<?xml version="1.0" encoding="utf-8"?>
<recommendedContent xmlns="http://api.mspoke.com">
    <recommendedItem id="20090101_19_1153"
                     title="Glutamine Supplement May Fight Effects of &lt;em&gt;H. pylori&lt;/em&gt; Infection"
                     score="-0.005"
                     href="http://www.medpagetoday.com/Gastroenterology/PepticUlcerDisease/tb/13740?impressionId=1265782004715"
                     
      SAN FRANCISCO, April 15 -- Extra glutamine in the diet could protect against gastric damage caused by &lt;em&gt;Helicobacter pylori&lt;/em&gt; infection, according to a mouse study.
              &lt;p&gt; 
              &lt;p&gt;Infected mice fed a diet supplemented with 5% L-glutamine (total 6.9%) had significantly less gastric inflammation and hyperplasia than those fed a diet with 1.9% glutamine, Susan J. Hagen, Ph.D., of Beth Israel Deaconess Medical Center in Boston, and colleagues found.
              &lt;p&gt; 
              &lt;p&gt;Supplemental L-glutamine also appeared to improve early immune response to &lt;em&gt;H. pylori&lt;/em&gt; infection, they reported in the May 2009 &lt;em&gt;Journal of Nutrition&lt;/em&gt;.
              &lt;p&gt; 
              &lt;p&gt;Glutamine is a nonessential amino acid found in beef, chicken, fish, eggs, dairy products, and some grains and vegetables. L-glutamine -- the biologically active isomer of glutamine -- is also widely available in commercial dietary supplements promoted for bodybuilding. 
              &lt;p&gt; 
              &lt;p&gt;&quot;Glutamine supplementation may be an alternative therapy for reducing &lt;em&gt;H. pylori&lt;/em&gt;-associated pathology,&quot; the researchers said.
              &lt;p&gt; 
              &lt;p&gt;Antibiotics plus a proton pump inhibitor are the recommended first-line treatment to eradicate &lt;em&gt;H. pylori&lt;/em&gt;, which reduces the inflammation that promotes gastric cancer development.
              &lt;p&gt; 
              &lt;p&gt;However, a recent review suggested that regimens for &lt;em&gt;H. pylori&lt;/em&gt; eradication are losing efficiency, largely due to drug resistance. 
              &lt;p&gt; 
              &lt;p&gt;Dr. Hagen&apos;s group also noted that cost, side effects, and patient compliance hamper mass treatment strategies, while eradication therapy is not recommended for asymptomatic patients or those with dyspepsia without ulcer disease.
              &lt;p&gt; 
              &lt;p&gt;Given the interest in alternatives such as vaccines and dietary strategies, the researchers looked at dietary glutamine, which they had previously shown protects against cell death from &lt;em&gt;H. pylori&lt;/em&gt;-produced ammonia.
              &lt;p&gt; 
              &lt;p&gt;They divided 105 mice into two groups fed either a standardized diet with 1.9% glutamine or the same diet with supplemental L-glutamine replacing carbohydrates for 5% of total calories.
              &lt;p&gt; 
              &lt;p&gt;After two weeks on these diets, the mice were further allocated to an uninfected sham group or infection with &lt;em&gt;H. pylori&lt;/em&gt;.
              &lt;p&gt; 
              &lt;p&gt;Throughout the 20-week follow-up period, the diet groups remained similar in weight gain and mean &lt;em&gt;H. pylori&lt;/em&gt; colonization levels. 
              &lt;p&gt; 
              &lt;p&gt;This was reassuring, Dr. Hagen&apos;s group noted, because the bacteria also use glutamine to produce ammonia. 
              &lt;p&gt; 
              &lt;p&gt;&quot;One concern we had originally was that &lt;em&gt;H. pylori&lt;/em&gt; growth and colonization would be enhanced by a L-glutamine-containing diet and &lt;em&gt;H. pylori&lt;/em&gt;-related pathology would be more severe with this diet regime,&quot; they wrote.
              &lt;p&gt; 
              &lt;p&gt;While serum antibody levels to the bacteria were unaffected by extra glutamine in the mouse diet, some early immune responses were elevated in gastric tissues, though these effects dissipated by week 20. 
              &lt;p&gt; 
              &lt;p&gt;Among the T-helper 1 cytokines, the proinflammatory interleukin-1b increased significantly more with L-glutamine by six weeks postinfection than with a low glutamine diet (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.05). 
