Mae F. Go

Role of Helicobacter pylori infection in gastroduodenal injury and gastric prostaglandin synthesis during long term/low dose aspirin therapy: a prospective placebo-controlled, double-blind randomized trial

OBJECTIVES:Whether gastric infection with Helicobacter pylori increases the risk of gastric mucosal injury during long term/low dose aspirin therapy is unknown. We examined whether H. pylori infection enhances upper GI mucosal damage, assessed endoscopically, in volunteers given low dose aspirin. We studied 61 healthy men and women, 29 with and 32 without active H. pylori infection.METHODS:We treated volunteers for 45 days with a placebo or aspirin (either 81 mg every day or 325 mg every 3 days). Gastroduodenal mucosal damage was then assessed by endoscopy, as was gastric histology and ex vivo gastric mucosal prostaglandin E2 and F2α synthesis rates.RESULTS:Erosive disease from low dose aspirin (erosions and/or ulcers) occurred in 50% of H. pylori–infected volunteers and in 16% of their noninfected counterparts (p = 0.02). Aspirin caused a significantly higher average mucosal injury score in the gastric antrum in H. pylori–infected participants than in noninfected subjects (p = 0.03), and two H. pylori–infected subjects developed antral gastric ulcers. Subjects with H. pylori gastritis treated with the placebo had nearly 50% higher gastric mucosal prostaglandin (E2 plus F2α) synthesis rates than their noninfected counterparts (108 ± 6 ng/g/min versus 75 ± 6 ng/g/min, p < 0.001). Aspirin reduced mucosal prostaglandin synthesis to similar levels in infected and noninfected participants.CONCLUSIONS:Long term/low dose aspirin therapy led to more gastric mucosal damage when H. pylori gastritis was present than when it was absent, despite similar degrees of gastric mucosal prostaglandin depletion.

Presence of the cagA Gene in the Majority of Helicobacter pylori Strains Is Independent of Whether the Individual Has Duodenal Ulcer or Asymptomatic Gastritis

Background Helicobacter pylori infection presents as many different diseases, including asymptomatic gastritis, peptic ulcer disease, and gastric cancer. Although the virulence factor(s) responsible for different H. pylori‐related diseases have not been identified, several candidate genes are being investigated for such an association. The polymerase chain reaction (PCR) frequently is used to assess the presence of genetic factors associated with pathogenesis of disease; the cagA gene and its product have been postulated to have a disease‐specific relationship to peptic ulcer and gastric cancer because of differential expression in these diseases compared to histological gastritis alone.

Hepatitis C Knowledge among Primary Care Residents: Is Our Teaching Adequate for the Times?

BACKGROUND:Increasingly, primary care (PC) physicians will be the first to encounter patients with hepatitis C virus (HCV) infection.AIM:To determine opinions and practices of PC residents regarding HCV.METHODS:We administered a one-page questionnaire to 180 PC residents at five U.S. training programs.RESULTS:Respondents were distributed equally across postgraduate year, 83% were U.S. graduates, and 44% had seen >11 (HCV) patients in the past year. Residents tested for HCV in persons with: increased transaminases (83%), history of blood transfusion (46%), multiple tattoos (57%), +ANCA (16%), and alcohol abuse (31%). Sixteen percent of respondents tested all patients. Forty-one percent would vaccinate HCV patients for hepatitis A and 65% for hepatitis B while only 19% and 78% knew the respective vaccination schedules. Although no vaccine is available, 66% recommended vaccination for HCV. Only 37% and 29%, respectively, reported HCV genotype 1 as most common and most resistant to treatment. Fifty-three percent recommend liver biopsy before treating HCV. Only 52% reported α-interferon (IFN) with ribavirin as initial treatment for HCV while 28% recommend ribavirin or lamivudine alone or combinations of IFN and lamivudine or amantadine. As contraindications to treatment, 33% reported AIDS with PCP infection, 19% coronary artery disease, and 19% suicidal ideation. Sixty-nine percent felt that there was insufficient information on HCV.CONCLUSIONS:Many PC residents lack adequate knowledge of recommended guidelines for the management of HCV. Many test for HCV in inappropriate situations, are unclear regarding available vaccines and their administration, and are uncertain about current treatment. Education of PC residents on guidelines for detection and management of HCV must be improved.

