis vomicæ</td> - <td>gr. ¼</td> - </tr> - <tr> - <td colspan="3">Fiat capsule or cachet, 1 every three or four hours.</td> - </tr> -</table> - -<p>In robust subjects the colchicine may be given in larger doses. -Luff states that few patients will tolerate ⅟₅₀ grain, because of -the diarrhœa and griping pains produced. He found that -colchicine (⅟₇₀ grain), in combination with henbane and nux vomica -in the form of a pill, rapidly relieved gout when taken every three -or four hours.</p> - -<p>Or as a substitute we may use the <i>salicylate of colchicine</i>, -the dose of which is ⅟₆₀ grain. Colchicine is readily soluble in -methyl salicylate, and is conveniently administered in the form -of capsules, each containing ⅟₂₅₀ gram (Martindale). In acute -gout one capsule may be given every two hours, or two -capsules three or four times a day. These doses are well within -the limits of safety, and, if necessary, may be combined with nux -vomica and belladonna; but with the alkaloids, as with the -colchicum itself, it is essential that the bowels should be kept -freely opened. Also with the waning of the pain and inflammation -the colchicine or its salicylate should be given less frequently, -so as to obviate any depression.</p> - -<p><i>Atophan.</i>—This is a yellowish cream-coloured amorphous -powder of the composition 2-phenylchinolin 4-carbonic acid. -Its use has been much extolled both in <i>acute</i> and <i>subacute</i> gout. -The dose ranges from 30-45 grains daily for three to four days, -according to some authorities, but others consider that it may be -taken for prolonged periods with advantage. It is most conveniently -exhibited in the form of tablets containing 4 or 8 grains. -<i>Agotan</i>, a drug identical with that formerly sold under the German -registered name “atophan,” is supplied in the form of crystalline -powder and in 7½-grain tablets, and appears to be equally efficient.</p> - -<p>Atophan is incompatible with sodium bicarbonate and other -alkalies <i>in vitro</i>, but Martindale and Westcott “did not find it -incompatible with potassium iodide.” It has been repeatedly -noted that, following the intake of atophan, the uric acid content -of the <i>blood</i> falls and the <i>urinary uric-acid output</i> increases. -Weintraud in gouty patients on a <i>purin-free</i> diet noted that -after atophan the quantity of uric acid excreted in the urine was<span class="pagenum"><a id="Page_380"></a>[380]</span> -more than doubled, but subsequently the excretion fell below -normal.</p> - -<p>Even in healthy individuals when taking atophan the urine -becomes turbid from the presence of <i>urates</i>. This excess of uric -acid in the urine may in gouty individuals be precipitated in the -urinary tract, and so induce an attack of <i>gravel</i>. Consequently -Weintraud advises that the drug be taken with <i>alkalies</i>, either -sodium bicarbonate or alkaline waters. Drs. Jansen and Plum, -of Copenhagen, during their recent visit to the Royal Mineral -Water Hospital, Bath, informed me that they had met no instances -of <i>gravel</i>, but in several of their cases atophan had induced -<i>urticaria</i>.</p> - -<p>As to the simultaneous intake of <i>alkalies</i>, while the precaution -is probably desirable, I have known gouty patients take atophan -<i>without</i> alkalies for several weeks in full doses without any apparent -ill effects. Brugsch, indeed, states that in <i>polyarthritis urica</i> the -subjects are able to take 15-30 grains of atophan per diem for -a year without any affection of the kidneys. Moreover, uric acid -excretion was increased throughout the whole period, and when -the drug was discontinued, the pains recurred.</p> - -<p>As to the usurpation of colchicum by atophan, I do not think -it is at all likely, for it does not, I consider, exert the specific -effect of the former on the gouty inflammatory process, taking the -humbler <i>rôle</i> of obviating the formation or promoting the absorption -and elimination of <i>uratic deposits</i>. In other words, colchicum -influences the <i>causa causans</i> of gouty inflammation, atophan only -the <i>consequences</i> or <i>sequels</i> thereof.</p> - -<p>The most favourable juncture at which to prescribe atophan -is <i>at the close of a paroxysm</i>. I have myself been much impressed -with the manner in which it produces softening and palpable -diminution in the size of tophaceous deposits, so much so, -indeed, that I feel sure we have in this drug a valuable agent -wherewith to <i>prevent the formation of uratic deposits</i>.</p> - -<p>A two or three weeks’ course of atophan after an acute attack -is, I have found, very advantageous, in doses of 30-45 grains -per diem, after meals. It may, for the special reasons given, be -well combined with an alkaline stomachic mixture taken half an -hour or more before food.</p> - -<table class="rx"> - <tr> - <td>℞</td> - <td>Potassii bicarbonatis</td> - <td>gr. 15</td> - </tr> - <tr> - <td></td> - <td>Sodii bicarbonatis</td> - <td>gr. 20</td> - </tr> - <tr> - <td></td> - <td>Spts. ammoniæ aromat.</td> - <td>♏︎ 20</td> - </tr> - <tr> - <td></td> - <td>Tinct. zingiberis fort.</td> - <td>♏︎ 5</td> - </tr> - <tr> - <td></td> - <td colspan="2">Inf. aurantii co. ad unciam.</td> - </tr> - <tr> - <td colspan="3">Fiat haustus, thrice daily well diluted with water.</td> - </tr> -</table> - -<p><span class="pagenum"><a id="Page_381"></a>[381]</span></p> - -<p>To sum up, our medicinal treatment of acute gout consists in -<i>initial purgation</i>, followed by maintenance of an adequate daily -evacuation; secondly, the exhibition of <i>colchicum</i> or its active -principle and continuance of the same in diminishing doses until -pain and inflammatory phenomena have departed. With the -passing of the paroxysm <i>atophan</i> should be resorted to in -combination with an alkaline stomachic mixture. Supervision -of the subject should not cease until the digestive and assimilative -functions have, as far as possible, attained functional efficiency, -for it is certain that this is the most important point in the -management of the gouty constitution. Conjoined therewith, -the bowels should never be allowed to become constipated, the -urine maintained free from acid lithates, and the skin active by -regular exercise.</p> - -<p><i>Alternative Remedies in Acute Gout.</i>—Of the various drugs -advocated as substitutes for colchicum the salicylate group alone -seems to have evoked something like enthusiasm. Thus Germain -Sée affirmed that sodium salicylate was the best remedy for gout, -whether of acute or chronic type. In this country Haig strongly -upheld its claim. On the other hand, Ebstein, when he used this -salt in acute gout, found that the inflammation, though it quickly -subsided in one joint, immediately reappeared in another, even -though the administration of the drug was continued.</p> - -<p>Lecorche, again, though he found it useful in <i>acute</i> gout, was -equally certain that it was altogether inferior to colchicum. It -did lessen the pain and the violence of the paroxysm, but in no -way shortened its duration. But, on the other hand, he attached -a <i>prophylactic</i> value to it in chronic gout marked by recurring -subacute attacks. His method was to give it in the intervals -of paroxysms in doses of from 60-80 grains a day, whereby he -claimed to abort attacks, prevent ankyloses, and facilitate -absorption of uratic deposits.</p> - -<p>As to its mode of action, salicylate of soda, both in gouty and -healthy subjects, determines an immediate increase in the uric -acid excretion, 30-60 per cent. The increase, however, is but -ephemeral, the excretion of uric acid sinking gradually to normal -in about forty hours, and this whether the drug be persisted with -or not. The increase in total nitrogen excretion does not reach -10 per cent.</p> - -<p>Discussing this mode of response, MacLeod (who noted the same -after citrates) is of opinion that salicylate of soda and citrate act, -not by influencing the metabolic processes that originate uric -acid, but by promoting the excretion thereof. Walker Hall and -Magnus Levy, albeit, suggest that the increase is due to diminution -in the normal destruction of purins in the organism, with resulting<span class="pagenum"><a id="Page_382"></a>[382]</span> -transmission of the same in larger quantities to the kidneys for -excretion. It is possible therefore that in the presence of -sodium salicylate there is diminished oxidation of uric acid.</p> - -<p>Bain, however, studying the elimination of nitrogen in a gouty -subject, found, contrary to expectation, that after sodium -salicylate there ensued only a small increase in the uric acid, with -a slight augmentation of the alloxur bases relative to the acid. -We see therefore that all the above observers agree that an -<i>increased uric acid output</i> in the urine follows the administration -of salicylate of sodium, though they differ in opinion as to the -manner of its production.</p> - -<p>As to the employment of salicylate of soda in <i>acute</i> gout, -it must, I think, be seldom called for, save in the presence of -<i>idiosyncratic</i> sensitiveness to <i>colchicum</i>. Now, though of this -latter much has been written, yet I venture to affirm it is -exceptional, and the adverse symptoms are attributable rather to -injudicious dosage of the individual than to inherent peculiarities -on his side in respect to this valuable drug.</p> - -<p>If we should encounter such an instance, there is no objection -to our giving the salicylates of sodium or potassium a trial, -especially in an acute febrile attack occurring in a healthy subject. -In isolated cases the relief to pain may be swift and striking; but, -generally speaking, the results are neither so decisive nor so prompt -as those obtained in suitable cases by colchicum. The potassium -and lithium salicylates are usually given the preference, and they -may be combined with citrate or bicarbonate of potash. If the -latter salt be used, the draught will prove more grateful if given in -effervescent form, viz., by the addition of citric acid or lemon juice.</p> - -<p>Frequently it happens that the patient, to begin with, has been -placed on colchicum, and, symptoms of irritation having supervened, -the drug has had to be withdrawn. The tardy resort then -to salicylates is fortunately rather beneficial than otherwise, -for, apart from its analgesic effect, it reinforces the increased uric -acid output in the urine that follows the attack, and so tends to -counteract the tendency to uric acid deposition.</p> - -<p>There is yet another contingency in which resort to salicylates -may be indicated, viz., in those long-standing cases of <i>chronic gout -with recurring exacerbations</i> in which the colchicum, formerly -beneficial, has now through acquired tolerance become impotent. -Here, either during or immediately after the acute phases, the -salicylates may be exhibited, if the stomach be tolerant and there -be an absence of <i>cardiac</i> or <i>renal</i> degeneration. As to the employment -of salicylates in massive doses in the <i>inter-paroxysmal periods</i> -as a <i>prophylactic</i> measure, I think this is better attained by -occasional courses of <i>atophan</i>.</p> - -<p><span class="pagenum"><a id="Page_383"></a>[383]</span></p> - -<p>Lastly, there are instances in which both colchicum and -salicylates appear to be contra-indicated. In this event we may -either rely simply on <i>alkalies</i>—and we have Duckworth’s -authority that in many cases of <i>acute gout</i> they have proved -satisfactory—or we may adopt Sir Alfred Garrod’s plan of -giving <i>quinine</i> (2½-5½ grains) suspended by tragacanth in -combination with the bicarbonate or citrate of potash. By -this means the pyrexia is controlled, and, according to the -above authority, any tendency on the part of the disorder to -wander from joint to joint; and he holds it especially valuable -in those <i>subacute</i> attacks that so commonly chequer the course -of <i>chronic</i> gout.</p> - -<p><i>Thyminic</i> or nucleotin-phosphoric acid in doses of 5-10 grains -has also been highly eulogised, being held to have an affinity for -and a solvent action on uric acid. But Walker Hall, while he -agrees that the results obtained in gout are encouraging, yet -from his own experiments does not find that “the improvement -is at all associated with any change in uric acid excretion—a result -which also applies to citerin.”</p> - -<p>As to <i>quinic acid</i> and its synthetic combinations, their popularity -seems to have been evanescent. It is claimed that “urosin” or -lithium quinate speedily controls the acute manifestations of -gout, this apparently without any evidences of cinchonism, even -though given in 7½-grain tablets ten times daily in acute -paroxysms. Others give quinic acid in combination with -piperazine, <i>i.e.</i> “sidonal” in doses of 1-1½ grains per diem. -But of these, as well as of many other vaunted specifics, I feel -inclined to say, with Bianca, “Old fashions please me best; I -am not so nice to change true rules for new inventions.”</p> - -<p><i>Anodynes in Acute Gout.</i>—On this point it may be recalled that -such was the prejudice at one time against colchicum that -Ebstein thought it preferable to relieve the pain of acute gout by -hypodermic injections of morphia, which, he thought, acted -“quicker, more easily, and with less danger.” Fortunately, -however, it is only very exceptionally that colchicum fails to -mitigate the pain in acute gout.</p> - -<p>In rebellious instances salicylate of soda in full doses for a few -hours sometimes succeeds. Hypodermic injections of morphia -must rarely, if ever, be called for, and I have never had occasion -to invoke them. In fact, opium in any form is best avoided, and -if unavoidable is best given in the form of Dover’s powder in -combination with aspirin and phenacetin, viz., 2½ grains of each -in a cachet at bedtime. Luff in some cases found a full dose of -extract of hyoscyamus a very useful anodyne, and if sleeplessness -through pain prevails, advises 7 grains of veronal or 10 grains of<span class="pagenum"><a id="Page_384"></a>[384]</span> -trional. Sir William Whitla’s “routine hypnotic in gout” is -paraldehyde.</p> - -<p>All these are preferable to opium in any form, for we deal with -a disease in which <i>defective elimination</i> is a prominent feature, -and that we should exhibit unnecessarily a drug which inhibits -all excretory processes save that subserved by the skin seems -wholly irrational. Of this we have an object lesson in the clay -stools that in some gouty subjects, as Burney Yeo remarked, -persist for some days after even a very small dose of morphia. -My own rule is to rely on colchicum as far as possible, and for any -extra anodyne effect on local applications, to the consideration -of which I now proceed.</p> - -<h4><i>Local Measures in Acute Gout.</i></h4> - -<p>The affected limb must be kept at rest on a firm pillow and -slightly raised above the body level. The inflamed part should -be protected from pressure by a cradle. In the majority of -instances, as the elder Garrod long since pointed out, the only -local application needed is cotton wool covered with oiled silk, -evenly and lightly bandaged. By this means the joint surface -is kept both warm and moist, and moisture is important, as dry -heat is not grateful and seems to aggravate the pain. The -dressing soon becomes wet, requires changing two or three times -in the twenty-four hours, when dry warm wool should again -be applied, and in this way a local vapour bath of sorts is provided -for the inflamed part.</p> - -<p>If pain be marked, hot fomentations or stupes or even a foot-bath -may be substituted. At one time warm spirituous lotions -on lint covered with oiled silk were popular, whisky and water -being much in vogue. Others (Pye-Smith) spoke well of a lotion -containing 1 drachm of sulphuric ether to 6 ounces of water. -Some pack the joint with warm alkaline lotions to which opium -or belladonna, or both, are added; but, whether dealing with -spirituous or alkaline lotions, all are agreed that <i>cold</i> applications -should be carefully shunned.</p> - -<p>As to anodyne preparations, we suffer from what may be truly -described as <i>un embarras de richesse</i>; but the inexplicable -variability of response is such that it is always well to have another -shot in one’s therapeutic locker. Practically all the analgesic -remedies in use have been recommended by some one or other as -useful for the relief of pain in acute gout. The mere enumeration -of these might be indefinitely extended, for in truth every one -has a favourite remedy wherewith to meet certain indications,<span class="pagenum"><a id="Page_385"></a>[385]</span> -and the good results obtained are exactly proportional to the skill -displayed in exhibiting their use. We should not, however, resort -forthwith to the more potent analgesics. It is wiser to give the -simpler remedies a prior trial, such as poppy-head fomentations. -If these fail, the liniment or unguentum methyl salicylatis co. -may be tried, applied on lint covered with oiled silk and a flannel -bandage. Equal parts of chloroform and belladonna or of opium -and menthol liniment are also very soothing when sprinkled on -lint and covered with cotton wool.</p> - -<p>In the more intense cases with great local sensitiveness the -following preparations may be lightly applied to the affected -area with a brush. Anodyne colloid is one of the most -reliable, or we may use glycerine of belladonna or atropine, -subsequently covering the part with warm, moist dressings or -spongiopiline enveloped in oiled silk, cotton wool, and a flannel -bandage. In using atropine preparations, however, care must be -exercised, as absorption through the unbroken skin may readily -cause toxic symptoms.</p> - -<p>In less acute types or as local sensitiveness declines various -ointments may be gently rubbed into the affected joint, and in -this way the beneficial effects of massage superadded. The most -suitable unguents are those containing methyl salicylate in -hydrous wool fat with or without menthol, or the methyl -salicylate may be mixed with equal parts of olive oil and applied -with friction. Used in this way, it is rapidly absorbed, and is -much to be preferred to the natural oil of winter-green, which not -infrequently proves very irritating to the skin.</p> - -<p>Under the influence of one or other of the foregoing methods, -the pain in these forms of acute gout is usually quickly subdued. -Occasionally, however, owing to incomplete absorption of -inflammatory exudate, the case proves more obstinate, and a -variable degree of pain and stiffness lingers on in the affected -articulation.</p> - -<p>If means permit, the ideal course to pursue is for the patient to -be sent to some spa where, conjointly with the general treatment, -he may enlist the advantage of hydrotherapy, massage, and so -forth. In default of such facilities, we must of course fall back -upon friction with liniments, being careful not to induce tenderness -of the joint. Of these there are endless varieties, those containing -ammonia, turpentine, camphor, or capsicum being most in -vogue. Inasmuch as their efficacy is largely referable to the -rubbing which accompanies their use, we should favour preparations -containing oleic acid, either alone or diluted with a fatty -oil. As an oily liniment perhaps one of the most useful is the -linimentum succini co., containing equal parts of the oils of amber<span class="pagenum"><a id="Page_386"></a>[386]</span> -and clove combined with twice the quantity of olive oil, or one -of the following excellent combinations may be selected:—</p> - -<table class="rx"> - <tr> - <td>℞</td> - <td>Olei origani vel olei terebinthini</td> - <td rowspan="2" style="vertical-align: middle;">Partes æquales.</td> - </tr> - <tr> - <td></td> - <td>Linimenti ammoniæ.</td> - </tr> - <tr> - <td colspan="3">To be applied with friction to the affected part.</td> - </tr> -</table> - -<table class="rx"> - <tr> - <td>℞</td> - <td>Ætheris</td> - <td>1 drachm.</td> - </tr> - <tr> - <td></td> - <td>Linimenti belladonnæ</td> - <td>½ ounce.</td> - </tr> - <tr> - <td></td> - <td>Tinct. capsici</td> - <td>To 2 ounces.</td> - </tr> - <tr> - <td colspan="3">To be well rubbed into painful parts night and morning.</td> - </tr> -</table> - -<p>When a joint is the seat of fixed pain with definite thickening, -it may be necessary to resort to <i>blisters</i>; but frequently they are -so utilised as to merit the aspersion of “adding additional distress -to unrelieved pain.” They are of course unsuitable for cases -with <i>acute serous effusion</i> of recent origin; but are often beneficial -when applied over joints, bursæ, or tendon sheaths, when the seat -of <i>long-standing passive distension</i>.</p> - -<p>Garrod held them of most advantage in <i>gout</i> of <i>asthenic</i> character -with lingering effusion; but he thought them inadvisable in the -later stages of gout with <i>defective kidneys</i> and where the joints -were the seat of massive uratic deposits, as in the last event sores -difficult of healing may follow.</p> - -<p>In the vast majority of instances such drastic counter-irritation -is unnecessary, as the pain usually relents to less strenuous -measures. For the dissipation of exudates and thickening -nothing is superior to iodine and mercurial preparations. Painting -with strong iodine may occasion soreness, but not if the glycerinum -iodi be used. Better still is it if we use iodine preparations that -admit of gentle inunction. The iodide of potassium and soap -liniment is of course most reliable, or we may use one of the -proprietary preparations, <i>e.g.</i>, leukion. The oleate of mercury -(10 per cent.) is often useful, and if pain linger on in the joint, -may be combined with morphia (½ grain to 1 drachm). Ichthyol -lanoline also deserves mention, and is best rubbed in after a -fomentation followed by a dry pack. It is extremely probable -that the stimulant and absorbent action of these agents is -markedly reinforced by the <i>friction</i> which accompanies their -usage.</p> - -<p>In conclusion, it must be recalled that the swelling, stiffness, -and pain are of dual origin, viz., in part due to <i>inflammatory -products</i> and in part to <i>uratic deposits</i>, and it is the former that -will be the most influenced by the foregoing measures. As to the -means available for the reduction or dissipation of <i>tophaceous</i> -matter, we shall best postpone their consideration until we come -to discuss the treatment of tophi.</p> - -<p><span class="pagenum"><a id="Page_387"></a>[387]</span></p> - -<p><i>Ionisation in Acute Gout.</i>—The introduction of medicinal -substances into the interior of the joints by means of an electrical -current is now in extensive vogue, both as a means of relieving -pain and promoting absorption in periarticular and synovial -affections. It is of course in the more accessible or superficial -articulations that its beneficial effects are most easily attainable.</p> - -<p>The sensitiveness of the parts in acute gout is such that I have -never felt justified in invoking ionisation therein. Nevertheless -Finzi tried it in two cases of acute gout. Instant relief of pain -and diminution of swelling followed the first <i>séance</i>, while in -sequence to a second all local tenderness disappeared. Finzi -used a combination of lithium and iodine, the former at the -positive and the latter at the negative pole. I would only add -that in non-gouty forms of arthritis, if relief of pain be desired, -<i>salicylic</i> ions, by general consent, would appear to be the most -reliable. As far as I know, most authorities confine ionisation to -<i>chronic</i> articular gout, and to this I shall refer later.</p> - -<p><i>Massage.</i>—The success that follows the application of stimulant -or absorbent preparations in the after-treatment of acute gout -largely depends on the skill and persistence with which the -rubbing or kneading is performed. Hence it is that treatment -by external medication has been largely superseded, and rightly -so, by skilled <i>massage</i>, the outstanding advantages of which find -increasing appreciation.</p> - -<p>It need hardly be said that massage is contra-indicated in the -acute, and its use should be confined to the <i>subacute</i>, stage. Moreover, -I would suggest that its aid be sought more frequently during -the <i>decline of acute attacks</i>, instead of its being reserved, as it very -largely is, for the more chronic varieties of articular gout. In -the latter instance organisation of the inflammatory products -has already ensued, and their dispersal is correspondingly more -difficult, whereas in the former the soft nature of the effused -material renders dissipation more easy and, what is more important, -minimises the chances of recurrence. Gentle massage also -will promote the <i>absorption</i> and <i>resolution</i> of <i>tophi</i>, for the uratic -deposits, even when pre-existing, are often found after an attack -to be <i>softened and more mobile</i>, and now is the time to profit by -these changes, so as to compass their elimination.</p> - -<p>In these <i>subacute</i> stages, of course, vigorous excitation must -be avoided, <i>effleurage</i> or <i>light stroking</i> being the only permissible -measure at this stage; and of course it should be exercised -<i>centripetally</i>. In presence of any marked sensitiveness, too, it -is advisable that <i>derivative</i> massage of the limb above the joint -should always precede any direct friction of the latter.</p> - -<p>The measure of success will depend on the technique of the<span class="pagenum"><a id="Page_388"></a>[388]</span> -masseur. If he be unskilful or rough, aggravation of the inflammatory -process will almost certainly ensue, with prolongation of -stiffness and pain. He should proceed tentatively, the energy -displayed being gradually increased as the parts grow more -tolerant of manipulation.</p> - -<p>Again, it is at the close of a massage <i>séance</i> that <i>passive movements</i> -are most advantageously employed, and where irritation -and pain follow their performance, gentle centrifugal stroking of -the actual joint surface will exercise a grateful, soothing effect.</p> - -<p><i>Surgical Methods.</i>—The intensity of the inflammation and -swelling in acute gout has, as before said, sometimes led to its -confusion with <i>purulent arthritis</i>. It was just such a mishap that -led Riedel to discuss seriously the operative treatment of gout -when of <i>monarticular</i> type, <i>e.g.</i>, in the great toe joint. He cites -the case of a man, aged forty-five, suffering with acute gout of -classic site which was operated on under the impression that the -joint contained pus. None issued, but the synovial membrane -was found covered with urates. The latter were removed, the -wound healed in five weeks, and no recurrence of articular gout -followed till fourteen years after. The second example occurred -in a lady seventy years of age, who likewise suffered an acute -attack of gout in the right great toe joint. An incision was made -and the revealed urates removed, and the wound healed in a few -weeks, and no subsequent attacks followed!</p> - -<p>Despite the apparent good results obtained, one can scarcely -believe that incision and removal of urates during <i>acute</i> gout -will ever be seriously considered. Nevertheless the apparent -impunity, if not actual benefit, that followed the above operative -interference does, I think, indicate that in these aseptic days we -need be less timorous; in other words, that, while the operative -treatment of acute gout is unnecessary, yet in <i>chronic</i> cases -surgery has its sphere. But to this I shall return later, when -discussing the treatment of tophaceous deposits in chronic gout.</p> - -<hr class="chap x-ebookmaker-drop"> - -<div class="chapter"> - -<p><span class="pagenum"><a id="Page_389"></a>[389]</span></p> - -<h2 class="nobreak" id="CHAPTER_XXIX">CHAPTER XXIX<br> -<span class="smaller">MEDICINAL AND OTHER MODES OF THERAPY (<i>continued</i>)—INTER-PAROXYSMAL -PERIOD</span></h2> - -</div> - -<h3><span class="smcap">Treatment in the Inter-paroxysmal Period</span></h3> - -<p>Despite the fact that <i>heredity</i> plays so dominant a <i>rôle</i> in the -genesis of gout, how relatively scanty the attention paid to -<i>prophylactic</i> measures! It is the <i>second</i>, never the initial, attack -of gout that we endeavour to avert. Surely to inhibit the -development rather than to prevent the recurrence of the malady -is the better part. The idea is not wholly utopian, for such -shrewd observers as Scudamore, Austin Flint, and others, were -convinced that by timely and judicious intervention a threatened -outbreak might be averted or at least its severity mitigated.</p> - -<p>It was to this end that in a preceding chapter I urged the -desirability of more attention being paid to the <i>prodromal</i> -symptoms of gout and the clarifying light that might be thrown -on otherwise inexplicable derangements by the disclosure of a -<i>hereditary</i> tendency thereto. The failure to elicit such familial -predisposition is but too common, and so those who may be led -to expect the gout by inheritance are bereft of all the benefit that -might accrue from a prophylactic regimen.</p> - -<p>The indications may, indeed, be more explicit, for, apart from -hereditary proneness, some subjects, even though they may -never have experienced an <i>articular</i> outbreak, yet exhibit <i>tophi</i>, -and therewith frequently suffer from gastric or hepatic -disturbance. Obviously, is not this the opportune time for -<i>prophylaxis</i>—the institution of hygienic and dietetic rules -conjoined with the occasional use of medicines? For the -“potentially” gouty, as Scudamore said, cannot “too early be -taught to pay the most careful regard to their constitution, nor -too surely confirm the best habits by long practice.” We hear -much nowadays of the “beginnings” of disease, and who can -doubt that this is a fruitful sphere for their study?</p> - -<p>Unfortunately it is, as a rule, only when the disease has made -its invasion that we wake up to our responsibilities in this respect; -but happily even then we may do much to prevent consolidation -of its tyranny, for even in those who have experienced regular -gout there are derangements to correct, warnings to note, if we -do but take heed. Of these the more common are dyspepsia<span class="pagenum"><a id="Page_390"></a>[390]</span> -and costiveness, signs of portal congestion, etc., not to mention -local symptoms, <i>i.e.</i>, the onset of pricking and tenderness in -already existing tophi, twinges in the toes, etc.</p> - -<p>We see therefore that in regard to the prophylaxis of gout the -victims fall into two main groups, <i>i.e.</i>, firstly, the “potentially” -gouty, who as yet have not experienced arthritic outbreaks, and, -secondly, those who have, and wish to obviate their recurrence. -Happily the premonitory gastric symptoms, though varied in -character, are in both instances more or less similar; nor need -I say that in either alike medicinal measures are but the smallest -part of the <i>prophylaxis</i>, whose chief stay and strength must be -the golden rule of <i>temperance</i> in eating and drinking conjoined with -adequate exercise. For, whatever our views as to the <i>proximate</i> -origin of gout, there is every reason to suppose that -the principal <i>exciting</i> cause resides in the <i>alimentary</i> canal. -As Sydenham long since said, “The more closely I have -thought upon gout, the more have I referred it to indigestion -or to the impaired concoction of matters both in the -parts and the juices of the body.” Even so to-day do medical -men suffering from gout tell me that they, like Sydenham, -have found by experience that almost invariably <i>dyspeptic</i> -symptoms are the forerunners of attacks, and that their -avoidance or timely correction is the best means wherewith to -avert paroxysms.</p> - -<p>As to the nature of the “indigestion,” it is of <i>subacute</i> or <i>chronic</i> -type, and only very exceptionally is it acute. As to symptomatology, -there is nothing distinctive about the “dyspepsias” of -the “gouty,” save perhaps their marked tendency to recurrence, -the facility with which they are occasioned by trivial causes, their -frequent obduracy to ordinary measures, and their response to -such as take cognisance of the constitutional factor.</p> - -<p>Nevertheless such is the frequency and persistence often of -gastric derangements in the “gouty” that it may safely be -affirmed that the treatment of these subjects in their <i>inter-paroxysmal</i> -periods is essentially that of the “dyspeptic.” It is, -in truth, the basal indication in their therapy, for correction of -the “gouty” man’s digestive disabilities is the surest way to -prevent articular outbreaks, or, failing this, to postpone their -recurrence or mitigate their severity.</p> - -<p>The primary object of medicinal treatment is the restoration -to <i>functional efficiency</i> of the <i>alimentary</i> tract and its <i>accessory -glands</i> and maintenance of the action of the <i>kidneys</i> and <i>skin</i>. -While <i>diet</i> and general hygienic regulations are all essential, we -often have to fight the vicious inclination of the victim who is -desirous that some medicine may be found which will avert the<span class="pagenum"><a id="Page_391"></a>[391]</span> -threatened gout without his being obliged to forego his accustomed -indulgence.</p> - -<p>He must be promptly and firmly disabused of this fallacy. -Indiscriminate drugging is the bane of these cases. They fly from -one remedy to another rather than give up this or that excess, and -so frequently superimpose a “drug dyspepsia” upon the original -disorder.</p> - -<p>The most common form of indigestion in the “gouty” is <i>atonic</i> -dyspepsia. The primary indication is, of course, to correct the -dietetic errors, <i>i.e.</i>, to remove the cause, and, secondly, to stimulate -the secretory and motor power of the stomach. To this end, the -alkalies and alkaline carbonates should be administered shortly -before meals in combination with nux vomica, bitters, and -carminatives.</p> - -<table class="rx"> - <tr> - <td>℞</td> - <td>Mag. carb.</td> - <td>gr. 10</td> - </tr> - <tr> - <td></td> - <td>Sodæ bicarb.</td> - <td>gr. 15</td> - </tr> - <tr> - <td></td> - <td>Tinct. nucis vomicæ</td> - <td>♏︎ 7</td> - </tr> - <tr> - <td></td> - <td>Spts. chloroformi</td> - <td>♏︎ 10</td> - </tr> - <tr> - <td colspan="3">Infus. calumbæ ad unciam, ter in die sumenda ante cibos.</td> - </tr> -</table> - -<p>In the milder type of case the above may suffice, supplemented, -if necessary, by some gentle aperient. Unfortunately in many -instances the condition is apt to become complicated by <i>fermentation</i> -with <i>excessive formation of organic acids</i>. It is to these -that the “acid risings” are due, and <i>not to excess of HCL</i>. Indeed, -the reverse is the case, viz., a <i>deficiency of HCL</i>. It is this that is -responsible for the fermentation with the production of butyric, -lactic, and acetic acids. Moreover, in middle-aged “gouty” -subjects of sedentary habits there is often superadded <i>motor -defect</i>, which may end in <i>dilatation</i>.</p> - -<p>For treatment of this condition careful <i>dieting</i> alone may suffice. -Indeed, attention to general health often succeeds where <i>stomachic</i> -therapy alone conspicuously fails. The medicinal indications in -these cases will vary according to the stage at which they are seen. -In the milder forms we may stimulate the flow of gastric juice -by alkalies and bitters before meals, or hydrochloric acid after -food may be taken to replace the defect.</p> - -<p>Now, theoretically speaking, this may sound very simple, but -in practice it is often not so. Moreover, the less the attention -paid to correction of diet and faulty habits, the more bewildering -and disappointing the effect of drugs. Conversely, the more care -expended on the selection of food and hygienic measures, the less -need for drugs and the clearer the indications for such as may be -helpful.</p> - -<p>Thus simply under a revised diet the acid eructations may<span class="pagenum"><a id="Page_392"></a>[392]</span> -wholly disappear and the subject suffer only with languor, -discomfort, or drowsiness after meals. Here dilute hydrochloric -acid combined with strychnine and pepsine after food will be -found useful.</p> - -<p>On the other hand, many of these patients are impatient of -dietetic control, yet nevertheless clamour for relief of their -“acid” eructations. In such cases <i>alkalies</i> must be given an -hour or so <i>after</i> meals to correct the excess of <i>organic acids</i>. The -same may be combined with antiseptics—carbolic, B. naphthol, -creosote, etc.—or some artificial digestive, such as <i>papain</i>, -<i>pancretin</i>, or <i>taka-diastase</i>.</p> - -<table class="rx"> - <tr> - <td>℞</td> - <td>Bismuth carb.</td> - <td>gr. 15</td> - </tr> - <tr> - <td></td> - <td>Calcii carb.</td> - <td>gr. 5</td> - </tr> - <tr> - <td></td> - <td>Acid. carbol. pur.</td> - <td>♏︎ ½</td> - </tr> - <tr> - <td></td> - <td>Oleum cajeput</td> - <td>♏︎ 2</td> - </tr> - <tr> - <td colspan="3">Fiat cachet, 1 or 2 an hour or more after meals.</td> - </tr> -</table> - -<p>The <i>calcium</i> and <i>bismuth</i> carbonates are best, inasmuch as, -though they act slowly, they give rise to no <i>secondary hypersecretion</i>. -Of digestive adjuvants in these cases, Luff speaks -highly of taka-diastase (gr. 2½) immediately before meals in -addition to bismuth and alkalies. The taka-diastase assists the -digestion of carbohydrate foodstuffs, and so lessens or inhibits the -formation of organic acids. But as a digestive adjuvant in these -cases of “dyspepsia” with acid eructations <i>papain</i> is most -useful, acting in acid, alkaline, or neutral media. This indifference -on its part enables us to combine it with alkalies, and so attain -the dual effect of reinforcing the digestive capacity and neutralising -hyperacidity.</p> - -<table class="rx"> - <tr> - <td>℞</td> - <td>Mag. carb. pond.</td> - <td>gr. 15</td> - </tr> - <tr> - <td></td> - <td>Sodii bicarb.</td> - <td>gr. 10</td> - </tr> - <tr> - <td></td> - <td>Papain</td> - <td>gr. 3</td> - </tr> - <tr> - <td></td> - <td>Oleum caryophylli</td> - <td>♏︎ ½</td> - </tr> - <tr> - <td colspan="3">Fiat cachet, 1 or 2 after meals when acidity is at its height.</td> - </tr> -</table> - -<p>Our forefathers in such cases thought highly of rhubarb and -magnesia, and certainly in hospital patients some such -combination as the following is invaluable in so-called “gouty -dyspepsia”:—</p> - -<table class="rx"> - <tr> - <td>℞</td> - <td>Mag. carb.</td> - <td>gr. 10</td> - </tr> - <tr> - <td></td> - <td>Sodii bicarb.</td> - <td>gr. 15</td> - </tr> - <tr> - <td></td> - <td>Acid. carbol. pur.</td> - <td>♏︎ 1</td> - </tr> - <tr> - <td></td> - <td>Tinct. rhei co.</td> - <td>♏︎ 15</td> - </tr> - <tr> - <td></td> - <td>Spts. chloroformi</td> - <td>♏︎ 15</td> - </tr> - <tr> - <td colspan="3">Inf. caryophylli ad unciam, ter in die post in cibos.</td> - </tr> -</table> - -<p><span class="pagenum"><a id="Page_393"></a>[393]</span></p> - -<p>Almost always in these cases more or less <i>constipation</i> prevails, -which must be corrected. To this end, of course, the magnesia -contained in one of the above cachets may be all that is -necessary; but often it is not so, especially if the subject be -taking bismuth. Moreover, inasmuch as we have to take -cognisance of the <i>constitutional</i> taint in these individuals, we may -with advantage give an occasional aloetic pill containing colchicum -or a nightly dose of guaiacum and sulphur. Again, if the urine -be scanty, we may substitute a morning draught of phosphate -of soda (¼-½ ounce), which not only stimulates the liver, but -exercises also an antacid and diuretic effect.</p> - -<table class="rx"> - <tr> - <td>℞</td> - <td>Ext. colchici</td> - <td>gr. ¼</td> - </tr> - <tr> - <td></td> - <td>Aloin</td> - <td>gr. ¼</td> - </tr> - <tr> - <td></td> - <td>Menthol</td> - <td>gr. ½</td> - </tr> - <tr> - <td></td> - <td>Ext. rhei</td> - <td>gr. 1</td> - </tr> - <tr> - <td colspan="3">Fiat pil., 1 alternis noctibus sumenda.</td> - </tr> -</table> - -<p>As soon as the symptoms of fermentation and organic acidity -relent to the above or similar measures we should, if possible, -dispense with drugs and rely wholly on diet and general hygienic -regulations; but unfortunately a case of <i>atonic</i> “dyspepsia,” -if of prolonged duration, gradually merges into one of <i>chronic -gastritis</i>. Especially in those given to alcoholic indulgence do -we meet with a condition of <i>mucous catarrh</i>, with its associated -<i>deficiency of hydrochloric acid</i>. Indeed, apart from <i>alcoholic</i> -excess, such is the frequency in “gouty” subjects of this form of -“dyspepsia,” <i>i.e.</i>, <i>fermentation with excess of organic acids</i>, that -I am inclined to think that the <i>subacidity</i> which permits of such -developing is, if I may say so, the inherent digestive disability -in “gouty” subjects. Unquestionably <i>hyperacidity</i>—<i>i.e.</i>, excess -of organic acids due to <i>hypochlorhydria</i>—is in their instance -infinitely more common than hyperchlorhydria, or excess of -HCL, that is, much more frequent than the latter as differentiated -from organic acidity by the only possible means, viz., an -examination of the stomach contents.</p> - -<p>Again, accepting the view that <i>infections</i> are the chief excitants -of gouty paroxysms, the desirability of reinforcing the antiseptic -action of the gastric juice is obvious. In other words, the -defensive powers of the stomach against intruding microbes must -be raised by prescribing <i>hydrochloric acid</i>. For this purpose it is -well to use <i>strong</i> or <i>fuming</i> hydrochloric acid in doses of from -5-10 minims, freshly mixed at the time of administration with -6-8 ounces of water, and the same taken at every meal. The -hydrochloric acid may with convenience be placed in a drop -bottle, and beginning with 5 minims, an extra minim may be<span class="pagenum"><a id="Page_394"></a>[394]</span> -added every few days until 10 or 15 minims are taken at each -meal.</p> - -<p>Some years ago Armstrong, of Buxton, spoke highly of its value -in <i>alimentary toxæmia</i>, which is precisely the condition we are -confronted with in gout. Falkenstein, again, highly eulogises -it in the latter disorder. He gives from 40-60 drops of pure -hydrochloric acid in a large quantity of effervescing water each -day. It is taken during meals, and the dilution with water is -arranged so that the patient is struck by the acid taste. The -diet taken was an ordinary one, and yet Falkenstein noted that -the dyspeptic symptoms disappeared and the attacks of gout -grew more rare and much less severe. As an alternative to water, -either still or effervescing, the hydrochloric acid in from 5-15 -drops may be given in mucilage, or, if preferred, we may give -the dilute hydrochloric acid in some such form as the following:—</p> - -<table class="rx"> - <tr> - <td>℞</td> - <td>Acid. hydrochlor. dil.</td> - <td>♏︎ 10-15</td> - </tr> - <tr> - <td></td> - <td>Glycerin pepsinæ</td> - <td>dr. 1</td> - </tr> - <tr> - <td></td> - <td>Liq. strych. hyd.</td> - <td>♏︎ 3</td> - </tr> - <tr> - <td></td> - <td>Tinct. capsici</td> - <td>♏︎ 1</td> - </tr> - <tr> - <td colspan="3">Inf. aurantii co. ad unciam, ter die sumenda statim post cibos.</td> - </tr> -</table> - -<p>Sometimes it so happens that while taking the above acid -mixture the subjects an hour or more after meals complain of -acidity. If so, it is due to fermentation, and at the time of its -occurrence must be met by an adequate dose of an alkali with or -without some antiseptic preparation. It goes without saying -that if such can be referred to dietetic errors—food-bolting, etc.—these -also must be corrected.</p> - -<p>In these cases, too, the <i>liver</i> is frequently inactive, though often -their attacks of “biliousness” signify nothing but <i>constipation</i>; -but when there are definite signs of hepatic torpor we may -substitute for the hydrochloric acid in the above mixture the -dilute nitro-muriatic acid. Simultaneously we may occasionally -at night give a pill containing calomel, iridin, or podophyllin -combined with aloes and belladonna, or we may instead invoke -colchicum as a <i>cholagogue</i>, following it up in either case the -morning after by a saline purge. As a substitute we may -in suitable cases order every morning for some days a full dose -of Rubinat, Hunyadi Janos, or other bitter water.</p> - -<p>So much for the more common derangements of the <i>inter-paroxysmal</i> -period and the measures wherewith to combat them. -Collectively their aim is <i>the restoration to functional efficiency of -the alimentary canal and its accessory glands</i>, this to the end that, -as far as possible, a condition of <i>intestinal asepsis</i> may be attained,<span class="pagenum"><a id="Page_395"></a>[395]</span> -with its correlated diminution of the excitants most fertile of -outbreaks.</p> - -<p>Nevertheless, from time to time, either from failure of the -patient’s co-operation or other mischances, our best efforts at -<i>prophylaxis</i> fail, and it becomes clear that an attack is <i>imminent</i>. -What then, save brisk <i>purgation</i>, can be done to avert the -threatened outbreak? Our forefathers, in cases in which the -fits recurred periodically and might be forecast with tolerable -accuracy, were accustomed some time <i>before the threatened attack</i> -to place the subject on a rigorous diet, this in combination with -a course of <i>alkalies</i>, those of <i>soda</i> being given the preference in -<i>dyspeptic</i> or <i>hepatic</i> disturbance and those of <i>potash</i> when the -<i>urine</i> was <i>scanty</i>.</p> - -<p>That this was sound treatment and abundantly justified by -the results is well acknowledged, and all I would suggest is that -this is yet another juncture at which <i>atophan</i> is indicated, viz., -<i>immediately before a paroxysm</i>. At this particular time the -<i>urinary output</i> of <i>uric acid</i> is often <i>diminished</i>, a clear indication -for enlistment of atophan, which <i>increases uric acid elimination</i>. -I note that both Retzlaff and Brugsch consider it an especially -advantageous time for its exhibition. As a <i>prophylactic</i> measure -the former gives 30-45 grains daily for three days at intervals of -a fortnight, and if cardialgia or heartburn ensues, adds ¼-½ -teaspoonful of bicarbonate of soda to each gramme of the drug.</p> - -<p>Lastly, we have to recollect, too, that colchicum is credited -with some <i>prophylactic</i> powers. Some, it is true, discountenance -its employment in the inter-paroxysmal period, on the plea that -it tends to favour <i>recurrence</i> and <i>chronicity</i> of attacks. While I -think it is better to reserve it for <i>acute</i> or <i>subacute</i> attacks, still -I have not found that colchicum, given in what Sir Thomas -Watson called <i>alterative</i> doses, is anything but beneficial, provided -that it be taken <i>intermittently</i>, not continuously, for long periods. -As to special indications for its employment, I think it is more -effectual in aborting a threatened attack when, in addition to -dyspeptic phenomena, the imminence of a fit is betokened by -what may be termed specific harbingers thereof, <i>i.e.