              &lt;p&gt; 
              &lt;p&gt;The same was true at six weeks for T-helper 2 cytokines interleukin-4, interleukin-10, and transforming growth factor-b (all &lt;em&gt;P&lt;/em&gt;&amp;lt;0.05).
              &lt;p&gt; 
              &lt;p&gt;This immune modulation was reflected in greater inflammation in gastric tissue on histopathology at six weeks among infected L-glutamine group mice.
              &lt;p&gt; 
              &lt;p&gt;But by week 20, the L-glutamine diet resulted in lower inflammation levels than the control diet.
              &lt;p&gt; 
              &lt;p&gt;While all the infected mice showed the expected histopathology changes in the stomach, mean scores for foveolar hyperplasia and hyperplastic gland length were lower with L-glutamine supplementation at 20 weeks compared with controls (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.05). 
              &lt;p&gt; 
              &lt;p&gt;These results suggested that &quot;mucosal barrier disruption and immune cell recruitment were reduced, rather than facilitated, by L-glutamine,&quot; the researchers concluded.
              &lt;p&gt; 
              &lt;p&gt;They noted that a higher level of dietary glutamine might offer even greater protection, with further study warranted. 
              &lt;p&gt; 
              &lt;p&gt;&lt;table cellspacing=&quot;0&quot; hspace=&quot;1&quot; style=&quot;border-style:solid; border-width:1px; border-color:#8dabbc; font-family:arial; font-size:12px; background-color:#DBE9F2; padding:5px 5px 5px 5px;&quot;&gt;
&lt;tr&gt;&lt;td&gt;The study was supported by grants from the National Institutes of Health.
              &lt;p&gt; 
              &lt;p&gt;Dr. Hagen reported receiving honoraria and paid travel expenses from the Ajinomoto and Kotobuki Pharmaceutical Companies for speaking at meetings or giving lectures about data concerning glutamine.&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;
             
    </recommendedItem>
    <recommendedItem id="20090101_19_1732"
                     title="DDW: Combination Pill Protects NSAID Users from Ulcers"
                     score="-0.005"
                     href="http://www.medpagetoday.com/MeetingCoverage/DDW/tb/14496?impressionId=1265782004715"
                     
      CHICAGO, June 2 -- A pill combining ibuprofen (Motrin) and the acid-suppressing H2 antagonist famotidine (Pepcid) significantly reduced development of gastric and duodenal ulcers relative to ibuprofen alone, researchers reported here.
              &lt;p&gt; 
              &lt;p&gt;From 10.5% to 11.5% of patients receiving the combination product developed gastric or duodenal ulcers in two six-month randomized trials, compared with 20% to 23% of those taking just ibuprofen (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.05), reported Loren A. Laine, M.D., of the University of Southern California, here at Digestive Disease Week.
              &lt;p&gt; 
              &lt;p&gt;Dr. Laine said the combination pill, known as HZT-501, might improve adherence in patients on chronic nonsteroidal anti-inflammatory drug (NSAID) therapy. 
              &lt;p&gt; 
              &lt;p&gt;Published guidelines recommend that these patients take acid-suppressing drugs, too, in order to reduce development of ulcers, he said.
              &lt;p&gt; 
              &lt;p&gt;&quot;We also know that most patients who have increased GI risk are not taking these protective therapies,&quot; he told attendees. &quot;Decreased adherence is associated with significantly greater risk of ulcer or bleeding.&quot;
              &lt;p&gt; 
              &lt;p&gt;HZT-501 combines 800 mg of ibuprofen and 26.6 mg of famotidine in a tablet for dosing three times daily.
              &lt;p&gt; 
              &lt;p&gt;Dr Laine reported results for two parallel, 24-week studies: REDUCE-1, which enrolled 875 patients with a primary endpoint of gastric ulcer development; and REDUCE-2, with 600 patients and a primary endpoint of all upper GI ulcers.
              &lt;p&gt; 
              &lt;p&gt;The patients, all 40 to 80 years old, were expected to require NSAID treatment for at least six months because of osteoarthritis or other common conditions that required the anti-inflammatories.
              &lt;p&gt; 
              &lt;p&gt;Exclusion criteria included the presence of ulcers or more than five gastric or duodenal erosions at baseline endoscopy.
              &lt;p&gt; 
              &lt;p&gt;Patients were not allowed to take anti-ulcer medications other than the study drug. Low-dose aspirin was allowed.
