Stomach Ulcers: Cause and Cure - At Last

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Stomach Ulcers: Cause and Cure -- At Last

Over the past decade -- lost in the general hubbub over health reform, AIDS, Ebola virus and flesh-eating bacteria -- there came news of a remarkable medical achievement: Dr. Barry Marshall, an Australian physician, announced that peptic ulcer disease was caused by a chronic bacterial infection of the stomach. And if bacteria were the problem, antibiotics were the cure. Potentially, stomach ulcers could now be eliminated, never to reappear.

Peptic ulcers can occur in either the stomach or the duodenum (the region of the small intestine closest to the stomach). Duodenal ulcers are the most common; one person in 10 is affected at some time in his or her life. Stomach ulcers -- called gastric ulcers -- develop in about one person in 30. All told, ulcers affect nearly 25 million Americans; and four million of those affected suffer chronic symptoms.

Cures in medicine are hard to come by, so when a physician announces that he can eradicate a painful and widespread affliction, it would seem reasonable to assume that such an announcement would attract enthusiastic attention. A walk down the aisles of a neighborhood pharmacy should convince anyone that this particular accomplishment would be more than welcome -- and sorely needed. Drugstore shelves hold dozens of antacids and gastric remedies. Our stomachs, it seems, are often on our minds.

The Cause: Durable Bugs

Physicians assumed for decades that the stomach was largely excused from bacterial infection. After all, they reasoned, what bacillus could possibly survive the hostile conditions of the stomach? The major constituent of gastric juice is hydrochloric acid, which breaks down the protein we ingest. Hydrochloric acid can be used to etch metal; surely (the doctors reasoned) it would kill any bugs that might have the temerity to set up shop in the stomach.

The culprit that Dr. Marshall discovered was Helicobacter pylori, an adaptable bacterium that lives within the layer of mucus that protects the stomach from the acid it produces. H. pylori defies the conventional wisdom that says it shouldn't be able to grow in so inhospitable an environment: By creating a small alkaline bubble that neutralizes the surrounding acid, the bacteria can flourish.

Marshall discovered that H. pylori infected a large percentage of individuals suffering from gastric or duodenal ulcers. The organism also lives in people who do not suffer from ulcers, but only those who experience an inflammatory response to H. pylori become ulcer candidates. Once the stomach's mucus layer is breached, the area beneath becomes vulnerable to the corrosive effects of stomach acid; pain and bleeding are the result. In some life-threatening situations, an ulcer can perforate, breaking through the stomach wall completely. In neglected cases, hemorrhage followed by sudden death can occur. Approximately seven percent of patients with bleeding peptic ulcers will die from the condition.

Marshall advanced his theory on the causes and cure of ulcers in 1985. His ideas "received a cool reception" (as he put it) at meetings of gastroenterologists. Undoubtedly his colleagues experienced some embarrassment over the fact that so simple an explanation had eluded them for so long.

The drug companies, too, viewed Marshall's results skeptically. They were not inclined to pursue new avenues of ulcer research so long as their current products remained so profitable. Ulcers offered an ideal corporate opportunity: a chronic disease that could be treated effectively but that was not eradicated by drugs. Millions of ulcer patients would need medication for lengthy periods; many, for the rest of their lives.

Stopping the Acid

Before Marshall proposed that antibiotics could cure ulcers, treatment for the disease was guided by discoveries made in the 1960s. Experts at that time assumed that surplus stomach acid secretion caused ulcers. Hyperacidity (the experts said) was provoked by stress, overindulgence or spicy foods. Preventing or reducing acid secretion (the theory went) should subdue the pain and irritation of ulcers. This prevention or reduction of acid secretion was guaranteed to have much longer lasting benefits than antacids -- the only medications then available for ulcers -- which merely neutralized the stomach acid.

Scientists reasoned that by understanding the mechanism of acid secretion they might find a means of suppressing it. They subsequently discovered that histamine -- a hormone-like molecule better known for producing runny noses and hives -- plays a key role in the stomach's secretion of gastric acid. Histamine triggers acid secretion when, in response to ingested food, it is released in the stomach and binds to a cell-surface receptor on acid-producing gastric cells. When histamine is prevented from binding, acid secretion is suppressed.

The first histamine blocker for ulcer therapy was introduced in 1977. Tagamet (cimetidine) went on to achieve stunning success; by the early 1980s it was one of the most widely prescribed drugs in America, with sales topping $1 billion. Tagamet lost its patent protection in 1994, but by then it had already been succeeded as the favorite ulcer medication of physicians by Zantac (ranitidine). Zantac, which won approval in 1983, achieved billion-dollar-plus status several years later. A third drug, Pepcid (famotidine), duplicated the success of its two predecessors. The most recent addition to this class of drugs was Axid (nizatidine).