</i>, pricking and -tenderness in existing tophi, twinges in the toes, etc.</p> - -<p>In conclusion, are we not in this matter of the <i>prophylaxis</i> of -gout somewhat too prone to resort, both in and out of season, -to what we are pleased to term <i>special medication</i>? Almost every -week some new and of course infallible “uric acid solvent” is -lauded <i>ad nauseam</i> in the press. Are not we ourselves, too, -somewhat overanxious to go with the tide in prescribing these -vaunted “gout specifics”?</p> - -<p>The true aim of <i>prophylaxis</i> is rather to <i>prevent</i> the incidence<span class="pagenum"><a id="Page_396"></a>[396]</span> -of those <i>functional derangements</i> that in some subtle way determine -the disturbances in <i>nuclein</i> metabolism, with <i>secondary</i> accumulation -of <i>uric acid</i> in the organism. That drugs, such as atophan, -which diminish the uric acid content of the blood and increase its -urinary output, fulfil an invaluable <i>rôle</i> in ridding the system -of excessive amounts of this chemical outcast, I fully admit.</p> - -<p>Albeit, this achievement does but deal with the <i>consequences</i> or -<i>sequels</i>, not the exciting causes, of gout. In truth, there is no -short cut to the cure of gout. Only under suitable treatment, -applied to meet all the necessities of individual cases, will any -long immunity from its onslaughts be secured or their intensity -attenuated.</p> - -<hr class="chap x-ebookmaker-drop"> - -<div class="chapter"> - -<p><span class="pagenum"><a id="Page_397"></a>[397]</span></p> - -<h2 class="nobreak" id="CHAPTER_XXX">CHAPTER XXX<br> -<span class="smaller">MEDICINAL AND OTHER MODES OF THERAPY (<i>continued</i>)—CHRONIC -ARTICULAR GOUT AND ASSOCIATED MORBID CONDITIONS</span></h2> - -</div> - -<h3><span class="smcap">Chronic Articular Gout</span></h3> - -<p>The gastric derangements that precede acute gout nearly always -become aggravated when the disease is permanently established. -Consequently from time to time many of the measures outlined -in previous paragraphs must be resorted to. But there is this -also to be borne in mind, that in these later stages of the evolution -of the disorder the intervals of relative health grow shorter and -shorter. The victim lies more or less always under the shadow -of the malady, and its peculiar impress on the constitution becomes -more and more ingrained. Therewith his sensitiveness to the -<i>exciting</i> causes becomes more and more pronounced.</p> - -<p>To detect and thereafter to eliminate the most fruitful excitant -of articular outbreaks in individual examples will form no small -portion of the task that falls on physician and patient alike. In -the majority, it will be some indiscretion of food or drink; in -some, insufficient exercise; in others, intellectual strain or worry, -etc. By determining the particular nature of the excitant in -the individual under review we arrive at his <i>personal idiosyncrasy</i>—a -matter of much moment in <i>prophylaxis</i>.</p> - -<p>Moreover, with increasing experience the physician cannot -help noting that the vulnerability to assaults varies in different -subjects. Thus the development of gouty paroxysms in some -will be found to be associated with <i>gastro-intestinal</i> or <i>hepatic</i> -derangements, in others with <i>defects of elimination</i> through -<i>kidneys</i>, <i>bowels</i>, or <i>skin</i>.</p> - -<p>In short, these cases must be approached in a catholic frame of -mind, and the success of medicinal therapy will depend on the -judgment and clinical acumen displayed in meeting the ever-varying -necessities of individual instances, not by an almost -flippant prescribing of alkalies or, it may be, iodides, colchicum, -or guaiacum. All these are valuable, but only if invoked with -discrimination, and not after stereotyped or routine fashion.</p> - -<p>The <i>joints</i> in these cases are the seat of <i>chronic</i> change, and -though they call for due attention, it is the <i>constitutional</i> taint -that is of paramount importance. How best shall we influence<span class="pagenum"><a id="Page_398"></a>[398]</span> -this? How else save by recognition of the morbid content of -the <i>blood</i> and cleansing of the impurities with which it is charged?</p> - -<p>I have before stated my belief that <i>functional derangements</i> of -the <i>alimentary canal</i> are the <i>determining</i> cause. It is through -their agency that the toxicity of the blood plasma ensues. In -the vast majority of cases these constitute the dominant departure -from physiological righteousness. It is to these that the <i>high -uric acid content</i> of the <i>blood</i> may presumably be referred. Yet -nevertheless <i>retention</i> of the same in the form of <i>tophi</i> may be -relatively slight. Is it that in their instance the avenues of -<i>excretion</i> are more permeable?</p> - -<p>In others, again—not necessarily those with more pronounced -dyspeptic symptoms—the retention of uric acid proceeds apace. -Clinically the explanation appears to be that cases with massive -<i>tophaceous deposits</i> often display <i>renal</i> changes. In other words, -it is the channels of <i>elimination</i> that appear to be at fault.</p> - -<p>But, more than likely, these superficial differences hark back -to infinitely more subtle inward disparities, to <i>tissue peculiarities</i> -of function, with correlated variations in their <i>retention capacity -for uric acid</i>. Here again the clinician waits upon the bio-chemist, -and meanwhile must base his differential treatment on -somewhat coarser indices.</p> - -<p>Thus in one class of case the toxicity of the blood seems -attributable to dyspepsia or mal-assimilation, and the physician’s -efforts must be concentrated on correction of the same. In -another type such may be absent, and yet uric acid accumulates, -tophi multiply, and his attention turns to the kidneys, the avenues -of excretion. In others, again, both symptom complexes may be -combined, and his resourcefulness is taxed to the utmost to meet -these several necessities, for, as Sydenham wisely said, “the -weakness of all the digestions and the loss of natural strength in -the several parts are the essence of gout. Each must be dealt -with.”</p> - -<p>Nor must we forget that long-continued gout engenders not -only a depravation of general nutrition, but paves the way also -for the insidious production of structural organic changes. In a -word, it favours the onset of <i>pre-senilism</i>, with all that such -connotes. So it is that in these subjects, too often past the -meridian of life, we have not only gout to combat, but the grisly -appanage of oncoming age.</p> - -<p>It is this larger view of our responsibilities that we must cultivate -if our treatment of chronic gout is to be in any sense rational, and -not wholly haphazard. Also, if my contention be correct that the -<i>alimentary canal</i> is the <i>fons et origo mali</i>, the major source of the -provocatives of gout, then the basal and essential part of our<span class="pagenum"><a id="Page_399"></a>[399]</span> -therapy must be <i>diet</i> and <i>regimen</i>. As to the subsidiary medicinal -indications, it will perhaps be more convenient if I proceed to -discuss shortly the use of the various drugs that experience has -shown to have been of most avail in chronic gout.</p> - -<p><i>Alkalies.</i>—It was formerly thought that by increasing the -<i>alkalescence of the blood</i> its solvent effect on <i>uratic deposits</i> was -enhanced and their formation thereby delayed or prevented. -But subsequent researches by Sir William Roberts conclusively -proved to his mind “that alkalescence as such has no influence -whatever on the solubility of sodium biurate.”</p> - -<p>Luff, again, from his investigations, held that administration -of the ordinary <i>alkalies</i>, of <i>lithium</i> salts, of <i>piperazine</i>, and of -<i>lysidine</i>, with the object of removing gouty deposits, appears to -be useless. He also claims that no general acidity of the system -is associated with gout, and no relationship exists between the -acidity of the urine and the alkalinity of the blood.</p> - -<p>Nevertheless let us not sin against light, which is exactly what -we are very prone to do if we allow ourselves to be obsessed by -<i>uric acid</i> and overlook the records of clinical experience. Take -Sir Thomas Watson; he, without any reference to uric acid -elimination, recommended as a prophylactic against gout 15 -grains of bicarbonate of potash in combination with tincture of -rhubarb and some light bitter, to be taken <i>every day</i>. Fagge, -again, observes, “Alkalies are decidedly useful in gout,” and the -same views were held by the elder Garrod, Lecorche, and Dieulafoy, -etc.</p> - -<p>In short, forgetting for the moment the existence of uric acid -and shedding all hope of their dissolving <i>tophi</i>, we find that -<i>alkalies</i> have ample justification besides for their employment. -They are valuable as <i>antacids</i>, <i>diuretics</i>, and as <i>alteratives</i>, and, -moreover, their routine employment has been tried and approved.</p> - -<p>In other words, the benefit of alkalies depends, not upon any -special solvent effect upon <i>uratic deposits</i>, but upon their remedial -influence upon associated and, I believe, causally related <i>gastric</i> -and <i>hepatic</i> disorders, and through these on general metabolism. -Albeit, let us be guided by rational considerations when we invoke -their aid.</p> - -<p>The fact that alkalies are incapable of dissolving <i>tophi</i> is a clear -indication that that deleterious habit of <i>continuously</i> taking -potash and lithia water is not only unnecessary, but undesirable. -Alkalies should be prescribed in short courses and to meet special -indications, <i>i.e.</i>, <i>intermittent</i>, not continuous, administration.</p> - -<p>Thus in the minor <i>gastric</i> disturbances which in chronic gout -we are constantly called upon to treat there is no doubt as to the -superiority of the <i>sodium</i> compounds. Moreover, apart from their<span class="pagenum"><a id="Page_400"></a>[400]</span> -value in <i>gastric</i> or <i>intestinal</i> catarrh, we have to note their -usefulness in dyspeptic states complicated by <i>torpid liver</i>.</p> - -<p>When <i>constipation</i> exists, the sodium bicarbonate may be -combined with magnesia, and all will admit the striking benefit -attained by short courses of these drugs with the addition of -rhubarb, some simple bitter infusion, quinine, or strychnine, all -rendered more effective by the addition of some carminative or -aromatic.</p> - -<p>Sydenham’s electuary was compounded of gastric tonics, and -the more recent Portland and Pistoja powders are in this respect -but an imitation thereof. Indeed, <i>stomachics</i> are the most -valuable tonics in gout. Lastly, it is in the <i>inter-paroxysmal</i> -periods of <i>chronic</i> gout that the sodium compounds are indicated, -when the joints, though enlarged, are quiescent, and the more -prominent symptom in the clinical picture is lack of <i>gastric tone</i>, -with or without acidity.</p> - -<p>As to the <i>potash</i> compounds, it is during and immediately after -articular paroxysms of acute or subacute gout that they find -their chief sphere of usefulness. Apart from this, they are, -because of their <i>diuretic</i> properties, valuable at all times in cases -in which the renal secretion appears to be deficient. The -bicarbonate, citrate, or acetate of potash are the most valuable. -The last-named is the most diuretic, but is rarely used, the citrate -enjoying more favour, being more palatable and most eligible -when no direct <i>antacid</i> effect is desired, in which case it should -be replaced by the bicarbonate.</p> - -<p>In those instances in which the <i>skin</i> is notably inactive Garrod -thought highly of the phosphate of ammonium, holding that -“there is much clinical evidence to prove its value in the treatment -of chronic gout.” Many, like Burney Yeo, believe that a -combination of soda and potash compounds acts better than -when either is given singly. Thus Garrod in cases in which the -action of the liver was defective frequently used the bicarbonate -of soda in combination with the citrate of potash.</p> - -<p>As to the <i>lithium</i> salts, general opinion has it that their value -in the treatment of gout has been greatly over-estimated, and that -they are not so serviceable as the potassium and sodium salts. -They are also more toxic and lowering, and Luff some years ago -issued the following <i>caveat</i>: “I constantly meet with patients -suffering from cardiac depression, and even dilatation, as the -result of the excessive and continued consumption of lithia -tablets, which are so persistently, so speciously, and so wrongly -vaunted as curative of gout.”</p> - -<p>In conclusion, it will be seen that clinical experience testifies -with no doubtful voice to the value of most salines. At the same<span class="pagenum"><a id="Page_401"></a>[401]</span> -time it is clear, also, that we should use discrimination, seeing that -some, as Garrod says, are “certainly more adapted to particular -cases than others.” They should also be given well diluted, in -moderate doses, and not continuously but intermittently. These -rules should certainly be followed when alkalies are invoked in -gout, not for local <i>antacid</i> effect, but for their general influence on -metabolism. Moreover, at the close of a course of alkalies for -this purpose, we may often with advantage place the subject on -acids in combination with quinine, nux vomica, or strychnine.</p> - -<p><i>Alteratives.</i>—Of these the salicylates and the benzoates are, by -some, greatly prized, in that they act especially on uric acid, -promoting the elimination thereof. The benzoates are favoured -in examples in which the kidneys are not above suspicion, the -latter disability contra-indicating the use of the salicylates. -Some, like Ewart, advocated a course of benzoates in alternation -for periods of a week or a fortnight with a saline treatment. -By Lecorche and Haig, salicylate of soda in doses of 60 grains -or more per diem was advocated continuously for prolonged -periods.</p> - -<p>In my opinion, salicylates are best used during a paroxysm, -when, for some reason, colchicum is contra-indicated, or immediately -after, to promote elimination of uric acid and to minimise -or inhibit the development of <i>tophi</i>. As to the benzoates of -sodium and potassium, they are now rarely, if ever, prescribed, -though hexamine is growing in favour as a “urinary antiseptic -diuretic and anti-lithic.” Occasionally I have met with B. coli -infections in gout, and in such cases one of the preparations of -hexamine, with lithium or sodium benzoates, is of value, whilst -among the laity urodonal stands in high repute as a means of -removing uric acid and allied bodies.</p> - -<p><i>Iodides.</i>—Turning to well-tried alterative remedies, there is -no doubt that the <i>iodides</i> well deserve their high repute in the -treatment of chronic gout. Thus in subacute and obstinate -swelling of the joints, and alike in painful gouty affections of the -muscles, fasciæ, and nerve sheaths, iodine in one or other of its -forms is <i>par excellence</i> our most reliable remedy.</p> - -<p>In no type of case is it more serviceable than when the joint -inflammation is of low asthenic type—enlarged, stiff, and painful. -It may be given in some such combination as the following:—</p> - -<table class="rx"> - <tr> - <td>℞</td> - <td>Pot. iodidi</td> - <td>gr. 5-10</td> - </tr> - <tr> - <td></td> - <td>Pot. bicarb.</td> - <td>gr. 15</td> - </tr> - <tr> - <td></td> - <td>Spts. ammon. aromat.</td> - <td>♏︎ 20</td> - </tr> - <tr> - <td></td> - <td>Vin. colchici.</td> - <td>♏︎ 5</td> - </tr> - <tr> - <td></td> - <td>Tinct. capsici.</td> - <td>♏︎ 1</td> - </tr> - <tr> - <td colspan="3">Inf. aurantii co. ad unciam ter in die sumenda post cibos.</td> - </tr> -</table> - -<p><span class="pagenum"><a id="Page_402"></a>[402]</span></p> - -<p>If colchicum be contra-indicated, a useful substitute to quell -pain is tincture cimicifugæ in 15-minim doses. The dose of the -iodide need not exceed 3-5 grains, as, from my observation, no -appreciable advantage is gained by larger doses. <i>Iodine-albumen</i> -compounds may be substituted for the alkaline iodides as less -likely to cause derangement of the stomach, inasmuch as assimilation -is believed to take place in the intestine. Thus <i>iodo-protein</i> -may be administered in doses from 10-15 grains. A tablet -containing 10 grains is equivalent to 1 grain of combined iodine. -Excretion being taken as the measure of absorption, it has -been experimentally shown that, six hours after administration, -a lower percentage of iodine was excreted in the case -of iodised protein than with potassium iodide. In other words, -the iodine-albumen compound yield up their iodine to the -system at a slower rate. In short, they disintegrate more slowly -and are, therefore, the more likely to exert a longer continued -activity.</p> - -<p>An organic compound of iodine with vegetable albumen, <i>i.e.</i>, -<i>iodo-glidine</i>, has been somewhat extensively used in gout, as -being <i>non-depressant</i>. Said to undergo almost complete -disruption in the intestines, it is slowly absorbed without toxic -symptoms. Iodo-casein and seroden, a combination of iodine -with blood proteins, are similar preparations, with which, if -necessary, the alkaline iodides may be replaced.</p> - -<p>More recently the advantages of <i>collosol</i> preparations of <i>iodine</i> -have been emphasised, and these colloidal solutions, unquestionably, -have an increasing sphere of usefulness in all cases of gout -where iodine is indicated. It has been truly said, collosols “are -not new drugs, they are simply familiar drugs in a new form—a -form in which their therapeutic potency is greatly heightened -while their undesirable properties are reduced to vanishing -point.”</p> - -<p>Doubtless, collosols exist in a form very meet for assimilation, -inasmuch as they conform to the essentially colloidal character -of all the normal fluids and secretions of the organism. Moreover, -toxins or bacterial poisons appear also to exist in colloidal form, -and also, according to A. B. Searle, “to a large extent in the -reactions which create immunity.”</p> - -<p>These physical similarities between collosols and the bodily -fluids and tissues ensure their ready assimilation with minimal -constitutional disturbance. Inasmuch as the colloidal -state, too, predicates low chemical affinity, the combination -and absorption of collosol preparations take place gradually and -uniformly.</p> - -<p>For internal administration colloidal iodine is prepared in<span class="pagenum"><a id="Page_403"></a>[403]</span> -aqueous suspension. It is stated that the whole of the iodine is -absorbed in molecular combination with protein. An iodo-amino -acid results, and ultimately reaches the blood-stream. -Arrived there, it, through its reducing action on lipoids, exerts -an alterative effect.</p> - -<p>The dose of collosol iodine ranges from 1-4 teaspoonfuls daily -after meals. It does not cause nausea if the amount be slowly -increased, and only exceptionally does it set up iodism. In -these respects it has an undoubted advantage over the alkaline -iodides. As to whether they will wholly usurp the place of -this latter is, I think, very doubtful; this, if only for the convenience -with which the alkaline iodides lend themselves to -combination with other alterative remedies. But in individuals -intolerant of iodide of potassium they are excellent substitutes -when the indication is to improve and modify the general metabolism.</p> - -<p>Lastly, too, apart from their use in <i>chronic gouty arthritis</i>, we -have to recollect that the iodides are the most reliable means we -possess of influencing the <i>renal</i> and <i>vascular</i> changes so often -associated with gout. Garrod doubted if they possessed any -power of promoting the dissipation of <i>uratic deposits</i>, but their -power of eliminating <i>lead</i> must not be lost sight of when treating -gout in the subjects of <i>plumbism</i>. Obviously, when invoked for -this purpose or to arrest or retard degenerative processes in -kidneys and vessels, their administration must be continued for -long periods—six to eight weeks. The same persistence, too, is -demanded to remove the inflammatory products in the joints. -Simultaneously or alternately short courses of <i>atophan</i>—30-40 -grains for two to three days in a month or oftener in more -severe cases—will also be of help in dislodging articular deposits -in the form of tophi.</p> - -<p><i>Guaiacum.</i>—Many years ago, Sir Alfred Garrod<a id="FNanchor_62" href="#Footnote_62" class="fnanchor">[62]</a> highly eulogised -the value of this drug in the treatment of chronic gout. Said he, -“There is no remedy of which I can speak so confidently. I have<span class="pagenum"><a id="Page_404"></a>[404]</span> -known patients who have been confined to their beds for many -weeks with asthenic chronic gout so far recover within two or three -days under the use of this remedy as to be able to walk about.” -He held that it exerted a specific action on the fibrous tissues, -and advocated its exhibition in chronic forms of gout with feeble<span class="pagenum"><a id="Page_405"></a>[405]</span> -circulation. He adds the further interesting differentiation -regarding the employment of guaiacum as opposed to iodide of -potassium. Both these drugs he held valuable when the fibrous -coverings of the joints were especially affected. If the articular -pains were increased by warmth, iodide of potassium is “peculiarly -indicated”; but, under such circumstances, “the use of guaiacum -is either altogether contra-indicated or, at least, it should be -administered in combination with iodide of potassium or some -other saline.”</p> - -<p>As to its mode of action, Bain noted that, while the excretion -of urea fell somewhat, that of uric acid was markedly increased. -But he found, also, that “neither the phosphorus pentoxide -nor the bases showed a corresponding increase—thereby denoting -that this drug probably acts, not by increasing the production -of uric acid, but by eliminating a part of that stored in the blood.” -Moreover, it was noted that the increased uric acid excretion did -not cease with cessation of the drug, but continued for some time -after, the patient’s condition meanwhile undergoing amelioration. -Bain considers that his researches confirm the opinion arrived at, -on empirical grounds, by Sir Alfred Garrod—that guaiacum was -a powerful prophylactic agent in gout.</p> - -<p>Returning to its method of exhibition, it must be admitted that -it is most unpalatable when given in the form of a mixture, and -is preferably prescribed in a cachet or tablet. The resin of -guaiacum may be given in doses of from 5-15 grains, and the -larger doses may excite nausea or purging. In smaller amounts, -however, it merely exerts a beneficial laxative effect; it is also -useful in cases where the liver is torpid. This latter action may -be reinforced by simultaneous administration of calomel in -fractional doses.</p> - -<table class="rx"> - <tr> - <td>℞</td> - <td>Hydrarg. sub chlor.</td> - <td>gr. ⅟₁₀</td> - </tr> - <tr> - <td></td> - <td>Guaiaci resinæ</td> - <td>gr. 3</td> - </tr> - <tr> - <td></td> - <td>Sulph. precip.</td> - <td>gr. 3</td> - </tr> - <tr> - <td colspan="3">Fiat. cachet. Ter in die sumenda post cibos.</td> - </tr> -</table> - -<p>Such is useful as a corrective in intestinal fermentation when -given for three or four days, after which the calomel may be -withdrawn and the guaiacum and sulphur continued in doses -adequate to produce a daily evacuation.</p> - -<p>The compound confection of guaiacum or the Chelsea Pensioner -Powder have also stood the test of time, and may be taken in the -appropriate dose daily for weeks. Personally, I have for years -employed a cachet containing guaiacum, iodide of potassium, -colchicum, and cinchona as a prophylactic measure in the inter-paroxysmal -periods of chronic gout.</p> - -<p><span class="pagenum"><a id="Page_406"></a>[406]</span></p> - -<p>I would here, too, advance a plea for the use of guaiacum as -the most useful laxative for constipation in the gouty, and in -combination with sulphur where there is inactivity of the skin. -The following is an excellent and well-tried formula:—</p> - -<table class="rx"> - <tr> - <td>℞</td> - <td>Sulph. precip.</td> - <td></td> - </tr> - <tr> - <td></td> - <td>Pulv. guaiaci</td> - <td></td> - </tr> - <tr> - <td></td> - <td>Pot. bitart. āā</td> - <td>ʒj.</td> - </tr> - <tr> - <td></td> - <td>Pulv. tragac. co.</td> - <td>ʒij.</td> - </tr> - <tr> - <td colspan="3">Fiat pulv., ½ to 1 teaspoonful to be taken stirred up - in water or milk at bedtime.</td> - </tr> -</table> - -<p>Such is a useful laxative and, during the day, may be often -advantageously combined, in lingering articular gout, with a -mixture containing iodide of potash, nux vomica, and cinchona. -Luff, by the bye, holds that iodide of potash acts more beneficially -when given in the compound decoction of sarsaparilla—the latter -also is lauded by Garrod as having properties somewhat similar -to guaiacum.</p> - -<p>In conclusion, the subjects of long-standing gout not infrequently -are anæmic. In such cases iron is often not well borne, -and has been said to favour recurrence of acute attacks. Small -doses, however, of a less astringent form agree well, always provided -that the bowels are kept freely open. The ammonio-citrate, the -iodide of iron, or one or other of the organic iron compounds are -most suitable. These may be given alone or in combination with -arsenic. For improving the general condition and promoting the -nutrition of such subjects, Robin speaks highly of the following:—</p> - -<table class="rx"> - <tr> - <td>℞</td> - <td>Acidi arseniosi</td> - <td>gr. ⅟₈₀</td> - </tr> - <tr> - <td></td> - <td>Potassii iodidi</td> - <td>gr. 1</td> - </tr> - <tr> - <td></td> - <td>Pulveris rhei</td> - <td></td> - </tr> - <tr> - <td></td> - <td>Extracti gentianæ</td> - <td>āā q.s.</td> - </tr> - <tr> - <td colspan="3">Misce. Fiat pilula i. “Two pills to be taken daily at meal time.”</td> - </tr> -</table> - -<p>In drawing to a close our discussion of the drugs most useful -in the treatment of chronic articular gout, it will be noted that -our usage of them is largely <i>empirical</i>, viz., the outcome of -experience. We do not know exactly their mode of action, but -this we do know, that they have stood the most searching of tests—that -of <i>results</i>. That we should be largely, if not entirely, ignorant -of their mode of action is regrettable, but no reason whatever -why we should discard them in favour of newer compounds -administered on some pseudo-rational basis.</p> - -<p>What we need in gout is, rather, what Harry Campbell calls -“a broad commonsense-rationalism—not a meddling finnicking -pseudo-rationalism.” Ignorant of the intimate etiology of gout, -we are not as yet capable of determining the exact nature of the -underlying morbid processes. Much less are we in a position to<span class="pagenum"><a id="Page_407"></a>[407]</span> -devise a rational system of drug treatment whereby to antagonise -the same. For us, then, the wiser, if more humble, <i>rôle</i> of correcting, -if we may, such obvious deviations from physiological -righteousness as we may discern, but ever mindful that we -assist, not thwart, the subtle workings of the <i>vis medicatrix -naturæ</i>, whereby the balance of the nuclein exchanges is restored.</p> - -<h4><i>Local Measures in Chronic Articular Gout</i></h4> - -<p>When treating of these in relation to <i>acute</i> articular gout, -we dealt with the topical applications best calculated to achieve -the absorption of <i>inflammatory</i> exudates and mitigation of the -pain and stiffness associated therewith. It now remains for us -to discuss the treatment of that specific product of gouty inflammation, -viz., <i>uratic deposition</i>.</p> - -<p><i>Treatment of Tophi.</i>—Subcutaneous tophi in the neighbourhood -of joints sometimes become tense and painful, and restrict the -movements of the adjacent articulations. Garrod held that the -continuous application of pledgets soaked in solutions of carbonate -of lithia or of potash to tophaceous swellings had some power in -reducing their size, and even effecting, in some cases, their total -absorption. Also, with the intent of dissipating collateral -<i>inflammatory</i> thickening, he sometimes used a solution composed -of equal parts of iodide of potassium and carbonate of lithia.</p> - -<p>More recently, Robin states that the resolution of tophi may -be hastened by local applications of mineral waters containing -magnesia and sodium chloride or a solution of sodium perborate, -these affixed with considerable pressure over the harder parts of -the tophus, gentle massage of which, he thinks, at other times, will -aid absorption.</p> - -<p>Luff, however, on this point, holds that “the application of the -so-called solvents externally to affected joints is useless, as they -are not solvents of sodium biurate,” and I am inclined to agree -with him that but little is to be hoped for from this method of -treatment. A more effectual method of local medication is by -the electrolytic introduction of drugs.</p> - -<p><i>Ionisation.</i>—We may enlist <i>cataphoresis</i>, either for its <i>analgesic</i> -or its <i>sclerolytic</i> effect. If relief of pain be desired, the electrolytic -introduction of the salicylic ion from a cathode of a 2 per cent. -sodium salicylate solution is most valuable. A current of 20-40 -milliamperes, but only gradually raised, should be passed for -twenty to thirty minutes. Too frequent applications of the latter -strength may cause injury to the skin, and, in Lewis Jones’s -opinion, are inadvisable oftener than twice a week.</p> - -<p>If we wish to exercise a favourable stimulant effect in alterations -of nutrition and atrophy caused by gouty inflammation, the<span class="pagenum"><a id="Page_408"></a>[408]</span> -<i>chlorine</i> ion definitely accelerates return to the normal state. -Six-fold pads of ample size, soaked in a warm solution of sodium -chloride, are used as a cathode and bandaged round the joint. -The other “indifferent” electrode, similar in nature, is applied -to different parts at different sittings, and in this way the pathway -of the current through the joint changed. Currents up to 100 -or even 200 milliamperes may be tolerated when applied to the -knee; but the intensity of the current should only be raised -gradually, as the burns that sometimes ensue occasion no small -pain to the subject as well as discomfiture to the operator.</p> - -<p><i>Iodine</i> has a like sclerolytic action, and is commonly held to be -superior to that of chlorine. On the other hand, the iodine ion -is much less readily tolerated by the skin, and, according to Leduc, -the necessary reduction in intensity of the current employed goes -far to nullify the greater sclerolytic effect it may possess.</p> - -<p>In chronic gouty arthritis we are, as before remarked, confronted -not only with inflammatory products, but also with -<i>uratic deposits</i>. Fortunately, these latter also are benefited by -the electrolytic introduction of the lithium ion under an anode -of <i>lithium chloride</i>. The current serves a double purpose in this -case, for it not only drives in the lithium, but removes the <i>uric -acid</i> ion which is to be found in the electrode. Edison, some years -ago, suggested ionisation with <i>lithium</i> in gout, and the good results -he obtained have since been abundantly confirmed by others.</p> - -<p>The Schnee four-cell bath may be used where ionisation is -indicated. It possesses obvious facilities for local or sectional -application, as drugs can be added to the water in the cell and -carried through the skin by means of the continuous current. -Thus, in cases of large gouty deposits, the joint may be placed in -a bath containing a 2 per cent. solution of iodide of lithium or -of 5 per cent. bicarbonate of potash. The positive electrode is -then located in the bath, while the negative pole, moistened with -hot water, is applied to the lumbar region. Working with lithium -in this manner, Bordier detected the presence of <i>uric acid</i> in the -fluid of the bath, thus demonstrating introduction of the cation-lithium -and removal of the <i>anion-uric acid</i> at one and the same -time. In this way proof is adduced that the lithium penetrates -the tissues, and coming directly into contact with <i>uratic deposit</i>, -tends partly to dissolve it.</p> - -<p>To achieve the dual purpose, viz., <i>absorption</i> of <i>inflammatory</i> -and <i>uratic deposits</i>, we may with advantage give the chlorine or -iodine ions, for their sclerolytic effect on the tissues, in alternate -sittings with the lithium ions. When time is no great object, -two or three <i>séances</i> a week will suffice, but where time presses, the -sittings, according to Leduc, may be given daily, always provided<span class="pagenum"><a id="Page_409"></a>[409]</span> -that the position of the electrode and therewith the direction of -the current in its passage through the joint be changed at each -application. It is necessary to emphasise the fact that the use -of too mild currents is futile, and to secure adequate results a -prolonged series of <i>séances</i> is necessary. Also I would suggest -that the simultaneous taking of a course of atophan would appear -to be indicated.</p> - -<p><i>Surgical Treatment.</i>—In pre-antiseptic days, catastrophes, -<i>e.g.</i>, <i>erysipelas</i>, <i>gangrene</i>, etc., having occasionally followed the -evacuation or removal of tophi, it was deemed inadvisable to -interfere with them by any surgical methods. But, the danger -of sepsis having been largely removed, it is now regarded as quite -permissible to attempt the removal of uratic deposits for aesthetic -reasons, or, more cogently, when they give rise to pain or restrict -the movement of the related articulations.</p> - -<p>Moreover, the old view that incision or evacuation of tophi was -followed by obstinate <i>ulceration</i> is not borne out by modern -experience. Thus my colleague Lindsay found that healing takes -place quite naturally provided the incision is made over the more -healthy skin towards the base of the swelling. With this I am -in agreement, and furthermore would suggest that tophi when of -large size and fluctuating are better opened with aseptic precautions -than allowed to evacuate their contents spontaneously, -for in this last event suppuration ensues, the sores become troublesome, -and remain open for a long time. Sir Alfred Garrod in -such circumstances advised touching up of the indolent parts -with nitrate of silver.</p> - -<p>In my search through the literature I have only come across -two instances in which operation has been undertaken for the -removal of gouty deposits in relation to tendon sheaths, bursæ, -and skin. These were performed by Alexis Thomson. In one -the subject was a medical man, aged thirty, the subject of inherited -gout. Multiple tumour-like nodules, ranging in size from a pea to -a cherry, were located over the knuckles, and the same were -attached to the extensor tendons and moved with them. At the -patient’s request, they were removed on account of their unsightliness. -Their dissection from the tendons was achieved with some -difficulty, and healing, though retarded a little by watery discharge -from the wounds, was “in the end quite satisfactory.”</p> - -<p>The other example occurred in a tailor, aged thirty-seven, in -whom massive tophi developed at many sites. The larger -deposits were located over the left external malleolus, the left -olecranon, and the right malleolus. Because of their exposure -to injury and pressure, removal of these various gouty tumours -was decided upon. In all save the specially large swelling over the<span class="pagenum"><a id="Page_410"></a>[410]</span> -left external malleolus this was easily accomplished by cutting -through the surrounding healthy tissues. But that at the site -named “was so fixed to the bone that it had to be separated with -a chisel; it was then seen that the chalky deposit occupied spaces -in the spongy interior of the bone, and in the substance of the -internal lateral ligament; the removal of the chalky material in -the area of the wound was carried out more satisfactorily -by scrubbing the tissues with gauze and hot water than -with the sharp spoon. The peronei tendons exhibited a very -pretty deposit of urates under the endothelium covering -them.”</p> - -<p>Healing of the wounds took place very satisfactorily, and nine -months later the general health was excellent; no further -tophaceous deposits had accumulated, and the scars of the wound -had remained quite sound. As Alexis Thomson observed, that -though, even as this particular case showed, <i>spontaneous disappearance -of tophi may follow a subsequent attack of gout</i>, still such -could not be hoped for in the case of a massive deposit in the left -internal malleolus, invading as it did the interior of the bone. He -sums up his conclusions in the following words: “My own -experience is limited. So far as it goes, it establishes not only the -safety of the removal of gouty tumours by surgical means, but -also the improvement in the general health which follows the -removal of large masses of urates from the exposed parts -of the body. So far as appearances are concerned, the substitution -of linear scars for unsightly tumours is a decided improvement.”</p> - -<p>Now, if we take Riedel’s two instances of <i>acute</i> gout and their -tolerance of incision and local cleansing of urates and the equally -happy tolerance exhibited by Alexis Thomson’s two cases of -<i>chronic</i> gout, we see that, in these days of aseptic surgery, even -<i>gouty arthritis</i> can no longer be regarded as outside the pale of -operative interference. But, as a <i>caveat</i> against rash ventures, -I would point out that recently I canvassed the desirability of -operation in a case of massive tophaceous deposits in the hands -and feet; but fortunately a skiagraph was taken which revealed -that several of the phalangeal shafts had at some sites in their -length undergone total absorption.</p> - -<p>Nevertheless, given sound general health and failure of other -modes of treatment, I think that operative measures should be -seriously considered, for in the more inveterate types of -tophaceous gout the crippledom and painful ulceration -renders the victim’s life a misery, and one incapable of -appreciable amelioration by medicinal or other methods of -therapy.</p> - -<p><span class="pagenum"><a id="Page_411"></a>[411]</span></p> - -<h3><span class="smcap">Treatment of Associated Morbid Conditions</span></h3> - -<p>When dealing with the clinical account, it was pointed out that -acute gout is frequently complicated by symptoms pointing to -involvement of the fibrous tissues in muscles and nerve sheaths; -moreover, that both during <i>acute</i> attacks and alike in the <i>inter-paroxysmal</i> -periods gouty subjects are prone to two special -varieties of fibrositis, viz., <i>lumbago</i> and <i>sciatica</i>. I may add, -too, that in these individuals it is not uncommon for them to -suffer with these local varieties of fibrositis from time to time -prior to the advent of <i>regular</i> or <i>articular</i> gout.</p> - -<p><i>Fibrositis.</i>—As Bassett Jones and I in our work on fibrositis -have dealt exhaustively with the treatment of its various forms, -our remarks here must necessarily be devoted largely to the -general principles of therapy, and for further details we would -refer the reader to our treatise on the subject.</p> - -<p>Whatever the type of fibrositis we are confronted with, the -therapeutic indications are precisely similar to those advocated -for <i>articular</i> gout. In other words, the indispensable preliminary -measures are to control the production, absorption, and elimination -of <i>toxins</i>. To this end, we must secure adequate evacuation of -the bowels, free action of the skin, and diuresis. These ends will -the more surely be attained if at the onset a temporary fast be -enjoined, or a suitable dietary with copious drinking of bland, -unirritating fluid. The general malaise and <i>pyrexia</i> indicate -clearly that these cases of acute fibrositis must be treated in -accordance with the general rules applicable to the febrile state.</p> - -<p><i>Acute Lumbago.</i>—Brisk purgatives are here our most efficient -allies, for there is usually marked functional derangement, with -high-coloured urine and dark, offensive fæces. In such cases it -is well to give 3-4 grains of calomel at night, followed in the -morning by a saline purge, and the same often has to be repeated -once or twice during the acute stage. Also the following prescription, -preferably rendered effervescent by adding a few grains -of citric acid to each dose, may swiftly abate the intensity of the -suffering:—</p> - -<table class="rx"> - <tr> - <td>℞</td> - <td>Pot. bicarb.</td> - <td>gr. 15</td> - </tr> - <tr> - <td></td> - <td>Pot. nitrat.</td> - <td>gr. 10</td> - </tr> - <tr> - <td></td> - <td>Vin. colchici</td> - <td>♏︎ 10-15</td> - </tr> - <tr> - <td colspan="3">Aquæ ad unciam, quartis horis sumenda.</td> - </tr> -</table> - -<p>Or, as in acute gout, we may give an initial large dose of 30-40 -minims of colchicum wine, with subsequent attenuation of the -same. It is in cases with scanty, high-coloured urine and costive -bowels that <i>colchicum</i> succeeds best. On the other hand, in some<span class="pagenum"><a id="Page_412"></a>[412]</span> -cases of acute lumbago the urine is copious and light-coloured, -and the bowels regular, and the fæces normal in appearance. -Here the value of the initial purge is not so apparent, and a -mixture containing <i>salicylates</i> and alkalies will be more likely to -give relief, aided, if necessary, by nightly doses of Dover’s powder, -followed by a morning draught of some aperient.</p> - -<p>Where the case shows some disposition to linger on in a sub-acute -form, and the urine still remains charged with lithates, a mixture -of citrate or nitrate of potash, spirits of nitrous ether, and infusion -of buchu should be given thrice daily. Sometimes, too, in -broken-down subjects with sluggish circulation, we have found -the addition of a few minims of tincture of digitalis most helpful -in clearing up the condition.</p> - -<p>Next to lumbago, pleurodynia is the most common muscular -type of fibrositis to be met with in the trunk. I have seen its -subsidence prove the signal for an outbreak of acute articular -gout in the great toe. This significant sequence indicates the -necessity of being alive to the possibility of a <i>gouty</i> basis in such -cases and the advisability of combining <i>colchicum</i> with our -remedies.</p> - -<p><i>Sciatica.</i>—This almost invariably is the outcome of a preceding -attack of lumbago, of which, indeed, it is but an extension. If -seen sufficiently early, and certainly when there are febrile -symptoms, a mercurial purge, followed by an alkaline and diuretic -mixture in combination with colchicum or salicylate of soda, -should be resorted to vigorously, so as to abort, if possible, the -attack.</p> - -<p>If the underlying constitutional anomaly has been correctly -diagnosed as gouty, the colchicum will exert its specific effect, and -quickly, and the more speedily the sooner it is exhibited in the -early stage. But even when seen later it is well worth trying the -following combination:—</p> - -<table class="rx"> - <tr> - <td>℞</td> - <td>Quin. hydrochloratis</td> - <td>½ drachm.</td> - </tr> - <tr> - <td></td> - <td>Pot. iodidi</td> - <td>2 drachms.</td> - </tr> - <tr> - <td></td> - <td>Vin. colchici</td> - <td>1 ounce.</td> - </tr> - <tr> - <td></td> - <td>Tinct. aurantii</td> - <td>2 ounces.</td> - </tr> - <tr> - <td></td> - <td>Aquam chloroformi</td> - <td>To 8 ounces.</td> - </tr> - <tr> - <td colspan="3">Sig., 2 teaspoonfuls in a wineglass of water twice a day.</td> - </tr> -</table> - -<p>Having regard also to the gouty origin, it is hardly necessary -to insist on regular and adequate evacuation of the bowels.</p> - -<p>Of all varieties of gouty fibrositis the <i>acute brachial</i> type is the -most difficult to treat, owing to the marked tendency to prolongation -of the acute stages. The only chance of cutting short such -an attack is not to treat lightly its earlier manifestations, but to<span class="pagenum"><a id="Page_413"></a>[413]</span> -bear in mind its evil potentialities; but only too often they -do not come under observation until the condition is well -established.</p> - -<p>Gowers, who has written so illuminingly on this particular type -of fibrositis, obtained the best results in the early stages from a -combination of nitrous ether, citrate of lithium, and colchicum, -with in addition, in the more intense forms, small doses of -perchloride of mercury. Of the salicylates, salicin and aspirin, -he speaks with but faint praise, and I have myself known them -afford but little aid.</p> - -<p>In reviewing the foregoing acute types of fibrositis, I would, as -to <i>relief of pain</i>, insist on internal medication of all sorts being -held as purely secondary to the infinitely more important matter -of procuring rest and fixation for the inflamed structures. -Immobilisation, indeed, supplemented by thermic and anodyne -applications, hardly, if ever, fails to alleviate the suffering. If -these prove futile, aspirin and phenacetin, either singly or in combination, -should be exhibited. Here I would remark also on the -value of cimicifuga, which I have found strikingly useful. Lastly, -only very exceptionally in my experience is morphia called for.</p> - -<p>In <i>chronic</i> or <i>recurring</i> forms of fibrositis we should mark any -deviation from health in the shape of gastro-intestinal or hepatic -derangement, while noting also any inactivity on the part of -the kidneys or skin. As to drugs, chief reliance must be placed -on the iodides guaiacum, arsenic, and sulphur. They are most -useful, of course, when exhibited during the early stages, before -organisation of the inflammatory products ensues. When hard -and resistant nodules or infiltrations have formed, their -administration is of little value.</p> - -<p>It is for this reason that I have elsewhere advocated early resort -to <i>local massage</i>, viz., at the close of acute attacks, as only by -this means can we hope to dissipate these new formations, the -persistence of which determines the inveterate tendency to -recurrence. In the space at my disposal it will be impossible to -consider in detail all the special modes of therapy—electrical, -thermal, hydrotherapeutic, etc.—and for this information I must -refer the reader to the next chapter.</p> - -<p><i>Oxaluria.</i>—This condition is sometimes met with in the gouty. -The subjects are often nervous, irritable, and languid, complaining -at the same time of vague pains, most frequently in the loins and -along the distribution of the sciatic nerve. It occurs more -commonly in persons of sedentary habit, and correction of this, -as well as revision of their diet, is almost the only effectual method -of getting rid of the complaint.