              &lt;p&gt; 
              &lt;p&gt;Patients took HZT-501 or 800 mg of ibuprofen three times daily in both studies for their 24-week duration.
              &lt;p&gt; 
              &lt;p&gt;Endoscopies were scheduled at specified intervals during treatment, and patients were excluded from the analysis if they didn&apos;t have at least one endoscopy after week six.
              &lt;p&gt; 
              &lt;p&gt;Dr. Laine reported data on 812 patients in REDUCE-1 and 570 in REDUCE-2 for whom follow-up endoscopy data were available.
              &lt;p&gt; 
              &lt;p&gt;In addition to finding significant reductions for gastric and duodenal ulcers combined, the dual agent was effective against each ulcer type individually in both trials.
              &lt;p&gt; 
              &lt;p&gt;HZT-501 patients developed gastric ulcers at rates of 10.0% and 9.7% in REDUCE-1 and REDUCE-2, respectively, compared with 19.8% and 17.9% for ibuprofen (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.05 for both comparisons).
              &lt;p&gt; 
              &lt;p&gt;Rates of duodenal ulcers with HZT-501 were 1.5% and 0.8% in the two studies, compared with 5.3% and 4.7% with ibuprofen, respectively (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.05 for both).
              &lt;p&gt; 
              &lt;p&gt;Dr. Laine also reported ulcer rates using life-table analysis, which he said accounts more accurately for different rates of study withdrawals.
              &lt;p&gt; 
              &lt;p&gt;The percentages were somewhat higher than in the raw proportions, but the magnitude of the differences between treatment groups did not change, and they remained statistically significant.
              &lt;p&gt; 
              &lt;p&gt;Dr. Laine did not report number-needed-to-treat data for ulcer prevention with HZT-501.
              &lt;p&gt; 
              &lt;p&gt;Session moderator Byron Cryer, M.D., of the University of Texas Southwestern Medical Center in Dallas, commented afterward that a combination product such as HZT-501 could fill a serious clinical need.
              &lt;p&gt; 
              &lt;p&gt;He said studies have proven that taking NSAIDs with an acid-suppressing drug such as misoprostol (a proton-pump inhibitor) or a high-dose H2 blocker reduces ulcer and gastrointestinal bleeding rates.
              &lt;p&gt; 
              &lt;p&gt;&quot;But when you look at the actual implementation of these data into clinical practice, there&apos;s this huge disconnect,&quot; he said.
              &lt;p&gt; 
              &lt;p&gt;&quot;People don&apos;t take the co-therapy. They just don&apos;t do it,&quot; said Dr. Cryer, who was not involved in the study.
              &lt;p&gt; 
              &lt;p&gt;A combination product, analogous to the &quot;polypills&quot; now common in cardiovascular medicine, could dramatically improve adherence.
              &lt;p&gt; 
              &lt;p&gt;Dr. Cryer said that would clearly justify the increased cost of such a product compared with the over-the-counter generic equivalents sold individually.
              &lt;p&gt; 
              &lt;p&gt;But he said the data reported by Dr. Laine left several important questions unanswered about HZT-501.
              &lt;p&gt; 
              &lt;p&gt;He said the study was too small to give firm clinical guidance on whether the drug was effective in important subpopulations such as people older than 65 and those taking low-dose aspirin.
              &lt;p&gt; 
              &lt;p&gt;Data reported by Dr. Laine indicated that all upper GI ulcers were significantly reduced in REDUCE-1 in patients on low-dose aspirin, 14.0% versus 33.3% for ibuprofen alone (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.05).
              &lt;p&gt; 
              &lt;p&gt;But a narrower difference in REDUCE-2 -- 14.9% for all ulcers with HZT-501 versus 27.5% for ibuprofen alone -- was not statistically significant.
              &lt;p&gt; 
              &lt;p&gt;Dr. Cryer also questioned whether reporting data for all upper GI ulcers was relevant. He said most NSAID-induced ulcers occur in the stomach, whereas H2 blockers such as famotidine tend to be most effective at reducing esophageal ulcers.
              &lt;p&gt; 
              &lt;p&gt;Although endoscopic ulcer data have become the standard outcome measure for phase III drug trials, Dr. Cryer said that, as a clinician, he would prefer to see data on symptomatic endpoints such as dyspepsia.
