Touch Cytology (A Reliable and Cost-Effective Method for Diagnosis of Helicobacter pylori Infection)

A variety of reliable methods are available fordetecting Helicobacter pylori (Hp) during uppergastrointestinal endoscopy. We evaluated the clinicalutility and cost-effectiveness of rapid urease test (RUT), touch cytology (TC), and histology (H).Two hundred thirty-eight consecutive patients (178without previous medical treatment and 60 formerlytreated with anti-Hp therapy) were tested for Hpinfection by RUT, TC, and H (H&E stain). Theinfection status for each patient was established by aconcordance of two test results. The time to carry outthe three tests and their cost were also calculated. Sensitivity of TC (100%) was significantlyhigher than that of RUT (86.8%; P < 0.001), but notthan that of H (94.9%). RUT was significantly morespecific than H (100% vs 95.6%; P < 0.05), but not than TC (96.4%). Hp infection was more frequentin the patients with chronic active gastritis than inthose with chronic nonactive gastritis (P < 0.001).No Hp infection was detected in absence of chronic antral inflammation. RUT resulted the cheapestmethod and H the most expensive; TC is faster andcheaper than H. When additional information about theseverity of mucosal damage or the presence of cell atypias is not necessary, histologicexamination can be omitted, and a cost-effectivestrategy for assessing Hp status might consist in takingtwo antral biopsies, the former for performing RUT andthe latter for preparing a slide by TC, whichshould be stained and examined only when the RUT resultis negative.     

Helicobacter pylori Infection and Peptic Ulcer Disease in Cirrhosis

An increased frequency of peptic ulcer diseaseis noted in patients with cirrhosis, but the role of H.pylori in this disorder remains to be determined. Thediagnosis of cirrhosis was confirmed by a combination of clinical, biochemical, radiological, andhistological methods. The severity of cirrhosis wasassessed by Pugh's modification of Child's criteria.Upper gastrointestinal endoscopy was performedconsecutively to evaluate the presence of varices andgastroduodenal mucosa. H. pylori status was assessed byhistology, urease test, and serology. In all, 130patients with cirrhosis were recruited into the study;there were 86 males and 44 females with a mean (SD)age of 54.4 (12.7) years. The H. pylori prevalence was76.2% . There was no difference in age between the H.pylori-positive and -negative cirrhotics (P = 0.29). The H. pylori prevalence revealed no differenceamong cirrhotics with Child A (77.8%), Child B (72.9%),and Child C (78.6%) (P = 0.8), and neither was there adifference in H. pylori prevalence in cirrhotics with and without congestive gastropathy (77% vs73.7% , P = 0.84). The prevalence of H. pylori incirrhotics with and without varices did not show astatistical difference (75% vs 81.8%, P = 0.68). There also was no difference in the H. pyloriprevalence between cirrhotic patients with and withoutpeptic ulcers (84.4% vs 69.7% , P = 0.09). Inconclusion, the prevalence of H. pylori or peptic ulceris independent of the severity of cirrhotic liver disease. Theassociation between H. pylori infection and peptic ulcerdisease is weak in cirrhosis.     

High Prevalence of Helicobacter pylori in Liver Cirrhosis (Relationship with Clinical and Endoscopic Features and the Risk of Peptic Ulcer)

In 153 consecutive patients with cirrhosis weassessed: (1) the prevalence of IgG to Helicobacterpylori and compared it with that found in 1010 blooddonors resident in the same area; and (2) therelationships of IgG to Helicobacter pylori with clinical andendoscopic features and with the risk of peptic ulcer.The IgG to Helicobacter pylori prevalence of cirrhoticswas significantly higher than in blood donors (76.5% vs 41.8%; P < 0.0005) and was notassociated with sex, cirrhosis etiology, Child class,gammaglobulins and hypertensive gastropathy. In bothgroups, the prevalence of IgG to Helicobacter pylori was significantly higher in subjects over 40. Amongpatients with cirrhosis a significantly higherprevalence of Helicobacter pylori was found in patientswith previous hospital admission (P = 0.02) and/or upper gastrointestinal endoscopy (P = 0.01) andpatients with peptic ulcer (P = 0.0004). Multivariateanalysis identified increasing age and male sex as riskfactors for a positive Helicobacter pylori serology and no independent risk factors for pepticulcer. The high prevalence of Helicobacterpylori-positive serology found in the present series isrelated to age and sex and might also be explained byprevious hospital admissions and/or uppergastrointestinal endoscopy. Our results do not confirmthe role of Helicobacter pylori as risk factor forpeptic ulcer in patients with liver cirrhosis.     

