Scholarly article on topic 'TRANSACTIONS OF THE AMERICAN SURGICAL ASSOCIATION'

TRANSACTIONS OF THE AMERICAN SURGICAL ASSOCIATION Academic research paper on "Clinical medicine"

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Academic research paper on topic "TRANSACTIONS OF THE AMERICAN SURGICAL ASSOCIATION"

ANNALS OF SURGERY

vol. 113

june, 1941

TRANSACTIONS

OF THE

AMERICAN SURGICAL ASSOCIATION

MEETING HELD AT THE GREENBRIER WHITE SULPHUR SPRINGS, WEST VIRGINIA april 28, 29. 30, 1941

ADDRESS OF THE PRESIDENT MARS AND AESCULAPIUS* David Cheeveh, M.D.

IiosTo.v, Mass.

Ox this rostrum, a Fellow of the Association lias stood each year since its founding and tried to find words adequately to express his feelings. Let each of my hearers put himself in my place, which he may sometime occupy, and think what he could say to make known at once his pride and sense of personal inadequacy in justifying the honor conferred upon him. He would

find, as do I, that mere words cannot avail.

During the threescore years of our existence as an Association, for hut one period—if we except the skirmish of 189S—have we faced war. In 1916, goaded by insults to our national sovereignty and moved by deep sympathy for the allied nations attacked by a common enemy, we stood on the brink of war, which prompted Le Conte to make his eloquent appeal for preparedness, medical as well as military. In 1917, committed to war but, under the protection of our sore-pressed Allies, feverishly preparing and still not actively engaged, Mixter, describing the war as conservative since it must be waged in the defense of humanity, pointed out its analogy to the duty required of those who must remain at home, to conserve and defend the high standards of sur-

* Delivered before the American Surgical Association, White Sulphur Springs, W. Va., April 28, 1941.

Annall of Sürßen June. 1 u t !

gery. In 1919 and 1920, Pilcher and Brewer described the influence of war surgerv 011 civil practice and discussed the methods and steps bv which civilian surgeons could be trained and organized for military needs and with Lund, in 1930, recounted the record of our Association and of the profession at large in the First World War. It is worth repeating. Of our Fellows, S3 per cent volunteered, among them 25 of the 33 Senior Fellows of an average age of 70. Ninety-four of the 11G commissioned officers were of field rank, and there were received 22 decorations and ten citations. Of the 14,35s medical officers who went overseas, 68 were killed in action or died of wounds, 212 survived wounds, 11 were missing in action or lost at sea. These surgeons and physicians of America, who volunteered or were drafted from civil life and, confronted by unaccustomed problems, made grievous mistakes and achieved glorious triumphs, as did their fellows in the line, like them, paid the price.

With our weight tilting the scale the war was won but the peace, it seems, was lost, for now, scarcely a score of years later, we stand again at the gates of Armageddon. Our idealism in undertaking to ensure the future of Democracy by waging a war to end war lias become a mockery. The same enemy confronts us, his purpose far more sinister, his strength vastly augmented by the devotion of the whole wealth and power of a great nation to the sole purpose of ruthless aggression, his resources multiplied by those of peace-loving, terrorized, conquered peoples; his mailed fist supported by allied ghouls whose nostrils tell them—falsely to be sure—of the expected kill. More dangerous is he because of his strength, but also because of the doctrine with which he has inoculated the people—a doctrine at once ludicrous, absurd but dreadful ¡11 its evil intent, of a superior race predestined by the Creator to prosper at the expense of all other peoples. This foe is bending all the agencies of the physio-chemical and psychologic sciences to llis purpose and showers death in its most ghastly forms 011 man, and destruction 011 the monuments of his civilization, to a degree which is callously designed to involve a nation in its totality if it refuses to submit. Gone or nearly so, 011 his part at least, are .the mitigations of the so-called rules of war, the chivalries of equal combat among men. The unarmed, the defenseless, the weak, the aged, the young of either sex have no privilege of even partial exemption, but rather suffer the more because they have not the strength for self-defense. And standing rock-like .against this monstrous, reckless, merciless destroyer stands the English-speaking Island Empire and her overseas' daughters, shorn by enemy subjugation of all her Allies save one, asking us to consider whether a precarious freedom can be enjoyed alone in case of her defeat.

