Can Screening for IgG Antibodies Against Helicobacter pylori Be Used in Clinical Practice? (Omit Endoscopy in Seropositive or Seronegative Patients?)

The objective of this study was to test thefeasibility of a screening strategy for IgG antibodiesagainst Helicobacter pylori in patients presenting withupper abdominal complaints. Biopsy specimens were taken for histological and microbiologicalinvestigations from consecutive patients undergoingupper gastrointestinal endoscopy. In addition, a serumsample was taken for detection of IgG antibodies against Helicobacter pylori, using an ELISA technique.Serum samples from 1294 consecutive patients wereavailable. IgG antibodies against Helicobacter pyloriwere present in 622 patients (48%), the remaining 671 (52%) were negative. If endoscopy had beenomitted in seronegative patients below the age of 45years, this would have resulted in 234 patients notendoscoped. However, it can be assumed that 62 of these patients would undergo endoscopy becauseof recurrent complaints due to underlying disease orabnormality. Therefore 182 of 1294 (14%) of endoscopieswould have been avoided. Application of this strategy on the total group of seronegatives would save353 of 1294 (27.3%) endoscopies. If endoscopy had beenomitted in seropositive cases below the age of 45 years,and these patients were treated with anti-Helicobactertherapy, an initial 145 endoscopies would have beenavoided. However, 26 of these patients would undergoendoscopy because of persistent complaints due tounderlying disease. Therefore 119 (9%) endoscopies would have been avoided.Applying this strategy in the total group ofseropositives would have saved 434 of 1294 endoscopies(34%). Applying the IgG screening strategy in allpatients would result in a significant number of endoscopiesbeing avoided in the seropositive group, 434 versus 353(P < 0.001). In conclusion, omitting endoscopy inseropositive cases, regardless of age, can reduce the workload more than omitting endoscopy inseronegative cases: 34% fewer endoscopies versus27%.     

Case Report: Urticaria During Triple Therapy for Helicobacter pylori Infection (Clinical Implications)

The widespread use of an ever-increasing numberof drugs is responsible for the multiple adversereactions observed by the clinician. Current practiceadvocates eradication of Helicobacter pylori infections, and this is achieved quite well by the use oftriple therapy (1). However, a survey of the recentliterature revealed that the safety of such regimens hasoften been discussed but never properly investigated (1-3). We describe a case in which adverseeffects were noted to each of the three components oftherapy.     

Suggestion Against an Oral-Oral Route of Transmission for Helicobacter pylori Infection (A Seroepidemiological Study in a Rural Area)

In this study the seroepidemiology of H. pyloriand Epstein-Barr virus was compared in the same setting.A sample of 705 subjects completed a structuredquestionnaire. A serum sample was drawn from each subject and assayed for H. pylori IgG.Antibodies to Epstein-Barr virus were determined in asubgroup of 466 subjects. Cross-tabulation of datashowed that 274 (58.8%) subjects were seropositive and20 (4.3%) were seronegative for both infections,17 (3.6%) were seropositive for H. pylori, and 155(33.3%) were seropositive for Epstein-Barr virus (oddsratio = 2.08, 95% confidence interval: 1.008-4.3).Nevertheless, the agreement between H. pylori andEpstein-Barr virus seropositivity was no better thanchance (kappa = 0.067) and the age-relatedseroprevalence curve of Epstein-Barr virus was similar in H. pylori seropositive and seronegativesubjects. Furthermore, multiple logistic regressionanalysis did not show any risk factor shared by bothinfections. The findings of this study do not support the hypothesis that H. pylori and Epstein-Barrvirus share a common mode of transmission. It can bespeculated that the oral cavity may not be an importantreservoir for H. pylori.     

Six-Day or Seven-Day Regimens with Ranitidine Bismuth Citrate plus High-Dose Clarithromycin and Tinidazole Are Both Effective Against Helicobacter pylori Infection

We compared the efficacy of two therapies toeradicate H. pylori infection including ranitidinebismuth citrate (400 mg twice daily), clarithromycin(500 mg twice daily), and tinidazole (500 mg twicedaily), administered for six or seven days. Eighty H.pylori-positive patients were consecutively recruitedand randomly subdivided into groups A and B, receivingone of the two treatment regimens. The H. pylori status was evaluated by means of histology andrapid urease test at entry, and by [¹³C]ureabreath test alone eight weeks after treatment. All 40patients in group A and 39/40 in group B completed the study. Thirty-six of 40 patients in thegroup A (90%) and 36 of 39 in the group B (92%) becameH. pylori-negative. Slight or mild side-effects occurredin 4/40 patients (10%) of group A and in 5/39 (13%) of group B. In conclusion, both regimenswe tested yielded high eradication rates with modestside effects. This is the first trial investigating atriple-drug RBC-based regimen administered for only six days.     