              &lt;p&gt; 
              &lt;p&gt;And, in fact, Dr. Laine reported that there were no significant differences between HZT-501 and ibuprofen alone in patient reports of dyspepsia or gastrointestinal complications.
              &lt;p&gt; 
              &lt;p&gt;Horizon has announced plans to file for U.S. marketing approval of HZT-501 sometime this year.
              &lt;p&gt; 
              &lt;p&gt;Other pills combining NSAIDs with acid suppressants are also in development.
              &lt;p&gt; 
              &lt;p&gt;Using a different approach to adherence problems, a product now on the market packages individual lansoprazole capsules with naproxen tablets into single-dose blister packs (Prevacid NapraPac).
              &lt;p&gt; 
              &lt;p&gt; 
              &lt;p&gt;&lt;table cellspacing=&quot;0&quot; hspace=&quot;1&quot; style=&quot;border-style:solid; border-width:1px; border-color:#8dabbc; font-family:arial; font-size:12px; background-color:#DBE9F2; padding:5px 5px 5px 5px;&quot;&gt;
&lt;tr&gt;&lt;td&gt;The study was funded by Horizon Therapeutics, developer of HZT-501.
              &lt;p&gt; 
              &lt;p&gt;Dr. Laine reported relationships with AstraZeneca, Horizon, Santarus, and TAP.
              &lt;p&gt; 
              &lt;p&gt;Dr. Cryer has consulted for AstraZeneca Pharmaceuticals, Merck, Pfizer, and TAP.&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;
          
    </recommendedItem>
    <recommendedItem id="20090101_19_3473"
                     title="ACG: New Pain Relievers Cause Less GI Injury (CME/CE)"
                     score="-0.005"
                     href="http://www.medpagetoday.com/MeetingCoverage/ACG/tb/16709?impressionId=1265782004715"
                     
      &lt;p&gt;SAN DIEGO -- Two investigational pain relievers demonstrated superior gastroprotection when compared with a conventional nonsteroidal anti-inflammatory drug (NSAID) in clinical trials reported here.&lt;/p&gt;
&lt;p&gt;A fixed-dose combination of naproxen and the proton pump inhibitor (PPI) esomeprazole reduced the incidence of gastric ulcers by as much as 82% compared with enteric-coated naproxen during six months of treatment. The combination drug significantly reduced the frequency and severity of dyspepsia as assessed by two different standardized scales.&lt;/p&gt;
&lt;p&gt;&quot;PN 400 [Vimovo] significantly reduced the incidence of NSAID-associated gastric ulcers in at-risk patients,&quot; Jay Goldstein, MD, of the University of Illinois in Chicago, said at the American College of Gastroenterology meeting.&lt;/p&gt;
&lt;p&gt;&quot;This fixed-dose combination drug was associated with fewer upper gastrointestinal symptoms and improved upper GI tolerability,&quot; he added. &quot;Our data suggest that optimizing adherence to gastroprotection may improve NSAID tolerability and may result in sustained use.&quot;&lt;/p&gt;
&lt;p&gt;The fixed-dose combination consists of 20 mg of immediate-release esomeprazole and 500 mg of enteric-coated naproxen. The drug design leads to sequential delivery of the two drugs, said Goldstein.&lt;/p&gt;
&lt;p&gt;PN 400 was compared with enteric-coated naproxen in two Phase III clinical trials involving patients at risk of ulcers from chronic use of nonsteroidal anti-inflammatory drugs (NSAIDs). The two trials included 434 and 420 patients, who were randomized to BID treatment with PN 400 or enteric-coated naproxen.&lt;/p&gt;
&lt;p&gt;Eligible patients had osteoarthritis, rheumatoid arthritis, or another condition requiring chronic NSAID therapy. They were free of ulcers (gastric and duodenal) at baseline. Enrollment included patients ages 50 and older with no history of ulcer and patients ages 18 to 49 who had a history of gastric or duodenal ulcer within the previous five years.&lt;/p&gt;
&lt;p&gt;The primary endpoint of both trials was the cumulative incidence of endoscopically proven gastric ulcers at six months. Secondary endpoints included patient-reported outcomes on the Severity of Dyspepsia Assessment (SODA) and Overall Treatment Evaluation of Dyspepsia (OTE-DP).&lt;/p&gt;