In the face of this chaos of material destruction and of spiritual degradation, of bleeding bodies and of hating souls one wonders whether we live in ail ordered world, where war is really an inevitable and perhaps a desirable condition. This viewpoint is found in the writings of social and moral philosophers from the beginning of recorded history to the present, and we are only too familiar with their pronouncements. Karl von Stengel, a German jurist who, in odd contradiction to his views, was a delegate to the first Hague Peace

Vu I il m« 113 Number G

Conference, says: "War has more often facilitated than hindered progress . . . great States like Germany and Italy are welded into nationalities only through blood and iron; . . . storm purifies the air and destroys the frail trees, leaving the sturdy oaks standing; ... War is the test of a nation's political, physical and intellectual worth." von Moltke wrote: "A perpetual peace is a dream and not even a beautiful dream. War is one of the Elements of order in the world established by God; the noblest virtues of man are developed therein." Ernest Renan declares: "W ar is one of the conditions of progress, ... it compels satisfied mediocrity to awaken from its apathy." And Theodore Roosevelt declared: "By war alone can we acquire those virile qualities necessary to win in the stem strife of actual life." Curiously enough a pacifist, upholding the moral over the natural law, may reach the same decision as the

militarist. Thus Edward Gruhh says: "Self-preservation is not the final law for nations any more than for individuals; . . . the progress of humanity may demand the extinction of the individual, and it may demand also the example and the inspiration of a martyr nation." It is not vouchsafed to us to make authoritative pronouncement on the validity of these views; each of us is guided by his experience and by his study of the humanities and of science. One concept, however, seems worth considering: If the existence of man upon this planet is counted back by tens of thousands of years to the Quarternary Period, or by hundreds of thousands of years into the Tertiary, it cannot be doubted that science has caused more fundamental changes in the conditions of his life in the last hundred, nav even the last fifty years, than occurred in the entire antecedent period. Perhaps the moralities based on the mores of the past are no longer tenable in a mechanized world.

We are on safe ground, however, if we affirm that the art and science of medicine throughout recorded history, has found opportunity for development in war—a development which also has found its application in peace. To go no further hack than 800 ii.c. we find a clinical observer named Homer, in a communication which he called the Iliad, describing in the ten-year contest between the well-greaved Greeks and the horse-taming Trojans 011 the plains of Troy, 110 less than 147 wounds by spear, sword, arrow, and slings which showed a mortality of 77.6 per cent. The army surgeon most often mentioned was Machaon, for when the Trojan Paudarus broke the truce by wounding Menelaus in the shoulder with an arrow, Agamemnon sent his Herald for "the hero Machaon, son of the blameless physician JEsculapius," who, having extracted the arrow head, "sucked out the blood and skillfully sprinkled on the wound soothing remedies." This was some 25 centuries or more before the Geneva Convention so that the Medical Corps were not protected by the Red Cross (nor are they now, 77 years later under the usages of totalitarian warfare) ; so it appears that the surgeons spent their spare time in combat, for Homer tells us that "Paris, the husband of fair-haired Helen, disabled Machaon, the Shepherd of the people performing prodigies of valor, wounding him 011 the right shoulder with a triple-barbed arrow." Idomeneus then prevailed 011 Nestor to carry Machaon from the fight in his armored chariot.

Annal» of Sitrserv June. 1 ¡M 1

"For," said lie, "a medical man is equivalent to many others, both to cut out arrows and to apply mild remedies."

Progress and indeed change of any sort were conspicuous by their absence through succeeding centuries, but always the wars furnished the school of experience for surgeons. Five hundred years after the sack of Troy, the Father of Medicine, Hippocrates said: "He who would become a surgeon therefore should join the army and follow it." Through the classic days of Greece and Rome, through the intellectual and cultural gloom of the Middle Ages, the thousand years between the downfall of the W estern and of the Eastern Empires, most of the time under the domination of the Galenic tradition, the art of medicine progressed but little and science not at all. Printing was invented but found at first 110 scientific gospel to spread abroad; the advent of gunpowder and firearms modified the tactics of warfare and the nature of wounds; the mariner's compass helped bring the questionable blessings of European civilization to aboriginal and pagan peoples. The physician of the period was attached to the persons of feudal overlords and princes, tile practice of surgery was relegated to barber-surgeons, incisors, tooth extractors, and quacks who ministered alike to soldiers and the common herd. There was little to suggest the near approach of the rediscovery of Greek culture and the activities of the dormant genius of western Europe, especially of Italy, which we call the Renaissance.