Comparison of Rapid Office-Based Serology with Formal Laboratory-Based ELISA Testing for Diagnosis of Helicobacter pylori Gastritis

Accurate and cost-effective diagnosis ofHelicobacter pylori gastritis has taken on majorimportance. Several serologic tests for the diagnosis ofH. pylori infection are commercially available. Wecompared the performance of the FlexSure HP rapid IgGantibody test with the conventional HM-CAP ELISA toevaluate whether qualitative office-based serology isreliable enough to replace formal laboratory-based testing. We assessed H. pylori status byconcordance in 100 consecutive patients with antralbiopsy, rapid urease, and 1 Ci[¹⁴C]ureabreath tests. Both antibody tests had good sensitivityand specificity (>86%). Concordance between the two antibodytests occurred in 87/93 patients (94%). Based on ourdata, the office-based FlexSure HP performed equallywell as the laboratory-based formal ELISA and may be a better choice for initial serologicdiagnosis in untreated patients.     

Prevalence of Upper Gastrointestinal Lesions and Helicobacter pylori Infection in Crohn's Disease

Crohn's disease can affect the upper gut withreported variable frequency, although concurrentHelicobacter pylori infection has been reported to below. We prospectively investigated the prevalence of esophageal, gastric, and duodenal lesions andHelicobacter pylori infection in 67 Crohn's disease, 41ulcerative colitis patients, and 43 controls. Symptoms,esophagogastroduodenoscopy, and multiple biopsies were performed on all patients consecutively.Endoscopic lesions were found in 63% of Crohn's diseasepatients, with a Helicobacter pylori prevalence of 28%. Granulomas were found in three patients. Twenty-two percent of the ulcerative colitis patients hadlesions, with a 29% prevalence of Helicobacter pyloriinfection. Half of the controls had pathologicalendoscopy, and Helicobacter pylori was positive in 40% of the cases. Subjective symptoms did notpredict the presence of endoscopic lesions orHelicobacter pylori infection in inflammatory boweldisease patients. Chronic gastritis and duodenitis arecommon in Crohn's disease patients, and the majorityare not associated with Helicobacter pyloriinfection.     

Evaluation of Two String Tests for Obtaining Gastric Juice for Culture, Nested-PCR Detection, and Combined Single- and Double-Stranded Conformational Polymorphism Discrimination of Helicobacter pylori

We have compared two gastric string tests forobtaining gastric juice for culture of Helicobacterpylori and for nested-PCR detection and PCR-basedcombined single- and double-stranded conformationalpolymorphism (SDSCP) discrimination of infecting strains.String test specimens were obtained from oneseropositive volunteer for 13 consecutive weeks. Thedistal 10 cm of each string was suspended in 1 ml salineand quantitatively cultured. An additional ninevolunteers with histories of upper-gastrointestinalcomplaints were given a string test for culture andnested-PCR assay. H. pylori isolates and/or gastricjuice from each volunteer were extracted for DNA andanalyzed by PCR-based SDSCP. Quantitative culture showedthat the Entero-test was four times as sensitive as theGastro-test but was more prone to contamination by oral flora. However, the two string testsare equally sensitive by PCR assays. Thus, theGastro-test is more suitable for culture detection of H.pylori, since it is less prone to oral contamination and its shorter length is better tolerated.SDSCP analysis of H. pylori DNA from four PCR-positivevolunteers without requiring culture showed fourdistinct profiles, indicating different infectingstrains. SDSCP analysis of strains isolated before andafter treatment of one volunteer had the same SDSCPprofile, suggesting endogenous reinfection by the samestrain.     

Helicobacter pylori Infection and Gastric Cancer (A Nested Case-Control Study in a Rural Area of Japan)

We conducted a seroepidemiological nested case-control study to determine the association of gastriccancer with Helicobacter pylori infection and atrophicgastritis. A cohort of 2858 participants in an annual multiphasic health check-up werefollowed for eight years. Data for 45 gastric cancercases and 225 sex-, age-, and address-matched controlsubjects were analyzed. Helicobacter pylori infectionwas determined by IgG antibodies, and atrophicgastritis was diagnosed by both serum pepsinogen I level(70 ng/ml) and the pepsinogen I/II ratio (3.0).Univariate analysis showed that Helicobacter pylori and atrophic gastritis were significantlyassociated with gastric cancer. In a multivariateanalysis, atrophic gastritis was associated withsignificantly increased risk of cancer (odds ratio,3.38; 95% confidence interval, 1.54-7.42); however,Helicobacter pylori was not associated with cancer (oddsratio, 1.84; 95% confidence interval, 0.59-5.72). Theseresults suggest that Helicobacter pylori infection alone is not directly associated with gastriccarcinogenesis but has an indirect relation to gastriccancer through the development of atrophicgastritis.     