&lt;p&gt;After six months, the incidence of gastric ulcers in the two trials was 23.1% and 24.3% with enteric-coated naproxen compared with 4.1% and 7.1% for the fixed-dose combination. The differences translated into reductions in ulcer incidence of 82% and 71% with the combination therapy (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.001 for both comparisons).&lt;/p&gt;
&lt;p&gt;Patient-reported outcomes showed significant advantages for PN 400 with respect to pain intensity, nonpain symptoms, and overall improvement and satisfaction with therapy (&lt;em&gt;P&lt;/em&gt;=0.017 to &lt;em&gt;P&lt;/em&gt;&amp;lt;0.001).&lt;/p&gt;
&lt;p&gt;Rates of adverse events were similar between treatment groups in both trials. The most common adverse events (erosive gastritis, erosive duodenitis, gastritis, and dyspepsia) all occurred less frequently with PN 400. Withdrawal due to adverse events occurred less often with PN 400 (14 and 24 versus 24 and 30 in the two trials).&lt;/p&gt;
&lt;p&gt;In response to a question from the audience, Goldstein acknowledged that use of nonprescription formulations of naproxen and a PPI would cost less, but he said adherence and persistence with therapy could be more problematic.&lt;/p&gt;
&lt;p&gt;In a separate presentation at the ACG meeting, Goldstein described a cyclooxygenase (COX)-inactive prodrug of naproxen that demonstrated pharmacokinetic equivalence to naproxen with significantly less gastric ulceration in a one-week randomized trial.&lt;/p&gt;
&lt;p&gt;He said the prodrug, LT-NS001, reflects an approach to gastroprotection that combines three common strategies: preventing inhibition of COX-1, enteric coating, and acid suppression.&lt;/p&gt;
&lt;p&gt;&quot;As a prodrug of naproxen, LT-NS001 has no COX-1 inhibition, minimal COX-2 inhibition, and is readily metabolized to naproxen after systemic absorption,&quot; he said.&lt;/p&gt;
&lt;p&gt;&quot;Animal studies suggest the agent is associated with less upper GI mucosal injury.&quot;&lt;/p&gt;
&lt;p&gt;Goldstein reported findings from a Phase I-II proof-of-concept study involving 120 healthy volunteers, who received randomized, blinded therapy for 7.5 days in the form of 1200 mg of LT-NS001 or 500 mg of naproxen, each drug administered once daily. The doses chosen represented pharmacokinetic equivalence between the drugs, he said.&lt;/p&gt;
&lt;p&gt;The primary efficacy endpoint was the day seven modified Lanza score of upper gastrointestinal mucosal injury. The Lanza scoring system ranges from 0 (no visible lesions) to 7 (ulcer &amp;gt;3 mm in diameter with unequivocal depth).&lt;/p&gt;
&lt;p&gt;Mucosal injury was assessed by endoscopy at baseline and day seven, and the Lanza score was determined for gastric and duodenal injury, as well as combined gastroduodenal injury. Baseline Lanza score averaged about 1.0 in both groups.&lt;/p&gt;
&lt;p&gt;Endoscopic findings at the end of the study resulted in a mean combined Lanza score 3.5 for naproxen and 2.8 for LT-NS001 (&lt;em&gt;P&lt;/em&gt;=0.031). Study participants who received the investigational agent also had fewer gastric ulcers (&lt;em&gt;P&lt;/em&gt;=0.020), fewer Lanza scores &amp;#8805;5 (&lt;em&gt;P&lt;/em&gt;=0.012), lower total gastric Lanza score (&lt;em&gt;P&lt;/em&gt;=0.005), and fewer gastroduodenal ulcers (&lt;em&gt;P&lt;/em&gt;=0.020).&lt;/p&gt;
&lt;p&gt;&quot;In this first human proof-of-concept study, the prodrug LT-NS001 was associated with less gastroduodenal mucosal injury than naproxen when dosed to provide equivalent exposure,&quot; Goldstein concluded. &quot;These findings need to be validated further in endoscopic trials of longer duration.&quot;&lt;/p&gt;

&lt;div style=&quot;float:left;border-style:solid;border-width:1px;border-color:#8dabbc;font-family:arial;font-size:12px;background-color:#DBE9F2;padding:5px;&quot;&gt;&lt;p&gt;The PN-400 studies were supported by Pozen.&lt;/p&gt;
    &lt;p&gt;Two co-authors of the abstract are employees of Astra Zeneca.&lt;/p&gt;
    &lt;p&gt;The LT-NS001 study was supported by Logical Therapeutics.&lt;/p&gt;
    &lt;p&gt;Goldstein disclosed relationships with Pfizer, AstraZeneca, TAP, Novartis, Pozen, Takeda/Sucampo, GlaxoSmithKline, Logical Therapeutics, Given, Merck, Amgen, Astellas Pharma US, PLX, Proctor &amp;amp; Gamble, Horizion, and Wyeth.