</p> - -<p>All vegetables rich in oxalates, such as rhubarb and spinach,<span class="pagenum"><a id="Page_414"></a>[414]</span> -must be eliminated, and likewise tea. At the same time, as Sir -Alfred Garrod suggests, we should, to influence the proportions -of the bases present in the urine, cut off all foods rich in calcium, -<i>i.e.</i>, milk and eggs. On the other hand, we should advise the -intake of such as are rich in magnesium and yet poor in oxalic -acid, viz., peas, beans, and coffee, and oxalate-free foods, such as -all kinds of meat.</p> - -<p>In my own person I suffered for some weeks with obstinate -lumbar pain, the cause of which appeared to be obscure until the -existing state of oxaluria was discovered by a professional -colleague. I would here emphasise the fact that when a case -of lumbar or sciatic pain is defiant of cure by the usual methods -of therapy we should always suspect this possibility of oxaluria, -for commonly the urine is copious and clear; hence perhaps the -frequency with which the condition is overlooked.</p> - -<p>As to medicinal measures, we should bear in mind that Sir John -Rose Bradford pointed out that the production of oxalates was -initially due to deficient HCL, with secondary fermentation of -foodstuffs, <i>i.e.</i>, carbohydrates, especially sugar. The primary -indication, then, is to reinforce the digestive capacities by -administering hydrochloric acid or, as many prefer the dilute -nitric muriatic acid, in combination with nux vomica, and in some -cases pepsin. As Sir William Whitla remarks, if organic acidity -be prominent, this may be intensified by mineral acids, in which -event alkalies combined with a few grains of papain two hours -after meals are indicated.</p> - -<p>In conclusion, the nerve element in these cases is so pronounced -that a thorough change of air and habits is often indicated, -combined with freedom from worry, abundance of exercise, and -a stimulating course of hydrotherapy.</p> - -<p><i>Glycosuria.</i>—The variety met with in the gouty, being of the -alimentary type, is usually very responsive to dietetic measures, -and these have been already dealt with. A course of spa treatment -is often the best possible mode of therapy for these cases.</p> - -<p>As to medicinal measures, these certainly should not be -embarked upon until the effect of dietetic revision has been -ascertained. If under their influence the glycosuria wholly -disappears, then drugs may be uncalled for, save perhaps -occasional aperients, antacids, or similar remedies of like nature. -If, on the other hand, the glycosuria cannot be kept under -control by dietetic measures, then recourse must be had to drugs. -Here it may be noted that guaiacum diminishes the amount of -sugar excreted, and it may be given a trial before resorting to -codeia. Generally speaking, when the case requires codeia it -has passed out of the realm of gouty glycosuria into that of true<span class="pagenum"><a id="Page_415"></a>[415]</span> -diabetes, the treatment of which grave disorder is beyond the -scope of this work.</p> - -<p><i>Hyperchlorhydria.</i>—The disorder is rare in gouty patients, and -its diagnosis from organic acidity cannot be made without -examination of the stomach contents. Moreover, when found to -be present an endeavour should be made to elucidate its cause. -If gastric and duodenal ulcer can be excluded and the condition -appears to be of the nature of a secretory neurosis, then the -underlying nervous defect will call for treatment.</p> - -<p>In some cases the exciting cause lies in errors of diet and habits -of living. These when faulty require correction; very often -in these cases it is not so much the nature of the food as the -hurried manner in which it is bolted that is responsible. At -times, when free from hurry or worry, they can eat any kind of -food with impunity. When the attacks are on, it frequently -happens that all types of food, whether easily digestible or not, are -equally provocative of acidity. We see then how large a part -general hygiene plays in the successful treatment of these cases.</p> - -<p>As to diet, this is, of course, of primary importance, the main -indications being the reduction or withdrawal of farinaceous foods, -and for a short period on a Salisbury regimen or some modification -thereof.</p> - -<p>The medicinal indication is to afford relief during the acute -attacks. Fortunately these are usually <i>intermittent</i>, and when -the occasion arises are fairly readily controlled by massive doses -of alkalies, frequently combined with an artificial digestive, -<i>i.e.</i>, papain. While magnesia and bicarbonate of soda are, as a -rule, invoked, others speak well of sodium phosphate (5 grams) -with menthol (0·25 gram), given two hours after each meal.</p> - -<p>Luff, discussing hyperchlorhydria in the gouty, highly extols -hopogan (magnesium peroxide), in doses from 20-30 grains, one -hour after food, the amount to be reduced if it causes purgation. -To inhibit excessive production of HCL, belladonna, in 5-minim -doses of the tincture, before meals results in reduction of acid -values, both absolute and relative, of the stomach contents, and, -moreover, relieves spasmodic contractions. Constipation in these -gouty subjects is best combated by an occasional nightly pill -containing colchicum in combination with aloes or other laxative. -Lastly, when digestion becomes more normal nervine tonics, such -as arsenic, valerian, and the like, may be given to correct, if -possible, the underlying nerve element in these troublesome -cases.</p> - -<p><i>Gouty Phlebitis.</i>—To obviate the risk of embolism, absolute -immobilisation of the affected limb is imperative, and it should -be slightly elevated and protected by a cradle. In many cases<span class="pagenum"><a id="Page_416"></a>[416]</span> -it will suffice if the limb be enveloped in cotton wool and a broad, -many-tailed bandage lightly and evenly applied. If the pain be -severe, equal parts of glycerine and the green extract of belladonna -should be smeared along the course of the inflamed vein and hot -fomentations applied. Internally saline aperients should be -given to secure daily evacuation of the bowels, and a mixture -containing iodide of potassium and ammonium carbonate taken -three or four times a day, to promote solution of the clot.</p> - -<p><i>Gouty Eczema.</i>—In these cases the primary indication is to -revise thoroughly the diet, to the end of correcting a frequently -associated gastro-intestinal derangement, notably any tendency -to constipation. If these the basal indications are not fulfilled, -all local forms of medication will be futile. As to these last, the -primary desideratum is to protect the parts from all accidental -irritants, and the chief source of offence is scratching by the -victim himself. Otherwise we should take every care to prevent -irritation by clothing, hard collars, etc.</p> - -<p>While cleanliness is essential, the soaps used should be of the -neutral kinds, or bran or barley-water substituted. Ointments -and lotions are best avoided. In the milder cases protection of -the parts is the essential. In the limbs this may be attained by -glyco-gelatine zinc; but on the neck, the groin, the inside of the -thighs or lower parts of the abdomen, the tragacanth pastes or -similar preparations are more suitable. Both the gelatine and the -pastes and varnishes may be readily medicated with drugs of -anti-pruritic properties, such as oil of cade, carbolic acid, resorcin, -or salicylic acid.</p> - -<p><i>Gouty Nephritis.</i>—This must be treated on the lines recognised -as suitable for <i>chronic Bright’s disease</i>, the underlying gouty -condition being always borne in mind, as also any contamination -with <i>lead</i>. As general measures any excess in eating or drinking -must be avoided, the skin kept active, and the bowels open; and -where possible favourable climatic conditions should be attained.</p> - -<p>Frequently the treatment resolves itself into that of the -associated arterio-sclerosis with high blood pressure. This we -should endeavour to control by regulation of the subject’s habits -in the matter of diet, work, exercise, etc., rather than by flying -forthwith to the use of <i>vaso-dilators</i>, premature resort to which -has often proved the beginning of the end.</p> - -<p>Moreover, I would, like many others, strongly deprecate the far -too prevalent practice of dilating to these subjects on the evil -potentialities of raised blood pressure. Not a few thenceforth -literally walk in the valley of the shadow, and the fear of sudden -death is ever before them. It is not only cruel, but frequently -unnecessary. Often the increase of tension is no more than their<span class="pagenum"><a id="Page_417"></a>[417]</span> -age would account for, and equally often no symptoms indicative -of raised blood pressure are complained of. Why then make the -subject miserable?</p> - -<p>By all means, take the blood pressure, but say as little as -possible about it. These people, in my experience, need more -often to be reassured than frightened. Only now and again does -one meet with individuals who must for their own sake be gravely -warned of the dangers incidental to their condition, men who, -despite the warnings afforded by giddiness, epistaxis, etc., will -not alter their ways of living.</p> - -<p>As to medicinal measures, all agree that an occasional blue pill -or a dose of calomel, ½-1 grain, for three or four nights in -succession, and followed in the morning by a saline purge, is one -of the most satisfactory procedures to adopt. Hand in hand with -this, a course of iodides, gr. 10-15 three times a day, for some -weeks, is also most beneficial. After six or eight weeks of the -above we may substitute a course of nitrites, <i>e.g.</i>, nitro-glycerine, -sodium nitrite, or erythrol tetranitrate. Nothing is better in the -milder cases than Sir Lauder Brunton’s formula, the efficacy of -which I have often proved:—</p> - -<table class="rx"> - <tr> - <td>℞</td> - <td>Sodium nitrite</td> - <td>gr. ½-2</td> - </tr> - <tr> - <td></td> - <td>Potassium nitrate</td> - <td>gr. 10-20</td> - </tr> - <tr> - <td></td> - <td>Potassium bicarb.</td> - <td>gr. 10-30</td> - </tr> - <tr> - <td colspan="3">Fiat pulvis, to be taken in a tumblerful of water every morning.</td> - </tr> -</table> - -<p>Needless to say, vaso-dilators should not be exhibited if signs -of waning cardiac power are evident. Also when there is much -albumen the use of mercurial purges calls for great discretion, -and saline aperients should be given the preference. Insomnia, -a frequent trouble in these cases, is best met by bromides, and I -agree with Luff that in gouty subjects sleeplessness is better -combated by measures which reduce arterial tension than by -resort to hypnotic drugs.</p> - -<p>Lastly, symptoms of cardiac dilatation and failure, which -should be suspected when the arterial pressure falls without the -previous use of vaso-dilators, will call for the exhibition of cardiac -tonics: digitalis, strophanthus, and strychnine; and threatened -uræmia may be postponed by a judicious dietary, saline purgation, -and diaphoretic measures.</p> - -<hr class="chap x-ebookmaker-drop"> - -<div class="chapter"> - -<p><span class="pagenum"><a id="Page_418"></a>[418]</span></p> - -<h2 class="nobreak" id="CHAPTER_XXXI">CHAPTER XXXI.<br> -<span class="smaller">CLIMATO-THERAPY, HYDRO-THERAPY, ETC</span></h2> - -</div> - -<h3><span class="smcap">Climate and Residence</span></h3> - -<p>While, naturally, individuals display wide differences in their -capacity of adjustment to variations in climate and season, there -is no doubt that the gouty, as a class, are abnormally deficient -in their power of adaptation in this respect. Said Hippocrates -in one of his aphorisms, “Podagrici affectus vere et autumno -plerumque moventur,” and this peculiar influence of <i>season</i>, viz., -the aptness of gout to recur in spring and autumn, especially in -its <i>early</i> stages, is a very singular feature.</p> - -<p>The increased incidence at these particular periods of the year -is, I think, a striking proof of their deficiency in the defensive -mechanisms that enable normal persons to withstand with comparative -impunity sudden transitions from cold to heat, dryness -to damp, and so forth. So it is that rapid changes in the surrounding -air, in its degree of warmth, or its motion by wind are -fertile of attacks. The east and north-easterly winds of spring -account for no few examples, as likewise inadequate protection -from cold or damp.</p> - -<p>In short, a <i>variable</i> climate is the most provocative of gout, that -is, most likely to elicit gouty manifestations in one predisposed -thereto. Conversely, stability in climate favours freedom from -attacks. Thus some obtain exemption from their gout by -removing to a hot climate, others when removed to one of cold, -dry character. Doubtless these differences in response hark back -to <i>individual constitutional peculiarities</i>.</p> - -<p>It is the vigorous plethoric persons, who eat too much, that do -well in dry, cold climates. The low temperature and dryness of -the air stimulate tissue changes, dispose them to active exercise -with consequent increased efficiency of digestion, assimilation, -and excretion.</p> - -<p>On the other hand, many victims of gout are spare feeders, -with feeble powers of digestion and metabolism, and for them a -mild, moderately warm and not too damp climate is the more -suitable, involving, as it does, less strain upon their capacities of -adjustment.</p> - -<p>If one may be permitted the generalisation, the ideal climatic<span class="pagenum"><a id="Page_419"></a>[419]</span> -conditions for the gouty are low relative humidity, abundant -sunshine, and a low rainfall. But, alas! too often, permanent -residence in such desirable surroundings is unattainable, and the -most that can be compassed is a brief sojourn in some more congenial -environment.</p> - -<p>Still, some discrimination must be shown in the matter of -choice, and the physician, while mindful of the gout, must envisage -the <i>individual</i> as a whole; for in advocating a change of climate -his hope is that he may remove or antagonise certain noxious -influences and coincidently restore the physiological machine as -near as can be to a state of functional efficiency.</p> - -<p>The former purpose will often be fulfilled by mere withdrawal -of the subject for a time from his usual calling and environment. -How frequently will simple <i>rest</i> and <i>recreation</i> succeed when -medicinal and other forms of therapy have wholly failed! And -how largely, may we remark, does the Vis Medicatrix Naturæ work -through the medium of things <i>psychic</i>, not physical, to achieve its -beneficent ends!</p> - -<p>Still, not always is it <i>rest</i> that is needed, and some regard must -be had to previous habits. Thus, for the <i>sedentary</i>, repair to a -<i>bracing</i> climate is indicated, some inland resort of moderate -elevation, where oxidation processes are quickened, and where if -they eat more they take more exercise, and so adequate elimination -is assured.</p> - -<p>On the other hand, for the elderly or old, or those enervated by -long-continued gout, a <i>sedative</i> climate must be sought, one marked -by mildness, dryness, and equability. Bath, with its low diurnal -range of temperature, is eminently suitable for this class of gouty -patient, who often stand but ill the, for them, too stimulating -qualities of more bracing localities, such as Llandrindod, Harrogate, -or Buxton, etc.</p> - -<p>Frequently, however, our choice is dominated by some <i>associated -morbid affection</i>. Our patient may suffer from a so-called -gouty <i>eczema</i>; if so, he must avoid cold, damp places, or windy -localities, and, for that matter, sea air often, at first at least, -aggravates the affection. Or it may be that he suffers with -“dyspepsia,” some catarrhal condition of the alimentary canal, -or a “sluggish liver.” For him, then, a dry inland health resort -of moderate or high altitude is preferable to one of sea level, which -will likely find him drowsy, indisposed to exercise, and a prey to -what he terms biliousness.</p> - -<p>If <i>renal</i> disease be a complication, he should seek a dry, warm -climate, and, if he can, winter abroad, say, in Upper Egypt or -Algiers, which, though it is warm and dry, is nevertheless somewhat -marred by the wide diurnal range of temperature and the<span class="pagenum"><a id="Page_420"></a>[420]</span> -not infrequent cold winds. If, therefore, very sensitive to vicissitudes -of temperature, the relatively dry, warm marine health -resorts of the Riviera are open to him.</p> - -<p>If to go abroad is out of the question, one of the mild southwestern -seaside resorts at home is eligible, <i>i.e.</i>, Bournemouth, -Sidmouth, or the more sheltered parts of Torquay, and Falmouth. -Again, if he show a tendency to <i>cardiac dilatation</i>, with or without -valvular disease, high altitudes will obviously be unsuitable, and -dry, inland resorts of moderate or low elevation should be given -the preference.</p> - -<p>Lastly, before despatching any gouty subject for a so-called -change, it is wise to elicit any personal <i>idiosyncrasies</i> that he may -be victimised by. In other words, find out his most vulnerable -points. Thus some gouty persons are able to brave cold and -damp with impunity, but pay dearly for the slightest indiscretion -in diet. They must therefore be warned that no climatic change, -however suitable, will absolve from the ill-effects of improper or -immoderate eating.</p> - -<p>Others again—the majority—are extremely sensitive to atmospheric -changes, and such good as they might derive from a well-selected -climate is nullified through thoughtless omission of simple -precautions against “chills.” In short, the victims of gout can -only ensure for themselves the beneficial effects of <i>climatic therapy</i> -if, at the same time, they vigilantly shield themselves from what -experience has shown to be, in their particular instance, the -most fertile extrinsic or intrinsic source of relapses or exacerbations -of their disorder.</p> - -<p><i>Choice of Residence.</i>—In these days it may savour of irony to -talk of a choice of residence where none is. Still, much of the -benefit accruing from a change of air will depend not only on the -place resorted to, but the situation of the dwelling or hotel, in -which the subject takes up his temporary abode. Thus in inland -resorts some parts of the town may lie in a hollow, others on -adjoining slopes or plateaux at an altitude higher by some hundreds -of feet. Sites like the latter are obviously unsuitable for -the victims of cardiac dilatation, etc. Again, where the patient’s -condition is such that he must perforce spend a large portion of -his time indoors, it is a matter of some moment that the situation -and aspect of the building and, more pertinently, the subject’s -suite or room be ascertained before he takes up residence.</p> - -<p>Apart from sanitary and hygienic considerations, the quality -of the cuisine, general comfort, class of society, have all to be -thought of, if the best results are to be obtained. They are not -unimportant details. How often is the benefit of a stay nullified -by uncongenial surroundings, by a gloomy outlook, the fret and<span class="pagenum"><a id="Page_421"></a>[421]</span> -jar of ill-assorted or discordant elements, that forbid that cheerful -intercourse that does much to restore that sense of <i>bien-être</i> so -eagerly sought.</p> - -<p>In short, attainment of the best results of climato-therapy can -only be achieved through the medium of a closer co-operation -between those who practise at health resorts or spas and the -patient’s usual medical attendant. But, meanwhile, for most -of us, our dwelling place doth rest upon our calling, and we -may take this for our comfort that climatic vicissitudes may -be greatly mitigated by a <i>well-situated</i> and <i>sanitary</i> residence. -I allude, of course, here to a <i>permanent</i> abode, and the gouty, if -he enjoy any latitude, should live in a house built on a <i>well-drained -gravel soil on a slope, sheltered from the north and -north-east winds</i>.</p> - -<p>Again, with the question of habitation is bound up the equally -important matter of <i>clothing</i>. By our forefathers <i>flannel</i> underwear -was deemed the most eligible, despite its low or deficient -power of absorption. But, without discussing the various -arguments adduced in favour of this or that particular fabric, I -would myself favour <i>silk</i> as being, perhaps, the ideal <i>underwear</i>; -next to this a single woollen or woven linen vesture, and it goes -without saying that, prone to excessive sweating as these gouty -subjects are, frequent changes are essential. The feet of the gouty -are their weak spot, and, apart from the correction of <i>static -deformities</i>, flatfoot, etc., it is extremely desirable that they not -only be well shod, but be especially careful not to sit about in wet -boots or socks.</p> - -<p>For the rest, their outer layers of clothing should be light, -warm, easy and not tight fitting. Extremely liable as they are to -lumbago and sciatica, they should be careful to enlist a thicker -fabric than is usual for the back of their waistcoats; while sufferers -from sciatica may, with advantage, insert a silk lining to -the seat of their trousers.</p> - -<p>Lastly, it is most important that the gouty, and of course all -persons, should dress according to the prevailing weather and not -according to the <i>time of year</i>. For them, more than any other -class of person, to doff summer and don winter clothing for no -other reason than some arbitrary date is fraught with mischances, -freedom from which would be purchased by a little commonsense.</p> - -<h3><span class="smcap">Exercise</span></h3> - -<p>It has been wisely said that “those threatened with gout -should imitate as far as practicable and consistent with comfort -the habits of agricultural labourers,” for sedentary occupations<span class="pagenum"><a id="Page_422"></a>[422]</span> -and idle ways not only favour the invasion of the disorder but -hasten its recurrence.</p> - -<p>How frequently, indeed, is it the direct outcome of an abrupt -change in habits—a hunting man, predisposed to gout, sustains -an accident, can no longer ride to hounds and takes to motoring. -Unless he forthwith curb his food intake, the disorder overtakes -him. Sometimes misfortune proves a blessing in disguise, as in -the case related by Van Swieten of an opulent and gouty old priest, -who, captured by Barbary corsairs and forced to work as a galley -slave, soon lost his gout.</p> - -<p>Again, it is notorious that in those in whom the brunt of the -disorder falls on the <i>lower</i> limbs, the outlook is more sombre than -in those more severely crippled in the hands. In short, capacity -for and willingness to take adequate exercise is one of the -most potent measures wherewith to fend off the gout. The -amount should be in proportion to the age, strength, and previous -habits. The exercise should be taken not after a spasmodic -but <i>systematic</i> fashion. For erratic, like excessive, exertion -often converts the expected benefit into the exciting cause of -an attack. The aim should be not exhaustion but wholesome -fatigue.</p> - -<p>Young and fairly vigorous persons, if previously sedentary or -indolent in habit, should take regular exercise, gradually increased. -In the middle-aged, especially if obese, it should be graduated -according to the capacity of their circulatory organs, and more -stress laid on respiratory exercises and dietetic restrictions. For -in their instance fatigue or over-exertion is easily induced, often -with grave consequences. Also, in long-standing cases, neurasthenic -from long-continued pain, it is well to begin more or less -tentatively, and in many cases to prescribe a course of <i>massage</i> -before proceeding to active exercise. For not seldom such -subjects have but a small fund of nerve energy to draw upon.</p> - -<p>In the gouty, even the malign influence of bad habits of living -is greatly mitigated by active exercise and labour. “The gout -very rarely visits the poor man’s cottage.” Nothing can so -effectually counteract a predisposition to the disorder, and what -Sydenham thought of its value we may guess from his trenchant -remarks on horse exercise. “And, indeed, I have often thought -if a person was possessed of as effectual a remedy as exercise is, -in this and most <i>chronic</i> diseases, and had the art likewise of -concealing it, he might easily raise a considerable fortune.”</p> - -<p>In conclusion, if healthful exercise of the body is imperative -for the gouty, I need scarcely labour the desirability also of congenial -and adequate exercise of the mental faculties. Adequate, -but not excessive, lest, like Sydenham, it reacts in added sickness.<span class="pagenum"><a id="Page_423"></a>[423]</span> -Otherwise absorption in some honourable pursuit will do much -to dissipate that tendency to introspection and depression so often -born of the consciousness of an ever-constant menace to long-continued -health.</p> - -<div class="poetry-container"> -<div class="poetry"> - <div class="stanza"> - <div class="verse indent0">“Orandum est, ut sit mens sana in corpore sano.”</div> - </div> -</div> -</div> - -<h3><span class="smcap">General Massage</span></h3> - -<p>In judiciously prescribed and skilfully applied massage we have -an agent of pre-eminent value in the treatment of gout. Indeed, -Sir William Temple—a martyr to the disease—when speaking of -the benefit of “friction,” frankly stated that “No man need have -the gout who can keep a slave.” In this there is much truth, for -the beneficial results of massage are not confined merely to the -affected joints or muscles, but, as a result of the improved circulation, -waste products are more readily excreted, the nerve -centres regain tone, and a general feeling of <i>bien-être</i> is promoted.</p> - -<p>It cannot be doubted that general massage of the trunk and -limbs accelerates the elimination of the chemical outcasts of -metabolism, and simultaneously, by ensuring a more adequate -supply of fresh blood to the tissues, must result in an access of -renewed vitality. Many, indeed, have adduced experimental -proof that such a quickening of the vital processes does ensue after -general massage. We should therefore, in elderly or feeble subjects, -or in those of sluggish habits, advocate from time to time a -course of general massage for its <i>prophylactic</i> effects.</p> - -<p>It is the more especially indicated in those gouty subjects prone -to attacks of <i>muscular fibrositis</i>—attacks of which are undoubtedly -favoured by the retention of the toxic and waste products of -muscular metabolism. Nothing, again, so facilitates the dissipation -of exudates, nodules, or thickenings in these structures, -for the treatment and prophylaxis of which massage is indispensable.</p> - -<p>In enlisting the <i>prophylactic</i> action of general massage, it is not -desirable that the <i>séance</i> should exceed forty minutes, and it -should in all cases be followed by an hour’s rest; to practise it -too soon after a meal is inadvisable, and in those cases in which -it favours the advent of sleep it is best undertaken in the late -evening.</p> - -<p>In conclusion, I would urge the importance of more interest -being taken by the physician himself in the technique of massage, -as I am assured that, if rationally and perseveringly practised, it -constitutes one of the most valuable adjuncts in the prophylaxis -of gout.</p> - -<p><span class="pagenum"><a id="Page_424"></a>[424]</span></p> - -<h3><span class="smcap">General Hydro-therapy</span></h3> - -<p>That hydro-therapy constitutes one of the most effective, if not -<i>the</i> most effective, methods of treating gout, is almost a truism, -if judged by that most “acid test”—Experience. The particular -applications we are about to discuss entail <i>exposure of the -whole body</i>. In other words, those measures directed more especially -to treatment of the <i>underlying causal state</i>—the correction of -that warp of metabolism or auto-toxic state of which the arthritic, -muscular, or other lesions are but local manifestations.</p> - -<p>It goes without saying that, with this for our objective, there is -much need for discrimination in the selection of measures suitable -for individual cases, and, naturally, the basis of such differential -treatment is <i>thorough physical examination</i> prior to embarking on -the course. Yet how frequently on their own initiative do these -subjects enter lightly upon a series of baths, mingling stimulant -and sedative procedures in haphazard fashion, unwitting that -hydriatric measures are capable of infinite harm when misapplied.</p> - -<p>For in hydro-therapy the personal equation is of prime importance, -varying with <i>individual reactive peculiarities</i>. In short, the -character of the response differs widely in different subjects, -efficiency or not of the nervous and circulatory functions being -the chief controlling factors. Hence accurate appraisement of -the reactive powers of the constitution to hot and cold applications -is the basis of rational hydro-therapy.</p> - -<p>Thus <i>nervous irritability</i> is <i>the</i> outstanding characteristic of some -gouty constitutions. They are therefore intolerant of extremes -of temperature, and for them sedative or sub-thermal baths are -the most suitable.</p> - -<p>Others suffer from <i>torpid circulation</i> and <i>sluggish vascular -response</i>, and in their instance, stimulant measures, hot or cold, -in sequence or in alternation, are indicated. Again, some are -<i>obese</i>, and others <i>lean</i>, and while of the twain the former react -more feebly, on the other hand, they stand prolonged courses of -hydro-therapy more satisfactorily. In contrast, the thin, though -they react well, are more readily exhausted, and so apt to suffer -from “secondary chill” or other untoward consequences.</p> - -<p><i>Prophylactic Measures.</i>—As we have noted, the “gouty,” more -than others, are intolerant of atmospheric vicissitudes. Accordingly, -if we would strengthen their defensive mechanisms in this -respect, we must endeavour to train them to react more -adequately to <i>cold</i> or <i>sub-thermal</i> impressions.</p> - -<p>Of the value of <i>thermal</i> applications in chronic gout I am convinced, -but, on the other hand, we must not blind ourselves to -the value—<i>prophylactically</i> speaking—of their judicious conjunction<span class="pagenum"><a id="Page_425"></a>[425]</span> -with <i>sub-thermal</i> or <i>cold</i> procedures. For these latter -stimulate oxidation processes, and in chronic gout, according to -many, there is deficient oxidation of protein waste, while, apart -from this, in the gouty obese there is imperfect oxidation of -adipose tissue.</p> - -<p>Prophylactic measures to be of any real avail must be <i>continuous</i>, -and spas or hydropathic establishments should indeed be -more alive to their educational responsibilities in this matter, -for the benefits of hydro-therapy as regards prophylaxis are -within the reach of all possessed of the convenience of a modern -bath-room.</p> - -<p>They should be taught to inure themselves by taking daily a -tepid bath followed by a cold shower or rain spray. If this be -too drastic, let them, while standing in warm or tepid water, -briskly rub the rest of the body with a coarse towel wrung out of -cold water, into which, if liked, salt has been added to the point -of saturation. In this way the tonic effects upon the skin of -hypo-thermal or cold applications may be invoked, and thereby its -undue sensitiveness is reduced and therewith the liability to -subsequent attacks.</p> - -<p>It now devolves upon us to consider under what circumstances -hydro-therapy is inadvisable, and, incidentally, those ill-effects -that indicate its modification or abandonment.</p> - -<p><i>Contra-indications and Untoward Complications.</i>—Authorities -generally seem unanimous on this point, viz., that the chief sphere -of hydro-therapy is in <i>chronic</i> or subacute gout. On the other -hand, they are equally unanimous in proscribing its exhibition -in <i>acute</i> forms of the malady. Speaking for myself of the Bath -waters, I am quite convinced that the distinguished physician, -Caleb Hillier Parry’s pronouncement, “that the Bath waters, -in no form whatever, are beneficial during the paroxysms of gout, -or in any inflammatory disposition which may exist in the -interval,” is not only true but capable of extension to all forms -of hydro-therapy as applied at this stage of the disorder.</p> - -<p>Nor do I think it advisable if <i>prodromal</i> symptoms suggestive -of the imminence of an attack are present. It is too, I think, -impolitic—after the subsidence of a severe attack—to resort too -quickly thereto, the more especially if there is a disposition to -what our forefathers termed “flying gout.” In either event, an -<i>acute outbreak</i> is most likely to ensue, and, though there is doubtless -some truth in the old idea that a gouty subject feels better -after an attack, still it is not, I think, the physician’s <i>rôle</i> to evoke -gout, but rather to prevent its explosion. Occasionally mischances -of this sort will happen, but only exceptionally, if the -foregoing safeguards be respected. Certainly if the patient seems<span class="pagenum"><a id="Page_426"></a>[426]</span> -palpably on the verge of an attack it is but discreet to postpone -baths until the good effects of free purgation and strict dieting -have been derived.</p> - -<p>Indeed, I would go further, in that I think that, under all circumstances, -a course of hydro-therapy should be preceded by <i>free -evacuation of the bowels</i>. We should then hear less of that disturbance -of the system known as “well-fever” or “poussée-thermale,” -which, it is not sufficiently recognised, may follow not only <i>internal</i> -but <i>external</i> use of mineral waters. I allude to <i>dyspepsia</i>, -<i>lassitude</i>, or <i>skin eruptions</i>, etc., symptoms which formerly were -thought to be of critical or beneficial nature, but which, I agree -with Dresch, are probably the result of an <i>auto-intoxication</i>, and, -as he thinks, more or less combined with an infection by the -bacillus coli. Should such symptoms supervene during a course, -the baths had better be omitted for two or three days <i>pending -their disappearance</i> under appropriate measures.</p> - -<p>In the same way, there are reservations regarding the suitability -of baths in <i>chronic</i> gout. Thus, if complicated by advanced -<i>cardiac</i> or <i>renal</i> disease, hydro-therapy is often <i>contra-indicated</i>, -and, in any instance under such circumstances, has to be undertaken -very cautiously. On the other hand, it is wonderful how -well many examples respond if due discrimination be exercised. -Especially suitable are those cases of gout and <i>renal</i> disease in -which the <i>heart</i> is hampered by increased <i>peripheral</i> resistance. -Such cases under Aix massage, frequently, as Bain and Edgecombe -pointed out, improve strikingly through the consequent -reduction of arterial pressure.</p> - -<p>Turning now to the <i>untoward results</i> or <i>complications of hydro-therapy</i>, -hot baths, if of too high a temperature or too prolonged, -may cause <i>vertigo</i>, <i>fainting</i>, or <i>palpitation</i>—an indication for reduction -in temperature and duration. Or, if douches are used, the -pressure may be excessive. <i>Insomnia</i>, again, may follow over-stimulation, -and our measures must be altered accordingly. Loss -of appetite and strength, too, may be the outcome of too drastic -treatment and excessive reaction.</p> - -<p>It is well, also, that during a course of hydro-therapy the -patient’s body weight be taken from time to time, and note made -whether he is gaining or losing in muscular strength. If weight -sink and, coincidently, strength increase, all is well with the -gouty obese; but if muscular capacity be waning, excessive -demands are being made on the subject’s oxidising and eliminative -processes.</p> - -<p>Examination of the <i>urine</i>, too, may yield indications of value. -A notable increase in the output of <i>chlorides</i> suggests excessive -tissue waste, and of <i>phosphates</i> too marked excitation of the nerve<span class="pagenum"><a id="Page_427"></a>[427]</span> -centres, and the appearance of albumen or sugar, if previously -absent, will indicate reduction in intensity of the hydriatric procedures. -In short, we should be alive to the profound influence of -hydro-therapy on general metabolism and the consequent necessity -of medical supervision throughout the course.</p> - -<h3><span class="smcap">Methods of Application of General Hydro-therapy</span></h3> - -<p>Subject to reservations, stimulant hydro-therapeutic procedures -are in <i>chronic</i> gout <i>the</i> special indication. Thermal waters, therefore, -are, generally speaking, the most suitable, and <i>cæteris paribus</i>, -the higher the temperature the greater the excitant action. Of -natural thermal baths, those of Bath, Aix-les-Bains, Gastein, -Wiesbaden, etc., enjoy great repute, and, judging from personal -experience of the first-named spa, I doubt not that—given due -discrimination—all waters of this group are unquestionably -beneficial.</p> - -<p>Having regard to their <i>radio-active</i> properties, the best results -are undoubtedly to be obtained by a combined bath, drink, and -inhalation cure. Simple immersion baths, deep or reclining, with -or without massive under-current douches, enjoy well-deserved -vogue for their general and local effects.</p> - -<p>Moreover, as the local douching exerts a sedative as well as a -resolvent effect, they prove most useful not only in articular gout, -but in the treatment of those frequent concomitants, <i>lumbago</i> and -<i>sciatica</i>. Their efficacy is much enhanced by coincident or subsequent -massage, and to increase the powers of resistance, such -hot baths should be followed by graduated sub-thermal or cold -applications.</p> - -<p>Sool-Bader, or natural thermal brine waters, exert a similar -effect, but such are not available in this country. But cold brine -baths—given at temperatures of 98° F. and upwards—are obtainable -at Droitwich, Harrogate, and Builth, and are invoked more -particularly in long-standing cases with great thickening of the -arthritic or related muscular structures.</p> - -<p>Again, gouty subjects not seldom suffer with <i>high blood pressure</i>, -and our treatment must be modified accordingly. Here we -may enlist what are known as <i>Aix massage</i> baths, which tend to -<i>lower</i> arterial pressure through the profound influence they exert -on metabolism, and the elimination of toxic and waste products. -As in warm immersion baths enervating after-effects are apt to -ensue unless the tonic-bracing action of a <i>terminal cold application</i> -be invoked. On the other hand, in some cases of chronic gout -the abdominal musculature is very flabby, with a tendency to -<i>visceroptosis</i> and <i>low blood pressure</i>. In their instance, a <i>Vichy<span class="pagenum"><a id="Page_428"></a>[428]</span> -bath</i>, inasmuch as it tends to <i>raise</i> the blood pressure, is preferable -to Aix massage.</p> - -<p>Another powerful method at our disposal for the elimination of -waste products is the <i>vapour</i> bath. It is not suitable for the old -and feeble, or those with advanced <i>cardiac</i> or <i>renal</i> disease, but it -is especially adapted to gouty subjects with <i>harsh</i>, <i>thickened</i> or -<i>irritable</i> skin, and those of <i>obese</i> habit.</p> - -<p>While the foregoing procedures, generally speaking, are eligible -for the more robust type of individual, we must have regard also -to those of delicate constitution, whose strength is sapped by long-continued -gout, or who show signs of pre-senilism. In such -instances, <i>sub-thermal</i> baths (82° to 97° F.) have a great sphere of -usefulness. Thus in the presence of <i>high arterial pressure</i>, a course -of immersion baths, say, at 93° F., combined with fan douches, -and applied according to the Bourbon-Lancy method, are very -effectual in reducing arterial tension. Of marked <i>sedative</i> action, -such neutral baths are peculiarly eligible also for all types of gout -associated with <i>insomnia</i>, irritable skin affections, or showing -signs of vasomotor instability.</p> - -<p>Moreover, these sub-thermal baths are valuable in articular gout -of subacute or lingering character if the douches used are of low -pressure, which latter is essential if the joints are sensitive. -Their therapeutic action is of course more pronounced in those -<i>natural mineral waters</i> which more nearly fulfil the requirements -of a neutral bath. Such are possessed in high degree by the -waters of Buxton, Ragatz, and Baden-Weiler, the average -temperature of which approximates to the point of thermal -indifference.</p> - -<h3><span class="smcap">Methods of Local Hydro-therapy</span></h3> - -<p>In one form or another, <i>douches</i> have for centuries been used -for chronic joint affections. Three factors have to be considered—the -volume, pressure, and temperature of the impinging water. -The size and form of the stream determine its thermic and -mechanical effect, and <i>cæteris paribus</i>, the more massive the -volume, the more marked the results produced.</p> - -<p>The pressure, again, is a most important factor, as the influence -on the circulatory and lymph flow in deep-seated tissues is directly -proportional to the force of delivery.</p> - -<p>We see, therefore, that in douches we have a weapon of great -power for good or ill, and the results achieved will be exactly -proportional to the judgment displayed in meeting individual -requirements in the matter of their temperature, duration, and -pressure.</p> - -<p>The space at our disposal forbids entering into great detail,<span class="pagenum"><a id="Page_429"></a>[429]</span> -and a few general principles are all that can be enunciated. Thus, -while extreme pressures are permissible in selected cases, they are -contra-indicated when dealing with regions the seat of pain. In -such instances we should always begin with mild measures, viz., -a tepid fan or spray douche (80° to 92° F.) of low (4 to 8 pounds) -pressure. These later may be replaced by a hot (104° to 110° F.) -broken jet, or rain douche, of 10 to 15 pounds pressure, and by -such graduated procedures pain will often be relieved.</p> - -<p>For the relief of <i>stiffness</i> and <i>swelling</i> alternating jets or sprays -are most suitable, the hot and cold douches being each of fifteen -to thirty seconds duration. The more remote the extremes of -temperature, and the more abrupt the transition from hot to cold, -the greater the excitant effect.</p> - -<p>Simultaneous massage greatly reinforces the stimulating and -absorbing action of douches, which latter also may in various -ways be advantageously combined with other local procedures, -viz., local vapour, hot air, and electric light baths.</p> - -<h3><span class="smcap">Treatment by Hyperæmia</span></h3> - -<p>Enhanced oxidation and destruction of nitrogen-containing -waste and toxins being one of the primary indications in the -treatment of all so-called auto-toxic states, it is not surprising -that hot air baths—both <i>luminous</i> and <i>non-luminous</i> types—are -so extensively employed in gout, either for their curative or -prophylactic action.</p> - -<p>For the practical details of their administration I must refer -the reader to special works on the subject, contenting myself with -a brief reference to their therapeutic indications. While all gouty -subjects at some period of their life-history may be eligible for -hot air baths, their use is contra-indicated in <i>pyrexia</i>. Nor are -they appropriate if the case is complicated by any irritable <i>skin -condition</i>, or in the graver forms of <i>glycosuria</i>. They are unsuitable, -too, if there are any evidences of <i>hyper-thyroidism</i>, from -which the gouty, no more than others, are immune.</p> - -<p>Again, in <i>cardiac dilatation</i> they must be exhibited with great -caution, and where extreme, are of course impermissible, as also -in the later stages of <i>chronic nephritis</i>. On the other hand, they -are eminently suitable for the treatment of <i>fibrositis</i> in gouty -persons, especially of obese type, nor does the presence of -<i>glycosuria</i> in such association constitute a bar to their use.</p> - -<p>Moreover, as a <i>prophylactic</i> measure, they are extremely well -adapted to those victims of gout who lead sedentary lives, as to -a limited extent they counteract the evil effects of muscular inactivity. -Here also, by the judicious use of graduated after-applications<span class="pagenum"><a id="Page_430"></a>[430]</span> -of cold or hypothermal grade, the undue sensitiveness -of the skin in these subjects is reduced, and their liability to -so-called “liver chills” diminished.</p> - -<p>In conclusion, it is the proper blending of their eliminative and -prophylactic qualities, according to individual needs, that constitutes -the key to rational treatment by hyperæmia. These -same postulates are applicable also to the various peat, mud, and -fango baths, whose action in essence depends on the varying -degree of hyperæmia they produce, and to which, in all probability, -their well-established efficacy in gouty affections is attributable. -That there are other valuable accessory methods of treatment—electrical, -hydro-electric, etc.—in vogue at spas, I am perfectly -aware, but the number of special works available for reference on -this point relieves me of the necessity of alluding to them in -detail.</p> - -<hr class="chap x-ebookmaker-drop"> - -<div class="chapter"> - -<p><span class="pagenum"><a id="Page_431"></a>[431]</span></p> - -<h2 class="nobreak" id="CHAPTER_XXXII">CHAPTER XXXII<br> -<span class="smaller">MINERAL SPRINGS AND CHOICE OF SPA</span></h2> - -</div> - -<h3><span class="smcap">Mineral Springs</span></h3> - -<p>Though many have tried, no one has yet been able to define -exactly what does and what does not constitute a “mineral -water.” Criterion after criterion has been suggested—chemical, -therapeutic, thermic, cryoscopic, ionic, etc.—but to all there seem -objections, and doubtless will be, pending the advent of more -exact knowledge regarding these—the most complex pharmacological -compounds in our Materia Medica.</p> - -<p>Naturally, “mineral waters” being so refractory of <i>definition</i>, -it follows that all suggested <i>classifications</i> are equally perplexing. -In fact, all attempts to reduce them to order according to their -generic and specific differences are, it must be admitted, unsatisfactory. -Perhaps the most serviceable differentiation at our -disposal at present is one based on their <i>chemical</i> composition. -As Sir Hermann Weber says, “a statement of the salts contained -in a mineral water often tells the ordinary medical man something -of the nature and probable effects of the water in question, -whilst the results of an analysis expressed in ‘ions’ would simply -bewilder him.”