Expression of bcl-2 in Autoimmune and Helicobacter pylori-Associated Atrophic Gastritis

Chronic atrophic gastritis can be induced eitherby H. pylori or by an autoimmune process. The proteinproduct of bcl-2, which is a protooncogene, blocksapoptosis. Aberrant bcl-2 expression has been found in 68% of atrophic gastritis patients. The aimof this study was to compare bcl-2 expression in 20autoimmune atrophic gastritis patients to that in 20 H.pylori-associated atrophic gastritis patients. Twenty patients with H. pylori antral gastritisbut without atrophy served as controls. The bcl-2expression was assessed by immunohistochemical stainingof gastric biopsies, using mouse anti-human bcl-2 monoclonal antibodies. Autoimmune atrophicgastritis patients were younger, mainly females, with asignificantly higher serum gastrin level than the H.pylori-associated atrophic gastritis group (P < 0.001). The bcl-2 was expressed in 10/20 (50%)of autoimmune atrophic gastritis patients, in 9/20 (45%)of H. pylori-associated atrophic gastritis patients (P= 0.73), and in 2/20 (10%) of controls. There was no correlation between bcl-2expression and the presence of intestinal metaplasia (P= 0.35). Our findings confirm that H. pylori-associatedatrophic gastritis and autoimmune atrophic gastritis are two different conditions, but with equalexpression of bcl-2. Excessive expression of bcl-2 isfound only in atrophic gastritis, but not in H. pyloriantral gastritis without atrophy.     

Seroprevalence of Helicobacter pylori, Incidence of Gastric Cancer, and Peptic Ulcer-Associated Hospitalizations in a Canadian Indian Population

The living conditions of many aboriginalcommunities in Canada may place their residents at riskfor H. pylori infection. Our aims were to determine: (1)the seroprevalence of H. pylori in a traditional Indian community, (2) the clinical relevance ofH. pylori infection in this population, and (3) if H.pylori could be identified by polymerase chain reactionfrom the local water. A demographic questionnaire was administered, and blood was collected fromsubjects in an Indian community in northwesternManitoba. The serum was analyzed by ELISA for IgG to H.pylori and to CagA. ABO and Lewis antigens were tested. Age-adjusted incidence of gastric cancer and ofhospitalizations associated with diagnoses of pepticulcer were determined for the Indian and non-IndianManitoba population in the years 1989-1993. Nested PCR was performed on lake water using H.pylori-specific primers and the amplicons probed with aninternal Dig-labeled probe. Three hundred six (59%) ofapproximately 518 individuals who were resident in the community at the time of the study wereenrolled. The ELISA for H. pylori was positive in 291(95%). There was no association between H. pyloriseropositivity and age, sex, gastrointestinalcomplaints, medications, housing characteristics, and ABOor Lewis antigen status. CagA was positive in 84.5% ofinfected subjects. The average annual age-adjustedincidence of hospitalizations associated with diagnoses of peptic ulcer disease in Manitoba was higherfor treaty-status Indians (394.3/100,000) than fornon-Indians (203.8/100,000), but gastric cancer rateswere similar (11.2/100,000 vs 11.6/ 100,000). No H. pylori DNA was detected in the lake water. Inconclusion, the seroprevalence of CagA-positive H.pylori is high in this representative Manitoban Indiancommunity. This may be associated with an increased risk for peptic ulcer disease but is notassociated with an increased risk for gastriccancer.     

