SECTION VIII--Editorial The edilorial contributions published in thi~ Journal represent only the opinions of theb" writers. Such being the case, thi~

Jotwnal is in no way responsible for editorial ezpreasions.

M E D I C I N A L T H E R A P Y T O

C O M B A T A M E B I A S I S

T H E recent "epidemic" of acute amebiasis which, appar- l e n t l y , flared up from Chicago s ancient sewage system with attendant food befoulment, revives former disputes re- garding the comparative worth of medicinal agents.

Persons who have secured their knowledge of endameba histolytica, of clinical amebiasls and of therapeutic remedies within the past six months hold far more definite opinions regarding curative medicinals than do clinicians and investi- gators who actually have been in close contact with amebiasis over many years.

It is quite a common experience--and rather a startling one to experts in human parasitology--to hear these clinical neophytes or those whose knowledge has been gained merely by reading literature, speak glibly on such-and-such a drug as being "specific" as an amebacide. To them, treatment of the infection means the simple exhibition of emetin and one of the arsenic or iodine-rich drugs, most of which latter drugs have been developed by foreign chemical firms and now are flooding the United States. Unfortunate tho' it be, medicinal therapy for amebiasis cannot be learned from read- ing advertising pamphlets or the slips in trade packages of drugs. Undoubtedly, much of the confusion extant comes from those made familiar with clinical amebiasis only during the past half year, attempting to use "specific" therapy as exampled by the "newer" drugs, endeavoring to fit the patient go what the advertising circular advises and failing to have a proper appreciation of how endarneba hislolytica produces its peculiar pathology, its clinical symptology and its con- stitutional effects. In acute amebiasis, with its fulminating symptoms, pathology is abrupt, extensive and diversified: in latent amebiasis, pathological damage may be organic and functional, yet symptoms need not be distressing or such as physicians with but reading knowledge of the affection might suspect as being even remotely connected with pathogenic protozoiasis.

To those clinicians or "armchair therapeutists" to whom human amebiasis has swung acutely into their professional ken and who speak so confidently of the need for the em- ployment of the "new" specific remedies, it should be told that before the market was filled with yatrin, treparsol, carbarzone, stovarsol, chinofon, vioform el al amebiasis. acute or latent, was treated probably quite as successfully as it now is by drugs which are named in standard pharmaco- poeias and which, not only are cheap and accessible, but are relatively harmless. When clinicians of vast experience have found reliable in therapy drugs so inexpensive and available as ipecac, emetin, emetin bismuth iodide, bismuth com- pounds and of the arsenicals, sodium cacadylate and the sal- varsans, it behooves the average practitioner to question the advisability or the necessity for the exhibition of the "new" arsenic or iodine-heavy compounds, mixtures or combinations so admittedly dangerous that no trade package is marketed without its accompanying circular of warning. There is much need for such warnings: one has but to see patients to whose amebiasis has been added medicinally-induced, extensive exfoliative dermatitis, optic atrophy, degenerative spinal cord or peripheral nerve damage or parenchymatous destruc- tion of the liver or the kidneys to realize that "specific" tho" the newer pharmaceuticals may be against endameba bisto- lytica in exercising their lethal properties, also, they may destroy the tissue of essential organs. When subjects are especially susceptible to arsenic or even to iodine, the "aller- gic" response to the exhibition of the newer amebacides may be prompt and startling. Brown says, "As both emetin and arsenic (treparsol) are poisons and may produce early or late

evidences of intoxication; these must not be used except under close suoervision." Unfortunately, one may not know in advance of giving these newer, patent drugs how sudden and disastrous may be the constitutional response. Evidence is accumulating which demonstrates that when such active remedies are administered during amebic dysentery, con- tinuance of exhausting diarrhoea and painful tenesmus can be ascribed to the therapy.

Much of the treatment of acate amebiasis is comprised by rest, systematically and of the part involved, proper food, good hygiene and expert nursing. Hypodermatic injections (seemingly most safely, subcutaneously) of small doses of emetin hydrochloride, over the dysentery-period, do much to relieve diarrhoea and urgency; what "specific" effect towards endameba hislolylica is exerted by emetin injections has not been determined. Certainly, properly controlled, the remedy is safe and beneficial. As Cushney observed, the parasites in both the intestinal canal and within the tissues are killed or rendered harmless by interval, oral exhibition of emetin-bismuth-iodide or ipecac. If one seeks an agent-- an arsenical--which brings systemic action against the pro- tozoa, small doses of neosalvarsan or of sodium cacadylate given intravenously are effective and readily controllable with respect to toxicity. Moreover, arsenic administered intravenously rapidly is effective and it is quickly eliminated. After the acute dysentery-stage of the affection has passed, large doses of bismuth subgallate and bismuth subnitrate pro- tect the injured gut and appear to have a definite effect towards controlling cyst maturation.

