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diff --git a/old/69874-0.txt b/old/69874-0.txt deleted file mode 100644 index ac10a87..0000000 --- a/old/69874-0.txt +++ /dev/null @@ -1,24349 +0,0 @@ -The Project Gutenberg eBook of Gout, by Llewellyn Jones Llewellyn - -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 -www.gutenberg.org. 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. - -Title: Gout - With a section on ocular disease in the gouty by W. M. Beaumont - -Author: Llewellyn Jones Llewellyn - -Contributor: W. M. Beaumont - -Release Date: January 24, 2023 [eBook #69874] - -Language: English - -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) - -*** START OF THE PROJECT GUTENBERG EBOOK GOUT *** - - - - - - -[Illustration: GOUTY ARTHRITIS. - -Note large tuberous swellings on knuckle and metacarpo-phalangeal joints -due to uratic deposits.] - - - - - GOUT - - BY - LLEWELLYN JONES LLEWELLYN, M.B. Lond. - - GOVERNOR AND SENIOR PHYSICIAN, ROYAL MINERAL WATER HOSPITAL, - BATH; FELLOW OF ROYAL SOCIETY OF MEDICINE; AUTHOR OF - “ARTHRITIS DEFORMANS”; CO-AUTHOR OF “FIBROSITIS”; CO-AUTHOR - OF “MALINGERING, OR THE SIMULATION OF DISEASE”; CO-AUTHOR OF - “PENSIONS AND THE PRINCIPLES OF THEIR EVALUATION”; CONTRIBUTOR - TO LATHAM AND ENGLISH’S “SYSTEM OF TREATMENT,” ALSO TO “OXFORD - ENCYCLOPÆDIA OF TREATMENT” AND TO “STUDENT’S TEXT-BOOK OF - SURGERY.” - - WITH A SECTION ON - OCULAR DISEASE IN THE GOUTY - - BY - W. M. BEAUMONT - - CONSULTING OPHTHALMIC SURGEON TO THE SOUTH-WESTERN - REGION OF THE MINISTRY OF PENSIONS; AUTHOR OF “INJURIES - OF THE EYES OF THE UNEMPLOYED, PROBLEMS IN PROGNOSIS,” ETC. - - ST. LOUIS - C. V. MOSBY COMPANY - 1921 - - _Printed in Great Britain._ - - - - - Dedicated - TO - MY WIFE - - - - -PREFACE - - -“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? - -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. - -Of these the very corner-stones are _chemical physiology_ and _chemical -pathology_, 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. - -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.” - -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 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. - -_Uric acid_ has apparently failed us as the _causa causans_. 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 _non-toxic_. Albeit, though I hold this view, I do not for -one moment suggest that _uric acid_ has nothing whatever to do with gout. -The fact that _tophi_, its pathognomonic stigmata, are compounded of -_biurate of soda_, would _per se_ stamp such an attitude as untenable. On -the other hand, _uric acid_ must be viewed at its proper perspective as a -_concomitant_ or _sequel_ of _gouty inflammation_, the essential cause of -which must be sought elsewhere. - -“The old order changeth, giving place to new,” and 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 timeworn conception of “gouty” arthritis as of purely -_metabolic_ 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 _infective element_ in its genesis. - -The extreme frequency with which _infective foci_ are met with in the -victims of gout, the frequency, too, with which exacerbations of the -disorder are presaged by _acute glandular affections_ of undeniably -_infective_ 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 _excitants_ thereof. - -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 _non-gouty_ forms of arthritis? Do we not hold them each and all as -evidences of _infection_? and, we may well ask, why not in gout? - -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 _gout_. 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. - -The “gouty” throats, like the “gouty” teeth, should be regarded not as -symptomatic of gout, but _etiologically_ related thereto. We should cease -to talk of “gouty” throats, teeth, etc., should renounce the prefix, -for there is nothing _specific_ of _gout_ either in the tonsillar, -pharyngeal, or dental lesions. We should instead view these various local -disorders in their true perspective as _foci_ of _infection, causally_ -related to the subsequent and _secondary_ “gouty” arthritis. - -Similarly, when we come to analyse the component elements of an acute -paroxysm of gout, how strongly indicative of the intrusion of an -_infective_ element the following features: the onset, temperature curve, -character of local articular changes of the disorder, the presence of -_leucocytosis_, with secondary anæmia and enlargement of the lymphatic -glands! Again, how suggestive the occasional complication of acute -gout by _lymphangitis_ and _phlebitis_! 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 _infection_. - -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.e._, uratic deposits, -or _tophi_, 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 _mechanical_. - -The intrusion of some other factor, “something vital, something -biological,” seems essential for the elucidation of _uratosis_, -_i.e._, uratic deposition. For this, _not uricæmia_, 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 -_non-toxicity_ of _uric acid_, can we on this basis account for the -_inflammatory_ phenomena of the disorder! - -Now _inflammatory reaction_ is, I hold, an invariable _antecedent_ in all -gouty processes, whether of _articular_ or _ab-articular_ site. Granted -that inflammatory reaction is a necessary prelude, the 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. - -Now, as I believe, “gouty” subjects are _ab initio_ 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 _infections_ 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.” - -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. - -From the bio-chemical aspect I owe much to the researches of Walker Hall, -and to those of our American _confrères_ Folin, Denis, Benedict, Pratt, -McLeod, Walker Jones, Gideon Wells, etc. - -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. - -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 cordial thanks are due for the -skiagraphs contained in this work. - -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. - -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. - -Lastly, I would express my thanks to my publisher, Mr. Heinemann, for -much consideration and many courtesies. - - LL. J. LL. - -31, UPPER BROOK STREET, W. 1. - - - - -TABLE OF CONTENTS - - - CHAPTER I - - HISTORICAL AND INTRODUCTORY - - 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 _pp._ 1-13 - - CHAPTER II - - THE PEDIGREE OF GOUT - - 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 _pp._ 14-20 - - CHAPTER III - - EARLIER THEORIES OF PATHOGENESIS - - Garrod’s Theory. Antagonistic Views. Histogenous Theories. - Antecedent Structural Changes. Hepatic Inadequacy. - Hyperpyræmia. Nervous Theories. Growing Scepticism as to - Garrod’s Pathogeny of Gout _pp._ 21-34 - - CHAPTER IV - - DEFINITION, CLASSIFICATION, ETIOLOGY, AND MORBID ANATOMY - - 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 _pp._ 35-58 - - CHAPTER V - - PATHOLOGY OF GOUT-PROTEIN METABOLISM - - 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 _pp._ 59-70 - - CHAPTER VI - - NUCLEIN METABOLISM - - 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 _pp._ 71-82 - - CHAPTER VII - - SOURCES OF URIC ACID - - 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 _pp._ 83-97 - - CHAPTER VIII - - FORMATION AND DESTRUCTION OF URIC ACID - - Distribution of the Enzymes. Stages in Disruption of Nucleic - Acid. Destruction of Uric Acid _pp._ 98-106 - - CHAPTER IX - - URIC ACID IN RELATION TO GOUT - - 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 _pp._ 107-116 - - CHAPTER X - - THE RENAL THEORY OF GOUT - - 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 _pp._ 117-132 - - CHAPTER XI - - URICÆMIA IN GOUT - - 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 _pp._ 133-148 - - CHAPTER XII - - URATOSIS IN RELATION TO GOUT - - 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? _pp._ 149-170 - - CHAPTER XIII - - THE RISE OF THE INFECTIVE THEORY - - 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 _pp._ 171-176 - - CHAPTER XIV - - GOUT AS AN INFECTION - - Local Foci of Infection: Dental, Nasal, Pharyngeal, etc. - Gastro-intestinal Disorders. Variation in Free HCL. Intestinal - Disorders. Infection or Sub—infection _pp._ 177-187 - - CHAPTER XV - - GOUT AS AN INFECTION (_continued_) - - 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 _pp._ 188-199 - - CHAPTER XVI - - CLINICAL ACCOUNT - - 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 _pp._ 200-213 - - CHAPTER XVII - - CLINICAL ACCOUNT (_continued_) - - 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 _pp._ 214-224 - - CHAPTER XVIII - - CLINICAL ACCOUNT (_continued_) - - 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 _pp._ 225-246 - - CHAPTER XIX - - ETIOLOGICAL AND CLINICAL DIAGNOSIS. - - 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 _pp._ 247-257 - - CHAPTER XX - - CLINICAL DIAGNOSIS (_continued_) - - 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 _pp._ 258-267 - - CHAPTER XXI - - CLINICAL DIAGNOSIS (_continued_) - - 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 _pp._ 268-274 - - CHAPTER XXII - - CLINICAL DIAGNOSIS (_continued_) - - 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 _pp._ 275-285 - - CHAPTER XXIII - - CLINICAL DIAGNOSIS (_continued_) - - Skiagraphy. Significance of Local Areas of Rarefaction. The - Radiographic Types of Gouty Arthritis. Differential Diagnosis. - Infective Arthritis. Hypertrophic or Osteoarthritis. Rheumatoid - or Atrophic Arthritis _pp._ 286-292 - - CHAPTER XXIV - - IRREGULAR GOUT - - Historical Account. Murchison’s Views. Retrocedent Gout. Gout - in the Stomach. Cardiac and Cerebral Forms. Other Irregular - Manifestations. Conclusions. Infantile Gout _pp._ 293-307 - - CHAPTER XXV - - OCULAR DISEASE IN THE GOUTY - - 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 _pp._ 308-326 - - CHAPTER XXVI - - TREATMENT OF GOUT - - 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 _pp._ 327-341 - - CHAPTER XXVII - - TREATMENT OF GOUT (_continued_) - - Regulation of Diet in the Gouty. The Individual Foodstuffs, - Proteins, Carbohydrates, Fats, Vegetables, Fruits, Condiments. - Special Dietaries. Amylaceous Dyspepsia. Hyperchlorhydria _pp._ 342-371 - - CHAPTER XXVIII - - MEDICINAL AND OTHER MODES OF THERAPY—ACUTE GOUT - - 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 _pp._ 372-388 - - CHAPTER XXIX - - MEDICINAL AND OTHER MODES OF THERAPY - (_continued_)—INTER-PAROXYSMAL PERIOD - - Prophylactic Measures. Treatment of Atonic Dyspepsia. - Hyperacidity due to Organic Acids. Treatment of - Hypochlorhydria. Alkalies, Atophan, and Colchicum as - Prophylactics _pp._ 389-396 - - CHAPTER XXX - - MEDICINAL AND OTHER MODES OF THERAPY (_continued_)—CHRONIC - ARTICULAR GOUT AND ASSOCIATED MORBID CONDITIONS - - 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 _pp._ 397-417 - - CHAPTER XXXI - - CLIMATO-THERAPY, HYDRO-THERAPY, ETC. - - 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 _pp._ 418-430 - - CHAPTER XXXII - - MINERAL SPRINGS AND CHOICE OF SPA - - 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 _pp._ 431-465 - - INDEX _pp._ 457-469 - - - - - -CHAPTER I - -HISTORICAL AND INTRODUCTORY - - -THE ANTIQUITY OF GOUT - -“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. - -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.” - -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 _osteoarthritis_.[1] 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 later date, that the condition was recognised _clinically_, as a -joint disorder, distinct from others of the same category. - -Small call to marvel thereat, for how much more arresting the clinical -_facies_ 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. - -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.” - -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 _quâ_ Rendu “these are countries in which we cannot -survive unless we are frugal.” - -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. - - -PREVALENCE OF GOUT IN THE ANGLO-SAXON PERIOD - -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 of barbarism. It is frequently noticed by -the Anglo-Saxon historian, and the name assigned to it is Fot-adl.” - -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.” - -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.[2] 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. - - -VIEWS OF THE HUMORALISTS - -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 _topographical_ designation, terming the affection, _podagra_, -_chirargra_, etc., according as foot or hand was the seat of the -disorder, while for polyarticular types the generic term _arthritis_ was -invoked. - -Nevertheless the old Greek physicians had their views as to its -pathology. Thus the source of the peccant humours resided for them in the -_brain_, 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 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 _neural_ and _humoral_ factors. And now to consider briefly the -individual views of the fathers of medicine. - - -THE APHORISMS OF HIPPOCRATES - -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, _ante usum veneris_, while in females its -incidence is usually delayed until after the menopause. - -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. - -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. - - “Tollere nodosam nescit medicina podogram.” - - _Ovid_, _Ep. ex Pont._, I, 3, 23. - -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. - -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. - -Said the hero of the Trago-podagra: - - “Irritantibus me - Soleo occupere multo iracundior - His vero qui cogitant nihil adversum mihi - Benignam adhibeo mentem, facilisque fio.” - -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. - -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 _par excellence_. But, for the true nature -of the disease, he, with humility and piety, avows that its secret origin -is known only to the gods. - -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. - -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 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. - -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 _Colchicum variegatum_, of similar -properties to the _Colchicum autumnale_. - -Paulus Ægineta, like most of his _confrères_, 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. - -Nor will any historical _résumé_ 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. - - -INTRODUCTION OF THE WORD “GOUT” - -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. - -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 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 _confrères_ in this respect void of offence. - -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. - -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 _primæ viæ_ and in -the secondary assimilating organs. He refrained from speculating as to -the constitution of the _materia peccans_, but as Trousseau observes, “he -made his _morbi seminium_ 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.” - - -EARLY VIEWS AS TO THE NATURE OF TOPHI - - “Et tophus scaber, et nigris exesa chelydris Creta.” - - _Georg._, ii., 214. - -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.” - -Nevertheless, our contempt need be chastened when we recollect 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. - -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. - -But the later view, doubtless the reflex of _etiological_ hypotheses, -was that tophi were of _tartareous_ nature, closely similar to that -encrusting the interior of wine casks. Hoffmann declared that the -_materies morbi_ 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. - -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, _ergo_, 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.” - -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. - - -THE “HONOUR OF THE GOUT” - -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 _bonâ fide_ gout. Let but the _roturier_ 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! - -Statesmen, warriors, literary men and poets loom large amongst its -victims. Lord Burleigh suffered greatly therefrom, and good 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!”[3] - -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. - -“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.” - - “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. - - “Verbo dicam, articularis hicce morbus (quod vix de quovis alio - adfirmaveris) divites plures interemit quam pauperes, plures - sapientes quam fatuos.” - -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 temperate Faroe Islanders. In truth, -although “the taint may be hereditary, it may be generated by a low diet -and abstinence carried to extremes.” - - -THAT GOUT CONFERS IMMUNITY FROM OTHER DISORDERS - -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:— - - “Blessed Gout, most desirable Gout, Sovereign Antidote - Of murdering Maladies; powerful corrector of Intemperance; - Deign to visit me with thy purging Fires, and throw off the - Tophous Injury which I may have suffer’d by Wine and Wit, - Too hard for the Virtue of a Devotee upon a Holy Festival. - But fail not thy humble Supplicant, who needs thy - Friendly Help, to keep his tottering Tenement in - Order: Fail him not, every Vernal and Autumnal - Æquinox.” - -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:— - - “Yet am I better - Than one that’s sick o’ the Gout: since he had rather - Groan so in perpetuity, than be cur’d - By the sure physician, death: who is the key - To unbar these locks.” - - _Cymbeline._ - -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 -thousand years, and which has reached even the thrones of princes, -where the disease commonly shows itself, viz., that gout prolongs life -(_que la goutte prolonge la vie_). 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.” - -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. - -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 ... - - ‘Multæ formæ infortunatorum, - Meditatio pœnæ, et consuetudo, - Podagros miseros consolentur.’ - - _Lucian._ - -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.” - -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 _will_ 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 sweat of his brow, and the chance of his -being visited with gout will be very small.” - - “O fortunatos nimium, sua si bona norint - Agricolas!” - - _Georg._, ii., 458. - - -GROWING INFREQUENCY AND ATTENUATION OF GOUT - -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 _arthritic_ phenomena of the disease; for in -those remote ages little or no account seems to have been taken of its -_irregular_ or _ab-articular_ 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 _gout_ amongst the ancient Greeks and Romans was -probably over-estimated. - -Can it be questioned that a large percentage of the cases of gout in -those bygone times consisted of undifferentiated _infective_ forms of -_arthritis_. _Syphilis_ and _gonorrhœa_ must have existed then as now, -and their _specific_ forms of _arthritis_, how easily confused with “rich -man’s gout!” Surely too, they, like ourselves, must have suffered with -states of _oral sepsis_, _pyorrhœa alveolaris_, etc., not to speak of -_infective disorders_, with their correlated _arthritides_. In short, the -_differentiation_ 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. - -But passing to more recent times, there is little doubt that the -classical type of _podagra_ 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. - -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 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.” - -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 _pari passu_ with the decline of regular -types the incidence of _irregular_ manifestations grew proportionately. - -In my experience the incidence of _regular_ gout has appreciably -diminished during the past twenty years. Moreover, such examples as -one has met with incline much more in character to the _asthenic_ than -to the sthenic variety of _podagra_. But, in contrast to many, I have -observed no increase in the _irregular_ 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. - -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. - - “Αυσιμελου Βάκχου, και λυσιμελους Αφοδίτης, - Γένναται θυχατηρ, λυσιμελὴς, Ποδὰγρα.” - - - - -CHAPTER II - -THE PEDIGREE OF GOUT - - -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. - -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. - -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.” - -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 -_articular_ 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. - - -ISOLATION OF ACUTE ARTICULAR RHEUMATISM FROM GOUT - -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. - -Dissociating the term “rheumatism” from its primitive interpretation, -Baillon restricted its usage to that particular group of symptoms we now -call _acute articular rheumatism_. 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. - - -TARDY DISSOCIATION OF CHRONIC GOUT FROM CHRONIC RHEUMATISM - -Bearing in mind the centuries that elapsed before the _acute_ articular -forms of gout and rheumatism were dissociated, one ceases to marvel that -the task, incomparably more difficult, of discriminating between the -_chronic_ forms of these diseases is even now barely accomplished. - -“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 “_L’arthritisme_,” 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 _chronic_ manifestations were with difficulty -dissociated, the former pointing to the terms “rhumatisme goutteux” and -“rheumatic gout” as tacit acknowledgments of our impotence. - -Nor did this view that _gout_ and alike _rheumatism_ are the outcome of a -_basic arthritic diathesis_ 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 -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.” - -Laycock also subscribed to Charcot’s view, and Sir Dyce Duckworth -confesses that the conception of “a basic diathetic habit of body -called _arthritic_ 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 _acute articular rheumatism_, and later in life develop _gout_, is -undeniable, as also the reverse, that a gouty subject may be harassed by -manifestations of chronic rheumatism or _fibrositis_. 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 _gout_ -and _rheumatism_. It is undeniable that the difficulty of differentiating -between the _chronic_ forms of these two disorders is great, for not even -the revelations of _skiagraphy_, 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. - - -IDENTIFICATION OF MUSCULAR RHEUMATISM - -But to resume our thread, one great step forward we owe to Cullen, who -not only differentiated _acute_ from _chronic_ articular rheumatism, but -also clearly portrayed the clinical distinctness from both of _muscular_ -rheumatism. In so doing, he materially assisted in the differentiation -of these same disorders from _gout_. But at the same time, owing to his -immoderate advocacy of “chill” as the one great cause of _rheumatism_ -in all its forms, he undoubtedly retarded progress. For immediately -there arose a cloud of witnesses who claimed a “rheumatic kinship” for a -myriad _visceral_ disorders, the victims of which had suffered exposure. -Thus throughout the seventeenth and eighteenth centuries many of the -conditions now assigned to _irregular gout_ were affiliated instead to -_rheumatism_. - - -DIFFERENTIATION OF CHRONIC GOUT FROM ARTHRITIS DEFORMANS - -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 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. - -Thus how much more swiftly would the clinical distinctness of chronic -articular gout from _rheumatoid arthritis_ 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 _chronic rheumatism_, of which he believed it to be an _apyretic_ -variety. But the importance of his researches resides in this—he pointed -out that it differed essentially from _gout_, 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. - -Nevertheless, if we except Musgrave’s work (1703), “Arthritis ex -Chlorosi,” which included some undoubted examples of _rheumatoid_ 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 _osteoarthritis_ 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. - -In 1800 Landre Beauvais published his clinical description of -_rheumatoid_ arthritis under the title “goutte asthenique primitif.” That -Beauvais, as Sir Archibald Garrod contends, included under this title -some cases of true _gout_ 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. - -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 _gout_, 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, while -the peculiar nodosities on the fingers are still associated with his name. - -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.” - -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 _rheumatoid_ arthritis -to the disorder in question. Nor can we refrain from recording Fuller’s -words that “the natural history of _rheumatic gout_ accords but little -with that of _acute rheumatism_, and is equally inconsistent with that of -true gout.” - - -CLEAVAGE OF ARTHRITIS DEFORMANS INTO TWO TYPES - -In reviewing the researches of the foregoing writers it will be clearly -seen that though they did yeoman service in differentiating broadly -_gout_ from the disorders grouped under _Arthritis Deformans_, 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. - -I allude in the first place to Charcot’s momentous discovery of the -_nerve arthropathies_, and secondly, to the cleavage of arthritis -deformans into the _rheumatoid_ or _atrophic_, and the _osteoarthritic_ -or _hypertrophic_ varieties. - -It is to Vidal that we are indebted for the first clinical description -of the _atrophic_ 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.” - -Notwithstanding this, Charcot, to our mind, unquestionably refers to -the category of _chronic articular gout_ certain of these examples of -Vidal’s _atrophic_ type of _arthritis deformans_. The reasons he adduces -for their _gouty_ 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 -_atrophic_ changes; on the other, he postulates them as _gouty_ even -though the _uratic deposits_ “either do not exist at all, or only mere -traces of them, or when only the articular cartilages are invaded by the -urate of soda.” It must be conceded that _chronic articular gout_ and -_rheumatoid_ or _atrophic arthritis_ are totally distinct affections. - -Now as to the _hypertrophic_ 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 _tophaceous_ form of chronic articular gout, -postulates the existence of another type, _arthritis deformans uratica_. -Unlike Charcot, however, he seems only to have included under this term -instances of the osteoarthritic or _hypertrophic_ variety. But like -Charcot, his claim that this particular variety is of _gouty_ nature -seems to rest on equally frail foundations, as witness his statement that -they “may be complicated with visible or invisible tophaceous deposits!” - -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, _gouty arthritis_ and -_osteoarthritis_ are wholly distinct disorders, of wholly different -origin. - -At this period of our historical _résumé_ we see that by the withdrawal -of these three great groups—_rheumatism_, the _nerve arthropathies_ and -_arthritis deformans_—the domain of gout has, through these several -allotments, undergone substantial shrinkage. - - -ELIMINATION OF THE INFECTIVE ARTHRITIDES - -Yet again was the territory of gout destined to undergo further -restriction, and this largely owing to the rise of the science of -_bacteriology_. For in light of recent improvements in _diagnostic_ -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 -_specific infections_. What, for example, of Hippocrates’ aphorism that -gout was unknown in youths—_ante usum veneris_—who can doubt that some of -his reputed cases of gout were examples of _gonococcal_ or _syphilitic_ -arthritis? - -What, too, of all the other infective arthritides—_influenzal_, -_pneumoccocal_, _scarlatinal_, _typhoidal_, _meningococcal_—to mention -only those actually affiliated to some specific organism. For gout, be -it noted, confers no exemption from other arthritic diseases, but how in -time past were such to be differentiated therefrom? - -Again, gouty subjects, as has been recently emphasised, are notoriously -prone to _pyorrhœa alveolaris_, and how difficult, given the supervention -of an _arthritis_ in such to define the causal agent—_gout_ or _sepsis_, -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 _traumatic_ or _static_ origin. - -That more of these alien joint disorders—_les pseudo-rheumatismes -infectieux_, 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 _infective -arthritides_, on the other hand to “gout” accrued a host of unrelated -_visceral_ disorders, not to mention affections of the _nervous_ and -_vascular_ structures, etc. - -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 _is_ gout, but through our growing perception of what is _not_ -gout. For of the _causa causans_ 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. - -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.” - -If to this be added the further differentiation, not only of the _nerve -arthropathies_, but also of the _infective arthridites_—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. - - - - -CHAPTER III - -EARLIER THEORIES OF PATHOGENESIS - - -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 _materia peccans_ 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 _effect_ and -not the cause of gout. - -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 _uric acid_. - -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 _uric acid_ in the _blood_ of the victims of _gout_ -allayed all doubts, and seemed then and for long after an all-sufficient -explanation of the protean manifestations of the disease. - -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 _uric acid_ theory. - - -GARROD’S THEORY - -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 _blood in abnormal quantities_, 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 _lead -poisoning_, 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. - -He further averred that gouty inflammation is _always_ accompanied by a -_deposition_ of _urate of soda_, crystalline and interstitial, in the -inflamed part. Also that “the deposited urate of soda may be looked upon -as the _cause_ 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.” - -In addition, Garrod postulated implication of the _kidneys_, probably -in the early, and certainly in the chronic stages of gout; and that the -renal affection, though possibly only _functional_ at first, subsequently -became _organic_, with alterations in the urinary secretions. - -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. - -On the other hand, the determining causes of a gouty fit are those which -induce a _less alkaline condition of the blood_, 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 -_no disease but true gout is there a deposition of uric acid_. - -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 -before, there was a growing suspicion that lithic (_uric_) acid was the -malign factor in the induction of gout, still it was not till Garrod’s -discovery of _uric acid_ in the _blood_ and _tissues_ of the “gouty,” -that any definite step towards the elucidation of the problem presented -by gout was attained. - - -ANTAGONISTIC VIEWS - -One aspect of Garrod’s theory that much exercised the minds of his -contemporaries was that for him _uric acid_ 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 _were_ 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 -_functional renal defect_ 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. - -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:— - -(1) In the blood or tissues, the so-called histogenous theories. - -(2) In the bodily structures, either inborn or induced. - -(3) In hepatic inadequacy. - -(4) In hyperpyræmia. - -(5) In the nervous system. - - -HISTOGENOUS THEORIES - -In his classic work, “On Urine” (1860), Parkes expressed his scepticism -as to the valency of Garrod’s assumption of a _primary renal inadequacy_. -In shrewd forecast of latter day views he was of opinion that both uric -and phosphoric acids existed in some untoward combination in the _blood_ -or _organs_, 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.” - -In 1866 Barclay lodged another objection to Garrod’s hypothesis, viz., -that the baneful influence of uric acid was _exercised passively and -physically_. Not only did he regard it as “far too mechanical,” but he -also strongly dissented from his axiom that gouty inflammation was -invariably attended by _uratic deposits_. 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 _in situ_ 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.” - -His own view was that the _primary change lay in the blood corpuscles_, -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 _symptom_, 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.” - -The imaginative insight of Barclay is very remarkable. If we substitute -the _white_ for the red corpuscles we see how closely his views accord -with those prevalent at the present time, when so important a _rôle_ in -the genesis of gout is attributed to the _leucocytes_. 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.” - -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 _symptomatic_ and not -causative of gout, coupling with it the suggestion that there was some -antecedent _nerve_ influence at work. - -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 _in the tissues_, and its action thereon, and is -especially characterised by _peculiar changes in the innervation of the -individual_.” - - -ANTECEDENT STRUCTURAL CHANGES - -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 _degeneration_, 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., _cartilages_. - -As to the _local_ 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 _specific_, viz., due invariably to mechanical irritation by -_uratic deposits_, 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 _nervous_ -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.” - -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.”[4] - -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 _necrosis_ of -the damaged textures. The initial nutritional derangement was ascribed -by him to the irritant effect of soluble _neutral sodium urate_. 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 of -a true gouty focus, claiming that he had detected such foci in cartilage, -tendons, kidneys, and connective tissue. - -Experimentally, Ebstein endeavoured to induce a gouty condition in -fowls by ligaturing both _ureters_, thus thrusting upon the circulation -the dammed-up uratic secretion. In other instances he administered -to the same animals subcutaneous injections of neutral _chromate_ of -_potassium_, attributing to this substance the power of inhibiting the -excretion of uric acid _viâ_ the kidneys through its action on the renal -parenchyma. Subsequently, after death he noted the incidence of _uratic -deposits_ in joints, muscles, tendon sheaths, and liver, the same being -more copious in those animals subjected to chromate injections. - -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. - -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 _uræmia_ rather than anything -approximating to gout. - -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.” - -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 _toxic_ 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 _necrosis_. - -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 _degeneration_ -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 _textural -degenerations_ in gouty subjects, either through heredity or acquirement. -For this observer, however, the basal factor in the production of the -disease was a diminished _alkalinity of the blood_, due to a surcharging -of it with acid and acid salts. Disagreeing with Garrod’s assumption -that _deficient renal elimination_ 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 _tissues_ 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 _nervous_ 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.” - -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 _rôle_ than that of a proximate -cause. It was, for him, but an _epi-phenomenon_, the accompaniment of a -_panarthritis_, the origin of which was as follows:— - -While not postulating the identity of rheumatoid arthritis in gout, he -yet held that both disorders originated in some obscure form of _atrophy_ -of the bone substance, and that the degenerative change also overtook the -cartilages and fibrous tissues of the joints. Subsequently, there ensued -a _necrosis_ 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 _leucocytosis_, and in -part to disintegration of the tissues. - - -HEPATIC INADEQUACY - -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 _lithæmia_. In other words, gout was the -outcome of a depraved condition of the blood, due to faulty digestion and -functional disturbance of the liver. - -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 _incomplete_ gout, -_e.g._, 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 -_accumulation of uric acid_. This, moreover, according to Murchison, was, -especially in the later stages of gout, reinforced by the concurrence -of _renal inadequacy_, which he also postulated as a factor in the -production of the disorder. - -The tendency to lithæmia Murchison held to be _hereditary_, 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.” - -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, _e.g._, in _leukæmia_, 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. - -Now, as we hope to show later, whatever be the proximate cause of gout -it is at any rate _not uric acid_. The fact, too, that higher degrees of -_lithæmia_ 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.” - -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 _irregular_ manifestation of gout. - -If we are compelled to adopt a more judicial attitude in regard to -lithæmia, what of the similar assumptions as to the relationship of -_lithuria_ or _lithiasis_ 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.e._, -_outside_ the economy, it renders even more improbable the hypothesis -that the two morbid phenomena are diverse expressions of the “gouty” -diathesis. - -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. - -Reverting now to Latham’s views as to the _hepatic_ origin of gout, we -find them very similar to those formulated by Murchison. He held that -the defective transmutation of glycocine into urea was 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. - - -HYPERPYRÆMIA - -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. - -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. - -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. - -Hare contended also that excessive intake of starch and sugar by -inducing a state of “glycogenic distension” of the liver, might 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. - - -NERVOUS THEORIES - -It may be noted _en passant_ 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. - -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. - -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.” - -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. - -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. - -We see, therefore, from the above, that Duckworth was well 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 _primary_ type -“the toxæmia is dependent on the gouty neurosis ... and is therefore a -secondary manifestation.” - -In _secondary_ or _acquired_ 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.” - -Albeit, it must be frankly admitted that Duckworth’s perception of gout -as a _tropho-neurosis_ 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 _peripheral_ nerves of the inflamed limb. In other -words, he regarded gouty arthritis as the outcome of a local _neuritis_, -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. - - -GROWING SCEPTICISM AS TO GARROD’S PATHOGENY OF GOUT - -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, the marked determining influence of the -_nervous_ factor in the problem.” - -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. - -To hasten the process of disillusionment there came from the side -of the physiologists the announcement, almost unanimous, that _uric -acid_, 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 _uric acid_, 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? - -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! - -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.” - -That the _uric acid theory_ should more than any other have found -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 _excess of uric acid in the blood_. It -survived and still survives the corroding test of time. Surely such must -be the _fons et origo mali_, and how obtrusive _the uratic deposits_, so -ready to hand, objective affirmations of the truth of their contention. - -This apparent simplicity how delusive! yet not wholly unprofitable. For -if in these latter days our knowledge of the life-history of _uric acid_ -and _purin bodies_ 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. - -Here it would appear opportune to outline our plan of procedure in -approaching this abstruse subject—_gout_. In the coming chapter we shall -attempt to define and classify the various types of the disorder before -passing on to discuss its _etiology_ and _morbid anatomy_. - -Now all will agree that the more recent revelations of _chemical -physiology_ and _chemical pathology_ have an intimate bearing on the -problem to be considered. We shall therefore, before proceeding to the -more purely _clinical_ aspects of the disease, deal with the modern -conceptions of _protein_ and _purin metabolism_, more especially the -latter. Subsequently our scrutiny will be narrowed to consideration of -the _chemical_ structure of _uric acid_, 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 _uric -acid excretion_, _uricæmia_, and _uratosis_. - -The inadequacy of the uric acid theory of the causation of gout will -then be discussed and the possible intrusion of an _infective_ element -in its genesis advocated. This accomplished, we shall proceed to the -section dealing with the clinical aspects of the disorder, its _regular_ -and so-called _irregular_ 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. - - - - -CHAPTER IV - -DEFINITION, CLASSIFICATION, ETIOLOGY, AND MORBID ANATOMY - - -DEFINITION AND CLASSIFICATION - -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.” - -But have we not by unjustifiable and unwarrantable assumptions -deliberately complicated the issue, in recklessly relegating to the -_gouty_ 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. - -The same is reflected in the earlier, and to a lesser extent in the -latter day definitions or _descriptions_, as some of them more aptly may -be designated, notably that put forward by Sir Charles Scudamore. - - “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.” - - 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 a brief definition, because the - disease is too complex in its nature to be distinguishable with - certainty by a few signs alone.” - - 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 _gouty diathesis_.” - - 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.” - - 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.” - -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. - -_Definition._—Gout is an hereditary disorder, the _intrinsic_ element of -which is an inborn instability of nuclein metabolism which may remain -latent, but under the influence of _extrinsic_ factors, _infections_, -becomes manifest, as betokened by local inflammatory tissue reactions in -joints or elsewhere the specific character of which is attested by the -associated _uratic deposition_. - - -CLASSIFICATION - -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 _irregular_ manifestations, but even the -former or _regular_ varieties of the disorder seem destined to undergo -considerable pruning. - -As to the classical podagra—_acute_ articular gout—no question can -arise as to the propriety of its retention in this category. But as to -the _chronic_ articular types we are on less certain ground, and to -discussion of this vexed question we now proceed. - -Let us take, for example, Sir Dyce Duckworth’s classification of the -_arthritic_ types of gout. He distinguishes the following forms:— - - (1) Acute articular gout. - (2) Chronic articular gout - -the latter (2) further subdivided into— - - (_a_) the “tophaceous” variety. - (_b_) the “deforming” variety. - -Of these twain the “tophaceous” form need not detain us, and why? Simply -and solely this—the _uratic deposits_ stamp the seal of specificity on -the disorder. In short, the presence of _tophi_ places the “gouty” origin -of the arthritis beyond the pale of cavil. - -Now, if we accept, as we must, the fact that _uratic deposition is the -solitary unequivocal clinical criterion of gout_, we are not, I contend, -justified in classing any _chronic_ arthritis as “gouty,” the victim of -which does not exhibit _tophi_ of articular or ab-articular site, either -clinically demonstrable or deducible from skiagraphic revelations. - -Nevertheless, be it noted _tophi_ do but bespeak the “gouty diathesis,” -not necessarily the “_gouty_” nature of an associated arthritis. For -clearly tophi, of _ab-articular_ location, may coexist with an arthritis -of _gonococcal_ 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 _the absence of tophi_, the diagnosis of an arthritis as “gouty” -is _presumptive_, not absolute. This even in acute classical outbreaks -in the _big toe_, viz., pending the finding or subsequent eruption of -_tophi_. - -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 _big toe_. It is an invaluable, -but not an _infallible_ clue; for, unfortunately, acute arthritic -diseases other than gout may elect to announce themselves in the great -toe. - -Moreover, there is nothing _specific_ in the external characters of -acute “gouty” inflammation, nothing in the objective changes which would -stamp them on sight as “gouty,” save only their _location in the great -toe_; nothing distinctive about the angry blush, œdema, and engorged -veins, all of which may be met with in _infective_ arthritis. There -may be, as Garrod with good reason affirms, a local _intra-articular_ -deposit of urate of soda, but this lies beyond our ken, presumptive but -undemonstrable. - -Let but the _initial_ outbreak of gout occur elsewhere than at the _big -toe_, say, _e.g._, in the _wrist_, _hand_, _ankle_, or _knee_, and we -are at once, diagnostically speaking, _en l’air_. In this _impasse_ how -impotent are we, and how painfully we realise that our diagnosis of -acute gout is largely _topographical_, not _etiological_! Not, strictly -speaking, etiologically diagnosable pending the eruption and detection -of _tophi_. In short, location _per se_ in the big toe is strongly -suggestive but not _diagnostic_ of “gout.” (_Vide_ Chapters on Diagnosis.) - -If this be done in the green, what then shall be done in the dry? -In other words, if so precarious our diagnostic foothold in _acute_, -how much more so in _chronic_ articular gout! for in the latter -even _topography_ may wholly fail us, what then our diagnostic -criterion?—_tophi_ and _tophi_ alone—aye, and demonstrable at that. - -Yet both Charcot and Duckworth would have us recognise not only a -tophaceous but a _non-tophaceous_ 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 _tophi_ “may not exist” or “be -invisible”! _Deformity_, say they, is its hall-mark, not _tophi_, and its -character forsooth, they add, is not only _not peculiar to gout_, but -clinically indistinguishable from the similar defacements met with in -_arthritis deformans_. Nor is Duckworth alone in his contention, for both -Ewart and Luff also recognise what they term “chronic deforming gout.” - -_Tophi_, 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. - -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 _tophaceous_ variety, is untenable. -Fraught, moreover, with risk, as I am satisfied that their so-called, -“deforming” type is largely made up of the _atrophic_ and _hypertrophic_ -forms of arthritis deformans. - - -SUGGESTED CLASSIFICATION OF ARTICULAR GOUT - -For myself, as to the classification of the articular types of gout, I -would divide them into: - - (1) Acute articular gout. - (2) Chronic articular gout. - -Under the first group I would place not only the acute _localised_ type, -but also those acute varieties of _polyarticular_ distribution. As to the -second category, I would exclude therefrom, for the reasons cited, the -so-called “_deforming_” varieties of chronic articular gout, recognising -only the so-called _tophaceous_ form. But I would place a different -interpretation on this term in opposition to that generally accepted; -for, by most writers the word _tophaceous_ is apparently limited in its -application to examples which, so to speak, exhibit _tophi_ 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 _idiosyncratic_ tendency to chalk-stones! -In other words, he would seem to suggest that there is a gout within -gout, that one displays _chalk-stones_, the other _not_. By inference, -Duckworth and his followers, by differentiating _tophaceous_ gout, -tacitly concur, and so “confusion twice confounded” results. - -This usage of the term “tophaceous” is unjustifiable and misleading. -The significance of tophi is _qualitative_ not _quantitative_. 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 “_tophaceous_ 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 _uratic deposits in situ or -elsewhere in his body_. On this and on no other grounds can a chronic -arthritis, with any show of certitude, be certified as truly “uratic” or -“gouty.” - -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 _gouty arthritis_ 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 -_rheumatism_ and _arthritis deformans_, and on the other from the _nerve -arthropathies_ and the _infective arthritides_, such laxity might be -condonable, but not, we think, in the present stage of our knowledge. - -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 _retrocedent_ 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. - - -ETIOLOGY AND MORBID ANATOMY - -To the antiquity of gout and no less its distinctive clinical _facies_, -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 which engender or tend to engender the disease! -For, _quâ_ its broad etiological factors, we find ourselves in accord -with the physicians of old, our experience a confirmation of their -old-time findings. - -Our forefathers, like ourselves, realised the innate complexity of the -problem, that in the development of the disorder both _heredity_ and -_environment_ played a _rôle_. In other words, that in the genesis of -gout not only _intrinsic_ but _extrinsic_ agencies were concerned. Of the -intrinsic influences the most important are age, sex, heredity, bodily -conformation, and individual peculiarities. - -_Age._—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 _infants_ at the breast! and in one -death therefrom. Garrod, too, met with two cases of classical type in -_girls_, both of them under _ten_ 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. - -For myself, I have never seen a case under thirty-five years of age, -and am sceptical as to the occurrence of _infantile_ gout of _regular_ -type, believing with Scudamore that “the commonly asserted cases which -represent the existence of the gout in very early youth are really -examples of _rheumatism_.” Nor am I less but more inclined to cavil at -the claims of Comby and others, as to the frequency in _children_ of -_irregular_ 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.” - -To sum up, the majority of cases of gout ensue between thirty-five and -fifty years of age. But, given a strong _hereditary_ taint, it may break -out in _youths_ and _young adults_, or haply even in _children_. 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; while in one instance, a lady -experienced her first classical attack of podagra in her ninety-first -year. - -_Sex._—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.e._, 81·6 per cent., -twenty-three women, _i.e._, 18·4 per cent. - -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 _regular_, 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. - -As to the current opinion that the _regular_ manifestations of gout -in women are of _asthenic_ 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 _gouty_ inflammation resolves itself into one -of inflamed _bunion_. Again, in but too many instances, women, showing -_Heberden’s nodes_, are held to have gout or “rheumatic gout.” The latter -term, as Pye-Smith observed, “is a bad name for _osteoarthritis_,” to -which category Heberden’s nodes belong. - -Judged by the one unequivocal diagnostic criterion, _i.e._, _tophi_, -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 _great toe_, -we see clearly that the diagnosis of gout in women is often a matter of -_assumption_ rather than of certitude. - -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. - -As to the why and wherefore of the relative immunity of _women_ 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 -_catamenial_ discharges to a certain extent are protective against gout, -for most authorities support Hippocrates’ aphorism, “Mulier podagra non -laborat nisi ipsi menstrua defecerint.” - -_Heredity._—By the ancient physicians gout was held to be 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 _purely hereditary_; but, on the other hand, the -belief, that it is often _acquired_ is widely countenanced. - -That gout is an _hereditary_ disease is, I think, beyond question, -and certainly, of all _arthritic_ disorders, gout furnishes by far -the greater number of instances in which _parents_ and _children_ 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 _acquired_. 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.” - -Nevertheless, Garrod’s experience, he tells us, convinced him that “in -this country gout is frequently _acquired_ 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 _innate_ or -_static_ morbid proclivities on the part of the “gouty,” and in the same -breath, as it were, are equally insistent that it may be “acquired” _de -novo_. Now, in the taking of family histories _positive_ evidence is -more valuable than negative. Surely, therefore, in the light of Garrod’s -and Luff’s findings, it is obvious that _heredity_ plays not merely an -important, but an _essential_ and _indispensable rôle_ 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 _acquired_. - -Personally, I therefore question whether the alleged acquisition _de -novo_ of gout is not _apparent_ rather than real. My own opinion is -that the _innate predisposition_ thereto is _always inherited_, and the -predisposing factors, that we presume may originate gout, are in reality -merely _excitants_ or _determining_ agents. In other words, the remote, -the primary or essential cause of gout, is an _inborn_ morbid tissue -potentiality, and in the absence of this intrinsic warp the various -contributory or exciting causes are impotent to evoke the disorder. - -Apart from _statistical_ proof of heredity, how else, save on the basis -of an _organic predisposition_ 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 _gout_; 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. - -It is not gout, but the _predisposition_ 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.e._, 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 _latent_ until _evoked_. Thus, the _females_ 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. - -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 _inherited -structural peculiarities_, with their correlated perversions of tissue -function. - -That such constitute the pathological groundwork of gout, is, I think, -further indicated by the fact that _“gouty” inflammation_, in virtue -of its associated _uratic deposition_, is _sui generis_. No tissues, -other than the _gouty_, react in this _specific_ fashion. Does not this -seem to indicate that the _inborn tissue peculiarities_ dictate, so to -speak, the _character_ of the pathological reaction; this indifferently, -whatever the nature of the so-called _predisposing_ causes which, if our -assumption be correct, are merely _provocative_ of gout, in other words, -do but evoke or make _manifest_ what is already latent. - -To sum up, on statistical, and more cogently, general clinical and -pathological grounds, my own conclusions are that— - - (1) Gout is always an hereditary disease. - - (2) The factors currently regarded as predisposing agencies are - in reality merely _determining_ agents, not the cause of gout, - but the _occasion of its appearance_. - - (3) In the absence of an hereditary taint, these same are - powerless to evoke the _specific_ manifestations of true - _“gouty” inflammation_ as estimated by associated _uratic - deposition_. - -_Bodily Conformation and Individual Temperament._—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 -_rete mucosum_, 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.[5] - -Of objective stigmata, I know of none, save _tophi_, that can be 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. - -Again, it has become a tradition with us that gout produces -characteristic _teeth_. 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 _recession of the gums_. Again, we must recollect that -there are several causes which may lead to the teeth being worn down more -quickly than normally. Thus the _formation of the jaw_ 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. - -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. - -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. - -One point, however, I would emphasise is, the frequency with which -potentially gouty persons suffer from local _syncopes_ and _asphyxias_ of -the hands. They are precisely similar to those met with in _rheumatoid_ -or _atrophic arthritis_, certain cases of which, as we shall see later, -have another affinity with gout, viz., _retardation in the output of -exogenous purin_. - -_Locality, Race, Climate, etc._—As to the geographical distribution of -gout, the salient fact would appear to be the almost complete restriction -of the disorder to the _temperate_ zone. Among the natives of Africa -gout, according to Livingstone, is unknown. 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. - -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 _hereditary_. - -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 _facile princeps_ 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. - -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. - -In Belgium, also, gout is not common, and in Greece it is much less -prevalent than in France or England. - -In regard to the incidence of gout, its greater prevalence in _temperate_ -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 _climate_. Thus the immunity of, _e.g._, 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. - -Gout, indeed, is more a matter of _morals_ 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. - -Formerly it was held that the incidence of gout in any country 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 _bête noir_ 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 _sole_ factors. - -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 _cum grano salis_. 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. - -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 -_unrecognised_ 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. -_Mirabile dictu_, the percentage was only 0·37, but a third more than -that of the Johns Hopkins Hospital! - -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 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.” - -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? - -_Food, Drink, and Occupation._—Gout, it has been well said, is the -“Nemesis of high living,” for, unquestionably _overeating_ is most -fertile in evoking any latent tendency thereto. Attempts to throw all the -blame on particular foodstuffs, _e.g._, 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, _e.g._, milk, are probably referable to the -_intestinal asepsis_ that such a regimen promotes. - -My experience, like that of others, is, that it is not the quality, but -the _quantity_ of the food that is responsible. Moreover, I believe that -the _toxicity_ of the blood plasma thus produced exerts its evil effects -_indirectly_, viz., by lowering the _vis resistantiæ_ of the individual -to _microbic_ 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 _cardio-vascular_, _hepatic_, and renal changes so -frequently associated with gout in its later stages. - -Reverting to _alcohol_, there are many who regard it as _par excellence_ -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 _all_ 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 _percentage content of -alcohol_. 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 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 _acidity_, _sugar content_, etc., can be impeached as -imparting to the alcohol its predisposing influence in this direction. -Incidentally, to those who advocate the primary _renal_ origin of gout, -one would propound the question, why is it that _distilled spirits_ are -less provocative of gout than wines, seeing these particular liquors are -so fruitful of _granular kidney_? - -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 _hepatic cirrhosis_, 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.” - -The relationship of _alcohol_ to gout is as erratic as it is to _atrophic -cirrhosis_. 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. - -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. - -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 -_nuclein_ metabolism, that the most venial alcoholic indulgence suffices -to evoke an outbreak. - -I incline, therefore, to the view that alcohol _per se_ is not a cause -of gout; in other words, alcohol will not, in the absence of a _gouty -heredity_, 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. - -That alcohol will produce the disorder even more swiftly and surely if -reinforced by _overeating_ also, cannot, I think, be gainsaid. As to the -_modus operandi_ of alcohol in inducing gout, I believe that it acts -_indirectly_, viz., by slowly sapping the protective mechanisms of the -body, and so paving the way to _infections_. - -Much stress has been laid on the fact that certain _occupations_ conduce -to gout; but, if we exclude _plumbers_, _painters_, or other workers -in _lead_, no other callings in life can be held to entail a specific -predisposition to its development, save in so far as they promote -_overeating_, _overdrinking_, and _inactivity_. - -It is well established that workers in _lead_ 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 _lead_; 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 _plumbism_, -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. - -In light of these findings the question naturally arose as to whether -lead impregnation _per se_ 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. - -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 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. - -As to proffered explanations of lead-gout some have sought it in the -production by this poison of _arterio-sclerosis_ and _chronic nephritis_. -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. - -The balance of evidence would appear to be in favour of the view that -lead _per se_ 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. - -As to its _modus operandi_, I think it exerts its effect through -derangement of the intestinal secretions, and so favours the migration -inwards into the system of pathogenic _bacteria_. - -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. - -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. - -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 _associated habits of living_; 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? - -_Mental and Physical Over-exertion, etc._—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 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.” - -It is doubtful if, in the absence of an _hereditary_ 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. - -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 _ardent students_.” -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: - - “Ut Venus enervat vires, sic copia vini, - Et tentat gressus, debilitatque pedes.” - -Doubtless, in some instances of this supposed origin, a _gonococcal_ -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. - - -SUMMARY - -In conclusion, we have now dealt with those factors currently regarded -as _predisposing_ causes of gout. Personally, as I have before said, the -differentiation of the foregoing from the so-called _exciting_ 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. - -In other words, the difference is _quantitative_ 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. - -But far more arresting are the numerous and well authenticated instances -in which local _trauma_ not only determines an outbreak but also its -locality. How frequently, too, have blows, strains, sprains, _fractures_, -_dislocations_, or other trivial or severe injuries, been the signal -for an attack. Now, as we hope to show later, _local foci of infection_ -are extremely _common_ in the _gouty_. Such are especially frequent in -the _teeth_, _tonsils_, _naso-pharynx_, etc. Is it not then extremely -probable that organisms may, _viâ_ the _blood-stream_, find their way -to a _joint_, the resistance of whose tissues has been lowered by a -_trauma_, however slight its degree? This I apprehend to be the true -explanation of the undoubted intimate connection between traumatisms and -arthritic outbreaks of gout. - -Of similar significance, too, the numerous instances on record in -which acute attacks of gout have followed acute _tonsillitis_, acute -_pharyngitis_, acute _parotitis_, etc. How frequently, also, competent -observers, such as Garrod, noted that _boils_ and _carbuncles_ frequently -appeared to be excitant of acute attacks. But to this important point, -the intrusion of an _infective_ 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— - - (1) Heredity is the sole _predisposing_ factor in gout. - - (2) That the differentiation between the usually cited - predisposing and exciting causes is unwarrantable. - - (3) That both alike are merely _determinants_. - - (4) That their influence as such in exciting outbreaks is - exerted through the medium of _infection_, this achieved either - directly or indirectly. - - -MORBID ANATOMY - -It has been truthfully affirmed that we know more of the _results_ or -products of gout, and less of its _essential_ nature, than of almost any -other disease. Thus the post-mortem history of the disorder is concerned -almost exclusively with more or less graphic accounts of the _uratic -deposits_, 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 _regular_ or _articular_ manifestations, for it is in and around the -joint structures that the deposits for the main part occur. - -As to the assumed localisations of the disease in the _internal_ organs, -there is no _anatomical_ evidence that they are due to an invasion of -the “gouty” inflammation. Not even the _renal_ changes, despite the -attestation, as it were, of the gouty process by _uratic deposits_ in the -_papillæ_, 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.” - -If, then, nothing distinctive can be claimed of the _renal_, 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 _renal_ as well as the other _visceral_ 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. - -The only morbid structural changes, therefore, that can legitimately be -defined as _specific_ of gout relate to its _regular_ or _articular_ -lesions. As to the _anatomical_ alterations in the articulations, their -specificity depends essentially on the _uratic deposits_, rather than -upon the associated inflammatory and degenerative processes. - -Given death during an _acute_ 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 _crystalline deposits_. Charged -therewith, not only is the synovia thick, but of a milky appearance. -Examined microscopically, it is found to contain the acicular crystals -of _sodium biurate_. The synovia has occasionally been found covered -with blood, but no _pus_ 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. - -Uratic deposit has a predilection for _cartilage_, and in some instances -is strictly confined thereto; but in the more _chronic_ forms it -permeates all the component elements of the articulation. In the synovial -membrane and fringes deposition takes place in 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. - -Inspected after death, the articular cartilages are seemingly overlaid -with a white mortar or chalk-like material, _i.e._, 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 -_upon_ the surface of the cartilage, but is located _interstitially_ in -its substance. - -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. - -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. - -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. _Pari passu_ 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 _primarily_ 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 -_secondarily_ to uratic deposition in the cartilage, of which indeed it -was but an extension. - -In reviewing the foregoing findings, it must be admitted that morbid -anatomy fails to shed light on the _essential_ 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 _morbid anatomy_ of gout is as yet but in its -infancy. - -_Histological_ examination of the _articular ends_ adjacent to gouty -joints reveals the presence of certain _cystic_ changes in the -_diaphyses_. 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. - -An interesting point noted by Berkart was that in many cases of “acute” -gout the articular cartilage was found apparently normal and devoid of -_uratic deposits_, 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. - -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 -_accompaniment_ of acute gouty inflammation, but it militates strongly -against his contention that uric acid deposition is the _cause_ of acute -gouty inflammation. It indicates the reverse, viz., that the uratic -deposition is the _consequence_ of a more vital underlying morbid process. - -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 _cystoid degeneration_. Its -starting point is in the _epiphyses_. Thence 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.” - -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. - -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. - -Berkart holds that the histological changes in the affected epiphyses -indicate that the cystoid degeneration is the outcome of an _anomaly_ of -the _vascular_ and _osseous_ 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. - -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. - -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 _uric -acid theory_, which, not to mention the many other obstacles to its -acceptance, has always laboured under the aspersion of being too -“mechanical” in conception. - -Moreover, his studies clearly indicate that not only the intra-articular -surfaces but the adjacent _bone-ends_ and _marrow_ 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 _fons et origo mali_ in gout. -Some more vital element must, I feel convinced, intrude, and I incline -to think an _infection_. Berkart himself brings forth evidence in favour -of this contention, inasmuch as he noted the frequent co-existence of -_lymphangitis_, so pronounced that the whole of the affected leg became -the seat of a _leuco-phlegmatic œdema_. - - - - -CHAPTER V - -PATHOLOGY OF GOUT—PROTEIN METABOLISM - - -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 _intermediary_ metabolic or bio-chemical change. - -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. - -We know much of the complex changes that take place in food prior to -absorption, and of the _modus operandi_ 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. - -In other words, little do we know of the relationship of _labile_, or -food-protein, to _tissue_ protein. True, the coarse fact of abnormal -protein loss in _renal_ disease may be revealed in the urine, as -likewise the waste of albumoses in _myeloma_, etc., and the incidence -of amino-acids in disease of the _liver_. Similarly, the appearance -of _cystin_ or of _alkapton_ 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! - -Complex, in truth, the problem here presented, than which none more -subtle exists in the realm of bio-chemistry. True, _quantitative_ -variations in the content of the urine as to _urea_, _uric acid_, etc., -undoubtedly bear a direct relation to _protein_ metabolism, but they give -us little, if any, substantial clue as to the particular metabolic warp -responsible. We see this particularly in regard to uric acid, so long -accredited with an essential _rôle_ in gout. - -Thus we cannot, on the basis of the _variations_ in its _excretion_ only, -presume to diagnose “gout.” This because even more extensive variations -occur in _healthy_ persons. On the other hand, attacks of gout never -occur when urates are absent from the _blood_. 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 _glycosuria_ -has been partially solved. - - -REVELATIONS OF THE BIO-CHEMIST - -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 _protein_, and more particularly of _purin_ -or _nuclein_ 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. - -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. - -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 -_chemical physiology and chemical pathology_, 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. - -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 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.” - -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. - -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. _Uric -acid_ has apparently failed us as the _causa causans_. We can, therefore, -no longer restrict our enquiry to _purin_, but must take cognisance -of _protein_ metabolism as a whole, for some, perhaps not unnaturally -despairing of the _uric acid_ hypothesis, are turning therefrom to -other end-products of metabolism, _e.g._, _creatinine_. 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 _purin_ bodies. - - -PROTEIN METABOLISM - -No longer can we, like the older physiologists, envisage _protein_ -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 _protein_ molecule must previously undergo -complete disruption into the _a-amino-acids_, its ultimate “building -stones,” this through the hydrolytic action of the digestive enzymes -of the alimentary tract. The fact that Fischer[6] was able to maintain -nitrogen equilibrium in animals fed with completely digested protein -mixtures is, of course, direct evidence in favour of his contention, -viz., that proteins undergo disruption into amino-acids. - - -THE FORMATION OF UREA - -The question as to whether urea, the end-product of general nitrogenous -catabolism, was derived from the _amino-acids_, 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 _portal blood_, during the -digestion of copious amounts of protein, proved futile. On the other -hand, the same workers found that free _ammonia_ was present in greater -amounts in the portal vein than in the systemic circulation. - -This, to their mind, seemed to indicate that the amino-acids, during -their passage through the intestinal mucous membrane, underwent -_deaminisation_. According to this view the _ammonia_, thus split off -from the amino-acids, was the precursor of _urea_. - -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 _amino-acids_ -were actually present in the _portal blood_. - - -FATE OF THE AMINO-ACIDS - -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.e._, are re-synthesised into the body’s own characteristic -tissues. - -The surplus amino-acids, viz., those not required for purposes of cell -repair, undergo deaminisation. Two residues then result, one represented -by ammonia, and the other by the remaining relics of the amino-acid -molecule. The former is excreted as _urea_ and the latter is oxidised to -produce energy. - -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. - -Comparably with those of exogenous origin, these amino-acids of -_endogenous_ 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 _urea_, etc. - -The main end-product, then, of protein metabolism is _urea_, with traces -of its forerunner _ammonia_. 