BACKGROUND AND STUDY AIM: We investigated whether dental disease might be associated with a higher recurrence of HELICOBACTER PYLORI infection after successful eradication by triple therapy.

PATIENTS AND METHODS: Consecutive patients with successful H. PYLORI eradication, defined by negative results for both histology and (13)C-urea breath test (UBT) performed 6 weeks after triple therapy, were enrolled in the study. Each patient was scheduled for serial UBT and dental assessments at the end of the first, second, and third years. Patients were categorized into a "dental disease" group or "no dental disease" group at the first-year follow-up. Patients in the dental disease group whose dental disease had been cured during the second- and third-year follow-up periods, were transferred to a "dental treatment" group.

RESULTS: The first-year H. PYLORI recurrence rate was higher in the 159 patients with dental disease than in those 200 patients without dental disease (13.2 % vs. 3.5 %, P < 0.001; relative risk [95 %CI], 4.2 [1.7 - 10.1]). At both the second-year and the third-year follow-up, the annual H. PYLORI recurrence rates were higher in the dental disease group than in the no dental disease group or dental treatment group (second year, 18.4 % vs. 2.8 % or vs. 5.7 %, P < 0.001; third year, 20 % vs. 3.8 % or vs. 6.3 %, P < 0.001). CONCLUSION: The presence of dental disease could predispose to recurrent H. PYLORI infection after successful eradication. Dental surveillance and care after H. PYLORI eradication is a rational step for preventing recurrence of H. PYLORI, especially in those with dental diseases.

Sheu BS, Cheng HC, Yang YJ, Yang HB, Wu JJ. Department of Internal Medicine, Medical College, National Cheng Kung University, Tainan, Taiwan.

Although many factors contribute to the development of peptic ulcers (ulcers of the stomach or duodenum), their underlying cause is infection with the bacterium Helicobacter pylori . Powerful stomach acid suppressants decrease pain and reduce ulcer size, but no matter, once they are stopped the ulcers commonly recur. To accomplish a permanent cure, it may be necessary to eliminate the underlying infection with H pylori .

Unfortunately, H pylori , is a tough bug to kill. Combination treatment with multiple drugs is required. However, even this may fail to eradicate it. Some research hints that cranberry juice may help.

Cranberry juice is best known as a treatment for bladder infections . It is thought to work by preventing adhesion of bacteria to the bladder. Preliminary evidence suggests that cranberry might similarly help prevent the adhesion of H pylori to the stomach wall. In theory, this could enhance the effectiveness of drug treatment by making it more difficult for the bacteria to “hide” in the tissue of the stomach wall.

A ninety day, double-blind, placebo-controlled study performed in China tested the effects of daily consumption of cranberry juice on individuals who were already infected with helicobacter (but who didn’t necessarily have ulcers). The results indicated that use of cranberry significantly decreased levels of H pylori in the stomach, presumably by causing some of the detached bacteria to be “washed away.”

However, while this was a promising finding, it did not directly address treatment or prevention of ulcers.

A more practical study was published in May 2007. This double-blind trial of 177 people with ulcers evaluated the use of cranberry as a support to standard therapy. All participants were given one week of treatment with a common triple-drug cocktail used to eradicate H pylori : omeprazole, amoxicillin, and clarithromycin (OAC). They were additionally given either placebo or cranberry juice during the week of OAC and continuing for two weeks afterwards. Researchers also looked at a third group attending the same clinic and who received only OAC.

The results were somewhat promising. In the study group at large, OAC plus cranberry was no more effective than OAC plus placebo or OAC alone. However, among female participants in the study, use of cranberry was associated with a significantly increased rate of helicobacter eradication as compared to placebo or no treatment.

Does this mean that women undergoing ulcer treatment may benefit from cranberry? Perhaps, but not necessarily. When a treatment fails to produce benefit in the entire group studied, researchers may, after the fact, go on a hunt for a subgroup who did benefit. The laws of chance alone ensure that they can almost always find one. Therefore, it is not clear whether cranberry actually did provide benefit, or whether this finding was merely a statistical fluke.