Modern science properly begins with Copernicus, who founded modern astronomy, and with Vesalius, author of the greatest medical book ever written, in a century which sparkles with great names in art, literature, philosophy, and medicine. AmbroTse Pare, "unquestionably the greatest surgeon of the Renaissance" gained an experience in the army of Francis II which led him to revolutionize the treatment of wounds, already modified by Paracelsus. On a certain battlefield, having exhausted his supply of "scalding oyle of Elders with a little Treacle mixed therewith" with which in accordance with tradition he cauterized the supposedly poisoned gunshot wounds, he substituted a bland "digestive made of the volke of an egg, ovle of Roses and Turpentine" and, having passed a night sleepless with anxiety, found those thus treated comfortable, well-rested, and with noiiinflamed wounds, which made him resolve "never again to cauterize any wounded with gunshot."- He further avoided unnecessary surgical trauma by reviving the ligature as a substitute for cauterization to arrest hemorrhage. Vesalius was a military surgeon under Charles V and may well have been inspired by the surgical problems of the battlefield to study and to teach anatomy. The same source may have supplied him with material for dissection. Harvey, whose demonstration of the circulation of the blood, and researches in anatomy, microscopy, and chemistry were the beginning of modern experimental physiology, served in the army, as did many of the greatest physicians of the seventeenth century—Descartes, Willis. Sydenham, Wiseman. This was an era of frightful epidemics of bubonic plague, typhus, dysentery; devouring famine stalked in the train of constant warfare; the Germanic states were all but ruined by the Thirty Years War.

Volume 113 Number 6

Prostitution was rife in the armies. Physicians and surgeons had problems enough with practically 110 scientific knowledge to aid them. The eighteenth century was an age of artificiality and gross materialism peopled by those, in Carlyle's cynical phrase, "»hose souls were extinct but stomachs well alive."

In a period of formal theories and systems, nevertheless, clinical advances of extraordinary significance were made: The therapeutic use of digitalis by Withering; the discovery of percussion by Auenbrugger; the introduction of the pulse-watch and of clinical thermometry; the harnessing of electricity for electrotherapy by Volta, Galvani and Franklin; the creation of immunity by inoculation with a kindred but harmless disease by Jenner which conferred on man the power, not always utilized, alas!, of controlling if not eliminating an ubiquitous and fatal pestilence. The provision of adequate care for troops became a definite function of government, and the camp and the battlefield continued to be the great practice schools for surgeons. Wound treatment became simpler, and apparently empiric observation prompted the use of antiseptic dressings long before Pasteur and Lister demonstrated microbic organisms, for we read of the packing of wounds with lint moistened with brandy, corrosive sublimate, balsam of Peru, tincture of myrrh, camphor, and turpentine. John Hunter's commanding figure dominates the surgical stage, and we must believe that much of his experience was gained as a military surgeon and finally as surgeon-general of the British Army; for the list of his chief contributions—the nature and treatment of shock, phlebitis, intussusception, chancre, chancroid, aneurysm, dental diseases, inflammation, and gunshot wounds indicate the source of much of his clinical material, which his use of the experimental method and knowledge of pathology made the establishment of surgery as a branch of scientific medicine. The development of surgery in America was promoted by the experience of the Revolutionary War, in the work of Morgan, Sbippen, Rush and Wrarren; the first American Pharmacopeia was prepared for the use of the Continental Army by Dr. William Brown, and the first book 011 surgery published in America was a Treatise 011 Wounds and Fractures by Dr. John Jones in 1776. To the end of this century and the beginning of the next belongs the amazing Larrev, surgeon-in-chief of the Grande Armee. participant in 60 battles and 400 engagements of the Napoleonic wars, originator of systematic first aid to the wounded, who advocated debridement and was adjudged to be worth in his own person a division of troops.