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., _creatine_ and _creatinine_. Some of -the amino-acids, too, are excreted unchanged in the urine. Lastly, to -these must be added those closely related substances, the _purin_ bodies, -the end-products of _nuclein_ as opposed to general protein metabolism, -of which latter _urea_ 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. - - -SEAT OF FORMATION OF UREA - -The _liver_, 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, _even after removal of the entire liver in -animals_, its production may not cease. - -Moreover, some researches of Otto Folin and W. Denis into _urea -formation_ seem to indicate that the older views call for revision. -Experimenting on cats, they injected them with _alanine_ and _glycocoll -nitrogen_ and other amino-acids as well as Witte’s _peptone_. They -were able to prove definitely that, at the end of an hour or more, the -formation of _urea_ from the absorbed amino-acids was unmistakably -demonstrable. Also they noted that interesting fact, that the “_urea -nitrogen_ obtained from the _hepatic blood_ is not larger than the urea -in the blood obtained at about the same time from the _iliac artery_.” -This they claim indicates that “_the liver has not brought about any -demonstrable specialised deaminisation_.” - -The experimental data forthcoming in their researches, while they prove -that the absorption of _amino-acids_ is very swiftly followed by the -formation of urea, does not afford any definite evidence as to the _site_ -of urea formation; but, as they rightly contend, we have no satisfactory -proof that _deaminisation_ and _urea formation_ is _localised_. -Consequently “we are not justified in assuming that the process is a -specialised process in the sense of being confined to some particular -organ.” - -Indeed, they bring forward evidence that the process of urea formation, -far from being localised to any particular organ, _i.e._, the liver, is -almost ubiquitous. - -Thus, experimenting with the injection of _alanine_, they noted that -prior to the same the muscle content of _non-protein nitrogen_ and _urea -nitrogen_ 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 _glycocoll_, 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. - -The significance of these figures is more striking when contrasted with -the fact that in the same subjects the urea nitrogen content of the -_hepatic_ blood did not exceed that obtained almost simultaneously from -the _iliac_ artery. The deduction made by Folin and Denis is that— - -(1) “_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._” - -(2) “_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._” - - -AMINO-ACIDS IN RELATION TO GOUT - -The vista opened up by these advances in physiology suggested -investigations into the _amino-acids_, their association with the output -of _uric acid_ in _gouty_ 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 _glycocoll_ or amino-acetic-acid. -Now, glycocoll plays a great _rôle_ in the organism as a _detoxicating_ -agent, rendering innocuous, _e.g._, benzoic and cholic acids by -transmuting them into _hippuric_ and _glycocholic_ acids. In short, the -body always has glycocoll at its disposal for coupling or combination -purposes. - -Now it appears likely that glycocoll can be split off from all the -amino-acids, a probability reinforced by the results of the 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. - -Ignatowski, working with the urine of _gouty_ patients, found -_amino-acids_ 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 _healthy_ 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 _glycocoll_ 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.” - -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 _glycocoll_. Lastly, Almagia has in gouty urines -detected the presence of _glyoxylic_ 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. - - -THE GLYCOCOLL THEORY OF GOUT - -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 -_hypoxanthine_, while the same was observed by Kionka in mice. These -findings suggest that, although _anatomical lesions_ are not apparent in -the _livers_ of “gouty” men, it is at least probable that _functional_ -damage results from the overeating of meat. - -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. _Urea_, in contrast to glycocoll, -markedly inhibits the formation of the acid salt. But if _glycocoll_ -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. - -It is reasonable, then, to suppose that if, as testified by Ignatowski -and Walker Hall, glycocoll is present in gouty _urine_, it is also -present in the _tissue fluids_ of the gouty individual, and so the -_precipitation_ of _uric acid_ is favoured. Glycocoll, normally, is -almost entirely transmuted into _urea_ by the urea-forming ferment of the -liver. - -Impressed by these considerations, Kionka advances the hypothesis that -gout is due to: - - (1) Functional changes in the liver, a depressed urea-ferment - action. - - (2) A deficient uric acid excretion by the kidney, possibly due - to the changed uric acid combinations in the blood. - - (3) These pathological conditions may be “hereditary” or - “acquired,” from overeating, alcohol, lead, etc. - -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.[7] - -For it is possible, as Kionka suggests, that normally uric acid, on its -way to urea, may pass through a _glycocoll_ stage. Now, in the gouty -individual the glycocoll may not be entirely transformed to _urea_, and -its excess in the _tissue fluids_ may lead to _uric acid deposits_. -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.” - -In healthy _cartilage_ 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 _tophi_. 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 _hepatic functional disability_ -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 _glycocoll_, 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 _gouty_ 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. - - -UREA EXCRETION IN GOUT - -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 _renal_ 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.). - -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. - -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 _nephritis_. Moreover, modern -workers tend more and more to rely not on analyses of the urine but -of the _blood_, 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 _urea_ nitrogen may be -normal.” - - -CREATINE AND CREATININE - -As before pointed out, it has been suggested that these substances may -be in some obscure way related to the genesis of _gout_. 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. - -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 _endogenous_ metabolism. Also of the creatine -and creatinine present in food a moiety may appear as creatine in the -urine. - -_Creatinine_ 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 _volume_ or _mass_ of the _voluntary muscles_, 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. _Creatine_, 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. - -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 _muscular tissues_. On this point we cannot do better than -quote the following words of Otto Folin:— - -“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 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.” - - -INBORN ERRORS OF METABOLISM - -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. - -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. - -In alkaptonuria the metabolic warp concerns the _aromatic_ groups, in -cystinuria the sulphur-containing radicles of the _protein_ molecule. -On the other hand, in pentosuria the origin of the endogenous pentose -is variously ascribed to the _nucleo-protein_ of the cell nuclei or to -galactose. Lastly, in gout it is in the metabolism of _nucleo-protein_, -or rather of the _nucleic acids_ of the cell nuclei that the flaw resides. - -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.e._, 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. - -Certain broad clinical resemblances also obtain. All members of the -group, including gout, display _hereditary_ tendencies. All occur much -more often in _males_ than in females. They all alike tend to persist -through life. Lastly, their distinctive chemical products, including uric -acid, are all apparently of _low toxicity_. - -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 _urinary_ concretions, and we -may recall that some authorities hold that gout and uric acid _calculi_ -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 _arthritis_, while the frequently associated -pigmentary change, _ochronosis_, has a predilection for deposition in the -cartilages of the ears and _joints_. - -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”! - -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 _intermediary_ and not a terminal product of -metabolism. All modern research, however, tends to indicate that uric -acid is an _end-product_, and, moreover, that there are no _uricolytic_ -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 _homogentisic acid_ met with in alkaptonuria is -a “chemical malformation,” _uric acid_ 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. - - - - -CHAPTER VI - -NUCLEIN METABOLISM - - -No hard and fast line can be drawn between the metabolism of protein -and that of nuclein. For though, morphologically speaking, the _nuclei_ -of cells are sharply differentiated from the circumambient _cytoplasm_, -and exhibit equally distinct staining reactions, yet, _chemically_, the -differences between them are _quantitative_ rather than qualitative. - -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 _nuclear_ changes that -we may best discern evidence of the initiation of _oxidation_ 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.” - -So much by way of prelude, but the story of the growth of our knowledge -of _nuclein_ as opposed to protein is so fascinating as to be worthy of a -slight digression. - - -THE ISOLATION OF NUCLEIC ACID - -Functionally regarded, the _nucleus_ 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 _nuclei_, -which remained as an insoluble grey powder. In this manner cell nuclei, -_free from protoplasm_, became available for chemical analysis. Treating -the insoluble nuclei thus obtained with dilute sodium carbonate, a -solution was formed. Acetic acid added thereto produced a flocculent -precipitate which was found to contain phosphorus, and responded to -protein colour tests. This substance Miescher christened by the name -of _nuclein_. Subsequent observers prepared nuclein from the nuclei of -_yeast_ cells and the _red blood corpuscles_ of birds. All nucleins are -insoluble acids which form soluble salts with sodium. But while they -respond to protein colour reactions they differ from _protein_ in that -they contain _phosphorus_ and _resist the solvent action of artificial -gastric juice_. - -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 _débris_, while -their digestive juices were as a rule inert. One startling change he -noted, that while, on the one hand, their _muscular_ tissue profoundly -wasted during their migration, their _organs of reproduction_ enlarged -enormously, the inevitable conclusion being that eggs and spermatozoa had -been created from muscle protein. - - -RESEARCHES ON SPERMATOZOA - -Struck by the opportunities for scientific investigation during the -spawning season, Miescher determined to resume his work upon _nuclein_. -Spermatic fluid or _lachsmilch_, being readily obtainable in great -quantities, he had to hand a mass of material admirably adapted for -chemical examination of the cell _nucleus_. The conclusion that the -_heads_ of the spermatozoa might be regarded as a _metamorphosed nucleus_ -seemed obvious, and the opportunity too good to be lost. - -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 -_protamine_, the latter _nucleic acid_. - -The presence of this salt protamine nucleate led to the conclusion that -nuclein was merely a salt of protein and nucleic acid. - - -THE DISCOVERY OF PURINS - -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. - -Alive to the import of the reaction, Miescher requested Piccard to -examine salmon sperm for _purin_ bases. Extracting the same with -hydrochloric acid, Piccard found _guanine_, and what he thought was -_hypoxanthine_, but which was in truth _adenine_. - -Another distinguished worker in this sphere, Kossel, noted that, -subjected to the action of hydrolytic agents, nucleins always yield -_purin derivatives_; also that the same were derived, not from the -_protein_ of the nuclein, but from the _nucleic acid_. 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 _nucleic acid_ became -recognisable as a definite entity, distinguishable from proteins and -other body elements, this latter differentiation by token of the _purin -bases_ which are contained in nucleic acid. - -Moreover, it led to the dissipation of the old belief that _uric acid_ -was an intermediate product of _protein_ metabolism, for the revelation -of purin bases as decomposition products of _nucleic acid_ 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 _nexus_ obtained between the -cell nucleus or _nucleic acid_ and uric acid. - -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:— - - (1) Conversion in the liver of ammonium lactate into uric acid. - (2) Some other, though unknown, process of formation. - -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. - - -URIC ACID A DERIVATIVE OF NUCLEIC ACID - -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 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 _uric acid_; but the experiment being repeated, without the -passage of air, _xanthine and hypoxanthine_ and not uric acid resulted. - -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 _before_ the purin groups were disengaged -from the nucleic acid, and definitely affirmed that the uric acid was not -produced by the oxidation of _free_ xanthine or hypoxanthine.) - -But, nevertheless, this pioneer established that in both _man_ and -rabbits _uric acid_ was derived from _nucleic acid_. Also, having -observed that when after starvation the food intake was resumed, a -_leucocytosis_ occurred, he announced his belief in the following theory. -Thus, he noted that _leukæmics_, whose blood showed a high leucocyte -count, excreted an unusually large amount of uric acid; consequently, -he came to the conclusion that _uric acid_ was formed from _defunct -leucocytes_. 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. - -This increased excretion of uric acid after the ingestion of food rich in -_nucleic acid_ has been amply confirmed; but all the earlier attempts to -achieve an increased excretion by the ingestion of _free_ purin bases, -as opposed to the _combined_ purin bases, existing as such in _nucleic -acid_, failed, although tried repeatedly. - -So much for the various stages by which our knowledge of the purin -derivatives of nucleic acid has been gradually acquired, for though -_purin bases_ had, from early times, been known to exist in _animal_ -tissues, their presence there could not be rationally accounted for prior -to the discovery of _nucleic acid_. - -It still remains for us to deal in detail with the further developments -of our knowledge which concern the _disruption of nucleic acid in the -body_ and the process by which _uric acid_ is derived therefrom. - -But before proceeding to consider in detail the complex series or -_enzymatic_ transformation that this entails, it will, I think, be wiser -to deal first with the _chemistry_ of uric acid, its _solubilities_, and -its _sources_, whether exogenous, endogenous or synthetic. - - -THE CHEMISTRY OF URIC ACID AND THE PURIN BODIES - -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. - -Of the purins in human urine, the most important is _uric acid_, 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 _protein_ gave rise to _uric acid_. 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 _purin_ the output thereof is considerably higher than -on a purin-free diet, this being due to the large amount of _nuclein_ -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. - - -CHEMICAL CONSTITUTION - -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). - -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 _purin_ which, though unimportant in itself, is yet interesting in -that it is the basic substance from which the following take origin:— - - Purin C₅H₄N₄ - Hypoxanthine C₅H₄N₄O Monoxy-purin } - Adenine C₅H₃N₄NH₂ Amino-purin } - Xanthine C₅H₄N₄O₂ Dioxy-purin } Purin Bases. - Guanine C₅H₃N₄ONH₂ Aminooxy-purin } - Uric acid C₅H₄N₄O₃ Trioxy-purin } - -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 _purin nucleus_ -C₅N₄ will become apparent from a study of the following structural -formulæ culled from Wells’ “Chemical Pathology”:— - - -STRUCTURAL FORMULÆ - - N (1)—C (6) N CH - C (2)—C (5)—N (7) HC C NH - C (8) CH - N (3)—C (4)—N (9) N C—N - - Purin nucleus. Purin. - -To describe the individual _derivatives of purin_ we have to indicate -to which particular atom of the _purin nucleus_ the combining groups -are attached. Thus, for example, _adenine_ in structure is classed as a -6-amino-purin, and accordingly has the following formula: - - N==C—NH₂ - | | - HC C—NH - ‖ ‖ \ - ‖ ‖ CH - ‖ ‖ / - N—C—N - - Adenine - (6-amino-purin). - - -Other important bodies built up round the purin nucleus C₅N₄, variously -designated as xanthine, alloxuric and nuclein bodies:— - - HN—C==O HN—C==O - | | | | - H₂NC C—NH O==C C—NH - ‖ ‖ \ | ‖ \ - ‖ ‖ CH | ‖ CH - ‖ ‖ // | ‖ // - N—C—N HN—C—N - - Guanine Xanthine - (2-amino-6-oxypurin). (2-6-dioxypurin). - - HN—C==O HN—C==O - | | | | - HC C—NH O==C C—NH - ‖ ‖ \ | ‖ \ - ‖ ‖ CH | ‖ C==O - ‖ ‖ // | ‖ / - N—C—N HN—C—NH - - Hypoxanthine Uric acid - (6-oxypurin). (2-6-8-trioxypurin). - - - H₃C—N—C==O HN==C==O - | | | | - | | CH₃ | | CH₃ - | | / | | / - O==C C—N O==C C—N - | ‖ \ | ‖ \ - | ‖ CH | ‖ CH - | ‖ // | ‖ / - H₃C—N—C—N H₃C—N—C—N - - Caffeine Theobromine - (1-3-7-trimethyl, (3-7-dimethyl, - 1-2-6-dioxypurin). 2-6-dioxypurin). - -It will be seen that the _purin bases_ stand in very close chemical -relationship to _uric acid_ in that the latter also is marked by -the possession of a group called the _purin nucleus_; indeed, the -relationship of uric acid to the purin bases is more intimate than to -_urea_ (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). - -The first product of the _oxidation_ of purin is _hypoxanthine_, long -recognised as a constituent of meat extracts. _Adenine_, the amino -derivative of hypoxanthine, is met with in combination with other -substances in _nuclear_ material. The second oxidation product of -purin is _xanthine_, and its amino derivative _guanine_, both of which -are found in the same substances as hypoxanthine and adenine. Further -oxidation of purin gives rise to _uric acid_. We have to recognise, -also, that in addition to the purins of animal origin there are some -also derived from _vegetables_, viz., the _methyl_ purins, caffeine, -theobromine, and theine. - -Now, as will be seen later, certain compounds, containing nitrogen and -phosphorus, constitute the chief, if not the exclusive, source of _uric -acid_. These substances, long known as _nucleins_ or _nucleo-proteins_, -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 _nucleic acid_. This, in that through the action of -ferments, it is from the nucleic acids that _uric acid_ and the _purin -bases_ are derived. - -But, apart from this, we have to recollect that nucleic acids yield -constituents other than purin bases, viz., the _pyrimidine bases_, -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 _urea_ radicles. -Moreover, it is believed that, though included in the makeup of nucleic -acid, they are not derived from purin but are _primary_ products. - - - { NH—CO { N==C—NH₂ { NH—CO - Thymine { CO C CH₃ Cytocine { CO CH Uracil { CO CH - { NH—CH { NH—CH { NH—CH - -To sum up, the characteristic constituents of _nucleic acid_ are the -purin bases (adenine, guanine, hypoxanthine, and xanthine), pyrimidine -bases (uracil, cytosine, thymine), phosphoric acid and a carbohydrate -group. - -We have now discussed the _chemical structure_ of uric acid and its -relationship to the _purin bases_; 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. - - -PROPERTIES OF URIC ACID - -When pure, uric acid is white in colour and crystallises in rhombic form. -In contrast to _urea_ it is very insoluble, but much less so in _blood -serum_ 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. - -The greater solubility of uric acid in blood plasma was, by Garrod and -Haig, attributed to the _alkalinity_ 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 _litmus_, a crude procedure as compared -with the use of _phenol-phthalein_, and Frankel’s _electro-potential_ -measurements. Working with these as criteria, it has been shown that -blood is normally _alkaline_ in only a _minority_ of cases, and indeed, -according to Flack and Hill, the plasma is in reality _neutral_. - -In the _urine_ uric acid and the urates are held in solution by the -neutral _phosphates_. 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. - - -URIC ACID IN THE BLOOD - -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 _quadriurate_. 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 _biurate_, 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, _e.g._, synovial sheaths. - -But, unfortunately for the valency of this otherwise plausible theory, -it was proved by Tunnicliffe, Rosenheim, and others, that _quadriurates_ -do not exist as definite chemical compounds; in short, it is generally -conceded that their existence should no longer be accepted. - - -GUDZENT AND SCHADE’S THEORIES - -Gudzent was of opinion that uric acid can only exist in the blood as -the _mono-sodium-urate_, of which there are two isomeric varieties, the -easily soluble unstable _lactam_, and the stable relatively insoluble -_lactim_ 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. - -Others, like Bechhold, maintain that the urates are present in the blood -in a _colloidal_ 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 _colloid_ 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.e._, -glycerine, urea, serum, albumen, nucleic acid, etc. But hitherto the -therapeutic possibilities suggested have not been invoked. - - -ORGANIC COMBINATIONS - -It will be recalled that purin bodies cannot be detected in the _blood_ -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 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.[8] - -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 _urates_, -the elimination of which only proceeds with difficulty; in other words, -the purins normally circulate in _organic_ combination and abnormally as -_salts_ of _sodium_. - -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. - -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 _nucleic_ -(thyminic) _acid_, 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 _thyminic acid_, but are excreted unchanged when ingested in a free -state. Thus, certain purins, _e.g._, _adenine_, 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. - -But Walker Hall, discussing the good results obtained by Schmoll and -Fenner from the administration of thyminic acid, states that his -experiments do not indicate that the improvement is at all associated -with any change in the _uric acid_ excretion. - -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,[9] on the other the nature -of the suggested uric acid organic complex is still unknown. - -Nay, more, Walker Hall, writing in 1913-14, states “there are many who -consider that the _sodium mono-urate_ 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 _free_ state and -not combined, as was at one time urged by several students of gout.” - - -COMPLEXITY OF THE PROBLEM - -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 _purin bases_ and _pyrimidin_ 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 _potassium_ must also -occur, and to these may be added, too, ammonium and calcium compounds in -small quantities. - -But more striking is his inference that the occurrence of _isomeric -forms_ of _uric acid_ suggests that _isomers_ of _purins_ and -_pyrimidins_ 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.[10] 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 response to -abnormal stimuli or excessive demand, other isomers may be formed.” - -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 _in vivo_; 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. - -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.” - -As to the _solubilities_ 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.” - -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 _sources_ of _uric acid_, whether of intrinsic or -extrinsic origin. - - - - -CHAPTER VII - -SOURCES OF URIC ACID - - -Uric acid, like the “purin bodies” (xanthine, hypoxanthine, guanine, -and adenine), is derived from _nucleins_, _i.e._, from the breaking -down of tissues rich in cells. The end-product of purin or nuclein -katabolism _uric acid_ represents but a further stage in the oxidation -of the _purin_ bodies. To the serial enzymatic transformations that mark -its derivation from _nucleic acid_ we shall allude later, but at this -juncture we are concerned not with the _mode_ of _formation_ of uric -acid, but with the sources thereof. - -In this sphere we are greatly indebted to the pioneer researches of -Burian and Schur. These observers noted that on a diet rich in _nucleins_ -(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 _exogenous_ and partly of _endogenous_ 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. - -Here it may be noted that all the ingested purins are not excreted in the -urine as uric acid, for some pass away as _purins_. Moreover, the amount -excreted will vary with the kind of purin ingested, and also with the -_species_ 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).[11] - -In amount about 0·4-0·7 gramme of uric acid is excreted in _human_ urine -daily, and the purin bodies, hypoxanthine, xanthine, and adenine, in -small quantities. - -Beyond exogenous and endogenous purins there is yet one other possible -source of uric acid, viz., its _synthetic formation_ 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 _urea_ -and _glycocine_, a finding afterwards confirmed by Latham. The theory -was then advanced that a similar synthesis might be effected by the -_kidneys_; but it was found that glycocine and urea, even when given in -excess to mammals, caused no change in the uric acid excretion. - -So much by way of preface to our detailed discussion _seriatim_ of the -various sources of uric acid, and to which we now pass on. - - -EXOGENOUS PURINS - -The foodstuffs that cause an increase in purin excretion are divisible -into three groups:— - - (_a_) Amino-purins. - (_b_) Oxy-purins. - (_c_) Methyl-purins. - -_Amino-purins._—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. - -The researches of Kossel and Horbaczewski showed that such augmentation -was mainly due to the production of uric acid from the _nuclein_ -substances of the food; in other words, it was due to the katabolism of -_nuclein_, the cleavage products of which comprise _adenine_ derived -from thymus, and _guanine_ 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. - -_Oxy-purins._—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 _free_ state, _e.g._, 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 _nucleic acid_ for its liberation. - -_Methyl-purins._—The nuclei of _vegetable_ cells also contain -nucleo-protein, and, therefore, can add their quota to the purin intake. -The most important are _caffeine_, _theobromine_, and _theophyllin_, 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 _purins_. Now it is doubtful whether the _methyl-purins_ lead -to the formation of _uric acid_ in the organism, or whether they are -excreted as purin bases in the urine. According to Stewart, a fractional -part of the _purin bases_ 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. - -From the foregoing data it will be obvious that the _exogenous_ urinary -purins are derived from _nuclein_ and certain _free xanthine bases_, and -that the influence of other nitrogenous foodstuffs in this direction is -practically negligible. - - -EXOGENOUS URIC ACID EXCRETION - -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. - - ---------------+-------------------+---------------- - | Total percentage | Percentage of - Diet. | of purin | exogenous - |substances in diet.| urinary purin. - ---------------+-------------------+---------------- - Beef | 0·06 | 0·030 - Coffee | 0·20 | 0·075 - Calf’s liver | 0·12 | 0·060 - Calf’s spleen | 0·16 | 0·080 - Calf’s thymus | 0·40 | 0·100 - ---------------+-------------------+---------------- - -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, reveal that, roughly speaking, 50 per -cent. of the purin content in food is excreted in the urine.[12] - -These figures must be taken as a broad average relating only to healthy -individuals upon diets capable of perfect assimilation. - -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 _uric acid_. -While this is true of free purins, on the other hand, when _bound_ -purins, _i.e._, 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 _purin_ as opposed to a -_purin-free_ diet. - -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 -_sweetbreads_, 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. - - ---------------+-------------+--------------+-------------+-------------- - |First period.|Second period.|Third period.|Fourth period. - | Purin-free | | | Purin-free - | diet. | | | diet. - ---------------+-------------+--------------+-------------+-------------- - Total urinary N| 8·9 | 8·7 | 9·1 | 8·8 - Urea N and NH₂ | 7·3 | 7·1 | 7·1 | 7·05 - Creatine | 0·58 | 0·55 | 0·56 | 0·47 - Purin N (total)| 0·11 | 0·17 | 0·26 | 0·10 - Uric acid N | 0·09 | 0·14 | 0·24 | 0·07 - Remainder N | 0·91 | 0·88 | 0·18 | 1·18 - ---------------+-------------+--------------+-------------+-------------- - -From a study of the table it will be noted that, following the -introduction of sweetbreads rich in _nucleins_, 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.e._, nucleins ingested, appears as uric acid in the urine. - - -FATE OF THE UNEXCRETED PURIN - -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 _nucleoside_ in which they occur, and that since they cannot form -uric acid, they are possibly excreted as _urea_ or in other forms. He -adds that only 50 per cent. of the nucleic acid nitrogen can be counted -on for the production of _uric acid_, viz., that in the guanine and -adenine groups. - -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 _uricase_, 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.” - -Lastly, Stewart, discussing the ultimate destiny of the absorbed -products of _nucleic acid_ 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.” - -Also, it should be recollected that the purin bases normally found in -human _fæces_ are in part of _exogenous_ origin, and are increased in -amount after the ingestion of meat extract or thymus. - - -ENDOGENOUS PURINS - -Even if we entirely eliminate all purin substances, by restricting the -diet to _purin-free_ foodstuffs (bread, milk, cheese, eggs and butter), -purin in the form of _uric acid_ is still excreted in the urine. - -To this moiety the term _endogenous_ 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 daily “wear and -tear” of cells. In other words, it is the outcome of the katabolism of -the _nucleo-protein_ of the body tissues. - - -SOURCE OF ENDOGENOUS PURINS - -_Is the nuclear destruction of localised or generalised distribution?_ - -Mares (and subsequently many other observers), having noted that, -following the ingestion of _purin-free_ 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 _secretory glands of the gastro-intestinal -tract_, following such intake. - -The effects yielded on uric acid excretion by those antithetic drugs, -atropine and pilocarpine, certainly seem to lend colour to Mares’ -hypothesis. - -Following the injection of _atropine_, the rise in uric acid output, that -normally follows the ingestion of protein, was inhibited. But in sequence -to _pilocarpine_, an _excitant_ and not like _atropine_, 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 _rôle_ played by the _digestive glands_ 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. - -In opposition, however, Burian, as the outcome of his experimental -studies, maintained that a _fractional_ portion only of the endogenous -uric acid could be derived from the _nucleo-protein of the body cells_. -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 _hypoxanthine_ of the -_inosinic_ acid present in _muscular_ 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. - - -PROTEINS AND THEIR DERIVATIVES - -A comparison of the influence of _proteins_ as contrasted with that of -their digested products, the _amino-acids_, it was thought, might furnish -a clue as to the extent of which the alleged activity of the _digestive -glands_ was responsible for the increased uric acid output that followed -the intake of non-purin protein food. - -Such was the supposition entertained by H. B. Lewis, M. S. Dunn, and E. -A. Doisy. Alive, moreover, to the deficiency of 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). - -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 _variations_ to be expected _normally_ in the subjects -when _fasting_. “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 _purin-free_ diet.[13] - -Passing now to the results obtained, it was noted that, after the intake -of three types of _purin-free_ protein food (egg white, cottage cheese, -and glidine), there ensued _a rise in uric acid output_, 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 _excretion -of the endogenous uric acid is increased by purin-free protein food_. - - -AMINO-ACIDS AND DICARBOXYLIC AMINO-ACIDS - -But the further interesting fact emerged, viz., that _glycocoll_ and -_alanine_, end-products of protein digestion, also _augmented_ uric acid -excretion; moreover, this even more swiftly than _proteins_, the maximum -being reached within two hours after their intake. - -In addition, like results followed the ingestion of the _dicarboxylic_ -amino-acids (glutaminic and aspartic acids), the increase in endogenous -uric acid excretion being even more pronounced than with glycocoll or -alanine. - -Now, it must be recalled that the _amino-acids_ represent the -_end-products_ 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 -_rises in endogenous uric acid_ observed following the ingestion of four -different amino-acids can be attributed to the _work of the digestive -glands_.” 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 _blood-stream_ to be stored -up temporarily in the _tissues_. - -The question that now confronted the observers was whether the -stimulation of nuclear metabolism was an _inherent_ property of -amino-acids. If so, “_substituted_ 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.” - -To this end, they selected _sarcosine_ or _methyl-glycocoll_ 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 _no_ 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 _inherent_ property of -_amino-acids_; in other words, that if an amino-acid when ingested does -not undergo disruptive katabolism, it is without effect on uric acid -excretion. - -Now _deaminisation_ is the first stage in the katabolism of -_amino-acids_, yielding as products _ammonia_ and _a-ketonic_ or _hydroxy -acids_. The ammonia thus formed normally undergoes conversion into _urea_ -and is excreted as such. In order to ascertain whether the _ammonia_ -stimulated uric acid excretion, _ammonium chloride_ was administered, -but no rise in the uric acid output above the normal level ensued. -Also, the ingestion of _urea_ seemed to entail no appreciable increase -in the uric acid elimination; in other words, these katabolic products -of the _nitrogenous_ moiety of the amino-acids are without effect. -As to the _non-nitrogenous_ intermediary products of the katabolism -of amino-acids, _i.e._, the _a-ketonic_ or _hydroxy acids_, it was -impossible to investigate the influence of these on the endogenous uric -acid elimination.[14] - -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 _nuclear katabolism_, but also _nuclear -anabolism_, may be accelerated by the presence of large amounts of -amino-acids. - -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 _intensified activity of the -digestive glands_. - -_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.”_ - -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 _nuclear_ disruption, -concurring with Burian’s view, that a moiety thereof may be derived from -the _hypoxanthine_ of _muscular_ tissue. - - -ENDOGENOUS URIC ACID EXCRETION - -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, _e.g._, -muscular exercise, the amount of the endogenous uric acid excreted is, -for the same individual, fairly _constant_, and this _irrespective of -diet_; but it is not the same for _different_ individuals, even those of -identical body weight. - -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. - -Now Burian and Schur’s original contention was that, in a given -individual on a _purin-free_ diet, the endogenous purin output was -_constant_, and this despite _marked_ variations in the amount of the -purin-free food digested. - -Recent researches, however, of Folin and of Hopkins and Hope, indicate -that this dictum must be modified to this extent, viz., that although it -is true that the endogenous excretion continues remarkably constant, with -_moderate_ variations in the amount of purin-free food, it is not so in -the presence of _marked_ variations. - -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 _urea_ and _uric acid_ excreted in the urine. - - ------------------+--------------+--------------+-------------- - | | Uric acid. | Amount of - Time. | Urea. Grams. | Milligrams. | urine. C.C. - ------------------+--------------+--------------+-------------- - 10-11 | 1·07 | 26 | 175 - 11-12 | 1·13 | 27 | 118 - 12-1 p.m. | 1·07 | 24 | 164 - 1-2 (meal). | 0·64 | 21 | 60 - 2-3 | 1·12 | 22 | 43 - 3-4 | 1·16 | 38 | 41 - 4-5 | 0·84 | 40 | 53 - 5-6 | 1·16 | 56 | 59 - 6-7 | 1·20 | 39 | 56 - 7-8 | 1·37 | 30 | 95 - 8-9 | 1·47 | 33 | 183 - 9-10 | 1·33 | 24 | 155 - 10-11 | 1·33 | 23 | 180 - ------------------+--------------+--------------+-------------- - -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 _uric acid_ 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. - -Horbaczewski referred such increase in uric acid excretion to a digestive -_leucocytosis_; 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 _after_ 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 _pneumonia_, 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 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. - -Lastly, Walker Hall, discussing endogenous uric acid excretion, -emphasises the necessity of discriminating between the _uric acid_ -output and the _total purin_ output. He reminds us that the actual cell -nucleins belong chiefly to the group of amino-purins, _i.e._, 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. - -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 _uric acid_ output varies considerably, the -_total purin_ 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 _uric acid_.” - -This being so, we shall now pass on to consider other conditions -influencing endogenous uric acid excretion. - - -FACTORS INFLUENCING ENDOGENOUS URIC ACID EXCRETION - -The output of endogenous uric acid excretion is influenced by (1) -Physiological conditions, (2) Pathological states, and (3) The ingestion -of certain drugs. - - -PHYSIOLOGICAL CONDITIONS - -It is now recognised that the purin bases of the body exist not only in -the bound form (nucleic acid), but also _free_, especially in _muscular_ -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, -_inosinic_ acid, a nucleotid first isolated from meat extract, yields -phosphoric acid and the purin base, _hypoxanthine_. In possession of -these facts, we shall be better able to appreciate the significance of -the researches of Burian and others. - -(_a_) _Muscular Exercise._—According to Burian a large increase in the -excretion of uric acid was found to follow _muscular exercise_. The same -observer also noted the presence of _hypoxanthine_ in 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 _muscular -action_, and that this substance or its precursor, _inosinic acid_, was -an important source of _endogenous uric acid_. 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 _purin bases_ failed of oxidation, and -consequently a larger amount of the same, as compared with uric acid, -passed into the circulation. - -Kennaway, discussing the effect of _muscular exercise_ on the excretion -of endogenous purins, noted that during unaccustomed exercise the _uric -acid output_ 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. - -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. - -(_b_) _Periodic Variations._—Leathes noted _diurnal_ and _nocturnal_ -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. - - -PATHOLOGICAL STATES - -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 _fevers_. 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 three _uric acid_ 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 _uric acid_ 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. - -In _leukæmia_ protein-destroying forces are at work, and the urine -contains large quantities of _uric acid_. The same is attributed to the -formation and destruction of enormous numbers of _leucocytes_, 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 _purin bases_, sometimes with, and -sometimes without increase in the uric acid; while others again have even -noted a decrease in uric acid and _phosphoric acid_ excretion. - -Apart from these contradictory findings, it would appear, according to -Magnus-Levy, that in _acute_ 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 _myelogenous_ variety being much more -marked than in the _lymphatic_ form. - -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 _nuclein katabolism_, with sequential appearance of _uric -acid_, _purin bases_, and _phosphoric acid_ 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. - -As to this question of the relationship of _leucocytosis_ to _uric acid -excretion_, 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 _leucocytosis does not invariably -accompany increased uric acid excretion_. Indeed, Hutchison and MacLeod -have recorded cases of _leucopenia_ without any reduction in the amount -of uric acid eliminated. - -Also, we have to recall that on a _purin-free_ diet the amount of -endogenous uric acid is more than can come from _nuclein_ destruction -in the body. As suggested by Burian, some may be derived from the -_hypoxanthine_ 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. - -In conclusion, it would appear that some _drugs_ 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. - - -SYNTHETIC FORMATION OF URIC ACID - -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 _synthesis_ is the chief -mode of formation of uric acid, homologous with the formation of _urea_ -in the liver of mammals. - -If this be true of birds, on the other hand, _splitting_ and _oxidation_ -of _nucleins_ is in _mammals_ 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 _purin-free_ 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 _marked_ 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 _non-purin_ 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). - -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. - -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., _lactic_, -_tartronic_ and _B-oxybutyric acids_. - -But, as MacLeod, discussing these experimental and clinical findings, -observes, there are to hand even more direct proofs that _purin -synthesis_ 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, _e.g._, 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. - -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 _nucleic acid_ 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 _splitting_ and -_oxidation_ of _nucleins_; in other words, that uric acid in the main -is derived from the _amino-purins_ by _deaminisation_ and subsequent -oxidation, and from the _oxy-purins_ directly by oxidation. - - - - -CHAPTER VIII - -FORMATION AND DESTRUCTION OF URIC ACID - - -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 _uric acid_ from _nucleic -acid_ 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. - -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 _yeast_, and the other from the _thymus -gland_; in other words, to representatives of the only two nucleic acids -in nature, one derived from the nuclei of _animal_ cells, the other from -the nuclei of _vegetable_ cells. - -A feature common to nucleic acids of animal and vegetable origin is -that, on hydrolysis with boiling mineral acid, they yield two purin -derivatives, _guanine_ and _adenine_, and a pyrimidin derivative, -_cytosine_. From thence as regards their remaining constituent elements -they display distinctions. Thus animal nucleic acids yield _thymine_, and -contain a _hexose_ group in their molecule. On the other hand, vegetable -nucleic acids give forth _uracil_ and possess a _hexose_ group. - -To sum up, _nucleic_ 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 _purin bases_ are always -present, yet, in respect of their _carbohydrate_ group, nucleic acids -display variations; this, according as they are of animal or vegetable -origin. If the former, the carbohydrate group is a _hexose_ (contains six -carbon atoms) with _thymine_. If the latter, it contains _pentose_ (five -carbon atoms) with _uracil_. - -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 _nucleic acid_ of animal -origin. - -[Illustration: STRUCTURAL FORMULA OF NUCLEIC ACID] - - -DISTRIBUTION OF THE ENZYMES - -The enzymes responsible for the disruption of the _nucleic acid_ 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 _liver_, _spleen_, -_thymus_, and _pancreas_ 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 _xanthine_ into _uric acid_, -viz., _xanthine-oxidase_, 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 and kidney. The dog, however, appears -to be an exception, _xanthine-oxidase_ being found in a variety of its -tissues. - -_Adenase_, 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 _adenine_ be injected subcutaneously in rats, it -undergoes oxidation, without abstraction of its amino group. - -On the other hand, _guanase_, also a deaminising enzyme, is in man to be -detected in the _kidney_, _lung_, and _liver_, 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 _guanine gout_ met with in swine. It is worthy of note also -that in pigs’ urine the content of purin bases exceeds that of uric acid. - -To sum up, in man the enzyme, _xanthine-oxidase_, which forms uric acid -from xanthine, is located chiefly or exclusively in the _liver_. This, -of course, represents the _final_ 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 _intestinal juices_ and -_wall_, and to a consideration _seriatim_ of these changes we now proceed. - - -STAGES IN DISRUPTION OF NUCLEIC ACID - -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 _nucleo-protein_ is subjected to the gastric juice a moiety of -protein is readily split off and hydrolysed to peptone and other products -of proteolysis. - -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 _nucleic acid_ -remains unaffected by the pancreatic juice, but, coming in contact with -the _succus entericus_, it undergoes partial decomposition through the -action of a ferment called nuclease or _nucleic_-acidase. Under its -disruptive effect the nucleic acids or _poly-nucleotides_ are further -split up into groups known as _nucleotides_. The two _pyrimidine_ -nucleotides split off and undergo no further change. But, through the -action of another ferment, _nucleotidase_, the _purin_ nucleotides are -further decomposed to yield _nucleosides_ (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). - -No further stage in hydrolysis of nucleic acid occurs in the intestine, -but the _nucleosides_ are again in turn split up after reaching the -tissues, particularly in the _spleen_, _liver_, and _thymus_. This, -under the action of specific enzymes, _nucleosidases_, which succeed in -breaking the nucleosides down into the so-called “building stones” of -the _nucleic acid molecule_, 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 _adenase_ -and _guanase_, converted and, by the removal of their amino group, -transformed, adenine into hypoxanthine, and guanine into xanthine, thus:— - - C₅H₅N₅ + H₂O = C₅H₄N₄O + NH₃; C₅H₅N₅O + H₂O = C₅H₄N₄O₂ + NH₃ - Adenine. Hypoxanthine. Guanine. Xanthine. - -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. - - C₅H₄N₄O O—C₅H₅N₄O₂; C₅H₅N₄O₂ O C₅H₄N₄O₃ - Hypoxanthine. Xanthine. Xanthine. Uric acid. - -[Illustration: SCHEME ILLUSTRATING THE PROBABLE STAGES IN THE PASSAGE OF -PURIN THROUGH THE BODY (WALKER HALL)] - -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 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 _nucleic -acid molecule_. Thus, the molecule in its entirety is termed a -_tetra-nucleotide_. 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 _di-nucleotides_, which immediately divide up -into four _mono-nucleotides_. These ferments are:— - -(1) _Phospho-nuclease_ (which splits off the phosphoric acid radicle, -leaving a nucleoside, guanosine or adenosine). - - - H₂PO₄—C₅H₈O₃—C₅H₄N₅O + H₂O----->H₃PO₄ + C₅H₉O₄—C₅H₄N₅O - Guanylic acid. Phospho-nuclease. Guanosine. - -(2) _Purin-nuclease_ (which splits off the purin radicle, viz., separates -out both phosphoric acid and carbohydrate groups, leaving free purin -bases). - - - H₂PO₄—C₅H₈O₃—C₅H₄N₅O + H₂O----->H₂PO₄—C₅H₉O₄ + C₅H₅N₅O - Guanylic acid. Purin-nuclease. Guanine. - -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 -_deaminising_ effect the amino group is abstracted, with the formation -of either free _oxy-purins_ or oxy-purins still bound in glucoside-like -combination with sugar. - -If the oxy-purins are free, the following is the reaction:— - - - C₅H₅N₅O + H₂O------>C₅H₄N₄O₂ + NH₃ - Guanine. Guanase. Xanthine. - -Should, however, the guanine glucoside be present:— - - - C₅H₉O₄—C₅H₄N₅O + H₂O------>C₅H₉O₄—C₅H₃N₄O₂ + NH₃ - Guanosine. Guanosine-deaminase. Xanthosine. - -In the latter instance a hydrolysing enzyme, _xanthosine-hydrolase_, 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:— - - - C₅H₅N₅ + H₂O------>C₅H₄N₄O + NH₃ - Adenine. Adenase. Hypoxanthine. - -or indirectly through the agency of adenosine-deaminase, the -hypoxanthine-glucoside (inosine) is formed, and subsequently the -hypoxanthine is split off. - -Xanthine and hypoxanthine are, therefore, now to hand, and given the -presence of oxygen, their oxidation to _uric acid_ ensues:— - - - C₅H₄N₄O + O---------------------> C₅H₄N₄O₂ - Hypoxanthine. Hypoxanthine-oxidase. Xanthine. - - C₅H₄N₄O₂ + O----------------->C₅H₄N₄O₃ - Xanthine. Xanthine-oxidase. Uric acid. - -Now, in man and the anthropoid apes, _uric acid_ is the end-product of -_purin_ 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 _allantoin_,[15] this -change taking place in most mammals chiefly in the _liver_. 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. - -[Illustration: DISRUPTION OF NUCLEIC ACID MOLECULE (AMBERG AND JONES).] - -In man, as in most mammals, uric acid is formed chiefly in the _liver_ -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. - - -DESTRUCTION OF URIC ACID - -_Uricolysis_, or the destruction of uric acid, is, in most mammals, -achieved through the agency of the oxidising enzyme _uricase_, which -oxidises uric acid to _allantoin_. 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 _allantoin_. 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, _e.g._, dogs, pigs, and rabbits, a large proportion of the purin -excretion assumes this form. - -Now, the absence of _uricase_, in _man_, is held to be proved by the -fact established by Wiechowski and others, viz., that uric acid, if -_injected subcutaneously_, 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, _nucleic acid_ or _purins_ are by no means -_quantitatively_ excreted in the urine, even though not only _uric acid_, -but also _allantoin_ and the _purin bases_, are included within the -estimate. According to most experiments, a considerable proportion of the -purin-nitrogen intake, about 50 per cent., is excreted as _urea_. - -The question then arises as to what becomes of that moiety of the _food -purins_ which fails to appear in the urine as _uric acid_. 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. - -Accordingly, if, as experimental feeding with _purins_ or _nucleic acid_ -appears to indicate, purins are destroyed in the body they “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 _in vitro_ 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. - -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 _impasse_ 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 _bacteria_. - -Stewart, however, in his “Physiology,” discussing _uricolysis_, maintains -that a considerable destruction of uric acid and other purin bodies -goes on in the body and mainly in the _liver_. 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 _liver_”; this, through the agency of a special ferment called the -_uricolytic enzyme_. - -Also, Flack and Hill, discussing the metabolism of _nuclein_, hold that -some of the uric acid thus formed may be transmuted into urea by an -uricolytic ferment present in the _liver_, muscles, and _kidneys_. 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.” - -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 _in vitro_; 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 be destroyed _in vitro_, it may -nevertheless be destroyed in the living animal.” - -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 _sub judice_. 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 _absence_ or a -_diminution_ in the amount or activity of this _uricolytic ferment_. - -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 _uric-acid-destroying enzyme exists -in the body_, it would seem that, _ipso facto_, man, through lack of this -capacity for rapid oxidation of uric acid, is, by this same disability, -rendered a potential victim of _uric acid retention_ and _deposition_. - -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, _uricase_ is wholly absent. In -respect of this _lack of a uric-acid-destroying ferment_, the Dalmatian -breed of dog has a _purin_ metabolism apparently identical with that of -man.[16] 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 _allantoin_ 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. - - - - -CHAPTER IX - -URIC ACID IN RELATION TO GOUT - - -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 -_uricæmia_ 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. - -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. - -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.e._, a notable increase in the excretion of uric acid -during the paroxysm. - -These results were again in 1900 confirmed by Chalmers Watson. An -exhaustive study of a series of cases of _acute gouty polyarthritis_ -convinced him that:— - - (1) The alkalinity of the blood is not diminished during the - attack. - - (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. - - (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 _de novo_ in search of the - cause of the acute paroxysm. - -The iconoclastic revelations of the foregoing researches may well form a -preface to our discussion of gout from the triple aspect of:— - - (1) Uric acid excretion. - (2) Uricæmia. - (3) Uratosis. - - -URIC ACID EXCRETION IN GOUT - -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. - -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.[17] But, fortunately, -we can now to some extent control and review our urinary findings in -light of the uric acid content of the _blood_. But we anticipate, and -meanwhile let us confine our discussion to the variations in uric acid -excretion that occur in _gout_, 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 -_acute_ attacks of the disorder, and subsequently the same as met with in -its more _chronic_ manifestations. - - -URIC ACID VARIATIONS IN ACUTE GOUT - -Generally speaking, there appears to be a consensus of opinion on the -following points:— - - (1) That in the _intervals_ between _acute_ attacks of gout the - elimination of uric acid lies within the normal limits, but that - - (2) For one or two days _prior_ to an acute attack an - appreciable _decline_ in the output of uric acid occurs. This, - however, is not so marked as the subsequent - - (3) _Increased_ output of uric acid _during_ 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. - - (4) Following attack a tardy decline in uric acid output to - former level. - -To sum up, during an attack of _acute_ gout the uric acid output stands -at a relatively low level between the paroxysms. But one or two days -before the oncoming attack a _diminution_ in uric acid output ensues. -In contrast with the outbreak of the attack, the uric acid excretion -_increases_ markedly, this enduring for a week or more, when the output -again _declines_. The augmented output _during_ the paroxysm is more -constant than the diminished excretion antecedent thereto. Now, while it -may be taken that the foregoing variations in _uric acid output_, 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.” - - -URIC ACID VARIATIONS IN CHRONIC GOUT - -It must never be forgotten that the _elimination of uric acid_ displays -wide _variations_, this even when the subject under investigation is on -a _constant_ 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.” - -None can gainsay the truth of these reflections, for, when placed on -a fixed diet, the uric acid output in the victims of _chronic gout_ -differs but little from that of _normal_ individuals on a similar regime; -save in this respect, that, following the intake of _purin-containing_ -substances, the period of augmented uric acid excretion that ensues is -_prolonged_ as compared with the normal. - - -RETARDED EXOGENOUS URIC ACID OUTPUT - -In 1901 Vogt showed that in gout the excretion of exogenous purins was -not only delayed but diminished. Giving simultaneously to a _gouty_ -subject and a _healthy_ individual a diet rich in purins, he found that, -in the former, _retention_ and _delayed excretion_ of _purins_ ensued. -Vogt’s findings were confirmed by Reach, Soetbeer, Pollak, Mallory, and -others. - -Brugsch and Schittenhelm also observed that, following the intake of -purin-containing substances, the exogenous uric acid excretion was -_retarded_ and _reduced_; 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. - -On the other hand, Walker Hall finds that, though there is _retardation_, -there is _no diminution_ 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.” - -The same observer states that, given _intravenous_ injection of acid -into a _normal_ 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 _atophan_, 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 _gouty_ -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 _sodium salicylate_ to vegetarians of five or more -years’ standing. To sum up, the above findings would appear to indicate -that:— - - (1) A gouty subject can excrete exogenous purins as adequately - as a normal man, but he takes longer to do so. - - (2) If the extra purins be taken during a course of atophan, - even this departure from normal is obliterated, _i.e._, the - customary delay in excretion is obviated.[18] - -But, unfortunately for the diagnostic valency of this symptom in gout, -viz., _retarded exogenous purin output_, it has not been found to be -_invariable_. 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 _not peculiar to gout_. - -The inference then would appear to be that:— - - (1) Reduction and retardation of the excretion of exogenous - purin, though common in gout, is not invariable. - - (2) The same is not peculiar to gout, but occurs in other - disorders. - - (3) Its diagnostic valency, as a characteristic feature of - gout, is correspondingly depreciated. - - -LOWERED ENDOGENOUS URIC ACID OUTPUT - -As a rule, gouty subjects, on a _purin-free_ diet, excrete less -endogenous uric acid than _normal_ persons. Thus, according to Walker -Hall, the average daily endogenous urinary uric acid output of a _normal_ -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.[19] - -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 _periods of high, and periods of low, -endogenous uric acid excretion_.” These variations, they hold, are not to -be accounted for by either mild or severe attacks of gout, for they occur -in the _attack-free_ period. - -Again Laird, investigating the elimination of endogenous uric acid in a -case of _chronic_ gout, noted that the output thereof was _sub-normal_, -and, as Brugsch and Schittenhelm observed, the same presented marked -_variations_. 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 _gouty_ -subjects, found that the output thereof is at its minimum before an acute -attack of gout. - -The foregoing observations would suggest that the _retention_ or delayed -excretion of uric acid applies both to _exogenous_ and _endogenous_ -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 _urine analysis_ have not been very -numerous.” Thus we cannot, on the basis of the _variations_ in _uric -acid excretion_, presume to diagnose gout; in other words, if we take -_urine analysis_ 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 _rheumatoid arthritis_, etc., there is a disturbance of _purin_ -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 -_uric acid_. - - -OTHER ANOMALIES IN EXCRETION IN GOUT - -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 _purin bases_ to -uric acid is unaltered in the urine of gouty subjects. - -Again, all _nucleins_ contain a _phosphoric_ 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 recall to the reader that in the chapter on -protein metabolism it was pointed out that the _amino-acids_, especially -_glycocoll_, are found in excess in “gouty” urines. - -In conclusion, it must, we fear, be admitted that the results of -_urinary analyses_ 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 _blood_ by modern methods can in any way shed further light on -this obscure problem. - - -PURIN METABOLISM IN OTHER DISORDERS - -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 _rheumatoid arthritis_ 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 _purin -metabolism_ in instances of rheumatoid arthritis. - -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.” - -W. J. Mallory, critically analysing Ackroyd’s cases, points out that he -used only _hypoxanthine_ in his studies; also that, while _hypoxanthine_ -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 _nucleinic acid_ 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. - -Alive to these advantages, Mallory, in addition to hypoxanthine, used -_nucleinic acid_ 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 _hypoxanthine_, showed -no deviation from the normal. On the other hand, when given _nucleinic -acid_, 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. - -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. - -“In these cases the period of increased uric acid excretion which -follows the administration of purin-containing substances is much -_prolonged_. Following the administration of purin-containing substances, -a considerable number of cases suffer from attacks of _sub-acute -arthritis_, accompanied in some cases by an increased uric acid -excretion.” - -It will be seen that in virtue of:— - - (1) The prolongation of the period of exogenous uric acid - excretion, and - - (2) Increased uric acid excretion during attacks of sub-acute - arthritis, - -certain cases of _rheumatoid arthritis_ manifest a certain resemblance to -gout, though, as Mallory remarks, “other features characteristic of that -disease are lacking.” - -It may be observed that the attacks of _sub-acute arthritis_ that ensued -in rheumatoid subjects followed the administration of _hypoxanthine_, -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 -_gouty_ 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 _nucleinic_ -acid to gouty subjects. - -Another feature worthy of note is that, in the cases of _rheumatoid -arthritis_ investigated by Ackroyd and Mallory, the percentage of -exogenous purin nitrogen excreted as uric acid nitrogen largely exceeds -that observed in any case of _gout_ available for comparison by these -authors. - -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.” - - -PURIN METABOLISM IN CHRONIC ALCOHOLISM AND PLUMBISM - -Quoting from Mallory’s contribution, we note that Pollak investigated the -purin metabolism in a series of cases of _chronic alcoholism_. In five -of the examples a marked derangement of _purin metabolism_ 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 _non-gouty_ 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. - -Mallory’s observations, too, on uric acid excretion in gout complicated -by _lead poisoning_ 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 _renal_ disease, while in -Mallory’s two cases such was absent, the urine being normal, and likewise -the blood pressure. - -Again, Pollak in a case of _lead gout_ noted an extremely _low endogenous -average_, 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 _renal_ disease. - -Reverting to Mallory’s conclusions, this observer’s studies of examples -of _gout_ with _lead poisoning_ 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”:— - - (1) Slight fluctuation in the endogenous excretion. - - (2) Low endogenous average. - - (3) Small percentage of exogenous purin nitrogen excreted as - uric acid nitrogen. - -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 _causa -causans_ 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. - - -INFANTILE GOUT - -Apart from the fact that gouty arthritis may occur in young children, -Comby and other observers have noted that children born of _gouty_ -parents display a tendency to inflammatory changes in the cutaneous -tissues and also in the mucous membranes. - -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 _gouty_, diabetic, and arthritic subjects. - -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 _purin metabolism_ identical with that met with in _gouty_ -patients. - -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 _blood_ may clarify and illumine the conflicting results obtained by -urine analysis. - -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 _renal_ origin of gout; for we take it that, with the phenomena -of _uric acid excretion_ in _gout_ 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. - - - - -CHAPTER X - -THE RENAL THEORY OF GOUT - - -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. - -Broadly speaking, the arguments adduced tend to concern themselves with -or rather to arise out of certain apparent _abnormalities_ in _uric acid -excretion_, currently held distinctive of gout, certain resemblances also -suggestive of a hidden _nexus_ between _gout_ and _renal_ disorders, -viz.:— - -(1) _Anomalies in uric acid excretion in gout._ - -(2) _Uricæmia, a condition common to gout and nephritis._ - -(3) _Uratosis, a feature also common to both disorders._ - -(4) _Occasional co-existence of gout and nephritis._ - - -ANOMALIES IN URIC ACID EXCRETION IN GOUT - -As to the variations in _purin_ excretion that occur in _gout_, 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 (_a_) the acute paroxysm, (_b_) the -excretion of exogenous purin. - -_The Acute Paroxysm._—Garrod, it will be recalled, claimed that during -an _acute_ 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 _blood_ and _urine_, which constituted the basis of his -hypothesis that gout was due to _renal inadequacy_, have, as previously -noted, been categorically disproved. - -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 _renal block_. It is that, _one or two days prior to -an acute attack_, an appreciable _decline_ in the output of uric acid -occurs. - -But this, be it noted, is neither so marked nor so constant as the -subsequent _increase_; in short, at the zenith of an acute attack, _an -augmented output of uric acid_ 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 _invariable_, an obvious _caveat_ against -hasty _etiological_ 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 _healthy_ individuals, and assuredly, _on the mere -basis of the fluctuations in uric acid excretion_, no diagnosis of gout -is possible. - -_Retarded Purin Elimination._—The mainstay in argument, however, as -advanced by more modern advocates of the renal theory of gout, is that a -_retarded output of exogenous purin_ 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 _rapidity of transport_ 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 _kidneys_, 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 _sodium mono-urate_ or in _organic_ -combination. - -Moreover, experimental _injections of uric acid_ into the _tissues_ or -_veins_ 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.” - -Again, given _intravenous_ injection of uric acid into a _normal_ -man, its excretion occupies several days, and it fails to appear -_quantitatively_ in the urine. But if administered during a course -of _atophan_, then the _whole_ amount injected is excreted within -twenty-four hours. If the same procedure be followed in a _gouty_ -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, _quâ_ uric acid excretion, in the _gouty -kidney_, one would scarcely expect a wholly _normal_ reaction thereto. -Surely some disparity would be disclosed, some aberration in response as -compared with _normal_ renal organs. - -Again, while McLester and others claim that atophan exerts “a selective -stimulating influence on uric acid excretion,” it is quite possible that -its _rôle_ may be otherwise explained. May it not influence the actual -_formation_ of uric acid, or, failing this, the _form_ in which it is -presented to the kidneys for excretion? Nicolaier and Dohrn, indeed, -believe that _atophan_ influences in some way purin metabolism within -the _muscles_ and so leads to _increased formation and excretion of uric -acid_. At any rate, whatever be the explanation of the action of atophan, -the fact that _healthy_ and _gouty_ kidneys react _alike_ thereto cannot -be interpreted as proof of defective capacity for uric acid elimination -in gouty subjects, indeed the reverse. - -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 _primary_ or _secondary_ to the gout. That the kidneys are frequently -functionally inefficient in the _later_ stages of gout may be conceded. -But what of the _initial_ 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 _auricular tophi_, have -yet experienced no frank attack of gout? - -In this connection we may note that McClure has recently emphasised -the fact that the _kidneys_, in the _later_ stages of gout, are often -_functionally_ deficient, and that, accordingly, the faulty elimination -of exogenous uric acid by gouty persons may be simply the result of such -_functional renal depression_; in other words, not due to gout, but to -the _secondary_ or _associated renal deficiency_. 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 _exogenous -uric acid elimination_ as an aid to the diagnosis of gout. Consequently, -he holds that before the diagnostic status of retarded purin -elimination, as a symptom of gout, can be established, an investigation -of the output of uric acid in the different types of _nephritis_ is -essential. - -From the foregoing it will be seen that we stand in urgent need of -further studies of _early_ or _oncoming_ gout and of _early nephritis_ -before we can with certitude impeach the _kidneys_ 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 -_invariable_ in gout. Nor, for that matter, is it _peculiar_ to gout, -considerations both of which, if confirmed, will still further discount -the _diagnostic_ significance of this phenomenon. - - -URICÆMIA IN NEPHRITIS - -Von Jaksch and Klemperer noted long since that in chronic interstitial -nephritis urates are always present in the _blood_. 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 _kidney_ be deficient, the -uric acid content thereof rises, sometimes to as high as from 15-20 mg. -per 100 c.c. - -But more interesting still the fact noted by Fine, viz., that even in -_early_ interstitial nephritis the same feature is well marked, _i.e._, -the blood may contain 4-8 mg. of uric acid per 100 c.c. Indeed, according -to this authority, increase in the _uric acid_ 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 _urea_ or -_creatinine_. The sequence would appear to indicate that the damaged -organ encounters greater difficulty in excreting _uric acid_ than these -other metabolites. - -But, _pari passu_ with the advance of the renal disease, retention of -_urea_ is superadded, and still later _creatinine_. So constant, indeed, -the sequence that, by determining the percentage amount of these three -_metabolites in the blood_, the measure of the renal mischief may be -gauged. - -But of striking significance is the further point established by Myers -and Fine, viz., that the blood content, in respect of _uric acid_, -_urea_, and _creatinine_, in _early nephritis_, is an almost exact -replica of that met with in typical cases of _gout_. 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. - - -URIC ACID, UREA N, AND CREATININE OF BLOOD IN GOUT AND EARLY AND LATE -NEPHRITIS - - ===========================+=====+===========+===========+========= - |Uric | Urea N. |Creatinine.|Systolic - Diagnosis. |acid.|Mg. to 100 | | blood - | |c.c. blood.| |pressure. - ---------------------------+-----+-----------+-----------+--------- - Typical cases of gout. | 9·5 | 13 | 1·1 | 230 - | 8·4 | 12 | 2·2 | 164 - | 7·2 | 17 | 2·4 | 200 - | 6·8 | 14 | 1·7 | - ---------------------------+-----+-----------+-----------+--------- - Typical early interstitial | 9·5 | 25 | 2·5 | 185 - nephritis. | 8·0 | 37 | 2·7 | 150 - | 5·0 | 37 | 3·9 | 130 - | 7·1 | 16 | 2·0 | - | 6·6 | 24 | 3·3 | 185 - | 6·3 | 18 | 2·1 | - | 8·7 | 20 | 3·6 | 100 - | 7·0 | 33 | 2·6 | 117 - | 6·3 | 31 | 2·1 | - | 6·3 | 23 | 2·4 | 150 - ---------------------------+-----+-----------+-----------+--------- - Chronic diffuse and | 8·0 | 80 | 4·8 | 240 - chronic interstitial | 4·9 | 17 | 2·9 | 170 - nephritis. | 8·3 | 72 | 3·2 | 238 - | 5·3 | 21 | 1·9 | 145 - | 9·5 | 44 | 3·5 | 210 - | 2·5 | 19 | 1·9 | 120 - | 7·7 | 67 | 3·1 | - | 6·7 | 17 | 1·6 | 165 - | 8·3 | 39 | 2·9 | - | 6·5 | 24 | 3·0 | 200 - ---------------------------+-----+-----------+-----------+--------- - Typical fatal chronic |22·4 | 236 | 16·7 | 210 - interstitial nephritis. |15·0 | 240 | 20·5 | 225 - |14·3 | 263 | 22·2 | 220 - |13·0 | 90 | 11·1 | 265 - | 8·7 | 144 | 11·0 | 225 - ---------------------------+-----+-----------+-----------+--------- - - (Myers and Fine: “Arch. Int. Med.,” 1916.) - -The salient feature of the table is, however, the fact that in _early -interstitial nephritis_ the retention of _uric acid_ precedes that of -_urea_ or _creatinine_. - -Its importance resides in the reflection that it lends support to those -who contend that _renal change_, leading to failure of excretion of uric -acid, _is the primary cause of gout_; in other words, it gives colour to -Magnus Levy’s contention that the phenomena of gout are referable to “a -deficient and restricted secretory power of the kidney.” The existence -of such a selective excretory incapacity, _i.e._, for _uric acid_, 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 _morphological_ change; in other words, he thinks it conceivable -that a _single_ function of the kidney can become almost exclusively -insufficient, though later real damage to the organ and a nephritis -frequently follow. - -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 _renal disorder_, marked simply by _functional -inability to excrete uric acid_. 