Historical impact to drive research in peptic ulcer disease.

The story of gastric acid secretion began with early ideas on gastric secretion (Spallanzani and de Réaumur, 17th century) and with first descriptions of food digestion (Dupuytren and Bichat, Beaumont, early 18th century), followed by proof that gastric juice contained acid (Prout, early 18th century). The research continued with first descriptions of gastric glands as the source of gastric acid and its changes upon digestive stimulus (Purkinje and Golgi, mid and late 19th century). The theory of 'nervism' - the neuro-reflex stimulation of gastric secretion by vagal nerve (Pavlov, early 20th century) was contrasted by a histamine-mediated concept of gastric secretion (Popielski and Code, mid 20th century). Thus, gastric acid and pepsin (Schwann, early 19th century) were found to be essential for food digestion and studies also pointed to histamine, being the most potent final common chemostimulator of oxyntic cells. The discoveries in etiopathogenesis of mucosal injury were marked by the famous dictum: 'No acid, no ulcer' ('Ohne saueren Magensaft kein peptisches Geschwür', Schwarz, 1910) that later induced the term of 'mucosal defense' and the notion that the breaking of 'gastric mucosal barrier' represents the initial step in the process of mucosal injury (Davenport, Code and Scholer, mid 20th century). The prostaglandins were shown to influence all major components of gastric mucosal barrier, described with the term 'cytoprotection' (Vane, Robert and Jacobson, 1970s). Beginning in the latter half of 19th century, the studies on gastric bacteriology that followed enabled the discovery of association between Campylobacter (Helicobacter) pylori and peptic ulcers (Warren and Marshall, 1980s) that led to worldwide major interventions in treating peptic ulcer disease. The surgical approach to peptic ulcer had been outlined by resection procedures (Billroth, Pean, Moynihan, late 19 century) and vagotomy, with or without drainage procedures (Jaboulay, Latarjet, Dragstedt, mid 20th century). Antacids, protective agents, anticholinergics, and later gastrin antagonists and prostaglandins were used for decades in the treatment of peptic ulcer, with differing effects. The advent of the concept of H(2)-receptor antagonists (Black, 1970s) and the discovery of acid (proton) pumps in parietal cells (Ganser, Forte and Sachs, late 1970s) paved the way for potent (H(2) antagonists) and profound acid inhibition (proton pump inhibitors) that revolutionized the treatment of acid-related disorders, including peptic ulcer disease. Worldwide, peptic ulcer and its complications remain the cause of significant morbidity, especially in older age groups, representing a major burden for ambulatory and hospital healthcare resources.