Although many studies have found an association between Helicobacter pylori infection and the development of gastric cancer, many aspects of this relation remain uncertain.

METHODS: We prospectively studied 1526 Japanese patients who had duodenal ulcers, gastric ulcers, gastric hyperplasia, or nonulcer dyspepsia at the time of enrollment; 1246 had H. pylori infection and 280 did not. The mean follow-up was 7.8 years (range, 1.0 to 10.6). Patients underwent endoscopy with biopsy at enrollment and then between one and three years after enrollment. H. pylori infection was assessed by histologic examination, serologic testing, and rapid urease tests and was defined by a positive result on any of these tests.

RESULTS: Gastric cancers developed in 36 (2.9 percent) of the infected and none of the uninfected patients. There were 23 intestinal-type and 13 diffuse-type cancers. Among the patients with H. pylori infection, those with severe gastric atrophy, corpus-predominant gastritis, and intestinal metaplasia were at significantly higher risk for gastric cancer. We detected gastric cancers in 21 (4.7 percent) of the 445 patients with nonulcer dyspepsia, 10 (3.4 percent) of the 297 with gastric ulcers, 5 (2.2 percent) of the 229 with gastric hyperplastic polyps, and none of the 275 with duodenal ulcers.

CONCLUSIONS: Gastric cancer develops in persons infected with H. pylori but not in uninfected persons. Those with histologic findings of severe gastric atrophy, corpus-predominant gastritis, or intestinal metaplasia are at increased risk. Persons with H. pylori infection and nonulcer dyspepsia, gastric ulcers, or gastric hyperplastic polyps are also at risk, but those with duodenal ulcers are not.
Of NCBI Publimed

Helicobacter pylori (H. pylori) is a bacterium that causes chronic inflammation of the inner lining of the stomach (gastritis ) in humans. This bacterium also is the most common cause of ulcers worldwide. H. pylori infection is most likely acquired by ingesting contaminated food and water and through person to person contact.

In the United States, 30% of the adult population is infected. (50% of infected persons are infected by the age of 60.) The infection is more common in crowded living conditions with poor sanitation. In countries with poor sanitation, 90% of the adult population can be infected.

Infected individuals usually carry the infection indefinitely unless they are treated with medications to eradicate the bacterium. One out of every six patients with H. pylori infection will develop ulcers of the duodenum or stomach.

H. pylori also is associated with stomach cancer and a rare type of lymphocytic tumor of the stomach called MALT lymphoma.

Accurate and simple tests for the detection of H. pylori infection are available. They include blood antibody tests, urea breath tests (TAUKIT Isomed), stool antigen tests, and endoscopic biopsies.

Blood tests for the presence of antibodies to H. pylori can be performed easily and rapidly. However, blood antibodies can persist for years after complete eradication of H. pylori with antibiotics. Therefore, blood antibody tests may be good for diagnosing infection, but they are not good for determining if antibiotics have successfully eradicated the bacterium.

The urea breath test (TAUKIT) is a safe, easy, and accurate test for the presence of H. pylori in the stomach. The breath test TAUKIT relies on the ability of H. pylori to break down the naturally occuring chemical, urea, into carbon dioxide which is absorbed from the stomach and eliminated from the body in the breath. Ten to 20 minutes after swallowing a capsule containing a minute amount of radioactive urea, a breath sample is collected and analyzed for radioactive carbon dioxide. The presence of radioactive carbon dioxide in the breath (a positive test) means that there is active infection. The test becomes negative (there is no radioactive carbon dioxide in the breath) shortly after eradication of the bacterium from the stomach with antibiotics. Despite the fact that individuals having the breath test are exposed to a minute amount of radioactivity, the breath test has been modified so that it also may be performed with urea that is not radioactive.