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.” - -Furthermore, Levy’s hypothesis involves the assumption that the excreting -functions of the kidney for _uric acid and urea_ are separate and -independent of each other, and to discussion of this we now pass on. - - -THE RELATIONSHIP, IF ANY, BETWEEN THE AMOUNTS OF URIC ACID AND OF UREA, -AND TOTAL NON-PROTEIN NITROGEN IN HUMAN BLOOD - -Taking samples of human blood from (1) _unselected insane_ subjects and -(2) _chronic nephritics_, 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.” - -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 _urea_ and _total non-protein -nitrogen_ of the _blood_ must in the main be inversely proportional to -the general efficiency of the _renal_ organs. Then, obviously, the same -law, too, should, in lack of some other plausible explanation, govern the -excretion of _uric acid_ also. But, as the above generalisation portends, -it is apparently not so. - -Fortunately, Folin and Denis prosecuted their study still further, -taking in examples of _gout_ (with and without clinically recognisable -_nephritis_), also instances of _leukæmia_ and _lead poisoning_. - -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.e._, _the apparent lack of any relationship -between the amount of uric acid and that of urea or total non-protein -nitrogen in the blood_. - -Now in _leukæmia_ the cause of the _uricæmia_ is _over-production_ of -uric acid, but in this instance the same is correlated with an increased -_elimination_ of uric acid by the kidneys. - -Turning to lead poisoning, the medicinal administration of lead acetate -results in a great _diminution_ of uric acid excretion, a response -consistent with the view that lead inhibits the excretory power of the -kidney for _uric acid_, the change, at first functional, becoming later -organic; for it is held that the _uricæmia_, associated with plumbism, -proves that the action of the lead is not due to inhibition of the -formation of uric acid. - -Lastly, as to gout, opinion still wavers as to whether or not the -excretion of uric acid in this disorder is appreciably _lowered_. On -the other hand, it is significant that the reverse is never claimed, -viz., that in gout the uric acid output is _abnormally raised_. Now, as -we saw in _leukæmia_, the _high uric acid blood content_ is accompanied -by a correspondingly _high uric acid output_; but, on the contrary, in -gout, despite the _accumulation of uric acid in the blood_, there is _no -parallel increase in its elimination_. - -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.” - -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.” - -Apart from this, there are several objections to Folin and Denis’ -assumption. - - -URICÆMIA NOT NECESSARILY DUE TO RENAL DEFECT - -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 _a marked increase in retention of uric acid in the blood_ -may result from the ingestion of purin bases even when _no evidence of -retention is found on examination of the urine_.” 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. - -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 _the uricæmia of the gouty is maintained in spite of a fair renal -elimination_.” - - -URICÆMIA NOT PECULIAR TO NEPHRITIS - -Again, a grave obstacle to the acceptance of Folin and Denis’ inference -is that uricæmia, though incidental to nephritis, is not peculiar thereto. - -Thus Roy Upham and Higley noted its presence in 85·6 per cent. of their -cases of _nephritis_; but, on the other hand, they found that no less -than 40 per cent. of another series of clinical cases, not _suffering -from nephritis_, also showed uricæmia. - -This would appear to indicate that, while uricæmia is an exceedingly -common symptom of early chronic interstitial nephritis, it is by no means -_specific_ for that disorder; in other words, its diagnostic valency as a -symptom of _nephritis_ is distinctly limited. - -_Reverting_ now to _gout_, 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 _initial_ 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 _increased_, constitutes strong proof of the reverse. - -Again, as modern investigations show, the variations in the uric acid -content of the _blood_, _re_ the incidence or intensity of attacks, are -most _erratic_. Far from its being essential that uricæmia be present, -acute attacks may occur with even a _sub-normal_ 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 _renal_ -origin. - -If it were so, one would expect no such vagaries in the uric acid content -of the blood. One would rather, given the existence _ab initio_ of a -_renal functional defect_, look for not only a permanent _uricæmia_, -but further, from time to time, augmentations and 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. - - -URICÆMIA DOES NOT NECESSARILY PORTEND GOUT - -If it were so, why does not every case of nephritis develop gout? -The researches of Myers and Fine have shown that _uric acid_ is the -nitrogenous metabolite that first _accumulates_ in the _blood_ in _early_ -interstitial nephritis. Only in its _later_ stages do urea and other -waste nitrogenous products undergo like retention therein. - -Now let us review these findings, _re_ nephritis, in light of another -statement by Folin and Denis, which runs as follows:— - -“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.” - -Is it not clear, then, that in the _early_ stages of _nephritis_, viz., -prior to retention of urea and other waste nitrogen, we have precisely -that isolated functional renal disability, _i.e._, _inability to excrete -uric acid_, that we postulate to be in operation in the _initial_ stages -of _gout_? - -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. - -To our mind, albeit, the disparity carries with it the inevitable -postulate that in gout some other factor intrudes, some _tertium quid_, -something vital, something biological, haply an _infection_. For even if -we grant, for the sake of argument, that _renal retention_, 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. - - -TO WHAT MAY BE ASCRIBED THE DEFICIENT ELIMINATING CAPACITY OF THE KIDNEY -FOR URIC ACID? - -Naturally the advocates of the renal theory had to account in some way -for the alleged functional disability of the kidney. Thus, Sir Dyce -Duckworth, recalling the occasional occurrence in hysteria of _anuria_, -held that, judging from the general phenomena of acute gout, “the -influence of the _nervous system_ ... must not be left out of account as -a possible determining factor for renal inadequacy.” - -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. - -Croftan considers the renal changes in gout identical with those of -chronic plumbism. From experiments with hypodermic injections of -_xanthine_ and _hypoxanthine_ over a prolonged period, he concludes that -the presence of minute quantities of purin bases in the circulation is -capable of producing _marked renal changes_. On the other hand, _uric -acid_, injected into the circulation of healthy animals for a period of -over three months, produced _no renal change_ whatever. - -As to this possibility, viz., that the _circulating uric acid_ might lead -to _nephritis_ in the _gouty_, 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 _gouty_ 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.” - -While they consider that such _urea_ and _total nitrogen retention may_ -possibly bespeak _latent_ or _incipient nephritis_, 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”! - -Again, some have attempted to account for the assumed renal incapacity -as being part of the _tissue peculiarity_ 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.” - -Naturally this suggests the further question, Are there any distinctive -_histological_ changes in the _gouty_ kidney? On this point Walker -Hall has some apposite reflections. Taking Folin’s figures as a -basis, it transpires that in _acute_ and _chronic nephritis_, also in -_arterio-sclerosis_, 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. - -Now in contrast thereto, the blood content in _gout_ and _lead poisoning_ -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 _per se_, 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 -_histological_ changes be taken as a criterion of functional efficiency, -then the _gouty_ kidney should be more capable of excreting freely than -the _diffuse nephritic_ organ. - -How does this work out in actual daily life? he asks. “0·5 gram, in -a _normal_ adult, represents the _average daily endogenous uric acid -excretion_ in the urine, while that of a _gouty_ 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.e._, 0·05 gram, is -distributed between the uric acid pent up in the tissues and the uratic -deposits, _i.e._, tophi.” Walker Hall tells us it has been stated that -about 0·01 gram suffices to cover the amount deposited as _tophi_ 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 _quantitative_, -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 _uricæmia_ is referable to _renal -inadequacy_, it is necessary to postulate _the presence of a poison -acting upon the renal tubules specifically_. - -In the gouty uric acid excretion is maintained at a “_low physiological -level to the very end_,” and it is easier, he thinks, to adopt the above -hypothesis as to its cause than “to conceive of a poison acting upon the -_nuclear_ processes in such a way as to induce a persistently low uniform -level” of purin excretion. - -This view, viz., of a _toxin_ 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 _atophan_. Always we have to recollect, too, that under -_normal_ conditions, even given a _constant_ diet, the elimination of -uric acid displays _wide variations_. Also the uric acid output in the -subjects of _chronic gout_, when placed on a _fixed_ diet, differs but -little from that of _normal_ 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. - -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 _onus probandi why_ gouty subjects should exhibit, or acquire, -such a disability. - - -URATIC DEPOSITS IN NEPHRITIS - -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 -_cartilage_ and _serous membranes_. At these sites they are frequently -detected post mortem, though they fail of _ante-mortem_ recognition. - -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 _renal_ -disease. Out of ninety-six cases presenting renal lesions, no less than -eighteen exhibited uratic deposits in the joints. - -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.” - -Levison, too, an ardent supporter of the primary renal origin of gout, -noted that all the subjects dying at the Communal 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. - -Luff, in the following table, shows the results of the examination of the -joints in seventy-seven cases of _granular kidney disease_. - - -----------------------------+---------------+---------------- - | | Uratic deposits - | No. of cases. | in joint or - | | joints. - -----------------------------+---------------+---------------- - Known to have had gout | 10 | 10 - Never known to have had gout | 67 | 31 - | -- | -- - Totals | 77 | 41 - -----------------------------+---------------+---------------- - -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.” - - -------------------------------+---------------+---------------- - | | Uratic deposits - | No. of cases. | in joint or - | | joints. - -------------------------------+---------------+---------------- - Marked granular kidney disease | 26 | 20 - -------------------------------+---------------+---------------- - -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. - -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 _known not to have had gout_. - - -DIFFERENTIATION OF URATIC DEPOSITS IN GOUT AND NEPHRITIS - -Uratic deposits, it is true, occur in both these disorders. But it is -with a difference. In gout the uratic deposit assumes the form of -_tophi_, 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. - -Again, in gout the deposition is _sudden_ and associated with an acute -paroxysm; while in nephritis it is _gradual_ and unassociated with -inflammatory reaction. - -In gout the uratic deposits are overt, manifest as _tophi_; in nephritis, -occult and unrevealed (ante-mortem). - -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. - -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. - - -CLINICAL ASSOCIATIONS OF GOUT AND GRANULAR KIDNEY - -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 _co-existence_ bespoke some hidden _nexus_, 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— - - (1) Some gouty subjects never develop granular kidney. - - (2) Some individuals with granular kidney never develop gout. - -Also we have to recall that— - - (1) Paroxysms of gout often occur for many years before the - symptoms of interstitial nephritis develop. - - (2) In persons of gouty stock acute attacks may ensue at an age - at which nephritis is practically unknown. - -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 life. In light of this, is it not readily -conceivable that both may arise independently, mere coincidences, both -evidences of _pre-senilism_? Hastings Gilford, indeed, classes gout -with syphilis, lead, and alcohol as amongst “the chief promoters of -pre-senility.” - -Again, certain toxic agents which predispose to or initiate renal -mischief also favour apparently the incidence of gout, _e.g._, _lead_ -and _alcohol_. 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 _causes_ 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. - -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. - -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 _renal_ origin. - -That the victim of gout, despite uricæmia and those unequivocal tokens, -_tophi_, 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, _arterio-sclerosis_ overtakes him with its -correlated _chronic nephritic_ change. - -Is not this very reminiscent of what Walker Hall reminds us of, -the sequence of events in _lead poisoning_ and _alcoholism_? “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.” - -In conclusion, therefore, we see that the weight of clinical evidence -is against the _primary renal_ 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? - - - - -CHAPTER XI - -URICÆMIA IN GOUT - - -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 _qualitative_, 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. - -But not until 1895 was a series of _quantitative_ 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. - -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 _precipitation_ (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. - -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. - - -FOLIN AND DENIS’S METHOD - -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 some of the qualitative methods -when once the technical difficulties are overcome.” He described it as -follows:— - -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 -_n_/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:— - - (20_V_)/(_RW_) mg. of uric acid per 100 grams blood,[20] - -where 20 represents depth in millimetres of standard solution, - - _R_, the depth of unknown solution, - _V_, the volume to which the unknown solution is diluted, - _W_, the weight of blood taken for the determination. - - -URIC ACID A NORMAL CONSTITUENT OF BLOOD - -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 _purin-free_ diet. On the other hand, if the subject’s blood was -found to contain _uric acid_, while on a purin-free diet, it was held a -characteristic feature of _gout_ and of prime diagnostic import. - -But, since the introduction of Folin and Denis’s method, it has been -established that uric acid is constantly present, in demonstrable -amounts, in _human_ blood. These authorities, using their _colorimetric_ -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.” - -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:— - - -URIC ACID, TOTAL NON-PROTEIN NITROGEN AND UREA NITROGEN IN BLOOD - -(The Figures represent Milligrams per 100 grams of Blood.) - - ------------------------------------+-----+-----------+--------- - |Uric |Non-protein| Urea - |acid.| nitrogen. |nitrogen. - ------------------------------------+-----+-----------+--------- - Rabbit (6 cases) |0·05 | 31 | 13 - Sheep (mixed blood) |0·05 | 28 | 13 - Pig (mixed blood) |0·05 | 32 | 14 - Horse (1 case, anti-toxin animal) |0·05 | 54 | 28 - Monkey (1 case, poliomyelitis) |0·05 | 60 | 38 - Beef (mixed blood) |0·2 | 24 | 14 - Cat (2 cases, diet, liver) |0·2 | 60 | 34 - Cat (2 cases, diet, milk and eggs) |0·2 | 67 | 37 - Cat (2 cases, diet, rice and cream) |0·2 | 31 | 20 - Chicken (6 cases, mixed blood) |4·9 | 32 | 8 - Duck (4 cases, mixed blood) |4·8 | 34 | 7 - Goose (1 case) |4·8 | 26 | 8 - ------------------------------------+-----+-----------+--------- - -The most striking feature of these findings is the marked contrast -between the uric acid blood content of _mammals_ 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 _birds_, in whose instance the origin -of uric acid is so different, it is present in relatively large amounts. -As Folin and Denis observe, the small amounts of _urea_ in the blood of -birds, as compared with that of mammals, is also worthy of note. - -Reverting now to the findings in human subjects, as observed by Folin and -Denis, these have been summarised as follows by Walker Hall:— - - -URIC ACID, TOTAL NON-PROTEIN NITROGEN AND UREA NITROGEN IN BLOOD - -(The Figures represent Milligrams per 100 grams of Blood.) - - -----------------------------------+----------+-----------+--------- - |Uric acid.|Non-protein| Urea - | | nitrogen. |nitrogen. - -----------------------------------+----------+-----------+--------- - Human, group 1 | 0·8 | 36 | 19 - Human, group 2 | 1·5 | 34 | 18 - Human, group 3 | 2·8 | 36 | 19 - Human, with blood pressures of 160 | 2·9 | 50 | 33 - Human, with blood pressures of 200 | 1·2 | 50 | 22 - Human, with blood pressures of 220 | 2·7 | 40 | 19 - Human, with blood pressures of 260 | 3·9 | 52 | 20 - Human, alcoholic | 1·0 | 43 | 29 - Human, chronic gout | 3·9 | 25 | 13 - Human, chronic gout | 4·4 | 30 | 15 - Human, chronic gout | 5·2 | 20 | 13 - Human, lead poisoning | 4·7 | 50 | 31 - Human, lead poisoning | 4·8 | 52 | 32 - Human, leukæmia | 3·1 | 33 | 14 - Human, acute nephritis with | | | - arterio-sclerosis | 2·7 | 40 | 19 - Human, chronic nephritis with | | | - arterio-sclerosis | 2·5 | 38 | 19 - -----------------------------------+----------+-----------+--------- - -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 _Psychopathic_ Hospital. - -It may be noted that of all the _mammals_ examined the blood of _man_ -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 _gout_ and _lead poisoning_ 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 -between the amount of uric acid and that of the urea or total non-protein -nitrogen in the blood. - -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 _psychopathic_ 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. - -As before stated, it was until recently maintained that in the blood -of _normal_ individuals, on a _purin-free_ diet, _uric acid_ was -undemonstrable. But McLester, utilising Folin’s method, found uric -acid in the blood of fifteen _healthy_ individuals, who had been on a -_purin-free_ 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 _average_ -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 -_purin-free diet_, while the patients studied by Adler and Ragle were of -all ages and on a _mixed_ diet.[21] - - -EFFECT OF EXOGENOUS PURINES - -As we are aware, the amount of uric acid excreted in the _urine_ -increases markedly on a _purin-rich diet_. But recent researches appear -to raise doubts as to whether the uric acid content of the _blood_ rises -correspondingly. Thus, according to Walker Hall, “a state of _uricæmia_ -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. _in normal_ adults, or even higher after an excessive intake of -_purin-rich_ foods. - -On the other hand, Denis, investigating the effect of ingested purin on -the uric acid content of the blood, found that in _normal_ individuals -_no increase in the circulating uric acid_ follows the intake; in other -words, the kidney, in _normal_ 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 _endogenous_ moiety -thereof has to be eliminated. - -Moreover, another factor, according to Folin and Denis, that operates -in the same direction is the _binding capacity of the tissues for uric -acid_. 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.” - -On the other hand, given damage to the _kidney_ (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.[22] - -Now, as to the second regulating factor, the _retention capacity_ of the -_tissues_ for _uric acid_, it may be said that the amount, in _normal_ -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. - -But, to resume, Denis also demonstrated that the uric acid content of -the blood in patients suffering from various _chronic diseases other -than gout_ was also not increased on a purin-rich diet. To sum up, the -researches of Denis would appear to indicate that:— - - (1) In _normal_ subjects _no increase_ in the _uric_ acid - content of the _blood_ follows exogenous purin intake. - - (2) The uric acid content of the blood in patients suffering - from chronic diseases, other than _gout_ or _renal_ disease, is - similarly _not_ augmented on a _purin-rich_ diet. - - (3) The _uric acid content_ of the _blood_ is _increased_ more - or less markedly, after a short period of purin feeding, in the - presence of defective _renal elimination_. - -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 -_psychiatric_ 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 -_purin-free_ 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 _purine-free_ 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 _gouty_ -subjects after the ingestion of purin-rich substances. - - -URIC ACID CONTENT OF BLOOD IN GOUT - -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 _mono-sodium urate_ than -it can hold in solution (1-8 mg.), in other words, it is in effect a -supersaturated solution of the relatively insoluble _lactim_ urate. - -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. - -At the time of examination the average uric acid content, irrespective of -the diet or condition, was 3·7 mg. In three patients on _ordinary diet_, -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 _purin-free_ 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. - -Seven patients, on a _mixed_ diet, and free at the time from symptoms of -gout, contained on the average 4·3 mg. of uric acid in their blood. - -On the other hand, examination of the blood in six patients on a -_purin-free_ diet, at the time manifesting no acute symptoms of gout, -revealed an average uric acid content of 3 mg. - -From the foregoing considerations it may be deduced that:— - - (1) In gout there is a condition not of uricæmia, but of - _hyper-uricæmia_. - - (2) That on the average the blood in _gouty_ subjects contains - twice as much uric acid as that of _non-gouty_ 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.). - - (3) In contrast with non-gouty subjects, the uric acid content - of the blood in _gouty_ subjects is augmented on a purin-rich - diet. - - (4) Both in the inter-paroxysmal periods and during attacks - the uric acid content of the blood, when on a _mixed_ diet, is - higher than when on a purin-free diet. - - -HYPER-URICÆMIA IN NON-GOUTY ARTHRITIS - -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 _constant_, in other forms of -arthritis it appears to be _transient_. - -He cites a case of _infective_ 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 _purin-rich_ diet. This difference is response to -exogenous purins in gouty, as opposed to _non-gouty_ arthritics, is well -illustrated in the following table. - - 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:— - - --------------------------------+-------+-------------+------------- - | Uric | Non-protein | Urea - | acid. | nitrogen. | nitrogen. - --------------------------------+-------+-------------+------------- - Mgs. per 100 gms. of blood. - Gout with purin dietary | 5·5 | 52 | 36 - Gout with purin-free food | 3·4 | 40 | 18 - --------------------------------+-------+-------------+------------- - - GOUTY POLYARTHRITIS (PRATT). - ---------------------------+----------+-----------------------+---------- - |Milligrams| |Milligrams - | of | | of - |uric acid | |uric acid - | in 100 | | in 100 - | gms. of | | gms. of - | blood. | | blood. - ---------------------------+----------+-----------------------+---------- - D. N. Gout. Purin-free | 3·1 |52 hours after eating | 5·8 - diet. | | 280 grams haddock | - | | roe. | - | |3 days after eating | 6·2 - | | 300 grams roast beef.| - K. Gout. Purin-free diet. | 2·4 |24 hours after eating | 3·0 - | | 270 grams roast beef.| - H. Gout. Purin-free diet. | 1·7 |3 days after eating | 3·6 - | | 150 grams thymus. | - P. Gout. Purin-free diet. | 2·1 |3 days after eating | 3·4 - | | 160 grams thymus. | - J. N. Gout. Purin-free | 2·2 |48 hours after eating | 8·7 - diet. | | 190 grams thymus. | - | --- | | --- - Average | 2·2 | Average | 5·1 - ---------------------------+----------+-----------------------+---------- - - NON-GOUTY POLYARTHRITIS (PRATT). - ---------------------------+----------+-----------------------+---------- - |Milligrams| |Milligrams - | of | | of - |uric acid | |uric acid - | in 100 | | in 100 - | gms. of | | gms. of - | blood. | | blood. - ---------------------------+----------+-----------------------+---------- - McC. Chronic polyarthritis.| 1·7 |24 hours after eating | 2·2 - Purin-free diet. | | 100 grams of thymus. | - M. Chronic polyarthritis. | 2·0 |24 hours after eating | 1·8 - Ordinary diet. | | 225 grams of thymus. | - H. Chronic polyarthritis. | 2·9 |47 hours after eating | 2·5 - Ordinary diet. | | 190 grams of thymus. | - | --- | | --- - Average | 2·1 | Average | 2·2 - ---------------------------+----------+-----------------------+---------- - -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 _gouty_ was 5·1 mg., -while in the _non-gouty_ 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 -_non-gouty_ subjects the uric acid content was found to be practically -unaltered twenty-four to forty-eight hours after the same purine intake. - -It would seem, therefore, that some _diagnostic_ importance may be -attached to the _hyper-uricæmia_ that is induced in _gouty_ subjects -after exogenous purines, as compared with its non-occurrence in non-gouty -subjects. - -Another interesting point elicited by Pratt was that in his _gouty_ -examples, although, after a purin meal, the uric acid content of the -_blood_ rose markedly, yet there was no apparent _delay_ or _diminution_ -in the output of _exogenous purin_ in the _urine_. 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 _gouty_ subjects -the excretion of _exogenous_ purin is _diminished_ and _retarded_. But -Pratt’s study of the blood shows that a marked increase and retention of -uric acid in the _blood_ may result from the ingestion of purin bases, -even when no evidence of retention is found on the examination of the -_urine_.[23] - -The clear inference from this is that it is desirable that our _urinary_ -findings in respect of _uric acid_ should be reviewed and controlled in -light of _blood examinations_ to the same end. - - -VARIATIONS IN URIC ACID CONTENT OF BLOOD INDEPENDENTLY OF DIET - -Considerable variations in the uric acid content of the blood, according -to Pratt, may occur both in _gouty_ and _non-gouty_ subjects, and which -cannot be attributed to any _purin intake_. Such oscillations, moreover, -may ensue within a short time. A patient of his, admitted to hospital -suffering from a severe attack of _gout_, was placed upon a _purin-free_ -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. - -Marked variations in the uric acid content of the blood may likewise -occur in _non-gouty_ subjects. After being on a _purin-free_ diet for two -days, a patient of Pratt’s, with _recurrent iritis_, had 2·2 mg., while a -few months after, when on a mixed diet, his blood contained only 0·8 mg. - -Again, great oscillations in the blood content of uric acid, independent -of diet, are sometimes found in cases of _non-gouty arthritis_. 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 _primary polyarthritis_ -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. - -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 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. - -The deductions that may be drawn from the foregoing findings are:— - - (1) That in _gouty_ subjects pronounced variations of the uric - acid content of the blood may occur which are not attributable - to the purin content of the food. - - (2) That in _non-gouty_ arthritis similar fluctuations in the - blood content of uric acid, irrespective of diet, also occur. - - (3) That in _normal_ persons, on a purin-free diet, the blood - content of uric acid, as far as is ascertained, does not show - such variations. - - -WHAT RELATION, IF ANY, EXISTS BETWEEN THE URIC ACID CONTENT OF THE BLOOD -AND ATTACKS OF GOUT? - -If uric acid be _causally_ related to gout, it would seem reasonable to -expect that the blood content thereof would stand in some clear relation -to the _incidence_ or _intensity_ of attacks. - -But, according to Pratt and others, no variations indicative of such -a relationship obtain. For, independently of _acute_ attacks, and, -moreover, in the absence of any pronounced _renal inadequacy_, the blood -of gouty subjects, even on a _purin-free_ diet, contains, as a rule, 4-9 -mg. of uric acid. - -More pertinently to our point, in the experience of Daniels and -McCrudden, it transpires that, contrary to the usually accepted teaching, -typical _acute_ attacks might occur without any variation in the _uric -acid content of the blood_ or its _excretion_. - -Nor did their iconoclastic findings cease here, for, _mirabile -dictu_! attacks ensued even when the uric acid blood content was at a -_sub-normal_ level; this latter, owing to the victims being at the time -on _atophan_, 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. - -Daniels and McCrudden, too, note that the uric acid content of the blood -in gouty subjects may be _persistently_ lowered, _even under the normal -average_. 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. - -Bass and Herzberg injected uric acid into the blood of gouty subjects -until its content thereof reached 10 mg. per 100 c.c., this without -any joint symptoms supervening. The same observers, aspirating _joint -fluids_ in _non-gouty_ subjects, noted that the uric acid content was -approximately the same as that of the blood. But, in contradistinction -thereto, in two _gouty_ subjects, victims of _uræmia_, 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. - -Furthermore, intravenous injection of uric acid engendered a lesser -degree of _uricæmia_ in the gouty—this despite _impaired renal -excretion_. To their mind, therefore, the inference was that the _bodily -tissues_ in gout display an enhanced capacity for taking up uric acid. - -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. - -To sum up, the main conclusions deducible from the foregoing clinical and -experimental findings would appear to be that:— - - (1) No constant relation has as yet been established between - the uric acid content of the blood and acute attacks of gout. - - (2) No variations in the same apparently herald or accompany - typical acute paroxysms. - - (3) Attacks may occur with a _sub-normal_ uric acid blood - content. - - (4) The tissues of gouty subjects apparently possess an - enhanced binding capacity in respect of uric acid. - - (5) _Given impaired renal excretion in gouty subjects_, - the uric acid content of the _joint fluid_ rises markedly, - exceeding that of the blood. - - -DISCUSSION OF THE FOREGOING DATA - -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 -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 _strictly normal -persons_ are all too few, the findings in _diseased_ 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. - -_The Significance of Uricæmia._—It is generally maintained that the -blood content of uric acid in gout is above normal. Yet the _excretion_ -of _uric acid_, save during acute attacks, rests within physiological -limits. Again, _à propos_ of our claim that the _blood_ is _surcharged_ -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 _uric acid_ per 100 c.c. of -blood serum before deposition tends to occur. On the other hand, _urates_ -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! - -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 _gout_? 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. - -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 _real_ or merely _apparent_. We can, it is true, -extract _uric acid_ and _urates_ from the blood-stream, but it does not -necessarily follow that it is as such that they circulate _in vivo_. -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 _sodium monourate_, or in _organic fusion_. -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. - -_Sources of Fallacy in Uric Acid Estimation._—With Folin’s findings as -his basis, Walker Hall estimates that, excluding the lymphatics and -lymph spaces, the entire blood-stream contains normally 70 mg. of uric -acid, _i.e._, 2 mg. of uric acid per 100 grams of blood, 3,500 c.c. -(total quantity of blood). - -Thence he argues that, inasmuch as about 1 litre of blood traverses -the kidney per minute, the total content thereof of _uric acid_ 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. - -Now, given immediate extraction of all the uric acid by the renal cells, -then the blood in the renal veins will become _free of uric acid_. If so, -the estimates of the uric acid content of the blood will reflect exactly -the measure of the _endogenous_ or _exogenous_ nuclein metabolism. But, -“if the renal vein blood is not _purin-free_, then the _estimations will -fail to yield a true picture of the activities of nuclein exchange_.” - -Again, as to the precise import of isolated estimates of the uric acid -blood content, we must recollect that the _excretion of purins_ is -not distributed evenly over the twenty-four hours, varying as it does -under the influence of food, exercise, sleep, and other factors. _A -propos_ of this, Pratt’s observations clearly show that both in _gouty_ -and _non-gouty subjects fluctuations in the uric acid blood content_ -also occur, and this independently of _diet_. To what, then, may these -variations be referred? Obviously a question of great moment, especially -when we recall the eccentric behaviour of the _blood uric acid_ in -relation to the incidence of _acute gouty attacks_. For, until the inward -meaning of these vagaries is revealed, the value of recorded estimates -must necessarily be discounted considerably. - -We must recall, too, that a certain moiety of the purins derived from -nuclein metabolism lags in the _lymph_ spaces and _lymphatics_, 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 _sodium ions_ than the blood, the -entry of the nucleins therein may be retarded and so lead to a still -further reduction of the blood content. - -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.” - -For, as before pointed out, the enzymes responsible for the ultimate -disruption of the _nucleosides_ 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. - -_Disabilities of Modern Tests._—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 _identical -blood samples_, arrived at results which vary widely. Nor, disconcerting -though it be, do the limitations of this mode of hæmo-analysis cease here. - -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 _isomer_ into another. But, -unhappily, the tests to hand fail of differentiation of the several -_tautomeric_ forms of uric acid. Also, as isomers of uric acid actually -exist, then _quâ_ Walker Hall, why not isomers of _purins_ and -_pyrimidins_ 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. - -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.” - -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 -_real_ 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 _supernormal nuclear activity_ of _generalised or_ localised -distribution. - -_Need for Further Investigations._—While none can doubt that, by means of -chemical investigation of the _blood_, the clinical problem of gout will -be elucidated to a much greater extent than has been possible by means of -_urine analysis_, still much remains to be done before recent findings -can be applied to the solution of the etiology of _gout_. - -The results of _blood analyses_ up to now have afforded us no clue as to -the intimate nature of the warp in _nuclein metabolism_. At the most, -the researches in this sphere do but make it increasingly clear that -uricæmia is _not the cause but the result_ of gout. - -Albeit, this conclusion does not justify us in putting out of court all -thought of _uric acid_ in connection with gout. Any tendency thereto -will be immediately checked when we recall that uratic deposits, _i.e._, -_tophi_ constitute the solitary unequivocal token of gout, and to this -aspect of the question the ensuing chapter will be devoted. - -Meanwhile, systematic investigations of the purin content of the blood, -not only in gouty but in _normal_ subjects, would surely dissipate much -of the obscurity that envelops this complex question. It were well, too, -that _blood_ and _urine_ analyses go hand in hand in our investigations. -How illumining these have been in connection with _atophan_, 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. - -Again, the _excretion of urinary purin_ 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, _e.g._, fever -infections, etc. - -Can it be doubted that the _blood_ 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 _tidal_ 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. - -What, too, as the above authority observes, of the influence on the -_gouty uricæmia_ 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.e._, “infantile gout.” - -We stand also in urgent need of knowledge as to the uric acid blood -content in the _early_ 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 _acute_ attacks, but even more under those conditions -which are presumed to determine their incidence. - -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.” - - - - -CHAPTER XII - -URATOSIS IN RELATION TO GOUT - - -The two salient features of the gouty diathesis are:— - - (_a_) The tendency to excess of uric acid in the blood, _i.e._, - _hyper-uricæmia_, and - - (_b_) The tendency to uratic deposition, _i.e._, _uratosis_. - -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. - -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. - -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. - -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. - -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. - - -CONSTITUTION OF TOPHI - - “Et tophus scaber, et nigris exesa chelydris Creta.” - - _Virgil, Georg._, ii., 214. - -The view that tophi were composed of chalk prevailed for centuries. As -we see such was the conception of Virgil, and in our 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. - - “Knots upon his gouty joints appear, - And chalk is in his crippled fingers found.” - - _Dryden, Pers._ - -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 _urate of soda_. - -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. - -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. - - -MARCHAND’S ANALYSIS - - Urate of soda 34·20 - Urate of lime 2·12 - Carbonate of ammonia 7·86 - Chloride of sodium 14·12 - Animal matter 32·53 - Water 6·80 - Loss 2·37 - ------ - 100·00 - ====== - - -LEHMANN’S ANALYSIS - - Urate of soda 52·12 - Urate of lime 1·25 - Chloride of sodium 9·84 - Phosphate of lime 4·32 - Cellular tissue 28·49 - Water, loss, etc. 3·98 - ------ - 100·00 - ====== - - -EBSTEIN AND SPRAGUE’S ANALYSIS - - Uric acid 59·70 - Tissue, organic matter 27·88 - Sodium oxide 9·30 - Potassium oxide 2·95 - Calcium oxide 0·17 - MgO, Fe, P₂O₅, S Traces. - -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 _biurate_ of _sodium_ and -_potassium_. But, as a rule, after a time _calcium_ 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 _calcium_ 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 _biurate of sodium_. - - -MODE OF FORMATION - -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. - -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.” - -It is, however, quite possible that some substance other than _urate of -soda_ 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 _uric acid -infarcts_, supposed to result from disruption of the nucleo-proteins -of the _fœtal nucleated red corpuscles_, take origin around injured -_epithelial_ cells, which latter form the nucleus. - -As to _gouty tophi_, too, it has been suggested that they form in -response to any _toxin_, resistance to which may involve death of the -tissue cells with consequent disruption of their _nucleins_ and formation -of _urates_. 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. - -In any case, whatever be the exact nature of the nucleus, the 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 _mucin_, animal or earthy matter. Hence, -the concretions display not only a _radiating_, but a _concentric_ or -_laminated_ structure. - -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 _crystalloids_ and _colloids_, evolved from -solutions of the same character. - -The importance of recognising the true nature of this binding substance, -_i.e._, mucin, merits a brief digression, in light of Ebstein’s view that -local tissue _necrosis_ 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. - -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 _framework_ of a crystalline deposit, though such were -currently regarded as _strands_ of _necrotic tissue_. - -But, to resume, tophi being blends of _crystalloids_ and _colloids_, we -must recollect that the suspension capacity of _colloidal_ 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 -_precipitation_ when _crystalloids_ 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 consequently depreciated, the crystalloids are -deposited in intimate relation with the colloids. - -Again, Schade has pointed out that colloids may precipitate in reversible -form or not. If in irreversible (_e.g._, fibrin) form, the concretion -will remain permanent. But if the colloidal precipitate is reversible, -it may be redissolved, as happens with the uric _acid infarcts_ of the -infant’s kidney. In conclusion, we see, therefore, _re_ 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 _formation of -tophi_. - - -LOCALISATION OF URATIC DEPOSITS - -Uratic deposits evince a decided predilection for _cartilages_, tendons, -muscles, and skin. This localised distribution of the depositions would -seem to suggest their dependence on _local tissue peculiarities_. Now -the presence of _sodium_ salts in a solution diminishes the solubility -of urates therein. Consequently, in seeking to explain the incidence of -_tophi_, it was suggested that _cartilage_ and _tendons_, being richer -in _sodium ions_ than the _blood_, this might account for the fact that -urates tend to be precipitated in these particular structures. - -Again, Almagia, working in Hofmeister’s laboratory, noted that thin -sections of _cartilage_, if left for some hours in a solution of sodium -urate, will take up _uric acid_. 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 _joint cartilage_, though apparently not in other tissues. - -This behaviour would appear to justify the conclusion that the observed -accumulation of uric acid in the cartilages in the presence of states -of _uricæmia_, may be explicable on this same basis. In any case, this -marked affinity of even _normal_ 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 _antecedent necrosis_ -precedes the _deposition of urates_. Still, even if we concede the fact -that _normal cartilage_ has a marked affinity for _uric acid_, how is it -that in _leukæmics_, despite their high blood content of _uric acid_, -no _uratic deposits_ ensue? Does not such disparity seem to indicate -that in gout some other factor intrudes? in other words, that the excess -of _sodium ions_ in particular tissues, while it may favour deposition -therein, is inadequate of itself to actually determine the formation of -tophi. - - -THE CAUSATION OF TOPHI - -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 _concomitants_ or _sequels_ of _gouty inflammation_. 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 _constitutional_ or -_systemic_, as well as _local_, factors. - - -SOLUBILITIES OF URIC ACID - -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 _diminished alkalinity_ of the blood and tissue -juices; but, as before pointed out, it has been established that the -alkalinity of the blood is _not_ reduced, and the theory has consequently -been abandoned. - -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 _tautomeric_ -types of _uric acid_, the blood in gouty subjects must at times be -in a state of _super-saturation_ with uric acid; and, moreover, that -equilibrium could only be restored through abstraction of the urates by -crystallisation. - -Unfortunately for this theory, it has been shown that the blood of gouty -subjects is not _super-saturated_ 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. - -But, to resume, Minkowski, it will be recalled, noted that from a -mixed solution of _uric_ and _nucleinic acids_ 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.” - -But, unfortunately for the value of this hypothesis, there is no proof -that _nucleinic acid_ 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.” - -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.” - -Continuing, Fürth reminds us that uric acid is much more soluble in -_blood serum_ than in water, and forthwith envisages this disparity in -light of the factors that affect solubility of uric acid in the _urine_. -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 _uric acid deposits in the tissues_.” 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.” - - -TOPHI IN RELATION TO URICÆMIA - -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 numerous and widely distributed large deposits -of sodium urate beneath the skin, yet the _blood content_ of _uric -acid_ 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 _multiple tophi_ is no indication -that a state of _hyper-uricæmia_ exists. - -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.” - -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 _rôle_ in tophi -formation. - -But as far as our discussion has advanced, we may, we think, be justified -in the following deductions:— - - (1) That tophi are blends of crystalloids and colloids and - subject to the complex conditions of solubility attaching to - such combinations. - - (2) That the relatively high sodium content of certain tissues, - _e.g._, cartilage, favours the incidence of uratic deposits - therein. - - (3) That tissue necrosis is not necessarily an antecedent to - uratic deposits. - - (4) That no relationship can be established between the - incidence or multiplicity of tophi and uricæmia. - -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. - - -TISSUE AFFINITIES FOR URIC ACID - -Injecting uric acid intravenously into _gouty_ subjects, Umber noted -that at times the whole was retained, but on some occasions was excreted -in fractional portions. On the other hand, a _normal_ 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 _special affinity of their -tissues for uric acid_. - -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 _whole_ is _not_ -recoverable from the urine. Now this incomplete excretion or _retention_ -of uric acid was attributed to _defective elimination by the renal -cells_; 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 _fixation of the uric acid in the blood serum_. -Accordingly, to our minds, it is permissible then to canvass the further -possibility adumbrated by Umber, viz., that an _increased affinity of -the tissues for uric acid_ 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 _uratic deposition_. - -This last hypothesis derives colour from the findings of Schmoll, Magnus -Levy, Vogt, Reach and Bloch, who noted that, after giving thymus to -_gouty_ 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 _chronic_ gout repeatedly resulted in acute outbursts of -the disease. Moreover, as we saw when discussing the _sources_ 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 _endogenous production of uric acid_; in other -words, that a more catholic attitude on our part is indicated, one which -would envisage it as the outcome of continuous and _general cellular_ -wear and tear. That an _increased cellular destruction_, as induced -experimentally, _e.g._, by exposure to Röntgen rays, is capable of -raising the _blood content_ of _uric acid_ in a _gouty_ subject, and of -precipitating a gouty paroxysm, may be inferred from the researches of P. -Linsen. - - -RETENTION CAPACITY OF TISSUES FOR URIC ACID - -It may be recalled that Wiechowski and others observed that in man, of -_parenterally_ 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 _retarded elimination_, the -_tissues_ 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. - -The case of _anuria_ 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. - -In the case of _pernicious anæmia_ no uric acid was demonstrable. The -_gouty_ subject had for twenty-five years suffered from typical attacks -and exhibited many auricular tophi. The following organs, in their -entirety, were analysed, the _liver_ (1,550 gram), no uric acid; _spleen_ -(290 gm.), 10 mg. uric acid (3·5 mg. per 100 gm.); _kidney_ (270 gm.), -no uric acid; _lung_ (930 gm.), 15 mg. uric acid (1·6 mg. per 100 gm.); -_muscle_ (440 gram), no uric acid; and _intestine_ (420 gram), no uric -acid. - -It will be seen that _uric acid was either absent or present in minimal -amounts_, and these results Schittenhelm and Wiener interpreted as -confirming their long advocated contention as to the _destructibility of -uric acid_ in the human organism. - -Morris S. Fine, from the results of similar investigations, considered -the failure of these observers to isolate _uric acid_ in these cases of -_anuria_ and _gout_ 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.” - -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. - -While it is unfortunate that Fine’s theory contained no instances -of _gout_, his findings are a definite proof that, to quote his own -words, _uric acid can be demonstrated in considerable concentrations -in human tissues_. Incidentally, also, his tissue analyses are flatly -contradictory to Schittenhelm and Weiner’s persistent contention, viz., -that the human organism _can decompose uric acid_. - -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. - - -TABLE I.—CONCENTRATION OF URIC ACID IN HUMAN TISSUES AND FLUIDS PER 100 -GRAMS OF MATERIAL - - ------------------+-------+-------+-------+---------+---------+ - Case. | E. E. | T. D. | S. H. | M. F. | C. M. | - |Uremia.|Uremia.|Uremia.|Diabetes.|Diabetes.| - ------------------+-------+-------+-------+---------+---------+ - | mg. | mg. | mg. | mg. | mg. | - Blood | 15·4 | 14·3 | 17·0 | 0·7 | 0·7 | - Pleural fluid | 16·7 | 15·9 | | | | - Ascitic fluid | 18·0 | | | | | - Pericardial fluid | | 14·3 | 18·0 | | | - Subcutaneous fluid| 18·0 | | | | | - Spinal fluid | 2·8 | 2·0 | 4·7 | | | - Skeletal muscle | 8·0 | 3·9 | 5·8 | 0·7 | 2·6 | - Heart muscle | 10·0 | 7·3 | 8·8 | | 1·2 | - Liver | 18·0 | 15·6 | 11·5 | | 5·0 | - Spleen | 12·6 | 14·3 | 9·1 | | 1·2 | - Skin | | 13·0 | | | | - ------------------+-------+-------+-------+---------+---------+ - - ------------------+-----------+---------- - Case. | S. T. | H. J. - |Amputation.|Pneumonia. - ------------------+-----------+---------- - | mg. | mg. - Blood | 0·7 | - Pleural fluid | | - Ascitic fluid | | - Pericardial fluid | | - Subcutaneous fluid| | - Spinal fluid | | - Skeletal muscle | 2·0 | - Heart muscle | | - Liver | | 4·0 - Spleen | | Trace - Skin | | - ------------------+-----------+---------- - - -TABLE II.—CONCENTRATION OF URIC ACID IN MISCELLANEOUS HUMAN TISSUES PER -100 GRAMS OF MATERIAL - - -----------------+------------ - Tissue. | Uric acid. - -----------------+------------ - | mg. - Pectoral muscle | 2·5 - Uterine muscle | 2·0 - Uterine muscle | 2·5 - Uterine muscle | 1·2 - Mixed tonsils | 1·7 - Thyroid | 0·0 - -----------------+------------ - -Again, as before alluded to, Bass and Herzberg found that intravenous -injection of uric acid caused less _uricæmia_ in the _gouty_, despite -diminished renal excretion. Hence, they concluded that _in gout the -retention capacity of the tissues for uric acid is augmented_. - -Fürth, an ardent advocate of Umber’s hypothesis, emphasises the fact -that Wiechowski was never able to detect any evidence of _uricolysis_ -in the human body. Continuing, he observes, if we reject all idea of -_uric acid retention in the tissues_, “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, “_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._” - -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 _precipitation or anchoring of urates -in the tissues in gout_ it is most desirable that further investigations -be made to discover whether in _gouty_ subjects the _tissue retention -capacity_ for _uric acid_ is _enhanced_. - -“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 _increased endogenous purin excretion_ that -follows ingestion of _purin-free_ food, were forced to reject the view -that it was solely derived from katabolism of the _nuclear_ substance -of the _digestive glands_, and to refer it instead to “wear and tear” -of the _body cells as a whole_. Precisely the same change in attitude, -we may remind our readers, has overtaken us in regard to the site of -_urea_ formation, viz., that not only the _liver_ cells, but those of the -muscles also participate in its production. - -While admitting that dogmatism is out of place, still to our mind this -theory of _tissue retention_ makes strong appeal. In light of it the -nebulous “gouty diathesis” seems on its way to become incarnate in some -_inborn peculiarity_ of _tissue-function_, a falling short of full -physiological activity, or, as M. Rendu termed it, a “_primordial vice of -nutrition_.” - -In other words, in gout there is no rift nor lack of finish in the -orderly sequence of enzymatic reactions that eventuate in _uric acid_. -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 _precipitated_ and _anchored_ in the -_tissues_, 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 _retention_ of uric acid, and more pertinently, its _fixation in the -tissues_ that constitutes the salient feature of gout. - -Now, all modern research tends to indicate that uric acid is not an -intermediary, but a _terminal_ product of metabolism, and, moreover, -that there are no _uricolytic_ ferments within the body whereby its -destruction can be accomplished. - -If we grant that— - - (1) Uric acid is not an intermediate but an end-product of - metabolism; and - - (2) That the human body is devoid of uric acid-destroying - enzymes, - -then it follows that man, _ipso facto_, is _potentially liable to uric -acid retention and deposition_, the same objectivated as _tophi_. In this -innate potentiality of and to _uratosis_ resides the “gouty” diathesis. - -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 _end-product_, then no further cleavage into -_urea_, etc., occurs, and in this connection the failure to discover -_uricolytic enzymes_ is significant. - -We have before proffered the suggestion that not only local, but -_constitutional_, or systemic influences also play a part in the origin -of tophi. Provisionally, therefore, we would infer that— - - (1) The tissues of gouty subjects display an abnormal affinity - for uric acid, _i.e._, an increased retention capacity for the - same; - - (2) That certain chemico-physical factors, previously alluded - to (content of sodium ions, etc.), favour the incidence of - uratic deposits in particular tissues. - -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 _latent tissue potentialities_, -inadequate of themselves to determine the eruption of _tophi_. - -Moreover, be it recalled that the _causa causans_ of gout must be -responsible not only for the incidence of _tophi_, but also for the more -dramatic features of gout, its _arthritic_ outbreaks, etc. To dissociate -the cause or causes of the uratic deposits from that of the joint -inflammations would indeed appear impermissible. - -But, taking this view, it is clear that, apart from the constitutional -and local factors above postulated, tophi and, alike, the arthritic -phenomena of gout, demand for their production the intrusion of some -further element, some _tertium quid_, vital and biological. To this end, -therefore, we purpose reviewing tophi in their _clinical_ aspects, as -herein possibly we may find some further clue to their exact mode of -genesis. - - -CLINICAL EVOLUTION OF TOPHI - -As to the clinical characters that mark the genesis and maturation -of tophi not a little conflict of opinion seems to obtain. Do tophi -arise painlessly or not? Do the uratic depositions occasion any local -inflammatory reaction? Or, are they merely concomitants or sequels -thereof? - -With what wearisome iteration has the same question been propounded in -regard of _gouty arthritis_. Are the attacks of pain and inflammation due -to deposits, or do the deposits take place at the site of inflammation? - -But, restricting our enquiries to tophi, we may remind the reader -that Aretæus, writing in the second century, A.D., made the following -observations: “Callosities also form in the joints; at first they -resemble abscesses, but afterwards they get more condensed, and the -humour being condensed is difficult to dissolve; at last they are -converted into hard white tophi (Πῶροι στερροὶ λευκοὶ), and over the -whole there are small tumours like _vari_ and larger, but the humour is -thick white and like hailstones” (Περὶ Αρθριτιδος). To our mind, it would -be difficult to emulate, much less to surpass, the succinct and, as we -believe, accurate picture here drawn of the various stages that mark the -life history of tophi. It will be noted that Aretæus says that in their -initial stages they “resemble abscesses,” and, turning to the writings of -the elder Garrod and others, we find abundant evidence that it is so. - -Discussing the more frequent incidence of tophi in the hands than in -the feet, Garrod describes the physical characters presented by tophi -in the making as seen in one of his examples of gout. “On the dorsal -surface of the second phalangeal joints of three fingers, small rounded -protuberances were observed, the skin over them being red; these -bulgings appeared soft, as if containing a thick fluid, but not the -slightest indication of white matter could be seen through the skin; -they might have been either gouty concretions in their early stage of -formation or some other form of swelling; from a simple inspection -I could form no opinion as to their true nature, but their history -convinced me that they arose from a deposit of urate of soda. Upon -puncturing one of the little swellings, full light was thrown upon -the case, as a thick white fluid immediately exuded, a drop of which -placed, under the microscope, with the use of polarised light, gave the -appearance represented in Fig. 1; the crystals were proved by analysis to -consist of urate of soda.” - -We see, therefore, that Aretæus and Garrod were at one in their -observation that tophi in their initial stages are betokened by _small -red swellings_; 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.” - -That Garrod held the swellings to be _inflammatory_ 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.” - -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.” - -Duckworth also noted that uratic deposits are _not always painless_ -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. - -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 -_tophi_ are associated with _inflammation_ and some measure of _pain_, -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. - -Moreover, we would emphasise the fact that _tophi_, more often than is -thought, occasionally precede by some years the outbreak of _arthritic_ -attacks. Both Duckworth and Garrod are quite definite on this, and we can -confirm them. - -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 _chilblains_. 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.” - -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 -_non-gouty_ origin, but the tophus, never! - -Reflecting on the foregoing considerations, we would submit— - - (1) That tophi are always preceded by local inflammatory - reaction of varying grades of severity, and that the uratic - deposits are sequels thereto; - - (2) That in their early stages their presence is betokened by - soft red swellings associated often with sensations of pricking - and tenderness; - - (3) That their transmutation into white pearly concretions is a - process that takes months to mature; - - (4) That tophi and arthritic outbreaks have a common causal - origin. - -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? - - -THE CAUSE OF THE INFLAMMATORY PHENOMENA - -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. - -Thus, the blood in _leukæmia_ 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 _uric acid_. 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. - -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. - -Obviously, with these revelations the uric acid theory was within -measurable distance of being uprooted. Deposed from its high 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 _rôle_, of originating any symptoms, much less gout, -in its entirety. In other words, is uric acid toxic or non-toxic? - - -NON-TOXICITY OF URIC ACID - -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 _irregular_ or _visceral_ -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 _toxic_ irritants. - -Perhaps the most cogent evidence of the slight toxic effects of uric -acid or urates is that derived from a study of the _uric acid infarcts_ -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. - -Again, we have the fact that in instances of _malnutrition in children_ -excess of uric acid may occasionally be found in the blood. Yet no -symptoms comparable to _gout_ occur, even though uric acid _calculi_ -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 -_mechanical_ irritation of the renal or vesical tissues. - -Turning to experimental researches, the evidence is cumulative as to the -_non-toxicity_ 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 thereof, save only that the -urine showed a large increase in uric acid. - -Again, Ransom, of New York, found that no systemic disturbance ensued in -two cases of _chronic nephritis_, 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. - -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 _materies morbi_ in -gout. - -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. - -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 -_normal_ 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, _uricæmia_ exists yet, despite -favouring circulatory conditions, they develop no gout. - -Garrod contended that the violent pain, intense inflammation, and -profound constitutional disturbance of acute gout were due to -_mechanical_ 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. - -But it is, as Ringrose Gore shrewdly observed, “against the 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 _precedes_ -the deposition of urates and that these latter, in short, are the -_consequence_ and not the cause of the gouty arthritis? - -Reverting to tophi, their experimental production, it is claimed, -has been achieved by His.[24] 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.”[25] Scarcely the -words in which to describe the poison responsible for gout! for, as we -have before stated, the agent that is responsible for _tophi_ must also -be capable of inducing the arthritic phenomena and other features of the -disorder. - -The sum of our reflections is that the _toxicity_ of uric acid has -been grossly over-estimated, and that, like its relative _urea_, it is -practically _non-irritating_ and _inert_; in other words, it cannot any -longer be regarded as the _essential cause_ of the _acute_ or _chronic_ -forms of _gout_, whether of _articular_ or _ab-articular_ 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.” - - -ARE THE PRECURSORS OF URIC ACID TOXIC? - -Naturally the upholders of the uric acid theory were loth to find their -fetish uric acid was allotted a meaningless _rôle_. 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 _bases_, the forerunners of -uric acid? Might not the blame lie with these? - -Straightway _xanthin_, _hypoxanthin_, _adenin_, etc., were credited with -pernicious potencies.[26] 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 _kidneys_ ensued, with -deposits resembling uric acid and urates in their substance. The fact, -too, that _guanin-gout_ was occasionally met with in swine, also lent -colour to their views. - -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. - -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 _hypoxanthin_. 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 _nucleinic acid_. - -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 _hypoxanthin_ and _nucleinic acid_ were _gouty_ -subjects, _i.e._, potentially liable to attacks at any moment. - -Even admitting the ingestion of, _e.g._, 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 _purin bases_ 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 _causal_ connection, would do well to recall Bacon’s dictum that -“there is in the human mind a peculiar tendency to dwell on affirmative -and to overlook negative instances.” - -In conclusion, we must affirm our belief that _neither uric acid nor -its precursors_ 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 _uric acid_ has nothing whatever -to do with gout. The fact that _tophi_, its pathognomonic stigmata, are -compounded of biurate of soda, would _per se_ stamp such an attitude as -untenable. On the other hand, _uric acid_ must be viewed in its proper -perspective as a concomitant or sequel of gout, the essential _cause_ of -which must be sought elsewhere. - - - - -CHAPTER XIII - -THE RISE OF THE INFECTIVE THEORY - - -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 _gastro-intestinal_ 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 _fons et origo mali_ in -gout was disturbance of the functions of the alimentary tract. - - “Indigestio viscorum pro origine proxima hujus morbi habitur.” - -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 _indigestion, or to the impaired concoction of matters both in the -parts and juices of the body_.” - -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 _nature_ -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.” - -Indeed, the great Boerhaave avowed his belief that gout was -_contagious_—a forecast, we may take it, of the modern theory of -_infection_. Subsequently his pupil, Van Swieten, went a step further, -maintaining that sometimes wives, while nursing husbands afflicted with -gout, contracted the malady! - -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.” - -But it must be freely acknowledged that, subsequent to Garrod’s discovery -of _uric acid_ in the blood in gout, the spell exercised by the _uric -acid theory_ was such that it dominated medical thought almost to the -exclusion of all other possibilities. 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 _uric acid_ was the _proximate cause_ of gout. - -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 _infective_ theory. His views postulated -what may be termed a _toxic tropho-neurosis_, wherewith to explain the -paroxysmal nature, the periodicity and protean symptomatology of the -disorder. - -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 -_acute gouty polyarthritis_. 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 _de novo_ in search of the cause of the acute paroxysm. - -He noted also the interesting fact that during acute attacks of gout a -very marked _leucocytosis_ 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.” - -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 _infective_ -origin of the disorder. - -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. As gout is capable of -being caused in any subject, it must be one of the bacilli normally found -in the intestinal canal.” - -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. - -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 _diminished or wholly lacking_, while, on the other hand, -lactic acid was present in some instances. - -In 1903 Woods-Hutchinson ably contended that “gout and lithæmia are mere -symptom names for a miscellaneous group of _chronic toxæmic processes_ -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 _rôle_ of the _liver_ 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.” - -In 1904 Falkenstein furnished collateral evidence that the starting -point of gout lay in a diseased condition of the _gastric glands_, those -responsible for the secretion of _hydrochloric acid_. 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. - -In the same year Chalmers Watson, as the outcome of investigations into -gout as it occurs in the _fowl_, held that:— - - (_a_) There is ample evidence to prove that the uric acid in - the blood is not the primary factor in gout, and - - (_b_) Uric acid can be deposited in cartilages and other - tissues, even in considerable amount, without the association - of any inflammatory phenomena. - -He concludes that the last-mentioned point clearly proves that:— - - (_c_) Uric acid is not the factor which causes the inflammatory - phenomena characteristic of the acute attack. - -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 _alimentary canal_, -holding that herein doubtless resides the clue to the solution of the -problem. - -_Post-mortem_ examination of the fowl revealed marked catarrh of _ileum_, -_duodenum_ and _large intestine_, while the pancreatic duct was filled -with catarrhal products. The congested _spleen_, apart from proliferation -of its endothelial elements, exhibited a marked increase in the number -of _granular leucocytes_ 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 _infection_ by the -_blood stream_. - -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. - -As to the inference that the defunct fowl fell a victim to acute -gout, Watson based it on the existence of the _uratic deposits_ 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 _pancreatic duct_ raises the question as to whether it -points to any connection between these changes and the common occurrence -of _glycosuria_ in gouty subjects. The alteration in the _leucocytes_ -merits notice in that similar changes were found by Watson in the blood -in _acute gouty polyarthritis_, the same, moreover, being subsequently -confirmed by Bain. - -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.” - - -SUGGESTION OF A SPECIFIC INFECTION - -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 _mucous colitis_ to be one of the initial -manifestations of gout, affirmed his belief that the _bacillus coli -communis_ was the responsible microbic agent. - -He claimed that this particular organism, during its passage through the -system, gives rise to a reducing agent which is subsequently transmuted -into _xanthin_ and _uric acid_. 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. - -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 -_gastro-intestinal derangements_, 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. - -Sikes, however, in 1907, discussing the _rôle_ 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.” - -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 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 _chemistry of the cell -protoplasm_. - - - - -CHAPTER XIV - -GOUT AS AN INFECTION - - -“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 _uric acid_, having lost its _etiological_ status, be -viewed in its right perspective as not the cause, but the _consequence_, -of gout. - -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 _metabolic_ 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 _infective_ element in its -genesis. - -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 _auto-toxæmia_ and _infection_ or _sub-infection_. 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. - - -LOCAL FOCI OF INFECTION - -The extreme frequency with which _infective foci_ 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 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. - -Nevertheless, their observations on “gouty” teeth are of deep interest, -though their significance was misinterpreted. - -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 _pyorrhœa alveolaris_, of -unprejudiced source, hence the more valuable. - -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 _epistaxis_, and the same after copious _hæmatemesis_, and -Todd several times observed such articular outbreaks after _venesection_. - -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 _boils and carbuncles_ -have come under my notice.” By Garrod and his contemporaries all these -various determinants of gouty paroxysms, _i.e._, loss of blood, etc., -were believed to exert their influence _viâ_ the _nervous_ system, with -consequent disturbed equilibrium of nutritive processes throughout -the body. But while it may be admitted that depression of the _vis -resistantiæ_ plays a part, it does so, I believe, by favouring the -occurrence of _infection_. - -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 _chronic dyspepsia_. Two years after (1909) Wynn, Wirgman -and Turner noted the invariable correlation of gout with local foci of -infection. In the majority, _pyorrhœa alveolaris_ was present. _Tonsillar -sepsis_, too, was not uncommon, and much more rarely _nasal_ disorders. -Again, out of fifty-two examples of so-called “gouty” throat Edward -McCracken found _pyorrhœa alveolaris_ to be present in thirty-nine, and -Fenner also tells us that this affection is common in the subjects of -gout. - -In truth, the victims of _gouty_ arthritis are no more immune from -_dental_ 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 _oral sepsis_ is extremely common in _gouty_ -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 _etiological_ -significance—can scarcely be overestimated. For their consequences, both -local and remote, are of paramount importance. - -Thus, G. I. Stewart’s recent observations have conclusively demonstrated -that “bad teeth” are causally related to _tonsillar_ affections. How -illumining this, in view of McCracken’s experiences in “gouty throats.” -As we saw, _pyorrhœa alveolaris_ 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 _acute tonsillitis_, of -lacunar or parenchymatous type, also that such attacks frequently precede -outbreaks of _arthritic_ 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. - -Again, acute and chronic _pharyngitis_ 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. -_Parotitis_, 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.” - -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 _glandular_ affections—these states of _oral sepsis_—in the -subjects of _gout_. Equally noteworthy is their insistence on the -constancy with which such local affections have proved harbingers -of oncoming _articular_ 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. - -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, 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 _infection_—“acute rheumatism,” “gonorrhœal arthritis,” etc.?—and we -may well ask, Why not in _gout_? - -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 -_infection_, and the arthritis _secondary_ thereto? Is not this same -interpretation in all probability true also of all forms of “gouty” -throats when followed by _arthritic_ outbreaks? - -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 _gout_. 