Molecular relationships of Helicobacter pylori strains in a family with gastroduodenal disease

Objective:Few studies have examined the genetic relationships of Helicobacter pylori strains affecting family members. Our aim was to do so.Methods:We characterized H. pylori isolates obtained from members of a single family presenting with various gastroduodenal diseases to examine H. pylori bacterial genetic similarity. Endoscopic evaluation with gastric mapping was performed on each individual to establish clinical and histological disease. Genomic DNA extracted from each H. pylori isolate was used to generate DNA fingerprints for each strain by REP-PCR. vacA genotypes and cagA presence were established by PCR.Results:Gastrointestinal diseases among the five members of this family included gastric adenocarcinoma in a 52-yr-old man (index patient), gastric MALT-lymphoma in the 73-yr-old mother; intestinal metaplasia (IV) and atrophic gastritis in the 48-yr-old brother; intestinal metaplasia (I-III) in the 47-yr-old brother, and a duodenal ulcer scar in the 42-yr-old sister. REP-PCR DNA fingerprints of H. pylori isolates from the index patient, his mother, and both of his brothers were identical or highly similar. By contrast, the H. pylori DNA fingerprint from the sister was markedly different from the H. pylori DNA fingerprints from the other family members. All isolates had the genotype cagA-positive and vacA slb/ml mosaic genotype.Conclusions:The DNA fingerprints of H. pylori strains obtained from members of this family with malignancy or premalignant histological disease were identical or highly similar and markedly different from the H. pylori DNA fingerprint from the sibling with duodenal ulcer disease. All H. pylori isolates within the family possessed genetic markers of enhanced virulence (presence of the cagA gene and vacA sl/ml mosaicism). In addition to host genetics and environmental factors, these findings suggest that infection with genetically similar H. pylori strains is a significant factor in determining the clinical outcome of an infection with H. pylori.

Peptic ulcer disease

Peptic ulcer disease is a common gastrointestinal disease whose management and treatment has changed dramatically over the last 25 years. Treatment of peptic ulcer disease has evolved from dietary modifications and antacids to gastric acid suppression with H2-receptor antagonists and proton pump inhibitors to eradication of Helicobactor pylori infection. Treatment of patients infected with H pylori using antibiotics has changed the natural history of peptic ulcer disease. As a result of H pylori treatment and other unknown factors ulcer disease is declining and complications from ulcer disease have diminished significantly.

The effect of galE gene inactivation on lipopolysaccharide profile of Helicobacter pylori.

Abstract. The galE gene product, UDP-galactose 4-epimerase, mediates the incorporation of galactose in extracellular polysaccharide materials such as the O-side chain of lipopolysaccharide (LPS). The O-side chain in H. pylori LPS has been shown to cross-react with Lewis x and/or y blood group antigens, suggesting its potential involvement in H. pylori-linked autoimmune disease. To study its role in H. pylori LPS biosynthesis, the galE gene was cloned, sequenced, and a galE-knockout H. pylori strain was constructed. The H. pylori galE gene encoded a protein of 344 amino acids with a molecular weight of 39K. The LPS profile from the galE-knockout H. pylori strain showed a lower molecular weight than that of the parental strain, indicating the involvement of the galE gene in LPS biosynthesis of H. pylori.

Helicobacter pylori strain and the pattern of gastritis among first-degree relatives of patients with gastric carcinoma.

Background. Relatives of gastric cancer patients have an increased risk of gastric cancer, possibly related to genetically‐related strains of Helicobacter pylori or a common environment.