Helicobacter pylori Infection and Atrophic Gastritis (A Nested Case-Control Study in a Rural Town in Japan)

A seroepidemiologic, nested case-control studywas conducted to evaluate the risk for atrophicgastritis associated with Helicobacter pylori infection.Atrophic gastritis was diagnosed on the basis of serum pepsinogen levels: pepsinogen I level70 ng/ml and pepsinogen I/pepsinogen II ratio3.0. Cases were 23 men and 39 women who were notdiagnosed with atrophic gastritis in 1987, but who were diagnosed with the condition in 1992. Controlswere the 120 men and 282 women who did not meet theserologic criteria for atrophic gastritis in either timeperiod. Neither cases nor controls had a history of upper gastrointestinal operations.Helicobacter pylori infection at the initial survey wasassociated with a significantly increased risk ofatrophic gastritis incidence for both sexes combined(odds ratio = 3.72; 95% confidence interval,1.78-7.79; P = 0.0005). Cigarette smoking andconsumption of alcohol and green-yellow vegetables werenot associated with incidence of atrophicgastritis.     

Use of Chopsticks for Eating and Helicobacter pylori Infection

Epidemiological data suggests that ethnic groupsusing chopsticks for eating have a higher prevalence ofH. pylori infection. This study investigated thecarriage of H. pylori in chopsticks after eating. Used chopsticks and saliva were collected fromasymptomatic individuals whose H. pylori status wasdetermined by [¹³C]urea breath test andserology. Both the saliva specimens and chopsticks werecultured and processed by polymerase chain reaction(PCR) for the detection of H. pylori . Furthermore,chopsticks used by hospital staff in the cafeteria werepooled for the detection of H. pylori by bacteriologic culture and PCR. Sixty-nine volunteers wererecruited in the first study and 45 (65%) were diagnosedto have H. pylori infection. While all cultures werenegative, H. pylori was detected by PCR in the saliva from 15 (33%) infected subjects and in thechopsticks from one (2%). Among the 12 sets of pooledchopstick-washing studied, H. pylori was detected by PCRin two sets. This study showed that H. pylori was rarely detected in chopsticks after eating andhence, the risk of contracting this infection via theuse of chopsticks is low.     

Development of Helicobacter pylori Infection Model in BALB/c Mice with Domestic cagA-Positive and-Negative Strains in Taiwan

We aimed to develop an H. pylori-infected mousemodel using clinically stored strains in Taiwan and totest whether development of H. pylori infection in an invivo animal model is related to the status of the cagA gene. A total of 100 male BALB/cmice, 6-8 weeks old, including 80 in the experimentalgroup and 20 in the control group, were used. Twoclinically stored H. pylori isolates, a cagA-positive and a cagA-negative strain, were selected toinduce the H. pylori infection in half (N = 40) of themice in the experimental group. Bacterial isolates of0.8 × 10⁹ CFU/ml were orally inoculatedin each mouse of the experimental group for threeconsecutive days. Ten mice in the control group weresacrificed to confirm the initial absence of H. pylori.Eight weeks after inoculation of the experimental group and no inoculation of the remaining 10mice of the control group, each mouse was killed.Gastrectomy was then performed for rapid urease test(CLOtest) and histology. In the control group, none of 20 mice had positive results from the CLOtestor histology. In contrast, excluding eight of 80 micethat died before the eighth week, 90.3% (65/72) of themice challenged with H. pylori showed persistent presence of H. pylori by histology. Theseverity of gastritis at the eighth week was moreevident in H. pylori-infected mice than in control andnoninfected mice (P < 0.05). Although gastritis wasmore severe in mice inoculated with thecagA-positive strain than with the cagA-negative strain,the rates of H. pylori infection in mice were notdifferent between cagA-positive and -negative strains(91.4% vs 89.2%, P > 0.05). In summary, storedstrains of H. pylori can be applied to induce aninfection model in BALB/c mice. The less virulentcagA-negative strain can induce H. pylori infection inmice as effectively as the cagA-positive strain. Thehigh prevalence of cagA-positive strains in Taiwanesepatients may be related to factors other than only thecagA gene of the bacteria.     

Chemical Structure of Bismuth Compounds Determines Their Gastric Ulcer Healing Efficacy and Anti- Helicobacter pylori Activity