Endoscopy is an accurate test for diagnosing H. pylori as well as the inflammation and ulcers that it causes. For endoscopy, the doctor inserts a flexible viewing tube (endoscope) through the mouth, down the esophagus, and into the stomach and duodenum. During endoscopy, small tissue samples (biopsies) from the stomach lining can be removed. A biopsy specimen is placed on a special slide containing urea (e.g., CLO test slides). If the urea is broken down by H. pylori in the biopsy, there is a change in color around the biopsy on the slide. This means that there is an infection with H. pylori in the stomach.

The most recently-developed test for H. pylori is a test in which the presence of the bacterium can be diagnosed with a sample of stool. The test uses an antibody to H. pylori to determine if H. pylori is present in the stool. If it is, it means that H. pylori is infecting the stomach. Like the urea breath test, in addition to diagnosing infection with H. pylori, the stool test can be used to determine if eradication has been effective shortly after treatment.

H. pylori is difficult to eradicate from the stomach because it is capable of developing resistance to commonly used antibiotics. Therefore, two or more antibiotics usually are given together with a PPI and/or bismuth containing compounds to eradicate the bacterium. (Bismuth and PPIs have anti-H. pylori effects.)

Examples of combinations of medications that are effective are:

a PPI, amoxicillin (Amoxil) and clarithromycin (Biaxin)

a PPI, metronidazole (Flagyl), tetracycline and bismuth subsalicylate

These combinations of medications can be expected to cure 70%-90% of infections. However, studies have shown that resistance of H. pylori (failure of antibiotics to eradicate the bacteria) to clarithromycin is common among patients who have prior exposure to clarithromycin or other chemically similar macrolide antibiotics (such as erythromycin). Similarly, H. pylori resistance to metronidazole is common among patients who have had prior exposure to metronidazole. In these patients, doctors have to find other combinations of antibiotics to treat the H. pylori. Antibiotic resistance is another reason why antibiotics should be used carefully and judiciously for the right reasons, and indiscriminant use of antibiotics for improper reasons should be discouraged.

Some doctors may want to confirm eradication of H. pylori after treatment with a urea breath test or a stool antigen test, particularly if there have been serious complications of the infection such as perforation or bleeding in the stomach or duodenum. Endoscopic biopsies to determine eradication of the bacteria are not necessary, and blood tests are not good for determining eradication since it takes many months for the antibodies to H. pylori to decrease. The best tests for determining eradication are the breath and stool tests discussed previously. Patients who fail to eradicate H. pylori with treatment are retreated, often with a different combination of medications.

Chronic infection with H. pylori weakens the natural defenses of the lining of the stomach against the ulcerating action of acid. Medications that neutralize stomach acid (antacids), and medications that decrease the secretion of acid in the stomach (H2-blockers and proton pump inhibitors or PPIs) have been used effectively for many years to treat ulcers. H2-blockers, include ranitidine (Zantac), famotidine (Pepcid), cimetidine (Tagamet), and nizatidine (Axid). PPIs include omeprazole (Prilosec), lansoprazole (Prevacid), rabeprazole (Aciphex), pantoprazole (Protonix), and esomeprazole (Nexium). Antacids, H2-blockers and PPIs, however, do not eradicate H. pylori from the stomach, and ulcers frequently return promptly after these medications are discontinued. Hence, antacids, H2-blockers or PPIs have to be taken daily for many years to prevent the return of the ulcers and the complications of ulcers such as bleeding, perforation, and obstruction of the stomach. Eradication of H. pylori prevents the return of ulcers and ulcer complications even after the medications are stopped. Eradication of H. pylori also is important in the treatment of the rare condition known as MALT lymphoma of the stomach. Treatment of H. pylori to prevent stomach cancer is controversial and discussed later.

Kerr JR, Al-Khattaf A, Barson AJ, Burnie JP.