It is not the intention of this communication to condemn utterly the use of strong arsenicals (stovarsol, carbarzone, etc.) or of iodine rich drugs (vioform) : our intent is to call the attention of physicians to the fact that amebiasis, even in its acute stage, long has and still can be handled satisfactorily and safely by drugs which are in the pharmacopoeia, which are inexpensive, available and not toxic. Certainly, years of experience throughout the world has given evidence in sup- port of this opinion. If the newer remedies are employed they should be administered only by those familiar with amebiasis and also with the toxic potentialities of, particularly, the arsenic compounds now being so widely distributed.

Recently there has been a tendency to omit colon instilla- tions from the therapeutic armamentarium of acute ame- biasis. DeRivas has proved that the thermal death-point of endameba hislolylica is but a few degrees above 100 F. When properly administered in suitable instances, undoubt- edly the daily or twice daily instillation of several liters of normal saline 'solution at a temperature of 110 degrees F. acts favorably against the trophozoites--perhaps cysts-- cleanses the lower bowel, limits the quantity and kind of the so frequently associated dysentery-producing bacteria and, to a patient greatly shocked and dehydrated by frequent bowel movements, contributes fluid in such quantity as may enable him to weather a crisis. One has only to observe the effects of slowly-given colon-irrigations, via the two-way tube of small calibre, to be convinced of the favorable influence of taking advantage of DeBivas' studies. "Medicated" lavages are of questionable benefit, from the viewpoint of the actual action of the drugs which they carry. Probably of least harm--and perhaps therapeutically efficient--is a 1-2500 solution of mercurochrome at a temperature of 110 degrees F. Evensuch instillation may have its chief efficacy in the heat and the fluid--but one may not say that mer- curochrome has no significance with regards its action on colon protozoa and dysentery-producing bacteria; its ~vefl known properties of penetrating tissue may diminish the activity of trophozoites in the bowel-wall.

Unless a former attack of the acute infection is known, latent or chronic amebiasis may escape recognition. It may

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148 AM~atc.~'~ JOURNAL OF DIGESTIVE DISEASES AND NUTRITION

be discovered at operation or when, during the course of an obscure ailment, endamebae unsuspectingly are found in the stools. Hence, therapy often is impossible unless the acute state of the affection develops. Atypical tumors or deformity of the colon, fibroses of the terminal ileum and cecum, liver abscess, recto-vaginal fistula, pelvic inflammation, dyspepsia associated with achlorhydria, anemia, often grave but atypical, are but some of the ways by which latent amebiasis exhibits itself. It is not to be wondered that surgical procedures dis- close anomalous lesions or precipitate fatal crises or that patients wander from physician to physician receiving only symptomatic treatment. Unless previous acute amebiasis has been known to have occurred or the history discloses that the patient has been in an environment where the possibilities of contaminated foods or water suggest amebiasis, latent ame- biasis commonly escapes special treatment.

Patients who have recovered from acute amebiasis require not alone the exhibition of amebacides--emetin-bismuth- iodide, an arsenical compound or bismuth, at intervals--but should be therapeutically and dietetically managed from the standpoints of chronic damage to liver and biliary tract, the pancreas, the hematopoetic system, functional deficiencies in digestive secretions, nervous and psychic anomalies. The management of chronic, "latent" amebiasis means more than regarding a ~ubject as a "carrier," more than the exhibition of drugs to forestall the effects possible from irregularly ma- turating cysts with release of trophozoites. The patient who has experienced amebic dysentery,, forever is an individual exhibiting varying degrees of organm and functional invalid- ism. With this conception, only can he be treated with hopes of being kept in reasonably good health. F.S.

G A S T R I C A C I D I T Y A N D A S S O C I A T E D

G A S T R I C D I S E A S E

"No acid, no ('peptic') ulcerl" is a frequently repeated dictum by so-called "gastroenterologists" and others. Its careless repetition has led to much confusion, etiologically and therapeutically. Moreover the dictum is not a true ap- preciation of gastric chemism when peptic ulcer exists.

Loose thinking, using the ideas of men long gone in lieu of individual cerebration together with the endless copying of statements from ancient literature into "modern" text-books are responsible for the continued acceptance that the action of free Hcl is the main agent responsible for the cause and the continuance of peptic ulcer. Undoubtedly, when primary disturbances in the gastric wall have left an area of dead or physiologically defenseless tissue, this tissue quickly is di- ges ted- jus t as would be food-proteins--when pepsin and free Hcl combine with it. In such circumstances, the chemi- cal action of free Hcl and pepsin plays a part in the first of what are natural steps in ulcer-healing; they clean the injured area of useless cellular detritus so that there is available a suitable surface upon which reparative epithelialization may progress. I t is true that this first spontaneous effort at cure actually may partially defeat its own purposes.