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 _etiologically_ related -thereto. We should cease to talk of “gouty” throats, teeth, etc., should -renounce the prefix, for there is nothing _specific_ of _gout_ either -in the tonsillar, pharyngeal, or dental lesions. We should instead view -these various local disorders in their true perspective as _foci of -infection_, _causally_ related to the subsequent and _secondary_ “gouty” -arthritis. - -_Gastro-Intestinal Disorders._—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. - -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. - -So much by way of prelude as to the probability—attested by clinical -observation and the results of treatment—that the _intestinal canal_ is -often the source of the responsible microbe or toxin. Let us now pass -to consider what factors other than an _oral sepsis_ may favour the -incidence of _functional_ disorders of the _alimentary_ tract. - -_Variations in Free HCL._—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 _diminished or wholly wanting_. - -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 _oral sepsis_ it is probable that a greater number are -swallowed than can be satisfactorily coped with. - -Given therefore excess of pathogenic organisms and _relative -insufficiency of free HCL_, conditions favourable to the growth of -bacteria ensue, while incidentally the chance of such reaching the -intestine is materially enhanced. - -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. - -In opposition to the foregoing, many hold that an _excess of free HCL_ -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. - -_Intestinal_ 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 -_succus entericus_ with its nucleotidase that plays the most important -digestive _rôle_ as regards nucleins, breaking them up into nucleosides -which are, to a large extent, absorbed as such. - -To resume, this condition of _intestinal indigestion_ 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 _intestinal derangement_. - -The clinical features presented are very variable. It is often -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 _intestinal stasis_, or to a _chronic infection_, with a -resultant catarrhal state of the mucosa, or to both causes combined in -varying proportions. - -But, be the explanation what it may, in our experience the most common -antecedent or concomitant of gout is _intestinal dyspepsia_. Its -secondary consequences are far reaching, especially if the small bowel be -involved, catarrh of which may lead to _reduction_ in the secretion of -_bile_ and _pancreatic juice_. - -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 _sugar_ in the -urine, the so-called “gouty” _glycosuria_. - -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 _bacterial flora_ in the bowel -undergo modifications. - -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. - -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 _chronic toxæmia_ -results. - - -SUMMARY - -It now devolves upon us to decide whether the phenomena of gout are best -explicable as the outcome of _auto-intoxication_, or of _infection_ or -_sub-infection_. The uric acid theory was in truth one of _auto-toxæmia_, -the varied manifestations of gout being attributed to mechanical or toxic -irritation by _uric acid_, the end-product of purin metabolism. But, as -we hope to have shown conclusively, uric acid is _not toxic_, and _per -se_ is apparently as innocuous as those other and intermediary products -of metabolism which give rise to cystinuria and alkaptonuria. - -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 _gout_. Rather, -according to Adami, do they approximate to those typical of _anaphylactic -shock_. - -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 _intestinal stasis_ 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. - -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. - -In short, it is but too clear from the foregoing brief _résumé_ of recent -experimental findings that, if _uric acid_ cannot be held responsible for -the causation of _gout_, there is no evidence likewise that the disorder -owes its genesis to any other of the as yet isolated _chemical_ 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 _infection_ or -_sub-infection_. - -_Infection or Sub-infection._—Our knowledge as to the exact manner in -which _local foci of infection_ 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 _streptococci_ are of common incidence -in the _tonsils_, and Rosenow and Brown from experimental observation -have established that these hemolysing organisms, migrating _viâ_ the -blood stream, exhibit a marked predilection for forming a fresh nidus -in the _gall bladder_. Here they may initiate a _cholecystitis_, and -secondly gallstones, and in sequence thereto the symptoms associated -with _gall-bladder-dyspepsia_. The same formidable list of sequels may -follow infection of the gall bladder from the _teeth_, _stomach_, or -_intestines_, notably from the vermiform appendix. - -In like fashion the origin of _appendicitis_ may be traced back to -_septic foci_ in the _mouth_, _tonsils_, _naso-pharynx_, or to the -_gastro-intestinal tract_. Here again there ensue the symptoms of -so-called _appendix-dyspepsia_. As in the case of the gall-bladder -variety, the _primary lesion_ in the _appendix_ may be _latent_, and the -exact diagnosis may be a matter of great difficulty, often indeed only -to be achieved _retrospectively_, viz., when abatement of the symptoms -follows ablation of the appendix. - -We see, therefore, how far-reaching are the consequences of _local foci -of infection_ in the _mouth_ or elsewhere. Now, the _gouty_ subject -enjoys no immunity from the remote sequels of local sepsis. But as a -rule, unfortunately, whatever be the nature of his _dyspeptic_ symptoms, -they are, like his _dental anomalies_, his _tonsillar inflammations_, -forthwith dismissed as _symptomatic_ of gout, not etiologically related -thereto. - -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. - -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 _gall-stones_. Senac, of Vichy, -claimed indeed that out of 166 cases of _biliary lithiasis_ 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 _biliary colic_. - -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 _gouty_, this when we are so constantly confronted with -_local foci of infection_ in the _mouth_, or elsewhere, which afford -us an explanation of the gastro-intestinal symptoms at once more -obvious and more rational. This also the more especially in that—as -far as subjective symptoms go—those deemed typical of so-called “gouty” -dyspepsia are indistinguishable from those met with in _appendix-_ or -_gall-bladder-dyspepsia_. Indeed, I might go further and point out -that the _variations in free HCL_ in the gastric juice—as observed in -_gout_—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 _gouty_ subject we endeavour to -elucidate the exact nature of the _underlying lesion_, but to this we -shall return again when discussing diagnosis. - -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 _glycosuria_. For an infected -gall-bladder may by extension determine a chronic _pancreatitis_. - -Lastly, what of the relationship of local foci of infection to _“gouty” -synovitis_ and _arthritis_? Is one focal infection more than another -particularly related to arthritides? Whatever be the true inference, -if we take _arthritides_ as a whole, nothing seems so efficient a -cause of their production as _oral sepsis_. Accordingly, some are -inclined to think that organisms, _e.g._, _streptococcus viridans_, at -the roots of the teeth or others in the tonsillar crypts, pass, _viâ_ -the blood-stream, _direct_ to the _joints_. 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. - -Those who favour the view that _direct infection viâ_ the blood from foci -of oral sepsis is the more probable _modus operandi_ are wont to produce -the following points in support of their view. Arthritis, they say, is -relatively rare in _enteric fever_. In yet another disorder, _dysentery_, -which gives every chance of absorption from the intestine, arthritis when -it occurs is seldom very acute, while in _appendicitis_ it is distinctly -uncommon. - -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. - -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. - -By _sub-infection_ is understood the fact that microbes carried into -the system undergo slight, if any, numerical increase, and do not set -up _foci of suppuration_. Here we may note that “gouty” inflammation, -however intense, never ends in _pus formation_. 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 -_chronic interstitial fibrosis_ is formed. - -Incidentally this is interesting, inasmuch as the _visceral_ organs in -gout evince a tendency to _fibrosis_. 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 _sub-infection_? - -The assumption gathers weight in light of the experimental proof adduced -by Adami that not only tubercle bacilli, but _streptococci_ and other -organisms, _taken orally_, can gain an entrance into the system. Upon -this basis we get a clear conception of the possible relationship of gout -to _local foci of infection_. 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 _joints_ or -other structures. - -Now, as pointed out, inflammatory states or _functional_ derangements -of the _alimentary_ 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 _intestinal flora_, -and promote their migration inwards in greater numbers? The inevitable -swiftness with which relapses 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. - -My conclusions then are that:— - - (1) The majority of cases of gout are marked by the presence - of _local foci of infection_, pyorrhœa alveolaris, tonsillar, - pharyngeal or nasal sepsis, etc., or by gastro-intestinal - derangements, constipation, etc. - - (2) The said local foci should be regarded not as symptomatic - of, but _etiologically_ related to, gouty arthritis, and that - the same is strongly indicated by the fact that - - (3) Acute _glandular_ affections of undeniably _infective_ - source—tonsillitis, pharyngitis, etc.—frequently and - immediately _precede_ acute paroxysms of _articular_ gout, and, - lastly, - - (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. - - - - -CHAPTER XV - -GOUT AS AN INFECTION (_continued_) - - -ANALYSIS OF THE ACUTE PAROXYSM - -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, _the big toe_, suggest an -_infection_. The abrupt onset, the local signs, the crisis, and no less -the subsequent swift restoration to health, how strikingly reminiscent -of an _exanthematous_ 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. - -Its fulminant _onset_, 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 _infection_? - -_The constitutional disturbance_ is often profound, certainly out of all -proportion to the severity and extent of the local phenomena. Especially -prominent are the _nervous_ 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 _paroxysmal neuroses_. But, given an infective element, what -more plausible than to attribute the nervous phenomena of gout to the -simultaneous action of its _toxins_ on the higher centres? - -The _temperature_ 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 _gonococcal_ -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. - -Albeit both the febrile disturbance and the local reaction display -infinite grades of severity. Thus, _acute gouty polyarthritis_ may be -_afebrile_ and the _asthenic_ 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 _toxæmia_. - -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.” - -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 _malaria_, they disclose an affinity, not for a malady -of nervous, but one of established _infective_, origin. - -Simultaneously with the onset of _pyrexia_ 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 _leucocytosis_. It may be of high grade. In a case of acute -gouty _polyarthritis_ recently under my care the leucocyte count reached -27,000. Even in a _subacute_ example of the classic _monarticular_ -type the leucocyte count attained 25,920. It was of _leucoid_ type and -attended by moderate anæmia due to deficiency of red corpuscles. - -Nor is leucocytosis restricted to the periods of exacerbation, but it -may be met with in the _inter-paroxysmal_ stages. In my experience, even -in cases of definitely _chronic_ type it may reach 14,000. The higher -grades of leucocytosis are obviously very suggestive of an _infection_, -and that lesser degrees should be encountered in examples of definitely -chronic type seems to point to gout being of the nature of a _chronic_ or -_serial_ infection. - -I would here add also that the converse of leucocytosis, viz., -_leucopenia_, 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, _e.g._, enteric, malaria, tuberculosis. In fact, it -suggests that gout may be the outcome of divers infections, and not due -to any specific organism. - -_Enlargement of the lymphatic glands_ 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 _lymphangitis_ 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.” - -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.” - -_Splenic enlargement_, states Duckworth, has been met with in many cases -of gout, and occasionally infarcts. But such splenic enlargement is, he -thinks, _not specifically_ related to gout, but is due to associated -conditions. Personally, I have not as yet met with splenic enlargement in -gout. - -This aside, is it not palpably significant of infection that Paget, -Garrod, and others, repeatedly noted the incidence of acute _phlebitis_ -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 _infection_ from the joint to -the related veins? - -Reverting to the _local articular phenomena_, they are not only -compatible with, but emphatically suggestive of, an _infective source_. -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, _e.g._, Scudamore, on the differentiation of acute gout, -not so much from acute rheumatism as from _erysipelas_ or _phlegmon_. -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 feature of gouty inflammation, viz., -it never results in _pus formation_. 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 _infective_ category? - -That Garrod’s _caveat_ 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 _pyæmic_ or _septic_ -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 _pyæmia_ as one of the -disorders to which gouty subjects were especially liable. - -Gouty inflammation resembles most other forms of the same morbid change, -but some, however, contend that the association of _œdema_ 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 -_infective_ arthritides. We need but recall the constancy with which -local œdema is met with in, _e.g._, _gonococcal_ arthritis. More typical -of gout, however, is the _desquamation of the cuticule_ that follows -the subsidence of the acute arthritis. Here we are reminded of the -similar peeling of the skin that occurs in another _infective_ disorder -associated with arthritis, _i.e._, _scarlatina_. - -Acute gout is _definitely paroxysmal_. 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.” - -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 _chronic_ 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. - -The _periodicity_ of gout was, as we have seen, well known to the -ancients. Its recurrence in early spring and late autumn has even been -celebrated in verse:— - - “On whose sacred internodial Altars I - Each Spring and Fall at least will sacrifice - Morbifick, painful loads of Matter tartarous, - With recrements of nervous juice impregnate.” - - “The Honour of the Gout,” by _Philander Misaurus_. - -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.” - -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 _infective_ origin. In this connection -it may be recalled that it was once described as “a tertian fever -terminating in fourteen days.” - -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 _colchicine_ has no action on the metabolism of _purins_ or on -the _kidney_. On the other hand, it causes a primary diminution followed -by a _marked increase_ in the number of _leucocytes_, which suggests -the possibility that it exerts its beneficial effects by combating -_infection_. - -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 _acute gouty polyarthritis_, aspirated the knee joint. The -results of _cytological_ examination were precisely such as are deemed -characteristic of arthritides of infective source. - -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 _infective_ element:— - - (1) The onset, temperature curve, the character of the local - phenomena, and course of the disorder. - - (2) The presence of _leucocytosis_ with secondary anæmia, and - exceptionally of _leucopenia_. - - (3) Enlargement of the lymphatic glands, and possibly of the - spleen. - - (4) Occasional complication of the acute articular disorder by - _lymphangitis_ and _phlebitis_. - - (5) The paroxysmal nature and periodicity of the disorder. - - (6) The compatibility of the morbid anatomical changes and the - cytological content of aspirated joint fluid with their genesis - by infection. - - -THE EVOLUTION AND LIFE HISTORY OF GOUT - -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. - -For the course of gout, like other arthritides of chronic type, is -not one of steady, uninterrupted progress, but one marked rather by -_periodic_ or _intermittent_ advances, as if seemingly due to a series -of successive _infections_ or _sub-infections_. One is reminded of -_gonococcal_ 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. - -Now, if the general course or evolution of _gouty_ arthritis is notably -similar to that of the specific infective arthritides, so, also, do the -clinical features approximate. Thus its _onset_, more often than not, is -_abrupt_ and attended by pyrexia of _irregular_ or _septic_ type, with an -occasional _leucocytosis_. - -Again, that not all cases of gout are of _acute fulminant_ type may -be admitted. We know that it may assume the guise of a fleeting -_arthralgia_ or “flying gout,” a transient _synovitis_, as well as an -acute _arthritis_ of _mono-_, _oligo-_, or _poly-articular_ extent. -This same _polymorphism_ in respect of the joint lesions in gout is a -replica of that met with in the _specific infective arthritides_. 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 -_restitutio ad integrum_ of more or less completeness follows. - -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 _uratic deposition_. Save in respect of this last, the analogy -is complete, and herein resides the specificity of gouty arthritis. - -Chalmers Watson, from his observations of “gouty deposits” in human -subjects in their relation to _tendons_, _cartilage_, and _bone_, came to -the conclusion that the _tout ensemble_ of the pathological lesions was -very reminiscent of that typical of the more chronic types of _infective_ -disorders. Thus necrotic areas in gouty tendons stood in such clear -relationship to the vascular supply as to suggest some infection _viâ_ -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. - -As to uratic deposits located in the _bones_, 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. - -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. - - -ANALOGIES BETWEEN GOUT AND THE SPECIFIC INFECTIVE ARTHRITIDES - -A striking parallel can be drawn between the varied manifestations of -gout and those met with in _specific infections_. But, to begin with, we -must recall that our attitude towards infective disorders, _e.g._, acute -rheumatism, gonorrhœa, etc., is altered in that we regard them now, not -as local, but _general_, systemic infections. - -Thus, following the revelations of bacteriologists, we now, for -example, recognise that in _gonococcal_ infection not only may there be -_articular_ involvement, but that _muscular_ and _nervous_ lesions may be -associated therewith. This same, also, in _acute articular rheumatism_. -True, its causal organism is still _sub judice_, but data accumulate as -to the frequency with which the _muscles_ are involved, and, to a less -extent, the sheaths of _nerves_. - -Take _dysentery_, again; it, too, as Sydenham pointed out, may be -complicated, not only by _arthritis_, but by _myalgias_, while more -recent experience emphasises the frequency with which _neuralgias_ -are associated therewith. In _syphilis_, also, the association of -_articular_, _muscular_, and _nerve_ lesions is well attested; and by -French physicians it is insisted that, in _tubercle_, myalgias and -neuralgias, as well as joint disorders, are infinitely more common than -is generally realised. - -To sum up, this _triad_ of _arthritic_, _muscular_, and _nerve_ lesions, -either serially or simultaneously, is the most common complication of -_specific infections_. Now, is not this same congeries of articular, -muscular, and nerve disorders precisely the clinical content of _gout_? - -Thus its _articular manifestations_ constitute the most striking feature -of the disease. As to the _muscular_ 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 _free_, especially in _muscular_ tissue, also -that from such free purin bases _uric acid_ can be as readily formed as -from those liberated by disruption of nucleic acid. - -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. - -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 _infections_? 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. - -We see, therefore, that in virtue of its tendency, not only to -_arthritic_, but also to _muscular_ and _nerve_ disorders, gout falls -into line with the _specific infections_. 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 -_gouty_ manifestations, all of them, susceptible of a like explanation, -viz., that they are the outcome of an _infection_? - -For, in reviewing the foregoing analogies, it cannot, we think, be denied -that in the aggregate they are emphatically suggestive of an infective -origin. - - -CORRELATION OF THE METABOLIC PHENOMENA OF GOUT WITH THE POSTULATED -INFECTIVE ELEMENT - -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. - -The outstanding conclusions that we felt justified in formulating were -that:— - - (_a_) Uric acid is not the cause but the _consequence_ of gout. - - (_b_) _Inflammatory reaction_ is, we believe, an invariable - precursor in all gouty processes. - -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.e._, uratic deposits or _tophi_, 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 _mechanical_. The intrusion of some other factor, -“some vital something biological,” seems essential for the elucidation -of _uratosis_, _i.e._, uratic deposition. For this, _not uricæmia_, 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 _non-toxicity_ of _uric acid_, can we, on this basis, account for the -_inflammatory_ phenomena of the disorder? - -_Inflammatory reaction_ is, we hold, an invariable _antecedent_ in all -gouty processes, whether of _articular_ or _ab-articular_ 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. - -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 _infection_ or -_sub-infection_. 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. - -The problem of gout, however, is not so simple. Its arthritis is peculiar -in that it is always accompanied or followed by _uratic deposition_, -which, be it noted, is not an ordinary sequel of inflammation. It is, in -short, the outcome of inflammation supervening in an individual of _gouty -diathesis_. What do we know of this latter? - -The researches of the bio-chemists reveal that _uric acid_ is the -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 _enzymatic abnormalities_. Thus, Adami and McCrae -suggest that gout is the outcome of _insufficient oxidation_, 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 _oxydases_, -inherited or acquired. - -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.” - -Indeed, in view of this, as hitherto ascertained, _absence of uricolytic -enzymes_, 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.” - -Now we have, we hope, shown that there is no evidence that the _uric acid -retention_ in gout is due to functional inability on the part of the -_kidney_ 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 _nephritis_, a condition of “latent -nephritis” is the cause of the uric acid retention and deposition. - -Similarly, there is at present no evidence forthcoming that the retention -of uric acid is due to _abnormal purin combinations_ in the _blood_. Nay, -according to Wells, on the best evidence obtainable, uric acid exists in -a _free_ state in the blood, and not combined, as has been urged by many -workers in this sphere. - -But if the cause of _uric acid retention_ lies neither in the _kidneys_ -nor in the _blood_, there must exist something abnormal in the gouty -individual which renders impossible what may be termed a _compensatory -uric acid excretion_. Now, as disclosed in the previous chapter, -experimental research, in diseases other than gout, has shown that the -_bodily tissues have an appreciable capacity for retention of uric -acid_ (Fine). This, moreover, gains probability from the fact that -Wiechowski, in his prolonged studies as to the possibility of uric acid -decomposition in the human body, was never able to detect any evidence -of _uricolysis_. Furthermore, on the clinical side, the fact that -_intravenous injection of uric acid_ does not produce a corresponding -degree of _uricæmia_ seems, as Bass and Herzberg suggest, to indicate -that in gout the _retention capacity of the tissues for uric acid is -augmented_. Lastly, in the precipitation and anchoring of urates in the -tissues in gout, we have objective proof, _i.e._, tophi, that the uric -acid is actually held in the tissues. - -Does not this seem to indicate that there are _peculiarities of tissue in -the gouty_? What, then, the subtle change that determines the _retention -and deposition_ of urates in the tissues in gout? - -May we not, with Walker Hall, hazard the reflection that there may be -differences between the _nucleotides_ of normal and gouty tissues? For, -doubtless, if there be peculiarities of tissue in the gouty, these will -be reflected in abnormalities of _tissue function and metamorphosis_. - -Gowlland Hopkins, discussing the metabolism of purins, holds that in gout -there is some disturbance or defect in the _fermentative functions of the -tissues_. Of a verity the range of _intranuclear_ activities offers scope -enough when we recollect that the cells of all tissues contain not only -_nucleinase_, but also _nucleotidase_ and _nucleosidase_. 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! - -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 _instability_ -of _nuclein metabolism_. 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.” - -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.e._, by _infection_; in other words, that, under the -influence of these morbific agents, the innate morbid potentialities of -the gouty become overt and manifest. - -The exact _modus operandi_ whereby the assumed organisms or their -toxins determine the _efflorescence_ of gout is uncertain. We know -that, following the intake even of _non-purin-containing foodstuffs_, -an _increase in uric acid excretion_ ensues, and that the same is the -outcome of the stimulation of _general_ nuclein metabolism. 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.” - -In conclusion, I would postulate that in _gouty_ subjects:— - - (1) There is an inherent abnormality or instability of - _nuclein_ metabolism, and conjoined therewith an enhanced - tissue affinity or augmented retention capacity for uric acid. - - (2) These latent tissue peculiarities, through the agency of - _infections_ or sub-infections, become manifest as gout. - - (3) The said organism or organisms excite inflammatory reaction - with sequential uratic deposition, either of articular or - ab-articular site. - - (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. - - (5) The local and general phenomena of gout, its paroxysmal - nature and tendency to periodicity, are most readily explicable - on the basis of a _chronic infection_ 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.” - - - - -CHAPTER XVI - -CLINICAL ACCOUNT - - -ACUTE LOCALISED GOUT - -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 _modus operandi_ 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. - -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.” - - -PRODROMAL SYMPTOMS - -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 _function_. - -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. - -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. - -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.” - -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.” - -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. - -But it may be objected, there is nothing _specific_ about these various -_functional_ disturbances. They are not more common in the _gouty_ 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. - -Now, if there be nothing _specific_ 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” symptoms should -be regarded not as symptomatic of gout, but as _etiologically_ related -thereto. - -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 _true origin_ of the -“dyspeptic” symptoms, who will deny that this is the more rational and -scientific mode of procedure? The timely elimination of _septic foci_ -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. - -It has been suggested that there is some statistical evidence that -“acute rheumatism” has declined in frequency since the introduction -of _tonsillectomy_. 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 _oral hygiene_ and timely and radical treatment of _local foci of -infection_. The fact that in _children_, victims of so-called _infantile -gout_, the _purin metabolism_ 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. - -Now, if there be nothing _specific_ of gout in the “dyspeptic” -derangements held _prodromal_ 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 _tophi in the ears or at other -sites sometimes antedate articular outbreaks_. - -Now given that an individual exhibits _auricular tophi_, one or many, can -anyone deny that he is “gouty,” nay more, that he has _gout_, this even -though he never has had, or may never have, an _articular_ outbreak? In -truth, the eruption of a _tophus_ in the _ear_ is as essentially a “fit -of gout” as if it had occurred at the classic site, the _big toe_. - -How vivid the light then thrown upon the import, the _etiological_ -significance, of otherwise inexplicable _functional_ derangements! -How grim the potentialities of, _e.g._, “dyspeptic” symptoms as -revealed by detection in the subject of a _tophus_! Whether viewed -from the _diagnostic_ or _prognostic_ aspect, its importance cannot -be overestimated. For let us not forget that the _tophus_ is the one -incontrovertible token of the “gouty diathesis.” This morbid localisation -is the sole outward expression of the inward and dominant pathological -trend. - -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 _gout_ from noting an _uratic -concretion_ in one _ear_. 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 _tophi_? - -For, far more often than is currently realised, their eruption -_antedates_ the _articular_ outbreaks.[27] Moreover, they may not be -solitary, but numerous, the _cutaneous gravel_ of older authors. In -truth, these cases of tophi, _uncomplicated_ by _articular_ lesions, -seem to merit some distinguishing term, representing as they do a purely -_ab-articular_ form of gout.[28] They constitute what might be termed -primitive elemental gout, of which the subsequent _articular_ outbreaks -are but an extension, a further manifestation of the “gouty diathesis.” -For it is just this same tendency to _uratosis_ or deposition of sodium -biurate, and this alone, that to our mind constitutes _gout_, 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. - -_Premonitory Symptoms of Tophus Formation._—While tophi may _antedate_ -articular attacks, we do not always meet with them as _mature_ -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 _pricking_ or _tenderness_ in the _ears_. - -Sometimes the pain in the ears is _acute_, 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 _fingers_. I have myself frequently known the -pain and soreness referred to chilblains, though later their tophaceous -nature was disclosed. - -Given such auricular pain and tenderness, we should examine the _pinna -for small red swellings_.[29] These, when definitely localised, should be -punctured and the thick white fluid which exudes examined microscopically -for _urate of soda_ 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 _pre-uratic_ 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 _pre-uratic_ stage. Needless to say, -all local sources of fallacy—Woolner’s tip, fibroid nodules, sebaceous -cysts—were excluded, while, in the lack of _crystalline_ proof, the -evidence in favour of the associated _arthritis_ being gouty rested -on its being at the classical site, the _great toe_. Moreover, as an -alternative explanation we have the possibility of _reabsorption_. 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 _acute_ attack, tophi may -diminish in size or even disappear, while coincidently fresh tophi form -at other sites. - -_Premonitory Articular Pains._—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.” - -In conclusion, we would urge that, given _gastric_ or _hepatic_ -disturbances, etc., in a subject predisposed by _heredity_ or _habits_ to -gout, we should note the presence or absence of the following:— - - (1) Pain, pricking, or tenderness in the ears, with or without - small red swellings. - - (2) Similar sensations at site of finger joints, with dorsal - swellings over which the skin may be red or unchanged. - - (3) The existence or not of pearly white concretions, _i.e._ - mature tophi (as tested microscopically), at the above sites or - elsewhere. - -Further signs that may be sought for in cases of doubtful nature, _i.e._ -_unevidenced by tophi_, would be:— - - (4) The presence of _uricæmia_. - - (5) A lowered or sub-normal output of uric acid in the urine. - - (6) Diminution or retardation of the output of exogenous purin. - -To take up the thread of our narrative regarding the _prodromal_ symptoms -which at any moment may give place to an _articular_ outbreak. The -_determinants_ or _exciting_ causes having been already dealt with in -the section on etiology, we shall here only note those symptoms or signs -that portend the _imminence_ 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. - -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. - -Reverting to more definite harbingers, it has been noted that the _urine_ -becomes _scanty_, and its content of _uric acid_ much _diminished_, 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 _pricking pains or tenderness_ are experienced at their site. -Scudamore, Garrod, and Duckworth are all agreed on this point. Another -sign noted by Sydenham was that the _veins_ of the _part_ about to -be affected become _engorged_—a feature confirmed by Trousseau and -others.[30] - - -THE ACUTE PAROXYSM - -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.[31] - -Still the subject feels better and more placid than his wont, seeks -his bed, and sinks to sleep (“sanus lecto somnoque committur”). 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 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. - -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 _bien-être_ 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. - -Initial attacks of gout are usually _monarticular_, but consideration -of the polyarticular variety will best be postponed until we come to -consider _acute gouty polyarthritis_. Also we think it will be more -convenient for us to defer discussion of _retrocedent_ 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. - - -DETAILED CONSIDERATION OF PHENOMENA - -_Onset._—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 _initial_ 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 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! - -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. - -Again to resume, it is by no means invariably the case that the onset is -_nocturnal_. 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. - -_Locality._—Gout in its classical form is _monarticular_ in distribution. -In 375 out of 512 _initial_ 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 _metacarpo-phalangeal_ 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 _upper_ limb, and even -in its most inveterate form the _shoulder_ and _hip_ joints are immune. -Personally, I have never seen a case of gout in the shoulder or hip; such -cases are usually examples of _osteo-arthritis_. - -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 -_left_ 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 _right_ side of the body. - -_Pain._—If we may accept the lurid imagery of its victims, even the -tortures of the Inquisition failed to transcend in agony the— - - “... pangs arthritic - that infest the toe of libertine excess.” - - _Cowper._ - -Sydenham said that at its onset the pain was as that of a dislocation -(_ossium dislocatio_). 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.” - -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.” - -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.[32] - -Apart from the personal factor, in _subacute_ cases the pain is notably -less severe than in the _acute sthenic_ form. The pain of gout, as a -rule, is more intense than that of _acute rheumatism_, and, I fancy, than -that of all other varieties of acute arthritis.[33] 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.” - -Lastly, in respect of the duration of the pain, it is not always -true that it wholly _intermits_ 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, on a -_crescendo_ 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. - -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. - -_General Phenomena._—Symptoms, other than those referable to the affected -part, vary widely in different cases. In this respect the acute _sthenic_ -forms contrast with the acute _asthenic_ 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 _cramps_ affecting muscles of the leg, thigh, and upper parts of -the body, are more or less prominent symptoms in a considerable number of -instances. - -The _pyrexia_ appears to be _symptomatic_, more or less in proportion to -the acuteness of the local phenomena. Comparably the highest temperatures -are usually met with in _sthenic_ 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 _acute asthenic_ forms, that -occur often in women (Garrod), may be wholly _afebrile_. - -_Changes in the Blood._—Apart from its increased content of uric acid, -further morbid changes take place in the blood in gout. - -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 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. - -More significant, however, is it that the blood in acute gout may show a -high grade _leucocytosis_ with _secondary anæmia_. - -In a case under my care of _acute gout_ at classic site, though by no -means of unusual severity, the following was the content of the blood -picture:— - - BLOOD COUNT. - - Red corpuscles, per c. mm. 3,692,000 = 73·8 per cent. - Hæmoglobin 80 ” - Colour index 1·08 ” - Leucocytes, per c. mm. 25,920 - - DIFFERENTIAL COUNT. - - Lymphocytes 8·0 per cent. = 2,074 per c. mm. - Large mononuclears 3·5 ” = 907 ” - Polymorphonuclears 87·0 ” = 22,550 ” - Eosinophiles 0·5 ” = 130 ” - Mast cells 1·0 ” = 260 ” - ----- - 100·0 - - The salient feature of the blood picture is the high grade - _leucocytosis_ of leucoid type with moderate anæmia—appearances - quite compatible with, and suggestive of, an _infective_ - 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.e._, the big toe. - -_Uric Acid Excretion._—If when on a _purin-free_ 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 _anacritical -stage of depression_). 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 _uric acid wave_. Subsequently, with the gradual subsidence of -the paroxysm, it again drops into what Umber termed the _post-critical -stage of depression_. 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. - -_Local Phenomena._—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 _engorgement_ of veins that _precedes_ the _articular_ -outbreak becomes more pronounced, extending from the vicinity of the -painful joint as far as the leg. The overlying 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 _abscess_, 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 _œdema_ is -perceptible. - -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 _œdema_ 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 _intra-articular effusion_ unless it be -the ankle joint that is involved. - -According to Duckworth, in the more _sthenic_ forms there may be local -_ecchymoses_. With the crisis the redness, œdema, and venous turgescence -die down. The previously distended skin becomes wrinkled, and with -complete subsidence of inflammation _desquamation_ ensues. This process -is generally attended with troublesome _itching_. It is most noticeable -about the _feet_ and _hands_, 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. - -The exquisite sensitiveness of the parts, as before noted, gives way to -_numbness_. The diminished sensibility, coupled with _stiffness_ 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. - -In acute _asthenic_ forms great contrasts appear. Pain and tenderness in -the toe may be moderate, but there may be little local heat or redness -and no _pyrexia_. But _œdema_ is generally in evidence, and the usual -_desquamation_ of skin follows. - -_Tophus Formation._—To the local changes that mark their eruption at -ab-articular sites we have already alluded. Here we would only reiterate -that their formation _follows_ 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 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.” - - - - -CHAPTER XVII - -CLINICAL ACCOUNT (_continued_) - - -ACUTE GENERALISED GOUT - -While gout may throughout its life history confine its ravages to the -_foot_, if not solely to the _toe joints_, it may, even in the _initial_ -attack, involve many articulations. Such cases usually, if not always, -occur in persons of marked _gouty heredity_. In its simplest forms the -orthodox _monarticular_ 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 _tarsal_ -joints, the _knee_ and the _hand_, may be invaded in the _first_ attack. -Occasionally, too, the disorder displays concomitantly its tendency -to involve other structures, _tendons_ and _aponeuroses_, _e.g._, the -_tendo Achillis_, _plantar fascia_. Such _widespread initial involvement_ -is usually preceded by _prodromal_ phenomena of unusual severity -and prolonged duration. These _initial_ attacks of _polyarticular_ -distribution are extremely rare. - -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—_series et -catena paroxysmulorum_, to invoke Sydenham’s expression. - -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. - -In such attacks not only the _feet_, _knees_, _hands_, and _elbows_, -may be promiscuously involved, but often also the _ligaments_, _bursæ_, -_tendon sheaths_, and _aponeuroses_. 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 _acute rheumatism_. -In other words, that _fixity_ distinctive of gout in its monarticular -forms is here exchanged for _mobility_, that specific quality of acute -rheumatism. - -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 _dorsum_ of the _hand_ and _foot redness_ and -_œdema_ will be prominent, and Scudamore noted that the flush might be -widely diffused, simulating _erysipelas_, with here and there small -_ecchymoses_. - -When structures more deeply placed, _i.e._, _tendon sheaths_ at ankle, -knee, and wrist, are singled out for attack, swelling is less marked and -redness of the skin more patchy in distribution. The _bursæ_ 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. - -Involvement of the _olecranon bursa_ 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 _acute gouty -polyarthritis_. The eight or ten physicians who had treated him had -all regarded the disease as _rheumatic fever_. 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 _gouty olecranon -bursitis_.”[34] Occasionally the bursæ when filled with uratic deposit -undergo _suppuration_ 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. - -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 _tendo Achillis_ is a favourite site, or the tendons of -the wrist, or the ligament of the patella. The same is true of the -_aponeuroses_, 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 tendon and nerve sheaths frequently outlast the -articular lesions, and may become the dominant element in the clinical -picture. - -Naturally, when not only joints, but _bursæ_ 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. - -Reverting to the _constitutional_ symptoms, the outstanding feature is -that, notwithstanding the widespread involvement of joints with manifest -local inflammatory reaction, the _pyrexia_ is of _moderate_ grade, and -so frequently, indeed, is it _afebrile_ that this peculiarity is of -diagnostic significance. - -_Changes in the Blood._—The findings are extremely interesting in view of -the high grades of _leucocytosis_ to be met with both in _pyrexial_ and -_apyrexial_ examples. - -In a case of _acute gouty polyarthritis_ 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 _tophi_, 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 _biurate_ crystals. His temperature rose nightly from 101° up to -102° F., with morning remissions. The left knee and wrist were the seat -of _effusion_, and some of the small finger joints were inflamed. - - BLOOD COUNT. - - Red corpuscles, per c. mm. 4,432,000 = 88·6 per cent. - Hæmoglobin 60 ” - Colour index ·68 ” - Leucocytes, per c. mm. 27,200 - - DIFFERENTIAL COUNT. - - Lymphocytes 9 = 2,450 - Large mononuclears 13 = 3,540 - Polymorphonuclears 78 = 21,220 - Eosinophiles 0 = 0 - Mast cells 0 = 0 - ----- - 100·0 - -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:— - - TOTAL COUNT. - - 44,800 per c. mm. (nearly all leucocytes). - - DIFFERENTIAL COUNT. - - Polymorphonuclears 92 - Lymphocytes 7 - Large mononuclears 1 - Eosinophiles 0 - Basophiles 0 - --- - 100 - -Attempts at culture on broth and agar proved _sterile_. In addition three -separate blood cultures, taken at intervals of a few days, on agar slopes -and broth, all gave _negative_ results. - -In another instance of _polyarticular_ distribution the subject was seen -during the _inter-paroxysmal_ period. He displayed auricular _tophi_, the -crystalline content of which was verified microscopically. - - BLOOD COUNT. - - Red corpuscles, per c. mm. 5,732,000 = 194·6 per cent. - Hæmoglobin 65 ” - Colour index ·57 ” - Leucocytes, per c. mm. 13,200 - - DIFFERENTIAL COUNT. - - Lymphocytes 34 = 4,490 - Large mononuclears 3 = 400 - Polymorphonuclears 61·5 = 8,120 - Eosinophiles ·1 = 130 - Mast cells ·5 = 66 - -Chalmers Watson some years previously investigated the blood in cases -of _acute gouty polyarthritis_ both during an exacerbation and in the -_inter-paroxysmal_ period. His findings were as follows:— - -During the _attack_ the films showed very marked _leucocytosis_. 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. - - “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 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. - - “_Blood plates._—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.” - -Shortly after Chalmers Watson, Bain published his results of blood -examination in _acute gouty polyarthritis_. He also noted the presence -of a distinct _leucocytosis_. 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.” - -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. - -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 _inter-paroxysmal_ 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. - - BLOOD COUNT. - - Red corpuscles 7,364,000 = 147 per cent. - Hæmoglobin 74 ” - Coloured index 0·5 ” - Leucocytes 21,400 - - DIFFERENTIAL COUNT. - - Lymphocytes 28·5 per cent. = 6,099 per c. mm. - Large mononuclears 2·5 ” = 535 ” - Polymorphonuclears 64 ” = 13,696 ” - Eosinophiles 3·5 ” = 749 ” - Basophiles 1·5 ” = 321 ” - -The blood picture, it will be seen, is one of erythræmia—a marked -leucocytosis, a normal differential percentage count, pronounced -secondary anæmia. - -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 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). - -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. - -As to the other general clinical features the _nervous_ 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 _monarticular_ sites, save only in the tendency to _relapses_. -Sweating is not a common feature, as in _acute rheumatism_. Neither does -acute _endocarditis_ 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 _nephritis_. - -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. - -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 -_presence of tophi_. 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.” - -In conclusion, before passing to consideration of _chronic articular -gout_, it will be convenient here to discuss certain _concomitant -phenomena_ 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. - - -COLLATERAL PHENOMENA OF GOUT - -The liability of acute articular gout to be complicated by _muscular_ -and _nerve_ disorders has already been briefly alluded to. Also it was -pointed out that in respect of this tendency gout displayed an analogy -with the _specific_ infections, viz., in that these latter too are prone -not only to arthritic, but to muscular and nerve, lesions also. - -Our forefathers, greatly exercised by this apparent overlapping 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.” - -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 _muscular_ and _nerve_ disorders as also -attributable to the underlying gout. Thus, so impressed was Garrod -with the frequency of the incidence of _lumbago_ and _sciatica_ in -_gouty_ 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 _irregular_ gout.” - -Duckworth, again, felt sure “that much so-called ‘muscular’ rheumatism -is really gouty,” and forthwith ranked its manifestations among the -_irregular_ 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.” - -Turning to the _nerve_ 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.” - -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. - -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 _gout_. 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 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.” - -Apart from the _simultaneous_ incidence of gout and _fibrositis_ in -the same subject, it is equally certain that the victims of a “gouty” -heritage are unusually prone to develop fibrositis. - -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 _lumbago_, its influence also being very obvious in the case -of _sciatica_ and other types of nerve sheath involvement. - -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 _gouty_ element is but too -frequently overlooked in examples of this affection. - -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 _lumbago_ and other types of _muscular_ -fibrositis, yet at the same time attribute to gout an important -etiological _rôle_ in the allied conditions _sciatica_ and _brachialgia_? - -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 _gout_. 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. - -That the _lumbar_ 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 _lumbago_. - -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 _sciatica_ and _brachialgia_. - -This position is untenable, and for the following reasons: the -pathological lesion in both instances is the same—viz., _fibrositis_; in -lumbago and deltoid rheumatism it implicates the sheaths and interstitial -tissues of the _muscles_, in sciatica and brachialgia the similar -investments of the _nerves_. - -Strictly speaking, therefore, any differentiation that we can effect -between muscular and neuralgic types of fibrositis is perforce merely -_topographical_. To draw _etiological_ 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. - -In light of such transitions of _muscular_ into _neuralgic_ 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 _ergo_ in the -closely associated and often antecedent muscular types of fibrositis. - -While insisting on the importance of gout as a _predisposing_ factor in -_fibrositis_, 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 -_tophi_, etc., were present. - - -INCIDENCE OF GOUTY STIGMATA IN VARIOUS TYPES OF FIBROSITIS - -Out of 343 instances of fibrositis of the _joints_ such stigmata of gout -were present in 118 males and nine females. Of _muscular_ types, taking -as our example _lumbago_, 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 proclivity. Lastly, out of -thirty-eight cases of lumbago complicated by right or left sciatica ten -were of the same diathesis. - -Passing in turn to consider this same factor in relation to _sciatica_, -we note that out of 142 examples twenty-four men and three women were -gouty. Occasionally, too, apart from _glycosuria_, it appears to be -responsible for bilateral sciatic pains, for in three examples of this -nature gout was present. - -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 _hip joint_, he yet affirms his belief that -“there are some in which the neuritis is a primary condition.” - -With this statement my own experience accords, but with a reservation, -viz., that the _sciatic neuritis_ is apparently _secondary_ to a lumbar -or _gluteal fibrositis_, with sequential involvement of the _sciatic -nerve sheath_ and extension to the nerve trunk. - -Taylor holds also that _anterior crural_ and _brachial neuritis_ may be -directly due to _gout_. 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.” - -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.” - -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. - -Lastly, I cannot confirm out of my own experience Duckworth’s statement -that “_herpetic_ attacks in all varieties of ‘gout’ are common.” Nor have -I seen _shingles_ co-exist with acute gout, neither have I come across -any examples of so-called _gouty spinal meningitis_! - -In conclusion, I would submit that:— - - (1) Acute articular gout is not infrequently complicated by - fibrositis. - - (2) The same infection that determines the articular outbreak - is responsible for the concomitant muscular and nerve phenomena. - - (3) Persons of gouty heritage are especially liable to - fibrositis, notably _lumbago_ and _sciatica_. - - (4) Gout predisposes to fibrositis in that the inherent - pathological attributes of gouty tissues favour the incidence - of _infection_. - -In regard of this last postulate, it is well known that _gouty_ persons -who contract _gonorrhœa_ are more prone than the _non-gouty_ to develop -_gonorrhœal rheumatism_, 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? - - - - -CHAPTER XVIII - -CLINICAL ACCOUNT (_continued_) - - -CHRONIC ARTICULAR GOUT - -In delineating the features of the _acute polyarticular_ variety, we have -to a certain extent trenched on the clinical territory of the _chronic_ -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.” - -The truth is that articular gout in this respect is very prone to -vagaries. Thus, in rare instances an attack of _acute_ or _sub-acute_ -gout, more particularly the latter, may merge without break into the -_chronic_ form of the disease.[35] 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. _Remissions_, but -not complete _intermissions_, occur, and every now and again intercurrent -acute attacks take place. - -But, the reader may observe, surely this is very reminiscent of _acute -gouty polyarthritis_, with its serial content of acute paroxysms?[36] -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. - -Not so, unfortunately, when such paroxysmal waves sweep over the subject -of long-standing or _chronic gout_. Not only do the recurrent acute -outbreaks occur with _increasing frequency_, but also with _increasing -length of duration_. It is here no longer a question of the intercurrent -acute attack lasting days, but _weeks_. 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. - -But a word here as to the variations in _distribution_ of the _articular -lesions_ in _chronic gout_. The well-marked _penchant_ of _acute_ -gout for the _great toe_ continues throughout the life history of the -disorder, the predilection for this site being equally a characteristic -of the _chronic_ type. As to the subsequent articular involvement, Garrod -held the sequence to be as follows: _heels_; _ankles_; _knees_; the -smaller articulations of the _hands_; lastly, the _shoulders_ and _hips_. -It has never been my lot to see either the shoulders or hips involved; -but I have seen _osteo-arthritis_ of the _hip_ in _men_ displaying -_auricular tophi_, and I am inclined to think that, in the presence of -the latter, it has sometimes been assumed that the hip mischief was of -_gouty_ nature—the “hip gout” of the older authors. - -Moreover, the _order of sequence_ is by no means invariable, for -oftentimes a local circumstance, _i.e._, _injury_ or _sprain_, determines -the location. Again, chronic gout is very erratic in respect of the -_number_ 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. - -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. - -Old gouty subjects are often of sallow or parchment-like complexion. -The _blood_ in these cases of polyarticular gout conforms in attenuated -degree, in the matter of leucocytosis and secondary anæmia, to that -observed in the more _acute_ types, as witness the following blood -pictures. - -All were males, the subjects of chronic articular gout of many -years’ standing. They all exhibited _tophi_, which were verified -microscopically. The examinations were conducted during the -inter-paroxysmal periods. - - (1) BLOOD COUNT. - - Red corpuscles, per c. mm. 4,832,000 = 96·6 per cent. - Hæmoglobin = 64 ” - Colour index = ·66 ” - Leucocytes, per c. mm. 11,000 - - DIFFERENTIAL COUNT. - - Lymphocytes 42 = 4,620 - Large mononuclears 4 = 440 - Polymorphonuclears 52·5 = 5,775 - Eosinophils 0 = 0 - Mast cells 1·5 = 165 - - (2) BLOOD COUNT. - - Red corpuscles, per c. mm. 5,040,000 = 100·8 per cent. - Hæmoglobin = 72 ” - Colour index = 0·72 ” - Leucocytes, per c. mm. 13,400 - - DIFFERENTIAL COUNT. - - Lymphocytes 15 = 2,010 - Large mononuclears 2·5 = 335 - Polymorphonuclears 78 = 10,452 - Eosinophils 1 = 134 - Mast cells 3·5 = 469 - - (3) BLOOD COUNT. - - Red corpuscles, per c. mm. 4,280,000 = 85·6 per cent. - Hæmoglobin = 66 ” - Colour index = 0·77 ” - Leucocytes, per c. mm. 12,000 - - DIFFERENTIAL COUNT. - - Lymphocytes 23 = 2,760 - Large mononuclears 3 = 360 - Polymorphonuclears 74 = 8,880 - Eosinophils 0 = 0 - Mast cells 0 = 0 - -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 -_tophaceous deposits_. But to detailed description of these latter we -shall return later. - -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 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 _arterio-sclerosis_. Their _blood pressure_ is -_raised_, their vessels tortuous and thickened, and the left ventricle -enlarged. - -As to the _variations in uric acid excretion_, these, as before remarked, -show no appreciable deviation from normal. Occasionally, however, there -is a tendency to _uric acid gravel_. 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 _albumen_ with -hyaline casts. - -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 _renal_ -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. - - “The life of all his blood - Is touched corruptibly, and his pure brain - (Which some suppose the soul’s frail dwelling-house) - Doth by the idle comments that it makes - Foretell the ending of mortality.” - - _Shakespeare._ - -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 _hereditary_ -tendency, and particularly in those in whom the _initial_ 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.” - -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 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. - -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.” - -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.” - - -THE JOINT DEFORMITIES OF CHRONIC GOUT - -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. - -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 -_hands_ and _individual fingers_, flail-like and semi-paralytic as they -so frequently become. - -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. - -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.e._, provided with a pedicle.” - -As shown in the coloured plate, the favourite site for their -development is the _dorsum_ of the _hand_ or the vicinity of the -_metacarpo-phalangeal_ or _mid-phalangeal_ 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. - -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, _are not located exactly at -the level of the articulation_. Unattached as they are to the _articular -ends_, 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 _erratic_, are not like _osteo-arthritic_ -nodules, erupted from and continuous with the articular bone ends. Again, -relatively independent of the contiguous tissues, they, unlike osseous -outgrowths, are slightly _movable_ in lateral directions. - -When of _recent_ incidence, their consistence is _soft_, and, be they -never so ancient, they do not attain the _density_ and _hardness_ of -_bony outgrowths_. 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.e._, subjacent uratic -deposits. - -In other particulars also they differ from bony outgrowths. The -tophaceous masses may _soften_ and _disappear_ after exacerbations of -_arthritis_, and others may form at different sites. Following such -absorption or difference in their location, some increase in joint -_mobility_ may happily ensue. This same fortunate occurrence may follow -discharge of the uratic masses through _ulceration_ and _perforation_ of -the skin. - - -TOPHI: THEIR EVOLUTION AND DISTRIBUTION - -In our chapter on _Uratosis_ we dealt with the chemical nature and mode -of formation of tophi. Also we affirmed our belief that tophi, whether -_articular_ or _ab-articular_ in site, were always _preceded by local -inflammatory reaction_, and to the clinical tokens of their impending -eruption we need not recur. Albeit this point, _i.e._, _antecedent_ -inflammation, is of such prime importance that we have not hesitated to -append to our text a lengthy footnote,[37] this because, as Garrod, who -quotes the same _in extenso_, rightly claims, the genesis and evolution -of tophi has never been so graphically depicted as in Moore’s description. - -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 _cause_, 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 _inflammation_ -even in the _ear_ 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.” _Subacute -gout_ sometimes occurs in the ears, says Duckworth, who furthermore -believed that the _indurations_ in the _cartilage_ observed by him -in _gouty_ subjects were the outcome of such attacks. Laycock, too, -long before noted that the ears of gouty subjects often appeared to be -“soldered.” - -_Pain or discomfort in auricular tophi often presages an oncoming -articular paroxysm._ “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 -_prognostic_ as well as diagnostic valency in that the incidence of pain -at their site may foretell the oncoming of _articular_ outbreaks. - -While, as before emphasised, the eruption of tophi may _antedate_ the -occurrence of _articular_ gout, on the other hand tophi may be present at -the joints, but lacking in the ears and all other _ab-articular_ sites. -Auricular tophi, extracted occasionally by patients, are sometimes shed -_spontaneously_. According to Duckworth’s statistics, in one-third of -all well-marked cases of gout the ears present tophi in the _helix_, the -_anti-helix_ and its _fossa_ and the _lobule_, and in some cases they may -be situated on the _posterior_ surface of the _pinna_. - - -OTHER SITES OF TOPHI - -Apart from the external ears, tophi are apt to form in various -localities. Most frequently they are situated in the vicinity of the -_joints_ and _bursæ_, especially that over the _olecranon_. 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:— - - “‘Nomine reque duplex ut nodus Gordius essem.’” - -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.” - -Often, however, their presence at length induces irritation of the -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. - -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.” - -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 _urates_ have _antiseptic_ properties. But Bendix (_Zeit. klin. -Med._, 1902) failed to demonstrate such qualities experimentally. The -truth would appear to be that, though gouty inflammation never ends -in _suppuration_, yet _abscess formation_ very commonly occurs in the -_peri-tophal_ 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.” - -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. - -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.” - -While they tend to aggregate themselves round the joints, yet tophi -sometimes invade the _integument_ of the _limbs_. They have been seen in -the skin over the _ulna_ and _tibia_, and commonly over the _olecranon_ -and _patella_. 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 -_thighs_ and _legs_. The case is not an isolated one, but the incidence -of subcutaneous uratic deposits in the limbs, save over _articulations_, -is exceptional. - -In the _palms_ of the _hands_ and the _pulps_ of the _fingers_, the -knuckles and phalanges, tophi are found not infrequently; and Trousseau -tells of a lady of sixty in whom the cutaneous _palmar folds_ of both -hands were “marked with radiating white lines such as are seen in those -who have long been employed in tempering plaster.”[38] Similar deposits -have been noted in the _plantar surface_ of the _feet_. - -Reverting to the _trunk_, uratic deposits have been found in the -_scapular_ region, also in the _perineum_. I have twice seen tophi -in the _corpora cavernosa_ of the penis. In the face, apart from the -ears, they have been found in the _alæ_ of the nose. In the _eyelids_ -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 _deposits_ of _urates_ on -the surface.” - -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.” - -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 deposition, the kidneys might be held as unsound and -undergoing sclerosis; and, according to Duckworth, the rule commonly -holds good. - - -AFFINITIES BETWEEN GOUT AND OTHER DISEASES - -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 _irregular_ -manifestations of gout. - -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 _irregular_ manifestations, _i.e._, -phlebitis, eczema, etc. - -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, _faute de mieux_, -relegated a large number of conditions whose pathology was inexplicable -to the nebulous domains of irregular gout. - - -GOUT IN RELATION TO GLYCOSURIA - -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 _irregular_ -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. - -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 _diabetes_. - -Following the installation of glycosuria, the tendency to paroxysmal -_articular_ 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 _vice versâ_. 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. - -It is generally held that glycosuria is most commonly associated with -_irregular_ forms of gout. But, in view of our ignorance of the intimate -nature of even _regular_ 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 _arthritic_ 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 _regular_ -attacks of gout, or those displaying those objective tokens pathognomonic -of the disorder, _i.e._, _tophi_. - -Again, James Taylor has recently reminded us that, if nerve affections -are relatively common in true _diabetes_, the same may be met with in -_gouty glycosuria_, even when of temporary duration. Thus symptoms -indicative of _peripheral neuritis_ may occur, _i.e._, lost knee jerks, -paræsthesiæ, and paresis of the lower limbs. Now, as this authority -pertinently observes, the subjects of _gouty glycosuria_ are frequently -given to _alcohol_. Consequently the question whether or not the -symptoms are due, not to sugar, but to _alcohol_, arises forthwith. - -In some undoubtedly the alcoholic factor plays a _rôle_, 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 _alcoholic neuritis_. -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 _gouty_ of a true _glycosuric -peripheral neuritis_ quite independent of _alcoholic peripheral neuritis_. - -Other concomitant nerve troubles noted in this association are _severe -intercostal neuralgia_ and, even more commonly, _neuralgia_ of the _fifth -nerve_, and to this may be added _migraine_ and that other neurosis -_asthma_. 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. - -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, _infective_ or _other_, should be excluded, this always, -but pre-eminently so in _brachialgia_, _sciatica_, and _trigeminal -neuralgias_. Nor even, should there be a history of classic _outbreaks_ -or blatant _tophi_ present, should we be less vigilant. - -By all means recognise the _gouty diathesis_. It often avails much -in treatment, but not if, _e.g._, _dental caries_, _antral disease_, -_cervical rib_, or _pelvic growth_ be overlooked, not to speak of recent -or concurrent sources of _infection_ or _toxic absorption_. - -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 _nerve_ troubles in a _gouty_ -person, _i.e._, a paræsthesia, itching, neuralgia, etc., we should always -suspect its presence.[39] Incidentally our search may reveal not only -sugar, but also _albumen_, and the latter may explain much that appeared -inexplicable. - - -GOUT IN RELATION TO PHLEBITIS - -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 -_irregular_ manifestations of the disease. - -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. - -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. - -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.” - -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. - -The instances most indicative of a _gouty_ origin are those in which the -veins of a limb, the seat of _acute gout_, 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 _varicose_ -condition of the veins of the legs of long standing existed in his series -of examples. - -Garrod recognises in addition a second type, in which phlebitis, -“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 _hereditary_. 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. - -In conclusion, for myself, I would suggest that the term “gouty” -phlebitis be restricted to those instances in which a limb, the seat of -_acute articular gout_, is complicated by _phlebitis_ of the veins of the -affected part. Here we are dealing with what is palpably an extension -of the gouty inflammation from the affected _joint_ to the _veins_, and -which, I venture to assert, is strongly confirmatory of the view that -an _infective_ element intrudes in “gouty” arthritis. We may recall -that, _e.g._, _gonorrhœal phlebitis_ of the lesser saphenous veins is -not so uncommon, while the frequency with which phlebitis complicates -_infections_ calls for no emphasis. - -Leaving aside these rare instances of _acute gout complicated by acute -phlebitis_, 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 _varicose veins_ of long standing, and _ipso facto_ 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 _familial_ 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 -_varicose veins_ is hereditary, and _ergo_ predicates an enhanced -liability to phlebitis? - - -CUTANEOUS DISORDERS - -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. - -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, 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 _arthritiques_ 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.” - -As to the skin disorders associated with _acute_ types of gout, perhaps -the most interesting and well ascertained is _herpes_. 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. - -The noteworthy liability of the gouty to these disorders is but another -proof that gout predisposes its victims to _infections_. 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 _big toe_. - -Passing to skin affections associated with _chronic_ 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. - -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. - -As to _psoriasis_, 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” _pruritis_ and _prurigo_, 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. - -As to frequency of incidence in the “gouty,” _eczema_ 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, 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. - -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. - - -GOUT AND NEPHRITIS - -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 _gout_ and _granular kidney_ -run to their fell end quite _independently_ of each other. - -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 _granular kidney_, which may pass to -its close without any suspicion of gout. - -Now, as we have seen, the primary _renal_ origin of gout fails of -demonstration. Is _gout_, then, _causally_ related to _granular kidney_, -or is there some less direct relation between them? - -As to this, to begin with, it is extremely rare that a “gouty” subject -develops _acute_ nephritis. In the exceptional instances when it -does occur it is either purely accidental or else the outcome of an -_exacerbation_ of a _previously existing interstitial nephritis_. - -The question then arises, Can gout when long continued originate _per -se_ 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 _specific_ of _gout_ in -the so-called “gouty” kidney. It is an _interstitial nephritis_, which -may assume the appearances of the ordinary “contracted kidney” or the -“arterio-sclerotic” type. There may be _uratic_ deposits at the apex of -the pyramids, or even an _uric acid calculus_; 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. - -Nor, _quâ_ _gout_ as a _causal_ 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. - -There being nothing _specific_ of _gout_ in the lesions of so-called -“gouty” kidneys, we must revert to the clinical findings to refute or -establish any _causal_ 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 _facies_ absolutely distinct the one from the other. - -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 need for further and more exact -researches in this sphere is but too obvious. - -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.e._, excess in alcohol, overeating, etc., that make for the eruption -of gout, are largely identical with those that promote the development -of _granular kidney_. 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.” - -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. - - -PROGNOSIS IN GOUT - -Gout _per se_ rarely, if ever, proves fatal. Certainly, as Sir Thomas -Watson long since said, “_gout in the extremities_ is not a mortal -disease.” When death did occur during or in close relation to an -_acute_ paroxysm, it was by our forefathers attributed either to its -_retrocession_ or to some _misplaced_ or _irregular_ manifestation. -Indeed, their attitude was very much that of the French physician who -observed: “La goutte articulaire est celle dont on est _malade_, et la -goutte interne est celle dont on _meurt_.” - -But, as we shall see later in our chapter on _Irregular_ Gout, most, -if not all, of their instances of the assumed translation of the -_materies morbi_ of gout to some vital organ are without foundation. The -demise, often dramatically sudden, was not due to _gout_, 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. - -Not that gout is salutary, lessens the liability to other diseases, or -promotes longevity. Very much the reverse—“a tendency to _recurrence_ 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 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. - -While these reflections are in the main, we think, justifiable, we must -recollect that in gout, as in other maladies, the elements of _prognosis_ -reside in the _individual_, 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. - -As to the axiom, generally accepted, that the earlier in life gout makes -its _début_, the more unfavourable the outlook, there are exceptions. -Where _longevity_ 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 -_albumen_ 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. - -“There dies not above one of a thousand of the gout, although I believe -that more die _gouty_,” wrote Graunt long years since; and this contains -a kernel of truth, for the _prognosis of gout_ rests in the main not on -the _gout_, but the _conditions correlated therewith_—the absence or not -of _complications_. 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 _regressive_ period of life. - -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 _arterio-sclerosis_ Huchard held _gout_ and lithiasis responsible -for no less than 693. An appalling indictment, but what of the long arm -of _coincidence_? For _age_ unquestionably is the chief factor in the -production of arterio-sclerosis, though many allot gout a dominant _rôle_ -in its genesis. This certainly is by no means proven. Still, whatever be -the relationship, _gout_ and _arterio-sclerosis_ are very often found -_in association_. If so, the prognosis will obviously rest, not on the -gout, but on the _vascular_ disease—the pulse tension. If therewith -be correlated _albuminuria_ and a displaced apex beat, the outlook is -unfavourable. - -Again, is the subject lean or obese? If the former, so much the better, -for _corpulency_ and _gout_ are a sinister combination. Gout in -itself, as previously observed, favours microbic invasion, and obesity -accentuates the liability. Moreover, the gouty obese are prone to -_arterio-sclerosis_ and _granular kidneys_, with sometimes a superadded -_glycosuria_, 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. - -Apart from arterial degeneration, we have to recollect the tendency to -_phlebitis_ of _recurrent_ type. This when present always carries with -it the risk of _embolism_ and sudden death. Cases therefore displaying -this proclivity to phlebitis must be judged accordingly. The gouty -_glycosuric_, 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. - -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. - -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 _alcohol_, 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. - -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,— - - “The rule of not too much, by temperance taught - In what thou eat’st and drink’st, seeking from thence - Due nourishment, not gluttonous delight.” - - _Milton._ - - - - -CHAPTER XIX - -ETIOLOGICAL AND CLINICAL DIAGNOSIS - - -ARTICULAR GOUT - -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 -_etiological_. This is the more likely to be attained if we shed all -preconceived ideas and prejudices. - - -ETIOLOGICAL DIAGNOSIS - -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 -_joint_ disorders, whose outward resemblances so oft hark back to inward -disparities. - -First, as to the manner of man, while one would not decry the hints -obtainable from _physiognomical_ 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. - -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.” - -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 _gout_ -than rheumatism, this only as a broad generalisation. - -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. - -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 _tophus_, 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 -_non_-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! - -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 -_etiological_, diagnosis. - -To narrow our field, we should, in the first place, exclude _gonococcal_ -infection, and failing this, influenza, syphilis, or any of the zymotic -or other disorders prone to be followed by or associated with _joint_ -affections. - -If none of such be forthcoming, we should search for _local foci of -infection_. 