</p> - -<p>“Probable effects,” says Weber, and, I think, advisedly; for -in estimating the effects of spa treatment how difficult to discriminate -between what is due to “mineral waters” and what is due -to change of air, diet, mode of life, and mental occupation. Yet, -again, how bewildering the fact that “waters” of the most varying -chemical content prove to be equally beneficial in gout. Small -wonder, then, that physicians sought to refer their therapeutic -efficacy not to their mineral constituents, but to the vehicle -common to all of them, viz., to the diluent and solvent action of -the <i>water</i> itself, its flushing effects in washing out urates and other -toxic substances.</p> - -<p>From this it was but a short step to the further assumption that, -other things being equal, the drinking of water at home would do -just as well as resorting to a mineral spring. But, as has been -shrewdly said, the “other things” never are “equal.” What of -the daily worries left behind, the change of air and scene, the -modifications of diet, the leisure for outdoor exercise, not to -mention hydro-therapy and other integral or collateral factors -of spa treatment?</p> - -<p><span class="pagenum"><a id="Page_432"></a>[432]</span></p> - -<p>But, even frankly admitting our ignorance, the lessons of -experience, nevertheless, can neither be flouted nor ignored, least -of all in the treatment of gout. “Mineral waters” are but used -<i>empirically</i>, says the critic, forgetful that the use of <i>colchicum</i> lies -open to the same aspersion. Especially valid the imputation, as -he thought, in regard to the so-called “simple” or “indifferent” -thermal waters. These—despite the testimony of centuries to -their worth—must be discarded in favour of some pseudo-rational -method, and this, forsooth, because their mode of action seems -inexplicable! Yet, by the irony of Fate, within a brief span these -“indifferent” waters were found to contain a substance—“radium”—whose -powers few, at present, pretend to gauge or -limit. There seems, in truth, a peculiar fitness in the coincidence -that it should be in this very group that experimental investigations -have proved so fruitful.</p> - -<p>Is it not, moreover, a striking fact that the waters of nearly all -the natural springs which for centuries have been used in the -treatment of gout are thus dowered, and those which are most -lowly mineralised seem to possess the greatest degree of radio-activity?<a id="FNanchor_63" href="#Footnote_63" class="fnanchor">[63]</a> -It was to their possession in varying measure of this -common property that the therapeutic efficacy of waters so -widely different in their chemical content was presumably in -large part attributable, viz., to their <i>radio-activity</i>.</p> - -<p>For alike in simple thermal, sulphurous, alkaline, sulphated -alkaline, or muriated waters, the presence of radio-activity has -been established. But if, <i>e.g.</i>, in the <i>simple thermal</i>, their therapeutic -potency is referable to their higher degree of radio-activity -and not to their mineral content, in others their relative deficiency -in radio-activity is compensated for by their <i>mineral</i> constituents—these -present in sufficient quantity to exert a <i>specific</i> action, -alterative, aperient, tonic, etc.</p> - -<p>In this matter of <i>mineral</i> content we are reminded of the -grievous controversy that has long obtained with regard to the -use of natural waters, the chief constituents of which are <i>sodium</i> -salts. Sir William Roberts, as we know, from his experiments, -ascertained that sodium salts promoted the conversion of the -quadriate into the biurate, thus augmenting the precipitation of -the latter.</p> - -<p>This behaviour on the part of the carbonates, bicarbonates, -and phosphates of sodium led him to the sweeping generalisation<span class="pagenum"><a id="Page_433"></a>[433]</span> -that all sodium salts, including the chloride, were, as far as practicable, -to be avoided by <i>gouty</i> subjects. Naturally, in conformity -with this view, such patients were warned to flee those spas whose -waters contained these peccant salts.</p> - -<p>Carried to its logical end, this dictum would have cut the gouty -off from, <i>e.g.</i>, the carbonate of soda waters of Vichy, the chloride -of sodium springs of Homburg, the sulphate of soda waters of -Karlsbad, not to mention the muriated (sodium chloride-containing) -sulphur waters of Harrogate, Llandrindod, etc., despite the -overwhelming clinical evidence as to their efficacy in certain cases -of gout.</p> - -<p>Fortunately, as Burney Yeo observed, “in spite of all the -theoretical denunciations of the use of sodium salts in gout, the -gouty, from all quarters of the globe, have resorted, and continue -to resort, in steadily increasing numbers, to those Continental -springs in which the salts of sodium are overwhelmingly predominant.”</p> - -<p>In short, Sir William Roberts’s experiments, while they dissipated -the fallacious view of the action of alkalies as solvents in the -blood of sodium biurate, have not for one moment imperilled the -clinical and practical estimate, deep-rooted in experience, of their -general utility in gout.</p> - -<p>For myself, I incline to the view of the French authors, who -would refer the value of alkalies and alkaline mineral waters in -gout rather to their general influence on metabolism than to the -now no longer tenable conception of their solvent action on -<i>uric acid</i>.</p> - -<p>Reflecting on the varied constituents of mineral springs and -the claim that each and all of them are of value in gout, one naturally -looks for certain conditions common to them all. These are, -as Burney Yeo rightly says,—</p> - -<div class="blockquote"> - -<p>(1) The quantity of water, more or less pure, taken into the -body under regulated conditions daily.</p> - -<p>(2) The altered mode of life, the regular exercise in the open -air, the modified diet, the early hours, the absence of -business cares.</p> - -<p>(3) In many foreign spas there is the drier and hotter Continental -climate.</p> - -<p>(4) The stimulating effect to excretion and “tissue change” -which the baths, douches, frictions, and manipulations -applied at most of them induce.</p> - -</div> - -<p>Now, admitting, as one freely does, the important influence -exerted by these factors on what may be termed the pathological -groundwork of gout, still it is equally certain that some -cases of gout do better than others at certain spas.</p> - -<p><span class="pagenum"><a id="Page_434"></a>[434]</span></p> - -<p>This leads me on to the further reflection that the favourable -or unfavourable reaction in different cases depends on the varying -nature of what I may term the “excitants” of gout. For the -deviations from health that evoke the disorder are manifold and -diverse, each carrying with it its own therapeutic indications. -Something more is needed than what may be termed a blind or -unintelligent “washing out” process. In every gouty patient -there is some functional flaw or defect, and <i>cæteris paribus</i>, that -natural spring will suit him best whose mineral or other content -is best calculated to correct or minimise his particular deficiency.</p> - -<p>In short, we must get rid of our too common habit of asserting -that this or that particular water is “indicated in all cases of -gout,” and its use “attended with the most remarkable results.” -The question that we should be more anxious to decide is, whether -of <i>all natural springs</i> this or that particular mineral water is <i>par -excellence</i> the one that will most surely and most swiftly correct -or minimise that particular functional derangement which in the -subject under review experience has shown to be the most fertile -source of gouty outbreaks. But to this we shall refer later when -dealing with the <i>individual peculiarities</i> upon which our <i>selection -of a spa</i> will depend.</p> - -<p>To sum up, in consonance with these views, the general principles -of spa treatment, as I take it, are:—</p> - -<div class="blockquote"> - -<p>(1) To correct or relieve those functional derangements, -gastro-intestinal or other, that appear to be the determining -causes or excitants of outbreaks of regular gout.</p> - -<p>(2) To reduce the toxicity of the blood plasma and tissues by -promoting the elimination of uric acid and toxins through -all avenues of excretion.</p> - -<p>(3) To restore the organism as far as possible to a state of health -or functional efficiency, and therewith to adopt such -prophylactic measures as shall diminish the liability to -recurrence of the disorder.</p> - -</div> - -<p>To discuss the application of these principles to all types of -mineral waters is beyond the compass of this work, and I shall -perforce have to confine myself very largely to discussion of the -salient properties of <i>radio-active</i> waters, with subsequently such -brief allusions to the salient therapeutic indications of other -varieties as may be indispensable to intelligent selection of a -spa in any individual case.</p> - -<h3><span class="smcap">Radio-active Waters</span></h3> - -<p>As to the physical properties of <i>radium</i>, it is, according to the -theory of transformation, a “changing element,” emitting alpha, -beta, and gamma rays, and in addition a radio-active emanation.<span class="pagenum"><a id="Page_435"></a>[435]</span> -This latter product exists in a gaseous form, and is the outcome -of the ceaseless metamorphosis taking place in radium itself, -each atom of which continuously ejects at high velocity an atom -of helium.</p> - -<p>This expulsion of helium having ensued, the parent atom no -longer exists as radium, but as <i>radium emanation</i>, or <i>niton</i>, as it -has more recently been designated. Now, from a therapeutic -point of view, the salient fact is that elicited by Lowenthal, viz., -that the active agent is not, as was previously thought, radium -itself, but the <i>emanation</i> derived from it.<a id="FNanchor_64" href="#Footnote_64" class="fnanchor">[64]</a></p> - -<p>Now, as a reference to our footnote shows, the Bath waters -are radio-active to a remarkable degree, and as Maché, Curie, and -Laborde hold that “the higher the emanation from a given -spring, the more striking are the physiological results,” a brief -reference thereto seems called for.</p> - -<p><i>Physiological Action of Radium Emanation.</i>—When inhaled, -radium emanation swiftly passes from the alveolar spaces of the -lungs into the blood, and thence to the tissue cells, which, according -to their specific solubility, absorb the same. Eventually, if<span class="pagenum"><a id="Page_436"></a>[436]</span> -the inhalation is prolonged sufficiently, saturation of the blood -therewith ensues, to be followed by its escape <i>viâ</i> the lungs, intestines, -kidneys, and skin.</p> - -<p>Taken orally, radium emanation, according to Lazarus, in -large amount, passes into the arterial blood, an observation confirmed -by other investigators experimenting on animals. Its -absorption into the blood takes place slowly from the intestines, -and its exit thence out of the system is, in like fashion, only -slowly effected, taking <i>hours</i> for complete excretion. On the -other hand, when <i>inhaled</i> the emanation is quickly absorbed and -as swiftly excreted, <i>i.e.</i>, within a few <i>seconds</i>. As to its power of -penetrating the <i>skin</i> most authorities are sceptical, but Engelmann -stoutly contends that he has proved that in immersion -baths the emanation does actually pass through the skin; but -pending further researches this question of cutaneous absorption -must remain <i>sub judice</i>.</p> - -<p>Again, radium emanation appears to be endowed with the -power of energising or activating the body ferments or enzymes, -in other words, can stimulate to greater efficiency the <i>proteolytic</i>, -<i>glycolytic</i>, and <i>diastatic ferments</i> that set in motion that long chain -of cleavage processes in the various foodstuffs, the necessary -prelude to their absorption, assimilation, and ultimate transmutation -into live protoplasm. Nay more, for the same mysterious -agent, it is claimed, can activate those oxidising enzymes which -initiate the equally intricate disruptive processes that mark the -disintegration of living protoplasm.</p> - -<p>Thus Neuberg, Lowenthal, Edelstein, and others contend that -they have demonstrated such an increase of efficiency on the part -of the autolytic enzymes responsible for cleavage of the protein -molecule into nitrogenous bases and amido-bodies. That radium -emanation should exert such a profound effect on organic metabolism, -both in its anabolic and katabolic phases, would, if -established, go far to dissipate the dark shadow of empiricism that -has for so long clouded the practice of mineral water drinking and -bathing. For it is precisely in those conditions collectively -termed “disorders of nutrition” that radio-active waters have -found their traditional <i>rôle</i>.</p> - -<h3><span class="smcap">Influence on Uric Acid Metabolism</span></h3> - -<p>In 1909 Gudzent, working in His’s clinic at Berlin, affirmed that -in gouty subjects uric acid vanishes from the blood in the presence -of radium emanation; moreover, that under the same conditions -tophi had been observed to melt away. The explanation proffered -by Gudzent was, that the emanation inhibited the transmutation<span class="pagenum"><a id="Page_437"></a>[437]</span> -of the unstable and more soluble <i>lactam</i> into relatively insoluble -and stable <i>lactim</i> urate, this latter being the salt found in the blood -of the gouty.</p> - -<p>W. His also claims that the gouty individual benefits by this -method of treatment, which, he maintains, not only reduces the -uric acid content of the blood, but dissipates uratic deposits in the -tissues. On the other hand, at the last Congress of Internists at -Wiesbaden (1912) Gudzent and His’s views, though stoutly supported -by some, were unacceptable to others, who, although they -admitted the favourable influence of radium emanation upon the -symptoms of gout, yet contended that its effects could with difficulty -be interpreted either in the sense of increasing the solubility -of the monourate of sodium or its decomposition into CO₂ and -ammonia.</p> - -<p>Thus E. V. Knaffl-Lenz and Wiechowski, working in the Vienna -Pharmacological Institute, were unable to confirm Gudzent and -His’s claim that treatment by radium emanations resulted in -destruction or increase in solubility of the mono-sodium urate. -On the other hand, in view of the admittedly favourable effect of -the emanation on gout, they suggest that it might be due to what -they term activation of an uric acid oxidase existing in the human -tissues. Yet another view is that in some obscure way radium -emanation facilitates the elimination of uric acid through the -kidneys.</p> - -<p>In regard to the claim that radium emanation has the power of -keeping uric acid compounds in their more easily soluble forms, -it is interesting to recall the conclusion arrived at by the <i>Lancet’s</i> -special commission for investigation of the Bath waters: “The -thermal waters of Bath exert a distinct solvent action on uric -acid; in our experiments, <i>e.g.</i>, it was shown that Bath waters -dissolved over five times the amount of uric acid that distilled -water would similarly take up at blood heat—<i>i.e.</i>, just under -100° F. Since the waters are drunk hot and used hot for bathing -purposes, this fact may have an important relation to the therapeutics -of Bath waters in the treatment of chronic gouty affections -and rheumatism.”</p> - -<p><i>Increased Excretion of Uric Acid.</i>—Delayed excretion of exogenous -purin is held to be one of the most characteristic signs of gout. -Now, following emanation treatment, Lowenthal and others have -noted that this disability on the part of the gouty was apparently -removed. For when, at the close of the course, the capacity for -dealing with exogenous purins was tested by the intake of large -amounts of purin bodies, excretion of the same ensued after a -normal fashion. It would seem then that there is not only -increased uric acid excretion actually during the progress of a<span class="pagenum"><a id="Page_438"></a>[438]</span> -<i>séance</i> of emanation, but also that this enhanced power of coping -with purins is maintained subsequently.</p> - -<p><i>Subjective Phenomena of Gout in Relation to Blood Content and -Excretion of Uric Acid.</i>—Now, as we have seen, it is claimed that -uric acid disappears from the blood in the presence of emanation. -But, while in the majority of instances amelioration of symptoms -follows reduction of the uric acid blood content, in others improvement -ensues even though the amount of uric acid in the blood -remains unaltered.</p> - -<p>Thus in one of His’s patients under radium emanation striking -amendment followed notwithstanding that the blood contained -uric acid. In another, the subject of multiple tophi, no uric acid -was found in the blood throughout the treatment, and yet the -victim had repeated attacks of gout during this period.</p> - -<p>Turning to the <i>excretion of uric acid in the urine</i>, similar discrepancies -emerge. Thus Mandel out of seven gouty patients under -treatment by radium emanation found that an increased uric acid -excretion ensued in two subjects. Of the remainder, in two no -alteration in average excretion took place, in two a slight diminution, -and in one a marked increase, to the extent of 50 per cent.</p> - -<p>Now in four of the seven cases an undoubted clinical and subjective -improvement was observed, although the uric acid curve -showed diminution rather than increase. It seems, therefore, -clear that the <i>beneficial effect of radio-active waters in gout</i> involves -something more than the <i>dissipation of the uric acid in the blood</i> -and <i>its increased elimination in the urine</i>.</p> - -<h3><span class="smcap">Therapeutic Action and Application</span></h3> - -<p>We have in previous sections emphasised the importance of -treating <i>local foci of infection</i>, in view of their possible causal -relationship to gout. For, uncertain as we are of the etiology of -the disorder, we cannot afford to neglect treatment of any possible -source of toxic absorption.</p> - -<p>Now a significant number of independent workers contend -that in the presence of radium emanation the growth of organisms -is retarded, if not actually inhibited. The same bactericidal power -has been claimed for radio-active waters even of low grade. -Should recent contentions as to the efficacy of the same in states -of <i>oral sepsis</i> be confirmed, it will constitute an important weapon -wherewith to combat not only the local, but the remote malign, -effects of sepsis in the mouth or its accessory cavities.</p> - -<p>Again, it is recognised that <i>pharyngeal</i> and <i>nasal</i> affections -when present derive benefit from the <i>inhalation</i> of <i>radio-active -waters</i> atomised by steam or air. In this connection it may be<span class="pagenum"><a id="Page_439"></a>[439]</span> -noted that, by an ingenious apparatus installed at Bath, the -natural “niton” gas is now extensively used for inhalation or -douching of the mouth and neighbouring cavities.</p> - -<p><i>Alimentary Disorders.</i>—Accepting the fact that <i>gastro-intestinal -derangements</i> are the most common <i>excitants</i> of gouty outbreaks, -it seems to me highly probable that the good effects of -radio-active waters are partly attributable to their mysterious -power of <i>activating the body ferments</i>. Thus, through their -stimulating action on the digestive enzymes, they may inhibit -the formation of abnormal substances, or, through their quickening -of the autolytic ferments, may hasten the disruption and excretion -of such when formed.</p> - -<p>How frequently in these cases do we find that some functional -hepatic or gastro-intestinal derangement is the prelude to a gouty -outbreak. Again, as pointed out, how often do these subjects -suffer with fermentative dyspepsia and “organic acidity,” with -associated lowered tolerance for carbohydrates. In such cases, -if given in copious quantity and frequently, the radio-active waters -prove most beneficial. This is in part attributable to the mechanical -flushing of the alimentary canal and tissues, and in part -perhaps to their activating influence on the digestive enzymes.</p> - -<p>In contrast to the foregoing, such abundant ingestion of the -waters is inadvisable in atonic types of dyspepsia marked by -dilatation and diminished secretion. But here again, if given -in small amounts, radio-active waters undoubtedly exercise a -beneficial effect. Also in those gouty subjects who suffer from -neurasthenia and nervous dyspepsia a similar favourable reaction is -frequently observed. This I apprehend to be due to the fact that -radium emanation exerts a <i>sedative</i> effect on the nervous system. -Thus it has been noted that guinea-pigs when exposed to radium -emanation drop into a state of somnolence and torpor. May -not this account for the undoubted fact that highly strung individuals -when subjected to a combined bath, drinking, and inhalation -cure become less irritable and lose their distressing tendency -to insomnia?</p> - -<p>Again, <i>intestinal irrigation</i> with these radio-active waters after -the Plombières technique is justly esteemed in those cases of -gout attributable to intestinal catarrhs and mucous colitis. The -constipation these subjects so frequently suffer from is counteracted, -and the regular removal of waste and toxic material -achieved.</p> - -<p>As to the morbid affections associated with gout, notably -fibrositis, it is well recognised that muscular and nerve types of -this disorder prove very amenable to a course of these waters. -Here I would lay stress, too, on the swiftness with which the<span class="pagenum"><a id="Page_440"></a>[440]</span> -<i>glycosuria</i> of gouty subjects vanishes under the same conditions. -The pruriginous and eczematous eruptions met with are also -favourably influenced by a combination of internal and external -treatment. I may note, too, that this mode of therapy is not -contra-indicated in <i>increased arterial blood pressure</i>. For it has -been shown by Deutelmoser, Saubermann, and others that under -the influence of radium emanations the blood pressure is reduced.</p> - -<p>As regards the administration of radio-active waters, it cannot -be doubted that the combined bath, drinking, and inhalation cure -is the most advantageous. The subcutaneous injection of -radio-active waters does not seem to possess any outstanding -advantages, while the danger of sepsis has always to be considered.</p> - -<p>As to the relative merits of artificial as opposed to natural -radio-active waters, it does not appear to me that the therapeutic -action of the former is swifter or more infallible than the products -that issue from nature’s laboratory. The limitations and -capacities of the latter have been fixed by centuries of experience, -and, as far as present researches go, the newly born commercial -imitation, at any rate as regards the treatment of gout, has yet -to prove itself endowed with a greater range of therapeutic -efficacy.</p> - -<h3><span class="smcap">Choice of Spa</span></h3> - -<p>While naturally my attention has been largely centred upon -the mineral waters of Bath, I would by no means convey the -impression that a <i>thermal radio-active</i> spring is the only one that I -think beneficial in the treatment of gout. Far from it, for if, from -my description, I appear to have claimed such to be universally -applicable to all gouty subjects, the explanation really resides in -the fact that the resources of most spas can be readily adapted so -as to suit different kinds of cases.</p> - -<p>Nevertheless, as I have said, I favour the tendency towards -<i>specialisation of spas</i>, as bit by bit the indications for their -differential application become more and more sharply defined. -In view, then, of this trend, it is manifestly only fair to our -patients that we endeavour to select that particular spa that seems -most eligible in their particular instance.</p> - -<p>Let us assume, then, that the subject is in such circumstances -that a certain latitude of choice is permissible. This being so, -the physician’s selection will be the more satisfactory if regard -is had not only to the gout, but to the <i>individual</i> himself, and not -the least important of the considerations involved have been -already embodied in my remarks on <i>climato-therapy</i>. For the -ideal sought, if I may again say so, is not only <i>physical</i>, but <i>psycho-physical</i>;<span class="pagenum"><a id="Page_441"></a>[441]</span> -and the physician who leaves out the mental element -will scarcely choose wisely.</p> - -<p>Narrowing our field to consideration of the <i>physical</i> requirements -of the subject under review, what manner of man is he, -<i>metabolically</i> speaking? Is he of <i>spare</i> habit, one in whom katabolic -changes hold sway and “the vital fires blaze more fiercely,” -or is he <i>obese</i>, one in whom anabolic processes are dominant, with -hoarding up of substance?</p> - -<p>Now, I have taken these two types, the <i>spare</i> and the <i>obese</i>, as -in gout we are dealing primarily with a “disorder of nutrition.” -<i>Cæteris paribus</i>, we wish to correct the morbid metabolic trend, -in other words provide differential treatment. Obviously the -salient indication in the <i>lean</i> individual is that he shall drink of a -spring which will tend to enhance digestive capacity and facilitate -assimilation of foodstuffs, with as its outcome increase of general -nutrition.</p> - -<p>To compass such effects, <i>muriated</i> chloride or common salt -waters are, other things being equal, most desirable; that is to -say, unless they are taken in such quantities as to produce catarrh -of the stomach and intestines, they <i>do not cause emaciation</i>. On -the contrary, I have, for example at Llandrindod, seen an increase -of weight in these persons ensue during, and, moreover, continue -after, a suitably arranged course of these waters. Among other -muriated waters in this country may be mentioned Llangammarch -Wells, which, as Sir Hermann Weber suggested, is suitable -in cases of chronic gout, “especially where any emaciation is to be -avoided,” and Woodhall Spa also deserves mention in this connection, -or, reverting to the Continent, the waters of Homburg, -Kissingen, Wiesbaden, Baden-Baden, etc., may be selected.</p> - -<p>The <i>muriated</i> (chloride-containing) <i>alkaline</i> waters are also -eligible in cases where loss of flesh is to be avoided, such as Ems, -Royat, Chatel Guyon, or La Bourboule. They should, for this -reason, be given the preference over the <i>simple alkaline</i> waters, -such as Vichy, Vals, Neuenahr.</p> - -<p>Reverting now to the <i>obese</i>, plethoric type of man, a heavy -eater and often of sedentary habit, what is the end to be achieved? -Here loss of flesh is to be courted, and a spa sought whose mineral -waters will by their action supplement the all-important dietetic -and regimenal treatment of the subject.</p> - -<p>The class of waters pre-eminently suitable will be those known -as the <i>sulphated</i> and the <i>sulphated alkaline</i> varieties, which, taken -internally, will through their purgative and diuretic effects assist -our purpose. The stronger varieties of the <i>sulphated</i> waters are -chiefly used as occasional aperients at home, as, generally speaking, -at the site of the spring there is no proper spa accommodation.<span class="pagenum"><a id="Page_442"></a>[442]</span> -We allude to Franz Joseph, Hunyadi Janos, Rubinat, and -Condal waters, etc.</p> - -<p>In England several <i>sulphated</i> springs exist, but, as far as their -use is concerned, may be regarded as obsolete. Perhaps the best -known is the original spring, no longer used, at Epsom, whence -the English term for magnesium sulphate, “Epsom salts.” -According to Weber, in Charles II.’s reign these native laxative -saline waters were taken at the wells early in the morning, and -Pepys in his diary tells how on August 11th, 1667, at seven -o’clock on a very cold morning, he found many people drinking -the waters at Barnet Wells.</p> - -<p>It is, however, the <i>sulphated-alkaline</i> springs that have achieved -the greatest reputation in this sphere, notably Karlsbad, Marienbad, -Franzensbad, Tarasp Schuls, etc., and perhaps of these -Marienbad is the most frequented. But in any case, in exercising -a choice, we should take into consideration not only the temperature -and mineralisation of the waters and their balneo-therapeutic -resources, but also the climate and the time of year. Thus, -for example, the climate at Tarasp is alpine, and the altitude of -Marienbad is over 2,000 feet, while that of Karlsbad is but 1,200. -Another point to consider is whether the obesity of the subject is -attended with <i>anæmia</i>. If so we may with advantage choose -Tarasp, which, in addition to sulphated alkaline, has <i>chalybeate</i> -waters, and the same dual advantages are to be found at -Marienbad.</p> - -<p>For those unable to go abroad the <i>muriated sulphated</i> waters of -Leamington or Cheltenham in this country are available. The -flat contour of these spas is very suitable for those cases in which -obesity is complicated by cardiac debility. I may note, too, that -Bain and Edgecombe, discussing the treatment of obesity at -Harrogate, speak well of the strong <i>muriated sulphur water</i>, substituted -in anæmic cases by a chalybeate water in conjunction -with an aperient.</p> - -<p>So much for the broader indications, <i>metabolically</i> speaking, -that should guide us in our choice of a spa. And now to consider -other special conditions which in the gouty call for consideration, -notably digestive disorders.</p> - -<p><i>Dyspepsia and Chronic Gastro-intestinal Disorders.</i>—In these -conditions it is especially imperative that we take a broad view, -particularly in respect of climate and altitude. Inland spas at -moderate or high altitudes are generally preferable. Doubtless -the beneficial result is in part due to the influence that change to -a mountainous region, with abundant open-air exercise, exerts on -the nervous system. But the same has its drawbacks in the -“gouty dyspeptics,” for often, as I have observed, they tend at<span class="pagenum"><a id="Page_443"></a>[443]</span> -first to overeat. As Weber rightly says: “The feelings of ‘sinking’ -and ‘lowness’ in the gouty and dyspeptic are frequently -mistaken by the patients themselves as indications for taking -food, stimulants, or tonic medicine.” In short, we must in their -instance institute immediately at the commencement of their -course the requisite dietetic innovations. Again, being in these -more bracing localities more disposed to take exercise, the adverse -effect on digestion of <i>over-fatigue</i> must be guarded against.</p> - -<p>Indeed, in the more aggravated types of so-called gouty dyspepsia -there is little doubt that sojourn in a <i>sanatorium</i> may at -first be advisable, so that the patient’s digestive disabilities may -be thoroughly studied by the help of test meals, while dietetic -treatment can be more readily and surely supervised.</p> - -<p>Passing to the question of <i>mineral waters</i>, there is no doubt that -a previous investigation of the <i>secretory</i> and <i>motor</i> functions of the -stomach would supply valuable indications as to the type of -“waters” most suitable. Incidentally, too, researches in this -line might tend to clear up the obscurity that enshrouds the mode -of action of mineral waters in cases of gouty and other forms of -dyspepsia. For experimental findings and clinical observations -are here somewhat conflicting.</p> - -<p>Thus it has generally been supposed that <i>simple alkaline</i> -mineral waters promote the secretion of acid gastric juice. But -Pawlow, experimenting on dogs, found that alkaline sodium salts -tended rather to <i>inhibit</i> than to stimulate gastric and pancreatic -secretions. In order, therefore, to reconcile his findings with the -well-ascertained benefit that follows their exhibition in gastric -disorders, he suggests that they prevent the too prolonged or -excessive secretion that is so often a concomitant of catarrhal -conditions.</p> - -<p>Adolf Bickel, again, has confirmed Pawlow’s conclusion that -the simple alkaline group of mineral waters depress rather than -stimulate the secretory activities of the gastric mucous membrane<a id="FNanchor_65" href="#Footnote_65" class="fnanchor">[65]</a>; -but Sir Hermann Weber, discussing Bickel and Pawlow’s deductions, -puts forward, as I think, a more reasonable hypothesis than -that advanced by the latter authority.</p> - -<p>Thus he suggests that “a possible explanation of the beneficial<span class="pagenum"><a id="Page_444"></a>[444]</span> -effects of alkaline salts in many digestive disorders (gouty -dyspepsia, irritable hyperacidity, etc.), in tendency to ‘biliousness,’ -and in various so-called ‘gouty manifestations’ is that these -salts when taken up into the circulation exercise a favourable -influence on the metabolic processes generally, thereby improving -the general health and thus indirectly, apart from any special -local action, helping to remove conditions of dyspepsia, gouty -bronchitis, etc.”</p> - -<p>From his experiments Bickel came to the conclusion that in -conditions of <i>subacidity</i> supervening on chronic gastric catarrh -the most suitable are <i>muriated</i> waters, or <i>muriated alkaline</i> waters, -or simple <i>gaseous</i> waters.</p> - -<p><i>Gastric Insufficiency, or Atonic Dyspepsia.</i>—Now, as I have -before emphasised, this is the functional gastric disorder most -commonly met with in the gouty; the <i>hyperacidity</i> is due to -<i>excess of organic acids</i>, and this, again, is the outcome of not -excess, but <i>deficiency, of HCL</i>. Now in cases of this nature with -<i>subacidity</i> of the gastric juice numerous observers—Von Noorden, -Dapper, Boas, and others—have reported an increase in the secretion -of hydrochloric acid following a course of <i>muriated</i> waters.</p> - -<p>My own clinical experience of the <i>muriated</i> waters of Llandrindod -abundantly confirms the results obtained by these authorities. -The enhanced digestive capacity of the patients is evidenced -by relief of epigastric pain and discomfort after meals and the -decline of flatulent distension. For, following the increased -secretion of hydrochloric acid, their intolerance of carbohydrates, -due to subacidity, disappears, and, fermentation no longer taking -place, the over-distended walls of the stomach gradually recover -tone. It is customary for patients to walk either during or after -the consumption of water. But in decidedly atonic conditions of -the stomach with dilatation it is better, as Ageron suggests, that -such subjects lie down after drinking. Nor must the beneficial -effect of muriated waters on the associated constipation be overlooked. -The daily thorough evacuation of the intestinal canal -minimises or prevents toxic absorption, and at the same time -depletes the overloaded portal system.</p> - -<p>The sources of blood contamination being removed, the general -symptoms of languor, drowsiness, and mental depression give -place to a more cheerful tone of mind. At the same time relaxation -from business, an outdoor life, and bracing air, with change -of scene and society, doubtless contribute to dissipate those feelings -of supreme misery which are the bane of the dyspeptic.</p> - -<p>As to the foregoing remarks, I have but chosen Llandrindod as -a type. Thus some of the Harrogate waters are equally eligible -for inclusion in the <i>muriated</i> as in the sulphurous group. Again,<span class="pagenum"><a id="Page_445"></a>[445]</span> -to these may be added Builth Wells and Llangammarch Wells, -the latter distinguished by its content of chloride of barium, which -is said to raise the blood pressure and promote diuresis through its -tonic action on the muscular coat of the arteries. Woodhall Spa, -too, calls for mention, the presence of iodides and bromides in its -muriated waters investing it, according to some, with special -alterative properties; lastly, the strong brine waters of Droitwich, -which find their special sphere in external application by -baths.</p> - -<p>As to the Continental springs in this category, the most noteworthy -are Homburg, Kissingen, and Kreuznach, the last decidedly -radio-active; while of <i>thermal muriated</i> waters Wiesbaden and -Baden-Baden are the most representative.</p> - -<p><i>Chronic Gastric Catarrh.</i>—In this condition, not uncommon in -the gouty, and which Ewald aptly characterises as “the best -fostered and widest spread of this world’s ills,” a deficiency of -gastric secretion with impaired motility is constantly present. -With this is frequently correlated distension of the small intestine, -due to abnormal fermentative and putrefactive changes in the food.</p> - -<p>Leaving aside the vexed question as to whether <i>muriated</i> or -saline waters can be regarded as direct excitants of gastric secretion, -it cannot be doubted that the prolonged and systematic -lavage of the stomach, ridding it of viscid mucus and hastening -the removal of retained fermenting foodstuffs, must favour -restoration of a healthy state of the mucous membrane, and thus -indirectly promote its secretory activities. Again, inasmuch as -the bulk of saline waters undergoes absorption in the small intestine, -the duodenal catarrh usually associated with this condition is -also markedly benefited by the removal of toxic accumulations. -Indeed, Niemeyer, discussing the therapeutic efficacy of mineral -waters in such states, goes so far as to remark that “the results -obtained are the most brilliant that have ever been attained in -medicine.” To achieve these salutary effects the “waters” must be -taken in amounts adequate to produce copious daily evacuation. -For, if insufficient to ensure this same, discomfort and distension -ensue pending the more tardy removal of the water by the -kidneys.</p> - -<p>Now, while in these cases the <i>muriated</i> waters above alluded to -are suitable, the <i>muriated alkaline</i> are equally eligible. Of these -the highest in repute are Royat, Chatel Guyon, and Saint Nectaire, -and in Germany Ems, Wildbad, Assmannshausen, and -Wildungen.</p> - -<p>Here a reservation in regard to Bickel’s researches, viz., it has -been found that in some cases of <i>chronic gastric catarrh</i> in <i>robust</i> -subjects <i>simple alkaline</i> springs, such as those of Vichy, Vals, and<span class="pagenum"><a id="Page_446"></a>[446]</span> -Neuenahr, have, despite his experimental findings, proved actually -beneficial. On the other hand, these same waters have this cogent -objection, that long courses are apt to cause depression and -emaciation, and, moreover, may aggravate the gastric trouble. -Worse still, these <i>simple alkaline waters</i> are more likely to produce -an attack of <i>acute gout</i>, whereas the <i>muriated alkaline</i> varieties -are free from these objections.</p> - -<p><i>Hyperchlorhydria.</i>—Bickel’s experiments led him to this further -conclusion, that in organic gastric disorders accompanied by -<i>excess of HCL</i> the <i>simple alkaline</i> and <i>sulphated alkaline</i> group are -to be preferred to the <i>muriated</i> waters.</p> - -<p>Now, inasmuch as some authorities hold hyperchlorhydria as -due to a <i>chronic glandular gastritis</i>, it would seem that these should -be given a trial. Personally, I have no practical experience that -I can draw upon for substantiation or refutation as to the correctness -of Bickel’s assumption. Nor have I on this question been -able to find any reference in the literature or clinical findings -emanating from these spas.</p> - -<p>Much controversy, again, obtains in regard of the usage of -<i>muriated</i> waters in these cases. Formerly their employment was -unreservedly condemned, but more extended experience has modified -this too dogmatic attitude. Albeit, that the results obtained -in hyperacidity (excess of HCL) are uncertain is undeniable, -and unfortunately it is impossible to foretell whether or no any -given case will derive benefit. The pronounced nerve element in -these cases, with probably other unknown factors, has doubtless -much to say to the conflicting clinical results.</p> - -<p>But the experience of most of us will accord with that of Dapper -and Von Noorden, that <i>muriated</i> waters, such as those of Homburg, -Kissingen, etc., often prove beneficial in cases of neurasthenia -with hyperacidity. On the other hand, it is equally true -that some examples of apparently the same nature derive no -benefit, indeed are aggravated. But, according to Von Noorden, -such are in the minority.</p> - -<p>Fortunately this secretion of an abnormally acid gastric juice -is relatively rare in the <i>gouty</i>. Being of the nature of a <i>secretory -neurosis</i>, it occurs most frequently in those of <i>neurotic</i> or <i>neurasthenic</i> -type. Now, holding the view that many cases of neurasthenia -are due primarily to toxic absorption, secondarily to -alimentary derangements, the beneficial effects observed are, I -presume, probably attributable in large part to the removal of -toxic accumulations through flushing. These deleterious substances -not being absorbed in such amounts as before, improvement -in the general nerve tone ensues, in which doubtless the -secretory mechanisms of the digestive system participate.</p> - -<p><span class="pagenum"><a id="Page_447"></a>[447]</span></p> - -<p>But, as we have seen, these same <i>muriated</i> waters prove most -salutary in precisely the opposite condition—<i>hypochlorhydria, or -deficiency of HCL</i>. That such a beneficial effect should ensue in -diametrically opposed states, viz., <i>hyper</i>- and <i>hypo</i>-acidity, gives -point, I think, to the contention that the action of <i>muriated</i> waters -on the digestive organs must in great part be exerted not locally, -but <i>indirectly</i>, that is, secondarily to improvement of the general -health and toning up of the nervous system.</p> - -<p>Indeed, the pronounced nerve element in these cases is probably -the explanation why, especially in instances palpably due to -mental fatigue, insomnia, etc., a course of baths or hydrotherapy -at some simple thermal spa, preferably those at certain altitudes, -such as Buxton, Wielbad, Gastein, Plombière, Ragatz, etc., often -suffices without any internal treatment.</p> - -<p><i>Functional Hepatic Disorders.</i>—Fothergill held that some -persons were born with “congenitally incompetent livers,” an -unwelcome legacy unduly incident among those of gouty heritage. -Now the intimate interdependence of hepatic and gastro-intestinal -disorders has long been recognised; indeed, the swiftness with -which retribution, in the shape of so-called “biliousness,” overtakes -those who fare not wisely, but too well, is proverbial even -among the laity.</p> - -<p>Thus chronic hyperæmia of the liver, due to stasis in the portal -area, commonly ensues in those gouty subjects who eat and drink -too much, especially alcohol. The same Nemesis awaits those -who lead too sedentary a life, and in the train of chronic constipation -develop such hepatic congestion, with in some instances -attacks of catarrhal jaundice.</p> - -<p>As to treatment of these cases by mineral waters, a preference -must be given to <i>alkaline</i>, <i>sulphated alkaline</i>, or <i>muriated</i> -waters, according to the special indications of individual cases. -Thus suppose the subject is stout and plethoric, and given perhaps -to hæmorrhoids or pruritis ani, then spas with <i>sulphated -alkaline</i> waters (Marienbad, Karlsbad, etc.) may be recommended. -But equally good results will follow a course at home of <i>muriated</i> -waters, or <i>muriated sulphur</i> waters, such as Harrogate, Llanwyrtid, -and Strathpeffer, etc.</p> - -<p>Bearing in mind that functional hepatic disorders are in large -part secondary to gastro-intestinal derangements, it is probable -that the beneficial effect of the above types of waters on the liver -is exerted indirectly, though we must recollect that the salts of -soda have a direct stimulant action on the hepatic function.<a id="FNanchor_66" href="#Footnote_66" class="fnanchor">[66]</a></p> - -<p><span class="pagenum"><a id="Page_448"></a>[448]</span></p> - -<p>Given in adequate doses, they act as mild, unirritating laxatives, -the daily evacuations thus produced relieving hepatic congestion -and coincidently any tendency to portal engorgement. Through -their dual action of flushing the digestive canal and stimulating -hepatic and gastro-intestinal secretory activities, we find the -explanation of the decided benefit that follows their use in gastric -catarrhs, especially of alcoholic origin, also in catarrhal jaundice, -incipient cirrhosis of the liver, and so-called abdominal -venosity.</p> - -<p>As we know, Sir Lauder Brunton long since pointed out that -the ingestion of saline mineral waters tends to counteract any -tendency to catarrh of the biliary passages, the biliary secretion -tending to become less viscid; consequently the passage of gall-sand -is promoted. Some, like Hans Kehr, of Holberstadt, advise -a course of saline waters <i>after</i> operations for the removal of gall-stones; -others advocate their employment <i>before</i> surgical intervention. -It is obvious, however, that their range of usefulness in -this affection must be limited and is largely to be attributed to -their power of mitigating inflammatory or catarrhal changes in -the gall bladder and its related ducts.</p> - -<p><i>Intestinal Derangements.</i>—Constipation is, as is well known, -the <i>bête noire</i> of the gouty, and, while the basal indications of its -therapy have to be carefully ascertained in every individual, -still much may be done by a properly chosen and adequately -supervised course of spa treatment. This, of course, entails -revision of the diet and habits, notably in regard to exercise; in -some of sedentary habit a mere change of air to a more bracing -climate, with its associated increase of exercise, may suffice; in -others of stout plethoric type a visit to one of the sulphated -alkaline spas will be of benefit; while in weaker subjects of the -lean kind muriated waters will be more suitable.</p> - -<p>In many the habitual constipation is due to a catarrhal condition -of the intestine. Trautner, as we know, considers that gout -originates in a mucous colitis. In France the gaseous muriated -waters of Chatel Guyon are in great vogue for chronic catarrhal -conditions of the intestines, especially those associated with -abdominal plethora and constipation. Indeed, because of its -success in these cases, it is sometimes called the French Kissingen.</p> - -<p>On the other hand, the Plombières Spa is the one that <i>par -excellence</i> devotes itself to the treatment of mucous colitis by a -combination of (1) intestinal douches, (2) sedative warm baths, -and (3) “under-water” douches directed against the abdomen.