A new drug with an entirely different mechanism for reducing acid secretion was also introduced in the 1980s. Prilosec (omeprazole) inhibited the so-called "proton pump" of acid-manufacturing stomach cells. This was a more direct method for stifling acid secretion, since it stopped production at the source. Omeprazole had an advantage over the histamine blockers: It was very effective in treating gastroesophageal reflux, a painful disorder in which stomach acid creeps up into the esophagus and erodes the lining of the tube where it enters the stomach.

These drugs all worked extremely well in alleviating the symptoms of ulcers, and they had few side effects. But they also shared a problem: When people stopped taking the drugs, their ulcers recurred. Fifty percent of those taking histamine blockers suffered a relapse within a year of stopping their medication. These drugs treated ulcers, but they did not cure them. Therapy would have to begin again, and the pattern of going off and on the drugs would have to be repeated -- sometimes for years. Since these drugs weren't cheap, the costs piled up. Each month-long round of therapy could cost up to $100 -- and that's without considering the cost of the doctor visits.

The Answer? Antibiotics

Marshall and his colleagues proposed a much cheaper alternative. They developed what has been termed "triple therapy," and it proved effective in curing ulcers permanently in most patients. Triple therapy calls for using two inexpensive antibiotics, metronidazole and tetracycline (or amoxicillin), in combination with bismuth a compound better known to us as Pepto-Bismol. Surprisingly, though it is an ancient stomach cure, bismuth's effectiveness was something of a mystery to scientists. It now appears that bismuth acts by coating the stomach lesions in which H. pylori flourishes, smothering the bacteria in the process.

Variations on the triple-therapy theme have since been developed. One variant that has enjoyed success is a combination of omeprazole with either amoxicillin or another antibiotic, clarithromycin. Based on clinical trials with patients whose only risk factor was H. pylori infection, this therapy cured ulcers permanently 90 percent of the time.

Despite its impressive record of success, the antibiotic cure for ulcers is not necessarily a sure thing. The drug regimen is not well tolerated by many patients, and their intolerance causes them to end their therapy prematurely. This in turn allows resistant bacteria to recover from the initial assault, and the resistant bacteria are then harder to kill when antibiotic therapy needs to be resumed.

Another problem is that not all ulcers are caused by H. pylori. Prominent among the other ulcer-causing villains are the nonsteroidal anti-inflammatory drugs, or NSAIDs. Aspirin, ibuprofen, naproxen sodium (Aleve) and ketoprofen (Orudis) are all members of this widely used class of over-the-counter analgesics. NSAIDs, notorious for their gastric side effects, are, in fact, a significant cause of ulcers -- specially in arthritis sufferers who take the drugs in large quantities and among regular consumers of alcohol. The NSAIDs have the unfortunate property of reducing production of the protective mucus that lines the stomach, and triple therapy is not effective for healing the ulcers caused by NSAIDs.

In 1994 the National Institutes of Health held a Health Consensus Conference on the treatment of peptic ulcer disease. The conference issued a report endorsing the antibiotic regimen for ulcer patients with a confirmed diagnosis of H. pylori infection.

Fortunately, diagnosing H. pylor is no longer the unpleasant experience it once was. Originally, a sample of tissue had to be collected through an endoscope, a flexible tube snaked down the throat. Now there are simple, noninvasive methods for diagnosing the infection. One method involves a blood test that assays for serum antibodies to the bacteria; another involves a breath test. Since triple therapy is so much cheaper than the alternatives and heals ulcers permanently, the savings to a health-care system already burdened by huge costs promise to be substantial.

The cure for H. pylori infection also promises another benefit: The bacteria are suspected of being a risk factor for the development of stomach cancer, and their eradication might reduce the incidence of this malignancy. Clinical trials to test this hypothesis are under way right now.

What About Heartburn?

But ulcers are not the only affliction our stomachs must endure: Almost everyone experiences heartburn at one time or another. If we can prevent ulcers, why can't we also defeat this common malady?

The answer is that long-lasting relief from heartburn has arrived. Anticipating that histamine blockers were on their last legs in the face of antibiotic therapy, the manufacturers have reduced the dosage of these drugs and received FDA approval for their use as heartburn therapy. Pepcid and Tagamet are available over the counter now; nonprescription forms of Zantac and Axid are on the way.

The makers of these drugs are involved in a bitter rivalry for, market share: Ads for Pepcid allege that it lasts longer than Tagamet and can prevent as well as treat heartburn. The manufacturer of Tagamet contests these claims, saying in its ads that Tagamet has been prescribed by physicians far more times than Pepcid.

While not as cheap as antacids, Pepcid and Tagamet are clearly longer acting, offering relief all night or all day. Doctors suggest that both drugs are outstanding. With a proven record of safety in millions of users, the new Pepcid and Tagamet formulas offer welcome relief to the estimated 95 million Americans who suffer occasionally from heartburn.

American Council on Science and Health, Inc.

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By David A. Schwartz

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