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, a nd looked forward to trials which could distinguish between sequence and co nsequence, between association and causation. The rationale of all the earl y studies was to reduce gastric acidity, but it soon became clear that any neutralization by single doses of antacids was brief and ineffective. Winke lstein's demonstration that patients with duodenal ulcer had higher aciditi es not only before and after meals but also through the night hours led him to introduce a new treatment, the alkalinized intragastric milk drip toget her 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. Wh en the new anticholinergic drugs were developed in the 1950s, they were fou nd to produce sustained hypoacidity and were tried as maintenance treatment , as an alternative to acid-lowering operations. The third Mount Sinai appr oach was to "attack the machinery of the acid-producing cell itself" by an inhibitor of the enzyme producing hydrogen ions. Tn 1939, this enzyme had b een thought to be carbonic anhydrase, but when Janowitz and Hollander teste d its inhibitor, acetazolamide, and showed marked but very brief acid inhib ition, they concluded that its action was too brief to be therapeutically u seful. The problem was to be solved decades later by H-2 receptor blockers from Britain and H(+)K(+)ATPase inhibitors from Sweden.