&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20090101_19_4203"
                     title="The Changing Face of Medicine, 1984-2009:"
                     score="-0.005"
                     href="http://www.medpagetoday.com/Gastroenterology/PepticUlcerDisease/tb/17694?impressionId=1265782004715"
                     
      &lt;div style=&quot;font-family:arial; font-size:14px; font: bold; color:#003399; line-height:14px; padding-top:3px;&quot;&gt;
			Once-Chronic Peptic Ulcers Now Curable				
			&lt;/div&gt;

&lt;br&gt;Frustrated by responses to his research, 33-year-old Barry Marshall, MBBS, ingested &lt;em&gt;Helicobacter pylori&lt;/em&gt; one day in 1984, and soon developed stomach pain, nausea, and vomiting: all signs of the gastritis he had intended to induce.&lt;br&gt;
&lt;br&gt;&quot;I didn&apos;t actually expect to become as ill as I did,&quot; he wrote in an autobiography, describing a defining moment in the work that ultimately led to the 2005 Nobel Prize he shared with a now-retired colleague, Robin Warren, MBBS.&lt;br&gt;
&lt;br&gt;The award had its roots in two papers published in &lt;em&gt;The Lancet&lt;/em&gt; in 1983 and 1984. In those articles, Warren and Marshall, now at the University of Western Australia in Perth, described an association between a new bacterium that would eventually be named &lt;em&gt;H. pylori&lt;/em&gt; and peptic ulcers, both duodenal and gastric.&lt;/p&gt;
&lt;p&gt;Warren and Marshall were convinced that the bacteria, successfully cultured after being left out inadvertently over a long holiday weekend, were causing the ulcers. But Marshall had met stiff resistance from gastroenterologists around the world when he broached the idea.&lt;/p&gt;
&lt;p&gt;The conventional wisdom was that ulcers were caused by excess acid in the stomach and that no living organism could exist long in such an acidic environment.&lt;/p&gt;
&lt;p&gt;As it turns out, &lt;em&gt;H. pylori&lt;/em&gt; produces ammonia to neutralize the area around it.&lt;/p&gt;
&lt;p&gt;Walter Peterson, MD, now a clinical professor at the University of Colorado Denver, was a member of the skeptical majority. He said Marshall called him and his colleagues the &quot;Acid Mafia.&quot;&lt;/p&gt;
&lt;p&gt;&quot;Barry Marshall came across as a zealot, as opposed to a scientist,&quot; he told &lt;em&gt;MedPage Today&lt;/em&gt;, describing Marshall as a good friend now.&lt;/p&gt;
&lt;p&gt;Marshall wrote in his Nobel Prize autobiography, &quot;I was met with constant criticism that my conclusions were premature and not well supported. When the work was presented, my results were disputed and disbelieved, not on the basis of science but because they simply could not be true.&quot;&lt;/p&gt;
&lt;p&gt;But a conviction that he was right and a sense of urgency surrounding the importance of reducing the burden of ulcers  --  which affect about 10% of Americans at some point in life  --  led him to famously use himself as an animal model.&lt;/p&gt;
&lt;p&gt;&quot;If I was right, then treatment for ulcer disease would be revolutionized. It would be simple, cheap, and it would be a cure,&quot; he wrote, using a word often considered taboo when discussing medical research.&lt;/p&gt;
&lt;p&gt;After fighting through years of ridicule, Marshall&apos;s zealotry paid off.&lt;/p&gt;
&lt;p&gt;&quot;We were wrong, he was right,&quot; Peterson said. &quot;And so I couldn&apos;t agree more that he got the Nobel Prize.&quot;&lt;/p&gt;
&lt;p&gt;It&apos;s now well established that &lt;em&gt;H. pylori&lt;/em&gt; is a major cause of peptic ulcers, with nonsteroidal anti-inflammatory drugs (NSAIDs) such aspirin, indomethacin, and the nonselective COX inhibitors sharing some of the blame.&lt;/p&gt;
&lt;p&gt;&quot;Nowadays, we know that most ulcers are caused by disruption in mucosal defense and not by excess acid,&quot; Peterson said.&lt;/p&gt;