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 _pyorrhœa alveolaris_. If _dentures_ 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 -_in situ_. The condition of “bridges” should be noted, fruitful sources -of sepsis as they are. Clinical examination of the mouth may prove -inadequate, as _buried roots_, _cysts_, or _abscesses_, not to mention -_alveolar rarefaction_, etc., demand for their detection _radiographs_. - -The _pharynx_ and _tonsils_ should be thoroughly investigated, for -disorders of these same are by no means uncommon in “gouty” subjects. -Any history of _aural_ or _nasal_ discharges demands the same careful -local examination; and, needless to say, the same course must be pursued -in regard of any _local infections_ of the _genito-urinary passages_. In -short, in _gouty_, as in _non-gouty_, forms of _arthritis_, thorough and -routine examination of every patient by modern _bacteriological_ methods -is imperative. - -Ignorant of the precise _etiology_ of _gouty_ arthritis, we can ill -afford to overlook any associated _infective_ foci which may prejudice -the well-being of the victim, as, for aught we know to the contrary, we -may be overlooking the very _fons et origo mali_. Compare our attitude -towards other arthritides of cryptic origin, how systematic our search -for _infective_ foci, and what a light has thereby been shed on their -intimate etiology! - -Here may we lodge a plea for routine examination of the blood in all -cases of _gout_? For, as shown, the findings, _leucocytosis_, etc., -have doubtless some profound significance. Apart from this, the routine -employment of _complement-fixation_ tests for the organisms responsible -for local infections might illumine the obscurity that overhangs this -complex problem of their relationship to remote pathological lesions. - -If up to now our search for local foci prove futile, it remains for us -to note the presence or absence of _functional derangements_ of the -_alimentary tract_, or its _accessory glands_. We must not, because we -think perhaps that the patient “looks gouty,” assume that his _dyspeptic_ -symptoms are of like origin. It is our duty to ascertain, if possible, -the precise nature and origin of the dyspepsia. - -We know that, given _oral sepsis_, sequential infections of the -_appendix_ and _gall bladder_ are not uncommon. Recently it has been -remarked that many _gouty_ 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.e._, dental sepsis, etc. - -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 _etiologically_ 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 _gall bladder_ or _appendix_ disease on the other. -What an aid to the location of adhesions the demonstration of _ileal_ -and _cæcal_ stasis, etc.! - -In obscure cases the _fæces_ may have to be scrutinised for evidences -of _pancreatic_ inefficiency, viz., bulky pale stools, undigested meat -fibres, and excess of neutral fat. Their _bacterial_ content, too, if -abnormally high, should be noted. As in other arthritides of unknown -origin, the results following the administration of _vaccines_ prepared -from the predominant organisms have been such as to suggest a causal -connection. - -The urine should be subjected to _chemical_ and _bacteriological_ -examination. As to _uric acid_, 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 _purin-free_ 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 _on the mere basis of the variations in uric acid excretion in the -urine_ presume to diagnose gout. - -To have any semblance of diagnostic value, the patient should be on a -_purin-free_ 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.” - -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. - -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 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. - -_As to uric acid in the blood_, 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 _confrères_ 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. - -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.” - -A _bacteriological_ examination of the _urine_ should be undertaken. -Trautner held _mucous colitis_ as one of the initial manifestations of -gout, and believes that the _bacillus coli communis_ 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 _B. coli_. He has also found streptococci in the urine -in acute gout, and these subjects certainly enjoy no immunity from other -forms of bacteriuria. - -It is beyond the scope of this volume to outline the methods of -differentiating and determining the exact organisms which may 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 _sub-infection_ 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.” - -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 -_etiological_, not merely nosological, diagnosis? - - -CLINICAL DIAGNOSIS - - -_Introductory Remarks_ - -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 _goutte_ from the Latin _gutta_, -it but expresses laconically the fanciful doctrine of those who so -christened it. - -What the old humoralists saw was the _tophus_, 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. - -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 _tophus_! Even as the vague -and shadowy constitutional warp known as the “rheumatic diathesis” -finds expression, or rather becomes incarnate, in fibrous _nodule_ and -_induration_, so also does the equally nebulous “gouty diathesis” become -objective, crystallised in the _tophus_. - - -THE DIAGNOSTIC STATUS OF TOPHI - -This problem calls for more critical consideration than is usually -accorded thereto. The tophus is, in truth, the touchstone of gout, yet -not a little controversy obtains as to the frequency of its incidence in -“gouty” subjects. - -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.” - -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. - -_Given the presence of tophi, the diagnosis of a “gouty diathesis” is -assured; in their absence it is but speculative._ - -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 _gout_—at any rate, those _unattested by tophi_—would now be -relegated to widely different categories. - -But this zeal for infinite cleavage and subdivision, so characteristic -of the modern school, far from diminishing, does but _accentuate_, the -_diagnostic_ valency of the tophus. It still remains _the_ 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. - -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 -_syphilitic_, _gonorrhœal_, and other forms of arthritis. - -“A name being so readily found for an obscure disease, the 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. - - -TOPHI IN RELATION TO ARTHRITIS - -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 -_tophi_ stamps any _concomitant arthritis_ as “gouty.” - -True, tophi are pathognomonic of gout, but their existence does not -confer on their host _immunity from all other forms of arthritis_. In -view of the increasing light shed upon joint disorders, who can doubt -that (and this not only for our forefathers) the _tophus_ has too often -proved a veritable snare, allaying all diagnostic doubts, lulling us into -false security? For an individual may, for example, exhibit _auricular -tophi_ and be the victim also of an _arthritis_, 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.” - -For it may be of specific infective origin, _gonococcal_, syphilitic, -pneumococcal, etc. _Quâ_ a concomitant arthritis, then, the diagnostic -significance of tophi, at any rate when of _ab-articular_ 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. - -_Conversely, in the absence of tophi, the diagnosis of an arthritis as -“gouty” is not absolute, but presumptive._ - -For in the lack of these objective stigmata how can the authenticity of -our diagnosis be established? Is it not when achieved a _nosological_ -rather than a diagnostic feat? Put otherwise, is not our diagnosis, -especially in _initial_ attacks, largely _topographical_? 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 _initial_ attacks of “gout” is very largely -_topographical_. Let but inflammatory trouble ensue in the _big toe_, 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 -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 _infection_ and, we may add, not less important, its -proneness to _static deformities_? But to this we shall recur when -discussing _differential_ diagnosis. - -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 _tophi_ should be exhaustive. If undiscoverable, why not be -honest with ourselves and recognise that our diagnosis is _presumptive_ -pending their development? - -Sir William Roberts on this point observes: “As a rule, diagnosis of -acute articular gout is easy, but exceptional cases of difficulty occur. -The _gouty_ character of the inflammation is _affirmed by the discovery -of uratic concretions_ in the rim of the ear or elsewhere.” - -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 _presence of tophi_ has settled the nature of a -trouble which in previous attacks has been regarded as ‘rheumatic.’” - -One may, we think, gather from these two statements the inference -that both these distinguished authorities hold _tophi_ to be the -_only infallible criterion_ upon which to base a diagnosis of _gouty -arthritis_. In my own practice I must affirm that I never feel justified -in christening any arthritis as _gouty_ unless I have discovered _tophi_, -and then only when to the best of my ability _all other known causes of -arthritis_ have been excluded. - - -FREQUENCY OF TOPHI IN TRUE GOUTY ARTHRITIS UNDERESTIMATED - -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 _lack tophi_ 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 _chronic_ gout. For who can doubt that -prior to the discovery of X-rays many cases of _osteoarthritis_, etc., -were thus erroneously labelled? Nor indeed, as we hope to show later, is -it improbable that similar fallacies obtained even in regard to _acute_ -types of gout, particularly when of _polyarticular_ distribution. - -It will be noted that we confine our criticisms to those examples of -“gouty” arthritis _unassociated with tophi_. But if, as we maintain, -our scepticism be justifiable, then it follows that it _diminishes_ to -an unknown extent the _percentage of cases of genuine “gouty” or uratic -arthritis which lack tophi_. - - -DIFFICULTY OF DETECTING TOPHI - -Apart from the probability of such erroneous relegation to the “gouty” -category of _non-gouty_ 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 _tophi_ are _absent_. 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. - -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.” - -Reflection upon the foregoing considerations leads me to the conclusion -that not only was Garrod right in his affirmation that “_gouty -inflammation is invariably attended with the deposition of urate of -soda_,” but more that _examples of true uratic arthritis which lack tophi -are exceptional_, and that _in their absence their diagnosis as such -cannot be with certitude established_. - -We have now, we trust, sufficiently defined our attitude towards the -tophus, the salient objective stigma of a “gouty diathesis,” and the -indispensable _rôle_ it plays in enabling us to establish the diagnosis -of articular gout. - - - - -CHAPTER XX - -CLINICAL DIAGNOSIS (_continued_) - - -ACUTE ARTICULAR GOUT—LOCALISED VARIETY - -The nonchalance with which not a few writers dismiss the diagnosis of -_acute gout_ when located in the _great toe_ 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 -_differential_ diagnosis, they are at pains to discriminate between it -and _acute articular rheumatism_, which _re_ classical outbreaks in the -_toe_ seems a little superfluous! But not a word of _traumatic_ lesions, -_infective_ processes and _static_ deformities, all infinitely more -likely stumbling-blocks. - -Did all cases conform to the classic type, _acute sthenic gout_, 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 _asthenic_ 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.” - -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 _facies_? Physicians of those days were haunted with the -fear of confounding it with _erysipelas_ and _phlegmon_. Still, while no -such fears apparently beset us to-day, it were well to walk circumspectly. - -Thus, recently a friend of mine came across an instance of what he deemed -_acute gout_ in a _metacarpo-phalangeal_ 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! - -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 _big -toe_ is the _site of predilection_ for the _initial_ manifestation, it -is not always so. The _primary_ outbreak may be located in any of the -smaller joints of the foot, or outside them in related structures: in -the _heel_, the _sole_, or the _tendo Achillis_. 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. - - -DIFFERENTIAL DIAGNOSIS - -Inasmuch as the primary outbreak may be located in any part of the foot, -we purpose, for reasons just cited, dealing _seriatim_ with gout in (1) -the big toe; (2) the instep; (3) the heel; (4) the sole. - - -GOUT IN THE BIG TOE - -_Infections._—There is no _â priori_ reason why any of the infections may -not find a nidus in the _first metatarso-phalangeal_ joint. Thus, Garrod, -as we know, held gouty subjects specially liable to _pyæmia_. In rare -instances, the primary focus has been in or near the _great toe_, and has -consequently been mistaken for _gout_. 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 _bladder_ troubles, -_piles_, etc., especially _any recent operation_ in this or other regions. - -Again, while gout in its _articular_ form is rarely, if ever, met with in -children, it must be recalled, on the authority of Sir James Goodhart, -that _rheumatism_ in their instance is occasionally limited to _one_ -joint. Moreover, this distinguished physician actually saw it localised -in the _great toe_, “in a case in which the subsequent course of the -disease showed that it was acute rheumatism.” - -_Acute Gonococcal Arthritis._—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! - -Of course in adolescents or in young adults _monarticular_ pain, with or -without swelling, heat, or redness, should not suggest “gout,” but an -_infective_ disorder either in the _joint_ or the related _bone-ends_. At -the same time middle-aged men enjoy no immunity from gonorrhœa, and we -may add that _gonococcal infection_ of the _metatarso-phalangeal_ 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 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. - -_Traumatic Lesions._—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. - -Again, joint disorder following _injury_ is usually _monarticular_, -whereas the same when the outcome of so-called “constitutional” causes is -generally _oligo_- or _poly_-articular. The relevancy of this is obvious -when we recall that _initial_ attacks of _gout_ are _monarticular_. -Accordingly, given a history of definite injury to the toe joint, the -question arises, Is it _acute gout_ or _acute traumatic arthritis_? this -especially if the subject has not had a previous attack of gout at this -site. - -Here I would lay stress on the fact that _indirect_ 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. - -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 -_septic absorption_ with _cellulitis_ and a mild degree of sapræmia, -evoking _arthralgic_ pains? - -In conclusion, without denying the potentialities of trauma, 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 _colchicum_ would of course be highly suggestive of -_gout_. - -_Acute Osteoarthritis._—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 _gout_. 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 _skiagraphy_ will suffice for differentiation of such -cases from _asthenic articular gout_. - - -STATIC FOOT DEFORMITIES - -_Hallux Valgus with Inflamed Bunion._—Scudamore in his “Treatise on Gout” -observes that “the bursal disease over the first joint of the great toe, -which is familiarly known as _bunion_, 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. - -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 _gout_.” 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 _medical attendant_. - -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 _gouty_ subject -may present this deformity. But when we recollect that _hallux valgus_ of -_slight degree_ “is almost universally present after middle childhood,” -we see that, given the presence of this static foot deformity, any -inflammatory process in the superjacent structures is infinitely -more likely to be due to an _inflammatory bursitis_ than to a _gouty -arthritis_. - -Given an inflamed bursa with cellulitis spreading over the dorsum of -the foot, confusion with _acute sthenic gout_ is all too easy. But in -our experience, _mirabile dictu_, 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 _toe_ and the frequency with which their footgear -is precisely adapted to produce _hallux valgus_. Given therefore the -presence of this static foot deformity, we should in the absence of -objective stigmata of gout, viz., _tophi_, suspend our diagnosis pending -observation of the results obtained by local treatment of the displaced -toe. - -_Hallux Rigidus._—This deformity is but too often overlooked, -and if marked by pain and more or less rigidity of the first -_metatarso-phalangeal_ 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. - -_Metatarsalgia._—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. - -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 -_callosities_ under the _heads_ of the _metatarsals_ is very suggestive -of this painful condition. - - -GOUT IN THE INSTEP - -Next to the metatarso-phalangeal joints, the _tarsal_ articulations are -the most frequent site of _initial_ attacks of gout. Here again we would -insist on the necessity of excluding _infections_ of the _tarsal joints_ -or _shafts_ and even more important, _static foot deformities_. - -_Gonococcal Arthritis._—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 _tarsus_ and _metatarsus_ were attacked in five -instances. In the more acute cases the periarticular swelling, local -heat, and pink blush may be confused with _acute gout_. The resemblance -is enhanced in that, as in gout, the overlying _tendon sheaths_ are -liable to become inflamed and distended with fluid. - -_Tuberculous and Syphilitic Disease of the Tarsal Joints or the Related -Joints._—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. - -_Pes Planus._—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 _abruptly_ on a _painful_ 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.[40] - -The frequency with which the _local_ and _referred_ pains of _flatfoot_ -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. - -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 -_hallux valgus_ with related _bursal thickenings_. 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 _gout_. In addition, as is so frequent in hallux valgus, -there was associated therewith a _bilateral flatfoot_, and it may be -added that in the left foot a _hammer-toe_ 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 _chronic villous synovitis_ 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, -_morbus dominorum_, 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.” - - -GOUT IN THE HEEL - -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.” - -_Referred Pain._—Pain in the heel affords many loopholes for -misinterpretation. It may, as Sir James Paget pointed out many years -ago, be symptomatic of a _renal calculus_. In my own experience it is -sometimes complained of by the subjects of _internal hæmorrhoids_, 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 symptom sometimes complained of by the victims of -_enlarged prostate_. - - -LOCAL SOURCES OF FALLACY - -If the pain and tenderness be located on the _under_-surface of the os -calcis, there are several misconceptions possible. - - (1) Careful examination may reveal a tendency to flatfoot, the - pain being referable to strain on the posterior insertion of - the plantar fascia. - - (2) The root of the trouble may be a gonococcal inflammation of - the plantar fascia, or of the periosteum covering the os calcis. - - (3) A skiagram may show the existence of a bony spur on the - inferior surface of the os calcis. - - (4) The bursa under the os calcis may be inflamed. - - (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. - -If the pain and tenderness be located on the _posterior_ surface of the -os calcis, or in the tendo Achillis, the following should be excluded -before assigning the trouble to “gout”:— - - (1) _Post-calcaneal Bursitis._—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.) - - (2) _Synovitis of the Tendo Achillis._—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. - - -GOUT IN THE SOLE - -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 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 -_plantar neuralgia_. - -_Plantar Neuralgia._—Occasionally, as we have pointed out elsewhere, -the pain is of almost unendurable severity. It constitutes one of the -types of so-called _partial sciatica_, 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 _ball of the great toe_, 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 _alcoholism_ -and _hysteria_. - -_Erythromelalgia._—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 _ball of the great toe_, -the heel, or outer or inner side of the foot, we see the danger of its -being too easily referred to “gout.” - -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. - -In drawing to a close our remarks on the diagnosis of _acute gout_ in -the _foot_, we would emphasise the fact that in all such cases the -bare feet should be thoroughly examined. For, apart from _infective_ -and _traumatic_ lesions, the frequency with which the various _static -foot deformities_ are confused with “gout” is incredibly common. That -_gout may co-exist with hallux valgus_ 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.e._, 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. - - -ANOMALOUS SITES FOR INITIAL OUTBREAKS - -While _primary_ attacks are in the vast majority of instances localised -to the _foot_, if not actually to the _toe_, it is well to recollect -that very rarely the _knee_, the _wrist_, _elbow_, or _ankle_ may be the -chosen spot. In such cases there is need for exceptional caution before -committing oneself to a diagnosis of _gout_. Certainly not until all -other known causes of _acute arthritis_ of _monarticular_ type have been -excluded. - -If in the _knee_ or _wrist_, any possibility of _injury_ or _strain_ -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.e._, gonococcal, etc. If there be no -history of such, a painstaking search should be made for any local foci -of infection, _e.g._, 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. - -If, notwithstanding a meticulously careful investigation, no cause can be -assigned, we may entertain the possibility of its being _gout_, the more -legitimately if the subject be a middle-aged man coming of gouty ancestry -and exhibiting himself tokens of this diathesis, _i.e._, _tophi_. 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. - -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.” - - - - -CHAPTER XXI - -CLINICAL DIAGNOSIS (_continued_) - - -ACUTE GOUTY POLYARTHRITIS - -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. - -Now, while in _initial_ outbreaks of gout it is exceptional for more than -_one_ joint to be affected, it is not always so. For sometimes in those -strongly predisposed by _heredity_ not one, but _many_ joints, may be -implicated in the _primary_ attack. Such cases, however, are extremely -rare. - -As a rule, this _acute gouty polyarthritis_ occurs in individuals who -have already experienced articular paroxysms at the classic site; but -in the subsequent polyarticular attacks the _toe_ 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. - -Confronted then with an _acute polyarthritis_ of obscure nature marked by -pain, redness, swelling, and pyrexia, what are the points necessary to -establish it as being of gouty origin? - -The sex and age should be noted, also the heritage, habits, and -occupation. A history of _previous attacks located in the big toe_ would -be of prime value. The presence of a cardiac _valvular_ lesion, while it -would suggest a previous attack of _acute rheumatism_, would in no wise -negative the possibility of the subject developing _gout_ 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 _acute polyarthritis_ is of _gouty_ than of rheumatic -origin. - -As to the character of the pyrexia, it is usually of _low_ grade; but -if the condition be _afebrile_, it is even more suggestive of a _gouty_ -arthritis. But recollect, too, that the pyrexia in _gonococcal_ arthritis -is also of low grade or absent. - -There is nothing distinctive of _gout_ 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 -_infective_ arthritis. - -As to _uric acid excretion_, Osler, who was deeply interested in this -type of arthritis, held that any _lowering_ of the ratio of the _uric -acid_ to the _urea excretion_ 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 _any variations in the uric acid output_ -ensuing _pari passu_ with their rise and wane. - -Last, but most important of all, a thorough search must be instituted -for _tophi_, not only in the ears, but elsewhere. If anything could -emphasise the indispensable _rôle_ played by _tophi_ in the diagnosis -of gout, it would be our utter inability to effect in their absence -a diagnosis of these _acute_ types of _gouty polyarthritis_. The -establishment of the existence _in situ_ of such _articular uratic -deposits_ 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 _ab-articular_ site, then we must withhold our decision pending the -exclusion of certain other joint disorders, to the differentiation of -which we now proceed. - - -DIFFERENTIAL DIAGNOSIS - -The class of disorders that call for discrimination are those of -infective origin. In the first place, _acute articular rheumatism_ -must be excluded; nor is it less necessary that we should eliminate -_gonorrhœal_ and _syphilitic_ types; while, last, but not least, that -vast group, the _undifferentiated infective arthritides_, is but too -often a source of confusion. - - -ACUTE ARTICULAR RHEUMATISM - -Unquestionably many cases of _acute gouty polyarthritis_ have been -confounded with _acute articular rheumatism_, and _vice versâ_. 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 gout was supposed to have been transferred from the extremities -to the heart as an example of the latter error.” - -It is only, of course, with that type of acute gouty polyarthritis -accompanied by _pyrexia_, and not the _afebrile_ variety, that confusion -with acute articular rheumatism is possible. What then are the points of -discrimination? - - ACUTE ARTICULAR RHEUMATISM. ACUTE GOUTY - POLYARTHRITIS. - - Age and sex Most common between ages Maturity and old - of fourteen and thirty. age. Males. - Predominance of males Females markedly - after twenty. exempt. - - Heredity Very disputable. Very pronounced. - - Onset Usually abrupt and often Insidious, with - with tonsillitis. premonitory - gastro-intestinal - symptoms. - - General symptoms High fever, sometimes Moderate pyrexia. - hyperpyrexia. Profuse Marked daily - acid sweats. remissions. - - Distribution of Preference for large joints Small joints, hand - lesions and markedly mobile. or foot often - involved. Fixity - typical. - - Local characters Joints exhibit slight reddish Scarlet hue and - flush. No subsequent œdema with later - desquamation. No residual peeling of cuticle - change. and itching. - Tendency to - involvement of - bursæ and tendons. - - Pain Chiefly evoked by movement. Spontaneous, more - intense. - - Duration Twenty to thirty days, Six weeks to three - sometimes longer. months. - - Associated Cardiac lesions common. Tophi. Occasionally - phenomena glycosuria and - albuminuria. - - Therapeutic test Salicylates a specific. Not so in gout, but - colchicum takes - this _rôle_. - - -ACUTE GONOCOCCAL ARTHRITIS - -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 _afebrile_ variety of acute _gouty_ -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, and while _pyrexia_ may be present, and -often is, in gout, its absence is, I think, a valuable diagnostic sign.” - -This is of course true, but it still remains necessary, for reasons -above cited, to eliminate _acute gonorrhœal arthritis_. 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 _conjunctivitis_ or _iritis_ as further evidence of -the articular affection being “gouty.” It is far more likely to be -_gonococcal_. 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. - -To sum up, the following are distinctive characters of _generalised_ -gonorrhœal arthritis:— - -_Etiology._—History or presence of urethral discharge and isolation of -the gonococcus. - -_Onset._—Insidious, seldom acute. - -_General Symptoms._—Absent or slight relatively to extent and severity of -joint mischief. Pyrexia, low grade or absent. - -_Distribution of Lesions._—Preference for large joints. Special liability -of sacro-iliac, chondro-costal synchondroses, sterno-clavicular, -tibio-fibular, and temporo-maxillary joints. - -_Local Characters._—Persistent passive effusion or peri-articular boggy -swelling, with redness and local heat. No tendency to migrancy. Joint -swelling very persistent. - -_Associated Phenomena._—Involvement of fasciæ, especially plantar, -and of tendon sheaths, very distinctive, while coincident iritis or -conjunctivitis is almost diagnostic. - - -SECONDARY SYPHILITIC ARTHRITIS - -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 _intermittent -fever_ of _secondary syphilis_ is usually present. The detection of -periosteal nodes in addition to the joint swellings should arouse -suspicion, while the presence of _secondary syphilides_ and the rapid -response to _specific_ treatment will be confirmatory. - -I well recollect some years ago a young farmer being sent to me by a -medical man as suffering from _gouty arthritis with gouty eczema_. The -eruption was a typical _roseola_, and the condition promptly cleared up -under _anti-syphilitic_ treatment. - - -ACUTE RHEUMATOID OR ATROPHIC ARTHRITIS - -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 _facies_ 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. - -_Age and Sex._—Most common in young women. - -_Onset._—More or less acute. - -_General Symptoms._—Continuous low grade pyrexia, quick pulse, and rapid -emaciation, and commonly concomitant gastro-intestinal derangements. - -_Distribution of Lesions._—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. - -_Local Characters._—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. - -_Associated Phenomena._—Trophic and vasomotor changes prominent, but _no -tendency to cardiac lesions_. - - -INFECTIVE ARTHRITIS OF UNDIFFERENTIATED TYPE - -It were well in approaching any acute polyarthritis of obscure -nature to bear in mind the axiom that _any or all infections may be -complicated by arthropathies_, 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 _specific_ forms of infective arthritis, as -far as seems necessary, have been dealt with, but those rarer forms -not referred to, viz., _influenzal_, _pneumococcal_, _dysenteric_, -_meningococcal_, etc., have also to be borne in mind, if the history -reveal any recent occurrence of these disorders. - -Still far more common than any of these are the _acute infective -arthritides_ of _undifferentiated_ type. As we before remarked, an -extraordinary general clinical resemblance obtains between these types of -joint disorder and _acute gouty polyarthritis_. Indeed, _in the absence -of tophi_, their differentiation is well-nigh impossible. Even the blood -picture in both types of the disorder is strikingly similar in the matter -of _leucocytosis_ and _secondary anæmia_. - -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 _acute gouty polyarthritis_ -(as evidenced by external tophi or deposits in bone or cartilage with -variations in uric acid output) and also an equally definite _infective -arthritis_, yet between those two there is a very considerable number of -cases that present some of the factors suggestive of _gout_ and other -factors suggestive of an _infectious arthritis_, and there is where the -difficulty comes.” - -This is precisely the state of affairs, and one may well ask where _gout_ -ends and _infection_ begins. Let us take an example. A man exhibiting -_tophi_, the subject also of _pyorrhœa alveolaris_, develops an _acute -polyarthritis_. What then is the nature of the joint disorder? There is -a gouty element in his case, as attested by _tophi_, also an infective -element, as evidenced by _oral sepsis_. - -Now are we to regard such a case as one of _infective arthritis_ of -_undifferentiated_ type occurring in a _gouty_ subject, or are we to -proceed on the assumption that the presence of _tophi_ negatives the -possibility of infection and forthwith to class it as a case of _acute -gouty polyarthritis_ of so-called _metabolic_ origin? - -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 _gouty_ -or in that of _infective_ 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 _non-gouty_ subjects. - -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 _peri-articular_ tissues are -the seat of demonstrable _uratic deposits_, while the X-ray changes -within the joint proper, the bone and cartilage, are typically those met -with in _infective_ arthritis? - -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 _acute gouty polyarthritis_ is -itself but a form of _infective arthritis_ which derives its _specific_ -character from the associated _uratic deposits_. - -As to differentiation of the latter from these cryptic infective -arthritides, this will rest mainly on— - -(1) The presence of tophi; - -(2) A history of previous attacks in the great toe; - -(3) A swift response to colchicum. - -In addition, acute gouty polyarthritis is confined to _middle-aged -males_, while no period of life is immune from infective arthritis, and -both sexes are equally liable. - -Again, acute gouty polyarthritis may be _afebrile_. 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. - -Lastly, the _uric acid output_ 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. - -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. - -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. - -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 _non-gouty_ as -opposed to a gouty subject. - - - - -CHAPTER XXII - -CLINICAL DIAGNOSIS (_continued_) - - -CHRONIC ARTICULAR GOUT - -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, _apart from uratic deposits_, the -anatomical lesions that ensue in joints the seat of long-continued gout -have no _specific_ 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 _destitute of uratic deposits_. - -In our chapter on _classification_ we emphasised the desirability of -restricting the usage of the term chronic articular gout to that type -long since known as _tophaceous_ 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.[41] - -As to _osteoarthritis_, I do not for a moment deny that _uratic -deposits_ 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. - -But such to our mind are to be regarded as merely instances of -_osteoarthritis_ 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. - -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.” - -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. - -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. - - -CHRONIC MONARTICULAR GOUT - -Occasionally gout in its recurrences clings obstinately to the great -_toe_ and _tarsal_ joints. But since the advent of _radiography_ -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., -_osteoarthritis_. 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.e._, _static deformities_, 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 _larger_, -articulations. - - -MONARTICULAR GOUT IN LARGE ARTICULATION A RARITY - -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. - -Thus, if it be the knee, it may be a referred pain due to hip disorder, -_e.g._, _osteoarthritis_ or _tuberculous_ 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 _neoplasm_ in the -bones. - -On the other hand, suppose the subject come complaining not much of pain -in his joint, but more troubled because of its _enlargements_. If now -on examination we find also that there is little or no tenderness, but -simply a condition of _peri-articular thickening_ or _intra-articular -effusion_, 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 -_tophi_ in his ears. - -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 _syphilitic_ -arthritis, both secondary and tertiary, is relatively _painless_. But it -is the much rarer _tertiary_ form, be it remembered, which is usually -_monarticular_. By the bye, too, we should never forget that a _Charcot’s -joint_ is also painless. - -Coming now to the _objective_ phenomena, is the case predominantly one -of peri-articular infiltration or intra-articular effusion? As to the -former, while you never know, still _tuberculous_ joint disease is -exceptionally rare at the age at which we usually meet gout. On the -other hand, _gummatous synovitis_, 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. - -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 _monarticular_ disorder _injury_ -is far and away the most frequent. Not a few cases of monarticular -joint disease come annually to the Royal 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 -_hydrarthrosis_ 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 _gonorrhœa_ or _syphilis_ than to either of them. - -But the reader may say, this dissertation notwithstanding, Where does -_gout_ come in? Precisely so, and if his experience tallies with mine, he -will find that chronic articular gout localised in _one_ of the _larger_ -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 _uratic deposits in situ_ in the peri-articular -tissues, the cartilage or bones as revealed by _skiagraphy_, or in the -related bursæ. - -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 _osteoarthritis_; and in the -vast majority, I had almost said all, it is the latter morbid process -that will be found responsible. - -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. - - -CHRONIC GOUT OF OLIGO-ARTICULAR DISTRIBUTION - -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 _asthenic_ and -_afebrile_ types of gout in which two or more joints may be the seat of a -chronic gouty arthritis. In my experience it is the _knees_ 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 _uratic deposits_. -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 _osteoarthritis_. The related _bursæ_, too, are often -the seat of _deposits_, 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. - - -ITS CONFUSION WITH CHRONIC VILLOUS SYNOVITIS - -The frequency with which this misconception occurs is very noticeable. If -a _middle-aged_ woman of florid complexion and _corpulent_ 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 _gout_, 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 _par excellence_ at which -women develop the morbid vagaries associated with “irregular gout.” - -Now, as Bassett Jones and I have pointed out in a previous work, this -condition, _symmetrical villous synovitis_ of the _knees_, is a very -common joint disorder in _women_ at or near the _menopause_. Frequently -they give a history of numerous _pregnancies_, or of _rapidly increasing -obesity_, while with or without this latter they display a _faulty -postural attitude_, indicative of lowered muscular and ligamentary tone. -Following in the wake of these, the subject develops a _symmetrical -flatfoot_, which, according to the stage at which it is seen, may be of -flexible or rigid type. - -Now, such is the mutual _static interdependence_ of the component parts -of the lower limb that this condition of flatfoot promotes or favours -the incidence of _villous overgrowths_ in the proximal joints, the -_knees_. As to the _modus operandi_ 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 _varicose veins_ or suffers from a _general -lack of tone in her muscular or ligamentary structures_, this tendency to -venous engorgement of the knees is much enhanced.” - -“Under the influence of these mechanical factors and their associated -circulatory disturbances, _thickening and enlargement of the synovial -fringes ensue_. 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 _pari passu_.” - - -VILLOUS SYNOVITIS STATIC AND NON-GOUTY IN ORIGIN - -In short, the joint disorder is fundamentally of _static or mechanical_ -origin, and, this being so, the results of _anti-gouty_ treatment are -open to a further misinterpretation. The victims, as we have said, -exhibit very generally a tendency to _obesity_. Now, Ebstein and many -others hold the view that _obesity and gout have affinities_. 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, _pari -passu_ 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 _gouty_ origin attribute, and, we think, wrongly, the -beneficial results attained to correction of the underlying “gouty” habit. - -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. - - -CLINICAL SYMPTOMS OF VILLOUS SYNOVITIS - -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. - -Objectively the joint shows either general enlargement or swelling -localised to the _supra_- or _infra-patellar_ regions. Intra-articular -effusion which comes and goes is a very characteristic feature. On -palpation a peculiar soft silken crepitus will be heard 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. - -The diagnosis of villous synovitis should not be considered complete -without _skiagraphy_ being undertaken to reveal or exclude osteophytic -outgrowths. For the subjective symptoms and signs of _early_ -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 _primary_ or _pre-osteophytic_ phase, often of prolonged duration, -whose clinical characteristics are those of villous hypertrophy; (2) -a _secondary_ or _terminal_ stage, in which bony and cartilaginous -outgrowths make their appearance. - -Other symmetrical disorders of the knees that may be wrongly ascribed to -gout are hydrarthrosis and gummatous synovitis. - -_Bilateral Hydrarthrosis._—Given effusion into both knees which is -_passive_, _copious_, and _persistent_ rather than recurrent, then its -possible _infective_ origin must be carefully canvassed. The common -sources are _gonorrhœa_, _syphilis_, and _tubercle_. 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. - -As to the _intermittent_ type of hydrarthrosis, the remarkable -_periodicity_ in incidence of the effusion will suffice to obviate any -possibility of confusion. - -_Peri-synovial and Peri-bursal Gummata._—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. - - -CHRONIC GOUT OF POLYARTICULAR DISTRIBUTION - -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. - -In these polyarticular forms the most distinctive joint deformities are -those met with in the _hands_ or feet, more particularly the former. The -excrescences produced are the outcome of successive _uratic deposits_. -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. - -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 _biurate_ crystals. - -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:— - - (1) Tophi when of recent incidence are _soft_, and when of long - standing are never so dense or so hard as bony outgrowths. - - (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. - - (3) Uratic deposits are _not located exactly at the level of - the articulation_. They do not adapt themselves to the contour - or shape of the bone-ends. - - (4) Unlike osseous growths, they may be slightly movable in - lateral directions. - - (5) Tophi may _soften_ or _disappear_ after exacerbations of - arthritis. - - -DIFFERENTIAL DIAGNOSIS - -The conditions likely to be confused with chronic polyarticular gout are -osteoarthritis, rheumatoid arthritis, and the multiple arthropathies met -with in affections of the central nervous system. - - -OSTEOARTHRITIS - -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 _hip_, the _shoulder_, and -the _spine_—sites rarely, if ever, attacked by gout. - -Unlike gout, constitutional symptoms, pyrexia and so forth, are generally -absent; muscular atrophy is slight, hardly ever pronounced, likewise -muscular spasm and contracture. - - -LOCAL CHARACTERS OF JOINT SWELLINGS - -These are best appreciated in the small joints of the hand. -Osteoarthritis has an affinity for _terminal_ 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. - -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.[42] - -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. - - -RHEUMATOID ARTHRITIS - -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. - -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. - - -LOCAL CHARACTERS OF JOINT SWELLINGS - -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. - - -NERVE ARTHROPATHIES - -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. - -These remarkable joint affections will be distinguished by their -fulminant onset with marked effusion and absence of _pain_, 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. - - -HÆMOPHILIC ARTHRITIS - -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. - -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. _Quâ_ 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 -_personal and family tendency_ to hæmorrhages is the most important clue. - - - - -CHAPTER XXIII - -CLINICAL DIAGNOSIS (_continued_) - - -SKIAGRAPHY - -As an aid to the differentiation of _gouty_ from _non-gouty_ forms of -_arthritis_ skiagraphy has scarcely fulfilled the somewhat optimistic -claims at one time made on its behalf. As to _acute_ gout, radiography -reveals nothing abnormal in the bones, though Tousey holds that this of -itself at once enables us to exclude _osteomyelitis_, which, he says, -“these cases sometimes resemble.” - -Turning now to _chronic articular gout_, Huber in 1896 drew attention -to certain _focal areas of rarefaction_, 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. - -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 _uratic deposits_ 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. - -Similar focal areas of decreased density were noted by Strangeways in -certain cases of _rheumatoid arthritis_, and both he and Burt found it -impossible on the X-ray findings to differentiate between these and gout, -_i.e._, without invoking the aid of clinical data. - -[Illustration: Radiographs of the Foot and Hand, showing extensive bony -and other changes in long-standing Gout.] - -Apart from these transparent areas, Wynne many years ago pointed out that -small _nodes_ or _bony deposits_ are sometimes met with flanking the -sides of the phalanges. More recently Ironside Bruce by _radiography_ -has again drawn attention to these bony outgrowths near the extremities -of the phalanges (Bruce’s nodes). At first these were thought by Bruce -to be composed of _urates_, but Strangeways from a study of macerated -specimens has demonstrated their true _bony_ nature, and also that -_uratic deposits are not opaque to X-rays_, as was formerly thought. - -In skiagrams of chronic gout all stages of _ankylosis_ 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. - -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 _focal areas -of rarefaction_ 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 _gouty_ -arthritis. - -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 _tophi_ 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. - -In accordance with their contention, McClure and McCarty record their -radiographic findings in a series of cases all of which exhibited -_tophi_, and from which sodium urate crystals were isolated. Now, in all -these cases the _focal areas of diminished density_, 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.” - -In addition, they examined the skiagrams of 100 cases of _chronic -arthritis_ which “had not been diagnosed clinically as _gout_.” 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.” - -Judging from the skiagraphic appearances, there seemed no reason to -suppose that the factors responsible for the production 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 -_uratic deposits_ in the bones; but it is at least possible that their -origin may be otherwise explained. - -Thus Nichols and Richardson have shown that, given _focal absorption of -lime salts_, changes apparently identical with those currently attributed -to the presence of _tophi_ may result. These same, though they may not be -demonstrable either macroscopically or microscopically, are detectable by -X-rays. - -Such foci of absorption, viz., areas of decreased density, frequently are -located in regions subjected to _pressure_. 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. - -Now, Strangeways has shown that it is impossible by radiography to detect -_tophi in bones_. Accordingly we have at present no means of deciding in -any given case whether the localised _transparent areas_ in the bones -are due to _tophi_ or to _focal absorption_ of lime salts. If we are to -cling to the conception that they are due to _tophi_, then it is clear -that _tophi in the bones_ are more common than is currently suspected, -and that, _ergo_, 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.” - -Yet these authorities hold that, despite the fact that they occur in -cases of _non-gouty_ 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:— - - (1) The focal areas of decreased density, heretofore considered - as peculiar to gout, are rarely absent in that disease. - - (2) Their absence would be some evidence against the existence - of gout in a given case. - - (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. - - (4) The focal areas of decreased density, usually held due to - tophi, are probably very often merely focal areas of absorption - of lime salts. - -In continuation these authorities have endeavoured to identify the nature -of the _arthritis_ that occurs in _gout_. 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 joints of the hands -and feet in gouty subjects. These, they consider, may be classified -conveniently as follows:— - - (1) Cases marked by _focal areas of rarefaction_, without any - other perceptible change; - - (2) Cases presenting, in addition to these translucent areas, - minor degrees of lipping at the articular margins; - - (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; - - (4) In addition to all the above changes, narrowing of certain - joint spaces with marked proliferative and atrophic changes - occurs. - -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 _tophi_. Moreover, it will be seen that the radiographic -changes in some are reminiscent of _atrophic_ or rheumatoid arthritis, -in others of _hypertrophic_ arthritis or osteoarthritis, while, -lastly, the appearances typical of _infective_ arthritis are also -represented. In addition, if we recall that _focal areas of rarefaction_, -indistinguishable from those met with in _gout_, also occur in all types -of _non-gouty_ arthritis, we at once see how impossible it is to detect -anything in the _radiographic_ findings distinctive of _gouty_ as opposed -to _non-gouty_ arthritides. - -McClure and McCarty, comparing the radiographic changes in gouty as -opposed to _non-gouty_ arthritis, observe that, though _rarefactive foci_ -occur in all varieties of _non-gouty_ arthritis, they are conjoined with -_other bony or joint changes_. On the other hand, _translucent_ areas -_unassociated with any bone or joint alterations_ have been found only -in _gout_. But whether this can be claimed as distinctive of _gouty -arthritis_ is, they think, uncertain, since relatively few opportunities -for X-ray examination of _non-gouty_ arthritis in its _early_ stages have -been forthcoming. - -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 _infective_ type of _non-gouty_ 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 nothing in the bony or arthritic changes that is _diagnostic_ of gout. - -For myself, I must admit that I have come to the same conclusion as -McClure and McCarty, viz., that the skiagraphic findings in _gouty_ and -_non-gouty_ 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 _skiagraphy_. The chief interest to my mind, -as I have previously observed, centres round those examples in which -_peri-articular tophi_ are associated with underlying bony and arthritic -changes (as revealed by X-rays) indistinguishable from those typical of -_infective_ arthritis of _non-gouty_ type. - -We have seen also that _local foci of rarefaction_ may be met with in -_infective_ arthritis of _non-gouty_ type. Moreover, the _proliferative_ -and marked _atrophic_ bony changes found in some instances of gouty -arthritis are quite compatible with their _infective_ origin. Witness -how impossible it is to differentiate skiagraphically between _atrophic_ -arthritis and _gouty_ arthritis, and at the same time let it not be -forgotten, on the other hand, that the dividing line between the -_infective_ arthritides and the more acute forms of _atrophic_ or -rheumatoid arthritis is by no means sharply defined. Review this also in -light of the fact of the close resemblance that obtains between _acute -articular gout_, especially the polyarthritic variety, and types of -arthritis of avowedly _infective_ origin, and we see at once how close -is the clinical similitude. We turn to _radiography_, 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 _tophi_, -and tophi alone, that we must base an absolute diagnosis of _gouty_ -arthritis. Moreover, since tophi are not detectable by _skiagraphy_, 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 _bacteriological_, data, which, it -is to be hoped, will before long be forthcoming. - - -DIFFERENTIAL DIAGNOSIS - -_Infective Arthritis._—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, 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. - -The new formation of bone in these destructive forms of arthritis -conforms in every way to that seen as a result of _septic osteitis_ or -periostitis. In other words, the osteophytic outgrowths take origin at -the _focus of infection_, wherever that may be, and not, as in _gout_ -and _osteoarthritis_, at the _margin of the cartilage_. Still one must -recollect that in gout _exostoses_ (Bruce’s nodes) develop sometimes at -the _sides_ of the phalanges. These outgrowths are not peculiar to gout, -but may be met with in _infective_ 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 _infective_ element in the genesis of _gouty arthritis_. - -_Hypertrophic or Osteo-arthritis._—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 _chronic gout_, 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 _tophi_. - -_Rheumatoid or Atrophic Arthritis._—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. - -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. - -Now, owing to the fact that in _gout_ also considerable disintegration of -the bone may result, the appearances in some instances may resemble those -found in the skiagraphs of _rheumatoid_ 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 _atrophic_ or -_rheumatoid_ arthritis the bone, though thin, maintains its outline, on -the other hand in _gout_ 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 _articular ends_ of the bone in -both instances are the seat of the disease. In other examples, however, -the _shafts_ of the bones being affected by the gouty disorder, they -may show punched-out areas. These latter, however, are but _focal areas -of rarefaction_ 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. - -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. - -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 -_tophi_. - - - - -CHAPTER XXIV - -IRREGULAR GOUT - - -“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. - -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. - -As for the unlicensed freedom too often exercised in relegating disorders -to this category, Rush would appear to have out-heroded Herod, _pace_ -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.” - -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 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.”[43] - -Truly, in light of this heavy indictment, one scarcely wonders that Rush -classed the domain of gout as limitless. But one must recollect that, -_nosologically_ 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? - -But _pari passu_ with advancing knowledge of the pathology of the -_nervous_ system and the rise of _hysteria_ to the status of a clinical -entity gout was shorn of the excrescences heaped on it by Laycock, Wells, -and others. - -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.” - -According to this authority, the deposit of _lithates in the urine_ is -a “manifestation of a morbid condition of the blood and of the entire -system,” the outcome of a _functional derangement of the liver_. Such -hepatic disturbance might endure for years without manifesting any other -symptom than a frequent _deposition of urates_ and occasionally _uric -acid in the urine_. But, added Murchison, the same if neglected “may -ultimately be the means of developing gout.” - -Clinically it manifested itself by a variety of symptoms—depression 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 _lithæmia_. -But his disciples, more ardent, set no limit to the manifestations of -_uric-acidæmia_. - -Not only gout, but _rheumatism_ 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 _lithæmia_. But -leaving aside the extravagant claims of Haig and his followers, the -impression even now is but too prevalent that _gout_ and _lithæmia_ 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 _uric acid_ is the _cause_ of gout. - -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 _functional disorder of the liver_ is the _fons et origo -mali_, much less that _uric acid_ 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.” - -Surely, if we are to make any pretence of reducing the phenomena of -_lithæmia or irregular gout_ to a scientific precision worthy of the -present status of medicine, we should fight shy of such sweeping -assertions. The _caveat_, 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.” - -Caustic as was this stricture, it was no less prophetic than apposite. -For recent _blood analyses_ have, as Pratt states, demonstrated that -there is _no increase of uric acid in the blood_ 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 -in invoking “gout.” For, as noted, all modern observations fail to -demonstrate the presence of _uricæmia_. 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 _toxic condition of the blood plasma_? 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 _lithæmia_, even -when undemonstrated, is held to be self-explanatory and final. - -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.” - -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. - -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. - -Having dealt with the broader and more extravagant claims made on behalf -of the clinical content of _irregular gout_, we now restrict our purview -to those disorders, chiefly _visceral_ 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. - - -RETROCEDENT GOUT - -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 -_inhibition_ of the _acute joint affection_ is followed by or coincides -with the development of serious _internal_ symptoms referable either to -the gastro-intestinal, cardio-vascular, or nervous system. Thus, there -may be, _e.g._, vomiting, diarrhœa, dyspnœa, cardiac arrhythmia, cerebral -hæmorrhage, delirium or coma. - -Naturally for our forefathers the abrupt subsidence of the joint disorder -with the incidence, as fulminant, of severe and alarming _visceral_ -symptoms appeared to be an example of true _metastasis_. 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. - -The retrocession of the articular affection in _acute_ examples of gout -ensues _abruptly_, 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 _cardiac_ pain has ensued -with syncopal attacks, sometimes fatal, while in others _gastro-enteric_ -symptoms of like gravity have developed. - -It is the _asthenic_ types of gout that, according to Duckworth, are most -prone to _metastasis_. 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 _acute sthenic gout_, -though in their instance less likely to occur spontaneously than in -sequence to depressing external agents, _e.g._, cold lotions, etc. - -Reviewing the recorded examples of _retrocedent gout_ 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 “_retrocedent gout_” 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 _visceral_ 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 _gouty metastasis_. - -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 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 _pork_ in the stomach. A caustic stricture, but -doubtless well merited. For the symptoms held typical of “gout in the -stomach” are but those of _gastric irritation_, with nothing to suggest -that they are of “gouty” origin. - -Again, as Brinton in his classic exposure of this clinical myth observes, -some of the recorded instances doubtless derive their melodramatic -aspects from unrecognised _biliary colic_. As he rightly says, some -of the cases instanced by Scudamore were jaundiced _usque ad unguem_. -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 _gallstones_, all wholly unguessed at in -those days? What, too, of the unrecognised and doubtless frequently -coincident _renal_ disease, with its menace of _uræmia_—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.e._, -_tabes dorsalis_? - -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 _anatomical_ -proof _post mortem_ 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.” - -Reverting to the _cardiac_ and _cerebral_ phenomena that have sometimes -followed the _retrocession_ of acute gout, the same difficulties confront -us. The conclusion that they are examples of _retrocedent gout_ is drawn -from premises which really do not support it. Strictly speaking, there is -nought but the _time relation_ to go upon, and the laconic comment “Non -sequitur” is obvious. - -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 _grounds_ have we for -assuming that the anginal, the syncopal attack, or the apoplexy is the -_consequence_ of gout, that it is exclusively due to the _materies morbi_ -of gout? - -The very disparity between the local lesions seems to exclude the -possibility of their being due to one and the same cause: in the joint, -acute _inflammation_; in the heart and brain, _degenerative_ changes. -Where then the nexus? Surely it is but a _time relation_, a coincidence, -the outcome of, _concurrent_ though _unrelated cardiac_ and _vascular_ -lesions. In short, the cases of so-called retrocedent “cardiac” -and “cerebral” gout usually resolve themselves into _cardio-mural -degeneration_, _arterio-sclerosis_, or _renal disease_. - - -OTHER IRREGULAR MANIFESTATIONS - -The more dramatic examples of retrocedent gout, as before stated, occur -mainly in the _acute_ 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. - -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 _inhibition_, while the latter term -signifies _deflection_ of the _materia peccans_ 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 _abruptly checked_, the same might _reflexly_ -precipitate the occurrence of internal lesions in structures undermined -by insidious and _pre-existing degenerative_ changes. In other words, -the aborted attack is not the cause, but the _occasion_, of the cardiac -failure, the apoplectic stroke, the uræmia, etc. - -On the other hand, given that such were due to actual _transference_ -of the gouty poison, one would expect that it would induce the same -_inflammatory_ phenomena in the viscera as in the joint. But there is no -_anatomical_ proof that such occurs, no evidence of an actual invasion of -the impeached viscus by the _gouty inflammation_. _Uratic deposits_ have, -it is true, been found _post mortem_ at the site of visceral lesions, -but, be it noted, generally in _degenerating_ tissue altered by other -morbid processes. Some, however, affirm that in such the gouty process -has _quâ_ the uratic deposits left, so to speak, its attestation behind -it. - -But any _degenerative_ focus may in a _gouty_ subject become the seat of -such a _deposition_. Yet it would be presumptuous to infer its gouty -origin from this fact alone. Such are common in _chronic nephritis_, 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? - -Were such uratic deposits located at the site of _inflammatory_ 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 _sequel_ -or concomitant of _acute gouty inflammation_. But it is not so. - -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 _scleroses_ so commonly met with in -_gout_, if due thereto, must owe their origin to some more vital agent -than _uric acid_, a few milligrammes more or less in the blood content -thereof. - -It will be seen then that the _anatomical_ evidence that gout can affect -the _internal_ 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 _visceral_ gout are wholly _clinical_. - -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 _presumptive_ and _retrospective_. - -The evidence that a relationship exists between _irregular_ and -_regular_ manifestations of gout rests upon the following sequences and -alternations of clinical events:— - - (1) The subsidence or disappearance of functional visceral - derangements following the development of articular gout; - - (2) Their occurrence directly after an articular paroxysm has - been apparently suppressed; - - (3) Their recurrence and alternation with arthritic outbreaks, - this in some instances repeatedly; - - (4) Lack of any appreciable cause for the functional - derangements and their indefinite anomalous character; - - (5) Their favourable response to specific gouty therapy. - -As before noted, _digestive_ troubles frequently precede the initial -outbreak of articular gout. The same likewise are frequent in chronic -cases between the intervals of arthritic seizures. - -Now it has been customary to regard the _alimentary_ or other -disturbances that precede an initial _articular_ attack as “gouty,” -and likewise those that intervene between the gouty paroxysms in -long-standing cases. In other words, in light of the subsequent -_articular_ 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 _sequence_ of clinical events, because the symptoms have -disappeared from, _e.g._, the stomach to reveal themselves in the joint -or joints, or _vice versâ_. - -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, _not_ gout. They should rather be regarded -as the _cause_, 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 _non-gouty_. They are very common _antecedents_ of, -_e.g._, _rheumatoid or atrophic arthritis_. Nevertheless we do not when -the _arthritic_ disorder _subsequently_ 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 _rheumatoid arthritis_. - -Now in the case of the latter we regard the _prodromal_ digestive -phenomena as probably indicative of some _infection_ located somewhere -in the _alimentary tract_. 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 _recurring infection_, followed as they -so uniformly are by _exacerbations_ of the _joint_ trouble. Is it not -time we adopted the same attitude towards the _gastric_ or _hepatic -functional_ disorders that punctuate the course of _chronic gout_ with a -periodicity that rivals that of the articular paroxysms? - -Unquestionably to my mind when we have regard to the extreme frequency -with which _local foci of infection_, _e.g._, oral sepsis, etc., are -found in gouty subjects, this would be the more rational attitude, the -one more in conformity with modern medical thought. - -But if we would condemn those who, in the presence of unequivocal tokens -of gout, label _antecedent_ or _intercurrent dyspepsias_, etc., as -“gouty,” what are we to say of those that even in patients who have never -had _regular gout_ or exhibited _tophi_ 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 _chronically inflamed appendix_. If so in this case, -how many so-called “gouty” acidities have resolved themselves into -_appendicular or gall-bladder dyspepsia_! - -My conclusion then is that the _gastro-intestinal_ disorders attributed -to gout cannot legitimately be regarded as examples of _irregular gout_. -They should not be held “symptomatic” of, but _etiologically_ related to, -_gout_, a view more calculated to lead to exact diagnosis and rational -therapy, and incidentally to elucidate the true nature of gout. - -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 -_antecedent_, _co-existing_, or _consecutive_ affections in certain -examples of gout, are not associated merely by _coincidence_. - -Disturbed _cardiac_ action is not uncommon in gouty subjects, -_palpitation_ and _arrhythmia_ and _syncopal_ threatenings, and -frequently symptoms difficult of differentiation from true _angina -pectoris_. - -I am reminded of an old physician whom I saw in consultation some years -ago, who suffered from alarming attacks of _precordial_ anxiety. He -was well on in the sixties, and very obese. He was convinced that his -cardiac irregularities, etc., were of _gouty_ 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 _urine_ for long since contained _excess of urates_. Having suffered -much of many physicians, he at last grew restive, took the bit between -his teeth, rushed to a 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 _mirabile dictu_, all his cardiac troubles -straightway ceased. - -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 _valvular_ lesion, though _mural -degeneration_ seemed likely. My own diagnosis was _flatulent dyspepsia -with secondary cardiac disturbance_, and finally _acute gout_, the -exciting cause of which, as I have so frequently seen, was a course of -_hydrotherapy_. The patient never regretted his venture, and, I am glad -to say, lived for some years. - -Such cardiac paroxysms are not uncommon in the “gouty,” and, alarming -though they are, I question if purely _functional_ disturbances of -this nature ever prove fatal. As to the _valvular lesions_ and _mural -degenerations_ observed in the “gouty,” there is little or no evidence -that they are dependent on gout. Indeed, the lack of a tendency to -_endocarditis_ is one of the criteria distinguishing gout from acute -rheumatism. I note that in one textbook _pericarditis_ is classed -among the cardiac manifestations of irregular gout. But it must not -be forgotten that _renal_ disease, a frequent concomitant of gout, -predisposes to _pericarditis_, which, indeed, occurs in granular kidney -even when unassociated with gout. - -As to the _respiratory organs_, such chronic maladies as _bronchitis_ -and _asthma_ 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 _asthmatic_ and _arthritic_ manifestations -may _alternate_. But we must recollect that _asthma per se_ has a -_paroxysmal_ tendency; it has a tendency to _periodicity_ 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” _pneumonia_, 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 _treatment_ of all associated affections. - -Of the _nervous_ 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 _alcoholism_, and likewise the _spinal paralyses_; while the -_convulsions_ and _comas_ were certainly almost always attributable to -_uræmia_. It would be held rash to-day to speak, like our forefathers, of -“gouty” _cystitis_, _urethritis_, or _orchitis_, for there is no evidence -of any pathological connection between them; and the same stricture is -also applicable to the many _cutaneous_ affections affiliated without -sound pretext to the _materies morbi_ of gout. - -In the early part of the nineteenth century the French school were most -insistent on the prevalence and variety of the cutaneous manifestations -of _l’arthritisme_; 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. - -_Conclusions._—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. - -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, _visceral_, _cutaneous_, 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,— - - “Quamvis enim cedere auctoritati debeam, rectius - tamen arbitror, in tanta re, ratione quam auctoritate - superari.”—_Lib. i., Ep. 20._ - -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 _uric acid_. 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 _infection_, the reader may rightly ask -whether the same agent may not be capable of evoking the _visceral_ or -_cutaneous_, as opposed to the arthritic, manifestations of gout. - -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 _irregular_ 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.” - -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” _arthritis_ 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, _e.g._, 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.” - - -INFANTILE GOUT - -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 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.” - -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! - -Comby also claims that these gouty children are especially liable to -recurrent or _cyclical vomiting_. 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 _uric acid crystals_ or a copious -deposit of _urates_ have been noted in their urine. - -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. - -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, _outside_ the body, whereas in _gout_ -the pathological error originates _within_ the organism. More apposite is -Uffenheimer’s observation, previously noted, that children of this type -suffer the same disturbances of _purin_ metabolism as are met with in -adult gouty subjects. - -If the fact is confirmed that the _output of exogenous purin_ in such -children is _diminished_ or _retarded_, 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 _regular_ gout such is _not -invariable_, 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:— - - “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.” - - - - -CHAPTER XXV - -OCULAR DISEASE IN THE GOUTY - -BY W. M. BEAUMONT - - -With the passing of Jonathan Hutchinson disappeared the premier British -exponent of _l’arthritisme_, that generic term so attractive to our -French _confrères_. 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. - -In referring to modern text-books we find Parsons[44] 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.” - -Werner[45] includes gout in a list of disorders of metabolism which -produce iritis “by means of toxins of a chemical nature.” - -Sim[46] 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.” - -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.” - -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. - -_Evidence of Gout in the Eye._—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. - -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:— - - (i.) That it sometimes happens that an undoubted attack of - articular gout aborts and is followed by symptoms referable - to a grave visceral disorder, _e.g._, gout in the stomach - (retrocedent gout); - - (ii.) That sometimes the converse occurs, viz., that an attack - of visceral disorder may suddenly be replaced by an acute - articular manifestation; - - (iii.) That such visceral derangements may alternate, not - only with articular, but also with other, such as cutaneous, - outbreaks; - - (iv.) That eye disease has been known to wax and wane in unison - with concurrent arthritic gouty manifestations; - - (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[47]; - - (vi.) That visceral symptoms in the gouty are anomalous and - inexplicable on any other basis; - - (vii.) That the treatment usually advocated for gout has a - favourable influence. - -_Deposition of Urates._—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 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. - -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:— - -In the _sclera_ on rare occasions we find osteomatous degeneration. - -In the _choroid_ 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. - -The _retina_ may undergo colloidal changes or be the site of carbonate of -lime or of cholesterin. - -The _vitreous_ may sparkle with showers of cholesterin. - -The _lens_ may contain both tyrosine and cholesterin. - -The _aqueous_ shows similar crystals. - -In the _iris_ degenerative calcareous or osseous deposits are -occasionally seen. - -The _cornea_ may be affected by hyaline degeneration with deposition of -lime salts. - -The _conjunctiva_ may be calcareous. - -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. - -But _urates_ are not found _in_ 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. - -_Gouty Diathesis._—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. - -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[48] that gout does not -cause iritis is directly challenged. For if it be granted that a sudden -outpouring of so non-toxic an acid _causes_ an acute inflammation—for -instance, in the synovia of the great 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? - -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. - -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. - -Nearly fifty years ago Jonathan Hutchinson drew up a “Report on the Forms -of Eye Disease which occur in connection with Rheumatism and Gout.”