Specificity of Polymerase Chain Reaction Monoclonality for Diagnosis of Gastric Mucosa-Associated Lymphoid Tissue (MALT) Lymphoma (Direct Comparison to Southern Blot Gene Rearrangement)

The specificity of polymerase chain reactionmonoclonality in the diagnosis of gastric lymphoma wasprospectively evaluated. Gastric mucosal tissue fromnormal gastric mucosa (N = 13), benign gastric ulcers (N = 3), chronic Helicobacter pylori gastritis(N = 3), gastric mucosa-associated lymphoid tissue (N =16), and gastric lymphoma (N = 15) was obtained.Polymerase chain reaction amplification of theheavy-chain framework 2A gene was performed. Thesensitivity and specificity of heavy-chain clonality, inthe detection of gastric lymphoma, were 73.3% and 45.7%,respectively. Determination of monoclonality bypolymerase chain reaction methodology is not an acceptabletechnique for confirming the diagnosis of gastriclymphoma as it is too sensitive, detecting minutepopulations of clonal lymphocytes that occur in benign diseases as well as larger populations ofclonal lymphocytes associated with malignant gastriclymphoproliferative diseases. Southern blot generearrangement testing should be utilized to determineclonality in the evaluation of gastric lymphocyticinfiltrates.     

Relationship of Helicobacterpylori CagA Status to Gastric Cell Proliferation and Apoptosis

Despite the fact that the association ofHelicobacter pylori with an increased risk of gastriccancer is well documented, the exact mechanisms of thisassociation have not been elucidated. Our aim was to shed some light on these mechanisms by studyingthe relationship of H. pylori CagA status to gastriccell proliferation and apoptosis, since both play animportant role in gastrointestinal epithelial cell turnover and carcinogenesis. We studied fiftypatients [32 men, 18 women, median age 39.5 years (range18-67)], referred for upper gastrointestinal endoscopy,from whom antral biopsies were taken. On biopsy specimens gastritis was estimated byscoring the severity of inflammatory infiltrate, and thepresence of atrophy and intestinal metaplasia were alsonoted. The gastric cell proliferation index (PI) was estimated by AgNOR staining, the epithelialapoptotic index (AI) was measured by special stainingfor apoptosis, and CagA status was determinedserologically by immunoblotting the sera of patientsagainst H. pylori antigens. Thirty-eight (76%) of the50 patients were H. pylori (positive) and 12 (24%) H.pylori (negative). Among the 38 H. pylori (+) patients,28 (73.6%) were CagA(+) and 10 (24.6%) CagA(-). In the H. pylori CagA(+) and CagA(-) groups,the PI values [median (ranges)] were 5 (4-7) and 3.7(3.5-5.5), respectively (P < 0.05). In addition thedifference in PI between the H. pylori CagA(+) and H. pylori (-) groups was highly significant (P< 0.001). Concerning apoptosis, in the H. pyloriCagA(+) and CagA(-) groups, the values for AI were 1(1-30) and 5.5 (1-35), respectively (P < 0.05). In addition, the difference in AI between theH. pylori CagA(-) and H. pylori (-) groups, wassignificant (P < 0.05). We conclude that H. pyloriCagA(+) strains induce increased gastric cellproliferation, which is not accompanied by a parallel increasein apoptosis. This might explain the increased risk forgastric carcinoma that is associated with infection byH. pylori CagA(+) strains.     