&lt;p&gt;Warren and Marshall&apos;s discovery revolutionized the management of peptic ulcer disease, which had been a chronic condition requiring continuous medications. Doctors blamed it on poor diet and stress.&lt;/p&gt;
&lt;p&gt;In the early 1980s, patients presenting with stomach pain would undergo endoscopy or X-ray to look for an ulcer.&lt;/p&gt;
&lt;p&gt;When doctors found one, they would treat the patient with agents to lower the levels of stomach acids  --  antacids into the late 1970s, followed by histamine&lt;sub&gt;2&lt;/sub&gt; receptor antagonists. More potent proton pump inhibitors wouldn&apos;t arrive until the FDA approved omeprazole (Prilosec) in 1989.&lt;/p&gt;
&lt;p&gt;So ulcers would heal but ultimately return.&lt;/p&gt;
&lt;p&gt;&quot;We could control the ulcer, but not cure the ulcer,&quot; Peterson said.&lt;/p&gt;
&lt;p&gt;According to David Graham, MD, of Baylor College of Medicine in Houston, &quot;It was a bad existence. [It was] very expensive, you had to frequently go to doctors and you had lots of X-ray examinations, or later, endoscopic examinations to show if an ulcer was present or not.&quot;&lt;/p&gt;
&lt;p&gt;Serious complications, such as gastrointestinal hemorrhage, strictures, and perforations, occurred in about 25% of patients, many requiring surgery. About 10% of those died, Graham said.&lt;/p&gt;
&lt;p&gt;Like Peterson, Graham doubted Warren and Marshall&apos;s findings.&lt;/p&gt;
&lt;p&gt;&quot;Dr. Marshall, when he first presented this, was young, a resident, and didn&apos;t know how the system worked,&quot; Graham said in an interview. &quot;And he believed that just because you could show people and it all made sense, that they would believe it. But you just need to do the studies to get the proof and show that if you eradicate the infection that the ulcer disease is also cured, and that takes time.&quot;&lt;/p&gt;
&lt;p&gt;Studies did confirm the causal role of &lt;em&gt;H. pylori&lt;/em&gt;, and Graham and Peterson eventually accepted the idea. They both became leading U.S. experts studying the bacteria and how to treat it.&lt;/p&gt;
&lt;p&gt;Peterson said he can&apos;t identify one turning point for acceptance of a causal role for &lt;em&gt;H. pylori &lt;/em&gt;but thinks it came after researchers around the world started to confirm the Australians&apos; findings and show that treating the infection cured the ulcers.&lt;/p&gt;
&lt;p&gt;Graham said official acceptance came at a 1994 National Institutes of Health consensus conference that concluded there was a strong link between &lt;em&gt;H. pylori&lt;/em&gt; and peptic ulcer disease  --  and that patients with ulcers and infection with the bacteria&lt;em&gt; &lt;/em&gt;required treatment with antibiotics and antisecretory drugs.&lt;/p&gt;
&lt;p&gt;&quot;I had been waiting for 10 years for this day and I felt a combination of relief and satisfaction that I had achieved what I set out to do,&quot; Marshall wrote.&lt;/p&gt;
&lt;p&gt;Even so, clinicians were slow to accept &lt;em&gt;H.&lt;/em&gt; &lt;em&gt;pylori&lt;/em&gt; as the cause of most ulcers.&lt;/p&gt;
&lt;p&gt;In a 1997 study in &lt;em&gt;Archives of Internal Medicine&lt;/em&gt;, researchers found that, in 1995, about three-quarters of ulcers were still being treated primarily with antisecretory medications. Only 5% of patients received antibiotics.&lt;/p&gt;
&lt;p&gt;It wasn&apos;t until 1996 that the FDA approved the first antimicrobial treatment for peptic ulcers  --  a combination of the antibiotic clarithromycin (Biaxin) and the proton pump inhibitor omeprazole (Prilosec).&lt;/p&gt;
&lt;p&gt;In 1997, responding to the clinical inertia, the CDC launched a national campaign to spread the word about &lt;em&gt;H. pylori &lt;/em&gt;and its treatment through public service announcements on television and radio.&lt;/p&gt;
&lt;p&gt;By the end of the 20th century, Graham said, the idea finally took hold.&lt;/p&gt;