<span class="pagenum"><a id="Page_449"></a>[449]</span> -Treatment by the Plombières method is now available at most -English spas, and, while I can speak highly of its benefits, I think -perhaps there is sometimes a tendency to resort to it after a -routine fashion irrespective of the presence of any special indications -for its usage. The after-results in some cases are not enviable, -and recently a distinguished surgeon informed me that he -had met with instances in which ill-advised and prolonged usage -of such irrigation resulted in an atonic condition of the colon.</p> - -<h3><span class="smcap">Associated Morbid Conditions</span></h3> - -<p><i>Glycosuria.</i>—The more chronic and benign forms met with in -gout frequently derive benefit from a course of mineral waters, -though, of course, revision of the diet and regimen in general are -essential concomitants thereof. Indeed, the high reputation -achieved by certain Continental spas—Karlsbad, Vichy, Neuenahr, -etc.—in this disorder is in large part due to the care and attention -bestowed on these the basal indications.</p> - -<p>In the gouty obese, with a tendency to piles and abdominal -plethora, the <i>sulphated alkaline</i> and <i>simple alkaline</i> waters, such as -Karlsbad, Vichy, Neuenahr, Brides-les-Bains, etc., are suitable, -and in this country the <i>muriated sulphurous</i> waters of Harrogate -and Llandrindod.</p> - -<p>In some of the gouty obese their bouts of glycosuria sometimes -alternate with attacks of uric acid gravel, and not infrequently -there is also present a slight degree of albuminuria. In these -cases the <i>earthy or calcareous</i> waters enjoy a considerable reputation, -notably Contrexéville, and not a few with uric acid gravel -and slight albuminuria resort to Wildungen.</p> - -<p>I have before alluded to the beneficial effects in glycosuria of -Bath waters, which, like Contrexéville and Wildungen, have an -earthy or calcareous content. For the less robust and lean type -of glycosuric Sir Hermann Weber recommends “simple thermal -baths, such as can be obtained at many resorts of moderate -elevation (Gastein, Wildbad, Buxton, Schlangenbad, and Ragatz).” -As an alternative, he states that “the internal use of muriated -alkaline or simple alkaline waters (Vichy, Neuenahr, Obersalzbrunn, -Royat, La Bourboule), in association with thermal baths or alone, -may often be recommended.”</p> - -<p><i>Oxaluria.</i>—This condition, like glycosuria, is often met with in -the gouty. It is of course often due to faulty diet, but in many -instances there is a strong nerve element in the case. In the -former instance dietetic restrictions are the basal indication. In -these cases, if there be constipation, a visit to the <i>muriated</i> springs -in this country or to Kissingen, Homburg, etc., is advisable.<span class="pagenum"><a id="Page_450"></a>[450]</span> -Otherwise, <i>alkaline</i> springs, <i>i.e.</i>, Vichy, or <i>alkaline earthy</i> springs, -such as Vittel, Contrexéville, or Martigny-les-Bains, may be given -the preference. For those instances in which the nerve element -is predominant the character of the mineral waters is quite subsidiary -compared with the all-important point of procuring the -subject freedom from worry.</p> - -<p><i>Gouty Phlebitis.</i>—It is believed that gaseous muriated waters, -both internally and in the form of baths, are useful in counteracting -any tendency to phlebitis. Obviously, if there be any -symptom or sign of existing phlebitis, any such procedure would -be fraught with risk. Still patients who have had phlebitis frequently -resort to such spas, notably Bagnoles-de-l’Orme, where -the resident physicians have made a special study of the constitutional -tendencies to chronic phlebitis. The waters are but -weakly mineralised, and may be classed in the simple thermal -group (81°-84° F.).</p> - -<p><i>Respiratory Disorders.</i>—While, as I have said, I deprecate any -notion of specific gouty types of bronchitis, asthma, etc., there is -no doubt that gouty subjects, like many others, are prone to -bronchial affections, and for such mineral water treatment at a -favourable season of the year, is equally beneficial. In gouty -bronchitics of plethoric type, courses of sulphated alkaline waters -will often do much to relieve the symptoms. Again, many -sulphur, muriated alkaline, and muriated spas, have achieved a -great reputation in the same sphere, <i>e.g.</i>, Ems, Royat, Eaux-Bonnes, -Baden-Baden, and Soden. Nor need we go outside our -own country, for many of our mountain health resorts are in -the summer months equally eligible for treatment of these -disorders of the respiratory system.</p> - -<p><i>Fibrositis.</i>—Adequately to describe all the methods, internal -and external, in vogue at spas for the treatment of, <i>e.g.</i>, chronic -lumbago and sciatica, would be quite futile in the space at my -command. I have the less compunction in being unusually -brief inasmuch as Bassett Jones and I have dealt exhaustively -with the subject in our work on fibrositis.</p> - -<p>The groundwork of successful treatment will rest on the application -of the general principles in force for the treatment of the -underlying gout. They will, of course, include internal and -external treatment by simple thermal waters, the thermal muriated -and thermal sulphurous waters, etc. Frequently, too, cold -muriated and other waters artificially heated are invoked for this -dual purpose.</p> - -<p>The benefits of external treatment by douches of varying -character will depend on the measure of discrimination exercised -in adapting their application to suit the individual necessities of<span class="pagenum"><a id="Page_451"></a>[451]</span> -the case. But I would here lodge a plea against the far too great -frequency with which such cases are sent to spas during the acute -phases, whereas it is only the subacute or chronic forms that are -eligible for treatment by hydrotherapy.</p> - -<p><i>Gouty Eczema.</i>—The climatic suitability of the spa is of primary -importance, and while, as a rule, cold, damp and windy localities -are to be avoided, still personal idiosyncrasy plays a large part in -the decision, some cases of eczema being aggravated by cold, others -by heat and sunlight.</p> - -<p>The spa treatment of gouty eczema has for its aim the correction -of the constitutional taint by the internal exhibition of -mineral waters in conjunction with baths. To this end, the eliminative -effects of courses of alkaline (Vichy, Vals), muriated -(Llandrindod), sulphurous (Harrogate, Strathpeffer, Llanwyrtid), -or muriated sulphurous waters (Uriage, Aix-la-Chapelle, etc.), are -often invoked with marked benefit.</p> - -<p>Again, the thermal muriated alkaline waters of Royat and the -arsenical springs of La Bourboule have acquired a great reputation -in gouty eczema, and in obstinate but non-pruriginous types -the prolonged tepid baths in vogue at Loèche-les-Bains, in Switzerland.</p> - -<p>In many instances of senile or atrophic type a course during -the summer of simple thermal baths is often beneficial. Buxton -is suitable, also Wildbad, Schlangenbad, Ragatz, etc. Lastly, -in eczema of seborrhœic type thermal sulphurous waters, <i>e.g.</i>, -Schinznach, Aix-les-Bains, Bagnères-de-Luchon, etc., are highly -commended.</p> - -<p><i>Uric Acid Gravel.</i>—Though, as before stated, there is no specific -connection between this disorder and gout, still the gouty no more -than others are immune therefrom. For the stout, plethoric, -and constipated, sulphated and sulphated alkaline springs are -indicated. But if, on the other hand, there is a tendency to -diarrhœa, these aperient waters must be renounced in favour of -simple alkaline springs. In those of less robust type the simple -thermal or earthy waters, notably Contrexéville and Wildungen, -are to be preferred, and failing these, the muriated waters.</p> - -<p><i>Arterio-sclerosis.</i>—It is hardly necessary to say that in all but -the slightest forms high altitudes are contra-indicated. In these -less advanced cases, if the subject be stout and plethoric, the -sulphated alkaline waters (Karlsbad, Marienbad, etc.) are useful; -while in thin persons the muriated waters are more suitable.</p> - -<p>In more advanced cases we may during summer advocate a -course of treatment at some simple thermal spa, such as Buxton, -and many of these cases do well at Bath during the spring, or -they may be sent to Bourbon Lancy, which has been termed the<span class="pagenum"><a id="Page_452"></a>[452]</span> -French rival to Nauheim, because of the excellent results obtained -in cases of raised blood pressure.</p> - -<p><i>Chronic Nephritis.</i>—Clearly in these cases a quiet life, without -mental worry, gentle and not excessive exercise, with residence -in an equable climate, are the primary indications. In the early -stage, when the patient’s condition is good, the tension not high, -and the quantity of albumen small, the subjects derive much -benefit from an annual visit to certain mineral springs. Not that -mineral waters have any curative influence; they merely help the -interstitial circulation and promote flushing.</p> - -<p>Of mineral waters the <i>simple thermal</i> or the <i>weak alkaline</i> are -generally considered the most eligible, <i>e.g.</i>, Vichy, which is useful -also in cases of combined albuminuria and glycosuria. In cases -with cardiac dilatation care should be taken not to prescribe -mineral waters in excessive amount. If complicated by anæmia, -chalybeate waters, according to Weber, are “not rarely useful.”</p> - -<p>Bain and Edgecombe, discussing gouty albuminuria, state that -the magnesia water of Harrogate, in combination with the old -sulphur, has a marked effect in reducing the absolute amount of -albumen in the urine, <i>e.g.</i>, from one-fourth by volume to a mere -trace. They add, that if the specific gravity of the urine be low -chalybeate water is indicated with, if necessary, a morning -aperient draught. If glycosuria and albuminuria co-exist, the -“sulphur waters may be tried tentatively” as the specific gravity -does not help us in these cases. “When in doubt, it is safer to give -an iron water and trust to diet and baths for a diminution in the -excretion of these substances.” Not a few of these cases find -their way to Bath and Buxton, often for relief of their increased -arterial tension, and the experience of most is that in the more -robust types a course of Aix massage is advantageous, while for -others more advanced in years baths after the Bourbon Lancy -method.</p> - -<h3><span class="smcap">Concluding Remarks on Spa Treatment</span></h3> - -<p>It is well that the potency and complexity of spa treatment be -realised, involving as it does not only drinking or internal treatment, -but also <i>balneotherapy</i>, <i>electro-therapy</i>, and all the other -accessory therapeutic methods now at command. With all -these powerful weapons to hand, it is obvious that their use -demands a corresponding degree of discrimination, this even in -cases otherwise suitable, and here a word as to the types of gout -most suitable for the <i>internal</i> exhibition of mineral waters.</p> - -<p>In this matter the rules laid down for hydrotherapy, or the -<i>external</i> use of waters, are in the main applicable. In other -words, <i>acute cases of gout are always ineligible</i>, as likewise those<span class="pagenum"><a id="Page_453"></a>[453]</span> -instances in which an attack appears imminent or those in which -recovery from an <i>acute</i> paroxysm is barely accomplished. On -the other hand, mineral waters are indicated in <i>chronic</i> gout and -in the <i>inter-paroxysmal</i> periods that mark the <i>early</i> stages of the -disorder. Indeed, I know of no other treatment that is as effectual, -and, with Sir William Roberts, “I do not think, therefore, -that gouty patients, if they can afford the time and expense, -should forego the advantages of the time-honoured practice of a -visit to a mineral spring.”</p> - -<p>But, to attain the best results of spa treatment, not only should -the cases be suitable, but they should be despatched at the right -<i>season</i>. Even in spas that are open all the year round we should -try to select the most congenial month. Thus, if the subject -is intolerant of heat, we should not advise him, say, to go to Bath -in July or August, or, for that matter, during the hottest summer -months to Aix-les-Bains, Baden-Baden, Wiesbaden, Neuenahr, etc. -If he has to take his course at this period of the year, and a -thermal spring is indicated, Buxton will be more suitable than -Bath, and we have a large choice of other spas in more bracing -localities, such as Harrogate, Llandrindod, Strathpeffer. In -short, some discrimination must be exercised. Again, if a course -be indicated in the winter, we should favour those spas where the -hotels are in proximity to the springs, so as to obviate unnecessary -exposure, <i>e.g.</i>, Bath, Wiesbaden, Helouan, etc.</p> - -<p>As to <i>duration</i> of a course, there is, I think, in many spas a too -great tendency to be dominated by tradition. Not only is the -duration of the cure arbitrarily fixed, but, still worse, the drinking -of the waters, the bathing, and even the dietaries are frequently -in danger of becoming stereotyped, with, as a consequence, a lack -of that eclecticism necessary in the best interests of individual -cases. A certain amount of routine is unavoidable, and has this -advantage, that persons find it easier to submit to irksome -restrictions when they see others conforming thereto. But -even so there is ample scope for such modifications as may be -required, and upon their adoption the success of spa treatment -mainly depends.</p> - -<p>If arbitrary rules in respect of drinking, bathing, etc., are to be -deprecated, the same applies with unvarying fixity to the duration -of a cure for all cases. Generally speaking, three to four weeks -is the average stay at spas. But obviously it should be -varied to suit the patient’s condition, and in many instances of -chronic gout it may with advantage be extended to six or eight -weeks.</p> - -<p>Again, I think perhaps in this country the advantages of an -<i>after-cure</i> are insufficiently realised. In this respect our Continental<span class="pagenum"><a id="Page_454"></a>[454]</span> -brethren set us an example, attaching the greatest -importance as they do to an after-cure, especially after a course -of laxative waters, <i>e.g.</i>, Karlsbad, Marienbad, and Kissingen. -Certainly to plunge forthwith into work immediately after a cure -leads but too often to another breakdown and the undoing of any -advantages that may have been reaped. Of late I have noted, -especially in business men, a tendency to interrupt even their -course by travelling considerable distances on <i>non-bathing</i> days -to attend to their affairs. The folly of this is obvious, and the -results are almost invariably unsatisfactory. Indeed, in these all -too strenuous days one almost despairs of <i>after-cures</i>, for it is -difficult enough oftentimes to prevail on people to stay even for -their course of three weeks, and frequently one is asked to conduct -their treatment after a more intensive fashion, and so abridge it -to a fortnight or even a week!</p> - -<p>As to the nature and site of the resorts suitable for an <i>after-cure</i> -it is impossible to lay down general rules, as individual -peculiarities have to be considered. But the physician who prescribes -such ought, as Sir Hermann Weber remarks, “to be -acquainted with the nature of the locality recommended, if possible -by personal visits, and the reports of thoroughly judicious -people.” For, as he rightly says, there are numerous places in -the British Isles perfectly suitable for an after-cure, to mention -but a few in England, Ilkley, Ben Rhydding, Malvern, Haslemere, -Church Stretton, Crowborough; in Scotland, Braemar, Ballater, -etc.; and in Wales, Llanberis, Llangollen, etc.</p> - -<h3><span class="smcap">Spas from a National Aspect</span></h3> - -<p>But brief reflection on the foregoing considerations suffices to -make it clear that the various spas and health resorts with which -this country, through Nature’s beneficence, has been so bountifully -endowed, are but members one of another, in short <i>complementary</i>, -not antagonistic, as I fear is sometimes thought. This -latter is a view to be discarded in favour of a more rational conception -of these various centres from their collective aspect as -integral parts of a therapeutic whole.</p> - -<p>Now what, in a word, is the outstanding feature of our national -life to-day? <i>Co-operation</i>—a veritable furore of national and -international effort such as the world has never seen. Spas, too, -must fall in line with the national trend, must organise and -co-operate, if they would play their full <i>rôle</i> in the drama of -reconstruction. Now, from the point of view of the State, the -true objective in therapeutics is the achievement and maintenance -of national efficiency—the production of healthy citizens, sound<span class="pagenum"><a id="Page_455"></a>[455]</span> -economic units. This then is the high purpose with which those -responsible for spas must ever be animated—an aim only to be -attained by their whole-hearted co-operation one with the other.</p> - -<p>The lay custodians, too, of spas must increasingly realise that -they do but hold in trust their healing springs to be safeguarded -in the interests of the community. Mineral waters, like coal, -issue from the bowels of the earth. Both are <i>natural</i> products; -both are <i>national</i> assets. I doubt not that the growing movement -for effectual popular control so rapidly obtaining a grip -over the political and economic life of the nation will shortly be -extended to our spas, with, as its outcome, their <i>unification</i> and -<i>co-ordination</i> under the controlling influence of a central body of -experts vested with plenary powers to inspect, control, and -inspire the development of these hydrotherapeutic centres. -“Salus populi suprema est lex.”</p> - -<hr class="chap x-ebookmaker-drop"> - -<div class="footnotes"> - -<div class="chapter"> - -<p><span class="pagenum"><a id="Page_456"></a>[456]</span></p> - -<h2 class="nobreak" id="FOOTNOTES">FOOTNOTES</h2> - -</div> - -<div class="footnote"> - -<p><a id="Footnote_1" href="#FNanchor_1" class="label">[1]</a> 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 <i>articular</i> -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:—</p> - -<p>“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 <i>débris</i>, -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).</p> - -</div> - -<div class="footnote"> - -<p><a id="Footnote_2" href="#FNanchor_2" class="label">[2]</a> 920 (S. Eng. Leg.), “There cam a goute In is knee, of Anguische gret.... So -longue, that is kneo to-swal.”</p> - -<p>1310 (In Wright Lyric), “A goute me hath ygreythed so, Ant other eveles monye -mo.”</p> - -<p>1377 (Langl., P. Pl.), “He ... gyued me in goutes, I may noughte go at large.”</p> - -<p>1400 (Lanfranc’s Cirurg.), “A man that hath arteticam, that is as myche to seie as -a goute.”</p> - -<p>1450 (M.E. Med. Bk., Heinrich), “Here wyth anoynte the goutes.”</p> - -<p>1566 (J. Alday, tr. Baoystuau’s Theat. World), “Their legges full of gouts.”</p> - -<p>1579 (Langham, Gard. Health, 1633), “For all goutes, seethe Leekes and Otemeale -with sheepes tallow, and apply them hot.”</p> - -<p>1590 (Spenser, F. Q.), “And eke in foote and hand A grievous gout tormented him -full sore.”</p> - -<p>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.”</p> - -<p>1704 (Fuller, Med. Gymn.), “There have been some Gouts ... which nothing could -remove but a very low Diet.”</p> - -<p>1732 (Pope, Ess. Man.), “So, when small humours gather to a gout The Doctor -fancies he has driv’n ’em out.”</p> - -<p>1822 (Ld. Eldon, in Twiss Life), “I found the King in bed yesterday. He has had -a pretty severe gout.”—<i>New English Dictionary, Oxford</i>, 1901. (<i>Ed. Sir James Murrary.</i>)</p> - -</div> - -<div class="footnote"> - -<p><a id="Footnote_3" href="#FNanchor_3" class="label">[3]</a> 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.</p> - -</div> - -<div class="footnote"> - -<p><a id="Footnote_4" href="#FNanchor_4" class="label">[4]</a> 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.”</p> - -</div> - -<div class="footnote"> - -<p><a id="Footnote_5" href="#FNanchor_5" class="label">[5]</a> <i>Physiognomy of the Goutily Disposed.</i>—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):—</p> - -<p>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.</p> - -<p><i>Form.</i>—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. -<i>Nutrition</i> active; digestion vigorous; appetite great for animal food and -alcoholic stimuli. <i>Respiration</i> deliberate, deep; circulation vigorous; animal heat -abundant; locomotion active; aptitude for exercise and outdoor amusements. -<i>Reproductive</i> powers active; innervation abundant, the mental powers vigorous and -enduring.</p> - -<p><i>Physiognomy of the Sanguine Gouty Cachexia.</i>—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.</p> - -<p>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.—<i>Med. Observation -and Research</i>, 2nd edition, pp. 96-98.</p> - -</div> - -<div class="footnote"> - -<p><a id="Footnote_6" href="#FNanchor_6" class="label">[6]</a> 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, <i>e.g.</i>, 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—<i>erepsin</i>. 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.</p> - -</div> - -<div class="footnote"> - -<p><a id="Footnote_7" href="#FNanchor_7" class="label">[7]</a> 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.</p> - -</div> - -<div class="footnote"> - -<p><a id="Footnote_8" href="#FNanchor_8" class="label">[8]</a> 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 <i>uric acid compound</i> can be split by means of an <i>enzyme</i>.” The compound exists, -not in the plasma, but in the <i>corpuscles</i>. 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.”</p> - -</div> - -<div class="footnote"> - -<p><a id="Footnote_9" href="#FNanchor_9" class="label">[9]</a> 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.</p> - -<p>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.”</p> - -</div> - -<div class="footnote"> - -<p><a id="Footnote_10" href="#FNanchor_10" class="label">[10]</a> “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 <i>in -vitro</i> may furnish a means for the elucidation of some of these questions.”—<i>Walker -Hall.</i></p> - -</div> - -<div class="footnote"> - -<p><a id="Footnote_11" href="#FNanchor_11" class="label">[11]</a> 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.—<i>Stewart’s</i> -“<i>Manual of Physiology</i>.”</p> - -</div> - -<div class="footnote"> - -<p><a id="Footnote_12" href="#FNanchor_12" class="label">[12]</a> 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.</p> - -</div> - -<div class="footnote"> - -<p><a id="Footnote_13" href="#FNanchor_13" class="label">[13]</a> 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.—“<i>Uric Add Metabolism</i>,” -11—<i>H. B. Lewis, M. S. Dunn, and E. A. Doisy, “Journal of Biological Chemistry,” -1918.</i></p> - -<p>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.</p> - -</div> - -<div class="footnote"> - -<p><a id="Footnote_14" href="#FNanchor_14" class="label">[14]</a> Quoting from the same article, <i>Journal of Biological Chemistry</i>, 1918, by Lewis, -Dunn and Doisy, these authorities observe that—<i>re</i> 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.”</p> - -</div> - -<div class="footnote"> - -<p><a id="Footnote_15" href="#FNanchor_15" class="label">[15]</a></p> - -<div class="figcenter illowp100" id="formula17" style="max-width: 20.3125em;"> - <img class="w100" src="images/formula17.jpg" alt=""> -</div> - -</div> - -<div class="footnote"> - -<p><a id="Footnote_16" href="#FNanchor_16" class="label">[16]</a> 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 <i>in vitro</i>, the inference is that -the presence of uric acid in the urine of the Dalmatian is not attributable to the <i>absence -of uricase in its tissues</i>. “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.”—<i>Journal of Biological Chemistry</i>, 1918.</p> - -</div> - -<div class="footnote"> - -<p><a id="Footnote_17" href="#FNanchor_17" class="label">[17]</a> 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:—</p> - -<div class="blockquote"> - -<p>(1) The amount of purin bodies taken in the food upon which chiefly depends the -amount of exogenous uric acid.</p> - -<p>(2) The amount of destruction of tissue nucleo-proteins.</p> - -<p>(3) The amount of purin bases formed in the muscle tissue.</p> - -<p>(4) The amount of conversion of purin bases into the uric acid.</p> - -<p>(5) The amount of destruction of uric acid, if any, occurring in the body.</p> - -<p>(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.</p> - -<p>(7) The retention of uric acid in the blood and tissues.</p> - -<p>(8) The power of the kidney to excrete uric acid.</p> - -<p>(9) The solubility of uric acid in urine—dependent upon the amount of neutral -phosphates present, the temperature, reaction and concentration thereof.</p> - -</div> - -</div> - -<div class="footnote"> - -<p><a id="Footnote_18" href="#FNanchor_18" class="label">[18]</a></p> - -<p class="center"><span class="smcap">Effect of Atophan on Exogenous Purins.</span> -(McLester, in “Archives of Internal Medicine.”)</p> - -<table class="borders"> - <tr> - <th rowspan="2">Date.</th> - <th rowspan="2">R. E.</th> - <th rowspan="2">Blood<br>Mg. U in<br>100 Gm.</th> - <th colspan="4">Twenty-four Hour Urine.</th> - </tr> - <tr> - <th>Amt. c.c.</th> - <th>U. Gm.</th> - <th>NH. Gm. N.</th> - <th>N. Gm.</th> - </tr> - <tr> - <td>5/28</td> - <td>——</td> - <td class="tdr">2·9</td> - <td class="tdr">1,150</td> - <td class="tdr">·46</td> - <td class="tdr">·58</td> - <td class="tdr">10·26</td> - </tr> - <tr> - <td>5/29</td> - <td>7 a.m.: 500 grams thymus. 2 p.m.: Blood</td> - <td class="tdr">3·2</td> - <td class="tdr">900</td> - <td class="tdr">·66</td> - <td class="tdr">·69</td> - <td class="tdr">10·96</td> - </tr> - <tr> - <td>5/31</td> - <td>7 a.m.: 500 grams thymus. 9 a.m.: Atophan, 2 p.m.: Blood</td> - <td class="tdr">1·1</td> - <td class="tdr">1,280</td> - <td class="tdr">·75</td> - <td class="tdr">·76</td> - <td class="tdr">11·16</td> - </tr> -</table> - -</div> - -<div class="footnote"> - -<p><a id="Footnote_19" href="#FNanchor_19" class="label">[19]</a> 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.”</p> - -</div> - -<div class="footnote"> - -<p><a id="Footnote_20" href="#FNanchor_20" class="label">[20]</a> 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:—</p> - -<p>(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 -<i>nickel</i> is the best of those tried.</p> - -<p>(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.</p> - -<p>(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 (<i>a</i>) the precipitation -of the uric acid by means of nickel acetate in a solution alkaline with sodium carbonate. -(<i>b</i>) The estimation of the uric acid in the precipitate by means of a dilute solution of -iodine.</p> - -<p>(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.</p> - -<p>(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.</p> - -<p>(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.</p> - -</div> - -<div class="footnote"> - -<p><a id="Footnote_21" href="#FNanchor_21" class="label">[21]</a></p> - -<p class="center"><span class="smcap">Uric Acid Estimation in Normal Individuals</span></p> - -<p class="center">(McLester, “Archives of Internal Medicine.”)</p> - -<p class="center"><i>Milligrams Uric Acid in 100 grams Blood.</i></p> - -<table> - <tr> - <td>J. C.</td> - <td class="tdr">0·5</td> - </tr> - <tr> - <td>H. D.</td> - <td class="tdr">0·6</td> - </tr> - <tr> - <td>M. D.</td> - <td class="tdr">0·6</td> - </tr> - <tr> - <td>A. B.</td> - <td class="tdr">0·8</td> - </tr> - <tr> - <td>R. C.</td> - <td class="tdr">0·9</td> - </tr> - <tr> - <td>H. D.</td> - <td class="tdr">0·9</td> - </tr> - <tr> - <td>J. G.</td> - <td class="tdr">0·0</td> - </tr> - <tr> - <td>S. M.</td> - <td class="tdr">1·1</td> - </tr> - <tr> - <td>R. D.</td> - <td class="tdr">1·3</td> - </tr> - <tr> - <td>L. S.</td> - <td class="tdr">1·4</td> - </tr> - <tr> - <td>L. H.</td> - <td class="tdr">1·7</td> - </tr> - <tr> - <td>R. O.</td> - <td class="tdr">2·1</td> - </tr> - <tr> - <td>H. H.</td> - <td class="tdr">2·5</td> - </tr> - <tr> - <td>J. M.</td> - <td class="tdr">2·5</td> - </tr> - <tr> - <td>R. E.</td> - <td class="tdr">2·9</td> - </tr> -</table> - -<p class="center"><span class="smcap">Uric Acid of Blood in Disease.</span> (McLester, “Archives of Internal Medicine.”)</p> - -<p class="center"><i>Milligrams in 100 grams Blood.</i></p> - -<table> - <tr> - <td>Mitral lesion</td> - <td class="tdr">0·5</td> - </tr> - <tr> - <td>Rheumatic fever</td> - <td class="tdr">0·6</td> - </tr> - <tr> - <td>Acute syphilis</td> - <td class="tdr">0·8</td> - </tr> - <tr> - <td>Chronic tuberculous pleurisy</td> - <td class="tdr">0·8</td> - </tr> - <tr> - <td>Pneumonia</td> - <td class="tdr">1·2</td> - </tr> - <tr> - <td>Pneumonia</td> - <td class="tdr">1·3</td> - </tr> - <tr> - <td>Sciatica</td> - <td class="tdr">1·3</td> - </tr> - <tr> - <td>Typhoid fever</td> - <td class="tdr">1·4</td> - </tr> - <tr> - <td>Ulcer of stomach</td> - <td class="tdr">1·5</td> - </tr> - <tr> - <td>Pneumonia</td> - <td class="tdr">1·6</td> - </tr> - <tr> - <td>Amœbic dysentery</td> - <td class="tdr">1·6</td> - </tr> - <tr> - <td>Neurasthenia (?)</td> - <td class="tdr">1·7</td> - </tr> - <tr> - <td>Acute tuberculous pleurisy</td> - <td class="tdr">1·7</td> - </tr> - <tr> - <td>Chronic interstitial nephritis</td> - <td class="tdr">1·8</td> - </tr> - <tr> - <td>Malaria</td> - <td class="tdr">1·8</td> - </tr> - <tr> - <td>Pneumonia</td> - <td class="tdr">1·9</td> - </tr> - <tr> - <td>Uremia</td> - <td class="tdr">2·1</td> - </tr> - <tr> - <td>Polycythemia</td> - <td class="tdr">2·2</td> - </tr> - <tr> - <td>Graves’ disease</td> - <td class="tdr">2·5</td> - </tr> - <tr> - <td>Pneumonia</td> - <td class="tdr">2·7</td> - </tr> - <tr> - <td>Gout</td> - <td class="tdr">3·3</td> - </tr> - <tr> - <td>Arterial hypertension</td> - <td class="tdr">3·3</td> - </tr> - <tr> - <td>Intermittent gastric supersecretion</td> - <td class="tdr">3·7</td> - </tr> - <tr> - <td>Gout</td> - <td class="tdr">4·5</td> - </tr> -</table> - -</div> - -<div class="footnote"> - -<p><a id="Footnote_22" href="#FNanchor_22" class="label">[22]</a> 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.”</p> - -</div> - -<div class="footnote"> - -<p><a id="Footnote_23" href="#FNanchor_23" class="label">[23]</a> Magnus Levy and McClure have also noted that the excretion of exogenous -purin is not invariably retarded or diminished.</p> - -</div> - -<div class="footnote"> - -<p><a id="Footnote_24" href="#FNanchor_24" class="label">[24]</a> When experimentally injected, the urates are absorbed slowly by phagocytic -leucocytes and giant cells.—<i>Gideon Wells.</i></p> - -</div> - -<div class="footnote"> - -<p><a id="Footnote_25" href="#FNanchor_25" class="label">[25]</a> Because the gouty tophi do not suppurate, even when ulcerated, through the skin, -it has been suggested that the urates have antiseptic properties. Bendix (<i>Zeit. klin. -Med.</i>, 1902 (44), 165), however, could not demonstrate such antiseptic properties -experimentally.—<i>Gideon Wells.</i></p> - -</div> - -<div class="footnote"> - -<p><a id="Footnote_26" href="#FNanchor_26" class="label">[26]</a> 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.</p> - -</div> - -<div class="footnote"> - -<p><a id="Footnote_27" href="#FNanchor_27" class="label">[27]</a> “Tophi sometimes precede by some years ... the development of gouty attacks -in joints. The same is true also of auricular tophi.”—<i>Duckworth</i>: “<i>A Treatise on Gout</i>.”</p> - -</div> - -<div class="footnote"> - -<p><a id="Footnote_28" href="#FNanchor_28" class="label">[28]</a> “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 -<i>cutaneous gravel</i>, 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.”—<i>Trousseau’s</i> -“<i>Clinical Medicine</i>.”</p> - -</div> - -<div class="footnote"> - -<p><a id="Footnote_29" href="#FNanchor_29" class="label">[29]</a> <i>Redness</i> 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.</p> - -</div> - -<div class="footnote"> - -<p><a id="Footnote_30" href="#FNanchor_30" class="label">[30]</a> “Quod in omnibus podagricorum paroxysmis solemne est, insignior intumescentia -venerum membro vexato intertextarum se in conspectu dat.”—<i>Sydenham.</i></p> - -</div> - -<div class="footnote"> - -<p><a id="Footnote_31" href="#FNanchor_31" class="label">[31]</a> 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.</p> - -<p>“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 <i>very</i> advanced age, and in constitutions <i>very</i> 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.”—<i>Sydenham.</i></p> - -</div> - -<div class="footnote"> - -<p><a id="Footnote_32" href="#FNanchor_32" class="label">[32]</a> “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.”—<i>Longstreth</i>, “<i>On Gout</i>.”</p> - -</div> - -<div class="footnote"> - -<p><a id="Footnote_33" href="#FNanchor_33" class="label">[33]</a> “The pain is altogether disproportionate to the other signs of inflammation, -and, even more, to the consequent structural changes in the inflamed part.”—<i>Paget.</i></p> - -<p>As to the peculiar character of the pain, Duckworth states: “Nothing at all like -it occurs in any other joint disease.”</p> - -</div> - -<div class="footnote"> - -<p><a id="Footnote_34" href="#FNanchor_34" class="label">[34]</a> 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.”</p> - -</div> - -<div class="footnote"> - -<p><a id="Footnote_35" href="#FNanchor_35" class="label">[35]</a> “<i>Regular gout</i> may <i>supervene suddenly, and be chronic</i>; that is to say, its outbreak -need not have been preceded by paroxysms in any way characteristic of acute gout.”—<i>Trousseau</i>, -“<i>On Gout</i>.”</p> - -</div> - -<div class="footnote"> - -<p><a id="Footnote_36" href="#FNanchor_36" class="label">[36]</a> 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.”</p> - -</div> - -<div class="footnote"> - -<p><a id="Footnote_37" href="#FNanchor_37" class="label">[37]</a> Mr. James Moore, surgeon to the Second Regiment of Life Guards (<i>Medico-Chirurgical -Transactions</i>, 1809, Vol. I.):—</p> - -<p>“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.</p> - -<p>“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.</p> - -<p>“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.</p> - -<p>“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.”</p> - -</div> - -<div class="footnote"> - -<p><a id="Footnote_38" href="#FNanchor_38" class="label">[38]</a> 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.</p> - -</div> - -<div class="footnote"> - -<p><a id="Footnote_39" href="#FNanchor_39" class="label">[39]</a> In this connection the tendency of gouty glycosurics to exhibit boils and sometimes -carbuncles should not be forgotten.</p> - -</div> - -<div class="footnote"> - -<p><a id="Footnote_40" href="#FNanchor_40" class="label">[40]</a> 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.”</p> - -</div> - -<div class="footnote"> - -<p><a id="Footnote_41" href="#FNanchor_41" class="label">[41]</a> In support of this contention, I would note that Charcot, while he gives us an -inimitable account of the <i>tophaceous</i> variety of gout, introduces also another variant, -as he deems it, of <i>chronic articular gout</i>. 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 <i>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</i>.” It cannot, we think, be doubted that the clinical content of this -group is largely made up of <i>rheumatoid</i> or <i>atrophic arthritis</i>. The evidence that these -examples, <i>quâ</i> <i>uratic deposits</i>, are of “gouty” nature, is obviously very slender.</p> - -<p>Reverting to Sir Dyce Duckworth, this authority also recognises two varieties of -chronic articular gout: (<i>a</i>) tophaceous gout; (<i>b</i>) chronic deforming gout, with as its -synonym <i>arthritis deformans uratica</i>. As to the clinical content of this latter group he -writes: “The fingers, hands, and wrists show various deformities depending on <i>over-growth</i> -of <i>articulating ends of bone</i>, <i>cartilage</i>, ligaments, and bursæ. <i>These may be complicated -with visible or invisible tophaceous deposits</i>.” 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., <i>osteoarthritis</i>.</p> - -</div> - -<div class="footnote"> - -<p><a id="Footnote_42" href="#FNanchor_42" class="label">[42]</a> 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.</p> - -</div> - -<div class="footnote"> - -<p><a id="Footnote_43" href="#FNanchor_43" class="label">[43]</a> Sir Spencer Wells in his “Practical Observations on Gout and its Complications -and on the Treatment of Joints stiffened by Gouty Deposits.”</p> - -<p>“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.’”—<i>Laycock</i>: -“<i>Nervous Diseases of Women</i>.”</p> - -</div> - -<div class="footnote"> - -<p><a id="Footnote_44" href="#FNanchor_44" class="label">[44]</a> “Diseases of the Eye” (1918), p. 258.</p> - -</div> - -<div class="footnote"> - -<p><a id="Footnote_45" href="#FNanchor_45" class="label">[45]</a> “Diseases of the Eye” (1919).</p> - -</div> - -<div class="footnote"> - -<p><a id="Footnote_46" href="#FNanchor_46" class="label">[46]</a> “Diseases and Injuries of the Eye” (1913).</p> - -</div> - -<div class="footnote"> - -<p><a id="Footnote_47" href="#FNanchor_47" class="label">[47]</a> Kruckmann, <i>Med. Klinik.</i>, 1910, No. 38.</p> - -</div> - -<div class="footnote"> - -<p><a id="Footnote_48" href="#FNanchor_48" class="label">[48]</a> <i>Proc. Roy. Soc. Med.</i>, Ophth. Section, 1914, p. 66.</p> - -</div> - -<div class="footnote"> - -<p><a id="Footnote_49" href="#FNanchor_49" class="label">[49]</a> <i>Ophth. Hosp. Reps.</i>, VII., p. 287, 1873.</p> - -</div> - -<div class="footnote"> - -<p><a id="Footnote_50" href="#FNanchor_50" class="label">[50]</a> “Diseases of the Eye” (1854), p. 558.</p> - -</div> - -<div class="footnote"> - -<p><a id="Footnote_51" href="#FNanchor_51" class="label">[51]</a> <i>Brit. Med. Journ.</i>, 1885, R. Clement Lucas.</p> - -</div> - -<div class="footnote"> - -<p><a id="Footnote_52" href="#FNanchor_52" class="label">[52]</a> <i>Lancet</i>, 1920, Vol. I., p. 500, Browning.</p> - -</div> - -<div class="footnote"> - -<p><a id="Footnote_53" href="#FNanchor_53" class="label">[53]</a> <i>Archives d’Ophtalmologie</i>, Vol. XII., p. 623.</p> - -</div> - -<div class="footnote"> - -<p><a id="Footnote_54" href="#FNanchor_54" class="label">[54]</a> A very rare form of iritis was described by the late Mr. Doyne as guttate iritis -(<i>Trans. Ophth. Soc.</i>, 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.</p> - -</div> - -<div class="footnote"> - -<p><a id="Footnote_55" href="#FNanchor_55" class="label">[55]</a> <i>Brit. Med. Journ.</i>, 1903, Vol. II., p. 138.</p> - -</div> - -<div class="footnote"> - -<p><a id="Footnote_56" href="#FNanchor_56" class="label">[56]</a> “Gout” (1876), p. 450.</p> - -</div> - -<div class="footnote"> - -<p><a id="Footnote_57" href="#FNanchor_57" class="label">[57]</a> <i>Clin. Soc. Trans.</i>, Vol. XI., p. 132, 1898.</p> - -</div> - -<div class="footnote"> - -<p><a id="Footnote_58" href="#FNanchor_58" class="label">[58]</a> “Medical Ophthalmoscopy,” 3rd edition, p. 267.</p> - -</div> - -<div class="footnote"> - -<p><a id="Footnote_59" href="#FNanchor_59" class="label">[59]</a> <i>Practitioner</i>, 1909, Vol. II., p. 61.</p> - -</div> - -<div class="footnote"> - -<p><a id="Footnote_60" href="#FNanchor_60" class="label">[60]</a> 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.”</p> - -</div> - -<div class="footnote"> - -<p><a id="Footnote_61" href="#FNanchor_61" class="label">[61]</a> “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.”</p> - -</div> - -<div class="footnote"> - -<p><a id="Footnote_62" href="#FNanchor_62" class="label">[62]</a> Sir Archibald Garrod has suggested that guaiacum has a distinct effect in reducing -the amount of uric acid excreted, <i>i.e.</i>, 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.</p> - -<p>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.</p> - -<p>Joulie employs this method of indicating the constituents of urine by ratios; <i>cf.</i> Vol. I., -p. 736. Thus, taking a specimen of urine with the following “normal” factors in -grams per litre:—</p> - -<table> - <tr> - <td>Specific gravity</td> - <td class="tdr"><span class="sp4">1017·8</span></td> - </tr> - <tr> - <td>Excess of solids over water</td> - <td class="tdr"><span class="sp4">17·8</span></td> - </tr> - <tr> - <td>Physiological acidity in terms of H₂SO₄</td> - <td class="tdr">0·849</td> - </tr> - <tr> - <td>Total P₂O₄</td> - <td class="tdr">2·083</td> - </tr> - <tr> - <td>Cl</td> - <td class="tdr">6·865</td> - </tr> - <tr> - <td>Urea</td> - <td class="tdr"><span class="sp2">18·75</span></td> - </tr> - <tr> - <td>Uric acid</td> - <td class="tdr">0·416</td> - </tr> - <tr> - <td>Hippuric acid</td> - <td class="tdr"><span class="sp4">1·3</span></td> - </tr> - <tr> - <td></td> - <td class="tdr">(<i>mean</i>).</td> - </tr> -</table> - -<p>One may express the constituents as the following percentage ratios:—</p> - -<table> - <tr> - <th></th> - <th colspan="3">Normal.</th> - </tr> - <tr> - <td>“R.A.”—Ratio of physiological acidity to excess of solids over water</td> - <td>4·77</td> - <td style="padding-left: 0.25em; text-indent: 0;"> - <table style="margin: 0;"> - <tr> - <td class="nw">0·849 × 100</td> - </tr> - <tr> - <td class="tdc bt">17·8</td> - </tr> - </table> - </td> - <td></td> - </tr> - <tr> - <td>“R.P.”—Ratio of total P₂O₄ to excess of solids over water</td> - <td></td> - <td class="tdr">11·17</td> - <td></td> - </tr> - <tr> - <td>“R.U.”—Ratio of urea to excess of solids over water</td> - <td></td> - <td class="tdr">100·53</td> - <td></td> - </tr> - <tr> - <td>“R.U.A.”—Ratio of uric acid to excess of solids over water</td> - <td></td> - <td class="tdr">2·33</td> - <td></td> - </tr> - <tr> - <td>“R.H.A.”—Ratio of hippuric acid to excess of solids over water</td> - <td></td> - <td class="tdr"><span class="sp2">7·3</span></td> - <td></td> - </tr> - <tr> - <td>“R.P./R.A.”—Ratio of phosphoric acid to ratio of acidity - (Joulie’s factor, <i>cf.</i> Vol. I., p. 737)</td> - <td></td> - <td class="tdr">2·45</td> - <td></td> - </tr> - <tr> - <td>Ratio of uric acid, for example, is arrived at thus</td> - <td></td> - <td style="padding-left: 0.25em; text-indent: 0;"> - <table style="margin: 0;"> - <tr> - <td class="nw">0·416 × 100</td> - </tr> - <tr> - <td class="tdc bt">17·8</td> - </tr> - </table> - </td> - <td>= 2·33</td> - </tr> -</table> - -<p>The results which we obtained are given in the following table:—</p> - -<p class="center"><i>Effects of Guaiacum Resin on the Urine of a Normal Individual.</i></p> - -<table class="borders"> - <tr> - <th></th> - <th>Date.</th> - <th>Sp. Gr.</th> - <th>Urea.</th> - <th>Uric Acid.</th> - <th>Hippuric Acid.</th> - <th>“R.U.A.”</th> - <th>“R.H.A.”</th> - </tr> - <tr> - <td>With guaiacum</td> - <td>28/12/11</td> - <td class="tdr">1·0107</td> - <td class="tdr">2·29</td> - <td class="tdr"><span class="sp2">0·09</span></td> - <td class="tdr"><span class="sp2">0·09</span></td> - <td class="tdr">4·43</td> - <td class="tdr">4·34</td> - </tr> - <tr> - <td>With guaiacum</td> - <td>29/12/11</td> - <td class="tdr">1·0247</td> - <td class="tdr">1·29</td> - <td class="tdr"><span class="sp2">0·08</span></td> - <td class="tdr"><span class="sp4">0·1</span></td> - <td class="tdr">3·34</td> - <td class="tdr">4·04</td> - </tr> - <tr> - <td>With guaiacum</td> - <td>1/1/12</td> - <td class="tdr">1·0215</td> - <td class="tdr">2·56</td> - <td class="tdr">0·015</td> - <td class="tdr"><span class="sp2">0·15</span></td> - <td class="tdr">4·88</td> - <td class="tdr">6·97</td> - </tr> - <tr> - <td>With guaiacum</td> - <td>2/1/12</td> - <td class="tdr">1·0141</td> - <td class="tdr">2·82</td> - <td class="tdr"><span class="sp2">0·10</span></td> - <td class="tdr"><span class="sp4">0·2</span></td> - <td class="tdr"><span class="sp2">4·2</span></td> - <td class="tdr">8·20</td> - </tr> - <tr> - <td>Without guaiacum</td> - <td>4/1/12</td> - <td class="tdr">1·0229</td> - <td class="tdr">2·42</td> - <td class="tdr"><span class="sp2">0·06</span></td> - <td class="tdr"><span class="sp4">0·1</span></td> - <td class="tdr">2·62</td> - <td class="tdr">4·36</td> - </tr> - <tr> - <td>Without guaiacum</td> - <td>5/1/12</td> - <td class="tdr">1·0249</td> - <td class="tdr">2·42</td> - <td class="tdr"><span class="sp2">0·08</span></td> - <td class="tdr"><span class="sp4">0·2</span></td> - <td class="tdr">3·16</td> - <td class="tdr">8·03</td> - </tr> - <tr> - <td>Without guaiacum</td> - <td>8/1/12</td> - <td class="tdr">1·0255</td> - <td class="tdr">3·09</td> - <td class="tdr"><span class="sp2">0·10</span></td> - <td class="tdr">0·225</td> - <td class="tdr">4·11</td> - <td class="tdr">8·12</td> - </tr> - <tr> - <td>With guaiacum</td> - <td>11/1/12</td> - <td class="tdr">1·0233</td> - <td class="tdr">2·56</td> - <td class="tdr"><span class="sp2">0·09</span></td> - <td class="tdr"><span class="sp4">0·1</span></td> - <td class="tdr"><span class="sp2">3·7</span></td> - <td class="tdr">4·29</td> - </tr> - <tr> - <td>With guaiacum</td> - <td>12/1/12</td> - <td class="tdr">1·0213</td> - <td class="tdr">1·88</td> - <td class="tdr">0·075</td> - <td class="tdr"><span class="sp4">0·1</span></td> - <td class="tdr">3·05</td> - <td class="tdr">4·69</td> - </tr> - <tr> - <td>Without guaiacum</td> - <td>24/1/12</td> - <td class="tdr">1·0239</td> - <td class="tdr">2·42</td> - <td class="tdr"><span class="sp2">0·08</span></td> - <td class="tdr">0·038</td> - <td class="tdr">3·45</td> - <td class="tdr">1·57</td> - </tr> - <tr> - <td>Without guaiacum</td> - <td>25/1/12</td> - <td class="tdr">1·0229</td> - <td class="tdr">2·15</td> - <td class="tdr"><span class="sp2">0·06</span></td> - <td class="tdr"><span class="sp2">0·05</span></td> - <td class="tdr">2·61</td> - <td class="tdr">2·18</td> - </tr> -</table> - -<table> - <tr> - <td>Average uric acid ratio under guaiacum resin</td> - <td class="tdc">=</td> - <td class="tdr">3·39</td> - </tr> - <tr> - <td>Average uric acid ratio without guaiacum resin</td> - <td class="tdc">=</td> - <td class="tdr">3·19</td> - </tr> - <tr> - <td>Average hippuric acid ratio under guaiacum resin</td> - <td class="tdc">=</td> - <td class="tdr">5·43</td> - </tr> - <tr> - <td>Average hippuric acid ratio without guaiacum resin</td> - <td class="tdc">=</td> - <td class="tdr">4·49</td> - </tr> -</table> - -<p>The quantity of hippuric acid normally found is known to vary enormously, <i>e.g.</i>, -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.</p> - -<p>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.</p> - -</div> - -<div class="footnote"> - -<p><a id="Footnote_63" href="#FNanchor_63" class="label">[63]</a> “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.”—“<i>Climato-therapy and Balneo-therapy</i>,” <i>by Sir Hermann Weber</i>.</p> - -</div> - -<div class="footnote"> - -<p><a id="Footnote_64" href="#FNanchor_64" class="label">[64]</a></p> - -<p class="center"><span class="smcap">Sir William Ramsay’s Analysis of the Bath Waters.