Relationship Between Persistence of Helicobacter pylori and Dysplasia, Intestinal Metaplasia, Atrophy, Inflammation, and Cell Proliferation Following Partial Gastrectomy

Helicobacter pylori and partial gastricresection are risk factors for gastric cancer. Our aimswere to investigate the presence of H. pylori inpostgastrectomy patients and to correlate that withalterations in mucosal architecture and cell proliferation.One hundred fifty-one endoscopic biopsies from 22patients, (15-47 years of age, mean 29.2 years)following partial gastrectomy with Billroth IIreconstruction for peptic ulcer disease, were examined for thepresence of H. pylori using Giemsa staining. Sectionswere scored for grade of hyperplasia, intestinalmetaplasia, dysplasia, inflammation, and atrophy.Immunohistochemistry for proliferative cell nuclear antigen (PCNA)was used to characterize cell proliferation. H. pyloriwas observed in 17/22 (77.3%) of patients or in 57/151(37.7%) of biopsies. Metaplasia was seen in 18/22, chronic atrophic gastritis in 20/22, and cysticglandular dilation in 21/22 patients. The highest typeof metaplasia in each patient was: four Type I, fiveType IIA and nine Type IIB. Dysplasia was present in 16 biopsies from nine patients. H. pyloriwas more prevalent in intestinal metaplasia type I(44.8% of biopsies), than in type IIA (32.7%) or typeIIB (25%). No H. pylori was detected in regions showing dysplasia or cystic glandular dilation. H.pylori colonization was associated with degree ofinflammation (P = 0.00001) and cell proliferation (P =0.0001). In conclusion, H. pylori is commonly seen many years after gastrectomy, it is associated withan increased epithelial cell proliferation, and it isnot present in areas of histologic markers ofpremalignancy (type IIB metaplasia anddysplasia).     

Attenuation of Hydrophobic Phospholipid Barrier Is an Early Event in Helicobacter felis-Induced Gastritis in Mice

Helicobacter pylori infection has been linked tothe development of gastritis which can then progress toa number of disease entities including peptic ulcerdisease and gastric cancer. Since the pathogenic mechanism by which the bacteria causesgastritis is unresolved, we employed a model system, theH. felis-infected mouse to investigate the temporalrelationship between bacterially-induced alterations in the hydrophobic phospholipid barrier of thestomach and the development of gastritis. In the presentstudy, C57BL/6 mice were inoculated with 10⁹CFU of H. felis and the changes in gastric wet weight, histology, surface hydrophobicity,phospholipid/phosphatidylcholine concentration,phospholipase A₂ activity, and the pH ofcollected gastric juice were measured 0.5-2 monthspostinoculation. In related experiments, we investigated the effects oftreating H. felis infected mice with antibiotic/bismuththerapy on the above gastric properties. It wasdetermined that both gastric surface hydrophobicity and phospholipid composition were significantlyattenuated as early as 2-4 weeks postinfection,preceding signs of mucosal inflammation and glandularatrophy as indicated by increases in gastric wet weight, pH and a disappearance in parietal cells. Theseearly H. felis-induced changes in gastric surfacehydrophobicity and phospholipid concentration werereversed by antibiotic/bismuth therapy. Based on these results we conclude that H. felis infectioninduces an early transformation of the stomach from ahydrophobic to an acid-sensitive hydrophilic state thatmay trigger the subsequent development ofgastritis.     

Clinical Significance of Helicobacter pylori Seropositivity and Seronegativity in Asymptomatic Blood Donors

To determine the clinical significance ofHelicobacter pylori seropositivity and seronegativity inhealthy blood donors, we carried out a serologicalevaluation of Helicobacter pylori status and endoscopy in a healthy blood donors population. In all,1010 donors were screened for Helicobacter pylori by IgGELISA and assessed for pepsinogen I and gastrin levelsby RIA; 298 IgG seropositive and 61 seronegative subjects underwent endoscopy with biopsies. Of359, 165 were also tested for CagA by western blotting.Of the 298 IgG seropositives, 274 were shown to beinfected on biopsy testing. Endoscopy revealed 70 peptic ulcers, 41 cases of erosive duodenitis,and two gastric cancers. In all 105 seropositive donorswere tested for CagA and 69 were CagA positive [34/58gastritis (58.6%), 24/35 duodenal ulcer (68.6%) and 11/12 gastric ulcer (91.6%)].Histologically active/chronic gastritis was associatedwith CagA: 88.4% vs 50% (CagA seropositive vsseronegative). Of the 61 IgG seronegatives, 59 werenegative on biopsy testing. At endoscopy three had duodenitis. Ofthe 60/61 IgG seronegatives tested for CagA, one had amoderate reaction. Duodenal ulcer donors showed higherpepsinogen I levels than donors without duodenal ulcers (97.7 g/ml vs 80.9 g/mlrespectively). Screening for Helicobacter pylori andanti-CagA seropositivity and pepsinogen I can identifyindividuals likely to have gastroduodenal pathology evenin the absence of symptoms.