[49] - -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. - -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. - -Osteoarthritis also seems to have been included as one of the gouty -diseases, probably because _post-mortem_ 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 _long standing_, 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. - -_The significance of tophi_, 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 _facies_, -although the etiological causes are diverse. But in none do we find any -appearances pathognomonic of gout. - -The argument that because a patient has tophi therefore the 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. - -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. - -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. - -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. - -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 the generalisation “arthritic iritis.” “Not being able,” -he tells us,[50] “to determine the diathesis which predisposes to this -ophthalmia” (iritis), “I use _arthritic_ 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. - -In the following articular diseases the triad joint, muscle and nerve -disorders is not uncommonly linked with iritis:— - - Tuberculous arthritis; - Syphilitic arthritis; - Gonococcal arthritis; - Certain forms of specific arthritis: malarial, dysenteric, etc.; - Infective arthritis of undifferentiated type, as yet unaffiliated to - specific germs. - -In the following forms of arthritis iritis is less common:— - - Acute articular rheumatism; - Acute gout; - Osteoarthritis (hypertrophic); - Rheumatoid arthritis (atrophic). - -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. - -_The Relative Incidence of Iritis._—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. - -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 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. - -_No Uratosis, no Gout._—If we pin our faith to the equation - - Hyperuricæmia + Uratosis = Gout, - -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 _always_ accompanied with a deposit of urate of soda in the inflamed -part.” We should therefore expect that uratosis would occur _in situ_ -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 _fons et -origo mali_ of gout. - -_Metastasis._—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.[51] - -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.[52] - -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 _bacillus typhosus_, by the streptococcus of -erysipelas, and by that of puerperal septicæmia. - -De Grandmont[53] 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. - -_In erysipelas_ de Grandmont has seen a hyalitis from which a culture was -grown on gelatine that presented all the morphological characteristics of -erysipelas. - -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. - -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. - -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. - -_“Arthritic” Iritis._—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 _entente_ 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. - -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 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. - -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. - -_Frequency a Factor in Diagnosis._—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. - -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— - - (1) _That the frequency of the association was the essence of - the diagnosis_, - - (2) _That there was absence of any other recognised cause_, and - - (3) _In the former disease the effect of anti-syphilitic - therapy_? - -Applying these rules to gout, we find— - - (1) _No marked frequency of association of ocular disease and - gout_, - - (2) _That when iritis does occur there is often some other - possible source of origin_, and - - (3) _That anti-gout treatment has only a doubtfully beneficial - effect_. - -_“Gouty” Iritis is not a Clinical Entity._—Before a symptom or affection -can be classed as secondary to a primary disease there must be evidence -of a connection stronger than _post hoc, ergo propter hoc_. For instance, -in syphilis an iritis _frequently_ 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 _seldom_ occurs associated with gout, and when it does there are so -often 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. - -In the following table a comparison is made between types of iritis:— - -IRITIS. - - -----------------+-------+--------------+------------------+--------- - | Gout. | Syphilis. | Tubercle. |Toxæmia. - -----------------+-------+--------------+------------------+--------- - Pathognomonic | 0 |Gumma of iris.|Tubercles of iris.| 0 - symptoms. | | | | - -----------------+-------+--------------+------------------+--------- - -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.[54] - -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 _ocular_ symptom which -differentiates the disease from a similar one in _non-gouty_ 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. - -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. - -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 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. - -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 -_frequency_ of the combination to diagnose the cause. - -In writing on iritis in 1908,[55] 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. - -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 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. - -A man has iritis and tophi; _ergo_ 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? - -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. - -Concussion iritis would fall into line, for it is possible in this case -that the iris is rendered a _pars minoris resistentiæ_ 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. - -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 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. - -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[56]:— - - “_Gout of the Eye._—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. - - “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.” - -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 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. - -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. - -_Ocular Symptoms in Hyperuricæmia._—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. - -_In leukæmia_ 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. - -_In lead-poisoning_ 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. - -_In pneumonia_ we do not expect to find any ocular complications; in -spite of the uricæmia, the eyes are scatheless. - -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. - -In this congeries of ocular symptoms, marked by hyperuricæmia, we do -not find iritis included, and yet this is a commonly accepted _gouty_ -affection of the eye. - -_False Gout._—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. - -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. - -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. - -The sins of repletion in such patients may be relieved by the virtue of -abstinence, not by colchicum. - -_Retinal Hæmorrhage._—That retinal hæmorrhage may be caused by gout was -firmly maintained by Jonathan Hutchinson.[57] This opinion was shared by -Gowers, who states that the “influence seems well-established.”[58] - -Hutchinson pointed out that in cases of retinal hæmorrhage of 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 _æt._ 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.” - -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. - -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 _deus ex -machina_ 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 _viâ_ interstitial nephritis. In other -words, hæmorrhagic retinitis is the apanage of nephritis and the appendix -of gout. - -It is impossible to affirm that a retinitis is gouty, for there are no -distinctive features, but it occurs in gout when vascular 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. - -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.” - -James Taylor, writing on neuro-retinitis in the gouty,[59] states that— - - “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.” - -The opinion that cases of neuro-retinitis may be gouty is based upon -(_a_) the fact of the apparent absence of cardio-vascular disease -elsewhere, (_b_) 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. - -_Glaucoma._—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. - -_The conclusion_ I would arrive at is that it is unwarrantable to speak -of “gouty” ocular disease, for there is nothing in the character of the -inflammation specific of gout. We renounce the prefix in order— - - (1) That we may not be lulled into false etiological security, - and - - (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. - -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. - -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 _locus signi_ 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 _materies morbi_ 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.” - -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. - -With many of our patients, alas! considerations of expense compel us to -forego our aspirations. - -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. - -_Salus populi suprema lex._ - - - - -CHAPTER XXVI - -TREATMENT OF GOUT - - -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? - -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 _bottom of a well_; 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.” - -But although we cannot dissipate the inherent proclivities to the -disorder, we can, I think, claim to fulfil the humbler _rôle_, viz., -obviate their coming to fruition. Haply in the fulness of time we may -be able to influence the _endogenous_ factors that make for gout, may -through the labours of the bio-chemist be able to translate or assess -them in terms of _functional inefficiency_ of this or that particular -viscus. But meanwhile we must perforce content ourselves with the -eradication or control of the _exogenous_ factors of gout—the _excitants_ -whereby or through whose agency the malady from being _latent_ becomes -manifest and overt. - - -RADICAL TREATMENT OF LOCAL FOCI OF INFECTION OR TOXIC ABSORPTION - -When discussing the etiology of gout we emphasised the probability of -the intrusion of an _infective_ element in its genesis. We commented, -too, on the extreme frequency with which local infective foci are -encountered in _gouty_ subjects and the imperative necessity of their -early recognition and radical treatment. In doing so, we but conform -to what should be regarded as the salient canon in the treatment of any -form of _arthritis_, viz., a diligent search for a _focus of infection_. -A _monarticular_ 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. - -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. _Phlebitis_, 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. - -Again, _devitalised teeth_ 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 _viâ_ 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. - -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 _roots_ also, be ascertained. -For when we reflect that, in addition to _abscesses_, _cysts_, _buried -roots_, _inflamed_ and _impacted molars_ may be present, we see, if we -are to achieve a full and accurate diagnosis, _radiographs of the jaws_ -are essential. A single-plate negative is practically of no value. A -_series of films taken all round the mouth_ is the only satisfactory -procedure. Such give finer detail, and show up the interstices of the -teeth—the sites of predilection for _periodontal disease_ or _pyorrhœa -alveolaris_. - -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 _X-ray examination_ of the -_teeth_ 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 _gouty arthritis_. Usually the gout has been in full swing -for years. The patient’s _dyspeptic_ 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.” - -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. - -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 _painlessness_. Hence the ease with which _secondary infections_ -may ensue, _e.g._, in the _tonsils_, the _gastrointestinal tract_, etc., -while the original source may be altogether overlooked. - -The subjects of gout are often middle-aged or old. We should recollect -then that chronic _periodontitis_ may in their instance ensue in sequence -to _senile atrophy of the alveolus_. Recently in a patient of mine nearly -eighty, a sufferer from gout and sciatica, a persistent _pyrexia_, 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. - -Unfortunately no specific germ can as yet be saddled with the -responsibility for _pyorrhœa alveolaris_, though some would convict -the _endamœba buccalis_. _Spirillæ_ and _staphylococci_ form a -large proportion of the bacterial flora met with in _oral sepsis_, -but the results of _vaccine_ treatment would seem to indicate that -_streptococci_, _diplococci_, and _staphylococci_ are the most frequent -causes of complications. Still it must not be forgotten that the -_streptococcus viridans_ is by some held to be specially related to -_arthritis_. Hartzell (1915) invariably found it in the teeth and -peridental tissues in 220 patients suffering from arthritis. This -_streptococcus hæmolyticus_ frequently leads to _secondary tonsillar -sepsis_, and, as previously noticed, to subsequent _gall bladder -infection_, etc. - -Passing to _local treatment_, 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. - -Unquestionably, whether it be a matter of _curettage_, of “_pockets_,” -_alveolar abscesses_, or _extraction of teeth_, it is wiser to proceed -_gradatim_. 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 _surgical auto-inoculation_. -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.” - -Recurring attacks of _tonsillitis_—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 -_enucleation_ are the more emphatic when we note the increasing evidence -that _tonsillar sepsis_ may be etiologically related to _appendicitis_ or -_cholecystitis_. - -Again, as before pointed out, Wynn Wirgman noted that some cases of gout -are associated with _nasal_ disorder, and certainly in non-gouty forms -of arthritis expert treatment has reacted very beneficially on the joint -condition. Watson Williams has recently drawn attention to “_latent -sinusitis_” as a cause of _systemic infections_. He cites two cases of -chronic _rheumatoid arthritis_ which, previously resistant to treatment, -were greatly improved by operation on the _sphenoidal sinuses_. The -washings from the sinuses were free from pus, but on culture showed -growths, in the one case of _streptococcus albus_ and in the other of -_streptococcus aureus_ and _streptococcus brevis_. - -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 _gonococcal_ infection. Apart from this, we -should recollect that _cystitis_ is common in gouty subjects, and, -according to older authors, might occur as a result of “_metastasis_,” -not to mention the cases of so-called “gouty” _urethritis_, which, it -is claimed, not uncommonly supervenes at the end of an articular attack -of gout. Nor should we forget the _rectum_, 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 _rectal -ulcerations_ may be causally related to some forms of arthritis. - -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. - -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. - -But, obviously for the success of vaccine therapy, it is essential that -an accurate _bacteriological_ 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 _complement fixation tests_ 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. - - -DIET - -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, _mirabile dictu_, still avid for fresh -ventures? - -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 _individual_. 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, _gastro-intestinal -asepsis_. 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. - -_Diet in Acute Paroxysms._—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. - -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 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. - -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. - -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 _gastro-intestinal_ -and _hepatic_ derangements. Lastly, in acute _sthenic_ gout occurring in -a robust subject there is no need whatever for _alcohol_ in the _febrile_ -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. - -On the other hand, in acute _asthenic_ gout in an _elderly_ and perhaps -somewhat _debilitated_ 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 _young_ and _plethoric_ differs from that suitable for the -_old_ and _asthenic_. - -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.[60] 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 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. - -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 -_disease_, 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. - -Moreover, these cases of _acute gouty polyarthritis_, whether in the -middle-aged or old, very commonly run an _afebrile_ 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. - -Even when in these cases _pyrexia_ is present, it is rarely continuous, -but is diversified by _afebrile_ 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 _inter-paroxysmal_ stages we take full -advantage of these periods of enhanced digestive capacity. - -_Diet in Chronic Gout._—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.” - -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! - -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 _starvation_! Well would it -be if the evil done ceased with themselves, but unfortunately they seek -converts to whatever cult they affect. - -_The Fallacy of Fixed Dietaries._—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 _precursors of uric acid_. Its acceptance makes not for -flexibility in dieting, but rigid, undiscriminating routine. - -Apart from the violation of principle, the direct result is, that the -victim runs amok among the _carbohydrates_, with as a frequent penalty -an _acute_ 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.” - -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. _Pari passu_ his digestive capacity -rises and wanes. The regime therefore must be adapted and readapted to -his varying necessities. For it is the _patient_, and not the “gout,” -dictates the diet. But only too commonly the _disease_ is dieted, the -victim ignored—_hinc illæ lachrymæ!_ - -Our dietetic ventures must obviously rest on a sounder basis. This we do -know, viz., that _functional disturbances of digestion_ generally precede -a “gouty” paroxysm, and that their amelioration is followed by relief of -symptoms. The aim of our dietetic measures then is the _prevention of -digestive disturbances_, not the routine withdrawal or reduction of uric -acid precursors. - -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 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? - -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 _sui -generis_, all due to _one_ cause, the _materies morbi_ of _gout_, instead -of being merely “_excitants_” of gout and due to a variety of digestive -functional disabilities, and these of equally diverse origin? - -_Thorough Physical Examination a Necessary Prelude to Dieting._—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 _primary_ outbreak of _gout_ -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. - -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 _gastro-intestinal_ -derangements are causally related to outbreaks of _gouty arthritis_, -surely our remissness in this matter is somewhat surprising, the more so -in light of the heroic procedures, viz., _ileocolostomy_ and _colectomy_, -advocated in _rheumatoid arthritis_, a condition by many deemed related -to gout. - -Leaving such aside, none will, I think, deny not only the value of _test -meals_ for _free HCL variations_ and experimentation with all kinds of -foodstuffs, but also of X-ray examination of the _alimentary tract_. -How subversive of all preconceptions the revelations of radiography -in _gastric_ and _intestinal_ conditions, of what infinite value in -disentangling the ambiguous significance of purely subjective sensations! -Thus, alterations in _gastric_ tone, motility, and peristalsis may hark -back to remote lesions in _gall bladder_ or _appendix_, and these also -account for variations in free HCL. - -“Great eaters,” said Sydenham, “are liable to gout, and of these the -costive more especially”—an observation the truth of which all will -confirm. It may be taken as a maxim that nothing for the gouty is more -prejudicial than _constipation_. 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.e._, dyschezia. How else obtain this -information, save through X-ray examination? - -Any departure from normal in consistency, colour or content of the fæces -should be noted so as to identify _hepatic_ or _pancreatic_ 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 _glycosuria_ or _oxaluria_, or substances indicative -of excessive intestinal putrefaction. All these bear far more pertinently -on _diet_ than estimates of _uric acid_. - -The behaviour of the _skin_, 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 _obesity_ or undue _leanness_. -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? - -In the matter of _exercise_, 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. - -_Need for Collaboration of Clinician and Bio-chemist._—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. - -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.e._, -_tophi_. But can we say of him that he actually _now_ 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 are about to, but have not yet developed the -disorder, _i.e._, the “potentially” gouty. - -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 _latent_ -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 _functional capacity_ or _efficiency_ of the various -_viscera_? - -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 _viscus_ is -_functionally deficient_. There are signs that this boon will not be -long withheld, signs that not only can the functional efficiency of the -_stomach_ be tested, but also of the liver, kidneys, and even the spleen. - -Thus Labbe and Daughin study the colloidal nitrogen in the urine, and -find the ratio to the total nitrogen much augmented when the _functional -efficiency of the liver is depressed_. Again, Bauer and Spiegel use -the _bilirubin content_ of the _blood_ to the same end. They maintain -that there is a bilirubin threshold, the assessment of which denotes -the _functional capacity_ of the _liver_. In health the _blood content_ -thereof is surprisingly _uniform_. But in passive congestion of the -liver it rises very markedly, and the same after administration of -_cholagogues_. - -In like fashion the value of _blood urea_ concentration is extolled by -Kast and Wardell as a satisfactory index of the _functional power_ of the -_kidney_. The _uric acid_ content of the blood is by Baumann, Hansmann, -Davis, and Stevens regarded as a very delicate index of _renal_ 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 _spleen_, while Barton invokes the -administration of urea, chlorides, adrenalin, creatine, etc., to assess -the functional capacity of the _liver_, _kidney_ or _spleen_. - -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? - -We need to know more about the _endogenous_ 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 _sui generis_ character. How then in the “living” subject shall -these hidden morbid potentialities be identified? How save through the -medium of _function_, the outward expression of metabolic activities, in -other words by appraisement of the _functional capacity_ of the various -_viscera_? 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 -_functional_ powers, the efficiency or not of the _liver_, _kidneys_, etc. - -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 _functional deficiency_, -deficiency of the working capacities of the _stomach_, _liver_, or -_kidneys_, and perhaps find that the basal flaw in some lies in the -_liver_, in others in the _kidney_, and thus the older clinicians be -justified of their claims for “hepatic” or “renal” varieties of gout. - -That _exogenous_ factors, _i.e._, _infections_, 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 -_gastro-intestinal asepsis_. Albeit, _infections_ 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? - -The “soil” in gout is, I believe, one peculiarly favourable to microbic -invasion, and here again recent studies of the _cytology_ of the -blood bid fair to yield us some criterion whereby the “degree of body -resistance” to infections may be gauged. - -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 _exogenous_ excitants of the -malady. Ultimately, when researches now in progress have fructified, -we may be able to influence the _endogenous_ 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.” - -“_The Accessory Food Factors._”—“Due nourishment, not 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. - -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. - -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.” - -Of these elusive bodies but three as yet have been isolated: _fat-soluble -A_, _water-soluble B_, and _water-soluble C_. In infancy absence of the -first-named “vitamine” leads to _rickets_. Lack of the second engenders -_scurvy_, of the third _beri-beri_. - -But, apart from these well-defined “deficiency diseases,” McCarrison -has pointed out that the absence of these “accessory food factors” -leads to grave _functional_ 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. - -A heavy indictment, but, more pertinently to our subject, McCarrison -inclines to think that _bilious vomiting_, _cyclical acidosis_, _mucous -disease_, and other _metabolic_ disorders met with in _children_ 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 _infantile gout_. - -More arresting still is McCarrison’s observation that all the clinical -phenomena distinctive of “deficiency diseases” as a whole are apparently -the result of _nuclear_ starvation of all tissue cells. In short, these -“accessory food factors” are essential to _due nutrition of the nuclear -substance_. How interesting this in light of the generally accepted -view that “gouty” individuals are victimised by some inherent defect or -alteration of _nuclein_ 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 -we must strive for the stable maintenance or conservation of nuclein -metabolism? - -Again, as before stated, one of the results attaching to deficiency -of “vitamines” is _functional derangement of the organs of digestion -and assimilation_. Such disturbances are prominent in _gout_, and that -“errors of diet” play an important _rôle_ 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. - -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.” - -Such good, moreover, as we do compass, is, I think, exerted _indirectly_. -Even in the _inter-paroxysmal_ periods of the disorder, despite good or -perhaps exuberant health, gout is there. Its morbid tissue potentialities -are _latent_, though _functionally inactive_. To maintain this state of -_passivity_ is the aim of all dietetic measures, viz., to diminish or -withdraw the dietetic factors that are _provocative_ of gout. - -The diet most void of offence is one the least calculated to excite -_digestive disturbance_—one that makes more surely for _gastro-intestinal -asepsis_. 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 _infections_ and parasitic agencies are -often important causes in determining the _onset of symptoms_. - -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 _nuclein_ metabolism and associated specific local -reactions in certain tissues. - -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. - - - - -CHAPTER XXVII - -TREATMENT OF GOUT (_continued_) - - -REGULATION OF DIET IN THE GOUTY - -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. - -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. - -Do not irritate the patient with a strict dietary if avoidable. Far more -often than not it is the _quantity_, 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, _restriction_, 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. - -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. - -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 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. - -As to the _quality_ of the food, always recollect that “gouty” people -are very prone to _idiosyncrasies_; but the idiosyncrasy is purely -_personal_, 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. - -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—_dolor -acerrimum naturæ pharmacum_. The wise has only to be reminded of his own -experience, viz., that certain articles of diet infallibly disagree with -him—_verbum sapienti satis_. - -In dieting the “gouty” we should never forget that the _main groups -of foodstuffs must be duly represented_. 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. - -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 _simplicity_ 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 together -in the same meal, one hindering the digestion of the other.” - -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. - -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 _consommés_, 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.” - -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 _tea_. 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. - -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. - -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 _gastric -dilatation_ or _visceroptosis_. The same in _hyperacidity_, 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. - -Lastly, we should always endeavour to ascertain as nearly as possible -the actual amount of the food intake per diem. This 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. - - -THE INDIVIDUAL FOODSTUFFS - -_Proteins._—Ruthless cutting off of _protein_ 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, _mirabile -dictu_, white meat, _e.g._, rabbit, is more indigestible than red. - -Accordingly let your “gouty” patient eat animal food, at any rate at -_one_ meal, but let it be of _one_ 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 _him_ it be -_digestible_. 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. - -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.” - -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 _an excess of uric acid in the blood_, and that to increase -the content thereof is undesirable. Again, we know that in _normal_ men, -after ingestion of pancreas and thymus gland, the _uric acid_ output -in the urine is _markedly increased_. 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 _uric acid retention_. - -More pointed still is the fact that _acute_ outbreaks of gout have been -repeatedly brought on by administering _thymus_ to the subjects of -_chronic_ gout. Surely, in light of this, it is impolitic to approve of -_sweetbreads_ 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 _penchant_ for these foods, we -should at any rate advise their restriction or elimination. - -_Fish._—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.e._, sole, whiting, turbot, brill, cod, plaice, flounder, are -the preferable. On the other hand, the red-flesh fish, _i.e._, salmon, -mackerel, herring, sprat, pilchard, eel, etc., contain much fat, and are -more likely to upset the “queasy” stomachs of the “gouty.” - -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. - -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 _all_ “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 objection to a “gouty” individual eating them raw, and when “in -season,” but in moderation. - -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. - -_Carbohydrates._—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 _sugar_ -all will be well. Latterly, too, I have noticed that the ban is being -extended to _starchy_ foods also. - -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 _temporary_ 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 _quâ_ _uric acid_ carbohydrates may appear ideally -suitable, yet the “gouty” are unfortunately no more immune than others -from the _dyspeptic_ disturbances that almost infallibly ensue when sweet -foods are taken immoderately. - -It is this tendency in some “gouty” subjects to amylaceous dyspepsia that -has been wrongly extended into a law for _all_ 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. - -With this reservation, bread may be given as crisp toast, or rusks, or in -the form of _Zwiebach_. 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.” - -_Fats._—Apart from _obesity_, there does not seem to be any scientific -reason why fats should be denied to the “gouty.” All depends on their -_digestibility_, and in this they display variations. The fat of ducks -and geese is well dispensed with in favour of bacon fat and pork fat, -which are much more digestible. The fats of meat, when roasted or -browned, are best avoided. - -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.” - -_Vegetables._—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. - -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. - -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 _purin-free_. 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, preferably -those easily digestible, relatively poor in purins, or rich in potassium -salts. - -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. - -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. - -_Fruits_ 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. - -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. - -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 _non-gouty_. The objections to certain fruits, -_e.g._, strawberries, as to certain vegetables, _e.g._, 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. - -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 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. - -_Condiments._—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. - -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 _hyperchlorhydria_ 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. - -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. - -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 _fixed rules_ it savours of evil, this at any rate as far as the -dieting of _dyspeptic_ derangements of the “gouty” is concerned. To bring -into prominence my point, I would lay down the postulate that there is -_no specific form of “gouty” dyspepsia_. - -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 _organic acids_, butyric, lactic, or acetic, the outcome of -fermentation, or the condition may be one of hyperchlorhydria, or -excessive secretion of HCL. - -_Hyperacidity_ due to _organic acids_ is met with in some cases of -_atonic dyspepsia_, _chronic gastritis_, and _dilatation of the stomach_. -The free HCL is either diminished or absent. Differentiation of this type -from _hyperchlorhydria_ may be impossible without examination of the -stomach contents. - -Hyperchlorhydria _per se_ 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 _neurasthenia_ from which the “gouty” no more than others are -immune. - -Again, gout of long standing is often associated with _chronic gastric -catarrh_. Such is very common in beer-drinkers or men employed in -breweries. A state of _atonic dilatation of the stomach_ 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 _fibrotic -degeneration_. Also we have to recollect that the “gouty” are very -subject to obstinate _gastralgias_. - -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, _hypochlorhydria_. The _protein_ -dietary suitable for the former has in the presence of the latter to be -replaced by _carbohydrates_, despite their tendency to fermentation. -Again, if either condition be complicated by _dilatation_ other -exigencies must be met. The meal content must be light, not bulky, and -the fluid intake restricted. - -Again, the foregoing gastric disorders may be complicated by _glycosuria_ -or _albuminuria_, 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. - - -SPECIAL DIETARIES - -_Amylaceous Dyspepsia._—Not a few “gouty” subjects suffer from -atonic dyspepsia, with _acidity_ due to _organic acids_ arising from -fermentation. Frequently it appears to be the outcome of 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. - -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. _Fats_ of the more digestible sorts are also -desirable. Grilled but not fried fat bacon is easily digested. - -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. - -As a guide to the formulation of a dietary in such cases the following -may be suggested:— - -On awaking in the morning a tumbler of hot water should be slowly sipped. -A squeeze of lemon may be added if liked. - -_Breakfast._—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. - -_Lunch._—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 _after_ eating. - -_Afternoon Tea._—One or two cups of weak tea with milk or one cup of -cocoa. - -_Dinner_ (two courses only).—Fish of the kinds allowed for breakfast -without potatoes, or a slice of any tender meat, _e.g._, 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. - -If there be any suspicion of chronic gastritis, condiments and stimulants -must be renounced, but not in purely atonic dyspepsia, 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. - -_Hyperchlorhydria._—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. - -In these cases of superacidity the most suitable foods are _proteins_, -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. _Farinaceous_ -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. - -Coffee is best abstained from, and cocoa and tea freshly made with half -milk substituted. Soups are best avoided. If with the _hyperacidity_ -there be associated any degree of _atonic dilatation_, 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 _hyperacidity_ do well on three meals per diem provided they are -separated by an adequate interval. - -If the foregoing measures prove ineffectual the _carbohydrate_ content -of the food should be withdrawn, and the patient limited to a strictly -_meat_ 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 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 (_Zwiebach_) 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. - -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. - -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. - -_Hypochlorhydria._—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. - -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. - -_Hyperuricæmia._—As far as is known, the endogenous moiety of urinary -uric acid is uninfluenced by diet. On the other hand, 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. - -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. - -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 _raison d’être_ the baseless assumption -that _uric acid_ is the _fons et origo mali_. - -I am very doubtful of the intrinsic merits claimed for it. I do not -think it exerts a direct or _specific anti-gouty_ influence. Such -advantages as do accrue are referable, in my opinion, to the greater -measure of _intestinal asepsis_ that such a regimen promotes. It is -suitable, therefore, in cases in which there are evidences of _intestinal -putrefaction_. Distinctly unappetising, it is useful, too, as a -disciplinary measure for those prone to overeating. - -Its advocates claim that it tends to diminish the _excess of uric acid -in the blood_. But, as was pointed out when dealing with uricæmia, -_variations_ may occur in the _uric acid content of the blood -independently of diet_. Moreover, acute attacks have been observed even -when the uric acid blood content was at a _sub-normal_ level. - -To place all “gouty” subjects on a _purin-free_ 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. - -_The Reduction of Obesity._—Unfortunately obesity is a common associate -of gout, and with it not infrequently comes _glycosuria_. 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. - -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. - -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.” - -Again, there is the _static_ 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. - -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:— - - “Make less thy body hence, and more thy grace; - Leave gormandising; know the grave doth gape - For thee thrice wider than for other men.” - -There are so many dietetic methods of treating obesity that 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. - -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. - -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 _pari passu_ 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. - -_Glycosuria._—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, _e.g._, 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, and -other vegetables, while he may eat freely of butter, bacon, and other -fats. - -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. - -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 _alimentary_ glycosuria. But we -should also remember that exceptionally a case of gouty glycosuria may -emerge into one of true _diabetes_. - -_Albuminuria._—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. - -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 _general condition_ 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.” - -Lastly, up to this juncture all our suggested dietetic modifications -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.” - - -BEVERAGES IN GOUT - -It cannot be gainsaid that the beneficial effects of so-called “water -cures” are in great measure referable to the increased amount of _water_ -ingested during their progress. Absorbed in the main in the small -intestine, it passes into the general blood stream, whence it is excreted -_viâ_ 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. - -By general consent, the water ingested should be preferably _hot_. 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. - -It is also claimed that the increased elimination of water _viâ_ 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. - -The point at issue, however, is whether or no this increase in the amount -of _urea_ excreted can be held to indicate enhanced tissue change in the -nitrogenous elements in the body fabric. - -Winternitz claims that it does, in contrast to Von Noorden, who holds -that nitrogenous tissue change and the formation of _urea_ and _uric -acid_ are _uninfluenced_ by the amount of water imbibed. In further -contradistinction some contend that following the ingestion of water the -_excretion of uric acid_ is _diminished_. - -Fortunately for “gouty” subjects, the beneficial effects of water -flushing of their systems occur independently of any _coincident increase -in their uric acid output_. 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 _asthenic_ 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.” - -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. - -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.” - -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, -_e.g._, those of Bath, etc., are among those whose efficacy in gout is -beyond question. - -Again, how can we reconcile with this view the prevalent practice of -placing “gouty” subjects, temporarily at any rate, on a _milk_ 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 _personal idiosyncrasy_. - -Lastly, as to _tea_ and _coffee_, 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. - - -ALCOHOL IN GOUT - -Said Sir Thomas Watson: “I am sure it is worth any _young_ 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 _gouty -parents_ the incumbent duty of bringing up their children as _total -abstainers_. 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.” - -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. - -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:— - - (1) The children of “gouty” parents should be brought up as - total abstainers. - - (2) The incidence of a first attack in a young man should be - the signal for abstinence from alcohol in all forms. - - (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. - - (4) In middle-aged or old subjects habituated to the use or - abuse of alcohol _abstemiousness_, not abstinence, is the safer - course. - - -THE VARIOUS ALCOHOLIC BEVERAGES - -_Malt Liquors._—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. - -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 _gout-inducing power_ malt liquors, like wines, display great -variations. - -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 is the small beer in -our own country, which in foreign countries may be replaced by weak -wine-and-water.” - -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 _idiosyncrasy_, a _mild_ -beer not containing more than from 3 to 6 per cent. of alcohol will do -him not more, but less, harm than _whisky_. - -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.” - -I think then in this matter of _malt liquors_, 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— - - (1) It be a “light” beer, in which the “bitter” principles - predominate, and the extractives are small in amount[61]; - - (2) It be “sound” and not “turned” beer, and of course free - from any possibility of _lead_ impregnation; - - (3) It be taken in moderation, not exceeding one to two pints - per diem; - - (4) The “gouty” subjects by whom it is taken be physically - active; - - (5) Due respect be paid to _personal idiosyncrasy_, reserving - its use for those in whom its effects are definitely - _stomachic_ and _tonic_, while discountenancing its use when - followed by _heaviness_, _drowsiness_, and _biliousness_. - -As to _cider_, there is no doubt that the partially fermented or 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.” - -_Wines._—When we come to consider _wines_, we are on very uncertain -ground, this especially if we base our opinion too much on the _chemical_ -analysis of this or that variety. The current belief is that the most -unsuitable wines are those that contain large amounts of _alcohol_, -_sugar_, or _free acid_. Then we discover it is not the amount of -_alcohol_ 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 _whisky_ is the favourite beverage; _ergo_ whisky _par excellence_ -is _the_ drink for the “gouty,” and so we find ourselves in this -_impasse_: we fulminate against _alcohol_ as _the_ cause of gout, and -in the same breath advise our “gouty” patients to drink precisely those -fluids containing the highest percentage thereof. - -True, when we turn to _wines_ we find that it is precisely those that -are richest in _alcohol_ that most potently predispose to gout, _e.g._, -port. But seeing that _whisky_ contains infinitely more _alcohol_ 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 _acidity_ 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 _sugar_ 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. - -Now the most salient deduction from the foregoing considerations is our -inability at present on _chemical grounds_ to determine why certain -_wines_ 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 _quâ_ gout reside -in the _individual_, not in the character of the wine? We are far too -prone to say that this or that _wine_ is “gouty,” to say that this wine -gives you gout, and that not. - -The evil potentialities that make for gout reside not in this or that -particular wine, but in the _individual_. This or that wine does not give -him gout, but evokes or brings to fruition a morbid tendency already -_latent_ 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 _caveat_: Alcohol will not originate gout in a -_non-gouty_ subject, but it will almost infallibly in those in whom there -exists by heredity an inborn tendency to gout. In short, the “gouty” are -_hypersensitive_ to the evils of alcohol; the greater the need then for -_abstemiousness_ and self-restraint. - -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 _“gouty” individual_ 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 _whisky_. This -is done so light-heartedly that I do not wonder that the subject goes -away frequently with the idea that _whisky_ is not only innocuous, but -desirable. - -_The whisky-drinker is not immune from gout_, and I have no hesitation -in affirming that “light” _wines_ when fine, mature, and of a _good_ -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.” - -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 _personal -idiosyncrasies_ in this respect. In this way you elicit and utilise for -your ends the _individual’s_ own experience, the only experience that -counts. - -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 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. - -The sum of these erratic findings is that you must respect -_idiosyncrasy_. It is said that the best wine for a “gouty” subject is -the one that causes most _diuresis_. For myself, I am equally positive -that the worst wine for a gouty man is that which upsets his _stomach_, -which gives him some hours afterwards “acidity” or a feeling of “liver.” -Often, too, it is not the wine, but the _stomach_ into which it is put, -that is to blame. Thus the “gouty” subject with _atonic dyspepsia_ finds -a glass of sound wine helps digestion. On the other hand, if he suffers -from _hyperacidity_ or _chronic gastritis_, the reverse will probably be -the case. - -Again, it is not the name, but the _quality_, 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.” - -It seems opportune here to lodge a protest against _fashions_ 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 _all_ “gouty” subjects. - -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 _quantity_ 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 tactful reminder of the amount he is consuming per diem will -frequently come as a shock, often a very beneficial one. - -Apart from this, it is, I am sure, wise to fix the _daily amount_. 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. - -At other times the amount, though, strictly speaking, not excessive, -is so when judged in light of the victim’s _habits_. He may be an -intellectual worker, but _sedentary_, and he must either lessen his drink -or increase his exercise, or he may _overeat_ 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 _reduction_ of both. - -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 _personal -idiosyncrasy_ stands first. By this criterion, and none other, can the -_suitability_ of the wine be decided. Then the state of the _digestive_ -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, _glycosuria_, _albuminuria_, _raised blood pressure_, or -_cardiac degeneration_ 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. - -It will be seen that I have largely refrained from specifying the wines -_suitable_ or _unsuitable_ 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:— - -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 arrested before all the sugar has been exhausted, as in -Malaga. Again, wines which are both “strong” and “sweet,” _e.g._, Malaga, -sweet champagne, Tokay, etc., are more pernicious than those which are -“strong” yet “dry,” _e.g._, port, sherry, Madeira. - -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. - -It is interesting to recall, too, that Sydenham regarded _sherry_ 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. - -Turning to _port_, 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 _asthenic_ 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. - -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. 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 _quality_ 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.” - -If, on the whole, the most unsuitable wines for the “gouty” are the -strong sweet _spirituous_ or _liqueur_ wines, on the other hand the _red_ -or astringent and _white_ wines are the most esteemed. As to the _red_ -wines, there is no doubt that the delicate Gironde (Bordeaux) wines are -_par excellence_ 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.” - -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 _one_ or perhaps two -glasses somewhat diluted with water. Being a stronger and more tonic wine -than Bordeaux, it is useful in the more _asthenic_ 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. - -Reverting to _white_ 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 _vin de Grave_, all varieties of the latter being fairly “dry” and -light in character. On the other hand, the _white_ wines of Sauterne, -like some of the Hungarian wines—_i.e._, 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. - -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 _meal-times_, and -establishing a rigid rule as to _quantity_. 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 _quality_ of the -wine should be above suspicion, and if the expense is prohibitive, he had -best eschew wine altogether in favour of mature spirits. - -_Spirits._—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 _beneficial_ -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 _moderation_ be suitable for the “gouty,” whisky in _excess_ 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. - -In advising therefore a “gouty” subject to take whisky we should insist -that (1) it should be taken only at _meal-times_ and (2) only in -_moderation_. The habit of occasional “nips” at all times of the day -should be unreservedly condemned. As to what constitutes a _moderate_ -quantity is often a difficult question to decide. - -When feasible, I endeavour to limit the _daily allowance_ to _a -wine-glassful_, distributed over lunch and dinner. But it is quite -impossible to lay down hard and fast rules in a matter in which _personal -idiosyncrasy_ plays such a strong _rôle_. 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 individual under review seems apparently -compatible with no appreciable damage to health. - -Sometimes one of the frequent accompaniments of gout comes to -our assistance. It may be _raised blood pressure_, _glycosuria_, -_albuminuria_, _obesity_, etc. In such cases a word in season may reduce -an otherwise recalcitrant subject to reason. - -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 _habits_, whether _active_ or -_sedentary_, whether associated with overeating or not. For manifestly -all these bear on the point at issue. - -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. - - - - -CHAPTER XXVIII - -MEDICINAL AND OTHER MODES OF THERAPY—ACUTE GOUT - - -MEDICINAL THERAPY - -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. - -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 _rôle_ of the physician was that of the -bystander viewing the workings of the _vis medicatrix Naturæ_, 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 _laisser -faire_ 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? - -It may be admitted that an _initial_ 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. - -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 _colchicum_ 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. - - -ACUTE GOUT - -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 _arterial_ and _renal_ changes. - -The medicinal treatment of acute gout necessarily divides itself into -_constitutional_ and _local_ 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. - -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. - -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 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. - -Incidentally one may recall that the objections unfairly launched against -_colchicum_ took origin in the misconception that its good offices were -referable to its _cathartic_ 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 _gouty arthritis_ 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.” - -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 _colchicum_. At the same time we must not think -that mere _purgation_ 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. - -My own opinion is that, if seen just _before_ or just _after_ 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. - -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 drachms of sodium sulphate, a Seidlitz -powder, or a full dose of Carlsbad or Condal water. - -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. - -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:— - - ℞ Ext. colchici acet. gr. ½ - Ext. aloes barb. gr. 1 - Ext. hyoscy. vir. gr. 1 - Pil. hydrarg. gr. 1½ - Fiat pil., 1. - -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. - - -_Colchicum in Acute Gout._ - -Whatever be its mode of action, colchicum still remains _par excellence -the_ remedy for acute gout. As before noted, Dixon and Maiden hold -that _colchicine_ has no action on the _metabolism_ or _excretion_ of -_purins_, nor on the _kidneys_. On the other hand, it influences markedly -the _leucocytes_, their number in the circulation undergoing a primary -decrease and a secondary increase. Bain, it is true, found that under -colchicum a slight _increase in uric acid excretion_ occurred, but thinks -it extremely doubtful if its influence in this direction is invariable. - -That colchicine should exert such a marked effect in gout and yet -apparently be destitute of any influence on _uric acid excretion_ is of -course very striking. It calls, moreover, for more reflection on the part -of those who seem to contend that because a drug _increases uric acid -elimination_ it must necessarily be beneficial both for the gout as well -as for the victim. - -_Method of Administration._—In _initial_ 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. - -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 _visceral_ gout is present, or the urine contains much -_albumen_, no colchicum should be given. - -It is notorious that _old_ 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. - -_Preparations of Colchicum and Dosage._—Those most commonly in use are -the _tincture_ and _wine_ 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. - -By French physicians the tincture of colchicum is preferred, and by Robin -that extracted from the _flowers_ rather than the seeds. The dose of our -own official _Tinct. colchici seminum_ 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 _seeds_ 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 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. - -Turning now to discuss the most opportune juncture at which to administer -colchicum, certainly in the _initial_ and the earlier paroxysms we may -with advantage postpone the giving of colchicum pending _free clearance -of the bowels_. No harm will follow its being withheld until the _second_ -day. Indeed, many physicians, both British and Continental, counsel delay -in its exhibition until the fit is well established. - -Again, in _primary_ paroxysms—viz., while ignorant of the personal -equation in respect of _colchicum_—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:— - - ℞ Magnesii sulphatis gr. 60 - Magnesii carbonatis gr. 10 - Potassii citratis gr. 30 - Vini colchici ♏︎ 20 - Aquæ menthæ viridis ad unciam. - Misce. fiat mistura. Two tablespoonfuls with two of hot water every - three hours until bowels have been freely opened. - -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. - -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. - -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. - -In _subsequent_ paroxysms and alike in the _acute exacerbations_ -that chequer the course of _chronic_ gout we may, in the absence of -_idiosyncrasy_ 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:— - - ℞ Vini colchici ♏︎ 15-20 - Magnesii carbonatis gr. 15 - Magnesii sulphatis gr. 60 - Aquæ cinnamomi ad ℥j. - Fiat mistura, ℥ij. statim sumenda et ℥j. quartis horis p.p.a. - -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:— - - ℞ Ext. colchici gr. ¼ - Aloin gr. ⅛ - Ext. bellad. alcoh. gr. ⅛ - Capsicin gr. ⅟₂₀ - Ext. rhei gr. 1 - Fiat pil., 1. - -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:— - - ℞ Ext. colchici acet. gr. 1½ - Pulv. ipecac. co. gr. 1½ - Ext. colocynth co. gr. 1½ - Fiat pil., 1 nocte sumenda. - -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. - -_Colchicine._—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 the maximum administered during -twenty-four hours should not exceed ⅟₁₆ grain approximately. - -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:— - - ℞ Colchicine gr. ⅟₁₀₀ - Ext. belladon. alcoh. gr. ⅛ - Ext. nucis vomicæ gr. ¼ - Fiat capsule or cachet, 1 every three or four hours. - -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. - -Or as a substitute we may use the _salicylate of colchicine_, 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. - -_Atophan._—This is a yellowish cream-coloured amorphous powder of the -composition 2-phenylchinolin 4-carbonic acid. Its use has been much -extolled both in _acute_ and _subacute_ 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. _Agotan_, 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. - -Atophan is incompatible with sodium bicarbonate and other alkalies -_in vitro_, 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 _blood_ falls and -the _urinary uric-acid output_ increases. Weintraud in gouty patients -on a _purin-free_ diet noted that after atophan the quantity of uric -acid excreted in the urine was more than doubled, but subsequently the -excretion fell below normal. - -Even in healthy individuals when taking atophan the urine becomes turbid -from the presence of _urates_. This excess of uric acid in the urine may -in gouty individuals be precipitated in the urinary tract, and so induce -an attack of _gravel_. Consequently Weintraud advises that the drug be -taken with _alkalies_, 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 _gravel_, but in several of their cases atophan had induced -_urticaria_. - -As to the simultaneous intake of _alkalies_, while the precaution is -probably desirable, I have known gouty patients take atophan _without_ -alkalies for several weeks in full doses without any apparent ill -effects. Brugsch, indeed, states that in _polyarthritis urica_ 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. - -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 _rôle_ -of obviating the formation or promoting the absorption and elimination -of _uratic deposits_. In other words, colchicum influences the _causa -causans_ of gouty inflammation, atophan only the _consequences_ or -_sequels_ thereof. - -The most favourable juncture at which to prescribe atophan is _at the -close of a paroxysm_. 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 _prevent the formation of uratic -deposits_. - -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. - - ℞ Potassii bicarbonatis gr. 15 - Sodii bicarbonatis gr. 20 - Spts. ammoniæ aromat. ♏︎ 20 - Tinct. zingiberis fort. ♏︎ 5 - Inf. aurantii co. ad unciam. - Fiat haustus, thrice daily well diluted with water. - -To sum up, our medicinal treatment of acute gout consists in _initial -purgation_, followed by maintenance of an adequate daily evacuation; -secondly, the exhibition of _colchicum_ 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 _atophan_ -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. - -_Alternative Remedies in Acute Gout._—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. - -Lecorche, again, though he found it useful in _acute_ 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 _prophylactic_ 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. - -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. - -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 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. - -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 _increased uric acid output_ in the urine follows -the administration of salicylate of sodium, though they differ in opinion -as to the manner of its production. - -As to the employment of salicylate of soda in _acute_ gout, it must, I -think, be seldom called for, save in the presence of _idiosyncratic_ -sensitiveness to _colchicum_. 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. - -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. - -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. - -There is yet another contingency in which resort to salicylates may be -indicated, viz., in those long-standing cases of _chronic gout with -recurring exacerbations_ 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 _cardiac_ or _renal_ -degeneration. As to the employment of salicylates in massive doses in the -_inter-paroxysmal periods_ as a _prophylactic_ measure, I think this is -better attained by occasional courses of _atophan_. - -Lastly, there are instances in which both colchicum and salicylates -appear to be contra-indicated. In this event we may either rely simply -on _alkalies_—and we have Duckworth’s authority that in many cases of -_acute gout_ they have proved satisfactory—or we may adopt Sir Alfred -Garrod’s plan of giving _quinine_ (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 _subacute_ attacks that so -commonly chequer the course of _chronic_ gout. - -_Thyminic_ 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.” - -As to _quinic acid_ 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.e._ “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.” - -_Anodynes in Acute Gout._—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. - -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 trional. Sir William Whitla’s “routine hypnotic in gout” is -paraldehyde. - -All these are preferable to opium in any form, for we deal with a -disease in which _defective elimination_ 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. - - -_Local Measures in Acute Gout._ - -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. - -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 _cold_ applications -should be carefully shunned. - -As to anodyne preparations, we suffer from what may be truly described -as _un embarras de richesse_; 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, 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. - -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. - -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. - -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. - -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 and clove -combined with twice the quantity of olive oil, or one of the following -excellent combinations may be selected:— - - ℞ Olei origani vel olei terebinthini Partes æquales. - Linimenti ammoniæ. - To be applied with friction to the affected part. - - ℞ Ætheris 1 drachm. - Linimenti belladonnæ ½ ounce. - Tinct. capsici To 2 ounces. - To be well rubbed into painful parts night and morning. - -When a joint is the seat of fixed pain with definite thickening, it may -be necessary to resort to _blisters_; 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 _acute serous -effusion_ of recent origin; but are often beneficial when applied over -joints, bursæ, or tendon sheaths, when the seat of _long-standing passive -distension_. - -Garrod held them of most advantage in _gout_ of _asthenic_ character with -lingering effusion; but he thought them inadvisable in the later stages -of gout with _defective kidneys_ and where the joints were the seat of -massive uratic deposits, as in the last event sores difficult of healing -may follow. - -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, _e.g._, 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 _friction_ which -accompanies their usage. - -In conclusion, it must be recalled that the swelling, stiffness, and pain -are of dual origin, viz., in part due to _inflammatory products_ and in -part to _uratic deposits_, 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 _tophaceous_ matter, we shall best postpone -their consideration until we come to discuss the treatment of tophi. - -_Ionisation in Acute Gout._—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. - -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 _séance_, 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, _salicylic_ ions, by general consent, would appear to be the -most reliable. As far as I know, most authorities confine ionisation to -_chronic_ articular gout, and to this I shall refer later. - -_Massage._—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 _massage_, the outstanding -advantages of which find increasing appreciation. - -It need hardly be said that massage is contra-indicated in the acute, and -its use should be confined to the _subacute_, stage. Moreover, I would -suggest that its aid be sought more frequently during the _decline of -acute attacks_, 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 _absorption_ and _resolution_ of _tophi_, -for the uratic deposits, even when pre-existing, are often found after an -attack to be _softened and more mobile_, and now is the time to profit by -these changes, so as to compass their elimination. - -In these _subacute_ stages, of course, vigorous excitation must be -avoided, _effleurage_ or _light stroking_ being the only permissible -measure at this stage; and of course it should be exercised -_centripetally_. In presence of any marked sensitiveness, too, it is -advisable that _derivative_ massage of the limb above the joint should -always precede any direct friction of the latter. - -The measure of success will depend on the technique of the 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. - -Again, it is at the close of a massage _séance_ that _passive movements_ -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. - -_Surgical Methods._—The intensity of the inflammation and swelling in -acute gout has, as before said, sometimes led to its confusion with -_purulent arthritis_. It was just such a mishap that led Riedel to -discuss seriously the operative treatment of gout when of _monarticular_ -type, _e.g._, 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! - -Despite the apparent good results obtained, one can scarcely believe that -incision and removal of urates during _acute_ 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 -_chronic_ cases surgery has its sphere. But to this I shall return later, -when discussing the treatment of tophaceous deposits in chronic gout. - - - - -CHAPTER XXIX - -MEDICINAL AND OTHER MODES OF THERAPY (_continued_)—INTER-PAROXYSMAL PERIOD - - -TREATMENT IN THE INTER-PAROXYSMAL PERIOD - -Despite the fact that _heredity_ plays so dominant a _rôle_ in -the genesis of gout, how relatively scanty the attention paid to -_prophylactic_ measures! It is the _second_, 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. - -It was to this end that in a preceding chapter I urged the desirability -of more attention being paid to the _prodromal_ symptoms of gout and -the clarifying light that might be thrown on otherwise inexplicable -derangements by the disclosure of a _hereditary_ 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. - -The indications may, indeed, be more explicit, for, apart from hereditary -proneness, some subjects, even though they may never have experienced -an _articular_ outbreak, yet exhibit _tophi_, and therewith frequently -suffer from gastric or hepatic disturbance. Obviously, is not this -the opportune time for _prophylaxis_—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? - -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 and costiveness, signs of portal -congestion, etc., not to mention local symptoms, _i.e._, the onset of -pricking and tenderness in already existing tophi, twinges in the toes, -etc. - -We see therefore that in regard to the prophylaxis of gout the victims -fall into two main groups, _i.e._, 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 _prophylaxis_, whose chief -stay and strength must be the golden rule of _temperance_ in eating and -drinking conjoined with adequate exercise. For, whatever our views as to -the _proximate_ origin of gout, there is every reason to suppose that -the principal _exciting_ cause resides in the _alimentary_ 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 _dyspeptic_ symptoms are the -forerunners of attacks, and that their avoidance or timely correction is -the best means wherewith to avert paroxysms. - -As to the nature of the “indigestion,” it is of _subacute_ or _chronic_ -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. - -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 _inter-paroxysmal_ 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. - -The primary object of medicinal treatment is the restoration to -_functional efficiency_ of the _alimentary_ tract and its _accessory -glands_ and maintenance of the action of the _kidneys_ and _skin_. While -_diet_ 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 threatened gout without his -being obliged to forego his accustomed indulgence. - -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. - -The most common form of indigestion in the “gouty” is _atonic_ dyspepsia. -The primary indication is, of course, to correct the dietetic errors, -_i.e._, 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. - - ℞ Mag. carb. gr. 10 - Sodæ bicarb. gr. 15 - Tinct. nucis vomicæ ♏︎ 7 - Spts. chloroformi ♏︎ 10 - Infus. calumbæ ad unciam, ter in die sumenda ante cibos. - -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 _fermentation_ with _excessive -formation of organic acids_. It is to these that the “acid risings” are -due, and _not to excess of HCL_. Indeed, the reverse is the case, viz., a -_deficiency of HCL_. 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 _motor defect_, which may end in _dilatation_. - -For treatment of this condition careful _dieting_ alone may suffice. -Indeed, attention to general health often succeeds where _stomachic_ -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. - -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. - -Thus simply under a revised diet the acid eructations may 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. - -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 _alkalies_ must be given an hour or so _after_ meals to -correct the excess of _organic acids_. The same may be combined with -antiseptics—carbolic, B. naphthol, creosote, etc.—or some artificial -digestive, such as _papain_, _pancretin_, or _taka-diastase_. - - ℞ Bismuth carb. gr. 15 - Calcii carb. gr. 5 - Acid. carbol. pur. ♏︎ ½ - Oleum cajeput ♏︎ 2 - Fiat cachet, 1 or 2 an hour or more after meals. - -The _calcium_ and _bismuth_ carbonates are best, inasmuch as, though -they act slowly, they give rise to no _secondary hypersecretion_. 