&lt;p&gt;This process &quot;probably happened slower than it should have, but about as fast as new ideas travel through medicine.&quot;&lt;/p&gt;
&lt;p&gt;Now, the proportion of ulcers attributed to &lt;em&gt;H. pylori&lt;/em&gt; is declining as NSAIDs get more blame, although this varies depending on location.&lt;/p&gt;
&lt;p&gt;Graham said that at his center in Houston, about half of new ulcers are caused by &lt;em&gt;H. pylori&lt;/em&gt;, with the rest caused by NSAIDs.&lt;/p&gt;
&lt;p&gt;Peterson said that at a university hospital, like his in Denver, almost no ulcers are caused by &lt;em&gt;H. pylori&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;Ulcers caused by the bacteria are more frequent at centers caring for more socioeconomically disadvantaged populations.&lt;/p&gt;
&lt;p&gt;Graham said that the prevalence of &lt;em&gt;H. pylori&lt;/em&gt; was on the decline even before gastroenterologists started treating ulcers with antibiotics because of its fecal-oral transmission route.&lt;/p&gt;
&lt;p&gt;It&apos;s an infection that results from poor hygiene and sanitation, he said, one that doesn&apos;t transmit well between people. Quality sanitation already had the bacteria in retreat in developed countries, although &lt;em&gt;H. pylori&lt;/em&gt; remains a major problem in the developing world.&lt;/p&gt;
&lt;p&gt;In the U.S., management of patients with ulcers involves testing for the bacteria through biopsies taken during endoscopy or with less-invasive blood, fecal antigen, and urea breath tests.&lt;/p&gt;
&lt;p&gt;The &quot;test-and-treat&quot; approach says that if a patient shows signs of an ulcer and is positive for &lt;em&gt;H. pylori&lt;/em&gt;, he or she can be treated to eliminate the infection, without the need for endoscopic confirmation of an ulcer.&lt;/p&gt;
&lt;p&gt;&quot;The theory being that if they actually had an ulcer, by treating &lt;em&gt;H. pylori&lt;/em&gt; we would get rid of the ulcer, and if they didn&apos;t, then that&apos;s okay. Getting rid of &lt;em&gt;H. pylori&lt;/em&gt; was probably good in and of itself,&quot; Peterson said.&lt;/p&gt;
&lt;p&gt;According to the most recent guidelines from the American College of Gastroenterology, published in 2007, first-line treatments for &lt;em&gt;H. pylori&lt;/em&gt; ulcers include 10 to 14 days of therapy with a proton pump inhibitor, clarithromycin, and amoxicillin or metronidazole, or a proton pump inhibitor, bismuth, tetracycline, and metronidazole.&lt;/p&gt;
&lt;p&gt;Graham noted an increasing resistance to clarithromycin which is not well known by clinicians. However, he said &lt;em&gt;H. pylori&lt;/em&gt; is sensitive to many other antibiotics.&lt;/p&gt;
&lt;p&gt;In patients who show signs of an ulcer but who are &lt;em&gt;H. pylori&lt;/em&gt;-negative, endoscopy is required to confirm an ulcer.&lt;/p&gt;
&lt;p&gt;If it&apos;s determined that a patient has been taking an NSAID, stopping the drug and starting antisecretory therapy will heal most ulcers, according to Graham.&lt;/p&gt;
&lt;p&gt;Healing time varies based on the severity of the ulcer, with some of the deepest taking six or seven months to heal completely.&lt;/p&gt;
&lt;p&gt;But unlike the past, &quot;virtually every ulcer that we see is ultimately healed,&quot; Peterson said.&lt;/p&gt;
&lt;p&gt;One sign of the ultimate importance of Warren and Marshall&apos;s discovery: Graham said he was recently asked to condense five chapters on peptic ulcer disease in a major medical textbook into one chapter.&lt;/p&gt;
&lt;p&gt;&quot;Peptic ulcer disease has become a minor event and eventually will become historical as far as a concept,&quot; Graham said.&lt;/p&gt;
&lt;p&gt;&lt;em&gt;This article was developed in collaboration with ABC News. &lt;/em&gt;&lt;img src=&quot;http://www.medpagetoday.com/upload/2009/10/1/14357_1.jpg&quot; mce_src=&quot;http://www.medpagetoday.com/upload/2009/10/1/14357_1.jpg&quot; alt=&quot;&quot;&gt;&lt;/p&gt;
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