With the nineteenth century we are reaching modern times, where we can better realize the conditions attending the care of troops. Of all wars up to that time, the Crimean War of 1854-1S55 is said to have had the greatest teaching value in military medicine. Its success was nearly wrecked by utterly inadequate sanitary and supply service. In the combined British and French forces, four times as many men died from disease as from enemy action and the French suffered the highest recorded mortality rate from disease—253 per 1,000. Conditions at the base at Scutari were indescribably bad. Soldiers

DAVID CHEEVER Ann.i, or

June. 1 'J 4 ]

ill and dying of cholera, typhus, dysentery, and scurvy were crowded together with the wounded and the less seriously ill, without beds, often without bedding, without proper sanitary arrangements and supplies and without any epidemiologic precautions. There were no nurses. These scandalous conditions created indignation in England which resulted in the dispatch of a young woman, who was advocating the training of women for nursing services, Florence Nightingale, with a score of volunteers. The story of herWell-nigh magical transformation of pest houses into hospitals, of utter hopelessness into sanguine resolution is one of the most stirring epics of our race. In a futile and disastrous war a modest worker found the opportunity to create one of mankind's most blessed institutions, modern trained nursing. In our own War between the States were created for the first time organized ambulance corps and mobile field hospitals under canvas, and the importance of the medical corps in military campaigns was recognized by giving its officers increased rank and authority. Da Costa. Weir -Mitchell, and Keen found their opportunity in the special military hospitals established for the treatment of cardiac, pulmonary, and nervous diseases. It has been said that American neurology sprang from the war and grew up in the army. The experience in surgery gained by thousands of armv surgeons who returned to civil life tended to improve the level of practice in the community. Although the first official record of a military medical nature was published by the British Government after the Crimean War, the six volumes entitled The Medical and Surgical History of the War of the Rebellion constituted a most important contribution to military medicine and set a worthy standard of attainment. The Franco-Prussian War of 1S70 proved incontestably the importance of the elaborate sanitary preparations which were made by the Germans ; among their forces for the first time in history the battle losses exceeded the deaths from disease ", the incidence of and deaths from smallpox among the incompletely vaccinated French prisoners were five times those of the efficiently protected Germans. Lister's new antiseptic method first published in 1S67, which was bitterly opposed by most of the British profession outside of Scotland, was eagerly adopted by German army surgeons under the leadership of Volkmann, Mikulicz and Thiersch and passed this searching test successfully. Our skirmish with Spain-in 1S9S brought out in high relief that epidemics may be more serious than battles, for then, probably for the last time in history, typhoid fever exacted its dreadful toll by causing most of the 3.450 deaths from disease, contrasted with the 559 deaths from enemy action. The Boer War but two years later was the occasion of the first use of antityphoid vaccination 011 a scale large enough and with sufficient success to justify its general adoption. The Russo-Japanese War demonstrated anew the overwhelming value of carefully organized sanitary measures in maintaining health and morale before battle, and the possibilities of a highly developed field ambulance and first aid system supplemented by mobile hospitals in saving lives which would otherwise be lost by delay.

Volume 113 Number fi

The First World War was remarkable and unique in its mobilization and use of every branch of science and of art on a scale never before attempted, primarily in the production and perfection of engines of war and the training of men to use them, and secondarily in measures to maintain the morale of troops, prevent epidemic sickness, and get wounded men back on the firing line as quickly as possible. The improvement in wound treatment is shown by the fact that in our Civil War the mortality among wounded men who reached an hospital was 10.5 per cent and in the World War it was reduced to 4.5 per cent; nor does this tell the whole storv because the highly fertilized soil of France and Belgium was reeking with pathogenic organisms of all sorts, especially gas-forming anaerobes and tetanus bacilli which impregnated the uniforms of men caked with the dirt and mud of trench warfare. All the world knows of the researches of the English chemist Dakin and our own Carrel in developing the efficient method of wound disinfection which bears their name, the similar employment of eusol introduced by Smith, and the bis-nuith-iodoform-paraffin paste of Rutherford Brown. The more or less forgotten wound excision practiced a hundred years before by Larrev was revived as the modern debridement. The prompt reduction and immobilization of fractures was aided by reviving and popularizing the Thomas type of splint and the Balkan frame. The return to active duty of 70 per cent to So per cent of all nonfatal casualties in two months or less is eloquent testimony to the efficacy of these methods. Important studies of shock were made by Porter, Crile, Cannon, and others, and though the last word is still to be said 011 this subject, a standard and relatively satisfactory method of treatment was proposed and adopted. In England, Starling and Hill worked 011 the problems of asphyxiation bv war gasses, Mott studied shell shock, Lewis unraveled the mystery of neurocirculatory asthenia. In France, Marie studied injuries of the central and peripheral nervous systems and contributed to an understanding of their pathologic physiology. When wounds of certain regions were found to create special problems, as in the case of the cranial cavity and its contents, of face and jaws, of the thorax, they were gathered so far as possible into the hands of specialists who were enabled by the study of so many cases to formulate important principles of treatment. Never was such opportunity given to practice the plastic and reconstructive repair of ghastly disfigurements, or to restore to relative usefulness, at least, shattered bones and disorganized joints. The success of the sanitary measures taken both on the battle fronts and in cantonments constitutes one of the greatest triumphs of medical sanitary science. Preventive inoculation rendered harmless smallpox, typhoid fever, tetanus, diphtheria, and even the dysenteric diseases. The control of the vermin-borne diseases, typhus and trench fever, was accomplished by the adoption of a method of de-lousing which approached a science in its exactitude. The incidence of meningitis was lowered. There remained, however, problems still unsolved—influenza, pneumonia, measles, mumps, scarlet fever, and venereal diseases took their inevitable toll. The total deaths from disease in our forces were 50,174. Had the rates prevailing in our Civil War