The recognition of the role of Helicobacterpylori in the pathogenesis of peptic ulcer disease hasled to renewed interest in bismuth pharmacology sincebismuth compounds have both anti-Helicobacter pylori and ulcer healing properties. The precisechemical structure of current bismuth compounds is notknown. This has hindered the development of new andpotentially more efficacious formulations. We havecreated two new compounds,2-chloro1,3-dithia-2-bismolane (CDTB) and1,2-[bis(1,3-dithia-2-bismolane)thio]ethane (BTBT), withknown structure. In a rat model of gastric ulceration,BTBT was comparable to, and CDTB was significantly less effective thancolloidal bismuth subcitrate in healing cryoprobeinducedulcers. However, both BTBT and CDTB inhibited H. pylorigrowth in vitro at concentrations <1/10 that of colloidal bismuth subcitrate. The effects onulcer healing are not mediated by suppression of acidsecretion, pepsin inhibition, or prostaglandinproduction. Since all treated animals received the same amount of elemental bismuth, it appears thatthe efficacy of bismuth compounds varies with compoundstructure and is not simply dependent on the delivery ofbismuth ion. Because the structure of the novel compounds is known, our understanding of therelationship of bismuth compound structure and tobiologic activity will increase. In the future it may bepossible to design other novel bismuth compounds with more potent anti-H. pylori and ulcer healingeffects.     

Prevalence of Helicobacter pylori Infection in Children from Urban and Rural West Virginia

Our objective was to evaluate the prevalencerate of Helicobacter pylori (HP) in children from urbanand rural areas of West Virginia. In all, 1164 bloodsamples were collected from children who attended a local health fair, pediatric clinics, andemergency departments of four different hospitalslocated in urban and rural counties. Socioeconomicstatus was determined in 303 children. Serum HP antibody (IgG) was measured by enzyme immunoassay (EIA).A total of 468 (40%) samples were HP positive. HPacquisition correlated with increasing age, familycrowding, and community location (urban/rural) but not with gender, water source used (city/well), orsocioeconomic status. The prevalence rate of HP in thechildren of West Virginia is higher than any datapreviously reported from the United States. The results correlated with only few socioeconomiccriteria, suggesting that other factors may contributeto the increased prevalence of HP infection in thechildren of West Virginia.     

Predictive Factors and Prevalence of Follicular Gastritis in Adults with Peptic Ulcer and Nonulcer Dyspepsia

Follicular gastritis is an importanthistological entity, because it may progress to overtgastric MALT lymphoma. However, there is no universalagreement on whether there is any correlation offollicular gastritis with histological features of theantral mucosa or on the prevalence of folliculargastritis. To shed further light on these issues, westudied antral biopsies obtained from 735 adultpatients, who had participated in six consecutiveclinical trials. They included 348 patients withduodenal ulcer, 82 with gastric ulcer, and 305 withnonulcer dyspepsia. The Sydney classification system ofgastritis was used, using a score of 0-3 to grade degreeand activity of inflammation, gland atrophy, intestinalmetaplasia, and H. pylori colonization density.Follicular gastritis was defined as prominent lymphoid follicles with no lymphoepithelial lesion. Noneof the H. pylori-negative patients (N = 159) hadfollicular gastritis. Among H. pylori-positive patients,80/340 (23.5%) with duodenal ulcer, 5/77 (6.5%) withgastric ulcer, and 20/159 (12.6% ) with nonulcerdyspepsia had follicular gastritis (P < 0.001).Multivariate discriminant analysis selected thefollowing four significant predictor variables for follicular gastritis (Wilks =0.91, x² = 70.6, df = 4, P < 0.001):gastritis sum score, atrophic gastritis, age of thepatient, and disease. The prevalence of folliculargastritis was linearly correlated (y = 24.55 – 0.98x, r =–0.62, F_1,11 = 6.12, P = 0.03) with theage groups of the 576 H. pylori-positive patientsstudied. In conclusion, follicular gastritis is highlycorrelated with H. pylori-caused severe, activegastritis. It is mostly prevalent in the young H.pylori-infected patients with duodenal ulcer.     

Antibiotic Properties of Bovine Lactoferrin on Helicobacter pylori

To investigate a potential new treatment forgastric Helicobacter pylori infection, we have examinedthe use of the natural antibiotic lactoferrin, found inbovine milk, for activity against Helicobacter species both in vitro and in vivo. Lactoferrinwas bacteriostatic to H. pylori when cultured atconcentrations 0.5 mg/ml. Growth of H. pylori wasnot inhibited by another milk constituent, lysozyme, or by a metabolite of lactoferrin, lactoferricinB, but growth was inhibited by the iron chelatordeferoxamine mesylate. Lactoferrin inhibition of growthcould be reversed by addition of excess iron to the medium. Lactoferrin in retail dairy milk wasfound to be more stable intragastrically thanunbuffered, purified lactoferrin. Treatment of H.felis-infected mice with lactoferrin partially reversedmucosal disease manifestations. It is concluded thatbovine lactoferrin has significant antimicrobialactivity against Helicobacter species in vitro and invivo. Bovine lactoferrin should be further investigated for possible use in H. pylori infections inman.     