Peptic ulcer - - if we classify it as a lesion--really repre- sents a complication in a peculiar type of mural pathology-- i.e. true ulcers rarely develop from the visceral lumen outward; they arise when, locally, in the visceral wall, many agents, acting in similar fashion but with various degrees of inten- sity, have brought about such changes in vascular or cellular architecture as to "devitalize" or destroy mural tissue, himen- ward from the point of the mural defect. I t is necessary to hold this conception of "pre-ulcer" mural pathology if one is to think clearly regarding the significances of gastric contents in respect to the production of the "ulcer-stage" of the lesion, to appreciate such complications as hemorrhage or perfora- tion, to visualize repair or recrudescence and the effects of therapeutic programs.

"No acid, no ulcer" is a dictum of but partial truth, a slo- gan suited to those in whom there is warranted the suspicion that the plasma has "set" in their inter-ganglionic spaces; a clinical pseudo-aphorism whose acceptance undoubtedly, l~as prevented progress in the appreciation of a broad-based,

physiological conception of ulcer etiology and in the general application of a form of therapeutic regimen which is more than "rule-of-thumb" in scope and value.

Let it be recalled that "peptic," gastric ulcer occurs most frequently in the parts of the stomach not devoted to the elaboration and secretion of free Hcl. Where ulcer is most commonly located, the mucosa is concerned with pepsin production and, very intensely, with mixing the meal-mass and shaping it for ejection into the duodenum. In the alka- line duodenum arises the greatest number of "peptic" ulcers. They do not develop in that part of the duodenum on which "impinges" the acid chyme-stream. Unless the duodenum be anchored, that quickly-moving viscus presents an ever- changing segment to the gastric spurt of the fast moving chyme. The chyme becomes alkaline chyle within 18 inches of the pylorus, consequent upon free admixture with pan- creatic juice and bile. Within a few minutes and in a small space, occur rapid neutralization of chyme, saponification, intense ferment action and a series of physio-chemic se- quences: so composite a food as milk and cream may be within the lacteals in less than a half hour after its being introduced to the normal, adult, fasting stomach.

Thus, in health, there is scant opportunity for acid arising within the stomach, to be a factor in exerting a "corrosive action" upon duodenal mucosa. Indeed, why should such be regarded as necessary to ulcer production when within the duodenum is available trypsin--a protein-digestant.equal to, if not much more potent than is, the free Hcl-pepsm gastric admixture. Moreover, "peptic" ulcer (why not call duodenal ulcer "tryptic" ulcerP) of the duodenum does not appear until first there have occurred essential, pre-ulcer lesions in its wall. True enough, experimentally-produced "peptic" ulcer of the duodenum has been achieved or ulcer kept active on the basis of the "acid factor," but one must admit that ex- perimentally-produced ulcer is of a nature and course far different from true peptic ulcer arising spontaneously in man. Even under the most meticulous watchfulness of the shrewd- est and most wizardly technical investigator, "experimental" ulcer first is a maral and not a mucosal defect. When dam- aged surface tissue is made available to the action of Hcl- pepsin, of trypsin or of both, then, and then only does the ulcer-form lesion appear. All this is apart from the needed consideration of an abnormal sequence of digestive events, of changed innervation, circulation, muscle interplay or even of atypic alimentary canal food-mass secretion and bacterial flora. Further, even in the presence of all these artificial factors, experimenters have achieved true chronicity--a very striking characteristic of spontaneously arising ulcer--or have mimicked normal complications, in only a few of the ulcers which they have initiated. In spite of tremendous handicaps, in the tissues the urge to heal remains strong-- just as it does in spontaneously arising peptic ulcer of man if there be not too much or too freakish "treatment" exhibited.

"No acid, no ulcerl" Yet all experimenters and clinicians have had opportunity to observe peptic ulcer progressing to fatal hemorrhage or perforation in the presence of achlor- hydria, essential or medicinal.

Conversely, large amounts of solation of free Hcl, even of a titre in excess of normal, may be introduced into the stomachs of subjects affected with proved ulcers and yet clinical symptomatology is not aggravated: ulcers do not become more extensive and mucosal repair may be not de- layed. Some readers will recall the widely-employed pre- scription of "pepsin and hydrochloric acid" of the days of their early practices: it is still exhibited by physicians who are "old fashioned." Whether depending upon the series of healing events postulated by Hahnemann or by activities equally obscure, the facts stand that no one yet has proven that in such circumstances, peptic ulcers are accompanied by complications mor~ prompt or serious, b y longer periods of discomfort and disability or by greater mortality than when the basic principle of therapy has been the neutraliza- tion of "excess" free Hcl.

For not alone does the dictum "No acid, no ulcer" stress the supposedly harmful effects of free Hcl: it implies that, in