Annati «f surcfn June. 194 1

been the rule, the figures would have been 227,094, or four and one-half times greater. It is tempting to mention those of our Fellows, indeed those of the Allied Forces, whose share in these triumphs of healing and sanitation were most conspicuous, but it .might seem invidious when each played faithfully his appointed part as far as he was able, according to his opportunity.

In the interval of time since the First World War was ended by a premature armistice, the experience which it afforded has been reviewed, analyzed, evaluated, and applied to the needs of everyday life. The internecine war in Spain has supplied the opportunity for further clinical experiment, of which the most striking development has been in the treatment of wounds, especially compound fractures. The Carrel-Dakin and similar methods involving frequent irrigation, laborious and often painful dressings, the saturation of plaster fixation molds, and the inevitable interruption of treatment during transportation, constituted a great advance over many other antiseptic methods at the expense of serious difficulties of execution. Orr's personal experience of these difficulties and his study of the factors involved in the healing of infected wounds led him to adopt the method now widely known by his name, foreshadowed by Oilier of Lyon, by Lister himself, and by others, but perfected and brought to the somewhat incredulous attention of the medical world by an American surgeon. The method, which will be presented and discussed at our symposium, has achieved such amazing results ¡11 the hands of its advocates that it may constitute a revolutionary improvement in the treatment of certain classes of wounds.

Epidemiology and preventive medicine have steadily advanced. Tetanus and diphtheria will be all but abolished by immunization by toxoids. Pneumonia and epidemic meningitis, hitherto unsolved problems, are having their mortality rate cut in half and again in half by chemotherapy. Gonorrhea is aborted by the same means. For typhus and influenza there is as yet no dependable immunizing agent, but sanitary control is increasingly effective. The importance to war industries of the health of the workers has led to the intensive study of industrial hygiene; the diseases due to dust of various sorts, to lead and its compounds, to volatile organic solvents, to radiation, to welding and metallurgic processes, to the manufacture of nitro-explosives—all these and many more are yielding to control to a degree which is of greatest importance in civil life. Anxious study is being devoted to the serious functional disturbance caused by the conditions attending war aviation—anoxemia, low pressure, extreme cold, terrific speed with sudden variations as in dive-bombing and unprecedented nerve strain. It has. been stated that in the First World War of every 100 pilots killed, two died as the result of enemy action, eight from defective equipment, and 90 from defects in themselves, which means in the majority of instances fatal disturbances of normal physiology. The relative importance of the various elements in the treatment of shock is being tested, especially the use of plasma preserved in various ways and even of an artificially prepared plasma as a substitute for whole blood. The role played by vitamins in nutrition and the provision of vitamin-protected foods

volume 113 .MARS AND AESCULAPIUS

NimilHT c

to support maximum physical effort is being investigated on an unprecedented scale. Unlimited material for the study of the neuroses is at hand.

Unquestionably, the conditions attending war offer opportunities for gaining knowledge which is of permanent rather than of emergency value. As l.ord llordcr expresses it: "War is an evil tiling, but has done good, like a hormone, in activating the whole chemistry of the Nation." Regarded philosophically, it illustrates the unsolved paradox of human behavior, that the same intelligence should invent and cherish the things which safeguard, enrich, and beautify life, and permit their use to disfigure, degrade, and destroy it. It is said that in the sixteenth century the average duration of a human life in western Europe was 19 years; in the eighteenth century it had lengthened to 32 years; now it is 62 years, and this has been accomplished by the same intellectual processes of observation, experimentation, research, and judgment as were employed in the First World War to maim or slaughter 30 million human beings. The same chemists working in the same laboratory may synthesize elements to make tri-nitro-toluol to destroy life and a sulfonamide compound to save it. The same mechanical device operating 011 the same physical principles is used, as Doctor Fosdick says, to point a telescope at a constellation or to aim a siege-gun at a sleeping city. Science is accused of prostituting herself for ignoble and despicable ends—it is not Science herself but her generously bestowed gifts to Man which he chooses thus to employ. "It is clear," says Charles Seymour, "that the crux of the problem confronting 11s is the proper application of science to life."