Infectious Diseases Research Group, The University of Manchester, Clinical Sciences Building, Manchester Royal Infirmary, Oxford Road, Manchester M13 9WL, UK. jonathankerr@hotmail.com

Background

Helicobacter pylori has recently been detected in the stomach and trachea of cases of sudden infant death syndrome (SIDS) and proposed as a cause of SIDS. AIMS: To establish the incidence of H pylori in the stomach, trachea, and lung of cases of SIDS and controls. METHODS: Stomach, trachea, and lung tissues from 32 cases of SIDS and eight control cases were examined retrospectively. Diagnosis of SIDS was based on established criteria. Controls were defined by death within 1 year of age and an identifiable cause of death. Tissues were examined histologically for the presence of bacteria. Extracted DNA from these tissues was tested for H pylori ureC and cagA sequences by nested polymerase chain reaction and amplicons detected by enzyme linked immunosorbent assay (ELISA). The cut off for each ELISA for each of the tissue types was taken as the mean optical density plus two times the standard deviation of a range of negative controls.

Results

Ages of SIDS cases ranged from 2 to 28 weeks. Ages of controls ranged from 3 to 44 weeks. For the ureC gene, 25 SIDS cases were positive in one or more tissues compared with one of the controls. For the cagA gene, 25 SIDS cases were positive in one or more tissues compared with one of the controls.

Conclusions

There is a highly significant association between H pylori ureC and cagA genes in the stomach, trachea, and lung of cases of SIDS when compared with controls.

PMID: 11040154 [PubMed - indexed for MEDLINE]

Two Australians won the Nobel Prize in medicine Monday for a discovery that defied decades of medical dogma and revolutionized the treatment of ulcers. They showed that bacterial infection — not stress — causes ulcers in the stomach and intestine.

The 1982 discovery by Drs. Barry Marshall and Robin Warren eventually transformed peptic ulcer disease from a chronic, frequently disabling condition to one that can be cured by a short regimen of antibiotics and other medicines, said the Nobel Assembly of the Karolinska Institute in Stockholm.

Marshall, 54, and Warren, 68, discovered the bacterium Helicobacter pylori and uncovered its role in causing ulcers and stomach inflammation. The prize, with its $1.3 million check, gives the ultimate validation to an idea that initially drew skepticism and derision.

The Australians' bacterial theory of ulcers was "very much against prevailing knowledge and dogma," Staffan Normark, a member of the Nobel Assembly, said at a news conference in Stockholm. Most doctors believed ulcers came from stress and stomach acid.

To make his case, Marshall even deliberately infected himself by swallowing a culture of H. pylori.

"I developed a vomiting illness and had severe inflammation in the stomach for about two weeks," he told The Associated Press. "I didn't actually develop an ulcer, but I did prove that a healthy person could be infected by these bacteria, and that was an advance because the skeptics were saying that people with ulcers somehow had a weakened immune system and that the bacteria were infecting them after the event."

He and Warren believed the bacteria came first, causing inflammation, then ulcers. The experiment helped establish that. Warren, a retired pathologist, said it took a decade for others to accept their findings.

The long-standard teaching in medicine was that "the stomach was sterile and nothing grew there because of corrosive gastric juices," he said. "So everybody believed there were no bacteria in the stomach."

"When I said they were there, no one believed it," he added.

The two researchers began working together in 1981. "After about three years we were pretty convinced that these bacteria were important in ulcers and it was a frustrating time for the next 10 years though because nobody believed us," said Marshall, a researcher with the University of Western Australia.
"The idea of stress and things like that was just so entrenched nobody could really believe that it was bacteria. It had to come from some weird place like Perth, Western Australia, because I think nobody else would have even considered it."

Dr. David A. Peura, president of the American Gastroenterological Association, said the prize-winning work "revolutionized our understanding of ulcer disease" and "gave millions of people hope."