</span></p> - -<table> - <tr> - <td>Density of the water from King’s Well</td> - <td class="tdr">1·0166</td> - <td></td> - </tr> - <tr> - <td>Osmotic pressure equivalent to that of a salt solution containing per litre</td> - <td class="tdr"><span class="sp4">1·09</span></td> - <td class="nw">grams NaCl.</td> - </tr> -</table> - -<p>Volume of gas in twenty-four hours from—</p> - -<table> - <tr> - <th></th> - <th>Litres.</th> - <th></th> - </tr> - <tr> - <td>King’s Well</td> - <td class="tdr">4,927</td> - <td></td> - </tr> - <tr> - <td>Cross Spring</td> - <td class="tdr">218</td> - <td></td> - </tr> - <tr> - <td>Hetling Spring</td> - <td class="tdr">218</td> - <td>(estimated).</td> - </tr> - <tr> - <td></td> - <td class="tdr bt">5,363</td> - <td></td> - </tr> -</table> - -<p>Analysis of gas (King’s Well)—</p> - -<table> - <tr> - <th></th> - <th>Parts per<br>10,000.</th> - </tr> - <tr> - <td>Carbon dioxide</td> - <td class="tdr">360</td> - </tr> - <tr> - <td>Nitrogen, etc.</td> - <td class="tdr">9,640</td> - </tr> - <tr> - <td colspan="2">No oxygen, no hydrogen, no marsh gas.</td> - </tr> -</table> - -<p>The nitrogen contains—</p> - -<table> - <tr> - <td>Argon</td> - <td class="tdr">73·63</td> - </tr> - <tr> - <td>Neon</td> - <td class="tdr">23·34</td> - </tr> - <tr> - <td>Helium</td> - <td class="tdr">2·97</td> - </tr> -</table> - -<p>From all three wells in twenty-four hours—</p> - -<table> - <tr> - <th></th> - <th>Litres.</th> - </tr> - <tr> - <td>Argon</td> - <td class="tdr"><span class="sp3">39</span></td> - </tr> - <tr> - <td>Neon</td> - <td class="tdr">12½</td> - </tr> - <tr> - <td>Helium</td> - <td class="tdr">1½</td> - </tr> -</table> - -<p><i>Gases dissolved in Pump-room Water.</i>—This water contains 18·5 volumes of gas per 1,000 of water. Its composition is—</p> - -<table> - <tr> - <td>Carbon dioxide</td> - <td class="tdr">6·9</td> - </tr> - <tr> - <td>Nitrogen</td> - <td class="tdr">11·6</td> - </tr> -</table> - -<p>It had become somewhat aerated on drawing, but allowance has been made for -that.</p> - -<table> - <tr> - <th></th> - <th>Milligrams<br>per million<br>litres.</th> - </tr> - <tr> - <td>Radium in the water of the King’s Well</td> - <td class="tdr">0·1387</td> - </tr> - <tr> - <td>Niton (radium emanation) in the water of King’s Well</td> - <td class="tdr"><span class="sp4">1·73</span></td> - </tr> - <tr> - <td><span class="ditto">”</span> <span class="ditto">”</span> - <span class="ditto">”</span> <span class="ditto">”</span> of Cross Bath</td> - <td class="tdr"><span class="sp4">1·19</span></td> - </tr> - <tr> - <td><span class="ditto">”</span> <span class="ditto">”</span> - <span class="ditto">”</span> <span class="ditto">”</span> of Hetling Bath</td> - <td class="tdr"><span class="sp4">1·70</span></td> - </tr> - <tr> - <td><span class="ditto">”</span> <span class="ditto">”</span> - <span class="ditto">”</span> in the gas from King’s Well</td> - <td class="tdr"><span class="sp4">33·65</span></td> - </tr> -</table> - -</div> - -<div class="footnote"> - -<p><a id="Footnote_65" href="#FNanchor_65" class="label">[65]</a> 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.</p> - -</div> - -<div class="footnote"> - -<p><a id="Footnote_66" href="#FNanchor_66" class="label">[66]</a> 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.”</p> - -</div> - -</div> - -<hr class="chap x-ebookmaker-drop"> - -<div class="chapter"> - -<p><span class="pagenum"><a id="Page_457"></a>[457]</span></p> - -<h2 class="nobreak" id="INDEX">INDEX</h2> - -</div> - -<ul> - -<li class="ifrst"><b>A-amino-acids</b>, <a href="#Page_61">61</a></li> - -<li class="indx"><b>Aborigines</b>, gout unknown among, <a href="#Page_2">2</a></li> - -<li class="indx"><b>Abscess</b> formation in peri-tophal tissues, <a href="#Page_234">234</a></li> -<li class="isub1">skin resembling, in acute gout, <a href="#Page_212">212</a></li> - -<li class="indx">“<b>Accessory</b> food factors” in diet of gouty, <a href="#Page_339">339</a></li> - -<li class="indx"><b>Adenase</b>, <a href="#Page_100">100</a>, <a href="#Page_101">101</a></li> - -<li class="indx"><b>Adenine</b>, <a href="#Page_73">73</a>, <a href="#Page_75">75</a>, <a href="#Page_77">77</a>, <a href="#Page_98">98</a></li> - -<li class="indx"><b>Aetius’s</b> views on gout, <a href="#Page_6">6</a></li> - -<li class="indx"><b>Age</b> factor in gout, <a href="#Page_40">40</a></li> -<li class="isub1">influence of, on diet, in acute stage of gout, <a href="#Page_333">333</a></li> - -<li class="indx"><b>Agotan</b> in treatment of acute gout, <a href="#Page_379">379</a></li> - -<li class="indx"><b>Aix</b> massage baths, <a href="#Page_427">427</a></li> - -<li class="indx"><b>Alanine</b>, uric acid excretion augmented by, <a href="#Page_89">89</a></li> - -<li class="indx"><b>Albuminuria</b>, diet in, <a href="#Page_358">358</a></li> - -<li class="indx"><b>Alcohol</b> and gout, <a href="#Page_48">48</a></li> -<li class="isub1">hypersensitiveness of gouty to, <a href="#Page_365">365</a></li> -<li class="isub1">in febrile stage of sthenic gout, <a href="#Page_333">333</a></li> -<li class="isub1">in gout, <a href="#Page_361">361</a></li> -<li class="isub1">in subjects of gouty glycosuria, <a href="#Page_237">237</a></li> -<li class="isub1"><i>modus operandi</i> of, in induction of gout, <a href="#Page_49">49</a></li> -<li class="isub1"><i>plus</i> overeating, cause of gout, <a href="#Page_49">49</a></li> - -<li class="indx"><b>Alcoholism</b>, chronic, purin metabolism in, <a href="#Page_115">115</a></li> - -<li class="indx"><b>Alexander</b> of Tralles’s views on gout, <a href="#Page_5">5</a></li> - -<li class="indx"><b>Alimentary</b> canal, condition of, and gout, <a href="#Page_174">174</a></li> -<li class="isub1">disorders, effects of radio-active waters on, <a href="#Page_439">439</a></li> -<li class="isub1">tract, functional derangements of, in diagnosis of articular gout, <a href="#Page_249">249</a></li> -<li class="isub2">X-ray examination of, in treatment of gout, <a href="#Page_336">336</a></li> - -<li class="indx"><b>Alkalies</b> in inter-paroxysmal periods of gout, <a href="#Page_392">392</a></li> -<li class="isub1">in treatment of acute gout, <a href="#Page_383">383</a></li> -<li class="isub1">in treatment of chronic gout, <a href="#Page_399">399</a></li> - -<li class="indx"><b>Alkaline</b> waters, simple, spas for, <a href="#Page_441">441</a></li> - -<li class="indx"><b>Alkapton</b> in urine, <a href="#Page_59">59</a></li> - -<li class="indx"><b>Alkaptonuria</b>, <a href="#Page_69">69</a></li> - -<li class="indx"><b>Allantoin</b>, <a href="#Page_104">104</a></li> - -<li class="indx"><b>Alternatives</b> in treatment of chronic gout, <a href="#Page_401">401</a></li> - -<li class="indx"><b>Alveolus</b>, senile atrophy of, <a href="#Page_329">329</a></li> - -<li class="indx"><b>Amberg</b> and Jones’ scheme of formation of uric acid, <a href="#Page_104">104</a></li> - -<li class="indx"><b>America</b>, United States of, gout in, <a href="#Page_47">47</a></li> - -<li class="indx"><b>Amino-acetic-acid</b>, <a href="#Page_64">64</a></li> - -<li class="indx"><b>Amino-acids</b> and dicarboxylic amino-acids, <a href="#Page_89">89</a></li> -<li class="isub1">deaminisation of, <a href="#Page_62">62</a>, <a href="#Page_63">63</a></li> -<li class="isub1">fate of, <a href="#Page_62">62</a></li> -<li class="isub1">in portal blood, <a href="#Page_62">62</a></li> -<li class="isub1">in relation to gout, <a href="#Page_64">64</a></li> - -<li class="indx"><b>Amino-purins</b>, as source of uric acid, <a href="#Page_84">84</a></li> - -<li class="indx"><b>Amylaceous</b> dyspepsia, diet in, <a href="#Page_351">351</a>, <a href="#Page_352">352</a></li> - -<li class="indx"><b>Anacritical</b> stage of depression, <a href="#Page_211">211</a></li> - -<li class="indx"><b>Anæmia</b> in cases of long-standing gout, treatment of, <a href="#Page_406">406</a></li> -<li class="isub1">retention capacity of tissues for uric acid in, <a href="#Page_158">158</a></li> - -<li class="indx"><b>Anatomical</b> alterations in articulations, <a href="#Page_54">54</a></li> - -<li class="indx"><b>Anglo-Saxon</b> period, prevalence of gout in, <a href="#Page_2">2</a></li> - -<li class="indx"><b>Animal</b> cells, nucleic acid derived from, <a href="#Page_98">98</a></li> - -<li class="indx"><b>Animals</b>, various, uric acid blood content of, <a href="#Page_135">135</a></li> - -<li class="indx"><b>Ankylosis</b> in chronic gout, <a href="#Page_287">287</a></li> - -<li class="indx"><b>Anodyne</b> preparations in treatment of acute gout, <a href="#Page_384">384</a>, <a href="#Page_385">385</a></li> - -<li class="indx"><b>Anodynes</b> in acute gout, <a href="#Page_383">383</a></li> - -<li class="indx"><b>Antiquity</b> of gout, <a href="#Page_1">1</a></li> - -<li class="indx"><b>Anuria</b>, hysteria in, <a href="#Page_126">126</a></li> - -<li class="indx"><b>Aponeuroses</b>, gouty polyarthritis in, <a href="#Page_214">214</a></li> - -<li class="indx"><b>Appendicitis</b>, septic foci of, <a href="#Page_184">184</a></li> - -<li class="indx"><b>Appendix-dyspepsia</b>, <a href="#Page_184">184</a></li> - -<li class="indx"><b>Arab</b> physicians’ views on gout, <a href="#Page_6">6</a></li> - -<li class="indx"><b>Aretæus</b> the Cappadocian’s views on gout, <a href="#Page_4">4</a>, <a href="#Page_5">5</a></li> - -<li class="indx"><b>Arterio-sclerosis</b>, associated with gout, <a href="#Page_245">245</a></li> -<li class="isub1">blood-content in, <a href="#Page_127">127</a></li> -<li class="isub1">spa treatment of, <a href="#Page_451">451</a></li> - -<li class="indx"><b>Arthralgia</b>, fleeting, <a href="#Page_193">193</a></li> - -<li class="indx"><b>Arthritic</b> attacks, tophi formation preceding, <a href="#Page_164">164</a></li> -<li class="isub1">iritis, <a href="#Page_315">315</a></li> - -<li class="indx"><b>Arthritides</b>, specific infective, and gout, analogies between, <a href="#Page_194">194</a></li> - -<li class="indx"><b>Arthritis</b> deformans, cleavage into two types, <a href="#Page_18">18</a></li> -<li class="isub1">differentiation of, from chronic gout, <a href="#Page_16">16</a></li> -<li class="isub1">rheumatoid, and osteoarthritis, <a href="#Page_20">20</a></li> - -<li class="indx"><b>Arthritis</b>, gonococcal, acute, differential diagnosis from acute gouty polyarthritis, <a href="#Page_270">270</a></li> -<li class="isub3">from gout, <a href="#Page_259">259</a></li> -<li class="isub2">of tarsus and metatarsus, differential diagnosis from gout, <a href="#Page_263">263</a></li> -<li class="isub1">gouty, <a href="#Page_39">39</a></li> -<li class="isub2">definition of, <a href="#Page_20">20</a></li> -<li class="isub2">frequency of tophi in, <a href="#Page_255">255</a></li> -<li class="isub2">relation to local foci of infection, <a href="#Page_185">185</a></li> -<li class="isub1">Greek designation, <a href="#Page_3">3</a></li> -<li class="isub1">hæmophilia, differential diagnosis from chronic gout, <a href="#Page_285">285</a></li> -<li class="isub1">infective, of undifferentiated type, differential diagnosis from acute polyarticular gout, <a href="#Page_272">272</a></li> -<li class="isub2">skiagraphy in differential diagnosis of, <a href="#Page_290">290</a></li> -<li class="isub1"><span class="pagenum"><a id="Page_458"></a>[458]</span>non-gouty, hyper-uricæmia in, <a href="#Page_140">140</a></li> -<li class="isub1">rheumatoid, <a href="#Page_17">17</a></li> -<li class="isub2">differential diagnosis from chronic gout, <a href="#Page_284">284</a></li> -<li class="isub2">local character of joint swellings, <a href="#Page_284">284</a></li> -<li class="isub2">or atrophic, acute, differential diagnosis from acute gouty polyarthritis, <a href="#Page_272">272</a></li> -<li class="isub2">skiagraphy in differential diagnosis of, <a href="#Page_291">291</a></li> -<li class="isub1">syphilitic, differential diagnosis from chronic articular gout, <a href="#Page_277">277</a></li> -<li class="isub2">secondary, differential diagnosis from acute gouty polyarthritis, <a href="#Page_271">271</a></li> -<li class="isub1">tophi in relation to, <a href="#Page_254">254</a></li> - -<li class="indx"><b>Arthropathies</b>, nerve, differential diagnosis from chronic gout, <a href="#Page_284">284</a></li> - -<li class="indx"><b>Articular</b> gout, chronic, medicinal and other modes of therapy, <a href="#Page_397">397</a></li> -<li class="isub1">etiological diagnosis, <a href="#Page_247">247</a></li> - -<li class="indx"><b>Articular</b> lesions in chronic gout, distribution of, <a href="#Page_226">226</a></li> - -<li class="indx"><b>Asphyxias</b>, local, of hands, in gout, <a href="#Page_45">45</a></li> - -<li class="indx"><b>Atophan</b>, effect of, on exogenous purins, <a href="#Page_110">110</a></li> -<li class="isub2">on uric acid excretion, <a href="#Page_119">119</a></li> -<li class="isub1">indicated when gout attack imminent, <a href="#Page_395">395</a></li> -<li class="isub1">in treatment of acute gout, <a href="#Page_379">379</a></li> -<li class="isub1">in treatment of chronic gout, <a href="#Page_403">403</a></li> - -<li class="indx"><b>Auricular</b> tophi, <a href="#Page_202">202</a></li> - -<li class="indx"><b>Auto-intoxication</b> theory of gout, <a href="#Page_182">182</a></li> - -<li class="indx"><b>Auto-toxæmia</b> theory of gout, <a href="#Page_182">182</a></li> - -<li class="indx"><b>Avicenna’s</b> views on gout, <a href="#Page_6">6</a></li> - -<li class="ifrst"><b>Bacillus coli communis</b> as causative agent in gout, <a href="#Page_175">175</a></li> - -<li class="indx"><b>Bacterial</b> flora, intestinal, modifications in, <a href="#Page_182">182</a></li> - -<li class="indx"><b>Bacteriological</b> examination in diagnosis of articular gout, <a href="#Page_251">251</a></li> - -<li class="indx"><b>Baillon’s</b> dissociation of rheumatism from gout, <a href="#Page_15">15</a></li> - -<li class="indx"><b>Banting</b> method in reduction of obesity, <a href="#Page_357">357</a></li> - -<li class="indx"><b>Barclay’s</b> theories of ætiology of gout, <a href="#Page_23">23</a></li> - -<li class="indx"><b>Bath</b> as residence for gouty, <a href="#Page_419">419</a></li> - -<li class="indx"><b>Bath</b> waters, Sir W. Ramsay’s analysis of, <a href="#Page_435">435</a></li> - -<li class="indx"><b>Baths</b> in treatment of gout, method of application, <a href="#Page_427">427</a></li> - -<li class="indx"><b>Beaumont, W. M.</b>, ocular disease in the gouty, <a href="#Page_308">308</a></li> - -<li class="indx"><b>Beauvais’s</b> work on gout, <a href="#Page_17">17</a></li> - -<li class="indx"><b>Beer</b> as beverage in gout, <a href="#Page_362">362</a></li> - -<li class="indx"><b>Benzoates</b> in treatment of chronic gout, <a href="#Page_401">401</a></li> - -<li class="indx"><b>Berkart’s</b> theory of ætiology of gout, <a href="#Page_27">27</a></li> -<li class="isub1">views on gout, <a href="#Page_56">56</a></li> - -<li class="indx"><b>Beverages</b> in gout, <a href="#Page_359">359</a></li> - -<li class="indx"><b>Bismuth</b> carbonate in inter-paroxysmal periods of gout, <a href="#Page_392">392</a></li> - -<li class="indx"><b>Biurate</b> of soda in gouty tophi, <a href="#Page_151">151</a></li> - -<li class="indx"><b>Blisters</b> in treatment of acute gout, <a href="#Page_386">386</a></li> - -<li class="indx"><b>Blood</b>, changes in, in acute gout, <a href="#Page_210">210</a></li> -<li class="isub2">in chronic articular gout, <a href="#Page_226">226</a></li> -<li class="isub2">in gouty polyarthritis, <a href="#Page_216">216</a></li> -<li class="isub1">content in gout, <a href="#Page_189">189</a></li> -<li class="isub1">count in acute gout, <a href="#Page_211">211</a></li> - -<li class="indx"><b>Blood</b>, examination of, in diagnosis of articular gout, <a href="#Page_251">251</a></li> - -<li class="indx"><b>Blood</b>, human, relationship between amounts of uric acid, urea and non-protein nitrogen in, <a href="#Page_122">122</a></li> -<li class="isub1">in chronic interstitial nephritis, urates in, <a href="#Page_120">120</a></li> -<li class="isub1">in disease, uric acid of, <a href="#Page_137">137</a></li> -<li class="isub1">portal, amino-acids in, <a href="#Page_62">62</a></li> -<li class="isub1">routine examination of, in diagnosis of articular gout, <a href="#Page_249">249</a></li> -<li class="isub1">uric acid as normal constituent of, <a href="#Page_135">135</a></li> -<li class="isub1">uric acid content of, and gout, relation between, <a href="#Page_143">143</a></li> -<li class="isub2">effect of diet upon, <a href="#Page_141">141</a></li> -<li class="isub2">effect of exogenous purins on, <a href="#Page_137">137</a></li> -<li class="isub2">estimation of sources of fallacy, <a href="#Page_145">145</a></li> -<li class="isub2">in gout, <a href="#Page_133">133</a>, <a href="#Page_139">139</a></li> -<li class="isub1">uric acid in, <a href="#Page_24">24</a>, <a href="#Page_34">34</a>, <a href="#Page_78">78</a></li> -<li class="isub2">discovery of, <a href="#Page_21">21</a></li> -<li class="isub2">Folin and Denis’s method of determination, <a href="#Page_133">133</a></li> -<li class="isub2">forms of, <a href="#Page_145">145</a></li> -<li class="isub2">Gudzent and Schade’s theories, <a href="#Page_79">79</a></li> -<li class="isub2">non-protein nitrogen and urea nitrogen in (table), <a href="#Page_136">136</a></li> -<li class="isub1">variations in uric acid content independently of diet, <a href="#Page_142">142</a></li> - -<li class="indx"><b>Bodily</b> conformation, and gout, <a href="#Page_44">44</a></li> - -<li class="indx"><b>Boils</b>, gout following, <a href="#Page_53">53</a>, <a href="#Page_178">178</a></li> - -<li class="indx"><b>Bone</b>, conditions of, revealed by skiagraphy, in diagnosis of gout, <a href="#Page_286">286</a></li> - -<li class="indx"><b>Bones</b>, changes in, in gout, <a href="#Page_53">53</a></li> -<li class="isub1">focal areas of rarefaction in, revealed by skiagraphy, <a href="#Page_286">286</a>, <a href="#Page_287">287</a></li> - -<li class="indx"><b>Brandy</b> in gout, <a href="#Page_371">371</a></li> - -<li class="indx"><b>Bruce’s</b> modes, <a href="#Page_286">286</a></li> - -<li class="indx"><b>Bunion</b>, inflamed, differential diagnosis from gout, <a href="#Page_261">261</a></li> - -<li class="indx"><b>Burian</b> and Schur’s researches on sources of uric acid, <a href="#Page_83">83</a></li> - -<li class="indx"><b>Bursæ</b>, involved in gout, <a href="#Page_195">195</a></li> -<li class="isub1">tophi in, <a href="#Page_233">233</a></li> - -<li class="indx"><b>Bursitis</b>, olecranon, gouty, <a href="#Page_215">215</a></li> -<li class="isub1">post-calcaneal, in referred pain in heel, <a href="#Page_265">265</a></li> - -<li class="ifrst"><b>Cælius Aurelianus’s</b> views on gout, <a href="#Page_5">5</a></li> - -<li class="indx"><b>Caffeine</b>, <a href="#Page_85">85</a></li> - -<li class="indx"><b>Calcium</b> carbonate in inter-paroxysmal periods of gout, <a href="#Page_392">392</a></li> -<li class="isub1">salts in gouty tophi, <a href="#Page_151">151</a></li> - -<li class="indx"><b>Calculus</b>, urinary, <a href="#Page_29">29</a></li> - -<li class="indx"><b>Carbohydrates</b> in diet of gouty, <a href="#Page_347">347</a></li> - -<li class="indx"><b>Carbuncles</b>, gout following, <a href="#Page_53">53</a>, <a href="#Page_178">178</a></li> - -<li class="indx"><b>Cartilage</b>, morbid changes in, <a href="#Page_53">53</a></li> -<li class="isub1">uratic deposits in, <a href="#Page_52">52</a>, <a href="#Page_153">153</a></li> -<li class="isub2">in nephritis, <a href="#Page_128">128</a></li> - -<li class="indx"><b>Cataphoresis</b> in treatment of chronic articular gout, <a href="#Page_407">407</a></li> - -<li class="indx"><b>Cell</b> protoplasm, chemistry of, <a href="#Page_176">176</a></li> - -<li class="indx"><b>Celsus’s</b> views on gout, <a href="#Page_4">4</a></li> - -<li class="indx">“<b>Chalk-stones</b>,” <a href="#Page_150">150</a></li> - -<li class="indx"><b>Chalybeate</b> waters, spas for, <a href="#Page_442">442</a></li> - -<li class="indx"><b>Champagne</b> in gout, <a href="#Page_368">368</a></li> - -<li class="indx"><b>Charcot’s</b> discovery of nerve arthropathies, <a href="#Page_18">18</a></li> -<li class="isub1"><span class="pagenum"><a id="Page_459"></a>[459]</span>joint, differential diagnosis from chronic articular gout, <a href="#Page_277">277</a></li> - -<li class="indx"><b>Chemistry</b> of uric acid and purin bodies, <a href="#Page_75">75</a></li> - -<li class="indx"><b>Chilblains</b> confused with early stages of tophi formation, <a href="#Page_164">164</a></li> - -<li class="indx"><b>Chirargra</b>, Greek designation, <a href="#Page_3">3</a></li> - -<li class="indx"><b>Cholecystitis</b>, <a href="#Page_184">184</a></li> - -<li class="indx"><b>Cider</b> as beverage in gout, <a href="#Page_363">363</a></li> - -<li class="indx"><b>Claret</b> in gout, <a href="#Page_369">369</a></li> - -<li class="indx"><b>Climate</b> and gout, <a href="#Page_45">45</a></li> -<li class="isub1">and residence in treatment of gout, <a href="#Page_418">418</a></li> - -<li class="indx"><b>Climato-therapy</b> in gout, <a href="#Page_418">418</a></li> - -<li class="indx"><b>Clothing</b>, importance of, <a href="#Page_421">421</a></li> - -<li class="indx"><b>Cocoa</b> as beverage in gout, <a href="#Page_361">361</a></li> - -<li class="indx"><b>Coffee</b> as beverage in gout, <a href="#Page_361">361</a></li> - -<li class="indx"><b>Colchicine</b> in treatment of acute gout, <a href="#Page_378">378</a></li> - -<li class="indx"><b>Colchicum</b> in acute gout, <a href="#Page_192">192</a>, <a href="#Page_374">374</a>, <a href="#Page_375">375</a>, <a href="#Page_378">378</a></li> -<li class="isub2">contra-indicated, alkalies as substitute, <a href="#Page_383">383</a></li> -<li class="isub2">method of administration, <a href="#Page_376">376</a></li> -<li class="isub1">preparations and dosage of, <a href="#Page_376">376</a></li> -<li class="isub1">used by Aetius, <a href="#Page_6">6</a></li> - -<li class="indx"><b>Colitis</b>, mucous, initial manifestations of gout, <a href="#Page_175">175</a></li> - -<li class="indx"><b>Colloids</b> in gouty tophi, <a href="#Page_152">152</a></li> - -<li class="indx"><b>Collosol</b> iodine in treatment of chronic gout, <a href="#Page_402">402</a></li> - -<li class="indx"><b>Colorimetric</b> method of determining uric acid in blood, <a href="#Page_133">133</a></li> - -<li class="indx"><b>Colour</b> reaction test in blood analysis, <a href="#Page_133">133</a></li> - -<li class="indx"><b>Condiments</b> in diet of gouty, <a href="#Page_350">350</a></li> - -<li class="indx"><b>Constipation</b>, effect in gout, <a href="#Page_337">337</a></li> -<li class="isub1">in acute gout, treatment of, <a href="#Page_373">373</a></li> -<li class="isub1">in chronic gout, treatment of, <a href="#Page_400">400</a></li> -<li class="isub1">in inter-paroxysmal periods of gout, treatment of, <a href="#Page_393">393</a></li> - -<li class="indx"><b>Constitutional</b> disturbance in gout, <a href="#Page_188">188</a></li> -<li class="isub1">influences in formation of tophi, <a href="#Page_161">161</a></li> - -<li class="indx"><b>Corpora</b> cavernosa of penis, tophi in, <a href="#Page_235">235</a></li> - -<li class="indx"><b>Cramps</b> in acute gout, <a href="#Page_210">210</a></li> - -<li class="indx"><b>Cream</b>, effect of, on uric acid output, <a href="#Page_348">348</a></li> - -<li class="indx"><b>Creatine</b>, <a href="#Page_63">63</a>, <a href="#Page_67">67</a></li> -<li class="isub1">in urine of children, <a href="#Page_68">68</a></li> - -<li class="indx"><b>Creatinine</b>, <a href="#Page_61">61</a>, <a href="#Page_63">63</a>, <a href="#Page_67">67</a>, <a href="#Page_68">68</a></li> -<li class="isub1">in blood in gout and nephritis (table), <a href="#Page_121">121</a></li> - -<li class="indx"><b>Crystalline</b> deposits in synovial fluid, <a href="#Page_54">54</a></li> - -<li class="indx"><b>Crystalloids</b> in gouty tophi, <a href="#Page_152">152</a></li> - -<li class="indx"><b>Cytosine</b>, <a href="#Page_98">98</a></li> - -<li class="indx"><b>Cullen’s</b> differentiation of varieties of rheumatism, <a href="#Page_16">16</a></li> -<li class="isub1">theory of ætiology of gout, <a href="#Page_21">21</a></li> - -<li class="indx"><b>Cutaneous</b> disorders in gout, <a href="#Page_240">240</a></li> -<li class="isub1">gravel, <a href="#Page_203">203</a></li> - -<li class="indx"><b>Cuticule</b>, desquamation of, typical of gout, <a href="#Page_191">191</a></li> - -<li class="indx"><b>Cystin</b> in urine, <a href="#Page_59">59</a></li> - -<li class="indx"><b>Cystinuria</b>, <a href="#Page_69">69</a></li> - -<li class="indx"><b>Cystoid</b> degeneration in gout, <a href="#Page_56">56</a></li> - -<li class="ifrst"><b>Deaminisation</b> of amino-acids, <a href="#Page_62">62</a>, <a href="#Page_63">63</a></li> - -<li class="indx"><b>Deficiency</b> diseases and accessory food factors, <a href="#Page_340">340</a></li> - -<li class="indx"><b>Degeneration</b>, theories of, <a href="#Page_25">25</a>, <a href="#Page_27">27</a></li> - -<li class="indx"><b>Desquamation</b> in acute gout, <a href="#Page_212">212</a></li> - -<li class="indx"><b>Diabetes</b>, glycosuria and, <a href="#Page_60">60</a></li> - -<li class="indx"><b>Dicarboxylic</b> amino-acids, <a href="#Page_89">89</a></li> - -<li class="indx"><b>Diet</b>, effect of, on blood content of uric acid, <a href="#Page_141">141</a></li> - -<li class="indx"><b>Diet</b> on excretion of uric acid, <a href="#Page_83">83</a></li> - -<li class="indx"><b>Diet</b> in acute paroxysms of gout, <a href="#Page_332">332</a></li> -<li class="isub1">in albuminuria, <a href="#Page_358">358</a></li> -<li class="isub1">in amylaceous dyspepsia, <a href="#Page_351">351</a>, <a href="#Page_352">352</a></li> -<li class="isub1">in chronic gout, <a href="#Page_334">334</a></li> -<li class="isub1">in glycosuria, <a href="#Page_357">357</a></li> -<li class="isub1">in hyperchlorhydria, <a href="#Page_353">353</a></li> -<li class="isub1">in hyperuricæmia, <a href="#Page_354">354</a></li> -<li class="isub1">in hypochlorhydria, <a href="#Page_354">354</a></li> -<li class="isub1">in inter-paroxysmal periods of gout, <a href="#Page_391">391</a></li> -<li class="isub1">in reduction of obesity, <a href="#Page_357">357</a></li> -<li class="isub1">in treatment of gout, <a href="#Page_332">332</a></li> -<li class="isub2">“accessory food factors,” <a href="#Page_339">339</a></li> -<li class="isub2">carbohydrates, <a href="#Page_347">347</a></li> -<li class="isub2">collaboration of clinician and bio-chemist, need for, <a href="#Page_337">337</a></li> -<li class="isub2">condiments, <a href="#Page_350">350</a></li> -<li class="isub2">fats, <a href="#Page_347">347</a></li> -<li class="isub2">fish, <a href="#Page_346">346</a></li> -<li class="isub2">fruits, <a href="#Page_349">349</a></li> -<li class="isub2">idiosyncrasies of, <a href="#Page_343">343</a></li> -<li class="isub2">physical examination necessary before, <a href="#Page_336">336</a></li> -<li class="isub2">proteins, <a href="#Page_345">345</a></li> -<li class="isub2">regulations of, <a href="#Page_342">342</a></li> -<li class="isub2">vegetables, <a href="#Page_348">348</a></li> -<li class="isub1">variations of blood content of uric acid independently of, <a href="#Page_142">142</a></li> - -<li class="indx"><b>Dietaries</b>, fixed, fallacy of, in treatment of gout, <a href="#Page_335">335</a></li> - -<li class="indx"><b>Digestion</b>, disturbances of, prevention of, in treatment of gout, <a href="#Page_335">335</a></li> - -<li class="indx"><b>Digestive</b> glands, <i>rôle</i> of, in uric acid excretion, <a href="#Page_88">88</a></li> - -<li class="indx"><b>Diocletian</b>, edict by, <i>re</i> gout, <a href="#Page_5">5</a></li> - -<li class="indx"><b>Dislocations</b>, signalising attack of gout, <a href="#Page_53">53</a></li> - -<li class="indx"><b>Douches</b>, <a href="#Page_428">428</a></li> - -<li class="indx"><b>Dover’s</b> powder, with aspirin and phenacetin, in treatment of acute gout, <a href="#Page_383">383</a></li> - -<li class="indx"><b>Drink</b> and gout, <a href="#Page_48">48</a></li> - -<li class="indx">“<b>Drug</b> dyspepsia,” <a href="#Page_391">391</a></li> - -<li class="indx"><b>Drugs</b> influencing excretion of endogenous uric acid, <a href="#Page_96">96</a></li> - -<li class="indx"><b>Duckworth’s</b> classification of arthritic type of gout, <a href="#Page_36">36</a></li> -<li class="isub1">theory of ætiology of gout, <a href="#Page_33">33</a></li> - -<li class="indx"><b>Dyschezia</b> and gout, <a href="#Page_337">337</a></li> - -<li class="indx"><b>Dysenteric</b> arthritis, differential diagnosis from acute gouty polyarthritis, <a href="#Page_272">272</a></li> - -<li class="indx"><b>Dysentery</b>, complicated by arthritis and myalgias, <a href="#Page_194">194</a></li> - -<li class="indx"><b>Dyspepsia</b>, amylaceous, diet in, <a href="#Page_351">351</a>, <a href="#Page_352">352</a></li> -<li class="isub1">atonic, muriated waters in treatment of, <a href="#Page_444">444</a></li> -<li class="isub1">chronic, gout associated with, <a href="#Page_178">178</a></li> -<li class="isub1">“drug,” <a href="#Page_391">391</a></li> -<li class="isub1">gouty, no specific form of, <a href="#Page_350">350</a></li> -<li class="isub1">intestinal, preceding gout, <a href="#Page_182">182</a></li> -<li class="isub1">mineral waters in treatment of, <a href="#Page_443">443</a></li> -<li class="isub1">spas in treatment of, <a href="#Page_442">442</a></li> - -<li class="indx"><b>Dyspeptic</b> symptoms of acute localised gout, <a href="#Page_201">201</a></li> - -<li class="ifrst"><b>Ear</b>, pricking or tenderness in, <a href="#Page_203">203</a></li> -<li class="isub1">tophus in, <a href="#Page_202">202</a></li> - -<li class="indx"><b>Ears</b>, tophi in, antedating articular outbreaks, <a href="#Page_203">203</a></li> - -<li class="indx"><span class="pagenum"><a id="Page_460"></a>[460]</span><b>Ebstein</b> and Sprague’s analysis of tophi, <a href="#Page_150">150</a></li> - -<li class="indx"><b>Ebstein’s</b> theory of ætiology of gout, <a href="#Page_25">25</a></li> - -<li class="indx"><b>Ecchymoses</b>, local, in acute gout, <a href="#Page_212">212</a></li> - -<li class="indx"><b>Eczema</b>, gouty, spa treatment of, <a href="#Page_451">451</a></li> -<li class="isub2">treatment of, <a href="#Page_416">416</a></li> -<li class="isub1">in gout, <a href="#Page_241">241</a></li> - -<li class="indx"><b>Egypt</b>, osteoarthritis in, in ancient times, <a href="#Page_1">1</a></li> - -<li class="indx"><b>Endemic</b> areas of gout, <a href="#Page_46">46</a></li> - -<li class="indx"><b>Endogenous</b> purins, <a href="#Page_87">87</a></li> -<li class="isub1">origin of, <a href="#Page_83">83</a></li> -<li class="isub1">source of, <a href="#Page_88">88</a></li> -<li class="isub1">uric acid excretion, <a href="#Page_91">91</a></li> -<li class="isub2">factors influencing, <a href="#Page_93">93</a></li> -<li class="isub2">increased by purin-free proteid food, <a href="#Page_89">89</a></li> -<li class="isub2">pathological states influencing, <a href="#Page_94">94</a></li> -<li class="isub2">periodic variations of, <a href="#Page_94">94</a></li> -<li class="isub2">physiological conditions, <a href="#Page_93">93</a></li> - -<li class="indx"><b>Environment</b> in gout, <a href="#Page_40">40</a></li> - -<li class="indx"><b>Enzymes</b>, distribution of, <a href="#Page_99">99</a></li> -<li class="isub1">in intestinal juices and wall, <a href="#Page_100">100</a></li> - -<li class="indx"><b>Epistaxis</b>, gout following, <a href="#Page_178">178</a></li> - -<li class="indx"><b>Epithelial</b> cells, nucleus in gouty tophi, <a href="#Page_151">151</a></li> - -<li class="indx"><b>Erysipelas</b>, gouty arthritis simulating, <a href="#Page_215">215</a></li> - -<li class="indx"><b>Erythromelalgia</b>, differential diagnosis from gout, <a href="#Page_266">266</a></li> - -<li class="indx"><b>Etiological</b> diagnosis of articular gout, <a href="#Page_247">247</a></li> - -<li class="indx"><b>Exercise</b> in gout, importance of, <a href="#Page_421">421</a></li> -<li class="isub1">relation of, to gout, <a href="#Page_337">337</a></li> - -<li class="indx"><b>Exogenous</b> origin of purins, <a href="#Page_83">83</a></li> -<li class="isub1">purins as source of uric acid, <a href="#Page_84">84</a></li> -<li class="isub1">uric acid excretion, <a href="#Page_85">85</a></li> - -<li class="indx"><b>Exudative</b> diathesis, <a href="#Page_116">116</a></li> - -<li class="indx"><b>Eye</b>, deposition of urates in, <a href="#Page_309">309</a></li> -<li class="isub1">gout in, evidence of, <a href="#Page_309">309</a></li> -<li class="isub1">gouty diathesis in regard to, <a href="#Page_310">310</a></li> - -<li class="indx"><b>Eyelids</b>, uratic deposits in, <a href="#Page_235">235</a></li> - -<li class="ifrst"><b>Fæces</b>, examination of, in diagnosis of articular gout, <a href="#Page_250">250</a></li> -<li class="isub1">in treatment of gout, <a href="#Page_337">337</a></li> - -<li class="indx"><b>Fasciæ</b>, involved in gout, <a href="#Page_195">195</a></li> - -<li class="indx">“<b>Fat</b> soluble A,” <a href="#Page_340">340</a></li> - -<li class="indx"><b>Fats</b> in diet of gouty, <a href="#Page_347">347</a></li> - -<li class="indx"><b>Feet</b>, incidence of tophi in, <a href="#Page_162">162</a></li> -<li class="isub1">plantar surface of, tophi in, <a href="#Page_235">235</a></li> - -<li class="indx"><b>Fibrosis</b>, interstitial, chronic, <a href="#Page_186">186</a></li> -<li class="isub1">of visceral organs in gout, tendency to, <a href="#Page_186">186</a></li> - -<li class="indx"><b>Fibrositis</b> associated with acute articular gout, <a href="#Page_195">195</a></li> -<li class="isub1">associated with gout, treatment of, <a href="#Page_411">411</a></li> -<li class="isub1">gouty, acute brachial, treatment of, <a href="#Page_412">412</a></li> -<li class="isub1">incidence of gouty stigmata in types of, <a href="#Page_221">221</a>, <a href="#Page_222">222</a></li> -<li class="isub1">muscular, in gouty, massage in, <a href="#Page_423">423</a></li> -<li class="isub1">spa treatment of, <a href="#Page_450">450</a></li> - -<li class="indx"><b>Fingers</b>, deformed, in chronic gout, <a href="#Page_230">230</a></li> -<li class="isub1">pulps of, tophi in, <a href="#Page_235">235</a></li> - -<li class="indx"><b>Fischer’s</b> researches on protein molecule, <a href="#Page_61">61</a></li> - -<li class="indx"><b>Fish</b> in diet of gouty, <a href="#Page_346">346</a></li> - -<li class="indx"><b>Flatfoot</b>, pains in, differential diagnosis from gout, <a href="#Page_263">263</a></li> - -<li class="indx">“<b>Flying</b> gout,” <a href="#Page_193">193</a></li> - -<li class="indx"><b>Foci</b> of infection in gouty, <a href="#Page_53">53</a></li> -<li class="isub1">local, in gout, <a href="#Page_177">177</a></li> - -<li class="indx"><b>Foci</b>, relation to gouty synovitis and arthritis, <a href="#Page_185">185</a></li> - -<li class="indx"><b>Folin</b> and Denis’s method of determination of uric acid in blood, <a href="#Page_133">133</a></li> -<li class="isub1">researches into urea formation, <a href="#Page_63">63</a></li> - -<li class="indx"><b>Food</b>, cooking of, in diet of gouty, <a href="#Page_344">344</a></li> -<li class="isub1">influence on gout, <a href="#Page_48">48</a></li> - -<li class="indx"><b>Foods</b>, various, exogenous urinary purin in, amount of, <a href="#Page_85">85</a></li> - -<li class="indx"><b>Foot</b> deformities, static, differential diagnosis from gout, <a href="#Page_261">261</a></li> - -<li class="indx">“<b>Fot-adl</b>,” Anglo-Saxon name for gout, <a href="#Page_3">3</a></li> - -<li class="indx"><b>Fractures</b>, signalising attack of gout, <a href="#Page_53">53</a></li> - -<li class="indx"><b>Fruits</b> in diet of gouty, <a href="#Page_349">349</a></li> - -<li class="indx"><b>Function</b>, gout a disorder of, <a href="#Page_200">200</a></li> - -<li class="indx"><b>Functional</b> disturbances in gout, <a href="#Page_201">201</a></li> - -<li class="ifrst"><b>Galen’s</b> views on gout, <a href="#Page_2">2</a>, <a href="#Page_4">4</a></li> - -<li class="indx"><b>Gall-stones</b>, gout associated with, <a href="#Page_184">184</a></li> - -<li class="indx"><b>Gall-bladder dyspepsia</b>, <a href="#Page_184">184</a></li> - -<li class="indx"><b>Garrod’s</b> discovery of uric acid in blood of gouty persons, <a href="#Page_21">21</a></li> -<li class="isub1">pathogeny of gout, growing scepticism as to, <a href="#Page_32">32</a></li> -<li class="isub1">theory of ætiology of gout, <a href="#Page_22">22</a></li> -<li class="isub1">views on gout in the eye, <a href="#Page_320">320</a></li> - -<li class="indx"><b>Gastralgias</b> in gouty, <a href="#Page_351">351</a></li> - -<li class="indx"><b>Gastric</b> catarrh, chronic, gout associated with, <a href="#Page_351">351</a></li> -<li class="isub2">chronic, mineral waters suitable for, <a href="#Page_445">445</a></li> -<li class="isub1">glands, diseased conditions of, and gout, <a href="#Page_173">173</a></li> -<li class="isub1">insufficiency, muriated waters in treatment of, <a href="#Page_444">444</a></li> - -<li class="indx"><b>Gastro-intestinal</b> asepsis, importance of, in gout, <a href="#Page_332">332</a></li> -<li class="isub1">derangements in acute paroxysms of gout, <a href="#Page_333">333</a></li> -<li class="isub1">disorders and gout, <a href="#Page_180">180</a></li> -<li class="isub2">attributed to gout, <a href="#Page_299">299-302</a></li> -<li class="isub2">chronic, spas in treatment of, <a href="#Page_442">442</a></li> -<li class="isub2">mineral waters in treatment of, <a href="#Page_443">443</a></li> -<li class="isub1">tract, derangement of, cause of gout, <a href="#Page_170">170</a></li> - -<li class="indx"><b>Genito-urinary</b> passages, infection of, examination for, in diagnosis of articular gout, <a href="#Page_249">249</a></li> -<li class="isub1">tract, examination of, in treatment of gout, <a href="#Page_331">331</a></li> - -<li class="indx"><b>Geographical</b> distribution of gout, <a href="#Page_45">45-48</a></li> - -<li class="indx"><b>Gin</b> in gout, <a href="#Page_371">371</a></li> - -<li class="indx"><b>Glandular</b> affections in gouty subjects, <a href="#Page_179">179</a></li> - -<li class="indx"><b>Glaucoma</b>, gout and, <a href="#Page_324">324</a></li> - -<li class="indx"><b>Glycocine</b> and urea, interaction between, <a href="#Page_84">84</a></li> - -<li class="indx"><b>Glycocoll</b>, <i>rôle</i> of, <a href="#Page_64">64</a></li> -<li class="isub1">theory of gout, <a href="#Page_65">65</a></li> -<li class="isub1">uric acid excretion augmented by, <a href="#Page_89">89</a></li> - -<li class="indx"><b>Glycosuria</b> and diabetes, <a href="#Page_60">60</a></li> -<li class="isub1">associated with gout, treatment of, <a href="#Page_414">414</a></li> -<li class="isub1">diet in, <a href="#Page_357">357</a></li> -<li class="isub1">examination for, in treatment of gout, <a href="#Page_337">337</a></li> -<li class="isub1">gout and, co-existence of, <a href="#Page_185">185</a></li> -<li class="isub1">gout in relation to, <a href="#Page_236">236</a></li> -<li class="isub1">“gouty,” <a href="#Page_182">182</a></li> -<li class="isub1"><span class="pagenum"><a id="Page_461"></a>[461]</span>spa treatment of, <a href="#Page_449">449</a></li> - -<li class="indx"><b>Glyoxylic</b> acid in gouty urine, <a href="#Page_65">65</a></li> - -<li class="indx"><b>Gonococcal</b> arthritis of tarsus and metatarsus, differential diagnosis from gout, <a href="#Page_263">263</a></li> -<li class="isub1">infection, articular involvement, with muscular and nervous lesions, <a href="#Page_194">194</a></li> -<li class="isub2">differential diagnosis from gout, <a href="#Page_259">259</a></li> -<li class="isub2">exclusion of, in diagnosis of articular gout, <a href="#Page_248">248</a></li> - -<li class="indx"><b>Gore</b>, Ringrose, theory of pathology of gout, <a href="#Page_173">173</a></li> - -<li class="indx"><b>Gout</b>, acute, colchicum in, <a href="#Page_375">375</a></li> -<li class="isub2">definitely paroxysmal, <a href="#Page_191">191</a></li> -<li class="isub2">general phenomena of, <a href="#Page_210">210</a></li> -<li class="isub2">ionisation in treatment of, <a href="#Page_387">387</a></li> -<li class="isub2">local phenomena, <a href="#Page_211">211</a></li> -<li class="isub2">localised, clinical account, <a href="#Page_200">200</a></li> -<li class="isub3">dyspeptic symptoms of, <a href="#Page_201">201</a></li> -<li class="isub3">premonitory articular pains, <a href="#Page_204">204</a></li> -<li class="isub3">prodromal symptoms, <a href="#Page_200">200</a></li> -<li class="isub2">locality of, <a href="#Page_208">208</a></li> -<li class="isub2">medicinal treatment of, <a href="#Page_372">372</a></li> -<li class="isub2">onset of, <a href="#Page_207">207</a></li> -<li class="isub2">pain in, <a href="#Page_208">208</a></li> -<li class="isub2">paroxysm of, analysis of, <a href="#Page_188">188</a></li> -<li class="isub3">diet in, <a href="#Page_332">332</a></li> -<li class="isub3">symptoms of, <a href="#Page_205">205</a></li> -<li class="isub3">uric acid variations in, <a href="#Page_117">117</a></li> -<li class="isub2">surgical methods considered, <a href="#Page_388">388</a></li> -<li class="isub2">treatment of, alternative remedies in, <a href="#Page_381">381</a></li> -<li class="isub3">local measures, <a href="#Page_384">384</a></li> -<li class="isub2">uric acid excretion in, <a href="#Page_117">117</a>, <a href="#Page_211">211</a></li> -<li class="isub2">uric acid variations in, <a href="#Page_108">108</a>, <a href="#Page_117">117</a></li> -<li class="isub1">ætiology of, histogenous theories of, <a href="#Page_23">23</a></li> -<li class="isub2">nervous theories, <a href="#Page_31">31</a></li> -<li class="isub2">summary of, <a href="#Page_44">44</a></li> -<li class="isub2">theory of antecedent structural changes, <a href="#Page_25">25</a></li> -<li class="isub1">age factor in, <a href="#Page_40">40</a></li> -<li class="isub1">alcohol in, <a href="#Page_361">361</a></li> -<li class="isub1">amino-acids in relation to, <a href="#Page_64">64</a></li> -<li class="isub1">and fibrositis, incidence of, <a href="#Page_221">221</a></li> -<li class="isub1">and granular kidney, clinical associations of, <a href="#Page_130">130</a></li> -<li class="isub1">and immunity, early fallacies regarding, <a href="#Page_10">10</a></li> -<li class="isub1">and nephritis, <a href="#Page_242">242</a></li> -<li class="isub1">and other diseases, affinities between, <a href="#Page_236">236</a></li> -<li class="isub1">and rheumatoid arthritis, resemblance between, <a href="#Page_113">113</a></li> -<li class="isub1">and specific infective arthritides, analogies between, <a href="#Page_194">194</a></li> -<li class="isub1">antiquity of, <a href="#Page_1">1</a></li> -<li class="isub1">arterio-sclerosis associated with, <a href="#Page_245">245</a></li> -<li class="isub1">articular, acute, differential diagnosis, <a href="#Page_259">259</a></li> -<li class="isub3">localised, clinical diagnosis, <a href="#Page_258">258</a></li> -<li class="isub2">chronic, <a href="#Page_225">225</a></li> -<li class="isub3">alkalies in treatment of, <a href="#Page_399">399</a></li> -<li class="isub3">blood changes in, <a href="#Page_226">226</a></li> -<li class="isub3">clinical diagnosis of, <a href="#Page_275">275</a></li> -<li class="isub3">distribution of, <a href="#Page_226">226</a></li> -<li class="isub3">local measures in, <a href="#Page_407">407</a></li> -<li class="isub3">medicinal and other modes of therapy, <a href="#Page_397">397</a></li> -<li class="isub3">progress of disease, <a href="#Page_228">228</a></li> -<li class="isub3">surgical treatment, <a href="#Page_409">409</a></li> -<li class="isub2">classification of, author’s division, <a href="#Page_38">38</a></li> -<li class="isub2">clinical diagnosis of, <a href="#Page_252">252</a></li> -<li class="isub2">etiological diagnosis, <a href="#Page_247">247</a></li> -<li class="isub2">manifestations of, <a href="#Page_195">195</a></li> -<li class="isub1">as an infection, <a href="#Page_177">177</a></li> -<li class="isub1">auto-intoxication theory, summary, <a href="#Page_182">182</a></li> -<li class="isub1">beverages in, <a href="#Page_359">359</a></li> -<li class="isub1">blood content in, <a href="#Page_127">127</a></li> -<li class="isub2">uric acid and, relation between, <a href="#Page_143">143</a></li> -<li class="isub1">choice of spa in treatment of, <a href="#Page_440">440</a></li> -<li class="isub1">chronic, ankylosis in, <a href="#Page_287">287</a></li> -<li class="isub2">confusion with chronic villous synovitis, <a href="#Page_279">279</a></li> -<li class="isub2">diet in, <a href="#Page_334">334</a></li> -<li class="isub2">differentiation of, from arthritis deformans, <a href="#Page_16">16</a></li> -<li class="isub2">joint deformities of, <a href="#Page_229">229</a></li> -<li class="isub2">of oligo-articular distribution, <a href="#Page_278">278</a></li> -<li class="isub2">polyarticular, clinical features, <a href="#Page_282">282</a></li> -<li class="isub2">polyarticular, differential diagnosis, <a href="#Page_282">282</a></li> -<li class="isub2">tardy dissociation of, from chronic rheumatism, <a href="#Page_15">15</a></li> -<li class="isub2">uric acid variations in, <a href="#Page_109">109</a></li> -<li class="isub1">classification of, <a href="#Page_35">35</a>, <a href="#Page_36">36</a></li> -<li class="isub1">climate and residence in treatment of, <a href="#Page_418">418</a></li> -<li class="isub1">climato-therapy in, <a href="#Page_418">418</a></li> -<li class="isub1">clinical account of, <a href="#Page_200">200</a></li> -<li class="isub1">clothing and, <a href="#Page_421">421</a></li> -<li class="isub1">collateral phenomena of, <a href="#Page_219">219</a></li> -<li class="isub1">constipation and, <a href="#Page_337">337</a></li> -<li class="isub1">cutaneous disorders in, <a href="#Page_240">240</a></li> -<li class="isub1">definition of, <a href="#Page_35">35</a></li> -<li class="isub2">author’s, <a href="#Page_36">36</a></li> -<li class="isub1">derangement of gastro-intestinal tract as cause of, <a href="#Page_171">171</a></li> -<li class="isub1">elimination of infective arthritides from domain of, <a href="#Page_19">19</a></li> -<li class="isub1">endemic areas in, <a href="#Page_46">46</a></li> -<li class="isub1">etiology of, <a href="#Page_39">39</a></li> -<li class="isub1">evolution and life history of, <a href="#Page_193">193</a></li> -<li class="isub1">excretion in, anomalies of, <a href="#Page_112">112</a></li> -<li class="isub1">exercise in, importance of, <a href="#Page_421">421</a></li> -<li class="isub1">false, ocular symptoms, <a href="#Page_322">322</a></li> -<li class="isub1">glycocoll theory of, <a href="#Page_65">65</a></li> -<li class="isub1">Greek physicians’ views of pathology of, <a href="#Page_3">3</a></li> -<li class="isub1">growing infrequency and attenuation of, <a href="#Page_12">12</a></li> -<li class="isub1">guanine, in swine, <a href="#Page_100">100</a></li> -<li class="isub1">heredity and, <a href="#Page_41">41</a></li> -<li class="isub1">hydrotherapy, general, in treatment of, <a href="#Page_424">424</a></li> -<li class="isub2">local, in treatment of, methods of, <a href="#Page_428">428</a></li> -<li class="isub1">hyperpyræmia in ætiology of, <a href="#Page_30">30</a></li> -<li class="isub1">in big toe, differential diagnosis, <a href="#Page_259">259</a></li> -<li class="isub1">infantile, <a href="#Page_116">116</a>, <a href="#Page_305">305</a></li> -<li class="isub1">infective theory of, rise of, <a href="#Page_171">171</a></li> -<li class="isub2">summary, <a href="#Page_182">182</a>, <a href="#Page_183">183</a></li> -<li