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

EDITORIAL 149

the ulcer stomach, the gastric juice contains more than the "normal" quanlily of acid, that acid is present over an ex- tended digestion-period or both. Such assumptions appear in disregard of a literature recording innumerable series of reliable studies of gastric "test-meals" where normal or de- creased acidity or even achlorhydria has been associated with gastric ulcer. Well-known it is, that when ulcer lies in the duodenum, gastric free Hcl is apt to average considerably higher than when ulcer is of the stomach. Except in in- stances of pyloric stenosis, in which circumstances gastric secretions may not escape into the duodenum, it is rare that titration figures quantitatively estimating free Hcl cannot be equalled or excee4ed by titratiogl figures upon healthy sub- jects of similar ages and sex, or where ulcer is duodenal. Certainly, no one has yet brought forth evidence that degree of free Hcl bears any direct relationship to time required for healing in "peptic" ulcer, gastric or duodenal.

Clinicians of adequate experience and devoid of "acid blind spots" in their therapeutic eyes, frequently enough, have noted in their hospital records startlingly rapid com- pfications when ulcer patients are in most favorable situa- tions with respect nursing and food and when alkalies have been administered sufficiently to have brought about phys- iologic fatigue of the acid secreting glands--medicinal achlorhydria.

There is more than a suspicion that excess alkali is harmful, locally, to gastric and duodenal mucosae. It is well known that the first response to the exhibition of alkali is excessive free acid secretion: the stomach is attempting to neutralize the administered alkali--a "foreign body"--and restore nor- mal conditions for gastric digestion. After a period, peculiar to each individual and depending upon the chemical attri- butes of the alkali exhibited, the acid-secreting glands pour out a fluid in which the free Hcl gradually decreases while its mucus content increases. Eventually, there occurs "phys- iologic fatigue" of the acid-secreting glands: these glands cease excreting or their excretion is mucus. If mucus is ex- creted gradually it becomes more viscid and is excreted more slowly. Quite likely, this mucus has a protective value to the "open" ulcer--certainly, the proponents of mucin therapy would appear so to believe. If, when mucus has become the

• only product of what were acid-secreting glands, large vol- umes of excess alkali are administered--and particularly if they be administered constantly--the mucus, being soluble in excess alkali at body temperature, is "dissolved." In such circumstances, it loses whatever protective properties it may have been exerting. The denuded stomach mucosa lies bare to excess alkali--a physiologically foreign substance in the stomach and an agent apparently capable chemically of irritating "raw" mucous membrane or surfaces which, through ulcer occurrence already have been denuded of mucosa--certainly an agent inimical to tissues which have lost their normal epithelial protection and their mucus coat. One should not wonder that complications may occur under a medicinally maneuvered achlorhydria:--it is strange that they do not appear oftener. If the stomach did not quickly empty itself via the pylorus or by vomitus or if the thera- peutist did not employ gastric lavage in his "routine," doubt- less the injurious effects of excess alkali or of continuous alkalinization would be observed more frequently.

In normal digestion, the intermittent reflux, of pancreatic juice and bile to the stomach often may be observed. Where gastric tonus is increased and especially when powerful spasms of the pars pylorica are present, the sudden relaxation of spasm is a not to be neglected influence in what one may call "aspiration" of duodenal juices into the stomach. Such intruding secretions bathe the common ulcer-bearing area of the pars pyIorica. Whether or no acidity is present in stomach contents, the inflow of pancreatic juice and bile exerts a potent "digestant" activity upon damaged mucosa or visceral wall--more so if, previously, the gastric contents have been rendered alkaline by medicines. There is greater than a hint of evidence, investigative and clinical, that the

reflux of duodenal contents is a potent factor in retarding the healing of gastric ulcer. Certainly, after gastroenterostomy has been performed, should the jejunal loop permit stagna- tion of its contents, duodenal juices, inflowing through the anastomatic stoma, would appear definitely to have signifi- cance towards the causation of gastro-jejunal ulcer at points where surgical traumata have been exhibited or where slowly- disintegrating sutures interfere with normal cellular activity and repair. Few stomachs are free from regurgitated jejunal juices following the performance of gastro-jejunostomy.

In achlorhydria and in stomachs exhibiting normal gastric secretion, when mural, pre-ulcer lesions have diminished the physiologic function and defense of the mucosa or submucosal strala, there is reason to believe that, in certain circum- stances, bacteria-laden saliva becomes implanted at points of local damage, the bacteria proliferate there and, by their ]ytic properties, contribute to ulcer formation or its continuance. Similarly, bacteria brought by blood or lymph-streams to a pre-ulcer, mural defect may digest tissues in which the "X-factor" of protection is missing.

Finally, it should be recalled that when mural tissue--- particularly mucosa--has had its defense lowered or such has been lost, the peptid-splitting enzyme existing in normal blood-serum, holds possibilities for digesting the available protein derivitives of "divitalized" cellular structures. Herein may lie one of the chief etiologic factors in the causation of spontaneously arising "peptic" ulcer of man.

Apart from considerations regarding the significance of free Hcl towards gastric or duodenal ulcer, evidence rapidly is accumulating which indicates that certain quantitative variations in the secretion of pepsin (probably also of tryp- sinP) may exert more potent destruction of previously "divitalized" mural tissue than is to be expected from the action of free Hcl. Certainly, the work of Babkin and the Magill University Group suggests that newer methods for the quantitative estimation of gastric and duodenal enzymes disclose variations in ferment volume and ferment action which previously had been but meagerly known or appreci- ated. If future studies bear out the promise of those thus far available, one may rightly style gastric ulcer "peptic and, probably, duodenal ulcer "tryptic." Be that as it may, cor- rect appreciation of long-known facts and full cognizance of the newer investigations does much to diminish the accuracy of the dictum "No acid, no ulcer." But acceptance of newer interpretations and consideration of newer, available facts does much to disturb the smugness of those whose gastric and duodenal ulcer horizon--ethological and therapeutic--has been limited to the juggling of data on acidity and alkalinity.

F.S.

T H E S I Z E O F T H E J O U R N A L

The Editors and Publishers have been gratified in receiving much favorable comment with respect to the page size of the Journal. Many readers have inquired the reason for the adoption of so large a format. The chief reasons are that this large size page lends itself much better than smaller sizes to the display of illustrations and effects considerable economies in printing production. It is generally held by modern printers that the two column page promotes easy reading. Further, a great deal more reading matter can be served to the subscriber in this particular format than in any other size which meets the standard production requirements of the publication printer.

It has been the aim of the Editorial Staff to produce a Journal of distinctive appearance, and, judging by the hun- dreds of letters received, the ideal has been reached. We do not think that the size of the Journal, or of reprints can be, in any way, a handicap. Certainly any inconvenience caused in filing is more than compensated for by the advantages just mentioned. Every reader is invited to make his com- ments on this matter, should he feel inclined to do so.

F . S .