He read about the H. pylori theory in 1983 while serving as a gastroenterologist in the Army, and "I thought it was crazy," he recalled Monday.
But he and a colleague were intrigued, and soon they discovered they could cure ulcers in their own patients with antibiotics targeted at H. pylori. "It was such an intriguing theory that everybody tried to disprove it and couldn't, so we all became believers," said Peura, now a professor of medicine at the University of Virginia at Charlottesville.

Peura, who met Marshall when both worked at Virginia and considers him a friend, said Marshall's perseverance was responsible for the eventual acceptance of the theory. "Any lesser of a person probably would not have been able to withstand some of the ridicule and scorn that was thrown at him initially," Peura said.
As the two Nobel winners celebrated with family over champagne and beer in Perth, the Western Australia state capital, Warren said he was "very excited, also a little overcome." "Obviously, it's the best thing that can ever happen to somebody in medical research. It's just incredible," added Marshall in a telephone interview.

Their work has stimulated research into microbes as possible causes for other chronic inflammatory conditions, such as Crohn's disease, ulcerative colitis, rheumatoid arthritis and atherosclerosis, the Nobel assembly said in its citation.

The discovery came about after Warren had observed bacteria colonizing the lower part of the stomach of patients and noted that signs of inflammation were always present close to the bacteria. Marshall became interested in Warren's findings and together they launched a study of more patients.

Marshall also succeeded in cultivating the previously unknown bacterium from patient biopsies, in part because he accidentally left a sample in his lab over the Easter holiday in 1982 — unwittingly giving his cultures time enough for success.

Together, the two men found H. pylori present in almost all patients with stomach inflammation or ulcers in the stomach or the part of the small intestine called the duodenum.

Warren and Marshall's discovery paved the way for peptic ulcers to be cured by eradication of the bacterium with a combination of antibiotics and acid secretion inhibitors. As a result, "peptic ulcer disease is no longer a chronic, frequently disabling condition," the Nobel Assembly said. "In a country like Denmark, for example, peptic ulcer disease is now really a rare disease," Andersen told The Scientist. That effect can be directly attributed to Marshall and Warren's discovery, he said. Subsequent studies have shown that H. pylori colonizes the stomach in about 50% of all humans, causing disease in about 10-15% of infected individuals. Severe complications include bleeding and perforation and, in some people, H. pylori infection of the corpus region of the stomach can predispose to stomach cancer.

SUMMARY

Background
The precise choice of cut-off point for the 13C-urea breath test to define whether it is positive or negative represents a controversial issue.

Aim

To quantify the 13C-urea breath test result for several years following Helicobacter pylori eradication, and to evaluate the frequency and the significance of borderline d13CO2 values.

Methods

Two-hundred H. pylori eradicated patients confirmed by 13C-urea breath test (100 mg of urea, citric acid), and having had repeated this test yearly up to 5 years, were studied. d13CO2 values between 2 and 5& were considered as borderline results.

Results

Eight H. pylori recurrences were observed during 406 patient-years of follow-up (1.97% yearly). In two of eight reinfected patients, the reinfection was preceded by a negative d13CO2 value >2&. Borderline d13CO2 values were detected in 4% of the 606 urea breath tests performed, and in 25% when only patients in whom H. pylori recurrence was detected in subsequent urea breath tests were included (P < 0.05). The negative-predictive value of a post-treatment d13CO2 >2& for the diagnosis of H. pylori recurrence was 99%.

Conclusions

Positive and negative urea breath test results tend to cluster outside the range between 2& and 5&. Nevertheless, a borderline urea breath test dvalue (e.g. very close to the selected cut-off point) should be interpreted cautiously, and the result should probably be confirmed either by repeating the urea breath test or by other diagnostic methods. On the contrary, a d13CO2 value <2&very confidently confirms H. pylori eradication. Aliment Pharmacol Ther 23, 275–280

J . P. GISBERT, D. OLIVARES, I . JIMENEZ & J. M. PAJARES