Treatments of peptic ulcer.

From the late 19th century, Mount Sinai gastroenterologists declared their scepticism of the efficacy of all recommended treatments of peptic ulcer, and looked forward to trials which could distinguish between sequence and consequence, between association and causation. The rationale of all the early studies was to reduce gastric acidity, but it soon became clear that any neutralization by single doses of antacids was brief and ineffective. Winkelstein s demonstration that patients with duodenal ulcer had higher acidities not only before and after meals but also through the night hours led him to introduce a new treatment, the alkalinized intragastric milk drip together with atropine. One of the earliest controlled clinical trials at Mount Sinai compared different antacid regimes and showed that pH values above 3.5 were achieved in only about half of the patients on the various drips. When the new anticholinergic drugs were developed in the 1950s, they were found to produce sustained hypoacidity and were tried as maintenance treatment, as an alternative to acid-lowering operations. The third Mount Sinai approach was to attack the machinery of the acid-producing cell itself by an inhibitor of the enzyme producing hydrogen ions. In 1939, this enzyme had been thought to be carbonic anhydrase, but when Janowitz and Hollander tested its inhibitor, acetazolamide, and showed marked but very brief acid inhibition, they concluded that its action was too brief to be therapeutically useful. The problem was to be solved decades later by H2 receptor blockers from Britain and H+K+ATPase inhibitors from Sweden.