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 -_papain_ 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. - - ℞ Mag. carb. pond. gr. 15 - Sodii bicarb. gr. 10 - Papain gr. 3 - Oleum caryophylli ♏︎ ½ - Fiat cachet, 1 or 2 after meals when acidity is at its height. - -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”:— - - ℞ Mag. carb. gr. 10 - Sodii bicarb. gr. 15 - Acid. carbol. pur. ♏︎ 1 - Tinct. rhei co. ♏︎ 15 - Spts. chloroformi ♏︎ 15 - Inf. caryophylli ad unciam, ter in die post in cibos. - -Almost always in these cases more or less _constipation_ 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 _constitutional_ 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. - - ℞ Ext. colchici gr. ¼ - Aloin gr. ¼ - Menthol gr. ½ - Ext. rhei gr. 1 - Fiat pil., 1 alternis noctibus sumenda. - -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 _atonic_ “dyspepsia,” if of prolonged duration, gradually -merges into one of _chronic gastritis_. Especially in those given to -alcoholic indulgence do we meet with a condition of _mucous catarrh_, -with its associated _deficiency of hydrochloric acid_. Indeed, apart -from _alcoholic_ excess, such is the frequency in “gouty” subjects of -this form of “dyspepsia,” _i.e._, _fermentation with excess of organic -acids_, that I am inclined to think that the _subacidity_ which permits -of such developing is, if I may say so, the inherent digestive disability -in “gouty” subjects. Unquestionably _hyperacidity_—_i.e._, excess of -organic acids due to _hypochlorhydria_—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. - -Again, accepting the view that _infections_ 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 -_hydrochloric acid_. For this purpose it is well to use _strong_ or -_fuming_ 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 added -every few days until 10 or 15 minims are taken at each meal. - -Some years ago Armstrong, of Buxton, spoke highly of its value in -_alimentary toxæmia_, 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:— - - ℞ Acid. hydrochlor. dil. ♏︎ 10-15 - Glycerin pepsinæ dr. 1 - Liq. strych. hyd. ♏︎ 3 - Tinct. capsici ♏︎ 1 - Inf. aurantii co. ad unciam, ter die sumenda statim post cibos. - -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. - -In these cases, too, the _liver_ is frequently inactive, though often -their attacks of “biliousness” signify nothing but _constipation_; 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 _cholagogue_, 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. - -So much for the more common derangements of the _inter-paroxysmal_ period -and the measures wherewith to combat them. Collectively their aim is _the -restoration to functional efficiency of the alimentary canal and its -accessory glands_, this to the end that, as far as possible, a condition -of _intestinal asepsis_ may be attained, with its correlated diminution -of the excitants most fertile of outbreaks. - -Nevertheless, from time to time, either from failure of the patient’s -co-operation or other mischances, our best efforts at _prophylaxis_ -fail, and it becomes clear that an attack is _imminent_. What then, save -brisk _purgation_, 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 _before -the threatened attack_ to place the subject on a rigorous diet, this in -combination with a course of _alkalies_, those of _soda_ being given the -preference in _dyspeptic_ or _hepatic_ disturbance and those of _potash_ -when the _urine_ was _scanty_. - -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 _atophan_ is indicated, viz., _immediately before a -paroxysm_. At this particular time the _urinary output_ of _uric acid_ is -often _diminished_, a clear indication for enlistment of atophan, which -_increases uric acid elimination_. I note that both Retzlaff and Brugsch -consider it an especially advantageous time for its exhibition. As a -_prophylactic_ 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. - -Lastly, we have to recollect, too, that colchicum is credited with some -_prophylactic_ powers. Some, it is true, discountenance its employment -in the inter-paroxysmal period, on the plea that it tends to favour -_recurrence_ and _chronicity_ of attacks. While I think it is better to -reserve it for _acute_ or _subacute_ attacks, still I have not found that -colchicum, given in what Sir Thomas Watson called _alterative_ doses, -is anything but beneficial, provided that it be taken _intermittently_, -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.e._, -pricking and tenderness in existing tophi, twinges in the toes, etc. - -In conclusion, are we not in this matter of the _prophylaxis_ of gout -somewhat too prone to resort, both in and out of season, to what we are -pleased to term _special medication_? Almost every week some new and -of course infallible “uric acid solvent” is lauded _ad nauseam_ in the -press. Are not we ourselves, too, somewhat overanxious to go with the -tide in prescribing these vaunted “gout specifics”? - -The true aim of _prophylaxis_ is rather to _prevent_ the incidence of -those _functional derangements_ that in some subtle way determine the -disturbances in _nuclein_ metabolism, with _secondary_ accumulation of -_uric acid_ 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 _rôle_ in ridding the system of excessive amounts of -this chemical outcast, I fully admit. - -Albeit, this achievement does but deal with the _consequences_ or -_sequels_, 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. - - - - -CHAPTER XXX - -MEDICINAL AND OTHER MODES OF THERAPY (_continued_)—CHRONIC ARTICULAR GOUT -AND ASSOCIATED MORBID CONDITIONS - - -CHRONIC ARTICULAR GOUT - -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 _exciting_ causes becomes more and more pronounced. - -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 _personal idiosyncrasy_—a matter of much moment in -_prophylaxis_. - -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 _gastro-intestinal_ or _hepatic_ derangements, in others with -_defects of elimination_ through _kidneys_, _bowels_, or _skin_. - -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. - -The _joints_ in these cases are the seat of _chronic_ change, and though -they call for due attention, it is the _constitutional_ taint that is of -paramount importance. How best shall we influence this? How else save -by recognition of the morbid content of the _blood_ and cleansing of the -impurities with which it is charged? - -I have before stated my belief that _functional derangements_ of the -_alimentary canal_ are the _determining_ 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 _high uric acid content_ of the -_blood_ may presumably be referred. Yet nevertheless _retention_ of the -same in the form of _tophi_ may be relatively slight. Is it that in their -instance the avenues of _excretion_ are more permeable? - -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 _tophaceous deposits_ -often display _renal_ changes. In other words, it is the channels of -_elimination_ that appear to be at fault. - -But, more than likely, these superficial differences hark back to -infinitely more subtle inward disparities, to _tissue peculiarities_ -of function, with correlated variations in their _retention capacity -for uric acid_. Here again the clinician waits upon the bio-chemist, -and meanwhile must base his differential treatment on somewhat coarser -indices. - -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.” - -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 _pre-senilism_, 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. - -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 _alimentary -canal_ is the _fons et origo mali_, the major source of the provocatives -of gout, then the basal and essential part of our therapy must be _diet_ -and _regimen_. 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. - -_Alkalies._—It was formerly thought that by increasing the _alkalescence -of the blood_ its solvent effect on _uratic deposits_ 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.” - -Luff, again, from his investigations, held that administration of -the ordinary _alkalies_, of _lithium_ salts, of _piperazine_, and of -_lysidine_, 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. - -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 _uric -acid_ 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 -_every day_. Fagge, again, observes, “Alkalies are decidedly useful in -gout,” and the same views were held by the elder Garrod, Lecorche, and -Dieulafoy, etc. - -In short, forgetting for the moment the existence of uric acid and -shedding all hope of their dissolving _tophi_, we find that _alkalies_ -have ample justification besides for their employment. They are valuable -as _antacids_, _diuretics_, and as _alteratives_, and, moreover, their -routine employment has been tried and approved. - -In other words, the benefit of alkalies depends, not upon any special -solvent effect upon _uratic deposits_, but upon their remedial influence -upon associated and, I believe, causally related _gastric_ and _hepatic_ -disorders, and through these on general metabolism. Albeit, let us be -guided by rational considerations when we invoke their aid. - -The fact that alkalies are incapable of dissolving _tophi_ is a clear -indication that that deleterious habit of _continuously_ taking potash -and lithia water is not only unnecessary, but undesirable. Alkalies -should be prescribed in short courses and to meet special indications, -_i.e._, _intermittent_, not continuous, administration. - -Thus in the minor _gastric_ disturbances which in chronic gout we are -constantly called upon to treat there is no doubt as to the superiority -of the _sodium_ compounds. Moreover, apart from their value in _gastric_ -or _intestinal_ catarrh, we have to note their usefulness in dyspeptic -states complicated by _torpid liver_. - -When _constipation_ 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. - -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, _stomachics_ are the most valuable tonics in gout. -Lastly, it is in the _inter-paroxysmal_ periods of _chronic_ 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 _gastric tone_, with or without acidity. - -As to the _potash_ 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 -_diuretic_ 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 _antacid_ effect is desired, in which -case it should be replaced by the bicarbonate. - -In those instances in which the _skin_ 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. - -As to the _lithium_ 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 -_caveat_: “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.” - -In conclusion, it will be seen that clinical experience testifies with -no doubtful voice to the value of most salines. At the same 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 _antacid_ -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. - -_Alteratives._—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. - -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 _tophi_. 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. - -_Iodides._—Turning to well-tried alterative remedies, there is no doubt -that the _iodides_ 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 _par excellence_ our most -reliable remedy. - -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:— - - ℞ Pot. iodidi gr. 5-10 - Pot. bicarb. gr. 15 - Spts. ammon. aromat. ♏︎ 20 - Vin. colchici. ♏︎ 5 - Tinct. capsici. ♏︎ 1 - Inf. aurantii co. ad unciam ter in die sumenda post cibos. - -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. _Iodine-albumen_ 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 _iodo-protein_ 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. - -An organic compound of iodine with vegetable albumen, _i.e._, -_iodo-glidine_, has been somewhat extensively used in gout, as being -_non-depressant_. 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. - -More recently the advantages of _collosol_ preparations of _iodine_ 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.” - -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.” - -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. - -For internal administration colloidal iodine is prepared in 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. - -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. - -Lastly, too, apart from their use in _chronic gouty arthritis_, we -have to recollect that the iodides are the most reliable means we -possess of influencing the _renal_ and _vascular_ changes so often -associated with gout. Garrod doubted if they possessed any power of -promoting the dissipation of _uratic deposits_, but their power of -eliminating _lead_ must not be lost sight of when treating gout in the -subjects of _plumbism_. 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 -_atophan_—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. - -_Guaiacum._—Many years ago, Sir Alfred Garrod[62] 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 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 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.” - -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. - -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. - - ℞ Hydrarg. sub chlor. gr. ⅟₁₀ - Guaiaci resinæ gr. 3 - Sulph. precip. gr. 3 - Fiat. cachet. Ter in die sumenda post cibos. - -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. - -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. - -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:— - - ℞ Sulph. precip. - Pulv. guaiaci - Pot. bitart. āā ʒj. - Pulv. tragac. co. ʒij. - Fiat pulv., ½ to 1 teaspoonful to be taken stirred up in water - or milk at bedtime. - -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. - -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:— - - ℞ Acidi arseniosi gr. ⅟₈₀ - Potassii iodidi gr. 1 - Pulveris rhei - Extracti gentianæ āā q.s. - Misce. Fiat pilula i. “Two pills to be taken daily at meal time.” - -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 _empirical_, 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 _results_. 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. - -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 devise a rational system of drug treatment -whereby to antagonise the same. For us, then, the wiser, if more -humble, _rôle_ 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 _vis medicatrix naturæ_, -whereby the balance of the nuclein exchanges is restored. - - -_Local Measures in Chronic Articular Gout_ - -When treating of these in relation to _acute_ articular gout, we dealt -with the topical applications best calculated to achieve the absorption -of _inflammatory_ 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., _uratic deposition_. - -_Treatment of Tophi._—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 _inflammatory_ thickening, he sometimes used a -solution composed of equal parts of iodide of potassium and carbonate of -lithia. - -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. - -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. - -_Ionisation._—We may enlist _cataphoresis_, either for its _analgesic_ or -its _sclerolytic_ 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. - -If we wish to exercise a favourable stimulant effect in alterations of -nutrition and atrophy caused by gouty inflammation, the _chlorine_ 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. - -_Iodine_ 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. - -In chronic gouty arthritis we are, as before remarked, confronted not -only with inflammatory products, but also with _uratic deposits_. -Fortunately, these latter also are benefited by the electrolytic -introduction of the lithium ion under an anode of _lithium chloride_. The -current serves a double purpose in this case, for it not only drives in -the lithium, but removes the _uric acid_ ion which is to be found in the -electrode. Edison, some years ago, suggested ionisation with _lithium_ -in gout, and the good results he obtained have since been abundantly -confirmed by others. - -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 _uric acid_ in the fluid -of the bath, thus demonstrating introduction of the cation-lithium and -removal of the _anion-uric acid_ at one and the same time. In this way -proof is adduced that the lithium penetrates the tissues, and coming -directly into contact with _uratic deposit_, tends partly to dissolve it. - -To achieve the dual purpose, viz., _absorption_ of _inflammatory_ and -_uratic deposits_, 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 -_séances_ a week will suffice, but where time presses, the sittings, -according to Leduc, may be given daily, always provided 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 _séances_ is -necessary. Also I would suggest that the simultaneous taking of a course -of atophan would appear to be indicated. - -_Surgical Treatment._—In pre-antiseptic days, catastrophes, _e.g._, -_erysipelas_, _gangrene_, 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. - -Moreover, the old view that incision or evacuation of tophi was followed -by obstinate _ulceration_ 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. - -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.” - -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 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.” - -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, _spontaneous disappearance of tophi may follow a subsequent -attack of gout_, 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.” - -Now, if we take Riedel’s two instances of _acute_ gout and their -tolerance of incision and local cleansing of urates and the equally happy -tolerance exhibited by Alexis Thomson’s two cases of _chronic_ gout, we -see that, in these days of aseptic surgery, even _gouty arthritis_ can no -longer be regarded as outside the pale of operative interference. But, -as a _caveat_ 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. - -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. - - -TREATMENT OF ASSOCIATED MORBID CONDITIONS - -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 _acute_ attacks and alike in the _inter-paroxysmal_ periods -gouty subjects are prone to two special varieties of fibrositis, viz., -_lumbago_ and _sciatica_. 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 _regular_ or _articular_ gout. - -_Fibrositis._—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. - -Whatever the type of fibrositis we are confronted with, the therapeutic -indications are precisely similar to those advocated for _articular_ -gout. In other words, the indispensable preliminary measures are to -control the production, absorption, and elimination of _toxins_. 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 _pyrexia_ -indicate clearly that these cases of acute fibrositis must be treated in -accordance with the general rules applicable to the febrile state. - -_Acute Lumbago._—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:— - - ℞ Pot. bicarb. gr. 15 - Pot. nitrat. gr. 10 - Vin. colchici ♏︎ 10-15 - Aquæ ad unciam, quartis horis sumenda. - -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 -_colchicum_ succeeds best. On the other hand, in some 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 _salicylates_ 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. - -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. - -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 _gouty_ basis in such cases and the advisability of -combining _colchicum_ with our remedies. - -_Sciatica._—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. - -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:— - - ℞ Quin. hydrochloratis ½ drachm. - Pot. iodidi 2 drachms. - Vin. colchici 1 ounce. - Tinct. aurantii 2 ounces. - Aquam chloroformi To 8 ounces. - Sig., 2 teaspoonfuls in a wineglass of water twice a day. - -Having regard also to the gouty origin, it is hardly necessary to insist -on regular and adequate evacuation of the bowels. - -Of all varieties of gouty fibrositis the _acute brachial_ 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 bear in -mind its evil potentialities; but only too often they do not come under -observation until the condition is well established. - -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. - -In reviewing the foregoing acute types of fibrositis, I would, as to -_relief of pain_, 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. - -In _chronic_ or _recurring_ 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. - -It is for this reason that I have elsewhere advocated early resort to -_local massage_, 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. - -_Oxaluria._—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. - -All vegetables rich in oxalates, such as rhubarb and spinach, 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.e._, 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. - -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. - -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.e._, -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. - -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. - -_Glycosuria._—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. - -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 diabetes, the treatment -of which grave disorder is beyond the scope of this work. - -_Hyperchlorhydria._—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. - -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. - -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. - -The medicinal indication is to afford relief during the acute attacks. -Fortunately these are usually _intermittent_, and when the occasion -arises are fairly readily controlled by massive doses of alkalies, -frequently combined with an artificial digestive, _i.e._, 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. - -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. - -_Gouty Phlebitis._—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 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. - -_Gouty Eczema._—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. - -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. - -_Gouty Nephritis._—This must be treated on the lines recognised as -suitable for _chronic Bright’s disease_, the underlying gouty condition -being always borne in mind, as also any contamination with _lead_. 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. - -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 -_vaso-dilators_, premature resort to which has often proved the beginning -of the end. - -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 age would account for, -and equally often no symptoms indicative of raised blood pressure are -complained of. Why then make the subject miserable? - -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. - -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, _e.g._, 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:— - - ℞ Sodium nitrite gr. ½-2 - Potassium nitrate gr. 10-20 - Potassium bicarb. gr. 10-30 - Fiat pulvis, to be taken in a tumblerful of water every morning. - -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. - -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. - - - - -CHAPTER XXXI. - -CLIMATO-THERAPY, HYDRO-THERAPY, ETC - - -CLIMATE AND RESIDENCE - -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 _season_, viz., the aptness of gout to recur in -spring and autumn, especially in its _early_ stages, is a very singular -feature. - -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. - -In short, a _variable_ 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 _individual constitutional peculiarities_. - -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. - -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. - -If one may be permitted the generalisation, the ideal climatic -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. - -Still, some discrimination must be shown in the matter of choice, and the -physician, while mindful of the gout, must envisage the _individual_ 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. - -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 _rest_ and _recreation_ 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 _psychic_, -not physical, to achieve its beneficent ends! - -Still, not always is it _rest_ that is needed, and some regard must be -had to previous habits. Thus, for the _sedentary_, repair to a _bracing_ -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. - -On the other hand, for the elderly or old, or those enervated by -long-continued gout, a _sedative_ 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. - -Frequently, however, our choice is dominated by some _associated morbid -affection_. Our patient may suffer from a so-called gouty _eczema_; 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. - -If _renal_ 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 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. - -If to go abroad is out of the question, one of the mild southwestern -seaside resorts at home is eligible, _i.e._, Bournemouth, Sidmouth, or -the more sheltered parts of Torquay, and Falmouth. Again, if he show -a tendency to _cardiac dilatation_, 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. - -Lastly, before despatching any gouty subject for a so-called change, it -is wise to elicit any personal _idiosyncrasies_ 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. - -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 _climatic therapy_ 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. - -_Choice of Residence._—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. - -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 jar of ill-assorted or discordant -elements, that forbid that cheerful intercourse that does much to restore -that sense of _bien-être_ so eagerly sought. - -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 _well-situated_ and _sanitary_ -residence. I allude, of course, here to a _permanent_ abode, and the -gouty, if he enjoy any latitude, should live in a house built on a -_well-drained gravel soil on a slope, sheltered from the north and -north-east winds_. - -Again, with the question of habitation is bound up the equally important -matter of _clothing_. By our forefathers _flannel_ 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 _silk_ as being, perhaps, -the ideal _underwear_; 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 _static -deformities_, 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. - -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. - -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 -_time of year_. 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. - - -EXERCISE - -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 and idle ways not -only favour the invasion of the disorder but hasten its recurrence. - -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. - -Again, it is notorious that in those in whom the brunt of the disorder -falls on the _lower_ 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 _systematic_ 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. - -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 _massage_ before proceeding to active exercise. For not seldom such -subjects have but a small fund of nerve energy to draw upon. - -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 _chronic_ diseases, and had the art -likewise of concealing it, he might easily raise a considerable fortune.” - -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. 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. - - “Orandum est, ut sit mens sana in corpore sano.” - - -GENERAL MASSAGE - -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 -_bien-être_ is promoted. - -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 _prophylactic_ effects. - -It is the more especially indicated in those gouty subjects prone to -attacks of _muscular fibrositis_—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. - -In enlisting the _prophylactic_ action of general massage, it is not -desirable that the _séance_ 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. - -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. - - -GENERAL HYDRO-THERAPY - -That hydro-therapy constitutes one of the most effective, if not _the_ -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 _exposure of the whole body_. In other words, -those measures directed more especially to treatment of the _underlying -causal state_—the correction of that warp of metabolism or auto-toxic -state of which the arthritic, muscular, or other lesions are but local -manifestations. - -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 _thorough physical examination_ 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. - -For in hydro-therapy the personal equation is of prime importance, -varying with _individual reactive peculiarities_. 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. - -Thus _nervous irritability_ is _the_ 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. - -Others suffer from _torpid circulation_ and _sluggish vascular response_, -and in their instance, stimulant measures, hot or cold, in sequence -or in alternation, are indicated. Again, some are _obese_, and others -_lean_, 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. - -_Prophylactic Measures._—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 _cold_ or _sub-thermal_ -impressions. - -Of the value of _thermal_ applications in chronic gout I am -convinced, but, on the other hand, we must not blind ourselves to the -value—_prophylactically_ speaking—of their judicious conjunction with -_sub-thermal_ or _cold_ 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. - -Prophylactic measures to be of any real avail must be _continuous_, -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. - -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. - -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. - -_Contra-indications and Untoward Complications._—Authorities generally -seem unanimous on this point, viz., that the chief sphere of -hydro-therapy is in _chronic_ or subacute gout. On the other hand, they -are equally unanimous in proscribing its exhibition in _acute_ 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. - -Nor do I think it advisable if _prodromal_ 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 _acute outbreak_ 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 _rôle_ 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 -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. - -Indeed, I would go further, in that I think that, under all -circumstances, a course of hydro-therapy should be preceded by _free -evacuation of the bowels_. 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 _internal_ but -_external_ use of mineral waters. I allude to _dyspepsia_, _lassitude_, -or _skin eruptions_, 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 _auto-intoxication_, 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 _pending their disappearance_ under appropriate -measures. - -In the same way, there are reservations regarding the suitability of -baths in _chronic_ gout. Thus, if complicated by advanced _cardiac_ or -_renal_ disease, hydro-therapy is often _contra-indicated_, 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 _renal_ disease in which the _heart_ is hampered by increased -_peripheral_ resistance. Such cases under Aix massage, frequently, as -Bain and Edgecombe pointed out, improve strikingly through the consequent -reduction of arterial pressure. - -Turning now to the _untoward results_ or _complications of -hydro-therapy_, hot baths, if of too high a temperature or too -prolonged, may cause _vertigo_, _fainting_, or _palpitation_—an -indication for reduction in temperature and duration. Or, if douches -are used, the pressure may be excessive. _Insomnia_, 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. - -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. - -Examination of the _urine_, too, may yield indications of value. A -notable increase in the output of _chlorides_ suggests excessive tissue -waste, and of _phosphates_ too marked excitation of the nerve 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. - - -METHODS OF APPLICATION OF GENERAL HYDRO-THERAPY - -Subject to reservations, stimulant hydro-therapeutic procedures are in -_chronic_ gout _the_ special indication. Thermal waters, therefore, are, -generally speaking, the most suitable, and _cæteris paribus_, 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. - -Having regard to their _radio-active_ 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. - -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, _lumbago_ and _sciatica_. 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. - -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. - -Again, gouty subjects not seldom suffer with _high blood pressure_, -and our treatment must be modified accordingly. Here we may enlist -what are known as _Aix massage_ baths, which tend to _lower_ 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 _terminal cold application_ be invoked. On the other hand, in some -cases of chronic gout the abdominal musculature is very flabby, with a -tendency to _visceroptosis_ and _low blood pressure_. In their instance, -a _Vichy bath_, inasmuch as it tends to _raise_ the blood pressure, is -preferable to Aix massage. - -Another powerful method at our disposal for the elimination of waste -products is the _vapour_ bath. It is not suitable for the old and feeble, -or those with advanced _cardiac_ or _renal_ disease, but it is especially -adapted to gouty subjects with _harsh_, _thickened_ or _irritable_ skin, -and those of _obese_ habit. - -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, _sub-thermal_ baths -(82° to 97° F.) have a great sphere of usefulness. Thus in the presence -of _high arterial pressure_, 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 -_sedative_ action, such neutral baths are peculiarly eligible also for -all types of gout associated with _insomnia_, irritable skin affections, -or showing signs of vasomotor instability. - -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 _natural mineral waters_ -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. - - -METHODS OF LOCAL HYDRO-THERAPY - -In one form or another, _douches_ 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 _cæteris -paribus_, the more massive the volume, the more marked the results -produced. - -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. - -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. - -The space at our disposal forbids entering into great detail, 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. - -For the relief of _stiffness_ and _swelling_ 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. - -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. - - -TREATMENT BY HYPERÆMIA - -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 -_luminous_ and _non-luminous_ types—are so extensively employed in gout, -either for their curative or prophylactic action. - -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 _pyrexia_. Nor are they appropriate if the case is -complicated by any irritable _skin condition_, or in the graver forms of -_glycosuria_. They are unsuitable, too, if there are any evidences of -_hyper-thyroidism_, from which the gouty, no more than others, are immune. - -Again, in _cardiac dilatation_ they must be exhibited with great caution, -and where extreme, are of course impermissible, as also in the later -stages of _chronic nephritis_. On the other hand, they are eminently -suitable for the treatment of _fibrositis_ in gouty persons, especially -of obese type, nor does the presence of _glycosuria_ in such association -constitute a bar to their use. - -Moreover, as a _prophylactic_ 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 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. - -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. - - - - -CHAPTER XXXII - -MINERAL SPRINGS AND CHOICE OF SPA - - -MINERAL SPRINGS - -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. - -Naturally, “mineral waters” being so refractory of _definition_, it -follows that all suggested _classifications_ 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 _chemical_ 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.” - -“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 _water_ itself, its flushing effects in washing out urates -and other toxic substances. - -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? - -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 _empirically_, says -the critic, forgetful that the use of _colchicum_ 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. - -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?[63] 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 -_radio-activity_. - -For alike in simple thermal, sulphurous, alkaline, sulphated alkaline, -or muriated waters, the presence of radio-activity has been established. -But if, _e.g._, in the _simple thermal_, 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 _mineral_ constituents—these present in -sufficient quantity to exert a _specific_ action, alterative, aperient, -tonic, etc. - -In this matter of _mineral_ 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 _sodium_ 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. - -This behaviour on the part of the carbonates, bicarbonates, and -phosphates of sodium led him to the sweeping generalisation that all -sodium salts, including the chloride, were, as far as practicable, to be -avoided by _gouty_ subjects. Naturally, in conformity with this view, -such patients were warned to flee those spas whose waters contained these -peccant salts. - -Carried to its logical end, this dictum would have cut the gouty off -from, _e.g._, 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. - -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.” - -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. - -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 _uric acid_. - -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,— - - (1) The quantity of water, more or less pure, taken into the - body under regulated conditions daily. - - (2) The altered mode of life, the regular exercise in the - open air, the modified diet, the early hours, the absence of - business cares. - - (3) In many foreign spas there is the drier and hotter - Continental climate. - - (4) The stimulating effect to excretion and “tissue change” - which the baths, douches, frictions, and manipulations applied - at most of them induce. - -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. - -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 _cæteris paribus_, -that natural spring will suit him best whose mineral or other content is -best calculated to correct or minimise his particular deficiency. - -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 _all natural springs_ this or -that particular mineral water is _par excellence_ 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 _individual peculiarities_ upon which our -_selection of a spa_ will depend. - -To sum up, in consonance with these views, the general principles of spa -treatment, as I take it, are:— - - (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. - - (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. - - (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. - -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 _radio-active_ 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. - - -RADIO-ACTIVE WATERS - -As to the physical properties of _radium_, it is, according to the -theory of transformation, a “changing element,” emitting alpha, beta, -and gamma rays, and in addition a radio-active emanation. 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. - -This expulsion of helium having ensued, the parent atom no longer exists -as radium, but as _radium emanation_, or _niton_, 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 _emanation_ derived from -it.[64] - -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. - -_Physiological Action of Radium Emanation._—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 the inhalation is prolonged -sufficiently, saturation of the blood therewith ensues, to be followed by -its escape _viâ_ the lungs, intestines, kidneys, and skin. - -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 _hours_ for -complete excretion. On the other hand, when _inhaled_ the emanation is -quickly absorbed and as swiftly excreted, _i.e._, within a few _seconds_. -As to its power of penetrating the _skin_ 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 _sub judice_. - -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 _proteolytic_, _glycolytic_, -and _diastatic ferments_ 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. - -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 _rôle_. - - -INFLUENCE ON URIC ACID METABOLISM - -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 of the unstable and more soluble -_lactam_ into relatively insoluble and stable _lactim_ urate, this latter -being the salt found in the blood of the gouty. - -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. - -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. - -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 _Lancet’s_ special commission -for investigation of the Bath waters: “The thermal waters of Bath exert a -distinct solvent action on uric acid; in our experiments, _e.g._, 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.e._, 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.” - -_Increased Excretion of Uric Acid._—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 -_séance_ of emanation, but also that this enhanced power of coping with -purins is maintained subsequently. - -_Subjective Phenomena of Gout in Relation to Blood Content and Excretion -of Uric Acid._—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. - -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. - -Turning to the _excretion of uric acid in the urine_, 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. - -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 _beneficial -effect of radio-active waters in gout_ involves something more than -the _dissipation of the uric acid in the blood_ and _its increased -elimination in the urine_. - - -THERAPEUTIC ACTION AND APPLICATION - -We have in previous sections emphasised the importance of treating _local -foci of infection_, 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. - -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 _oral sepsis_ 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. - -Again, it is recognised that _pharyngeal_ and _nasal_ affections when -present derive benefit from the _inhalation_ of _radio-active waters_ -atomised by steam or air. In this connection it may be 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. - -_Alimentary Disorders._—Accepting the fact that _gastro-intestinal -derangements_ are the most common _excitants_ 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 _activating the -body ferments_. 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. - -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. - -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 _sedative_ 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? - -Again, _intestinal irrigation_ 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. - -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 _glycosuria_ 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 _increased arterial blood pressure_. For it has been -shown by Deutelmoser, Saubermann, and others that under the influence of -radium emanations the blood pressure is reduced. - -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. - -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. - - -CHOICE OF SPA - -While naturally my attention has been largely centred upon the mineral -waters of Bath, I would by no means convey the impression that a _thermal -radio-active_ 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. - -Nevertheless, as I have said, I favour the tendency towards -_specialisation of spas_, 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. - -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 _individual_ himself, and not the least important of -the considerations involved have been already embodied in my remarks on -_climato-therapy_. For the ideal sought, if I may again say so, is not -only _physical_, but _psycho-physical_; and the physician who leaves out -the mental element will scarcely choose wisely. - -Narrowing our field to consideration of the _physical_ requirements of -the subject under review, what manner of man is he, _metabolically_ -speaking? Is he of _spare_ habit, one in whom katabolic changes hold sway -and “the vital fires blaze more fiercely,” or is he _obese_, one in whom -anabolic processes are dominant, with hoarding up of substance? - -Now, I have taken these two types, the _spare_ and the _obese_, as in -gout we are dealing primarily with a “disorder of nutrition.” _Cæteris -paribus_, we wish to correct the morbid metabolic trend, in other words -provide differential treatment. Obviously the salient indication in the -_lean_ 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. - -To compass such effects, _muriated_ 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 _do not cause emaciation_. 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. - -The _muriated_ (chloride-containing) _alkaline_ 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 _simple alkaline_ waters, such as Vichy, Vals, -Neuenahr. - -Reverting now to the _obese_, 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. - -The class of waters pre-eminently suitable will be those known as -the _sulphated_ and the _sulphated alkaline_ varieties, which, taken -internally, will through their purgative and diuretic effects assist our -purpose. The stronger varieties of the _sulphated_ waters are chiefly -used as occasional aperients at home, as, generally speaking, at the site -of the spring there is no proper spa accommodation. We allude to Franz -Joseph, Hunyadi Janos, Rubinat, and Condal waters, etc. - -In England several _sulphated_ 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. - -It is, however, the _sulphated-alkaline_ 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 _anæmia_. If so we may with advantage choose -Tarasp, which, in addition to sulphated alkaline, has _chalybeate_ -waters, and the same dual advantages are to be found at Marienbad. - -For those unable to go abroad the _muriated sulphated_ 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 _muriated sulphur water_, substituted in anæmic cases by a -chalybeate water in conjunction with an aperient. - -So much for the broader indications, _metabolically_ 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. - -_Dyspepsia and Chronic Gastro-intestinal Disorders._—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 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 -_over-fatigue_ must be guarded against. - -Indeed, in the more aggravated types of so-called gouty dyspepsia there -is little doubt that sojourn in a _sanatorium_ 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. - -Passing to the question of _mineral waters_, there is no doubt that a -previous investigation of the _secretory_ and _motor_ 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. - -Thus it has generally been supposed that _simple alkaline_ mineral waters -promote the secretion of acid gastric juice. But Pawlow, experimenting on -dogs, found that alkaline sodium salts tended rather to _inhibit_ 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. - -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[65]; 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. - -Thus he suggests that “a possible explanation of the beneficial -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.” - -From his experiments Bickel came to the conclusion that in conditions of -_subacidity_ supervening on chronic gastric catarrh the most suitable are -_muriated_ waters, or _muriated alkaline_ waters, or simple _gaseous_ -waters. - -_Gastric Insufficiency, or Atonic Dyspepsia._—Now, as I have before -emphasised, this is the functional gastric disorder most commonly met -with in the gouty; the _hyperacidity_ is due to _excess of organic -acids_, and this, again, is the outcome of not excess, but _deficiency, -of HCL_. Now in cases of this nature with _subacidity_ 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 _muriated_ waters. - -My own clinical experience of the _muriated_ 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. - -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. - -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 _muriated_ as in the sulphurous group. Again, 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. - -As to the Continental springs in this category, the most noteworthy are -Homburg, Kissingen, and Kreuznach, the last decidedly radio-active; while -of _thermal muriated_ waters Wiesbaden and Baden-Baden are the most -representative. - -_Chronic Gastric Catarrh._—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. - -Leaving aside the vexed question as to whether _muriated_ 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. - -Now, while in these cases the _muriated_ waters above alluded to are -suitable, the _muriated alkaline_ are equally eligible. Of these the -highest in repute are Royat, Chatel Guyon, and Saint Nectaire, and in -Germany Ems, Wildbad, Assmannshausen, and Wildungen. - -Here a reservation in regard to Bickel’s researches, viz., it has been -found that in some cases of _chronic gastric catarrh_ in _robust_ -subjects _simple alkaline_ springs, such as those of Vichy, Vals, and -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 -_simple alkaline waters_ are more likely to produce an attack of _acute -gout_, whereas the _muriated alkaline_ varieties are free from these -objections. - -_Hyperchlorhydria._—Bickel’s experiments led him to this further -conclusion, that in organic gastric disorders accompanied by _excess -of HCL_ the _simple alkaline_ and _sulphated alkaline_ group are to be -preferred to the _muriated_ waters. - -Now, inasmuch as some authorities hold hyperchlorhydria as due to a -_chronic glandular gastritis_, 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. - -Much controversy, again, obtains in regard of the usage of _muriated_ -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. - -But the experience of most of us will accord with that of Dapper and Von -Noorden, that _muriated_ 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. - -Fortunately this secretion of an abnormally acid gastric juice is -relatively rare in the _gouty_. Being of the nature of a _secretory -neurosis_, it occurs most frequently in those of _neurotic_ or -_neurasthenic_ 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. - -But, as we have seen, these same _muriated_ waters prove most salutary -in precisely the opposite condition—_hypochlorhydria, or deficiency of -HCL_. That such a beneficial effect should ensue in diametrically opposed -states, viz., _hyper_- and _hypo_-acidity, gives point, I think, to the -contention that the action of _muriated_ waters on the digestive organs -must in great part be exerted not locally, but _indirectly_, that is, -secondarily to improvement of the general health and toning up of the -nervous system. - -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. - -_Functional Hepatic Disorders._—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. - -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. - -As to treatment of these cases by mineral waters, a preference must -be given to _alkaline_, _sulphated alkaline_, or _muriated_ 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 _sulphated alkaline_ waters (Marienbad, -Karlsbad, etc.) may be recommended. But equally good results will follow -a course at home of _muriated_ waters, or _muriated sulphur_ waters, such -as Harrogate, Llanwyrtid, and Strathpeffer, etc. - -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.[66] - -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. - -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 _after_ -operations for the removal of gall-stones; others advocate their -employment _before_ 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. - -_Intestinal Derangements._—Constipation is, as is well known, the _bête -noire_ 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. - -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. - -On the other hand, the Plombières Spa is the one that _par excellence_ -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. 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. - - -ASSOCIATED MORBID CONDITIONS - -_Glycosuria._—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. - -In the gouty obese, with a tendency to piles and abdominal plethora, the -_sulphated alkaline_ and _simple alkaline_ waters, such as Karlsbad, -Vichy, Neuenahr, Brides-les-Bains, etc., are suitable, and in this -country the _muriated sulphurous_ waters of Harrogate and Llandrindod. - -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 -_earthy or calcareous_ waters enjoy a considerable reputation, notably -Contrexéville, and not a few with uric acid gravel and slight albuminuria -resort to Wildungen. - -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.” - -_Oxaluria._—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 _muriated_ springs in this country -or to Kissingen, Homburg, etc., is advisable. Otherwise, _alkaline_ -springs, _i.e._, Vichy, or _alkaline earthy_ 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. - -_Gouty Phlebitis._—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.). - -_Respiratory Disorders._—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, _e.g._, 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. - -_Fibrositis._—Adequately to describe all the methods, internal and -external, in vogue at spas for the treatment of, _e.g._, 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. - -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. - -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 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. - -_Gouty Eczema._—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. - -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. - -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. - -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, _e.g._, Schinznach, Aix-les-Bains, -Bagnères-de-Luchon, etc., are highly commended. - -_Uric Acid Gravel._—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. - -_Arterio-sclerosis._—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. - -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 French rival to Nauheim, because of the -excellent results obtained in cases of raised blood pressure. - -_Chronic Nephritis._—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. - -Of mineral waters the _simple thermal_ or the _weak alkaline_ are -generally considered the most eligible, _e.g._, 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.” - -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, _e.g._, -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. - - -CONCLUDING REMARKS ON SPA TREATMENT - -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 _balneotherapy_, _electro-therapy_, 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 _internal_ exhibition of -mineral waters. - -In this matter the rules laid down for hydrotherapy, or the _external_ -use of waters, are in the main applicable. In other words, _acute cases -of gout are always ineligible_, as likewise those instances in which -an attack appears imminent or those in which recovery from an _acute_ -paroxysm is barely accomplished. On the other hand, mineral waters are -indicated in _chronic_ gout and in the _inter-paroxysmal_ periods that -mark the _early_ 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.” - -But, to attain the best results of spa treatment, not only should the -cases be suitable, but they should be despatched at the right _season_. -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, _e.g._, Bath, -Wiesbaden, Helouan, etc. - -As to _duration_ 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. - -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. - -Again, I think perhaps in this country the advantages of an _after-cure_ -are insufficiently realised. In this respect our Continental brethren -set us an example, attaching the greatest importance as they do to -an after-cure, especially after a course of laxative waters, _e.g._, -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 _non-bathing_ 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 _after-cures_, 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! - -As to the nature and site of the resorts suitable for an _after-cure_ -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. - - -SPAS FROM A NATIONAL ASPECT - -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 _complementary_, 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. - -Now what, in a word, is the outstanding feature of our national life -to-day? _Co-operation_—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 _rôle_ 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 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. - -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 _natural_ products; both are _national_ -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 _unification_ and _co-ordination_ 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.” - - - - -FOOTNOTES - - -[1] Ewart, discussing the antiquity of gout, observes that it is -“certainly as ancient as civilisation,” and as far as we can identify -them in the accounts handed down from remote ages, the etiology, the -leading symptoms, the outward characters of the _articular_ gout of the -ancients were practically the same as belong to gout in our own times! -But of its relative prevalence in antiquity we have no means of judging. -Continuing, he holds that “the ultimate lesions of gouty arthritis and -its pathology are presumably as immutable as those of osteoarthritis.” -This may be so, but such objective evidence as we possess certainly -points to the greater antiquity of osteoarthritis as the following -quotation from our work, “Arthritis Deformans,” testifies:— - -“During the course of some excavations undertaken by the Survey -Department of the Egyptian Government in that tract of Nubia lying -immediately south of the First Cataract, over 6,000 bodies were brought -to light, comprising among them representatives of all periods from -early pre-dynastic times down to the fifth century after Christ. As the -result of their examination of this vast accumulation of human _débris_, -Professor Elliot Smith, in the Nubian Survey Bulletin, states that “The -disease which shows itself with by far the greatest frequency in the -bodies of all periods is rheumatoid arthritis” (Osteoarthritis). - -[2] 920 (S. Eng. Leg.), “There cam a goute In is knee, of Anguische -gret.... So longue, that is kneo to-swal.” - -1310 (In Wright Lyric), “A goute me hath ygreythed so, Ant other eveles -monye mo.” - -1377 (Langl., P. Pl.), “He ... gyued me in goutes, I may noughte go at -large.” - -1400 (Lanfranc’s Cirurg.), “A man that hath arteticam, that is as myche -to seie as a goute.” - -1450 (M.E. Med. Bk., Heinrich), “Here wyth anoynte the goutes.” - -1566 (J. Alday, tr. Baoystuau’s Theat. World), “Their legges full of -gouts.” - -1579 (Langham, Gard. Health, 1633), “For all goutes, seethe Leekes and -Otemeale with sheepes tallow, and apply them hot.” - -1590 (Spenser, F. Q.), “And eke in foote and hand A grievous gout -tormented him full sore.” - -1697 (Dryden, Virg. Georg.), “From Winter keep Well fodder’d in the -Stalls, they tender Sheep.... That free from Gouts thou mayst preserve -thy Care.” - -1704 (Fuller, Med. Gymn.), “There have been some Gouts ... which nothing -could remove but a very low Diet.” - -1732 (Pope, Ess. Man.), “So, when small humours gather to a gout The -Doctor fancies he has driv’n ’em out.” - -1822 (Ld. Eldon, in Twiss Life), “I found the King in bed yesterday. He -has had a pretty severe gout.”—_New English Dictionary, Oxford_, 1901. -(_Ed. Sir James Murrary._) - -[3] Pitt, in one of his last letters to the Marquess Wellesley, deplores -his slow recovery from severe attacks of gout with which, by the bye, the -statesman Fox was likewise affected. - -[4] Both Norman Moore and Bowlby subsequently upheld Ord’s view that -uratic deposits only occur in tissues already degenerated. “Ebstein’s -view has been modified by Von Noorden, who holds that a special ferment -leads to the tissue change, to which the deposit of the urate is -secondary.” - -[5] _Physiognomy of the Goutily Disposed._—Taking the principles as laid -down by Laycock, the peculiarities of those thus affected fall under the -head of the sanguine arthritic diathesis. (That careful observer did -not fail to note the modifying influences of gout upon struma and other -cachexia.) Thus may be compared the physiognomy of the diathesis and its -associated cachexia (developed in time):— - -Blood-vessels numerous; heart large and powerful; blood-corpuscles -numerous; skin over malar bones highly vascular (florid complexion); -skin fair, firm, oleaginous, perspirable; eyes blue; hair thick, not -falling easily; teeth massive, well-enamelled, regular, even, undecayed -in advanced life; malar bones flattened; head symmetrical; nasal bones -well-formed, nose aquiline or of mixed form; lower jaw massive; lips -symmetrical. - -_Form._—Figure for the most part tall; thorax broad at the summit; ribs -well-curved; abdomen full; muscles firm, large; limbs large, robust; gait -erect, well-poised. _Nutrition_ active; digestion vigorous; appetite -great for animal food and alcoholic stimuli. _Respiration_ deliberate, -deep; circulation vigorous; animal heat abundant; locomotion active; -aptitude for exercise and outdoor amusements. _Reproductive_ powers -active; innervation abundant, the mental powers vigorous and enduring. - -_Physiognomy of the Sanguine Gouty Cachexia._—Blood-vessels largely -developed over the malar bones and varicose; skin oily, yellow from -subcutaneous deposit of fat; hair thick and white; teeth numerous, -discoloured, crusted with tartar; lips bluish, nose reddish, -hypertrophied; arcus senilis; abdomen pendulous; limbs thick; joints -nodose; nodosities on the ends of the fingers, lobes of ears, fascia of -muscles, and tendons; respiration hurried, wheezing; pulse intermittent, -irregular; stomach flatulent; digestion acid; urine loaded with lithates; -temper irritable; mind sometimes enfeebled. - -The local diseases of the arthritic cachexia are principally seen -in adult males past the age of forty-five. They consist especially -in chronic inflammation of the muscular and articular tissues; in -calcification of the basilar and coronary arteries, and of the cardiac -valves. These changes give rise to hæmorrhagic apoplexy, angina pectoris, -cardiac hypertrophy and dilation; and to secondary pulmonary affections, -as emphysema, pulmonary apoplexy, and asthma. Irritation of the mucous -surfaces may give rise to nephritis, pharyngeal and laryngeal coughs, and -diarrhœa.—_Med. Observation and Research_, 2nd edition, pp. 96-98. - -[6] According to Fischer the protein molecule can be split up into -amino-acids, di-amino-acids, aromatic-amino-acids, nitrogenous -derivatives of the benzene ring, pyrimidine bases, pyrrolidine -derivatives, cystin, and ammonia. During proteolysis the amino-acids -exist in groups, _e.g._, glycine and leucine (glycyl-leucine), two -leucine radicles (alanyl-leucine), etc.—which combinations Fischer -termed polypeptides, and some of which he has been able to produce -synthetically. Furthermore, Fischer proved that nitrogen equilibrium can -be maintained in animals by feeding them upon these polypeptide products -of proteolytic digestion which no longer gives the biuret reaction. The -derivation of amino-acids, etc., from peptone is the outcome of the -action of a special intestinal ferment—_erepsin_. This enzyme is found -not only in the alimentary tract, but in all tissues of the body, its -action being especially developed in the renal tissues. - -[7] Glycocoll in solution dissociates more H-ions than OH-ions. In the -presence of alkalies this acid character is more marked, so that it tends -to throw the uric acid salts out of solution. The inhibitory influence of -the urea upon the precipitation of uric acid from solutions is due to its -basic nature. - -[8] Recent researches by S. R. Benedict show that uric acid, in the blood -of most mammals, exists in combination, but not in that of the bird. -Fresh ox-blood (Folin method) contains only 0·30005 gram, free uric acid -per 100 grams of blood. But after boiling the protein-free blood filtrate -with hydrochloric acid the uric acid content was about ten times as high. -Moreover, this same augmented uric acid content was found to exist “in -whole blood that had been allowed to stand for some time, indicating -that the _uric acid compound_ can be split by means of an _enzyme_.” The -compound exists, not in the plasma, but in the _corpuscles_. MacLeod, to -whose work on bio-chemistry we are indebted, remarks that “It is of some -significance that after thus setting free the uric acid, there should be -about 50 per cent. more of it present in the blood of the ox than in that -of the bird, where most exists in a free state in the serum, although the -urine of the ox contains only the smallest trace of uric acid, and that -of the blood is loaded with it. Investigation of the condition of uric -acid in human blood is at present in progress.” - -[9] According to Sir William Roberts, there are three compounds of uric -acid (H₂U)—the neutral urate, M₂U, in which the metal replaces all the -displaceable hydrogen, the biurate, MHU, in which half the displaceable -hydrogen is replaced by the metal, and the quadriurate H₂UMHU, in which -one-fourth of the displaceable hydrogen of two molecules is replaced by -the metal. - -Hutchison and Tidy suggest “that if Roberts’ salt be considered as NaHU. -MH₂U instead of Na. HU, his hypothesis remains unaltered, whilst much -of the criticism urged against it is nullified. The possibility of such -a substance is shown by the existence of the compound LiHU₄HU. Roberts’ -theory, or such a modification, is not inconsistent with Von Noorden’s -views if these intermediate salts be regarded as within the tabernacle of -organic combinations from which the kidneys can split off and excrete the -uric acid.” - -[10] “If further investigations yield facts which sustain such an idea, -it may be more easy to comprehend the types of the demands which are made -upon the renal functions.... One of the next stages of research will be -the determination of the behaviour of renal tissue to the various purin -isomers. This may lead on to the identification of the types of nuclein -derivations and their precise cellular origin. Perhaps this in turn may -reveal whether there are any differences between the nucleotides of -normal and gouty tissues. To this end progress in the technics of the -cultivation of tissues _in vitro_ may furnish a means for the elucidation -of some of these questions.”—_Walker Hall._ - -[11] As a further illustration of the differences which may exist in the -purin metabolism in different kinds of animals, in man and the anthropoid -apes the quantity of purin bases in the urine is small in proportion -to the quantity of uric acid. In the pig, which is included among the -animals that form allantoin from uric acid, the purin bases exceed -the uric acid in amount, whereas in the dog, which likewise excretes -allantoin, the purin bases exist in very small amount compared with the -uric acid.—_Stewart’s_ “_Manual of Physiology_.” - -[12] The findings of Soetbeer and Ibrahim also indicate that 50 per cent. -of the exogenous purin bodies undergo oxidation to uric acid, and 50 per -cent. undergo further disruption and are excreted as urea or intermediate -bodies. - -[13] The subject of the experiments—a healthy male (M. S. D.), 22 years -of age and 58 kilos in weight—was placed for over six months upon a -meat-free low protein diet, free also from purin-containing beverages. -This with the exception of a few meals in the holidays, during which -a small amount of meat was taken. “No attempt was made to secure a -quantitative uniformity of the diet.” On the evening preceding the day -of an experiment a light supper was eaten, and no further food was -ingested until the completion of the day’s experiment, save the substance -whose influence on uric acid excretion was to be studied. The urine was -collected hourly, 200 c.c. of water being ingested hourly throughout the -experimental period.—“_Uric Add Metabolism_,” 11—_H. B. Lewis, M. S. -Dunn, and E. A. Doisy, “Journal of Biological Chemistry,” 1918._ - -Two other men also served as subjects. Many of the experiments were -duplicated, and similar results obtained with these other subjects, but -inasmuch as the experiments with M. S. D. were more comprehensive and -extended over a longer period of time, the data of these experiments -alone are presented. - -[14] Quoting from the same article, _Journal of Biological Chemistry_, -1918, by Lewis, Dunn and Doisy, these authorities observe that—_re_ -glycocoll and alanine, Lusk concluded that “the chemical stimulation -of protoplasm which is responsible for the phenomena of increased heat -production (specific dynamic action) results from the action of their -intermediary products, glycocollic and lactic acids, rather than from -the amino-acids themselves. The phenomena of the stimulation of uric -acid metabolism by amino-acids run parallel to those of the specific -dynamic action of the amino-acids (except in the case of the dicarboxylic -amino-acids), and it is possible that the same chemical factors are -responsible for both.” - -[15] - - C₅H₄N₄O₃ + O + H₂O------>C₄H₆N₄O₃ + CO₂ - Uric acid. Uricase. Allantoin. - -[16] Experimenting on a Dalmatian coach-hound, Gideon Wells was able to -confirm Benedict’s observation that it excretes large quantities of uric -acid. But inasmuch as the liver of this same dog was able to destroy uric -acid _in vitro_, the inference is that the presence of uric acid in the -urine of the Dalmatian is not attributable to the _absence of uricase in -its tissues_. “The kidney did not exhibit uricolytic activity. Neither -the liver nor spleen converted xanthine into uric acid, but the liver -deaminised both guanine and adenine.”—_Journal of Biological Chemistry_, -1918. - -[17] Wells, in his “Chemical Pathology,” observes that the amount of uric -acid that appears in the urine depends upon a variety of factors which -may be summarised as follows:— - - (1) The amount of purin bodies taken in the food upon which - chiefly depends the amount of exogenous uric acid. - - (2) The amount of destruction of tissue nucleo-proteins. - - (3) The amount of purin bases formed in the muscle tissue. - - (4) The amount of conversion of purin bases into the uric acid. - - (5) The amount of destruction of uric acid, if any, occurring - in the body. - - (6) Possibly upon the capacity of the tissues to synthesize - uric acid; and in case such power to synthesize uric acid - exists upon the presence of the precursors of uric acid in the - body. - - (7) The retention of uric acid in the blood and tissues. - - (8) The power of the kidney to excrete uric acid. - - (9) The solubility of uric acid in urine—dependent upon the - amount of neutral phosphates present, the temperature, reaction - and concentration thereof. - -[18] EFFECT OF ATOPHAN ON EXOGENOUS PURINS. (McLester, in “Archives of -Internal Medicine.”) - - -----+--------------------------+--------+------------------------------ - | | | Twenty-four Hour Urine. - | | Blood +-------+-------+-------+------ - Date.| R. E. |Mg. U in| Amt. | | NH. | - | |100 Gm. | c.c. |U. Gm. |Gm. N. |N. Gm. - -----+--------------------------+--------+-------+-------+-------+------ - 5/28 | ---- | 2·9 | 1,150 | ·46 | ·58 |10·26 - 5/29 |7 a.m.: 500 grams thymus. | | | | | - | 2 p.m.: Blood | 3·2 | 900 | ·66 | ·69 |10·96 - 5/31 |7 a.m.: 500 grams thymus. | | | | | - | 9 a.m.: Atophan, 2 p.m.:| | | | | - | Blood | 1·1 | 1,280 | ·75 | ·76 |11·16 - -----+--------------------------+--------+-------+-------+-------+------ - -[19] Walker Hall states that: “Taking the total volume of blood at three -and a half litres, and the volume passing through the lungs as four -and a half litres per minute, and through the kidneys as one litre per -minute, and the solubility of lactim-urate as 0·1 grm. per 4,000 c.c. -of blood, it would seem that the average daily output of 0·5 grm. could -be suspended in the quantity of blood passing through the lungs in five -minutes or through the kidneys in twenty minutes normal.” - -[20] Criticising the colorimetric method on the ground that “different -workers obtain on the same blood samples results which vary -considerably,” L. J. Curtman and A. Lehrman have devised a new volumetric -method for the determination of uric acid in blood. The following is the -summary of their researches:— - -(1) An experimental study of a number of metallic salts as precipitants -for uric acid in a solution alkaline with sodium carbonate was made. The -results showed that _nickel_ is the best of those tried. - -(2) A 0·0004 N iodine solution was found suitable for the estimation of -small amounts of uric acid provided certain conditions are adhered to. - -(3) Based upon the above considerations, a new method has been developed -for the determination of uric acid in blood, the chief features of which -are (_a_) the precipitation of the uric acid by means of nickel acetate -in a solution alkaline with sodium carbonate. (_b_) The estimation of the -uric acid in the precipitate by means of a dilute solution of iodine. - -(4) The method was applied with good results to aqueous solutions of uric -acid as well as to blood serum to which known amounts of uric acid were -added. - -(5) Low and inconsistent results were obtained when the method was -applied to sheep’s blood to which known amounts of uric acid were added. -This was shown to be due to the inadequacy of the procedure generally -employed, for the coagulation and preliminary treatment of the blood. -The colorimetric method when used in the analysis of samples of the same -blood also gave low and inconsistent results for the same reason. - -(6) Comparison tests show that the volumetric method is fully as accurate -as the colorimetric method, and possesses the advantage of requiring no -special apparatus. - -[21] URIC ACID ESTIMATION IN NORMAL INDIVIDUALS - -(McLester, “Archives of Internal Medicine.”) - -_Milligrams Uric Acid in 100 grams Blood._ - - J. C. 0·5 - H. D. 0·6 - M. D. 0·6 - A. B. 0·8 - R. C. 0·9 - H. D. 0·9 - J. G. 0·0 - S. M. 1·1 - R. D. 1·3 - L. S. 1·4 - L. H. 1·7 - R. O. 2·1 - H. H. 2·5 - J. M. 2·5 - R. E. 2·9 - -URIC ACID OF BLOOD IN DISEASE. (McLester, “Archives of Internal -Medicine.”) - -_Milligrams in 100 grams Blood._ - - Mitral lesion 0·5 - Rheumatic fever 0·6 - Acute syphilis 0·8 - Chronic tuberculous pleurisy 0·8 - Pneumonia 1·2 - Pneumonia 1·3 - Sciatica 1·3 - Typhoid fever 1·4 - Ulcer of stomach 1·5 - Pneumonia 1·6 - Amœbic dysentery 1·6 - Neurasthenia (?) 1·7 - Acute tuberculous pleurisy 1·7 - Chronic interstitial nephritis 1·8 - Malaria 1·8 - Pneumonia 1·9 - Uremia 2·1 - Polycythemia 2·2 - Graves’ disease 2·5 - Pneumonia 2·7 - Gout 3·3 - Arterial hypertension 3·3 - Intermittent gastric supersecretion 3·7 - Gout 4·5 - -[22] However, as Walker Hall reminds us, Taylor, writing in 1912, -stated, “That the margin of safety with regard to renal excretion is an -exceedingly narrow one, that the kidney excretes uric acid slowly, and -that its powers are soon overstepped.” - -[23] Magnus Levy and McClure have also noted that the excretion of -exogenous purin is not invariably retarded or diminished. - -[24] When experimentally injected, the urates are absorbed slowly by -phagocytic leucocytes and giant cells.—_Gideon Wells._ - -[25] Because the gouty tophi do not suppurate, even when ulcerated, -through the skin, it has been suggested that the urates have antiseptic -properties. Bendix (_Zeit. klin. Med._, 1902 (44), 165), however, could -not demonstrate such antiseptic properties experimentally.—_Gideon Wells._ - -[26] Levinthal, in a personal experiment, injected half a gram of xanthin -dissolved in piperazine into his cubital vein. A few days later, after a -moderate strain upon the limbs through dancing, he was suddenly seized -with a fairly acute painful attack in one of his knees, attended with -some swelling and local heat. - -[27] “Tophi sometimes precede by some years ... the development -of gouty attacks in joints. The same is true also of auricular -tophi.”—_Duckworth_: “_A Treatise on Gout_.” - -[28] “While, however, tophaceous concretions generally show themselves -after attacks of articular gout, cases occur, as I have already told you, -in which the secretion of calcareous matter takes place irrespective of -any arthritic attack. This sort of _cutaneous gravel_, if I may employ a -comparison based on the great analogy between the composition of urinary -gravel and tophaceous concretions, gravel of the skin, constitutes the -sole manifestation of the diathesis, and is accompanied merely by a -slight feeling of pain, of pricking unattended by any disturbance of the -general health.”