An audit of the utility of in-patient fecal occult blood testing

Abstract OBJECTIVES: Recent surveys of physician practice have suggested the existence of excessive, inappropriate use of the fecal occult blood test (FOBT). We studied the implementation of this test in hospitalized patients. METHODS: We performed a retrospective chart review of 1000 randomly selected patients who had been discharged from the Medicine service at four teaching hospitals. Patient demographics, clinical presentation, presence or absence of overt GI bleeding, and use of medications that might affect the FOBT were recorded. Reviewers assessed whether patients who had FOBT would have been candidates for colon resection if asymptomatic colon cancer had been found. RESULTS: Digital rectal examination was documented in 44.8% of patients; the findings were recorded in only 9%. A total of 421 patients had FOBT on admission, usually on stool obtained at digital rectal examination. Of the patients with a positive FOBT, 17% had active GI bleeding. Only 41.1% of patients with a positive FOBT were referred to the gastroenterology service. In 70.5% of patients, FOBT could be considered inappropriate because of factors such as age, active GI bleeding, or use of aspirin or other nonsteroidal anti-inflammatory drugs. CONCLUSIONS: The FOBT, which is validated only for colorectal cancer screening, is often performed inappropriately in patients admitted to the hospital. This test should be restricted in hospital practice. It would be preferable to identify patients who are appropriate candidates for colorectal cancer screening at the time of hospital discharge and to advise them about the appropriate performance of the FOBT at home.

REP-PCR fragments as biomarkers for differentiating gastroduodenal disease-specific Helicobacter pylori strains.

We previously identified four potential putativegastroduodenal disease fragments by using theinterspersed repetitive extragenic palindromic DNAsequence based PCR (REP-PCR) technique. We investigated these fragments with regard to their diseasespecificity. The putative disease-specific REP-PCRfragments were cloned, mapped by restriction enzymes,cross-hybridized, and confirmed by Southernhybridization. The four fragments were also used as probesagainst REP-PCR amplicons from H. pylori isolatesobtained from gastritis (N = 20), duodenal ulcer (N =30), and gastric cancer patients (N = 30). Three ofthese fragments (1.4- and 0.76-kb for gastritis; 1.35kb for duodenal ulcer) were amplified without anydiscrimination between any disease-specific H. pyloriisolates. However, amplification following hybridization with the fourth 0.81-kb fragment was observedonly from gastritis (60%) and duodenal ulcer (52%) butwith none (0%) of gastric cancer patients. Nucleotidesequence analysis of the 0.81-kb fragment revealed that it was an open reading frame of thehypothetical protein HP0373 matched to the position of380,966 to 383,068 nucleotides of the H. pylori completegenome sequence. Hence, the REP-PCR sequence was not a extragenic palindromic DNA sequence. Thehypothetical protein was also present in all the testedisolates. The REP-PCR fingerprinting technique is usefulto differentiate disease-specific H. pylori strains based on the interspersed repetitiveextragenic palindromic DNA sequences; however, it maynot be useful to identify disease-specific virulencedeterminant(s) without being confirmed by DNA sequence analysis and functional studies.

Proinflammatory activation of neutrophils and monocytes by Helicobacter pylori is not associated with cagA, vacA or picB genotypes

Chronic Helicobacter pylori infection is associated with mucosal inflammation. The aim of the present study was to assess human neutrophil and monocyte activation induced by H pylori strains with different virulence genotypes. Bacterial sonicates from 12 strains were used to induce phagocyte up‐regulation of adherence molecule CD11b, assessed by fluorescence flow cytometry, and oxidative burst responses, assessed by chemiluminescence. A dose‐dependent induction of the expression of CD11b was observed with sonicate from all H. pylori strains on both neutrophils and monocytes. Strains negative for cagA and picB genes had the same inducing activity of upregulation of CD11b as strains positive for these genes. A vacA‐S2 type strain had the same activity as vacA‐S1 type strains. The induction of toxic oxygen radicals by H. pylori‐activated neutrophils gave higher median values for the cagA‐positive strains than for the cagA‐negative strains. For the monocyte chemiluminescence response, cagA‐negative strains gave higher median values compared to cagA‐positive strains. We conclude that upregulation of the neutrophil and monocyte adherence molecule CDllb induced by H. pylori sonicates is not associated with the presence of cagA, picB or mosaic pattern of vacA, and that cagA, picB‐negative strains and vacA‐S2 strains retain their inflammatory capacity.