It is probable that when major disasters threaten the world, as when Attila and his Huns, and later Jenghis Khan and his Mongols, swept over most of western Europe, the civilized world must have felt that the supreme crisis was at hand and that civilization hung in the balance. May it not be that at the present moment—iS months after the outbreak of the Second World War—we are facing the most fearful crisis of all ? When Homer sang of Troy, there sat upon the summit of Olympus aegis-bearing Zeus, with his staff of lesser gods: his consort, large-eyed Juno, far-darting Apollo, spear-brandishing Minerva, laughter-loving Venus, and the renowned artificer, Vulcan. They were quite human in their attributes—these gods; they loved and quarreled, laughed and wept, and knew the quality of mercy, and the nature of their guidance of men upon the earth below mirrored these qualities. Nigh 3,000 years have passed, Zeus is dethroned and there stands upon Olympus a sinister figure wearing as insignia a twisted cross—a figure cruel, ruthless, savage, yet armed with every weapon of destruction provided by enlightened science and industry. The satellites about him are but slavish executives of his evil will. Twenty nations and principalities cower and bleed beneath the rain of fire and steel which he has loosed and not one small voice among the mighty people whom he rules cries out in shame and protest.

Again Britain and her daughter nations, bleeding but with heads unbowed, stand against this monstrous thing. Again America is moving to their side;

DAVID CHEEVER f s™>

again the weight ol her power will press down the scale-pan wherein lie liberty and justice. When the victory shall he won, let our--care be that mankind shall also win the peacc by lavishing on its nurture something of the same energy, treasure, and self-sacrifice which is poured into the lap of Mars.

SURGERY AND THE SULFONAMIDES

The practical problems of surgery that come up in conncction with the use of these drugs can for the most part be solved by keeping in mind the pathology of the process under treatment and relating the pathology to the mode of action of the sulfonamide compounds.

In the first place, a contaminated wound, a compound fracture, or a wound resulting from a colon resection is a fresh wound with an amount of necrotic tissue in it which varies with the nature of the wound, the effectiveness of debridement in that wound, and the duration of the wound after the trauma. The presence of sulfonamide inhibitors is usually low in these wounds, and. therefore, sulfanilamide therapy is particularly effective in preventing the outgrowth of the contaminating organisms in these wounds. We arc tending, most generally, to use sulfanilamide as the drug of choice in wound prophylaxis of this sort, partly because we feel that in general it is a little safer than the other sulfonamides. We do not get the kidney complications that can occur with sulfathiazole. and. for the time being, we arc tending to stick to sulfanilamide in this particular prophylactic use. Later on there may be reason to change, but for the present I think sulfanilamide is the drug of choice. In such traumatic wounds, infection can be prevented either by the administration of the drug by mouth or by introducing the drug locally into the wound either in the form of crystals or in the form of solutions. The high concentrations which can be obtained with local application will tend to prevent the outgrowth of types of bacteria such as staphylococci which might be resistant to the smaller concentrations obtainable with oral administration.

There is no reason yet to believe, however, that the local implantation or application of sulfanilamide in such wounds should be used as a substitute entirely for the systematic administration.

I will not attempt to go into the chemistry of these sulfonamide inhibitors except to say that they are at present in very high concentration in products of tissue necrosis. Any infection which brings about an extensive degree of tissue breakdown or digestion or necrosis, whatever you want to call it. results in enzymatic degradation of the tissue and liberates a large amount of these sulfonamide inhibitors, which will in turn prevent or tend to prevent the effective bacteriostatic action of the sulfonamides.

Some aspects of this subject of the mode of action with sulfonamides are still in a state of controversy. We all tend to have our own ideas, and I feel myself that not every point in my own- hypothesis has been established beyond question.

—John S. Lockwood. M.D.. Phila..—Round Table Conferences on Recent Advances in Chemotherapy. Pennsylvania Medical Journal. 44. No. 5, 580-592. 1941.