—_Trousseau’s_ “_Clinical Medicine_.” - -[29] _Redness_ of the skin overlying a developing tophus is not -invariable. In a case recently under my care, the dorsum of the -mid-phalangeal joints was the seat of small soft localised swellings. -The superjacent skin was unchanged in colour. Aspiration of the contents -by a hypodermic syringe disclosed the presence of a turbid white fluid, -which, when microscopically examined, was found loaded with the acicular -crystals of sodium biurate. - -[30] “Quod in omnibus podagricorum paroxysmis solemne est, insignior -intumescentia venerum membro vexato intertextarum se in conspectu -dat.”—_Sydenham._ - -[31] Sydenham’s classical description: “Towards the end of January or -the beginning of February suddenly, and with scarcely any premonitory -feelings, the disease breaks out. Its only forerunner is indigestion -and crudity of the stomach, which troubles the patient for some weeks -previous to the attack. His body also feels swollen, heavy, and -windy—symptoms which increase from day to day until the fit breaks out. -But a few days before this torpor comes on, and a feeling of flatus along -the legs and thighs. Besides this, there is a spasmodic affection, whilst -the day before the fit the appetite is unnaturally hearty. The victim -goes to bed in good health and sleeps. About two o’clock in the morning -he is awakened by a severe pain, generally in the great toe, more rarely -in the heel, ankle, or instep. This pain is like that of a dislocation -of the bones of these parts, and is accompanied by a sensation as of -chilly water poured over the membranes of the suffering joint. Then -follow chills and shivers and a little fever. The pain, which was at -first moderate, becomes gradually more intense, and while it increases -the chills and shivers die out. Every hour that passes finds it greater, -until at length at night-time it reaches its worst intensity, and -insinuates itself with most exquisite cruelty among the numerous small -bones of the tarsus and metatarsus, in the ligaments of which it is -lurking. Now it is a violent stretching and tearing of the ligaments, now -it is gnawing pain, and now a pressure and tightening. So exquisite and -lively meanwhile is the feeling of the part affected that it cannot bear -the weight of the bedclothes nor the jar of a person walking in the room. -Hence the night is passed in torture and a restless rolling first to one -side, then to the other, of the suffering limb, with perpetual change of -posture, the tossing about of the body being as incessant as the pain of -the tortured joint, and being at its worst as the fit is coming on. Hence -the vain efforts by change of posture, both in the body and the limb -affected, to obtain an abatement of the pain. - -“This comes only towards the second or third hour of the morning (a -whole day and night after the first outbreak of the fit), such time -being necessary for the moderate digestion and dispersion of the -peccant matter. The patient then has a sudden respite, which he falsely -attributes to the last change of position. A gentle perspiration is -succeeded by sleep. He wakes freer from pain and finds the part recently -swollen. Up to this time the only visible swelling has been that of -the veins of the affected joint. Next day (perhaps for the next two or -three days), if the generation of the gouty matter have been abundant, -the part affected is painful, getting worse towards evening and better -towards morning. A few days after the other foot swells, and suffers -the same pains. The pain in the latter regulates the state of the one -first attacked, for the more acutely it is tortured the more perfect -is the abatement of suffering and the return of strength in the other. -Nevertheless, there is a repetition in the second case of all the misery -of the first both as regards intensity and duration. Sometimes during the -first days of the disease the peccant matter is so exuberant that one -foot is insufficient for its discharge. It then attacks both, and that -with equal violence. Generally, however, it takes the feet in succession. -After it has attacked each foot the fits become irregular both as to the -time of their coming and as to their duration. One thing, however, is -constant—the pain increases at night and abates in the morning. Now a -series of lesser fits like these constitute a true attack of gout, long -or short, according to the age of the patient. To suppose that an attack -two or three months in length is all one fit is erroneous. It is rather -a series of minor fits. Of these the latter are milder and more limited -in their extent than the former, so that the peccant matter is discharged -by degrees, and recovery follows. In strong constitutions, when the -previous attacks have been few, a fortnight is the length of an attack. -With age and impaired habits gout may last two months. With _very_ -advanced age, and in constitutions _very_ much broken down by previous -gout, the disease will hang on till the summer is far advanced. For the -first fourteen days the urine is high-coloured, has a red sediment, -and is loaded with gravel. Its amount is less than a third of what the -patient drinks. During the same period the bowels are confined. Want of -appetite, general chills towards evening, heaviness, and a troublesome -feeling even in the parts which are free from the attack, attend the fit -throughout. As it goes off the foot itches intolerably, mostly between -the toes; the cuticle scales off, and the feet desquamate, as if venomed. -The disease being disposed of, the vigour and appetite of the patient -return, and this in proportion to the violence of the last fits. In the -same proportion the next fit either comes on or keeps off. Where one -attack has been sharp, the next will take place that time next year, not -earlier.”—_Sydenham._ - -[32] “Pain is better borne by the poor man, as I have had opportunities -of seeing, than by the man who acquired or promoted his gout with two or -three bottles of port wine daily, with the surroundings which such luxury -implies.”—_Longstreth_, “_On Gout_.” - -[33] “The pain is altogether disproportionate to the other signs of -inflammation, and, even more, to the consequent structural changes in the -inflamed part.”—_Paget._ - -As to the peculiar character of the pain, Duckworth states: “Nothing at -all like it occurs in any other joint disease.” - -[34] Sydenham noted that “sometimes the morbific matter is thrown upon -the elbows and occasions a whitish swelling, almost as large as an egg, -which becomes gradually inflamed and red.” - -[35] “_Regular gout_ may _supervene suddenly, and be chronic_; that is -to say, its outbreak need not have been preceded by paroxysms in any way -characteristic of acute gout.”—_Trousseau_, “_On Gout_.” - -[36] As Trousseau puts it: “Regular chronic gout, in respect of the -frequency of the recurrence of the paroxysms, resembles acute gout with -successive paroxysms, there being this capital difference, however, that -its attacks are longer and during the intervals are not entirely absent.” - -[37] Mr. James Moore, surgeon to the Second Regiment of Life Guards -(_Medico-Chirurgical Transactions_, 1809, Vol. I.):— - -“This effusion” (meaning the milky fluid containing the urate of soda) -“occurs not only during fits of gout, but likewise in the intervals; and -as the extremities, particularly the hands and feet, are the principal -seat of gout, it is there the greatest accumulation of chalk takes place. -Though this process is usually preceded and accompanied by inflammation, -the chalk is never inclosed in a cyst, like pus in an abscess. It lies -usually in the cellular membrane, in the bursæ mucosæ, or in the cavities -of the joints. I have even seen it thrown out between the cutis and the -cuticle. But, as the gouty inflammation is of the erythematous kind, -there is no extravasation of coagulable lymph, and no new-formed covering -surrounding the chalk. This point is of the first importance, and -explains many of the peculiarities of gout, which is generally considered -as a phlegmon. But the absence of coagulable lymph in the inflamed parts -I consider as full evidence of the inflammation being erythematous. - -“The chalky liquid when first secreted gives to the finger the feeling -of fluctuation, and cannot be distinguished from the ordinary serous -effusion of gout. But unfortunately the absorbents cannot suck up the -chalky particles. The consistence of the liquid therefore becomes thicker -and thicker, till at last nothing remains but a hard mass. When even a -considerable effusion of this kind occurs, the quantity of chalk which -ultimately remains is comparatively small, as by far the greater quantity -is merely serum. It therefore usually requires repeated effusions to -form any great mass of chalk, and the consistency depends upon its age -and the activity of the absorbents. The quantity at last accumulated by -repeated paroxysms is in some instances immense, which augments very -seriously the sufferings of the gouty. The distress, however, is not -owing to any irritating quality in the chalk, but to its obstructing the -motion of the tendons and joints, occasioning often complete anchylosis, -and pressing and distending the surrounding parts by its bulk. It acts, -therefore, by mechanically embarrassing the machine of the body, and not -upon the living principle, for it will often remain for years in parts -highly sensible without exciting the slightest pain or inflammation. -Although these concretions are of so mild a nature, they often are the -cause of extensive mischief, bursting externally, occasioning ulcers -very difficult to heal. When a violent fit of the gout attacks a chalky -tumour, the appearance is frequently very alarming, the new paroxysm -being accompanied with a fresh serous and chalky effusion, which, added -to the old deposit of chalk, occasions a prodigious swelling; the cutis -when distended to the utmost opens, yet sometimes the cuticle remains -entire. The chalky or serous liquid may then be seen through the -semi-transparent epidermis. The surrounding integuments appear of a deep -red, or of a purple hue, threatening mortification, while the pain is -excruciating. - -“At length the cuticle gives way, a discharge of serum and chalk takes -place, and a remission of all the symptoms usually follows. During the -whole of this alarming process suppuration never occurs; but soon after -the opening has taken place suppuration commences, and pus and chalk are -then discharged from the ulcer. There are several unexpected occurrences -in the progress of such ulcerations. When an opening is formed, the -whole of the chalk never escapes, and its complete evacuation is often -a very tedious process; this is owing to its being diffused through the -cellular membrane, as in the cells of a sponge. One cell must sometimes -give way after another, and small portions of chalk are successively -thrown out, so that months and even years pass away before the whole -is discharged. It also frequently happens that the orifice contracts -and closes over, leaving portions of chalk underneath. This kind of -cicatrix sometimes stands its ground, but more commonly breaks out again -and again to discharge chalk. Even openings into joints, which are so -dangerous when occasioned by other extraneous bodies, are often attended -with no serious symptoms when the joint is filled with chalk. On such -an accident happening a surgeon unacquainted with these peculiarities -might be tempted to propose large openings, or even amputation, as the -only resource for hindering extensive inflammation and carious bones. But -if he treats the disease mildly, he will find that no such severe plans -are requisite, for the parts will probably fall into a very tranquil or -indolent state; a sore will continue for a certain period, discharging -pus, and occasionally a bit of chalk, till at last the orifice will -close up. Independent of the opening formed by a fit of the gout, the -skin, stretched over a mass of chalk, is sometimes thinned, absorbed, -and pierced by mere pressure. At other times this is effected by common -inflammation and suppuration. When openings take place in these milder -ways, a less quantity of chalk is usually evacuated; but this depends -entirely upon the degree of inflammation. When the suppuration is great, -it naturally detaches and washes out a greater quantity of chalk. - -“The last peculiarity is the rarest, namely, that a dry, hard piece of -chalk shall pierce the skin, and remain like an excrescence, without -exciting either inflammation or suppuration.” - -[38] According to Adler, about one-tenth as much uric acid is excreted in -the sweat as in the urine, sweat containing 0·1 mg. per cubic centimetre. - -[39] In this connection the tendency of gouty glycosurics to exhibit -boils and sometimes carbuncles should not be forgotten. - -[40] Max Strunsky, of New York, discussing the frequency with which -by the older physicians gouty forms of arthritis were confused with -gonorrhœal, syphilitic, and other undifferentiated forms of infective -arthritis, makes the following observation: “Also flatfeet must have -added herds of cases, for this pathological entity was as yet unknown. -The rich man in pursuit of his pleasure and the poor man from prolonged -standing at his labour strained their arches then as they do now, and -women by their ultra-fashionable shoes, which fashion decreed upon -them in certain periods of history, produced painful feet which were -undoubtedly mistaken for gout. That patients with local foot trouble were -treated for gout the writer can speak from experience. A typical case -is of a woman who came to his office two years ago. She had broken-down -anterior arches. Hallux valgus, hammer-toes, and bunions were present, -and the heels were small and undeveloped. Her feet were one mass of pain, -and they looked infantile, reminding one of a Chinese woman. All her -adult life she wore high-heeled, narrow, pointed, tight shoes. She said -that for twenty years she had been treated for gout.” - -[41] In support of this contention, I would note that Charcot, while -he gives us an inimitable account of the _tophaceous_ variety of gout, -introduces also another variant, as he deems it, of _chronic articular -gout_. The joint changes in this latter are marked by what he terms -“a thorough atrophy,” including the superjacent skin, which “is pale, -shining and polished.” With this are associated ankyloses, angular -deflections, and partial dislocations. The joints, he states, “may be -absolutely free from swelling, for example when the extra-articular urate -deposits _either do not exist at all, or only mere traces of them, or -when only the articular cartilages are invaded by the urate of soda_.” -It cannot, we think, be doubted that the clinical content of this group -is largely made up of _rheumatoid_ or _atrophic arthritis_. The evidence -that these examples, _quâ_ _uratic deposits_, are of “gouty” nature, is -obviously very slender. - -Reverting to Sir Dyce Duckworth, this authority also recognises two -varieties of chronic articular gout: (_a_) tophaceous gout; (_b_) chronic -deforming gout, with as its synonym _arthritis deformans uratica_. As -to the clinical content of this latter group he writes: “The fingers, -hands, and wrists show various deformities depending on _over-growth_ of -_articulating ends of bone_, _cartilage_, ligaments, and bursæ. _These -may be complicated with visible or invisible tophaceous deposits_.” As to -these anatomical alterations, Duckworth regards them as “similar to, but -not the same as, those induced by rheumatic disease.” But he adds: “It is -very rare for the deformities of true gout to attain the gross characters -peculiar to chronic rheumatic arthritis; they are altogether of lesser -degree in the majority of the worst instances.” From a careful study of -their anatomical characters, I cannot avoid the conclusion that they were -in the main examples of the hypertrophic variety of arthritis deformans, -viz., _osteoarthritis_. - -[42] As Sir W. Hale White has pointed out, “pads” not uncommonly develop -on the dorsal aspects of the mid-phalangeal joints. They range in size -from a split pea to a hazel nut. Histologically they are the outcome of -an excessive overgrowth of fibrous tissue beneath the corium. They in -no way involve the joints, but, according to Hale White, they have been -confused with osteoarthritis. Their frequent association with Dupuytren’s -contracture might conceivably lead to their confusion with gout also, -inasmuch as that deformity is so widely attributed to a “gouty” habit. - -[43] Sir Spencer Wells in his “Practical Observations on Gout and its -Complications and on the Treatment of Joints stiffened by Gouty Deposits.” - -“Of the many cases related by authors as anonymous disease by far the -greater portion were connected with a gouty diathesis, as indicated both -by the formation of calculi, by the occurrence of regular paroxysms -of gout, and by the descent of the individual from gouty ancestors; -they are cases, in fact, which would have been better understood and -better treated if they had been termed ‘anomalous gout’; but as the -subjects are young females, they are of course set down as ‘anomalous -hysteria.’”—_Laycock_: “_Nervous Diseases of Women_.” - -[44] “Diseases of the Eye” (1918), p. 258. - -[45] “Diseases of the Eye” (1919). - -[46] “Diseases and Injuries of the Eye” (1913). - -[47] Kruckmann, _Med. Klinik._, 1910, No. 38. - -[48] _Proc. Roy. Soc. Med._, Ophth. Section, 1914, p. 66. - -[49] _Ophth. Hosp. Reps._, VII., p. 287, 1873. - -[50] “Diseases of the Eye” (1854), p. 558. - -[51] _Brit. Med. Journ._, 1885, R. Clement Lucas. - -[52] _Lancet_, 1920, Vol. I., p. 500, Browning. - -[53] _Archives d’Ophtalmologie_, Vol. XII., p. 623. - -[54] A very rare form of iritis was described by the late Mr. Doyne as -guttate iritis (_Trans. Ophth. Soc._, Vol. XXX., p. 91) because the -appearances resembled drops of lymph on the margin of the pupil. In his -view it was a true form of gouty iritis, but the diagnosis does not seem -to have been confirmed by other observers. Even if we grant that his -view is possibly correct, we must beware how we generalise on a basis of -exceptions and freaks. - -[55] _Brit. Med. Journ._, 1903, Vol. II., p. 138. - -[56] “Gout” (1876), p. 450. - -[57] _Clin. Soc. Trans._, Vol. XI., p. 132, 1898. - -[58] “Medical Ophthalmoscopy,” 3rd edition, p. 267. - -[59] _Practitioner_, 1909, Vol. II., p. 61. - -[60] Sydenham, discussing a milk diet, observes that “it has done good -as long as it has been rigidly attended to. The moment, however, that -the patient swerves from it a hair’s breadth, and the moment he betakes -himself to the diet of a healthy man (no matter how mild and simple), the -gout returns worse than ever.” - -[61] “The lighter beers of Germany, Austria, and Scandinavia, appear to -be harmless for the gouty unless taken immoderately. Residents in towns -goutily disposed, leading sedentary lives, are seldom long tolerant even -of light laager beer.” - -[62] Sir Archibald Garrod has suggested that guaiacum has a distinct -effect in reducing the amount of uric acid excreted, _i.e._, it -was thought that the uric acid is eliminated in some other form, -possibly hippuric acid. Accordingly Martindale and Westcott conducted -investigations to determine whether this resin increases or decreases the -elimination of uric acid from the human body. - -A normal individual took guaiacum resin in 5-grain doses daily in the -morning, and the uric acid was estimated in the urine the same afternoon. -Hippuric acid was also estimated in specimens of the same urine by the -method given by Allen, “Chemistry of Urine,” p. 186. After a day’s -interval the acids were estimated on several days without administration -of the drug. The two series were then repeated on the same lines after -an interval. Seeing that the diet of the individual could not well be -controlled in weighed amounts of food, as would strictly be necessary for -an investigation of this kind, it was thought that to express the results -in percentage ratios of uric acid to excess of solids (R.U.A.) over water -might yield more comparable results. - -Joulie employs this method of indicating the constituents of urine by -ratios; _cf._ Vol. I., p. 736. Thus, taking a specimen of urine with the -following “normal” factors in grams per litre:— - - Specific gravity 1017·8 - Excess of solids over water 17·8 - Physiological acidity in terms of H₂SO₄ 0·849 - Total P₂O₄ 2·083 - Cl 6·865 - Urea 18·75 - Uric acid 0·416 - Hippuric acid 1·3 - (_mean_). - -One may express the constituents as the following percentage ratios:— - - Normal. - - “R.A.”—Ratio of physiological acidity to excess - of solids over water 4·77 0·849 × 100 - ----------- - 17·8 - - “R.P.”—Ratio of total P₂O₄ to excess of solids over - water 11·17 - “R.U.”—Ratio of urea to excess of solids over water 100·53 - “R.U.A.”—Ratio of uric acid to excess of solids over - water 2·33 - “R.H.A.”—Ratio of hippuric acid to excess of solids - over water 7·3 - “R.P./R.A.”—Ratio of phosphoric acid to ratio of acidity - (Joulie’s factor, _cf._ Vol. I., p. 737) 2·45 - - Ratio of uric acid, for example, is arrived at thus 0·416 × 100 - ----------- = 2·33 - 17·8 - -The results which we obtained are given in the following table:— - -_Effects of Guaiacum Resin on the Urine of a Normal Individual._ - - -----------------+---------+-------+-----+------+------+--------+-------- - | Date. | Sp. |Urea.| Uric | Hip- |“R.U.A.”|“R.H.A.” - | | Gr. | | Acid.| puric| | - | | | | | Acid.| | - -----------------+---------+-------+-----+------+------+--------+-------- - With guaiacum | 28/12/11| 1·0107| 2·29| 0·09 | 0·09 | 4·43 | 4·34 - With guaiacum | 29/12/11| 1·0247| 1·29| 0·08 | 0·1 | 3·34 | 4·04 - With guaiacum | 1/1/12| 1·0215| 2·56| 0·015| 0·15 | 4·88 | 6·97 - With guaiacum | 2/1/12| 1·0141| 2·82| 0·10 | 0·2 | 4·2 | 8·20 - Without guaiacum | 4/1/12| 1·0229| 2·42| 0·06 | 0·1 | 2·62 | 4·36 - Without guaiacum | 5/1/12| 1·0249| 2·42| 0·08 | 0·2 | 3·16 | 8·03 - Without guaiacum | 8/1/12| 1·0255| 3·09| 0·10 | 0·225| 4·11 | 8·12 - With guaiacum | 11/1/12| 1·0233| 2·56| 0·09 | 0·1 | 3·7 | 4·29 - With guaiacum | 12/1/12| 1·0213| 1·88| 0·075| 0·1 | 3·05 | 4·69 - Without guaiacum | 24/1/12| 1·0239| 2·42| 0·08 | 0·038| 3·45 | 1·57 - Without guaiacum | 25/1/12| 1·0229| 2·15| 0·06 | 0·05 | 2·61 | 2·18 - -----------------+---------+-------+-----+------+------+--------+------- - - Average uric acid ratio under guaiacum resin = 3·39 - Average uric acid ratio without guaiacum resin = 3·19 - Average hippuric acid ratio under guaiacum resin = 5·43 - Average hippuric acid ratio without guaiacum resin = 4·49 - -The quantity of hippuric acid normally found is known to vary enormously, -_e.g._, between 0·02 and 0·25 per cent. From this we deduced, for -purpose of this investigation, a mean normal R.H.A. of 7·3. A number of -other investigations were conducted on analogous lines, but need not be -recorded. - -From the results of these experiments one notices an average increase -of uric and hippuric acids during the “+ guaiacum” periods. It is not -possible to draw a conclusion without further corroboration. The amount -of each acid from day to day is seen to be erratic, and the process of -estimation of hippuric acid is not accurate. - -[63] “Weakly mineralised thermal muriated waters, such as those of -Baden-Baden in Germany, and Bourbon-Lancy in France, which in character -and action approach the simple thermal group, may also show great -radio-activity. In fact, the Büttquelle of Baden-Baden in this respect -rivals some of the most radio-active springs of Gastein. Of Bourbon-Lancy -springs, according to A. Piatot, the least mineralised are the most -radio-active.”—“_Climato-therapy and Balneo-therapy_,” _by Sir Hermann -Weber_. - -[64] SIR WILLIAM RAMSAY’S ANALYSIS OF THE BATH WATERS. - - Density of the water from King’s Well 1·0166 - - Osmotic pressure equivalent to that of - a salt solution containing per litre 1·09 grams NaCl. - -Volume of gas in twenty-four hours from— - - Litres. - King’s Well 4,927 - Cross Spring 218 - Hetling Spring 218 (estimated). - ----- - 5,363 - ----- - -Analysis of gas (King’s Well)— - - Parts per 10,000. - Carbon dioxide 360 - Nitrogen, etc. 9,640 - No oxygen, no hydrogen, no marsh gas. - -The nitrogen contains— - - Argon 73·63 - Neon 23·34 - Helium 2·97 - -From all three wells in twenty-four hours— - - Litres. - Argon 39 - Neon 12½ - Helium 1½ - -_Gases dissolved in Pump-room Water._—This water contains 18·5 volumes -of gas per 1,000 of water. Its composition is— - - Carbon dioxide 6·9 - Nitrogen 11·6 - -It had become somewhat aerated on drawing, but allowance has been made -for that. - - Milligrams per - million litres. - - Radium in the water of the King’s Well 0·1387 - Niton (radium emanation) in the water of King’s Well 1·73 - ” ” ” ” of Cross Bath 1·19 - ” ” ” ” of Hetling Bath 1·70 - ” ” ” in the gas from King’s Well 33·65 - -[65] Bickel in a series of experiments in which the acid contents as -well as the total amount of gastric juice were considered obtained the -following results: simple gaseous waters (Apollinaris, Giesshübl), -muriated waters (Rakoczy spring of Kissingen, Wiesbaden, Kochbrunnen), -and muriated alkaline waters (Ems, Selters), all of them, as compared to -distilled water and ordinary tap water, rather increased than decreased -the specific secretory activity of the gastric mucous membrane, whereas -simple alkaline waters (Vichy) and sulphated alkaline waters (Karlsbad) -had a slight tendency to diminish, and the sulphated “bitter” waters -(Hunyadi Janos water) decidedly diminished, the gastric secretory -activity, although “bitter” waters sometimes induced a watery flow from -the gastric mucosa, which increased the fluid contents of the stomach. - -[66] Bain, of Harrogate, from his observations on a man with permanent -cutaneous biliary fistula, found that the old sulphur spring of Harrogate -increased both the quantity of bile and the bile solids. This, he thinks, -may “fairly be taken as an index of the degree to which it stimulates the -liver, and is, in fact, the most reliable indication of the value of a -cholagogue.” - - - - -INDEX - - - =A-amino-acids=, 61 - - =Aborigines=, gout unknown among, 2 - - =Abscess= formation in peri-tophal tissues, 234 - skin resembling, in acute gout, 212 - - “=Accessory= food factors” in diet of gouty, 339 - - =Adenase=, 100, 101 - - =Adenine=, 73, 75, 77, 98 - - =Aetius’s= views on gout, 6 - - =Age= factor in gout, 40 - influence of, on diet, in acute stage of gout, 333 - - =Agotan= in treatment of acute gout, 379 - - =Aix= massage baths, 427 - - =Alanine=, uric acid excretion augmented by, 89 - - =Albuminuria=, diet in, 358 - - =Alcohol= and gout, 48 - hypersensitiveness of gouty to, 365 - in febrile stage of sthenic gout, 333 - in gout, 361 - in subjects of gouty glycosuria, 237 - _modus operandi_ of, in induction of gout, 49 - _plus_ overeating, cause of gout, 49 - - =Alcoholism=, chronic, purin metabolism in, 115 - - =Alexander= of Tralles’s views on gout, 5 - - =Alimentary= canal, condition of, and gout, 174 - disorders, effects of radio-active waters on, 439 - tract, functional derangements of, in diagnosis of articular gout, - 249 - X-ray examination of, in treatment of gout, 336 - - =Alkalies= in inter-paroxysmal periods of gout, 392 - in treatment of acute gout, 383 - in treatment of chronic gout, 399 - - =Alkaline= waters, simple, spas for, 441 - - =Alkapton= in urine, 59 - - =Alkaptonuria=, 69 - - =Allantoin=, 104 - - =Alternatives= in treatment of chronic gout, 401 - - =Alveolus=, senile atrophy of, 329 - - =Amberg= and Jones’ scheme of formation of uric acid, 104 - - =America=, United States of, gout in, 47 - - =Amino-acetic-acid=, 64 - - =Amino-acids= and dicarboxylic amino-acids, 89 - deaminisation of, 62, 63 - fate of, 62 - in portal blood, 62 - in relation to gout, 64 - - =Amino-purins=, as source of uric acid, 84 - - =Amylaceous= dyspepsia, diet in, 351, 352 - - =Anacritical= stage of depression, 211 - - =Anæmia= in cases of long-standing gout, treatment of, 406 - retention capacity of tissues for uric acid in, 158 - - =Anatomical= alterations in articulations, 54 - - =Anglo-Saxon= period, prevalence of gout in, 2 - - =Animal= cells, nucleic acid derived from, 98 - - =Animals=, various, uric acid blood content of, 135 - - =Ankylosis= in chronic gout, 287 - - =Anodyne= preparations in treatment of acute gout, 384, 385 - - =Anodynes= in acute gout, 383 - - =Antiquity= of gout, 1 - - =Anuria=, hysteria in, 126 - - =Aponeuroses=, gouty polyarthritis in, 214 - - =Appendicitis=, septic foci of, 184 - - =Appendix-dyspepsia=, 184 - - =Arab= physicians’ views on gout, 6 - - =Aretæus= the Cappadocian’s views on gout, 4, 5 - - =Arterio-sclerosis=, associated with gout, 245 - blood-content in, 127 - spa treatment of, 451 - - =Arthralgia=, fleeting, 193 - - =Arthritic= attacks, tophi formation preceding, 164 - iritis, 315 - - =Arthritides=, specific infective, and gout, analogies between, 194 - - =Arthritis= deformans, cleavage into two types, 18 - differentiation of, from chronic gout, 16 - rheumatoid, and osteoarthritis, 20 - - =Arthritis=, gonococcal, acute, differential diagnosis from acute - gouty polyarthritis, 270 - from gout, 259 - of tarsus and metatarsus, differential diagnosis from gout, 263 - gouty, 39 - definition of, 20 - frequency of tophi in, 255 - relation to local foci of infection, 185 - Greek designation, 3 - hæmophilia, differential diagnosis from chronic gout, 285 - infective, of undifferentiated type, differential diagnosis from - acute polyarticular gout, 272 - skiagraphy in differential diagnosis of, 290 - non-gouty, hyper-uricæmia in, 140 - rheumatoid, 17 - differential diagnosis from chronic gout, 284 - local character of joint swellings, 284 - or atrophic, acute, differential diagnosis from acute gouty - polyarthritis, 272 - skiagraphy in differential diagnosis of, 291 - syphilitic, differential diagnosis from chronic articular gout, - 277 - secondary, differential diagnosis from acute gouty - polyarthritis, - 271 - tophi in relation to, 254 - - =Arthropathies=, nerve, differential diagnosis from chronic gout, - 284 - - =Articular= gout, chronic, medicinal and other modes of therapy, 397 - etiological diagnosis, 247 - - =Articular= lesions in chronic gout, distribution of, 226 - - =Asphyxias=, local, of hands, in gout, 45 - - =Atophan=, effect of, on exogenous purins, 110 - on uric acid excretion, 119 - indicated when gout attack imminent, 395 - in treatment of acute gout, 379 - in treatment of chronic gout, 403 - - =Auricular= tophi, 202 - - =Auto-intoxication= theory of gout, 182 - - =Auto-toxæmia= theory of gout, 182 - - =Avicenna’s= views on gout, 6 - - - =Bacillus coli communis= as causative agent in gout, 175 - - =Bacterial= flora, intestinal, modifications in, 182 - - =Bacteriological= examination in diagnosis of articular gout, 251 - - =Baillon’s= dissociation of rheumatism from gout, 15 - - =Banting= method in reduction of obesity, 357 - - =Barclay’s= theories of ætiology of gout, 23 - - =Bath= as residence for gouty, 419 - - =Bath= waters, Sir W. Ramsay’s analysis of, 435 - - =Baths= in treatment of gout, method of application, 427 - - =Beaumont, W. M.=, ocular disease in the gouty, 308 - - =Beauvais’s= work on gout, 17 - - =Beer= as beverage in gout, 362 - - =Benzoates= in treatment of chronic gout, 401 - - =Berkart’s= theory of ætiology of gout, 27 - views on gout, 56 - - =Beverages= in gout, 359 - - =Bismuth= carbonate in inter-paroxysmal periods of gout, 392 - - =Biurate= of soda in gouty tophi, 151 - - =Blisters= in treatment of acute gout, 386 - - =Blood=, changes in, in acute gout, 210 - in chronic articular gout, 226 - in gouty polyarthritis, 216 - content in gout, 189 - count in acute gout, 211 - - =Blood=, examination of, in diagnosis of articular gout, 251 - - =Blood=, human, relationship between amounts of uric acid, urea and - non-protein nitrogen in, 122 - in chronic interstitial nephritis, urates in, 120 - in disease, uric acid of, 137 - portal, amino-acids in, 62 - routine examination of, in diagnosis of articular gout, 249 - uric acid as normal constituent of, 135 - uric acid content of, and gout, relation between, 143 - effect of diet upon, 141 - effect of exogenous purins on, 137 - estimation of sources of fallacy, 145 - in gout, 133, 139 - uric acid in, 24, 34, 78 - discovery of, 21 - Folin and Denis’s method of determination, 133 - forms of, 145 - Gudzent and Schade’s theories, 79 - non-protein nitrogen and urea nitrogen in (table), 136 - variations in uric acid content independently of diet, 142 - - =Bodily= conformation, and gout, 44 - - =Boils=, gout following, 53, 178 - - =Bone=, conditions of, revealed by skiagraphy, in diagnosis of gout, - 286 - - =Bones=, changes in, in gout, 53 - focal areas of rarefaction in, revealed by skiagraphy, 286, 287 - - =Brandy= in gout, 371 - - =Bruce’s= modes, 286 - - =Bunion=, inflamed, differential diagnosis from gout, 261 - - =Burian= and Schur’s researches on sources of uric acid, 83 - - =Bursæ=, involved in gout, 195 - tophi in, 233 - - =Bursitis=, olecranon, gouty, 215 - post-calcaneal, in referred pain in heel, 265 - - - =Cælius Aurelianus’s= views on gout, 5 - - =Caffeine=, 85 - - =Calcium= carbonate in inter-paroxysmal periods of gout, 392 - salts in gouty tophi, 151 - - =Calculus=, urinary, 29 - - =Carbohydrates= in diet of gouty, 347 - - =Carbuncles=, gout following, 53, 178 - - =Cartilage=, morbid changes in, 53 - uratic deposits in, 52, 153 - in nephritis, 128 - - =Cataphoresis= in treatment of chronic articular gout, 407 - - =Cell= protoplasm, chemistry of, 176 - - =Celsus’s= views on gout, 4 - - “=Chalk-stones=,” 150 - - =Chalybeate= waters, spas for, 442 - - =Champagne= in gout, 368 - - =Charcot’s= discovery of nerve arthropathies, 18 - joint, differential diagnosis from chronic articular gout, 277 - - =Chemistry= of uric acid and purin bodies, 75 - - =Chilblains= confused with early stages of tophi formation, 164 - - =Chirargra=, Greek designation, 3 - - =Cholecystitis=, 184 - - =Cider= as beverage in gout, 363 - - =Claret= in gout, 369 - - =Climate= and gout, 45 - and residence in treatment of gout, 418 - - =Climato-therapy= in gout, 418 - - =Clothing=, importance of, 421 - - =Cocoa= as beverage in gout, 361 - - =Coffee= as beverage in gout, 361 - - =Colchicine= in treatment of acute gout, 378 - - =Colchicum= in acute gout, 192, 374, 375, 378 - contra-indicated, alkalies as substitute, 383 - method of administration, 376 - preparations and dosage of, 376 - used by Aetius, 6 - - =Colitis=, mucous, initial manifestations of gout, 175 - - =Colloids= in gouty tophi, 152 - - =Collosol= iodine in treatment of chronic gout, 402 - - =Colorimetric= method of determining uric acid in blood, 133 - - =Colour= reaction test in blood analysis, 133 - - =Condiments= in diet of gouty, 350 - - =Constipation=, effect in gout, 337 - in acute gout, treatment of, 373 - in chronic gout, treatment of, 400 - in inter-paroxysmal periods of gout, treatment of, 393 - - =Constitutional= disturbance in gout, 188 - influences in formation of tophi, 161 - - =Corpora= cavernosa of penis, tophi in, 235 - - =Cramps= in acute gout, 210 - - =Cream=, effect of, on uric acid output, 348 - - =Creatine=, 63, 67 - in urine of children, 68 - - =Creatinine=, 61, 63, 67, 68 - in blood in gout and nephritis (table), 121 - - =Crystalline= deposits in synovial fluid, 54 - - =Crystalloids= in gouty tophi, 152 - - =Cytosine=, 98 - - =Cullen’s= differentiation of varieties of rheumatism, 16 - theory of ætiology of gout, 21 - - =Cutaneous= disorders in gout, 240 - gravel, 203 - - =Cuticule=, desquamation of, typical of gout, 191 - - =Cystin= in urine, 59 - - =Cystinuria=, 69 - - =Cystoid= degeneration in gout, 56 - - - =Deaminisation= of amino-acids, 62, 63 - - =Deficiency= diseases and accessory food factors, 340 - - =Degeneration=, theories of, 25, 27 - - =Desquamation= in acute gout, 212 - - =Diabetes=, glycosuria and, 60 - - =Dicarboxylic= amino-acids, 89 - - =Diet=, effect of, on blood content of uric acid, 141 - - =Diet= on excretion of uric acid, 83 - - =Diet= in acute paroxysms of gout, 332 - in albuminuria, 358 - in amylaceous dyspepsia, 351, 352 - in chronic gout, 334 - in glycosuria, 357 - in hyperchlorhydria, 353 - in hyperuricæmia, 354 - in hypochlorhydria, 354 - in inter-paroxysmal periods of gout, 391 - in reduction of obesity, 357 - in treatment of gout, 332 - “accessory food factors,” 339 - carbohydrates, 347 - collaboration of clinician and bio-chemist, need for, 337 - condiments, 350 - fats, 347 - fish, 346 - fruits, 349 - idiosyncrasies of, 343 - physical examination necessary before, 336 - proteins, 345 - regulations of, 342 - vegetables, 348 - variations of blood content of uric acid independently of, 142 - - =Dietaries=, fixed, fallacy of, in treatment of gout, 335 - - =Digestion=, disturbances of, prevention of, in treatment of gout, - 335 - - =Digestive= glands, _rôle_ of, in uric acid excretion, 88 - - =Diocletian=, edict by, _re_ gout, 5 - - =Dislocations=, signalising attack of gout, 53 - - =Douches=, 428 - - =Dover’s= powder, with aspirin and phenacetin, in treatment of acute - gout, 383 - - =Drink= and gout, 48 - - “=Drug= dyspepsia,” 391 - - =Drugs= influencing excretion of endogenous uric acid, 96 - - =Duckworth’s= classification of arthritic type of gout, 36 - theory of ætiology of gout, 33 - - =Dyschezia= and gout, 337 - - =Dysenteric= arthritis, differential diagnosis from acute gouty - polyarthritis, 272 - - =Dysentery=, complicated by arthritis and myalgias, 194 - - =Dyspepsia=, amylaceous, diet in, 351, 352 - atonic, muriated waters in treatment of, 444 - chronic, gout associated with, 178 - “drug,” 391 - gouty, no specific form of, 350 - intestinal, preceding gout, 182 - mineral waters in treatment of, 443 - spas in treatment of, 442 - - =Dyspeptic= symptoms of acute localised gout, 201 - - - =Ear=, pricking or tenderness in, 203 - tophus in, 202 - - =Ears=, tophi in, antedating articular outbreaks, 203 - - =Ebstein= and Sprague’s analysis of tophi, 150 - - =Ebstein’s= theory of ætiology of gout, 25 - - =Ecchymoses=, local, in acute gout, 212 - - =Eczema=, gouty, spa treatment of, 451 - treatment of, 416 - in gout, 241 - - =Egypt=, osteoarthritis in, in ancient times, 1 - - =Endemic= areas of gout, 46 - - =Endogenous= purins, 87 - origin of, 83 - source of, 88 - uric acid excretion, 91 - factors influencing, 93 - increased by purin-free proteid food, 89 - pathological states influencing, 94 - periodic variations of, 94 - physiological conditions, 93 - - =Environment= in gout, 40 - - =Enzymes=, distribution of, 99 - in intestinal juices and wall, 100 - - =Epistaxis=, gout following, 178 - - =Epithelial= cells, nucleus in gouty tophi, 151 - - =Erysipelas=, gouty arthritis simulating, 215 - - =Erythromelalgia=, differential diagnosis from gout, 266 - - =Etiological= diagnosis of articular gout, 247 - - =Exercise= in gout, importance of, 421 - relation of, to gout, 337 - - =Exogenous= origin of purins, 83 - purins as source of uric acid, 84 - uric acid excretion, 85 - - =Exudative= diathesis, 116 - - =Eye=, deposition of urates in, 309 - gout in, evidence of, 309 - gouty diathesis in regard to, 310 - - =Eyelids=, uratic deposits in, 235 - - - =Fæces=, examination of, in diagnosis of articular gout, 250 - in treatment of gout, 337 - - =Fasciæ=, involved in gout, 195 - - “=Fat= soluble A,” 340 - - =Fats= in diet of gouty, 347 - - =Feet=, incidence of tophi in, 162 - plantar surface of, tophi in, 235 - - =Fibrosis=, interstitial, chronic, 186 - of visceral organs in gout, tendency to, 186 - - =Fibrositis= associated with acute articular gout, 195 - associated with gout, treatment of, 411 - gouty, acute brachial, treatment of, 412 - incidence of gouty stigmata in types of, 221, 222 - muscular, in gouty, massage in, 423 - spa treatment of, 450 - - =Fingers=, deformed, in chronic gout, 230 - pulps of, tophi in, 235 - - =Fischer’s= researches on protein molecule, 61 - - =Fish= in diet of gouty, 346 - - =Flatfoot=, pains in, differential diagnosis from gout, 263 - - “=Flying= gout,” 193 - - =Foci= of infection in gouty, 53 - local, in gout, 177 - - =Foci=, relation to gouty synovitis and arthritis, 185 - - =Folin= and Denis’s method of determination of uric acid in blood, - 133 - researches into urea formation, 63 - - =Food=, cooking of, in diet of gouty, 344 - influence on gout, 48 - - =Foods=, various, exogenous urinary purin in, amount of, 85 - - =Foot= deformities, static, differential diagnosis from gout, 261 - - “=Fot-adl=,” Anglo-Saxon name for gout, 3 - - =Fractures=, signalising attack of gout, 53 - - =Fruits= in diet of gouty, 349 - - =Function=, gout a disorder of, 200 - - =Functional= disturbances in gout, 201 - - - =Galen’s= views on gout, 2, 4 - - =Gall-stones=, gout associated with, 184 - - =Gall-bladder dyspepsia=, 184 - - =Garrod’s= discovery of uric acid in blood of gouty persons, 21 - pathogeny of gout, growing scepticism as to, 32 - theory of ætiology of gout, 22 - views on gout in the eye, 320 - - =Gastralgias= in gouty, 351 - - =Gastric= catarrh, chronic, gout associated with, 351 - chronic, mineral waters suitable for, 445 - glands, diseased conditions of, and gout, 173 - insufficiency, muriated waters in treatment of, 444 - - =Gastro-intestinal= asepsis, importance of, in gout, 332 - derangements in acute paroxysms of gout, 333 - disorders and gout, 180 - attributed to gout, 299-302 - chronic, spas in treatment of, 442 - mineral waters in treatment of, 443 - tract, derangement of, cause of gout, 170 - - =Genito-urinary= passages, infection of, examination for, in - diagnosis of articular gout, 249 - tract, examination of, in treatment of gout, 331 - - =Geographical= distribution of gout, 45-48 - - =Gin= in gout, 371 - - =Glandular= affections in gouty subjects, 179 - - =Glaucoma=, gout and, 324 - - =Glycocine= and urea, interaction between, 84 - - =Glycocoll=, _rôle_ of, 64 - theory of gout, 65 - uric acid excretion augmented by, 89 - - =Glycosuria= and diabetes, 60 - associated with gout, treatment of, 414 - diet in, 357 - examination for, in treatment of gout, 337 - gout and, co-existence of, 185 - gout in relation to, 236 - “gouty,” 182 - spa treatment of, 449 - - =Glyoxylic= acid in gouty urine, 65 - - =Gonococcal= arthritis of tarsus and metatarsus, differential - diagnosis from gout, 263 - infection, articular involvement, with muscular and nervous - lesions, 194 - differential diagnosis from gout, 259 - exclusion of, in diagnosis of articular gout, 248 - - =Gore=, Ringrose, theory of pathology of gout, 173 - - =Gout=, acute, colchicum in, 375 - definitely paroxysmal, 191 - general phenomena of, 210 - ionisation in treatment of, 387 - local phenomena, 211 - localised, clinical account, 200 - dyspeptic symptoms of, 201 - premonitory articular pains, 204 - prodromal symptoms, 200 - locality of, 208 - medicinal treatment of, 372 - onset of, 207 - pain in, 208 - paroxysm of, analysis of, 188 - diet in, 332 - symptoms of, 205 - uric acid variations in, 117 - surgical methods considered, 388 - treatment of, alternative remedies in, 381 - local measures, 384 - uric acid excretion in, 117, 211 - uric acid variations in, 108, 117 - ætiology of, histogenous theories of, 23 - nervous theories, 31 - summary of, 44 - theory of antecedent structural changes, 25 - age factor in, 40 - alcohol in, 361 - amino-acids in relation to, 64 - and fibrositis, incidence of, 221 - and granular kidney, clinical associations of, 130 - and immunity, early fallacies regarding, 10 - and nephritis, 242 - and other diseases, affinities between, 236 - and rheumatoid arthritis, resemblance between, 113 - and specific infective arthritides, analogies between, 194 - antiquity of, 1 - arterio-sclerosis associated with, 245 - articular, acute, differential diagnosis, 259 - localised, clinical diagnosis, 258 - chronic, 225 - alkalies in treatment of, 399 - blood changes in, 226 - clinical diagnosis of, 275 - distribution of, 226 - local measures in, 407 - medicinal and other modes of therapy, 397 - progress of disease, 228 - surgical treatment, 409 - classification of, author’s division, 38 - clinical diagnosis of, 252 - etiological diagnosis, 247 - manifestations of, 195 - as an infection, 177 - auto-intoxication theory, summary, 182 - beverages in, 359 - blood content in, 127 - uric acid and, relation between, 143 - choice of spa in treatment of, 440 - chronic, ankylosis in, 287 - confusion with chronic villous synovitis, 279 - diet in, 334 - differentiation of, from arthritis deformans, 16 - joint deformities of, 229 - of oligo-articular distribution, 278 - polyarticular, clinical features, 282 - polyarticular, differential diagnosis, 282 - tardy dissociation of, from chronic rheumatism, 15 - uric acid variations in, 109 - classification of, 35, 36 - climate and residence in treatment of, 418 - climato-therapy in, 418 - clinical account of, 200 - clothing and, 421 - collateral phenomena of, 219 - constipation and, 337 - cutaneous disorders in, 240 - definition of, 35 - author’s, 36 - derangement of gastro-intestinal tract as cause of, 171 - elimination of infective arthritides from domain of, 19 - endemic areas in, 46 - etiology of, 39 - evolution and life history of, 193 - excretion in, anomalies of, 112 - exercise in, importance of, 421 - false, ocular symptoms, 322 - glycocoll theory of, 65 - Greek physicians’ views of pathology of, 3 - growing infrequency and attenuation of, 12 - guanine, in swine, 100 - heredity and, 41 - hydrotherapy, general, in treatment of, 424 - local, in treatment of, methods of, 428 - hyperpyræmia in ætiology of, 30 - in big toe, differential diagnosis, 259 - infantile, 116, 305 - infective theory of, rise of, 171 - summary, 182, 183 - inflammatory phenomena in, cause of, 165 - initial attacks usually monarticular, 207 - initial outbreaks of, anomalous sites for, 267 - sites of, 37 - in relation to glycosuria, 236 - in relation to phlebitis, 239 - in the heel, 264 - in the instep, 262 - in the sole, 265 - inter-paroxysmal period, treatment in, prophylactic measures, 389 - introduction of word, 6 - irregular, 293 - conclusions regarding, 304 - isolation of acute articular rheumatism from, 15 - lead workers predisposed to, 50 - leanness in, 337 - leucocytosis in, 172, 189 - life history of, 193 - local foci of infection, 177 - treatment of, radical, 327 - local syncopes and asphyxias of hands in, 45 - long-continued, favouring onset of pre-senilism, 398 - lumbago associated with, 221 - massage, general, in treatment, 423 - metabolic phenomena correlated with postulated infective element, - 195 - mineral springs in treatment of, 431 - monarticular, chronic, differential diagnosis of, 276, 277 - morbid anatomy of, 39, 53 - morbid conditions associated with, treatment of, 411 - obesity in, reduction of, 356 - ocular disease in, 308 - frequency a factor in diagnosis, 316 - onset of, symptoms, 188 - organic predisposition to, 43 - other conditions classified as, in early times, 12 - pathogenesis of, earlier theories of, 21 - pedigree of, 14 - periodicity of, 191 - phenomena of, detailed account of, 207 - predisposing causes of, summary of, 52 - prevalence of, in Anglo-Saxon period, 2 - prognosis in, 244 - renal theory of, 117 - restriction of, by elimination of other disorders, 19 - retarded purin elimination in, 118 - retention capacity of tissues for uric acid in, 158 - retrocedent, 39, 296 - irregular manifestations of, 299 - sex incidence of, 41 - skiagraphy in diagnosis of, 286 - specific organism suggested, 175 - sthenic, febrile stage of, alcohol and, 333 - structural changes, 54 - sub-infection theory, summary, 182, 183 - subjective phenomena of, in relation to blood content and - excretion - of uric acid, radium emanations and, 438 - “the honour of,” 8 - theory of hepatic inadequacy, 28 - tophaceous, 39 - treatment of, 327 - diet in, 332, 342 - fallacy of fixed dietaries, 335 - gastro-intestinal asepsis in, 332 - hyperæmia, 429 - physical examination necessary before dieting, 336 - prevention of digestive disturbances, 335 - uratic deposits in, 54 - differentiation from nephritis, 129 - localisation of, 153 - uratosis in relation to, 149 - urea excretion in, 66 - uric acid content of blood in, 139 - uric acid excretion in, 108 - anomalies in, 117 - uric acid in relation to, 107 - uric acid theory of, 21 - uric acid, urea and creatine in blood in (table), 211 - uricæmia in, 125, 133 - not cause, but result, of, 148 - variations in excretion in, diagnosis of, 60 - - =Gouty= arthritis, definition of, 20 - phlebitis, 240 - polyarthritis, acute, 214 - stigmata in types of fibrositis, 222 - - “=Gravel=, cutaneous,” 203 - immunity from, 29 - - =Greek= physicians, terms used for forms of gout, 3 - views of pathology of gout, 3 - - =Guaiacum= in treatment of chronic gout, 403 - resin, effects on urine, 405 - - =Guanase=, 100, 101 - - =Guanine=, 73, 75, 77, 98 - gout in swine, 100 - - =Gudzent= and Schade’s theories of uric acid in blood, 79 - - =Gummata=, peri-bursal, 281 - peri-synovial, 281 - - =Gums=, recession of, early, 45 - - - =Hæmatemesis=, gout following, 178 - - =Hæmo-analysis=, 147 - - =Hæmophilic= arthritis, differential diagnosis from chronic gout, - 285 - - =Hæmorrhage=, retinal, and gout, 322 - - =Hair=, premature whitening of, 45 - - =Hallux= rigidus, differential diagnosis from gout, 262 - valgus with inflamed bunion, differential diagnosis from gout, 261 - - =Haly Abbas’s= views on gout, 6 - - =Hand=, gouty polyarthritis in, 214 - - =Hands=, deformed, in chronic gout, 230 - incidence of tophi in, 162 - local syncopes and asphyxias in gout, 45 - palms of, tophi in, 235 - - =Hare’s= theory of ætiology of gout, 30 - - =Heart= affections in gouty subjects, 302 - - =Heberden’s= differentiation of rheumatoid arthritis from gout, 17 - nodes, 41, 283 - - =Heel=, gout in, 264 - referred pain in, differential diagnosis in, 264 - local sources of fallacy, 265 - - =Hepatic= derangement in acute paroxysms of gout, 333 - inadequacy theory of ætiology of gout, 28 - - =Heredity= in gout, 8, 28, 40, 41, 214 - - =Herpes= in acute gout, 241 - - =Hexose= group in vegetable nucleic acids, 98 - - =Hippocrates=, aphorisms of, on gout, 4 - - =Histogenous= theories of ætiology of gout, 23 - - =Historical= survey, 1 - - =Horbaczewski’s= experiments on uric acid, 73 - - =Hot-air= baths, 429 - contra-indications to use of, 429 - - =Hutchinson= on gout and rheumatism, 15 - - =Hydrarthrosis=, bilateral, 281 - in chronic articular gout, 278 - - =Hydrochloric= acid, secretion of, and gout, 173 - strong or fuming, in inter-paroxysmal periods of gout, 393 - variations in, and gout, 181 - - =Hydro-therapy=, general, in treatment of gout, 424 - in acute gout, 385 - in treatment of gout, contra-indications and untoward - complications, 425 - methods of application, 427 - prophylactic measures, 424 - local, in treatment of gout, 428 - - =Hyperacidity= due to organic acids, 351 - in inter-paroxysmal periods of gout, 393 - - =Hyperæmia=, treatment of gout by, 429 - - =Hyperchlorhydria=, 181, 351 - associated with gout, treatment of, 415 - complicating gout, salt in diet contra-indicated, 350 - diet in, 353 - mineral waters suitable in treatment of, 446 - - =Hyperpyræmia= in ætiology of gout, 30 - - =Hyperuricæmia=, diet in, 354 - in gout, 140 - in non-gouty arthritis, 140 - ocular symptoms in, 321 - - =Hypochlorhydria=, 351 - diet in, 354 - - =Hypoxanthine=, 73, 75, 77 - - - =Indigestion=, intestinal, in gouty subjects, 181 - - =Infantile= gout, 116, 305 - - =Infection= in gout, local foci of, 177 - examination for in diagnosis of articular gout, 248 - theory of gout, 182, 183 - - =Infections=, differential diagnosis from acute localised articular - gout, 259 - specific, arthritic muscular and nerve lesions associated with, - 195 - diagnosis of, 19 - - =Infective= element in gout, correlated with metabolic phenomena, - 195 - - =Inflammation= and tophi formation, 164 - gouty, pus formation and, 191 - - =Inflammatory= phenomena in gout, cause of, 165 - - =Influenzal= arthritis, differential diagnosis from acute gouty - polyarthritis, 272 - - =Immunity= conferred by gout, early fallacies regarding, 10 - - =Inosinic= acid, 93 - - =Instep=, gout in the, 262 - - =Intestinal= canal, source of microbe or toxin in gout, 181 - derangements, mineral waters suitable in treatment of, 448 - dyspepsia preceding gout, 182 - indigestion in gouty subjects, 181 - irrigation with radio-active waters, 439 - juices and wall, enzymes in, 100 - - =Iodides= in treatment of chronic gout, 401 - value of, in renal and vascular changes, 403 - - =Iodine-albumen= compounds in treatment of chronic gout, 402 - - =Iodo-glidine= in treatment of chronic gout, 402 - - =Iodo-protein= in treatment of chronic gout, 402 - - =Ionisation= in treatment of acute gout, 387 - in treatment of chronic articular gout, 407 - - =Iritis=, “arthritic,” 315 - diseases commonly associated with, 313 - gouty, “not” a clinical entity, 316 - in gout, 308 - relative incidence of, 313 - - =Irregular= gout, 293 - - =Isomeric= forms of uric acid, 81 - - =Isomers= of purins, 81 - of pyrimidins, 81 - - - =Jaw=, formation of, 45 - - =Jaws=, radiographs of, in treatment of gout, 328 - - =Joint= cartilage, murexide reaction in, 153 - deformities of, chronic gout, 229 - - =Joints=, diaphyses of, cystic changes in, 56 - rheumatism of, 14 - stiffness of, after acute attacks of gout, 212 - swellings, local character of, in osteo-arthritis, 283 - local character of, in rheumatoid arthritis, 284 - tophi in, 233 - - =Juices=, gastric and intestinal, gout and, 173 - - - =Kidney= and kidneys, capacity of for eliminating uric acid, 125 - condition of, effect in blood content of uric acid, 138 - disease of, granular, and gout, clinical, association, 130 - joint examination in, results of, 129 - disease of, and gout, 242 - functionally deficient in late stage of gout, 119 - functional disorders of, 27, 28 - functional efficiency of, tests for, 338 - gouty, histological changes in, 127 - guanase in, 100 - uric acid elimination in, 119 - - =Knee=, gouty polyarthritis in, 214 - site of primary attack of gout, 267 - - =Kossel’s= discovery of purin bases, 73 - - - =Labile= protein, 59 - - =Latham’s= theory of hepatic origin of gout, 29 - - “=Lead= gout,” 50 - - =Lead=, elimination by iodides, 403 - poisoning, blood content in, 122, 123, 127 - ocular symptoms in, 321 - purin metabolism in, 115 - workers, predisposed to gout, 50 - - =Leanness= in gout, 337 - - =Lehmann’s= analysis of tophi, 150 - - =Leucocytosis=, 24, 27 - during acute attacks of gout, 172 - in gout, 189 - in gouty polyarthritis, 216 - relation to uric acid excretion, 95 - - =Leucopenia=, 96 - in gout, 189 - - =Leukæmia=, blood content in, 122, 123 - ocular symptoms in, 321 - uric acid in urine in, 95 - - =Levy’s= (Magnus) researches on gout, 107 - - =Limbs=, integument of tophi in, 235 - - =Lime= salts, focal absorption of, in bones, 288 - - =Liniments= in treatment of acute gout, 386 - - =Literature= of various periods, references to gout in, 3 - - =Lithæmia=, 294 - tendency to, 28, 33 - - =Lithiasis=, 29 - - =Lithium= salts in treatment of chronic gout, 400 - - =Lithuria=, 29 - - =Liveing’s= theory of ætiology of gout, 31 - - =Liver=, diseases of, amino-acids in, 59 - disorders of, functional, mineral waters suitable in treatment of, - 447 - enzymes in, 99 - functional efficiency of, tests for, 338 - glycogenic distension of, 31 - guanase in, 100 - main centre of production of urea, 63 - - =Living=, style of, effect on incidence of gout, 2 - - =Locality=, factor in gout, 45 - incidence of, in acute gout, 208 - - =Lucian= of Saramosta’s views on gout, 4 - - =Lumbago=, associated with gout, 221 - treatment of, 411 - - =Lung=, guanase in, 100 - - =Lymph= spaces, purins in, 146 - stream, sodium ions in, 146 - - =Lymphangitis=, co-existent with gout, 58 - in gout, 190 - - =Lymphatic= gland, enlargement of, in gout, 190 - - =Lymphatics=, purins in, 146 - - - =Malt= liquors in gout, 362 - - =Marchand’s= analysis of tophi, 150 - - =Massage=, general, in treatment of gout, 423 - in after-treatment of acute gout, 385, 387 - - =McCarrison’s= views on effect of absence of vitamines on functional - efficiency, 340 - - =McClure and McCarty’s= researches on bone conditions as revealed by - skiagraphy, 288, 289 - - =Meat=, over-eating of, functional damage resulting from, 65 - - =Meningococcal= arthritis, differential diagnosis from acute gouty - polyarthritis, 272 - - =Menstruation=, effect of, on incidence of gout, 41 - - =Mental= over-exertion and gout, 51 - - =Metabolic= phenomena of gout correlated with postulated infective - element, 195 - - =Metabolism=, alterations in, 30 - inborn errors of, 69 - nuclein, 71 - protein, 59, 61 - - =Metastasis= in relation to ocular gout, 314 - gouty, 297 - - =Metatarsalgia=, differential diagnosis from gout, 262 - - =Methyl-purins= as source of uric acid, 85 - - =Microbic= theory of gout, 175 - - =Miescher’s= researches on spermatozoa, 72 - on the nucleus, 71 - - =Milk= diet in acute paroxysms of gout, 332 - - =Mineral= springs, 431 - waters as beverage in gout, 360 - - =Monarticular= gout, differential diagnosis of, 276, 277 - - =Morphia=, hypodermic injections of, in acute gout, 383 - - =Mouth=, examination of, in diagnosis of articular gout, 248 - in treatment of gout, 328 - local foci of infection, results of, 184 - - =Murchison’s= theory of ætiology of gout, 28 - - =Murexide= reaction in joint cartilage, 153 - - =Muriated= chloride waters, spas for, 441 - sulphated waters, spas for, 442 - - =Muscles=, affections of, in gout, 195 - voluntary, relation of creatinine to, 68 - - =Muscular= exercise, uric acid excretion increased by, 93 - - =Myeloma=, waste of albumoses in, 59 - - - =Nails=, striated, fluted and brittle, 45 - - =Nasal= affections, radium emanations for, 438 - disorders, gout and, 178 - - =Naso-pharynx=, examination of, in treatment of gout, 328 - foci of infection, 53 - - =Necrosis=, local, in uratic deposition, 152 - relationship to gout, 25 - - =Nephritis=, acute and chronic, blood content in, 127 - chronic, spa treatment of, 452 - complicating gouty polyarthritis, 219 - early, blood content of uric acid, urea and creatine, similarity - to - gout, 120 - gout and, 242 - gouty, treatment of, 416 - uratic deposits in, 128 - differentiation from gout, 129 - uric acid, urea and creatine in blood in (table), 121 - uricæmia in, 120 - uricæmia not peculiar to, 124 - - =Nerve= arthropathies, differential diagnosis from chronic gout, 284 - Charcot’s discovery of, 18 - - =Nervous= phenomena of gout, 188, 304 - system, effect of gout on, 219 - theories of ætiology of gout, 31 - - =Neuralgia=, plantar, differential diagnosis from gout, 266 - - =Neuritis=, alcoholic peripheral, 238 - glycosuric peripheral, 238 - - =Neuro-lymphatismus=, 116 - - =Neuro-retinitis= in the gouty, 324 - - =Neurosis=, gouty, 31 - - =Neuroses=, paroxysmal, of gout, 188 - - =Nose=, alæ of, tophi in, 235 - - =Nuclease=, 100 - - =Nucleic= acid, 72, 77 - characteristic constituents of, 78 - disruption of, 100 - in body, 74 - formation of uric acid from, 98 - isolation of, 71 - metabolism of, in gout, 69 - molecules, 101 - of animal origin, structural formula of, 99 - physiological derivation of uric acid from, 73 - uric acid a derivative of, 73 - - =Nucleic-acidase=, 100 - - =Nuclein=, discovery of, 72 - metabolism, 71 - chemistry of, 60 - - =Nucleins=, 77 - phosphoric acid group in, 112 - - =Nucleo-proteins=, 77 - - =Nucleosidases=, 101 - - =Nucleosides=, 87, 100 - - =Nucleotidase=, 100 - - =Nucleotides=, 100 - - =Numbness= after acute attacks of gout, 212 - - - =Obesity= and gout, 245 - Ebstein’s views of affinity, 280 - in gout, 337 - reduction of, 356 - - =Occupation= and gout, 48 - - =Occupations= predisposing to gout, 50 - - =Ocular= disease in gout, 308 - - =Œdema= in acute gout, 212 - in gouty conditions, 191 - - =Olecranon= bursa, involved in gout, 215 - tophi in, 233, 235 - - =Oligo-articular= distribution of chronic gout, 278 - - =Oral= sepsis in gouty subjects, 179 - radium emanations and, 438 - treatment of, in gout, 330 - - =Ord’s= theory of ætiology of gout, 25 - - =Osler’s= views on gout, 36 - - =Osteoarthritis=, acute, differential diagnosis from gout, 261 - and chronic articular gout, 275, 276 - co-existing with gout, 19 - differential diagnosis from chronic articular gout, 278 - differential diagnosis from chronic gout, 283 - in ancient civilisations, 1 - local characters of joint swellings, 283 - of hip, with auricular tophi, 226 - skiagraphy in differential diagnosis of, 291 - - =Overeating= and gout, 48 - plus alcohol, cause of gout, 49 - - =Oxaluria= associated with gout, treatment of, 413 - examination for, in treatment of gout, 337 - spa treatment of, 449 - - =Oxidation= of purin, products of, 77 - - =Oxy-purins= as source of uric acid, 84 - formation of, 102 - - - =Pain= and tophi formation, 164 - in acute gout, 208 - in auricular tophi, 233 - referred, in heel, differential diagnosis of, 264 - - =Pains=, premonitory articular, in acute localised gout, 204 - - =Painters=, predisposed to gout, 50 - - =Pancreas=, enzymes in, 99 - - =Pancreatic= inefficiency, evidence of, in diagnosis of articular - gout, 250 - - =Pancretin=, 392 - - =Papain=, 392 - - =Parke’s= theories of ætiology of gout, 23 - - =Parotitis=, acute, gout following, 53 - in gout, 179 - - =Patella=, tophi in, 235 - - =Pathological= states influencing endogenous uric acid excretions, - 94 - - =Paulus Ægineta’s= views on gout, 6 - - =Pedigree= of gout, 14 - - =Pentosuria=, 69 - - =Peri-bursal= gummata, 281 - - =Perineum=, uratic deposits in, 235 - - =Periodic= variations in excretion of endogenous uric acid, 94 - - =Periodontitis=, chronic, 329 - - =Peri-synovial= gummata, 281 - - =Pes planus=, differential diagnosis from gout, 263 - - =Pharyngeal= affections, radium emanations for, 438 - - =Pharyngitis=, acute and chronic, in gouty subjects, 179 - acute, gout following, 53 - - =Pharynx=, examination of, in diagnosis of articular gout, 249 - - =Phlebitis=, gout in relation to, 239 - gouty, treatment of, 415 - in limb in articular gout, 190 - spa treatment of, 450 - treatment of gout and, 328 - - =Phospho-nuclease=, 102 - - =Physical= examination, necessity for, before dieting, in treatment - of gout, 336 - over-exertion and gout, 51 - - =Physiognomy= of the goutily disposed, 44 - - =Pinna=, small red swellings on, 204 - - =Planchon’s= views on gout, 6 - - =Plantar= neuralgia, differential diagnosis from gout, 266 - - =Pleurodynia= associated with gout, treatment of, 412 - - =Plumbers=, predisposed to gout, 50 - - =Plumbism= and gout, 60 - purin metabolism in, 115 - - =Pneumococcal= arthritis, differential diagnosis from acute gouty - polyarthritis, 272 - - =Podagra=, 12 - Greek designation, 3 - - =Polyarthritis=, articular, acute, differential diagnosis of, 269, - 270 - gouty, acute, 214 - clinical diagnosis of, 268 - diet in, 334 - blood changes in, 216 - distribution of, 214 - effect on nervous system, 219 - simulating erysipelas, 215 - non-gouty, uric acid blood content in, 141 - - =Polyarticular= distribution of gout, 214 - - =Poly-nucleotides=, 100 - - =Port= wine in gout, 364, 368 - - =Portal= blood, amino-acids in, 62 - - =Post-critical= stage of depression, 211 - - =Potash= compounds in treatment of chronic gout, 400 - - =Potassium= in gouty tophi, 151 - - =Prescriptions= for use in acute gout, 375, 377, 378, 379, 380, 386, - 391 - for use in chronic gout, 401, 405, 406 - for use in inter-paroxysmal periods of gout, 391, 392, 393, 394 - - =Pre-senilism=, long-continued gout favouring, 398 - - =Protamine=, 72 - - =Protein=, amino-acids in, number of, 64 - chemistry of, 60 - labile, 59 - metabolism, 59, 61 - urine content of urea, etc., in, 59 - tissue, 59 - - =Proteins= and their derivatives, 88 - in diet of gouty, 345 - - =Pulse= quickened in gout, 189 - - =Purgatives= in treatment of acute gout, 374 - - =Purin= bases, toxicity of, discussed, 168 - bodies, 34, 48, 63 - chemistry of, 75 - diet, uric acid excretion in, 86 - “free” diet, 355 - uric acid blood content in, 137 - uric acid excretion in, 86 - elimination, retarded, in gout, 118 - metabolism, chemistry of, 60 - in chronic alcoholism, 115 - in other disorders, 113 - in plumbism, 115 - nuclease, 102 - nucleus, arrangement of atoms, 76 - oxidation of, products of, 77 - scheme illustrating probable stages in passage through body, 101 - synthesis in mammals, 97 - unexcreted, fate of, 87 - - =Purins=, discovery of, 72 - endogenous, 83, 87 - source of, 88 - exogenous, 83 - as source of uric acid, 84 - effect of atophan on, 110 - effect on uric acid blood content, 137 - isomers of, 81 - of vegetable origin, 77 - - =Pus= formation, non-existence of, in gouty inflammation, 186, 191 - - =Pyæmia=, differential diagnosis from gout, 259 - - =Pyæmic= conditions confounded with gout, 191 - - =Pyorrhœa= alveolaris, and gout, 178 - and treatment of gout, 329 - exclusion of, in diagnosis of articular gout, 248 - - =Pyrexia= in acute gout, 210 - in gout, 189 - - =Pyrimidine= bases, 77 - - =Pyrimidins=, isomers of, 81 - - - =Quadriurate= in blood, 78, 79 - - =Quinic= acid in treatment of acute gout, 383 - - =Quinine= in treatment of acute gout, 383 - - - =Race= incidence of gout, 45-48 - - =Radio-active= properties of thermal waters, 427 - waters, physical properties of, 434 - - =Radium= emanation, increased excretion of uric acid through, 437 - influence on uric acid metabolism, 436 - physiological action of, 435 - subjective phenomena of gout in relation to blood content and - excretion of uric acid and, 438 - therapeutic action and application, 438 - - =Regular= gout, 13 - - =Renal= changes in gout, 54 - defect, uricæmia not necessarily due to, 123 - depression, functional, 119 - disease, abnormal protein loss in, 59 - theory of gout, 117 - uric acid infarcts, 151 - - =Residence=, choice of, 420 - - =Respiratory= disorders, spa treatment of, 450 - organs, affections of, in gout, 303 - - =Retinitis=, nephritic, 324 - - =Retrocedent= gout, 39, 296 - - =Rhazes’s= views on gout, 6 - - =Rheumatism=, acute articular, differential diagnosis from acute - gouty polyarthritis, 269, 270 - isolation from gout, 15 - muscular and nervous lesions associated with, 194 - confused with gout, 215 - chronic, tardy dissociation of, from chronic gout, 15 - differential diagnosis from gout, 259 - early use of term, 14 - muscular, identification of, 16 - - =Rheumatoid= arthritis, 17 - and gout, resemblance between, 113 - differential diagnosis from chronic gout, 284 - disturbance of purin metabolism in, 112 - or atrophic arthritis, differential diagnosis from acute - polyarticular gout, 272 - - =Roberts’, Sir William=, views on gout, 36 - - - =Salicylate= group as alternative remedy in treatment of acute gout, - 381 - of colchicine in treatment of acute gout, 379 - - =Salicylates= in treatment of acute gout, contra-indicated, alkalies - as substitute, 383 - in treatment of chronic gout, 401 - - =Salisbury= diet in hyperchlorhydria, 353 - method in reduction of obesity, 357 - - =Salt= in diet of gouty, 350 - - =Scapular= region, uratic deposits in, 235 - - =Scheele’s= discovery of uric acid, 8 - - =Schnee= four-cell bath in ionisation, 408 - - =Sciatica= associated with gout, treatment of, 411, 412 - - =Scudamore’s= definition of gout, 35 - - =Seneca’s= views on gout, 5 - - =Septic= conditions confounded with gout, 191 - - =Serapion’s= views on gout, 6 - - =Serous= membranes, uratic deposits in, in nephritis, 128 - - =Sex= incidence in gout, 41 - - =Shivering= at onset of acute paroxysm of gout, 188 - - =Sidonal= in treatment of acute gout, 383 - - =Silk= as underwear, 421 - - =Sinusitis=, latent, cause of systemic infections, 331 - - =Skiagraphy= in diagnosis of gout, 286 - in diagnosis of villous synovitis, 281 - in differential diagnosis of hypertrophic or osteo-arthritis, 291 - in differential diagnosis of infective arthritis, 290 - in differential diagnosis of rheumatoid or atrophic gout, 291 - - =Skin=, action of, consideration of, in treatment of gout, 337 - appearances of, and gout, 45 - defective elimination by, in chronic gout, treatment of, 400 - - =Sodium= biurate crystals in synovia, 52 - ions in lymph stream, 146 - mono-urate compound, 81 - salicylates of, in treatment of acute gout, 382 - - =Sole=, gout in, 265 - - =Solubilities= of uric acid and urates in gouty blood, 82 - - =Sool-Bader= baths, 427 - - =Spa=, choice of, in treatment of gout, 440 - treatment, duration of course of, 453 - in acute gout, 385 - of gout, principles of, 434 - remarks on, 452 - - =Spas= from a national aspect, 454 - - =Spermatozoa=, Miescher’s researches in, 72 - - =Spirits= in gout, 370 - - =Spleen=, enlargement of, in gout, 190 - enzymes in, 99 - functional efficiency of, tests for, 338 - - =Starchy= foods in diet of gouty, 347 - - =Static= foot deformities, differential diagnosis from gout, 261 - - =Stone= in Norfolk, 29 - - =Streptococci= in tonsils, 183 - - =Sub-infection= theory of gout, 182, 183 - - =Sub-thermal= baths, 428 - - =Succus= entericus, action on nucleic acid, 100 - - =Sugar= in diet of gouty, 347 - - =Sulphated= alkaline waters, spas for, 442 - waters, 441, 442 - - =Sweetbreads= in diet of gouty, effect of, 345, 346 - - =Swine=, guanine gout in, 100 - - =Sydenham’s= differentiation of rheumatism from gout, 15 - views on gout, 7 - - =Syncopes=, local, of hand, in gout, 45 - - =Synovia=, appearance in, in acute gout, 52 - - =Synovial= fluid, reaction of, 52 - - =Synovitis=, gouty, relation to local foci of infection, 185 - gummatous, differential diagnosis from chronic articular gout, 277 - of knees, differential diagnosis from gout, 264 - of tendo Achilles in referred pain in heel, 265 - perforative, 57 - villous, chronic, confusion with chronic gout, 279 - clinical symptoms of, 280 - static and non-gouty in origin, 280 - - =Synthetic= formation as source of uric acid, 84 - of uric acid, 96 - - =Syphilis=, articular, muscular and nerve lesions associated with, - 194 - - =Syphilitic= arthritis, secondary, differential diagnosis from acute - gouty polyarthritis, 271 - disease of tarsal joints, differential diagnosis from gout, 263 - - - =Taka-diastase=, 392 - - =Tarsal= joints, gonococcal arthritis of, differential diagnosis - from - gout, 263 - involved in gouty polyarthritis, 214 - tuberculous and syphilitic disease of, differential diagnosis from - gout, 263 - - =Tartareous= nature of tophi, views on, 8 - - =Tea= as beverage in gout, 361 - - =Teeth=, characteristic, in gout, 45 - conditions in gout, 178 - devitalised, examination of, in treatment of gout, 328 - foci of infection, 53 - - =Temperament=, and gout, 44 - - =Temperature= curve of gout, 188 - - =Tendo= Achilles, involved in gout, 215 - - =Tendon= sheaths, involved in gout, 195 - - =Tendons=, gouty polyarthritis in, 214 - uratic deposits in, 153 - - =Test= meals for HCL variations, 336 - - =Tests=, modern, for uric acid determination, disabilities of, 147 - - =Theobromine=, 85 - - =Theophyllin=, 85 - - =Throat=, gouty, 45 - - =Thymine=, 98 - - =Thyminic= acid, 80 - in treatment of acute gout, 383 - - =Thymus=, enzymes in, 99 - gland, nucleic acid derived from, 98 - in diet of gouty patients, effect of, 345, 346 - - =Tibia=, tophi in skin over, 235 - - =Tissue= affinities for uric acid, 157 - protein, 59 - - =Tissues=, human, concentrations of uric acid in, 159 - retention capacity of, for uric acid, 158 - effect on blood content, 138 - - =Toe=, big, gout in, differential diagnosis of, 259 - initial outbreak of gout in, 37, 188 - - =Tonsil=, site of infection in gout, 180 - - =Tonsillar= sepsis, gout and, 178 - - =Tonsillitis=, acute, gout following, 53 - in gouty subjects, 179 - treatment of, in gout, 330 - - =Tonsils=, examination of, in diagnosis of articular gout, 249 - foci of infection, 53 - streptococci in, 183 - - =Tophaceous= deposits in chronic articular gout, 227 - gout, 39 - - =Tophi=, analysis of, 150 - antedating articular attacks, 202 - auricular, 202 - pain in, 233 - clinical evolution of, 162 - constitution of, 149 - constitutional influences in, 161 - diagnostic status of, 252 - difficulty in detecting, 256 - early stages of, confused with chilblains, 164 - early views as to nature of, 7 - evolution and distribution of, 231 - formation preceding arthritic attacks, 164 - frequency of, in gouty arthritis, 255 - gouty, causation of, 154 - formation of, 151 - localisation of, 153 - radiating, concentric and laminated structure of, 152 - urate of soda, 150 - importance of, in diagnosis of acute gouty polyarthritis, 269 - in diagnosis of gout, 38 - in eyes, significance of, 311 - inflammatory nature of swellings in, 163 - in relation to arthritis, 254 - in relation to uricæmia, 155 - sites of, 233 - stage of small red swellings, 163 - treatment of, in chronic articular gout, 407 - - =Tophus= formation in acute gout, 212 - premonitory symptoms of, 203 - in ear, sign of gout, 202 - - =Trauma=, local, effect on gout, 53 - - =Traumatic= lesions, differential diagnosis from gout, 260 - - =Trousseau’s= views on gout, 36 - - =Tuberculous= disease of tarsal joints, differential diagnosis from - gout, 263 - joint disease, differential diagnosis from chronic articular gout, - 277 - - =Toxæmia=, alimentary, hydrochloric acid, 394 - chronic, 182 - - =Toxicity=, low, of chemical products, in gout, 69 - non-, of uric acid, 166 - - - =Ulna=, tophi in skin over, 235 - - =Uracil=, 98 - - =Urate= of soda in gouty tophi, 150 - - =Urates=, deposition of, in eye, 309 - - =Uratic= depositions as criterion of gout, 37 - deposits in gout, 54 - in gout and nephritis, differentiation of, 129 - in gout, localisation of, 153 - in nephritis, 128 - - =Uratosis= in gout, 149 - - =Urea= and glycocine, interaction between, 84 - end-product of protein metabolism, 63 - excretion in gout, 66 - excretion of ammonia as, 63 - formation of, 62 - Folin and Denis’s deductions, 64 - seat of, 63 - in blood in gout and nephritis (table), 121 - - =Ureters=, ligature of, 26 - - =Uric= acid, 75, 77 - a normal constituent in blood, 135 - an end-product, 70 - as a derivative of nucleic acid, 73 - blood content of, in various animals, 135 - variations independently of diet, 142 - chemical constitution of, 75 - concentrations in human tissues, 159 - content of blood and attacks of gout, relation between, 143 - in gout, 139 - deposition of, 22, 34 - destruction of, 98, 104 - determination of, disabilities of modern tests, 147 - diathesis, 294, 295 - discovery of, by Scheele, 8 - estimation of, sources of fallacy, 145 - excretions of, amount of, 75 - exogenous, 85 - in acute gout, 211 - in gout, 108 - anomalies in, 117 - increased by radium emanation, 437 - relation of leucocytosis to, 95 - exogenous purins as source of, 84 - formation of, Amberg and Jones’s scheme of, 103, 104 - from nucleic acid, 98 - gravel, spa treatment of, 451 - in the blood, 78 - forms of, 145 - in gout and nephritis (table), 121 - of gouty patients, discovery of, 21 - organic combinations of, 79 - infarcts, renal, 151 - in relation to gout, 107 - isomeric forms of, 81 - kidney capacity for eliminating, 125 - metabolism, influence of radium emanations on, 436 - non-toxicity of, 166 - of blood in disease (table), 137 - output, endogenous, lowered, 111 - exogenous, retarded, 109 - physical properties of, 78 - retention, capacity of tissues for, 158 - solubilities of, 154 - sources of, 83 - synthetic formation of, 84, 96 - theory of gout, 21 - tissue affinities for, 157 - variations in acute gout, 108 - variations in chronic gout, 109 - Wollaston’s researches on, 8 - - =Uric-acidæmia=, 295 - - =Uricæmia= and gout, 125 - in gout, 133 - in nephritis, 120 - not cause, but result, of gout, 148 - not necessarily due to renal defect, 123 - not peculiar to nephritis, 124 - significance of, 145 - tophi in relation to, 155 - - =Uricase=, 87, 104 - absence of, in man, 104 - - =Uricolysis=, 104 - - =Uricolytic= enzyme, 105 - ferment, absence or diminution of, 106 - - =Urine=, alkapton in, 59 - analysis of, in metabolism of gout, 113 - in treatment of gout, 337 - children’s, creatine in, 68 - cystin in, 59 - effects of guaiacum resin on, 405 - examination of, in diagnosis of articular gout, 250 - gouty, glyoxylic acid in, 65 - human, daily excretion of uric acid, amount of, 83 - scanty, before paroxysm of gout, 205 - - =Urosin= in treatment of acute gout, 383 - - - =Vaccine= therapy in treatment of gout, 331 - - =Vapour= baths, 428 - - =Vegetable= cells, nucleic acid derived from, 98 - - =Vegetables= in diet of gouty, 348 - - =Veins=, engorged, before paroxysm of gout, 205 - - =Venesection=, 4 - gout following, 178 - - =Vichy= bath, 428 - - =Vidal’s= atrophic form of arthritis deformans, 18 - - =Vinegar= in diet of gouty, 350 - - =Viscera=, functional capacity of, tests of, 338 - - =Visceral= organs, tendency to fibrosis in gout, 186 - - =Vitamines=, 340 - - =Volumetric= method of determination of uric acid in blood (Curtman - and Lehrman), 134 - - =Vomiting= in acute paroxysms of gout, 333 - - - =Wade’s= theory of nervous origin of gout, 32 - - =Water=, hot, advantages of, 360 - value of, as beverage in gout, 359 - - “=Water-soluble B=,” 340 - - “=Water-soluble C=,” 340 - - =Watson’s= (Chalmers) researches on gout, 107, 172 - - =Weir-Mitchell= method in reduction of obesity, 357 - - =Whisky= in gout, 364, 370 - - =Wines= as beverages in gout, 364 - general rules, 367 - individual and, 365 - importance of quality of, 366 - - =Wollaston’s= researches on uric acid, 8 - - =Wrist=, site of primary attack of gout, 267 - - - =Xanthine=, 75, 77 - - =Xanthine-oxidase=, 99 - - =Xanthosine-hydrolase=, 102 - - =X-ray= examination of alimentary tract in treatment of gout, 336 - - - =Yeast=, nucleic acid derived from, 98 - 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