To repair the fault or end the acid reign?
BACKGROUND
Despite the vast effort and expense devoted to the elucidation of the cause of esophagogastro-duodenal ulcer disease, relatively minimal progress has been made towards the understanding of causation. Since earliest times, it has been recognized that milk, chalk powder, or charcoal ameliorate the disease process and its symptoms. In addition, the avoidance of acidic or spicy foods provides some relief. Thus ulcer disease has been ascribed to acid or the consequences of hyperacidity. Reams of data and countless meetings have purported to confirm and support this viewpoint. Surprisingly, the co-secretion in the stomach of the powerful proteolytic enzyme pepsin has been virtually ignored as a pathogenetic agent. Marshalling distant antipodean resources, a novel bacteria, H. pylori, was identified as a significant causative agent in ulcer disease. To the amazement of nobody but gastroenterologists, it became apparent that there might be more than one cause for ulcer disease. Subsequently, both corporations and physicians seized the reins of multi-variant antibiotic therapy as a panacea for the third millennium treatment of peptic ulcer disease. Only a brave few have raised the issues of possible abnormalities in intrinsic mucosal function which might generate a locus minoris resistentiae. Defective mucosal repair mechanisms have barely been evaluated, since the regulation of normal mucosal healing is so poorly understood. Nevertheless, consideration of the therapeutic potential of mucosal protection has found support at both an intellectual and a clinical level. The more exciting recent possibility of the local delivery of growth factors which might promote healing has provided a unique opportunity for further therapeutic advance.


CONCLUSIONS
Indeed in the future the exogenous regulation of mucosal repair may provide a milieu conductive to the resolution of an old but ill-understood problem. It is certainly apparent that processes beyond parietal cell proton secretion are critical and require both delineation and management. The acid reign may be in decline but the site of the fault and its repair remain to be defined.
Modlin
I M
IM
Dept. of Surgery, Yale University School of Medicine, New Haven, Connecticut 06516, USA.
D004942:Esophagitis, Peptic / Q000209:etiology / Q000628:therapy; D005744:Gastric Acid / Q000378:metabolism*; D016481:Helicobacter Infections; D016480:Helicobacter pylori; D006801:Humans; D010437:Peptic Ulcer / Q000209:etiology* / Q000628:therapy / Q000821:virology