Helicobacter pylori Infection Has No Role in the Pathogenesis of Reflux Esophagitis

In a prospective study of consecutive patientswith reflux esophagitis and/or hiatal hernia andBarrett's esophagus, the prevalence of Helicobacterpylori was assessed. Antral biopsy specimens werestudied and a serum sample for detection of IgGantibodies against Helicobacter pylori was taken. As areference group patients presenting with a normalesophagus, stomach, and duodenum were taken. Refluxesophagitis was diagnosed in 118 patients, hiatal herniawithout esophageal inflammation in 109, and Barrett'sesophagus in 13. Helicobacter pylori was present in 74(30%) of these patients and in 204 (51%) of the reference group. Prevalence of Helicobacterpylori was significantly lower in all groups comparedwith the reference group (P < 0.001). There was nodifference when patients with esophagitis, Barrett'sesophagus, or hiatal hernia were compared. Patients withesophagitis and Helicobacter pylori in their antrum aresignificantly older than esophagitis patients withoutconcomitant Helicobacter infection, 61.5 (SD, 17) versus 53 (SD, 17) years (P < 0.001). Itis concluded that the prevalence of Helicobacter pyloriinfection in patients with gastroesophageal refluxdisease is significantly lower than in the reference group, irrespective of the severity ofesophagitis. Helicobacter pylori infection has no rolein the pathogenesis of reflux esophagitis.     

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.     

Role of Helicobacter pylori Infection on Upper Gastrointestinal Bleeding in the Elderly (A Case-Control Study)

Nonsteroidal antiinflammatory drug (NSAID) useis known to be associated with a high incidence of uppergastrointestinal tract bleeding in the elderly. Theincreased prevalence of Helicobacter pylori (HP) infection, which also occurs with age, suggeststhat an interaction between NSAID use and HP infectionmay explain the higher incidence of ulcer complicationsin the elderly. The aim of the present study was to determine if a relationship existsbetween HP infection and NSAID use in elderly patientswith upper gastrointestinal bleeding. This was a case-control study on 146 elderly patients (73/group). The bleeding group consisted of 37 males and 36females (mean age 80.4 years, range 70-96) with symptoms(hematemesis, melena, anemia with loss of more than 3 ghemoglobin), and endoscopic stigmata of bleeding. The control group consisted of 73 age- andsex-matched patients with the same endoscopic diagnosisbut with no endoscopic stigmata of bleeding. NSAID usewas evaluated by interview at the time of endoscopy, and HP infection was confirmed in all cases byhistology and the rapid urease test. Statisticalanalyses were performed using the chisquare test andlogistic regression. In both groups, 46.57% of patients were affected with gastric ulcer, 36.98% withduodenal ulcer, and 16.43% with erosive gastritis. Thebleeding group had a significantly higher percentage ofNSAID users (53.42% vs 19.17%, P < 0.0001) and a lower percentage of HP-positive patients(47.94% vs 72.60%, P = 0.004). The NSAID use pattern wasas follows: occasional users (sporadic, as needed duringthe previous week): 53.8% of bleeding cases and 50% of controls; acute users (continuoustherapy for less than one month): 17.9% of bleedingcases and 28.5% of controls; and chronic users(continuous therapy for more than one month): 28.2% ofbleeding cases and 21.4% of controls. The logisticregression demonstrated that NSAID use was significantlyrelated to an increase risk of bleeding both in gastric(odds ratio: 4.98, 95% CI: 1.83-13.6) and duodenal ulcer patients (odds ratio: 10.2, 95% CI: 2.25-46.7) while HP-positivity presented a significantinverse relationship with bleeding only in subjects withgastric lesions (odds ratio: 0.20, 95% CI: 0.07- 0.55). NSAID use and HP infection were alsoshown to be independent, unrelated factors, with theoverall risk of bleeding in HP-positive NSAID usersidentified to be significantly less than in HP-negative NSAID users. In conclusion, in elderlypatients: (1) NSAID use increases the risk of uppergastrointestinal bleeding while HP infection wasassociated with a low risk for gastric bleeding; and (2)the two factors are independent variables, thereforethe HP-positive NSAID user has a lower risk than theHP-negative NSAID user.