class="isub1">inflammatory phenomena in, cause of, <a href="#Page_165">165</a></li> -<li class="isub1">initial attacks usually monarticular, <a href="#Page_207">207</a></li> -<li class="isub1">initial outbreaks of, anomalous sites for, <a href="#Page_267">267</a></li> -<li class="isub2">sites of, <a href="#Page_37">37</a></li> -<li class="isub1">in relation to glycosuria, <a href="#Page_236">236</a></li> -<li class="isub1">in relation to phlebitis, <a href="#Page_239">239</a></li> -<li class="isub1">in the heel, <a href="#Page_264">264</a></li> -<li class="isub1"><span class="pagenum"><a id="Page_462"></a>[462]</span>in the instep, <a href="#Page_262">262</a></li> -<li class="isub1">in the sole, <a href="#Page_265">265</a></li> -<li class="isub1">inter-paroxysmal period, treatment in, prophylactic measures, <a href="#Page_389">389</a></li> -<li class="isub1">introduction of word, <a href="#Page_6">6</a></li> -<li class="isub1">irregular, <a href="#Page_293">293</a></li> -<li class="isub2">conclusions regarding, <a href="#Page_304">304</a></li> -<li class="isub1">isolation of acute articular rheumatism from, <a href="#Page_15">15</a></li> -<li class="isub1">lead workers predisposed to, <a href="#Page_50">50</a></li> -<li class="isub1">leanness in, <a href="#Page_337">337</a></li> -<li class="isub1">leucocytosis in, <a href="#Page_172">172</a>, <a href="#Page_189">189</a></li> -<li class="isub1">life history of, <a href="#Page_193">193</a></li> -<li class="isub1">local foci of infection, <a href="#Page_177">177</a></li> -<li class="isub2">treatment of, radical, <a href="#Page_327">327</a></li> -<li class="isub1">local syncopes and asphyxias of hands in, <a href="#Page_45">45</a></li> -<li class="isub1">long-continued, favouring onset of pre-senilism, <a href="#Page_398">398</a></li> -<li class="isub1">lumbago associated with, <a href="#Page_221">221</a></li> -<li class="isub1">massage, general, in treatment, <a href="#Page_423">423</a></li> -<li class="isub1">metabolic phenomena correlated with postulated infective element, <a href="#Page_195">195</a></li> -<li class="isub1">mineral springs in treatment of, <a href="#Page_431">431</a></li> -<li class="isub1">monarticular, chronic, differential diagnosis of, <a href="#Page_276">276</a>, <a href="#Page_277">277</a></li> -<li class="isub1">morbid anatomy of, <a href="#Page_39">39</a>, <a href="#Page_53">53</a></li> -<li class="isub1">morbid conditions associated with, treatment of, <a href="#Page_411">411</a></li> -<li class="isub1">obesity in, reduction of, <a href="#Page_356">356</a></li> -<li class="isub1">ocular disease in, <a href="#Page_308">308</a></li> -<li class="isub2">frequency a factor in diagnosis, <a href="#Page_316">316</a></li> -<li class="isub1">onset of, symptoms, <a href="#Page_188">188</a></li> -<li class="isub1">organic predisposition to, <a href="#Page_43">43</a></li> -<li class="isub1">other conditions classified as, in early times, <a href="#Page_12">12</a></li> -<li class="isub1">pathogenesis of, earlier theories of, <a href="#Page_21">21</a></li> -<li class="isub1">pedigree of, <a href="#Page_14">14</a></li> -<li class="isub1">periodicity of, <a href="#Page_191">191</a></li> -<li class="isub1">phenomena of, detailed account of, <a href="#Page_207">207</a></li> -<li class="isub1">predisposing causes of, summary of, <a href="#Page_52">52</a></li> -<li class="isub1">prevalence of, in Anglo-Saxon period, <a href="#Page_2">2</a></li> -<li class="isub1">prognosis in, <a href="#Page_244">244</a></li> -<li class="isub1">renal theory of, <a href="#Page_117">117</a></li> -<li class="isub1">restriction of, by elimination of other disorders, <a href="#Page_19">19</a></li> -<li class="isub1">retarded purin elimination in, <a href="#Page_118">118</a></li> -<li class="isub1">retention capacity of tissues for uric acid in, <a href="#Page_158">158</a></li> -<li class="isub1">retrocedent, <a href="#Page_39">39</a>, <a href="#Page_296">296</a></li> -<li class="isub2">irregular manifestations of, <a href="#Page_299">299</a></li> -<li class="isub1">sex incidence of, <a href="#Page_41">41</a></li> -<li class="isub1">skiagraphy in diagnosis of, <a href="#Page_286">286</a></li> -<li class="isub1">specific organism suggested, <a href="#Page_175">175</a></li> -<li class="isub1">sthenic, febrile stage of, alcohol and, <a href="#Page_333">333</a></li> -<li class="isub1">structural changes, <a href="#Page_54">54</a></li> -<li class="isub1">sub-infection theory, summary, <a href="#Page_182">182</a>, <a href="#Page_183">183</a></li> -<li class="isub1">subjective phenomena of, in relation to blood content and excretion of uric acid, radium emanations and, <a href="#Page_438">438</a></li> -<li class="isub1">“the honour of,” <a href="#Page_8">8</a></li> -<li class="isub1">theory of hepatic inadequacy, <a href="#Page_28">28</a></li> -<li class="isub1">tophaceous, <a href="#Page_39">39</a></li> -<li class="isub1">treatment of, <a href="#Page_327">327</a></li> -<li class="isub2">diet in, <a href="#Page_332">332</a>, <a href="#Page_342">342</a></li> -<li class="isub2">fallacy of fixed dietaries, <a href="#Page_335">335</a></li> -<li class="isub2">gastro-intestinal asepsis in, <a href="#Page_332">332</a></li> -<li class="isub2">hyperæmia, <a href="#Page_429">429</a></li> -<li class="isub2">physical examination necessary before dieting, <a href="#Page_336">336</a></li> -<li class="isub2">prevention of digestive disturbances, <a href="#Page_335">335</a></li> -<li class="isub1">uratic deposits in, <a href="#Page_54">54</a></li> -<li class="isub2">differentiation from nephritis, <a href="#Page_129">129</a></li> -<li class="isub2">localisation of, <a href="#Page_153">153</a></li> -<li class="isub1">uratosis in relation to, <a href="#Page_149">149</a></li> -<li class="isub1">urea excretion in, <a href="#Page_66">66</a></li> -<li class="isub1">uric acid content of blood in, <a href="#Page_139">139</a></li> -<li class="isub1">uric acid excretion in, <a href="#Page_108">108</a></li> -<li class="isub2">anomalies in, <a href="#Page_117">117</a></li> -<li class="isub1">uric acid in relation to, <a href="#Page_107">107</a></li> -<li class="isub1">uric acid theory of, <a href="#Page_21">21</a></li> -<li class="isub1">uric acid, urea and creatine in blood in (table), <a href="#Page_211">211</a></li> -<li class="isub1">uricæmia in, <a href="#Page_125">125</a>, <a href="#Page_133">133</a></li> -<li class="isub2">not cause, but result, of, <a href="#Page_148">148</a></li> -<li class="isub1">variations in excretion in, diagnosis of, <a href="#Page_60">60</a></li> - -<li class="indx"><b>Gouty</b> arthritis, definition of, <a href="#Page_20">20</a></li> -<li class="isub1">phlebitis, <a href="#Page_240">240</a></li> -<li class="isub1">polyarthritis, acute, <a href="#Page_214">214</a></li> -<li class="isub1">stigmata in types of fibrositis, <a href="#Page_222">222</a></li> - -<li class="indx">“<b>Gravel</b>, cutaneous,” <a href="#Page_203">203</a></li> -<li class="isub1">immunity from, <a href="#Page_29">29</a></li> - -<li class="indx"><b>Greek</b> physicians, terms used for forms of gout, <a href="#Page_3">3</a></li> -<li class="isub1">views of pathology of gout, <a href="#Page_3">3</a></li> - -<li class="indx"><b>Guaiacum</b> in treatment of chronic gout, <a href="#Page_403">403</a></li> -<li class="isub1">resin, effects on urine, <a href="#Page_405">405</a></li> - -<li class="indx"><b>Guanase</b>, <a href="#Page_100">100</a>, <a href="#Page_101">101</a></li> - -<li class="indx"><b>Guanine</b>, <a href="#Page_73">73</a>, <a href="#Page_75">75</a>, <a href="#Page_77">77</a>, <a href="#Page_98">98</a></li> -<li class="isub1">gout in swine, <a href="#Page_100">100</a></li> - -<li class="indx"><b>Gudzent</b> and Schade’s theories of uric acid in blood, <a href="#Page_79">79</a></li> - -<li class="indx"><b>Gummata</b>, peri-bursal, <a href="#Page_281">281</a></li> -<li class="isub1">peri-synovial, <a href="#Page_281">281</a></li> - -<li class="indx"><b>Gums</b>, recession of, early, <a href="#Page_45">45</a></li> - -<li class="ifrst"><b>Hæmatemesis</b>, gout following, <a href="#Page_178">178</a></li> - -<li class="indx"><b>Hæmo-analysis</b>, <a href="#Page_147">147</a></li> - -<li class="indx"><b>Hæmophilic</b> arthritis, differential diagnosis from chronic gout, <a href="#Page_285">285</a></li> - -<li class="indx"><b>Hæmorrhage</b>, retinal, and gout, <a href="#Page_322">322</a></li> - -<li class="indx"><b>Hair</b>, premature whitening of, <a href="#Page_45">45</a></li> - -<li class="indx"><b>Hallux</b> rigidus, differential diagnosis from gout, <a href="#Page_262">262</a></li> -<li class="isub1">valgus with inflamed bunion, differential diagnosis from gout, <a href="#Page_261">261</a></li> - -<li class="indx"><b>Haly Abbas’s</b> views on gout, <a href="#Page_6">6</a></li> - -<li class="indx"><b>Hand</b>, gouty polyarthritis in, <a href="#Page_214">214</a></li> - -<li class="indx"><b>Hands</b>, deformed, in chronic gout, <a href="#Page_230">230</a></li> -<li class="isub1">incidence of tophi in, <a href="#Page_162">162</a></li> -<li class="isub1">local syncopes and asphyxias in gout, <a href="#Page_45">45</a></li> -<li class="isub1">palms of, tophi in, <a href="#Page_235">235</a></li> - -<li class="indx"><b>Hare’s</b> theory of ætiology of gout, <a href="#Page_30">30</a></li> - -<li class="indx"><b>Heart</b> affections in gouty subjects, <a href="#Page_302">302</a></li> - -<li class="indx"><b>Heberden’s</b> differentiation of rheumatoid arthritis from gout, <a href="#Page_17">17</a></li> -<li class="isub1">nodes, <a href="#Page_41">41</a>, <a href="#Page_283">283</a></li> - -<li class="indx"><b>Heel</b>, gout in, <a href="#Page_264">264</a></li> -<li class="isub1">referred pain in, differential diagnosis in, <a href="#Page_264">264</a></li> -<li class="isub2"><span class="pagenum"><a id="Page_463"></a>[463]</span>local sources of fallacy, <a href="#Page_265">265</a></li> - -<li class="indx"><b>Hepatic</b> derangement in acute paroxysms of gout, <a href="#Page_333">333</a></li> -<li class="isub1">inadequacy theory of ætiology of gout, <a href="#Page_28">28</a></li> - -<li class="indx"><b>Heredity</b> in gout, <a href="#Page_8">8</a>, <a href="#Page_28">28</a>, <a href="#Page_40">40</a>, <a href="#Page_41">41</a>, <a href="#Page_214">214</a></li> - -<li class="indx"><b>Herpes</b> in acute gout, <a href="#Page_241">241</a></li> - -<li class="indx"><b>Hexose</b> group in vegetable nucleic acids, <a href="#Page_98">98</a></li> - -<li class="indx"><b>Hippocrates</b>, aphorisms of, on gout, <a href="#Page_4">4</a></li> - -<li class="indx"><b>Histogenous</b> theories of ætiology of gout, <a href="#Page_23">23</a></li> - -<li class="indx"><b>Historical</b> survey, <a href="#Page_1">1</a></li> - -<li class="indx"><b>Horbaczewski’s</b> experiments on uric acid, <a href="#Page_73">73</a></li> - -<li class="indx"><b>Hot-air</b> baths, <a href="#Page_429">429</a></li> -<li class="isub1">contra-indications to use of, <a href="#Page_429">429</a></li> - -<li class="indx"><b>Hutchinson</b> on gout and rheumatism, <a href="#Page_15">15</a></li> - -<li class="indx"><b>Hydrarthrosis</b>, bilateral, <a href="#Page_281">281</a></li> -<li class="isub1">in chronic articular gout, <a href="#Page_278">278</a></li> - -<li class="indx"><b>Hydrochloric</b> acid, secretion of, and gout, <a href="#Page_173">173</a></li> -<li class="isub1">strong or fuming, in inter-paroxysmal periods of gout, <a href="#Page_393">393</a></li> -<li class="isub1">variations in, and gout, <a href="#Page_181">181</a></li> - -<li class="indx"><b>Hydro-therapy</b>, general, in treatment of gout, <a href="#Page_424">424</a></li> -<li class="isub1">in acute gout, <a href="#Page_385">385</a></li> -<li class="isub1">in treatment of gout, contra-indications and untoward complications, <a href="#Page_425">425</a></li> -<li class="isub2">methods of application, <a href="#Page_427">427</a></li> -<li class="isub2">prophylactic measures, <a href="#Page_424">424</a></li> -<li class="isub1">local, in treatment of gout, <a href="#Page_428">428</a></li> - -<li class="indx"><b>Hyperacidity</b> due to organic acids, <a href="#Page_351">351</a></li> -<li class="isub1">in inter-paroxysmal periods of gout, <a href="#Page_393">393</a></li> - -<li class="indx"><b>Hyperæmia</b>, treatment of gout by, <a href="#Page_429">429</a></li> - -<li class="indx"><b>Hyperchlorhydria</b>, <a href="#Page_181">181</a>, <a href="#Page_351">351</a></li> -<li class="isub1">associated with gout, treatment of, <a href="#Page_415">415</a></li> -<li class="isub1">complicating gout, salt in diet contra-indicated, <a href="#Page_350">350</a></li> -<li class="isub1">diet in, <a href="#Page_353">353</a></li> -<li class="isub1">mineral waters suitable in treatment of, <a href="#Page_446">446</a></li> - -<li class="indx"><b>Hyperpyræmia</b> in ætiology of gout, <a href="#Page_30">30</a></li> - -<li class="indx"><b>Hyperuricæmia</b>, diet in, <a href="#Page_354">354</a></li> -<li class="isub1">in gout, <a href="#Page_140">140</a></li> -<li class="isub1">in non-gouty arthritis, <a href="#Page_140">140</a></li> -<li class="isub1">ocular symptoms in, <a href="#Page_321">321</a></li> - -<li class="indx"><b>Hypochlorhydria</b>, <a href="#Page_351">351</a></li> -<li class="isub1">diet in, <a href="#Page_354">354</a></li> - -<li class="indx"><b>Hypoxanthine</b>, <a href="#Page_73">73</a>, <a href="#Page_75">75</a>, <a href="#Page_77">77</a></li> - -<li class="ifrst"><b>Indigestion</b>, intestinal, in gouty subjects, <a href="#Page_181">181</a></li> - -<li class="indx"><b>Infantile</b> gout, <a href="#Page_116">116</a>, <a href="#Page_305">305</a></li> - -<li class="indx"><b>Infection</b> in gout, local foci of, <a href="#Page_177">177</a></li> -<li class="isub2">examination for in diagnosis of articular gout, <a href="#Page_248">248</a></li> -<li class="isub1">theory of gout, <a href="#Page_182">182</a>, <a href="#Page_183">183</a></li> - -<li class="indx"><b>Infections</b>, differential diagnosis from acute localised articular gout, <a href="#Page_259">259</a></li> -<li class="isub1">specific, arthritic muscular and nerve lesions associated with, <a href="#Page_195">195</a></li> -<li class="isub2">diagnosis of, <a href="#Page_19">19</a></li> - -<li class="indx"><b>Infective</b> element in gout, correlated with metabolic phenomena, <a href="#Page_195">195</a></li> - -<li class="indx"><b>Inflammation</b> and tophi formation, <a href="#Page_164">164</a></li> -<li class="isub1">gouty, pus formation and, <a href="#Page_191">191</a></li> - -<li class="indx"><b>Inflammatory</b> phenomena in gout, cause of, <a href="#Page_165">165</a></li> - -<li class="indx"><b>Influenzal</b> arthritis, differential diagnosis from acute gouty polyarthritis, <a href="#Page_272">272</a></li> - -<li class="indx"><b>Immunity</b> conferred by gout, early fallacies regarding, <a href="#Page_10">10</a></li> - -<li class="indx"><b>Inosinic</b> acid, <a href="#Page_93">93</a></li> - -<li class="indx"><b>Instep</b>, gout in the, <a href="#Page_262">262</a></li> - -<li class="indx"><b>Intestinal</b> canal, source of microbe or toxin in gout, <a href="#Page_181">181</a></li> -<li class="isub1">derangements, mineral waters suitable in treatment of, <a href="#Page_448">448</a></li> -<li class="isub1">dyspepsia preceding gout, <a href="#Page_182">182</a></li> -<li class="isub1">indigestion in gouty subjects, <a href="#Page_181">181</a></li> -<li class="isub1">irrigation with radio-active waters, <a href="#Page_439">439</a></li> -<li class="isub1">juices and wall, enzymes in, <a href="#Page_100">100</a></li> - -<li class="indx"><b>Iodides</b> in treatment of chronic gout, <a href="#Page_401">401</a></li> -<li class="isub1">value of, in renal and vascular changes, <a href="#Page_403">403</a></li> - -<li class="indx"><b>Iodine-albumen</b> compounds in treatment of chronic gout, <a href="#Page_402">402</a></li> - -<li class="indx"><b>Iodo-glidine</b> in treatment of chronic gout, <a href="#Page_402">402</a></li> - -<li class="indx"><b>Iodo-protein</b> in treatment of chronic gout, <a href="#Page_402">402</a></li> - -<li class="indx"><b>Ionisation</b> in treatment of acute gout, <a href="#Page_387">387</a></li> -<li class="isub1">in treatment of chronic articular gout, <a href="#Page_407">407</a></li> - -<li class="indx"><b>Iritis</b>, “arthritic,” <a href="#Page_315">315</a></li> -<li class="isub1">diseases commonly associated with, <a href="#Page_313">313</a></li> -<li class="isub1">gouty, “not” a clinical entity, <a href="#Page_316">316</a></li> -<li class="isub1">in gout, <a href="#Page_308">308</a></li> -<li class="isub1">relative incidence of, <a href="#Page_313">313</a></li> - -<li class="indx"><b>Irregular</b> gout, <a href="#Page_293">293</a></li> - -<li class="indx"><b>Isomeric</b> forms of uric acid, <a href="#Page_81">81</a></li> - -<li class="indx"><b>Isomers</b> of purins, <a href="#Page_81">81</a></li> -<li class="isub1">of pyrimidins, <a href="#Page_81">81</a></li> - -<li class="ifrst"><b>Jaw</b>, formation of, <a href="#Page_45">45</a></li> - -<li class="indx"><b>Jaws</b>, radiographs of, in treatment of gout, <a href="#Page_328">328</a></li> - -<li class="indx"><b>Joint</b> cartilage, murexide reaction in, <a href="#Page_153">153</a></li> -<li class="isub1">deformities of, chronic gout, <a href="#Page_229">229</a></li> - -<li class="indx"><b>Joints</b>, diaphyses of, cystic changes in, <a href="#Page_56">56</a></li> -<li class="isub1">rheumatism of, <a href="#Page_14">14</a></li> -<li class="isub1">stiffness of, after acute attacks of gout, <a href="#Page_212">212</a></li> -<li class="isub1">swellings, local character of, in osteo-arthritis, <a href="#Page_283">283</a></li> -<li class="isub2">local character of, in rheumatoid arthritis, <a href="#Page_284">284</a></li> -<li class="isub1">tophi in, <a href="#Page_233">233</a></li> - -<li class="indx"><b>Juices</b>, gastric and intestinal, gout and, <a href="#Page_173">173</a></li> - -<li class="ifrst"><b>Kidney</b> and kidneys, capacity of for eliminating uric acid, <a href="#Page_125">125</a></li> -<li class="isub1">condition of, effect in blood content of uric acid, <a href="#Page_138">138</a></li> -<li class="isub1">disease of, granular, and gout, clinical, association, <a href="#Page_130">130</a></li> -<li class="isub2">joint examination in, results of, <a href="#Page_129">129</a></li> -<li class="isub1">disease of, and gout, <a href="#Page_242">242</a></li> -<li class="isub1">functionally deficient in late stage of gout, <a href="#Page_119">119</a></li> -<li class="isub1">functional disorders of, <a href="#Page_27">27</a>, <a href="#Page_28">28</a></li> -<li class="isub1">functional efficiency of, tests for, <a href="#Page_338">338</a></li> -<li class="isub1">gouty, histological changes in, <a href="#Page_127">127</a></li> -<li class="isub1">guanase in, <a href="#Page_100">100</a></li> -<li class="isub1"><span class="pagenum"><a id="Page_464"></a>[464]</span>uric acid elimination in, <a href="#Page_119">119</a></li> - -<li class="indx"><b>Knee</b>, gouty polyarthritis in, <a href="#Page_214">214</a></li> -<li class="isub1">site of primary attack of gout, <a href="#Page_267">267</a></li> - -<li class="indx"><b>Kossel’s</b> discovery of purin bases, <a href="#Page_73">73</a></li> - -<li class="ifrst"><b>Labile</b> protein, <a href="#Page_59">59</a></li> - -<li class="indx"><b>Latham’s</b> theory of hepatic origin of gout, <a href="#Page_29">29</a></li> - -<li class="indx">“<b>Lead</b> gout,” <a href="#Page_50">50</a></li> - -<li class="indx"><b>Lead</b>, elimination by iodides, <a href="#Page_403">403</a></li> -<li class="isub1">poisoning, blood content in, <a href="#Page_122">122</a>, <a href="#Page_123">123</a>, <a href="#Page_127">127</a></li> -<li class="isub2">ocular symptoms in, <a href="#Page_321">321</a></li> -<li class="isub2">purin metabolism in, <a href="#Page_115">115</a></li> -<li class="isub1">workers, predisposed to gout, <a href="#Page_50">50</a></li> - -<li class="indx"><b>Leanness</b> in gout, <a href="#Page_337">337</a></li> - -<li class="indx"><b>Lehmann’s</b> analysis of tophi, <a href="#Page_150">150</a></li> - -<li class="indx"><b>Leucocytosis</b>, <a href="#Page_24">24</a>, <a href="#Page_27">27</a></li> -<li class="isub1">during acute attacks of gout, <a href="#Page_172">172</a></li> -<li class="isub1">in gout, <a href="#Page_189">189</a></li> -<li class="isub1">in gouty polyarthritis, <a href="#Page_216">216</a></li> -<li class="isub1">relation to uric acid excretion, <a href="#Page_95">95</a></li> - -<li class="indx"><b>Leucopenia</b>, <a href="#Page_96">96</a></li> -<li class="isub1">in gout, <a href="#Page_189">189</a></li> - -<li class="indx"><b>Leukæmia</b>, blood content in, <a href="#Page_122">122</a>, <a href="#Page_123">123</a></li> -<li class="isub1">ocular symptoms in, <a href="#Page_321">321</a></li> -<li class="isub1">uric acid in urine in, <a href="#Page_95">95</a></li> - -<li class="indx"><b>Levy’s</b> (Magnus) researches on gout, <a href="#Page_107">107</a></li> - -<li class="indx"><b>Limbs</b>, integument of tophi in, <a href="#Page_235">235</a></li> - -<li class="indx"><b>Lime</b> salts, focal absorption of, in bones, <a href="#Page_288">288</a></li> - -<li class="indx"><b>Liniments</b> in treatment of acute gout, <a href="#Page_386">386</a></li> - -<li class="indx"><b>Literature</b> of various periods, references to gout in, <a href="#Page_3">3</a></li> - -<li class="indx"><b>Lithæmia</b>, <a href="#Page_294">294</a></li> -<li class="isub1">tendency to, <a href="#Page_28">28</a>, <a href="#Page_33">33</a></li> - -<li class="indx"><b>Lithiasis</b>, <a href="#Page_29">29</a></li> - -<li class="indx"><b>Lithium</b> salts in treatment of chronic gout, <a href="#Page_400">400</a></li> - -<li class="indx"><b>Lithuria</b>, <a href="#Page_29">29</a></li> - -<li class="indx"><b>Liveing’s</b> theory of ætiology of gout, <a href="#Page_31">31</a></li> - -<li class="indx"><b>Liver</b>, diseases of, amino-acids in, <a href="#Page_59">59</a></li> -<li class="isub1">disorders of, functional, mineral waters suitable in treatment of, <a href="#Page_447">447</a></li> -<li class="isub1">enzymes in, <a href="#Page_99">99</a></li> -<li class="isub1">functional efficiency of, tests for, <a href="#Page_338">338</a></li> -<li class="isub1">glycogenic distension of, <a href="#Page_31">31</a></li> -<li class="isub1">guanase in, <a href="#Page_100">100</a></li> -<li class="isub1">main centre of production of urea, <a href="#Page_63">63</a></li> - -<li class="indx"><b>Living</b>, style of, effect on incidence of gout, <a href="#Page_2">2</a></li> - -<li class="indx"><b>Locality</b>, factor in gout, <a href="#Page_45">45</a></li> -<li class="isub1">incidence of, in acute gout, <a href="#Page_208">208</a></li> - -<li class="indx"><b>Lucian</b> of Saramosta’s views on gout, <a href="#Page_4">4</a></li> - -<li class="indx"><b>Lumbago</b>, associated with gout, <a href="#Page_221">221</a></li> -<li class="isub1">treatment of, <a href="#Page_411">411</a></li> - -<li class="indx"><b>Lung</b>, guanase in, <a href="#Page_100">100</a></li> - -<li class="indx"><b>Lymph</b> spaces, purins in, <a href="#Page_146">146</a></li> -<li class="isub1">stream, sodium ions in, <a href="#Page_146">146</a></li> - -<li class="indx"><b>Lymphangitis</b>, co-existent with gout, <a href="#Page_58">58</a></li> -<li class="isub1">in gout, <a href="#Page_190">190</a></li> - -<li class="indx"><b>Lymphatic</b> gland, enlargement of, in gout, <a href="#Page_190">190</a></li> - -<li class="indx"><b>Lymphatics</b>, purins in, <a href="#Page_146">146</a></li> - -<li class="ifrst"><b>Malt</b> liquors in gout, <a href="#Page_362">362</a></li> - -<li class="indx"><b>Marchand’s</b> analysis of tophi, <a href="#Page_150">150</a></li> - -<li class="indx"><b>Massage</b>, general, in treatment of gout, <a href="#Page_423">423</a></li> -<li class="isub1">in after-treatment of acute gout, <a href="#Page_385">385</a>, <a href="#Page_387">387</a></li> - -<li class="indx"><b>McCarrison’s</b> views on effect of absence of vitamines on functional efficiency, <a href="#Page_340">340</a></li> - -<li class="indx"><b>McClure and McCarty’s</b> researches on bone conditions as revealed by skiagraphy, <a href="#Page_288">288</a>, <a href="#Page_289">289</a></li> - -<li class="indx"><b>Meat</b>, over-eating of, functional damage resulting from, <a href="#Page_65">65</a></li> - -<li class="indx"><b>Meningococcal</b> arthritis, differential diagnosis from acute gouty polyarthritis, <a href="#Page_272">272</a></li> - -<li class="indx"><b>Menstruation</b>, effect of, on incidence of gout, <a href="#Page_41">41</a></li> - -<li class="indx"><b>Mental</b> over-exertion and gout, <a href="#Page_51">51</a></li> - -<li class="indx"><b>Metabolic</b> phenomena of gout correlated with postulated infective element, <a href="#Page_195">195</a></li> - -<li class="indx"><b>Metabolism</b>, alterations in, <a href="#Page_30">30</a></li> -<li class="isub1">inborn errors of, <a href="#Page_69">69</a></li> -<li class="isub1">nuclein, <a href="#Page_71">71</a></li> -<li class="isub1">protein, <a href="#Page_59">59</a>, <a href="#Page_61">61</a></li> - -<li class="indx"><b>Metastasis</b> in relation to ocular gout, <a href="#Page_314">314</a></li> -<li class="isub1">gouty, <a href="#Page_297">297</a></li> - -<li class="indx"><b>Metatarsalgia</b>, differential diagnosis from gout, <a href="#Page_262">262</a></li> - -<li class="indx"><b>Methyl-purins</b> as source of uric acid, <a href="#Page_85">85</a></li> - -<li class="indx"><b>Microbic</b> theory of gout, <a href="#Page_175">175</a></li> - -<li class="indx"><b>Miescher’s</b> researches on spermatozoa, <a href="#Page_72">72</a></li> -<li class="isub1">on the nucleus, <a href="#Page_71">71</a></li> - -<li class="indx"><b>Milk</b> diet in acute paroxysms of gout, <a href="#Page_332">332</a></li> - -<li class="indx"><b>Mineral</b> springs, <a href="#Page_431">431</a></li> -<li class="isub1">waters as beverage in gout, <a href="#Page_360">360</a></li> - -<li class="indx"><b>Monarticular</b> gout, differential diagnosis of, <a href="#Page_276">276</a>, <a href="#Page_277">277</a></li> - -<li class="indx"><b>Morphia</b>, hypodermic injections of, in acute gout, <a href="#Page_383">383</a></li> - -<li class="indx"><b>Mouth</b>, examination of, in diagnosis of articular gout, <a href="#Page_248">248</a></li> -<li class="isub1">in treatment of gout, <a href="#Page_328">328</a></li> -<li class="isub1">local foci of infection, results of, <a href="#Page_184">184</a></li> - -<li class="indx"><b>Murchison’s</b> theory of ætiology of gout, <a href="#Page_28">28</a></li> - -<li class="indx"><b>Murexide</b> reaction in joint cartilage, <a href="#Page_153">153</a></li> - -<li class="indx"><b>Muriated</b> chloride waters, spas for, <a href="#Page_441">441</a></li> -<li class="isub1">sulphated waters, spas for, <a href="#Page_442">442</a></li> - -<li class="indx"><b>Muscles</b>, affections of, in gout, <a href="#Page_195">195</a></li> -<li class="isub1">voluntary, relation of creatinine to, <a href="#Page_68">68</a></li> - -<li class="indx"><b>Muscular</b> exercise, uric acid excretion increased by, <a href="#Page_93">93</a></li> - -<li class="indx"><b>Myeloma</b>, waste of albumoses in, <a href="#Page_59">59</a></li> - -<li class="ifrst"><b>Nails</b>, striated, fluted and brittle, <a href="#Page_45">45</a></li> - -<li class="indx"><b>Nasal</b> affections, radium emanations for, <a href="#Page_438">438</a></li> -<li class="isub1">disorders, gout and, <a href="#Page_178">178</a></li> - -<li class="indx"><b>Naso-pharynx</b>, examination of, in treatment of gout, <a href="#Page_328">328</a></li> -<li class="isub1">foci of infection, <a href="#Page_53">53</a></li> - -<li class="indx"><b>Necrosis</b>, local, in uratic deposition, <a href="#Page_152">152</a></li> -<li class="isub1">relationship to gout, <a href="#Page_25">25</a></li> - -<li class="indx"><b>Nephritis</b>, acute and chronic, blood content in, <a href="#Page_127">127</a></li> -<li class="isub1">chronic, spa treatment of, <a href="#Page_452">452</a></li> -<li class="isub1">complicating gouty polyarthritis, <a href="#Page_219">219</a></li> -<li class="isub1">early, blood content of uric acid, urea and creatine, similarity to gout, <a href="#Page_120">120</a></li> -<li class="isub1">gout and, <a href="#Page_242">242</a></li> -<li class="isub1">gouty, treatment of, <a href="#Page_416">416</a></li> -<li class="isub1">uratic deposits in, <a href="#Page_128">128</a></li> -<li class="isub2"><span class="pagenum"><a id="Page_465"></a>[465]</span>differentiation from gout, <a href="#Page_129">129</a></li> -<li class="isub1">uric acid, urea and creatine in blood in (table), <a href="#Page_121">121</a></li> -<li class="isub1">uricæmia in, <a href="#Page_120">120</a></li> -<li class="isub1">uricæmia not peculiar to, <a href="#Page_124">124</a></li> - -<li class="indx"><b>Nerve</b> arthropathies, differential diagnosis from chronic gout, <a href="#Page_284">284</a></li> -<li class="isub1">Charcot’s discovery of, <a href="#Page_18">18</a></li> - -<li class="indx"><b>Nervous</b> phenomena of gout, <a href="#Page_188">188</a>, <a href="#Page_304">304</a></li> -<li class="isub1">system, effect of gout on, <a href="#Page_219">219</a></li> -<li class="isub1">theories of ætiology of gout, <a href="#Page_31">31</a></li> - -<li class="indx"><b>Neuralgia</b>, plantar, differential diagnosis from gout, <a href="#Page_266">266</a></li> - -<li class="indx"><b>Neuritis</b>, alcoholic peripheral, <a href="#Page_238">238</a></li> -<li class="isub1">glycosuric peripheral, <a href="#Page_238">238</a></li> - -<li class="indx"><b>Neuro-lymphatismus</b>, <a href="#Page_116">116</a></li> - -<li class="indx"><b>Neuro-retinitis</b> in the gouty, <a href="#Page_324">324</a></li> - -<li class="indx"><b>Neurosis</b>, gouty, <a href="#Page_31">31</a></li> - -<li class="indx"><b>Neuroses</b>, paroxysmal, of gout, <a href="#Page_188">188</a></li> - -<li class="indx"><b>Nose</b>, alæ of, tophi in, <a href="#Page_235">235</a></li> - -<li class="indx"><b>Nuclease</b>, <a href="#Page_100">100</a></li> - -<li class="indx"><b>Nucleic</b> acid, <a href="#Page_72">72</a>, <a href="#Page_77">77</a></li> -<li class="isub1">characteristic constituents of, <a href="#Page_78">78</a></li> -<li class="isub1">disruption of, <a href="#Page_100">100</a></li> -<li class="isub2">in body, <a href="#Page_74">74</a></li> -<li class="isub1">formation of uric acid from, <a href="#Page_98">98</a></li> -<li class="isub1">isolation of, <a href="#Page_71">71</a></li> -<li class="isub1">metabolism of, in gout, <a href="#Page_69">69</a></li> -<li class="isub1">molecules, <a href="#Page_101">101</a></li> -<li class="isub1">of animal origin, structural formula of, <a href="#Page_99">99</a></li> -<li class="isub1">physiological derivation of uric acid from, <a href="#Page_73">73</a></li> -<li class="isub1">uric acid a derivative of, <a href="#Page_73">73</a></li> - -<li class="indx"><b>Nucleic-acidase</b>, <a href="#Page_100">100</a></li> - -<li class="indx"><b>Nuclein</b>, discovery of, <a href="#Page_72">72</a></li> -<li class="isub1">metabolism, <a href="#Page_71">71</a></li> -<li class="isub2">chemistry of, <a href="#Page_60">60</a></li> - -<li class="indx"><b>Nucleins</b>, <a href="#Page_77">77</a></li> -<li class="isub1">phosphoric acid group in, <a href="#Page_112">112</a></li> - -<li class="indx"><b>Nucleo-proteins</b>, <a href="#Page_77">77</a></li> - -<li class="indx"><b>Nucleosidases</b>, <a href="#Page_101">101</a></li> - -<li class="indx"><b>Nucleosides</b>, <a href="#Page_87">87</a>, <a href="#Page_100">100</a></li> - -<li class="indx"><b>Nucleotidase</b>, <a href="#Page_100">100</a></li> - -<li class="indx"><b>Nucleotides</b>, <a href="#Page_100">100</a></li> - -<li class="indx"><b>Numbness</b> after acute attacks of gout, <a href="#Page_212">212</a></li> - -<li class="ifrst"><b>Obesity</b> and gout, <a href="#Page_245">245</a></li> -<li class="isub2">Ebstein’s views of affinity, <a href="#Page_280">280</a></li> -<li class="isub1">in gout, <a href="#Page_337">337</a></li> -<li class="isub1">reduction of, <a href="#Page_356">356</a></li> - -<li class="indx"><b>Occupation</b> and gout, <a href="#Page_48">48</a></li> - -<li class="indx"><b>Occupations</b> predisposing to gout, <a href="#Page_50">50</a></li> - -<li class="indx"><b>Ocular</b> disease in gout, <a href="#Page_308">308</a></li> - -<li class="indx"><b>Œdema</b> in acute gout, <a href="#Page_212">212</a></li> -<li class="isub1">in gouty conditions, <a href="#Page_191">191</a></li> - -<li class="indx"><b>Olecranon</b> bursa, involved in gout, <a href="#Page_215">215</a></li> -<li class="isub1">tophi in, <a href="#Page_233">233</a>, <a href="#Page_235">235</a></li> - -<li class="indx"><b>Oligo-articular</b> distribution of chronic gout, <a href="#Page_278">278</a></li> - -<li class="indx"><b>Oral</b> sepsis in gouty subjects, <a href="#Page_179">179</a></li> -<li class="isub1">radium emanations and, <a href="#Page_438">438</a></li> -<li class="isub1">treatment of, in gout, <a href="#Page_330">330</a></li> - -<li class="indx"><b>Ord’s</b> theory of ætiology of gout, <a href="#Page_25">25</a></li> - -<li class="indx"><b>Osler’s</b> views on gout, <a href="#Page_36">36</a></li> - -<li class="indx"><b>Osteoarthritis</b>, acute, differential diagnosis from gout, <a href="#Page_261">261</a></li> -<li class="isub1">and chronic articular gout, <a href="#Page_275">275</a>, <a href="#Page_276">276</a></li> -<li class="isub1">co-existing with gout, <a href="#Page_19">19</a></li> -<li class="isub1">differential diagnosis from chronic articular gout, <a href="#Page_278">278</a></li> -<li class="isub1">differential diagnosis from chronic gout, <a href="#Page_283">283</a></li> -<li class="isub1">in ancient civilisations, <a href="#Page_1">1</a></li> -<li class="isub1">local characters of joint swellings, <a href="#Page_283">283</a></li> -<li class="isub1">of hip, with auricular tophi, <a href="#Page_226">226</a></li> -<li class="isub1">skiagraphy in differential diagnosis of, <a href="#Page_291">291</a></li> - -<li class="indx"><b>Overeating</b> and gout, <a href="#Page_48">48</a></li> -<li class="isub1">plus alcohol, cause of gout, <a href="#Page_49">49</a></li> - -<li class="indx"><b>Oxaluria</b> associated with gout, treatment of, <a href="#Page_413">413</a></li> -<li class="isub1">examination for, in treatment of gout, <a href="#Page_337">337</a></li> -<li class="isub1">spa treatment of, <a href="#Page_449">449</a></li> - -<li class="indx"><b>Oxidation</b> of purin, products of, <a href="#Page_77">77</a></li> - -<li class="indx"><b>Oxy-purins</b> as source of uric acid, <a href="#Page_84">84</a></li> -<li class="isub1">formation of, <a href="#Page_102">102</a></li> - -<li class="ifrst"><b>Pain</b> and tophi formation, <a href="#Page_164">164</a></li> -<li class="isub1">in acute gout, <a href="#Page_208">208</a></li> -<li class="isub1">in auricular tophi, <a href="#Page_233">233</a></li> -<li class="isub1">referred, in heel, differential diagnosis of, <a href="#Page_264">264</a></li> - -<li class="indx"><b>Pains</b>, premonitory articular, in acute localised gout, <a href="#Page_204">204</a></li> - -<li class="indx"><b>Painters</b>, predisposed to gout, <a href="#Page_50">50</a></li> - -<li class="indx"><b>Pancreas</b>, enzymes in, <a href="#Page_99">99</a></li> - -<li class="indx"><b>Pancreatic</b> inefficiency, evidence of, in diagnosis of articular gout, <a href="#Page_250">250</a></li> - -<li class="indx"><b>Pancretin</b>, <a href="#Page_392">392</a></li> - -<li class="indx"><b>Papain</b>, <a href="#Page_392">392</a></li> - -<li class="indx"><b>Parke’s</b> theories of ætiology of gout, <a href="#Page_23">23</a></li> - -<li class="indx"><b>Parotitis</b>, acute, gout following, <a href="#Page_53">53</a></li> -<li class="isub1">in gout, <a href="#Page_179">179</a></li> - -<li class="indx"><b>Patella</b>, tophi in, <a href="#Page_235">235</a></li> - -<li class="indx"><b>Pathological</b> states influencing endogenous uric acid excretions, <a href="#Page_94">94</a></li> - -<li class="indx"><b>Paulus Ægineta’s</b> views on gout, <a href="#Page_6">6</a></li> - -<li class="indx"><b>Pedigree</b> of gout, <a href="#Page_14">14</a></li> - -<li class="indx"><b>Pentosuria</b>, <a href="#Page_69">69</a></li> - -<li class="indx"><b>Peri-bursal</b> gummata, <a href="#Page_281">281</a></li> - -<li class="indx"><b>Perineum</b>, uratic deposits in, <a href="#Page_235">235</a></li> - -<li class="indx"><b>Periodic</b> variations in excretion of endogenous uric acid, <a href="#Page_94">94</a></li> - -<li class="indx"><b>Periodontitis</b>, chronic, <a href="#Page_329">329</a></li> - -<li class="indx"><b>Peri-synovial</b> gummata, <a href="#Page_281">281</a></li> - -<li class="indx"><b>Pes planus</b>, differential diagnosis from gout, <a href="#Page_263">263</a></li> - -<li class="indx"><b>Pharyngeal</b> affections, radium emanations for, <a href="#Page_438">438</a></li> - -<li class="indx"><b>Pharyngitis</b>, acute and chronic, in gouty subjects, <a href="#Page_179">179</a></li> -<li class="isub1">acute, gout following, <a href="#Page_53">53</a></li> - -<li class="indx"><b>Pharynx</b>, examination of, in diagnosis of articular gout, <a href="#Page_249">249</a></li> - -<li class="indx"><b>Phlebitis</b>, gout in relation to, <a href="#Page_239">239</a></li> -<li class="isub1">gouty, treatment of, <a href="#Page_415">415</a></li> -<li class="isub1">in limb in articular gout, <a href="#Page_190">190</a></li> -<li class="isub1">spa treatment of, <a href="#Page_450">450</a></li> -<li class="isub1">treatment of gout and, <a href="#Page_328">328</a></li> - -<li class="indx"><b>Phospho-nuclease</b>, <a href="#Page_102">102</a></li> - -<li class="indx"><b>Physical</b> examination, necessity for, before dieting, in treatment of gout, <a href="#Page_336">336</a></li> -<li class="isub1">over-exertion and gout, <a href="#Page_51">51</a></li> - -<li class="indx"><b>Physiognomy</b> of the goutily disposed, <a href="#Page_44">44</a></li> - -<li class="indx"><b>Pinna</b>, small red swellings on, <a href="#Page_204">204</a></li> - -<li class="indx"><span class="pagenum"><a id="Page_466"></a>[466]</span><b>Planchon’s</b> views on gout, <a href="#Page_6">6</a></li> - -<li class="indx"><b>Plantar</b> neuralgia, differential diagnosis from gout, <a href="#Page_266">266</a></li> - -<li class="indx"><b>Pleurodynia</b> associated with gout, treatment of, <a href="#Page_412">412</a></li> - -<li class="indx"><b>Plumbers</b>, predisposed to gout, <a href="#Page_50">50</a></li> - -<li class="indx"><b>Plumbism</b> and gout, <a href="#Page_60">60</a></li> -<li class="isub1">purin metabolism in, <a href="#Page_115">115</a></li> - -<li class="indx"><b>Pneumococcal</b> arthritis, differential diagnosis from acute gouty polyarthritis, <a href="#Page_272">272</a></li> - -<li class="indx"><b>Podagra</b>, <a href="#Page_12">12</a></li> -<li class="isub1">Greek designation, <a href="#Page_3">3</a></li> - -<li class="indx"><b>Polyarthritis</b>, articular, acute, differential diagnosis of, <a href="#Page_269">269</a>, <a href="#Page_270">270</a></li> -<li class="isub1">gouty, acute, <a href="#Page_214">214</a></li> -<li class="isub3">clinical diagnosis of, <a href="#Page_268">268</a></li> -<li class="isub3">diet in, <a href="#Page_334">334</a></li> -<li class="isub2">blood changes in, <a href="#Page_216">216</a></li> -<li class="isub2">distribution of, <a href="#Page_214">214</a></li> -<li class="isub2">effect on nervous system, <a href="#Page_219">219</a></li> -<li class="isub2">simulating erysipelas, <a href="#Page_215">215</a></li> -<li class="isub1">non-gouty, uric acid blood content in, <a href="#Page_141">141</a></li> - -<li class="indx"><b>Polyarticular</b> distribution of gout, <a href="#Page_214">214</a></li> - -<li class="indx"><b>Poly-nucleotides</b>, <a href="#Page_100">100</a></li> - -<li class="indx"><b>Port</b> wine in gout, <a href="#Page_364">364</a>, <a href="#Page_368">368</a></li> - -<li class="indx"><b>Portal</b> blood, amino-acids in, <a href="#Page_62">62</a></li> - -<li class="indx"><b>Post-critical</b> stage of depression, <a href="#Page_211">211</a></li> - -<li class="indx"><b>Potash</b> compounds in treatment of chronic gout, <a href="#Page_400">400</a></li> - -<li class="indx"><b>Potassium</b> in gouty tophi, <a href="#Page_151">151</a></li> - -<li class="indx"><b>Prescriptions</b> for use in acute gout, <a href="#Page_375">375</a>, <a href="#Page_377">377</a>, <a href="#Page_378">378</a>, <a href="#Page_379">379</a>, <a href="#Page_380">380</a>, <a href="#Page_386">386</a>, <a href="#Page_391">391</a></li> -<li class="isub1">for use in chronic gout, <a href="#Page_401">401</a>, <a href="#Page_405">405</a>, <a href="#Page_406">406</a></li> -<li class="isub1">for use in inter-paroxysmal periods of gout, <a href="#Page_391">391</a>, <a href="#Page_392">392</a>, <a href="#Page_393">393</a>, <a href="#Page_394">394</a></li> - -<li class="indx"><b>Pre-senilism</b>, long-continued gout favouring, <a href="#Page_398">398</a></li> - -<li class="indx"><b>Protamine</b>, <a href="#Page_72">72</a></li> - -<li class="indx"><b>Protein</b>, amino-acids in, number of, <a href="#Page_64">64</a></li> -<li class="isub1">chemistry of, <a href="#Page_60">60</a></li> -<li class="isub1">labile, <a href="#Page_59">59</a></li> -<li class="isub1">metabolism, <a href="#Page_59">59</a>, <a href="#Page_61">61</a></li> -<li class="isub2">urine content of urea, etc., in, <a href="#Page_59">59</a></li> -<li class="isub1">tissue, <a href="#Page_59">59</a></li> - -<li class="indx"><b>Proteins</b> and their derivatives, <a href="#Page_88">88</a></li> -<li class="isub1">in diet of gouty, <a href="#Page_345">345</a></li> - -<li class="indx"><b>Pulse</b> quickened in gout, <a href="#Page_189">189</a></li> - -<li class="indx"><b>Purgatives</b> in treatment of acute gout, <a href="#Page_374">374</a></li> - -<li class="indx"><b>Purin</b> bases, toxicity of, discussed, <a href="#Page_168">168</a></li> -<li class="isub1">bodies, <a href="#Page_34">34</a>, <a href="#Page_48">48</a>, <a href="#Page_63">63</a></li> -<li class="isub2">chemistry of, <a href="#Page_75">75</a></li> -<li class="isub1">diet, uric acid excretion in, <a href="#Page_86">86</a></li> -<li class="isub2">“free” diet, <a href="#Page_355">355</a></li> -<li class="isub2">uric acid blood content in, <a href="#Page_137">137</a></li> -<li class="isub2">uric acid excretion in, <a href="#Page_86">86</a></li> -<li class="isub1">elimination, retarded, in gout, <a href="#Page_118">118</a></li> -<li class="isub1">metabolism, chemistry of, <a href="#Page_60">60</a></li> -<li class="isub2">in chronic alcoholism, <a href="#Page_115">115</a></li> -<li class="isub2">in other disorders, <a href="#Page_113">113</a></li> -<li class="isub2">in plumbism, <a href="#Page_115">115</a></li> -<li class="isub1">nuclease, <a href="#Page_102">102</a></li> -<li class="isub1">nucleus, arrangement of atoms, <a href="#Page_76">76</a></li> -<li class="isub1">oxidation of, products of, <a href="#Page_77">77</a></li> -<li class="isub1">scheme illustrating probable stages in passage through body, <a href="#Page_101">101</a></li> -<li class="isub1">synthesis in mammals, <a href="#Page_97">97</a></li> -<li class="isub1">unexcreted, fate of, <a href="#Page_87">87</a></li> - -<li class="indx"><b>Purins</b>, discovery of, <a href="#Page_72">72</a></li> -<li class="isub1">endogenous, <a href="#Page_83">83</a>, <a href="#Page_87">87</a></li> -<li class="isub2">source of, <a href="#Page_88">88</a></li> -<li class="isub1">exogenous, <a href="#Page_83">83</a></li> -<li class="isub2">as source of uric acid, <a href="#Page_84">84</a></li> -<li class="isub2">effect of atophan on, <a href="#Page_110">110</a></li> -<li class="isub2">effect on uric acid blood content, <a href="#Page_137">137</a></li> -<li class="isub1">isomers of, <a href="#Page_81">81</a></li> -<li class="isub1">of vegetable origin, <a href="#Page_77">77</a></li> - -<li class="indx"><b>Pus</b> formation, non-existence of, in gouty inflammation, <a href="#Page_186">186</a>, <a href="#Page_191">191</a></li> - -<li class="indx"><b>Pyæmia</b>, differential diagnosis from gout, <a href="#Page_259">259</a></li> - -<li class="indx"><b>Pyæmic</b> conditions confounded with gout, <a href="#Page_191">191</a></li> - -<li class="indx"><b>Pyorrhœa</b> alveolaris, and gout, <a href="#Page_178">178</a></li> -<li class="isub1">and treatment of gout, <a href="#Page_329">329</a></li> -<li class="isub1">exclusion of, in diagnosis of articular gout, <a href="#Page_248">248</a></li> - -<li class="indx"><b>Pyrexia</b> in acute gout, <a href="#Page_210">210</a></li> -<li class="isub1">in gout, <a href="#Page_189">189</a></li> - -<li class="indx"><b>Pyrimidine</b> bases, <a href="#Page_77">77</a></li> - -<li class="indx"><b>Pyrimidins</b>, isomers of, <a href="#Page_81">81</a></li> - -<li class="ifrst"><b>Quadriurate</b> in blood, <a href="#Page_78">78</a>, <a href="#Page_79">79</a></li> - -<li class="indx"><b>Quinic</b> acid in treatment of acute gout, <a href="#Page_383">383</a></li> - -<li class="indx"><b>Quinine</b> in treatment of acute gout, <a href="#Page_383">383</a></li> - -<li class="ifrst"><b>Race</b> incidence of gout, <a href="#Page_45">45-48</a></li> - -<li class="indx"><b>Radio-active</b> properties of thermal waters, <a href="#Page_427">427</a></li> -<li class="isub1">waters, physical properties of, <a href="#Page_434">434</a></li> - -<li class="indx"><b>Radium</b> emanation, increased excretion of uric acid through, <a href="#Page_437">437</a></li> -<li class="isub1">influence on uric acid metabolism, <a href="#Page_436">436</a></li> -<li class="isub1">physiological action of, <a href="#Page_435">435</a></li> -<li class="isub1">subjective phenomena of gout in relation to blood content and excretion of uric acid and, <a href="#Page_438">438</a></li> -<li class="isub1">therapeutic action and application, <a href="#Page_438">438</a></li> - -<li class="indx"><b>Regular</b> gout, <a href="#Page_13">13</a></li> - -<li class="indx"><b>Renal</b> changes in gout, <a href="#Page_54">54</a></li> -<li class="isub1">defect, uricæmia not necessarily due to, <a href="#Page_123">123</a></li> -<li class="isub1">depression, functional, <a href="#Page_119">119</a></li> -<li class="isub1">disease, abnormal protein loss in, <a href="#Page_59">59</a></li> -<li class="isub1">theory of gout, <a href="#Page_117">117</a></li> -<li class="isub1">uric acid infarcts, <a href="#Page_151">151</a></li> - -<li class="indx"><b>Residence</b>, choice of, <a href="#Page_420">420</a></li> - -<li class="indx"><b>Respiratory</b> disorders, spa treatment of, <a href="#Page_450">450</a></li> -<li class="isub1">organs, affections of, in gout, <a href="#Page_303">303</a></li> - -<li class="indx"><b>Retinitis</b>, nephritic, <a href="#Page_324">324</a></li> - -<li class="indx"><b>Retrocedent</b> gout, <a href="#Page_39">39</a>, <a href="#Page_296">296</a></li> - -<li class="indx"><b>Rhazes’s</b> views on gout, <a href="#Page_6">6</a></li> - -<li class="indx"><b>Rheumatism</b>, acute articular, differential diagnosis from acute gouty polyarthritis, <a href="#Page_269">269</a>, <a href="#Page_270">270</a></li> -<li class="isub3">isolation from gout, <a href="#Page_15">15</a></li> -<li class="isub3">muscular and nervous lesions associated with, <a href="#Page_194">194</a></li> -<li class="isub2">confused with gout, <a href="#Page_215">215</a></li> -<li class="isub1">chronic, tardy dissociation of, from chronic gout, <a href="#Page_15">15</a></li> -<li class="isub1">differential diagnosis from gout, <a href="#Page_259">259</a></li> -<li class="isub1">early use of term, <a href="#Page_14">14</a></li> -<li class="isub1"><span class="pagenum"><a id="Page_467"></a>[467]</span>muscular, identification of, <a href="#Page_16">16</a></li> - -<li class="indx"><b>Rheumatoid</b> arthritis, <a href="#Page_17">17</a></li> -<li class="isub2">and gout, resemblance between, <a href="#Page_113">113</a></li> -<li class="isub2">differential diagnosis from chronic gout, <a href="#Page_284">284</a></li> -<li class="isub2">disturbance of purin metabolism in, <a href="#Page_112">112</a></li> -<li class="isub1">or atrophic arthritis, differential diagnosis from acute polyarticular gout, <a href="#Page_272">272</a></li> - -<li class="indx"><b>Roberts’, Sir William</b>, views on gout, <a href="#Page_36">36</a></li> - -<li class="ifrst"><b>Salicylate</b> group as alternative remedy in treatment of acute gout, <a href="#Page_381">381</a></li> -<li class="isub1">of colchicine in treatment of acute gout, <a href="#Page_379">379</a></li> - -<li class="indx"><b>Salicylates</b> in treatment of acute gout, contra-indicated, alkalies as substitute, <a href="#Page_383">383</a></li> -<li class="isub1">in treatment of chronic gout, <a href="#Page_401">401</a></li> - -<li class="indx"><b>Salisbury</b> diet in hyperchlorhydria, <a href="#Page_353">353</a></li> -<li class="isub1">method in reduction of obesity, <a href="#Page_357">357</a></li> - -<li class="indx"><b>Salt</b> in diet of gouty, <a href="#Page_350">350</a></li> - -<li class="indx"><b>Scapular</b> region, uratic deposits in, <a href="#Page_235">235</a></li> - -<li class="indx"><b>Scheele’s</b> discovery of uric acid, <a href="#Page_8">8</a></li> - -<li class="indx"><b>Schnee</b> four-cell bath in ionisation, <a href="#Page_408">408</a></li> - -<li class="indx"><b>Sciatica</b> associated with gout, treatment of, <a href="#Page_411">411</a>, <a href="#Page_412">412</a></li> - -<li class="indx"><b>Scudamore’s</b> definition of gout, <a href="#Page_35">35</a></li> - -<li class="indx"><b>Seneca’s</b> views on gout, <a href="#Page_5">5</a></li> - -<li class="indx"><b>Septic</b> conditions confounded with gout, <a href="#Page_191">191</a></li> - -<li class="indx"><b>Serapion’s</b> views on gout, <a href="#Page_6">6</a></li> - -<li class="indx"><b>Serous</b> membranes, uratic deposits in, in nephritis, <a href="#Page_128">128</a></li> - -<li class="indx"><b>Sex</b> incidence in gout, <a href="#Page_41">41</a></li> - -<li class="indx"><b>Shivering</b> at onset of acute paroxysm of gout, <a href="#Page_188">188</a></li> - -<li class="indx"><b>Sidonal</b> in treatment of acute gout, <a href="#Page_383">383</a></li> - -<li class="indx"><b>Silk</b> as underwear, <a href="#Page_421">421</a></li> - -<li class="indx"><b>Sinusitis</b>, latent, cause of systemic infections, <a href="#Page_331">331</a></li> - -<li class="indx"><b>Skiagraphy</b> in diagnosis of gout, <a href="#Page_286">286</a></li> -<li class="isub1">in diagnosis of villous synovitis, <a href="#Page_281">281</a></li> -<li class="isub1">in differential diagnosis of hypertrophic or osteo-arthritis, <a href="#Page_291">291</a></li> -<li class="isub1">in differential diagnosis of infective arthritis, <a href="#Page_290">290</a></li> -<li class="isub1">in differential diagnosis of rheumatoid or atrophic gout, <a href="#Page_291">291</a></li> - -<li class="indx"><b>Skin</b>, action of, consideration of, in treatment of gout, <a href="#Page_337">337</a></li> -<li class="isub1">appearances of, and gout, <a href="#Page_45">45</a></li> -<li class="isub1">defective elimination by, in chronic gout, treatment of, <a href="#Page_400">400</a></li> - -<li class="indx"><b>Sodium</b> biurate crystals in synovia, <a href="#Page_52">52</a></li> -<li class="isub1">ions in lymph stream, <a href="#Page_146">146</a></li> -<li class="isub1">mono-urate compound, <a href="#Page_81">81</a></li> -<li class="isub1">salicylates of, in treatment of acute gout, <a href="#Page_382">382</a></li> - -<li class="indx"><b>Sole</b>, gout in, <a href="#Page_265">265</a></li> - -<li class="indx"><b>Solubilities</b> of uric acid and urates in gouty blood, <a href="#Page_82">82</a></li> - -<li class="indx"><b>Sool-Bader</b> baths, <a href="#Page_427">427</a></li> - -<li class="indx"><b>Spa</b>, choice of, in treatment of gout, <a href="#Page_440">440</a></li> -<li class="isub1">treatment, duration of course of, <a href="#Page_453">453</a></li> -<li class="isub2">in acute gout, <a href="#Page_385">385</a></li> -<li class="isub2">of gout, principles of, <a href="#Page_434">434</a></li> -<li class="isub2">remarks on, <a href="#Page_452">452</a></li> - -<li class="indx"><b>Spas</b> from a national aspect, <a href="#Page_454">454</a></li> - -<li class="indx"><b>Spermatozoa</b>, Miescher’s researches in, <a href="#Page_72">72</a></li> - -<li class="indx"><b>Spirits</b> in gout, <a href="#Page_370">370</a></li> - -<li class="indx"><b>Spleen</b>, enlargement of, in gout, <a href="#Page_190">190</a></li> -<li class="isub1">enzymes in, <a href="#Page_99">99</a></li> -<li class="isub1">functional efficiency of, tests for, <a href="#Page_338">338</a></li> - -<li class="indx"><b>Starchy</b> foods in diet of gouty, <a href="#Page_347">347</a></li> - -<li class="indx"><b>Static</b> foot deformities, differential diagnosis from gout, <a href="#Page_261">261</a></li> - -<li class="indx"><b>Stone</b> in Norfolk, <a href="#Page_29">29</a></li> - -<li class="indx"><b>Streptococci</b> in tonsils, <a href="#Page_183">183</a></li> - -<li class="indx"><b>Sub-infection</b> theory of gout, <a href="#Page_182">182</a>, <a href="#Page_183">183</a></li> - -<li class="indx"><b>Sub-thermal</b> baths, <a href="#Page_428">428</a></li> - -<li class="indx"><b>Succus</b> entericus, action on nucleic acid, <a href="#Page_100">100</a></li> - -<li class="indx"><b>Sugar</b> in diet of gouty, <a href="#Page_347">347</a></li> - -<li class="indx"><b>Sulphated</b> alkaline waters, spas for, <a href="#Page_442">442</a></li> -<li class="isub1">waters, <a href="#Page_441">441</a>, <a href="#Page_442">442</a></li> - -<li class="indx"><b>Sweetbreads</b> in diet of gouty, effect of, <a href="#Page_345">345</a>, <a href="#Page_346">346</a></li> - -<li class="indx"><b>Swine</b>, guanine gout in, <a href="#Page_100">100</a></li> - -<li class="indx"><b>Sydenham’s</b> differentiation of rheumatism from gout, <a href="#Page_15">15</a></li> -<li class="isub1">views on gout, <a href="#Page_7">7</a></li> - -<li class="indx"><b>Syncopes</b>, local, of hand, in gout, <a href="#Page_45">45</a></li> - -<li class="indx"><b>Synovia</b>, appearance in, in acute gout, <a href="#Page_52">52</a></li> - -<li class="indx"><b>Synovial</b> fluid, reaction of, <a href="#Page_52">52</a></li> - -<li class="indx"><b>Synovitis</b>, gouty, relation to local foci of infection, <a href="#Page_185">185</a></li> -<li class="isub1">gummatous, differential diagnosis from chronic articular gout, <a href="#Page_277">277</a></li> -<li class="isub1">of knees, differential diagnosis from gout, <a href="#Page_264">264</a></li> -<li class="isub1">of tendo Achilles in referred pain in heel, <a href="#Page_265">265</a></li> -<li class="isub1">perforative, <a href="#Page_57">57</a></li> -<li class="isub1">villous, chronic, confusion with chronic gout, <a href="#Page_279">279</a></li> -<li class="isub2">clinical symptoms of, <a href="#Page_280">280</a></li> -<li class="isub2">static and non-gouty in origin, <a href="#Page_280">280</a></li> - -<li class="indx"><b>Synthetic</b> formation as source of uric acid, <a href="#Page_84">84</a></li> -<li class="isub1">of uric acid, <a href="#Page_96">96</a></li> - -<li class="indx"><b>Syphilis</b>, articular, muscular and nerve lesions associated with, <a href="#Page_194">194</a></li> - -<li class="indx"><b>Syphilitic</b> arthritis, secondary, differential diagnosis from acute gouty polyarthritis, <a href="#Page_271">271</a></li> -<li class="isub1">disease of tarsal joints, differential diagnosis from gout, <a href="#Page_263">263</a></li> - -<li class="ifrst"><b>Taka-diastase</b>, <a href="#Page_392">392</a></li> - -<li class="indx"><b>Tarsal</b> joints, gonococcal arthritis of, differential diagnosis from gout, <a href="#Page_263">263</a></li> -<li class="isub1">involved in gouty polyarthritis, <a href="#Page_214">214</a></li> -<li class="isub1">tuberculous and syphilitic disease of, differential diagnosis from gout, <a href="#Page_263">263</a></li> - -<li class="indx"><b>Tartareous</b> nature of tophi, views on, <a href="#Page_8">8</a></li> - -<li class="indx"><b>Tea</b> as beverage in gout, <a href="#Page_361">361</a></li> - -<li class="indx"><b>Teeth</b>, characteristic, in gout, <a href="#Page_45">45</a></li> -<li class="isub1">conditions in gout, <a href="#Page_178">178</a></li> -<li class="isub1">devitalised, examination of, in treatment of gout, <a href="#Page_328">328</a></li> -<li class="isub1">foci of infection, <a href="#Page_53">53</a></li> - -<li class="indx"><b>Temperament</b>, and gout, <a href="#Page_44">44</a></li> - -<li class="indx"><b>Temperature</b> curve of gout, <a href="#Page_188">188</a></li> - -<li class="indx"><b>Tendo</b> Achilles, involved in gout, <a href="#Page_215">215</a></li> - -<li class="indx"><span class="pagenum"><a id="Page_468"></a>[468]</span><b>Tendon</b> sheaths, involved in gout, <a href="#Page_195">195</a></li> - -<li class="indx"><b>Tendons</b>, gouty polyarthritis in, <a href="#Page_214">214</a></li> -<li class="isub1">uratic deposits in, <a href="#Page_153">153</a></li> - -<li class="indx"><b>Test</b> meals for HCL variations, <a href="#Page_336">336</a></li> - -<li class="indx"><b>Tests</b>, modern, for uric acid determination, disabilities of, <a href="#Page_147">147</a></li> - -<li class="indx"><b>Theobromine</b>, <a href="#Page_85">85</a></li> - -<li class="indx"><b>Theophyllin</b>, <a href="#Page_85">85</a></li> - -<li class="indx"><b>Throat</b>, gouty, <a href="#Page_45">45</a></li> - -<li class="indx"><b>Thymine</b>, <a href="#Page_98">98</a></li> - -<li class="indx"><b>Thyminic</b> acid, <a href="#Page_80">80</a></li> -<li class="isub1">in treatment of acute gout, <a href="#Page_383">383</a></li> - -<li class="indx"><b>Thymus</b>, enzymes in, <a href="#Page_99">99</a></li> -<li class="isub1">gland, nucleic acid derived from, <a href="#Page_98">98</a></li> -<li class="isub1">in diet of gouty patients, effect of, <a href="#Page_345">345</a>, <a href="#Page_346">346</a></li> - -<li class="indx"><b>Tibia</b>, tophi in skin over, <a href="#Page_235">235</a></li> - -<li class="indx"><b>Tissue</b> affinities for uric acid, <a href="#Page_157">157</a></li> -<li class="isub1">protein, <a href="#Page_59">59</a></li> - -<li class="indx"><b>Tissues</b>, human, concentrations of uric acid in, <a href="#Page_159">159</a></li> -<li class="isub1">retention capacity of, for uric acid, <a href="#Page_158">158</a></li> -<li class="isub2">effect on blood content, <a href="#Page_138">138</a></li> - -<li class="indx"><b>Toe</b>, big, gout in, differential diagnosis of, <a href="#Page_259">259</a></li> -<li class="isub1">initial outbreak of gout in, <a href="#Page_37">37</a>, <a href="#Page_188">188</a></li> - -<li class="indx"><b>Tonsil</b>, site of infection in gout, <a href="#Page_180">180</a></li> - -<li class="indx"><b>Tonsillar</b> sepsis, gout and, <a href="#Page_178">178</a></li> - -<li class="indx"><b>Tonsillitis</b>, acute, gout following, <a href="#Page_53">53</a></li> -<li class="isub1">in gouty subjects, <a href="#Page_179">179</a></li> -<li class="isub1">treatment of, in gout, <a href="#Page_330">330</a></li> - -<li class="indx"><b>Tonsils</b>, examination of, in diagnosis of articular gout, <a href="#Page_249">249</a></li> -<li class="isub1">foci of infection, <a href="#Page_53">53</a></li> -<li class="isub1">streptococci in, <a href="#Page_183">183</a></li> - -<li class="indx"><b>Tophaceous</b> deposits in chronic articular gout, <a href="#Page_227">227</a></li> -<li class="isub1">gout, <a href="#Page_39">39</a></li> - -<li class="indx"><b>Tophi</b>, analysis of, <a href="#Page_150">150</a></li> -<li class="isub1">antedating articular attacks, <a href="#Page_202">202</a></li> -<li class="isub1">auricular, <a href="#Page_202">202</a></li> -<li class="isub2">pain in, <a href="#Page_233">233</a></li> -<li class="isub1">clinical evolution of, <a href="#Page_162">162</a></li> -<li class="isub1">constitution of, <a href="#Page_149">149</a></li> -<li class="isub1">constitutional influences in, <a href="#Page_161">161</a></li> -<li class="isub1">diagnostic status of, <a href="#Page_252">252</a></li> -<li class="isub1">difficulty in detecting, <a href="#Page_256">256</a></li> -<li class="isub1">early stages of, confused with chilblains, <a href="#Page_164">164</a></li> -<li class="isub1">early views as to nature of, <a href="#Page_7">7</a></li> -<li class="isub1">evolution and distribution of, <a href="#Page_231">231</a></li> -<li class="isub1">formation preceding arthritic attacks, <a href="#Page_164">164</a></li> -<li class="isub1">frequency of, in gouty arthritis, <a href="#Page_255">255</a></li> -<li class="isub1">gouty, causation of, <a href="#Page_154">154</a></li> -<li class="isub2">formation of, <a href="#Page_151">151</a></li> -<li class="isub2">localisation of, <a href="#Page_153">153</a></li> -<li class="isub2">radiating, concentric and laminated structure of, <a href="#Page_152">152</a></li> -<li class="isub2">urate of soda, <a href="#Page_150">150</a></li> -<li class="isub1">importance of, in diagnosis of acute gouty polyarthritis, <a href="#Page_269">269</a></li> -<li class="isub1">in diagnosis of gout, <a href="#Page_38">38</a></li> -<li class="isub1">in eyes, significance of, <a href="#Page_311">311</a></li> -<li class="isub1">inflammatory nature of swellings in, <a href="#Page_163">163</a></li> -<li class="isub1">in relation to arthritis, <a href="#Page_254">254</a></li> -<li class="isub1">in relation to uricæmia, <a href="#Page_155">155</a></li> -<li class="isub1">sites of, <a href="#Page_233">233</a></li> -<li class="isub1">stage of small red swellings, <a href="#Page_163">163</a></li> -<li class="isub1">treatment of, in chronic articular gout, <a href="#Page_407">407</a></li> - -<li class="indx"><b>Tophus</b> formation in acute gout, <a href="#Page_212">212</a></li> -<li class="isub2">premonitory symptoms of, <a href="#Page_203">203</a></li> -<li class="isub1">in ear, sign of gout, <a href="#Page_202">202</a></li> - -<li class="indx"><b>Trauma</b>, local, effect on gout, <a href="#Page_53">53</a></li> - -<li class="indx"><b>Traumatic</b> lesions, differential diagnosis from gout, <a href="#Page_260">260</a></li> - -<li class="indx"><b>Trousseau’s</b> views on gout, <a href="#Page_36">36</a></li> - -<li class="indx"><b>Tuberculous</b> disease of tarsal joints, differential diagnosis from gout, <a href="#Page_263">263</a></li> -<li class="isub1">joint disease, differential diagnosis from chronic articular gout, <a href="#Page_277">277</a></li> - -<li class="indx"><b>Toxæmia</b>, alimentary, hydrochloric acid, <a href="#Page_394">394</a></li> -<li class="isub1">chronic, <a href="#Page_182">182</a></li> - -<li class="indx"><b>Toxicity</b>, low, of chemical products, in gout, <a href="#Page_69">69</a></li> -<li class="isub1">non-, of uric acid, <a href="#Page_166">166</a></li> - -<li class="ifrst"><b>Ulna</b>, tophi in skin over, <a href="#Page_235">235</a></li> - -<li class="indx"><b>Uracil</b>, <a href="#Page_98">98</a></li> - -<li class="indx"><b>Urate</b> of soda in gouty tophi, <a href="#Page_150">150</a></li> - -<li class="indx"><b>Urates</b>, deposition of, in eye, <a href="#Page_309">309</a></li> - -<li class="indx"><b>Uratic</b> depositions as criterion of gout, <a href="#Page_37">37</a></li> -<li class="isub1">deposits in gout, <a href="#Page_54">54</a></li> -<li class="isub2">in gout and nephritis, differentiation of, <a href="#Page_129">129</a></li> -<li class="isub2">in gout, localisation of, <a href="#Page_153">153</a></li> -<li class="isub2">in nephritis, <a href="#Page_128">128</a></li> - -<li class="indx"><b>Uratosis</b> in gout, <a href="#Page_149">149</a></li> - -<li class="indx"><b>Urea</b> and glycocine, interaction between, <a href="#Page_84">84</a></li> -<li class="isub1">end-product of protein metabolism, <a href="#Page_63">63</a></li> -<li class="isub1">excretion in gout, <a href="#Page_66">66</a></li> -<li class="isub1">excretion of ammonia as, <a href="#Page_63">63</a></li> -<li class="isub1">formation of, <a href="#Page_62">62</a></li> -<li class="isub2">Folin and Denis’s deductions, <a href="#Page_64">64</a></li> -<li class="isub2">seat of, <a href="#Page_63">63</a></li> -<li class="isub1">in blood in gout and nephritis (table), <a href="#Page_121">121</a></li> - -<li class="indx"><b>Ureters</b>, ligature of, <a href="#Page_26">26</a></li> - -<li class="indx"><b>Uric</b> acid, <a href="#Page_75">75</a>, <a href="#Page_77">77</a></li> -<li class="isub1">a normal constituent in blood, <a href="#Page_135">135</a></li> -<li class="isub1">an end-product, <a href="#Page_70">70</a></li> -<li class="isub1">as a derivative of nucleic acid, <a href="#Page_73">73</a></li> -<li class="isub1">blood content of, in various animals, <a href="#Page_135">135</a></li> -<li class="isub2">variations independently of diet, <a href="#Page_142">142</a></li> -<li class="isub1">chemical constitution of, <a href="#Page_75">75</a></li> -<li class="isub1">concentrations in human tissues, <a href="#Page_159">159</a></li> -<li class="isub1">content of blood and attacks of gout, relation between, <a href="#Page_143">143</a></li> -<li class="isub2">in gout, <a href="#Page_139">139</a></li> -<li class="isub1">deposition of, <a href="#Page_22">22</a>, <a href="#Page_34">34</a></li> -<li class="isub1">destruction of, <a href="#Page_98">98</a>, <a href="#Page_104">104</a></li> -<li class="isub1">determination of, disabilities of modern tests, <a href="#Page_147">147</a></li> -<li class="isub1">diathesis, <a href="#Page_294">294</a>, <a href="#Page_295">295</a></li> -<li class="isub1">discovery of, by Scheele, <a href="#Page_8">8</a></li> -<li class="isub1">estimation of, sources of fallacy, <a href="#Page_145">145</a></li> -<li class="isub1">excretions of, amount of, <a href="#Page_75">75</a></li> -<li class="isub2">exogenous, <a href="#Page_85">85</a></li> -<li class="isub2">in acute gout, <a href="#Page_211">211</a></li> -<li class="isub2">in gout, <a href="#Page_108">108</a></li> -<li class="isub3">anomalies in, <a href="#Page_117">117</a></li> -<li class="isub2">increased by radium emanation, <a href="#Page_437">437</a></li> -<li class="isub2">relation of leucocytosis to, <a href="#Page_95">95</a></li> -<li class="isub1"><span class="pagenum"><a id="Page_469"></a>[469]</span>exogenous purins as source of, <a href="#Page_84">84</a></li> -<li class="isub1">formation of, Amberg and Jones’s scheme of, <a href="#Page_103">103</a>, <a href="#Page_104">104</a></li> -<li class="isub2">from nucleic acid, <a href="#Page_98">98</a></li> -<li class="isub1">gravel, spa treatment of, <a href="#Page_451">451</a></li> -<li class="isub1">in the blood, <a href="#Page_78">78</a></li> -<li class="isub2">forms of, <a href="#Page_145">145</a></li> -<li class="isub2">in gout and nephritis (table), <a href="#Page_121">121</a></li> -<li class="isub2">of gouty patients, discovery of, <a href="#Page_21">21</a></li> -<li class="isub2">organic combinations of, <a href="#Page_79">79</a></li> -<li class="isub1">infarcts, renal, <a href="#Page_151">151</a></li> -<li class="isub1">in relation to gout, <a href="#Page_107">107</a></li> -<li class="isub1">isomeric forms of, <a href="#Page_81">81</a></li> -<li class="isub1">kidney capacity for eliminating, <a href="#Page_125">125</a></li> -<li class="isub1">metabolism, influence of radium emanations on, <a href="#Page_436">436</a></li> -<li class="isub1">non-toxicity of, <a href="#Page_166">166</a></li> -<li class="isub1">of blood in disease (table), <a href="#Page_137">137</a></li> -<li class="isub1">output, endogenous, lowered, <a href="#Page_111">111</a></li> -<li class="isub2">exogenous, retarded, <a href="#Page_109">109</a></li> -<li class="isub1">physical properties of, <a href="#Page_78">78</a></li> -<li class="isub1">retention, capacity of tissues for, <a href="#Page_158">158</a></li> -<li class="isub1">solubilities of, <a href="#Page_154">154</a></li> -<li class="isub1">sources of, <a href="#Page_83">83</a></li> -<li class="isub1">synthetic formation of, <a href="#Page_84">84</a>, <a href="#Page_96">96</a></li> -<li class="isub1">theory of gout, <a href="#Page_21">21</a></li> -<li class="isub1">tissue affinities for, <a href="#Page_157">157</a></li> -<li class="isub1">variations in acute gout, <a href="#Page_108">108</a></li> -<li class="isub1">variations in chronic gout, <a href="#Page_109">109</a></li> -<li class="isub1">Wollaston’s researches on, <a href="#Page_8">8</a></li> - -<li class="indx"><b>Uric-acidæmia</b>, <a href="#Page_295">295</a></li> - -<li class="indx"><b>Uricæmia</b> and gout, <a href="#Page_125">125</a></li> -<li class="isub1">in gout, <a href="#Page_133">133</a></li> -<li class="isub1">in nephritis, <a href="#Page_120">120</a></li> -<li class="isub1">not cause, but result, of gout, <a href="#Page_148">148</a></li> -<li class="isub1">not necessarily due to renal defect, <a href="#Page_123">123</a></li> -<li class="isub1">not peculiar to nephritis, <a href="#Page_124">124</a></li> -<li class="isub1">significance of, <a href="#Page_145">145</a></li> -<li class="isub1">tophi in relation to, <a href="#Page_155">155</a></li> - -<li class="indx"><b>Uricase</b>, <a href="#Page_87">87</a>, <a href="#Page_104">104</a></li> -<li class="isub1">absence of, in man, <a href="#Page_104">104</a></li> - -<li class="indx"><b>Uricolysis</b>, <a href="#Page_104">104</a></li> - -<li class="indx"><b>Uricolytic</b> enzyme, <a href="#Page_105">105</a></li> -<li class="isub1">ferment, absence or diminution of, <a href="#Page_106">106</a></li> - -<li class="indx"><b>Urine</b>, alkapton in, <a href="#Page_59">59</a></li> -<li class="isub1">analysis of, in metabolism of gout, <a href="#Page_113">113</a></li> -<li class="isub2">in treatment of gout, <a href="#Page_337">337</a></li> -<li class="isub1">children’s, creatine in, <a href="#Page_68">68</a></li> -<li class="isub1">cystin in, <a href="#Page_59">59</a></li> -<li class="isub1">effects of guaiacum resin on, <a href="#Page_405">405</a></li> -<li class="isub1">examination of, in diagnosis of articular gout, <a href="#Page_250">250</a></li> -<li class="isub1">gouty, glyoxylic acid in, <a href="#Page_65">65</a></li> -<li class="isub1">human, daily excretion of uric acid, amount of, <a href="#Page_83">83</a></li> -<li class="isub1">scanty, before paroxysm of gout, <a href="#Page_205">205</a></li> - -<li class="indx"><b>Urosin</b> in treatment of acute gout, <a href="#Page_383">383</a></li> - -<li class="ifrst"><b>Vaccine</b> therapy in treatment of gout, <a href="#Page_331">331</a></li> - -<li class="indx"><b>Vapour</b> baths, <a href="#Page_428">428</a></li> - -<li class="indx"><b>Vegetable</b> cells, nucleic acid derived from, <a href="#Page_98">98</a></li> - -<li class="indx"><b>Vegetables</b> in diet of gouty, <a href="#Page_348">348</a></li> - -<li class="indx"><b>Veins</b>, engorged, before paroxysm of gout, <a href="#Page_205">205</a></li> - -<li class="indx"><b>Venesection</b>, <a href="#Page_4">4</a></li> -<li class="isub1">gout following, <a href="#Page_178">178</a></li> - -<li class="indx"><b>Vichy</b> bath, <a href="#Page_428">428</a></li> - -<li class="indx"><b>Vidal’s</b> atrophic form of arthritis deformans, <a href="#Page_18">18</a></li> - -<li class="indx"><b>Vinegar</b> in diet of gouty, <a href="#Page_350">350</a></li> - -<li class="indx"><b>Viscera</b>, functional capacity of, tests of, <a href="#Page_338">338</a></li> - -<li class="indx"><b>Visceral</b> organs, tendency to fibrosis in gout, <a href="#Page_186">186</a></li> - -<li class="indx"><b>Vitamines</b>, <a href="#Page_340">340</a></li> - -<li class="indx"><b>Volumetric</b> method of determination of uric acid in blood (Curtman and Lehrman), <a href="#Page_134">134</a></li> - -<li class="indx"><b>Vomiting</b> in acute paroxysms of gout, <a href="#Page_333">333</a></li> - -<li class="ifrst"><b>Wade’s</b> theory of nervous origin of gout, <a href="#Page_32">32</a></li> - -<li class="indx"><b>Water</b>, hot, advantages of, <a href="#Page_360">360</a></li> -<li class="isub1">value of, as beverage in gout, <a href="#Page_359">359</a></li> - -<li class="indx">“<b>Water-soluble B</b>,” <a href="#Page_340">340</a></li> - -<li class="indx">“<b>Water-soluble C</b>,” <a href="#Page_340">340</a></li> - -<li class="indx"><b>Watson’s</b> (Chalmers) researches on gout, <a href="#Page_107">107</a>, <a href="#Page_172">172</a></li> - -<li class="indx"><b>Weir-Mitchell</b> method in reduction of obesity, <a href="#Page_357">357</a></li> - -<li class="indx"><b>Whisky</b> in gout, <a href="#Page_364">364</a>, <a href="#Page_370">370</a></li> - -<li class="indx"><b>Wines</b> as beverages in gout, <a href="#Page_364">364</a></li> -<li class="isub1">general rules, <a href="#Page_367">367</a></li> -<li class="isub1">individual and, <a href="#Page_365">365</a></li> -<li class="isub1">importance of quality of, <a href="#Page_366">366</a></li> - -<li class="indx"><b>Wollaston’s</b> researches on uric acid, <a href="#Page_8">8</a></li> - -<li class="indx"><b>Wrist</b>, site of primary attack of gout, <a href="#Page_267">267</a></li> - -<li class="ifrst"><b>Xanthine</b>, <a href="#Page_75">75</a>, <a href="#Page_77">77</a></li> - -<li class="indx"><b>Xanthine-oxidase</b>, <a href="#Page_99">99</a></li> - -<li class="indx"><b>Xanthosine-hydrolase</b>, <a href="#Page_102">102</a></li> - -<li class="indx"><b>X-ray</b> examination of alimentary tract in treatment of gout, <a href="#Page_336">336</a></li> - -<li class="ifrst"><b>Yeast</b>, nucleic acid derived from, <a href="#Page_98">98</a></li> - -</ul> - -<p class="titlepage">THE WHITEFRIARS PRESS, LTD., PRINTERS, LONDON AND TONBRIDGE.</p> - -<div style='display:block; margin-top:4em'>*** END OF THE PROJECT GUTENBERG EBOOK GOUT ***</div> -<div style='text-align:left'> - -<div style='display:block; margin:1em 0'> -Updated editions will replace the previous one—the old editions will -be renamed. -</div> - -<div style='display:block; margin:1em 0'> -Creating the works from print editions not protected by U.S. copyright -law means that no one owns a United States copyright in these works, -so the Foundation (and you!) can copy and distribute it in the United -States without permission and without paying copyright -royalties. Special rules, set forth in the General Terms of Use part -of this license, apply to copying and distributing Project -Gutenberg™ electronic works to protect the PROJECT GUTENBERG™ -concept and trademark. Project Gutenberg is a registered trademark, -and may not be used if you charge for an eBook, except by following -the terms of the trademark license, including paying royalties for use -of the Project Gutenberg trademark. If you do not charge anything for -copies of this eBook, complying with the trademark license is very -easy. You may use this eBook for nearly any purpose such as creation -of derivative works, reports, performances and research. Project -Gutenberg eBooks may be modified and printed and given away—you may -do practically ANYTHING in the United States with eBooks not protected -by U.S. copyright law. Redistribution is subject to the trademark -license, especially commercial redistribution. -</div> - -<div style='margin-top:1em; font-size:1.1em; text-align:center'>START: FULL LICENSE</div> -<div style='text-align:center;font-size:0.9em'>THE FULL PROJECT GUTENBERG LICENSE</div> -<div style='text-align:center;font-size:0.9em'>PLEASE READ THIS BEFORE YOU DISTRIBUTE OR USE THIS WORK</div> - -<div style='display:block; margin:1em 0'> -To protect the Project Gutenberg™ mission of promoting the free -distribution of electronic works, by using or distributing this work -(or any other work associated in any way with the phrase “Project -Gutenberg”), you agree to comply with all the terms of the Full -Project Gutenberg™ License available with this file or online at -www.gutenberg.org/license. -</div> - -<div style='display:block; font-size:1.1em; margin:1em 0; font-weight:bold'> -Section 1. General Terms of Use and Redistributing Project Gutenberg™ electronic works -</div> - -<div style='display:block; margin:1em 0'> -1.A. By reading or using any part of this Project Gutenberg™ -electronic work, you indicate that you have read, understand, agree to -and accept all the terms of this license and intellectual property -(trademark/copyright) agreement. If you do not agree to abide by all -the terms of this agreement, you must cease using and return or -destroy all copies of Project Gutenberg™ electronic works in your -possession. If you paid a fee for obtaining a copy of or access to a -Project Gutenberg™ electronic work and you do not agree to be bound -by the terms of this agreement, you may obtain a refund from the person -or entity to whom you paid the fee as set forth in paragraph 1.E.8. -</div> - -<div style='display:block; margin:1em 0'> -1.B. “Project Gutenberg” is a registered trademark. It may only be -used on or associated in any way with an electronic work by people who -agree to be bound by the terms of this agreement. There are a few -things that you can do with most Project Gutenberg™ electronic works -even without complying with the full terms of this agreement. See -paragraph 1.C below. There are a lot of things you can do with Project -Gutenberg™ electronic works if you follow the terms of this -agreement and help preserve free future access to Project Gutenberg™ -electronic works. See paragraph 1.E below. -</div> - -<div style='display:block; margin:1em 0'> -1.C. The Project Gutenberg Literary Archive Foundation (“the -Foundation” or PGLAF), owns a compilation copyright in the collection -of Project Gutenberg™ electronic works. Nearly all the individual -works in the collection are in the public domain in the United -States. If an individual work is unprotected by copyright law in the -United States and you are located in the United States, we do not -claim a right to prevent you from copying, distributing, performing, -displaying or creating derivative works based on the work as long as -all references to Project Gutenberg are removed. Of course, we hope -that you will support the Project Gutenberg™ mission of promoting -free access to electronic works by freely sharing Project Gutenberg™ -works in compliance with the terms of this agreement for keeping the -Project Gutenberg™ name associated with the work. You can easily -comply with the terms of this agreement by keeping this work in the -same format with its attached full Project Gutenberg™ License when -you share it without charge with others. -</div> - -<div style='display:block; margin:1em 0'> -1.D. The copyright laws of the place where you are located also govern -what you can do with this work. Copyright laws in most countries are -in a constant state of change. If you are outside the United States, -check the laws of your country in addition to the terms of this -agreement before downloading, copying, displaying, performing, -distributing or creating derivative works based on this work or any -other Project Gutenberg™ work. The Foundation makes no -representations concerning the copyright status of any work in any -country other than the United States. -</div> - -<div style='display:block; margin:1em 0'> -1.E. Unless you have removed all references to Project Gutenberg: -</div> - -<div style='display:block; margin:1em 0'> -1.E.1. The following sentence, with active links to, or other -immediate access to, the full Project Gutenberg™ License must appear -prominently whenever any copy of a Project Gutenberg™ work (any work -on which the phrase “Project Gutenberg” appears, or with which the -phrase “Project Gutenberg” is associated) is accessed, displayed, -performed, viewed, copied or distributed: -</div> - -<blockquote> - <div style='display:block; margin:1em 0'> - This eBook is for the use of anyone anywhere in the United States and most - other parts of the world at no cost and with almost no restrictions - whatsoever. You may copy it, give it away or re-use it under the terms - of the Project Gutenberg License included with this eBook or online - at <a href="https://www.gutenberg.org">www.gutenberg.org</a>. If you - are not located in the United States, you will have to check the laws - of the country where you are located before using this eBook. - </div> -</blockquote> - -<div style='display:block; margin:1em 0'> -1.E.2. If an individual Project Gutenberg™ electronic work is -derived from texts not protected by U.S. copyright law (does not -contain a notice indicating that it is posted with permission of the -copyright holder), the work can be copied and distributed to anyone in -the United States without paying any fees or charges. If you are -redistributing or providing access to a work with the phrase “Project -Gutenberg” associated with or appearing on the work, you must comply -either with the requirements of paragraphs 1.E.1 through 1.E.7 or -obtain permission for the use of the work and the Project Gutenberg™ -trademark as set forth in paragraphs 1.E.8 or 1.E.9. -</div> - -<div style='display:block; margin:1em 0'> -1.E.3. If an individual Project Gutenberg™ electronic work is posted -with the permission of the copyright holder, your use and distribution -must comply with both paragraphs 1.E.1 through 1.E.7 and any -additional terms imposed by the copyright holder. Additional terms -will be linked to the Project Gutenberg™ License for all works -posted with the permission of the copyright holder found at the -beginning of this work. -</div> - -<div style='display:block; margin:1em 0'> -1.E.4. Do not unlink or detach or remove the full Project Gutenberg™ -License terms from this work, or any files containing a part of this -work or any other work associated with Project Gutenberg™. -</div> - -<div style='display:block; margin:1em 0'> -1.E.5. Do not copy, display, perform, distribute or redistribute this -electronic work, or any part of this electronic work, without -prominently displaying the sentence set forth in paragraph 1.E.1 with -active links or immediate access to the full terms of the Project -Gutenberg™ License. -</div> - -<div style='display:block; margin:1em 0'> -1.E.6. You may convert to and distribute this work in any binary, -compressed, marked up, nonproprietary or proprietary form, including -any word processing or hypertext form. However, if you provide access -to or distribute copies of a Project Gutenberg™ work in a format -other than “Plain Vanilla ASCII” or other format used in the official -version posted on the official Project Gutenberg™ website -(www.gutenberg.org), you must, at no additional cost, fee or expense -to the user, provide a copy, a means of exporting a copy, or a means -of obtaining a copy upon request, of the work in its original “Plain -Vanilla ASCII” or other form. Any alternate format must include the -full Project Gutenberg™ License as specified in paragraph 1.E.1. -</div> - -<div style='display:block; margin:1em 0'> -1.E.7. Do not charge a fee for access to, viewing, displaying, -performing, copying or distributing any Project Gutenberg™ works -unless you comply with paragraph 1.E.8 or 1.E.9. -</div> - -<div style='display:block; margin:1em 0'> -1.E.8. You may charge a reasonable fee for copies of or providing -access to or distributing Project Gutenberg™ electronic works -provided that: -</div> - -<div style='margin-left:0.7em;'> - <div style='text-indent:-0.7em'> - • You pay a royalty fee of 20% of the gross profits you derive from - the use of Project Gutenberg™ works calculated using the method - you already use to calculate your applicable taxes. The fee is owed - to the owner of the Project Gutenberg™ trademark, but he has - agreed to donate royalties under this paragraph to the Project - Gutenberg Literary Archive Foundation. Royalty payments must be paid - within 60 days following each date on which you prepare (or are - legally required to prepare) your periodic tax returns. Royalty - payments should be clearly marked as such and sent to the Project - Gutenberg Literary Archive Foundation at the address specified in - Section 4, “Information about donations to the Project Gutenberg - Literary Archive Foundation.” - </div> - - <div style='text-indent:-0.7em'> - • You provide a full refund of any money paid by a user who notifies - you in writing (or by e-mail) within 30 days of receipt that s/he - does not agree to the terms of the full Project Gutenberg™ - License. You must require such a user to return or destroy all - copies of the works possessed in a physical medium and discontinue - all use of and all access to other copies of Project Gutenberg™ - works. - </div> - - <div style='text-indent:-0.7em'> - • You provide, in accordance with paragraph 1.F.3, a full refund of - any money paid for a work or a replacement copy, if a defect in the - electronic work is discovered and reported to you within 90 days of - receipt of the work. - </div> - - <div style='text-indent:-0.7em'> - • You comply with all other terms of this agreement for free - distribution of Project Gutenberg™ works. - </div> -</div> - -<div style='display:block; margin:1em 0'> -1.E.9. If you wish to charge a fee or distribute a Project -Gutenberg™ electronic work or group of works on different terms than -are set forth in this agreement, you must obtain permission in writing -from the Project Gutenberg Literary Archive Foundation, the manager of -the Project Gutenberg™ trademark. Contact the Foundation as set -forth in Section 3 below. -</div> - -<div style='display:block; margin:1em 0'> -1.F. -</div> - -<div style='display:block; margin:1em 0'> -1.F.1. Project Gutenberg volunteers and employees expend considerable -effort to identify, do copyright research on, transcribe and proofread -works not protected by U.S. copyright law in creating the Project -Gutenberg™ collection. Despite these efforts, Project Gutenberg™ -electronic works, and the medium on which they may be stored, may -contain “Defects,” such as, but not limited to, incomplete, inaccurate -or corrupt data, transcription errors, a copyright or other -intellectual property infringement, a defective or damaged disk or -other medium, a computer virus, or computer codes that damage or -cannot be read by your equipment. -</div> - -<div style='display:block; margin:1em 0'> -1.F.2. LIMITED WARRANTY, DISCLAIMER OF DAMAGES - Except for the “Right -of Replacement or Refund” described in paragraph 1.F.3, the Project -Gutenberg Literary Archive Foundation, the owner of the Project -Gutenberg™ trademark, and any other party distributing a Project -Gutenberg™ electronic work under this agreement, disclaim all -liability to you for damages, costs and expenses, including legal -fees. YOU AGREE THAT YOU HAVE NO REMEDIES FOR NEGLIGENCE, STRICT -LIABILITY, BREACH OF WARRANTY OR BREACH OF CONTRACT EXCEPT THOSE -PROVIDED IN PARAGRAPH 1.F.3. YOU AGREE THAT THE FOUNDATION, THE -TRADEMARK OWNER, AND ANY DISTRIBUTOR UNDER THIS AGREEMENT WILL NOT BE -LIABLE TO YOU FOR ACTUAL, DIRECT, INDIRECT, CONSEQUENTIAL, PUNITIVE OR -INCIDENTAL DAMAGES EVEN IF YOU GIVE NOTICE OF THE POSSIBILITY OF SUCH -DAMAGE. -</div> - -<div style='display:block; margin:1em 0'> -1.F.3. LIMITED RIGHT OF REPLACEMENT OR REFUND - If you discover a -defect in this electronic work within 90 days of receiving it, you can -receive a refund of the money (if any) you paid for it by sending a -written explanation to the person you received the work from. If you -received the work on a physical medium, you must return the medium -with your written explanation. The person or entity that provided you -with the defective work may elect to provide a replacement copy in -lieu of a refund. If you received the work electronically, the person -or entity providing it to you may choose to give you a second -opportunity to receive the work electronically in lieu of a refund. If -the second copy is also defective, you may demand a refund in writing -without further opportunities to fix the problem. -</div> - -<div style='display:block; margin:1em 0'> -1.F.4. Except for the limited right of replacement or refund set forth -in paragraph 1.F.3, this work is provided to you ‘AS-IS’, WITH NO -OTHER WARRANTIES OF ANY KIND, EXPRESS OR IMPLIED, INCLUDING BUT NOT -LIMITED TO WARRANTIES OF MERCHANTABILITY OR FITNESS FOR ANY PURPOSE. -</div> - -<div style='display:block; margin:1em 0'> -1.F.5. Some states do not allow disclaimers of certain implied -warranties or the exclusion or limitation of certain types of -damages. If any disclaimer or limitation set forth in this agreement -violates the law of the state applicable to this agreement, the -agreement shall be interpreted to make the maximum disclaimer or -limitation permitted by the applicable state law. The invalidity or -unenforceability of any provision of this agreement shall not void the -remaining provisions. -</div> - -<div style='display:block; margin:1em 0'> -1.F.6. INDEMNITY - You agree to indemnify and hold the Foundation, the -trademark owner, any agent or employee of the Foundation, anyone -providing copies of Project Gutenberg™ electronic works in -accordance with this agreement, and any volunteers associated with the -production, promotion and distribution of Project Gutenberg™ -electronic works, harmless from all liability, costs and expenses, -including legal fees, that arise directly or indirectly from any of -the following which you do or cause to occur: (a) distribution of this -or any Project Gutenberg™ work, (b) alteration, modification, or -additions or deletions to any Project Gutenberg™ work, and (c) any -Defect you cause. -</div> - -<div style='display:block; font-size:1.1em; margin:1em 0; font-weight:bold'> -Section 2. Information about the Mission of Project Gutenberg™ -</div> - -<div style='display:block; margin:1em 0'> -Project Gutenberg™ is synonymous with the free distribution of -electronic works in formats readable by the widest variety of -computers including obsolete, old, middle-aged and new computers. It -exists because of the efforts of hundreds of volunteers and donations -from people in all walks of life. -</div> - -<div style='display:block; margin:1em 0'> -Volunteers and financial support to provide volunteers with the -assistance they need are critical to reaching Project Gutenberg™’s -goals and ensuring that the Project Gutenberg™ collection will -remain freely available for generations to come. In 2001, the Project -Gutenberg Literary Archive Foundation was created to provide a secure -and permanent future for Project Gutenberg™ and future -generations. To learn more about the Project Gutenberg Literary -Archive Foundation and how your efforts and donations can help, see -Sections 3 and 4 and the Foundation information page at www.gutenberg.org. -</div> - -<div style='display:block; font-size:1.1em; margin:1em 0; font-weight:bold'> -Section 3. Information about the Project Gutenberg Literary Archive Foundation -</div> - -<div style='display:block; margin:1em 0'> -The Project Gutenberg Literary Archive Foundation is a non-profit -501(c)(3) educational corporation organized under the laws of the -state of Mississippi and granted tax exempt status by the Internal -Revenue Service. The Foundation’s EIN or federal tax identification -number is 64-6221541. Contributions to the Project Gutenberg Literary -Archive Foundation are tax deductible to the full extent permitted by -U.S. federal laws and your state’s laws. -</div> - -<div style='display:block; margin:1em 0'> -The Foundation’s business office is located at 809 North 1500 West, -Salt Lake City, UT 84116, (801) 596-1887. Email contact links and up -to date contact information can be found at the Foundation’s website -and official page at www.gutenberg.org/contact -</div> - -<div style='display:block; font-size:1.1em; margin:1em 0; font-weight:bold'> -Section 4. Information about Donations to the Project Gutenberg Literary Archive Foundation -</div> - -<div style='display:block; margin:1em 0'> -Project Gutenberg™ depends upon and cannot survive without widespread -public support and donations to carry out its mission of -increasing the number of public domain and licensed works that can be -freely distributed in machine-readable form accessible by the widest -array of equipment including outdated equipment. Many small donations -($1 to $5,000) are particularly important to maintaining tax exempt -status with the IRS. -</div> - -<div style='display:block; margin:1em 0'> -The Foundation is committed to complying with the laws regulating -charities and charitable donations in all 50 states of the United -States. Compliance requirements are not uniform and it takes a -considerable effort, much paperwork and many fees to meet and keep up -with these requirements. We do not solicit donations in locations -where we have not received written confirmation of compliance. To SEND -DONATIONS or determine the status of compliance for any particular state -visit <a href="https://www.gutenberg.org/donate/">www.gutenberg.org/donate</a>. -</div> - -<div style='display:block; margin:1em 0'> -While we cannot and do not solicit contributions from states where we -have not met the solicitation requirements, we know of no prohibition -against accepting unsolicited donations from donors in such states who -approach us with offers to donate. -</div> - -<div style='display:block; margin:1em 0'> -International donations are gratefully accepted, but we cannot make -any statements concerning tax treatment of donations received from -outside the United States. U.S. laws alone swamp our small staff. -</div> - -<div style='display:block; margin:1em 0'> -Please check the Project Gutenberg web pages for current donation -methods and addresses. Donations are accepted in a number of other -ways including checks, online payments and credit card donations. To -donate, please visit: www.gutenberg.org/donate -</div> - -<div style='display:block; font-size:1.1em; margin:1em 0; font-weight:bold'> -Section 5. General Information About Project Gutenberg™ electronic works -</div> - -<div style='display:block; margin:1em 0'> -Professor Michael S. Hart was the originator of the Project -Gutenberg™ concept of a library of electronic works that could be -freely shared with anyone. For forty years, he produced and -distributed Project Gutenberg™ eBooks with only a loose network of -volunteer support. -</div> - -<div style='display:block; margin:1em 0'> -Project Gutenberg™ eBooks are often created from several printed -editions, all of which are confirmed as not protected by copyright in -the U.S. unless a copyright notice is included. Thus, we do not -necessarily keep eBooks in compliance with any particular paper -edition. -</div> - -<div style='display:block; margin:1em 0'> -Most people start at our website which has the main PG search -facility: <a href="https://www.gutenberg.org">www.gutenberg.org</a>. -</div> - -<div style='display:block; margin:1em 0'> -This website includes information about Project Gutenberg™, -including how to make donations to the Project Gutenberg Literary -Archive Foundation, how to help produce our new eBooks, and how to -subscribe to our email newsletter to hear about new eBooks. -</div> - -</div> -</body> -</html> |