The study of Helicobacter pylori in Malaysia has given several important insights into the epidemiology of the infection and pathogenesis of disease. Malaysia has a multiracial Asian population with three major Asian races living together-Malay, Chinese, and Indian. Races remain fairly distinct because of a paucity of interracial marriages. The "Racial Cohort Hypothesis" proposes that the infection occurs within racial groups rather than between. As such, the high prevalence among Indians (> 50%) and Chinese (40-50%) reflects the high prevalence in their countries of origin even though migration had taken place more than two generations before. The Malays have a comparatively low prevalence of about 10-20%. Despite the high prevalence of H. pylori, the Indians have a low gastric cancer incidence of less than 10 per 100 000 per year. This is in contrast to the Chinese who has an incidence in excess of 20 per 100 000 per year. We have called this the "Indian Enigma." The reason for this enigma is unclear and is the result of interaction between bacterial virulence factors, host susceptibility, and environmental factors. Phylogenetically, Chinese bacterial strains are distinct from Indians and Malays and are predominantly hpEastAsia/hsp EAsia. CagA EPIYA motifs among Chinese belong predominantly to the more virulent ABD motif. There is no clear distinguishing profile among host genetic factors. Environmental factors particularly diet may play an important role. Indians consume chilies and curries, which may be gastro protective, whereas Chinese consume more preserved and salted foods, which are thought to be carcinogenic.

Systematic reports on acute upper gastrointestinal bleeding in children/adolescents are scanty. The aim of this study is to analyze its presentation, pathology and outcome in Hong Kong.

A retrospective review of the hospital database for admissions up to the age of 18 years with signs of acute upper gastrointestinal bleeding between 1 June 1996 and 31 May 2006.

During the 10-year period 76 patients (55 boys) were admitted with signs of upper gastrointestinal bleeding. The median age was 13.5 (range 0.25-18) years. Melena and hematemesis were by far the most frequent presentations. Medication was implicated in 16 cases (21%) as the possible cause for the bleeding. Endoscopic findings were a duodenal ulcer in 57 (75%) patients (50 boys) and a gastric ulcer in eight (10.5%). Helicobacter pylori infection was identified in 42 (55%) patients, of which 38 were found in duodenal ulcer patients. Eleven patients (14.5%) had interventions to achieve hemostasis: six epinephrine spray only, three thermal probe and two vessel ligation. After a median follow-up time of 3.5 years six patients had a recurrent duodenal ulcer. Three patients died of unrelated illnesses.

Acute upper gastrointestinal tract bleeding in children and adolescents in Hong Kong is dominated by a duodenal ulcer in 75% of the patients. Acute bleeding is more frequent in boys (boy to girl ratio 2.6:1). Medication is a predisposing factor in 20% of the bleedings. Six patients (8%) have recurrent duodenal ulcers.

The gastric biopsy urease test is an accurate and robust diagnostic test for Helicobacter pylori infection. Large endoscopy units use their own homemade unbuffered ultra-rapid urease test for diagnosis of H. pylori infection but several commercial rapid urease tests are available.

To compare the accuracy and reaction time of a new biopsy urease test, HUITAI rapid urease test, in the diagnosis of H. pylori infection.

Consecutive patients presenting with dyspepsia to the endoscopy unit, University of Malaya Medical Center were recruited for the study. Patients who were previously treated for H. pylori infection or who had received antibiotics, proton pump inhibitors or bismuth compounds in the preceding 4 weeks were excluded. The H. pylori diagnosis was made based on the homemade rapid urease test, histology and culture of gastric biopsies. Biopsies from the antrum and corpus of the stomach were taken for this purpose. In addition, two antral and corpus biopsies were taken for the HUITAI rapid urease test. A positive diagnosis of H. pylori infection was made when the culture was positive or if both histology and the rapid urease test were positive. A negative diagnosis was made when all tests were negative. The positive reaction time of the HUITAI rapid urease test was carefully timed up to 60 min.

Two hundred and six patients were recruited in the study. One hundred and twelve were diagnosed as having an H. pylori infection while the other 94 patients were regarded as negative. There were no spoiled tests and no indeterminate results. The sensitivity of the HUITAI rapid urease test was 98.2% (95% confidence interval (CI): 93.7%, 99.8%), specificity, 99.0% (95% CI: 94.2%, 100%), positive predictive value, 99.0% (95% CI: 95.1%, 100%), negative predictive value, 97.9% (95% CI: 92.6%, 99.7%). The overall diagnostic accuracy for the HUITAI rapid urease test was 98.5% (95% CI: 96.6, 99.9). The median positive reaction time was 1.0 min (25-75% inter-quartile range [IQR]: 1.0-3.0 min).

The HUITAI rapid urease test is highly accurate for the diagnosis of an H. pylori infection and showed a very rapid positive reaction time.

Previous reports, based on surgery, showed duodenal ulcer (DU) to be more common in the rice-eating areas of southern India than in the northern wheat-eating areas.

Does this difference persist? Can it be explained by risk factors other than diet?

A total of 20 053 records from patients undergoing endoscopy for dyspepsia, and 590 endoscopy patients from two northern and two southern centers in India were studied prospectively. Records were scrutinized to determine the relative incidence of DU and non-ulcer dyspepsia in wheat- and rice-eating areas. Age, sex, length of history, smoking and medication were recorded. Three antral biopsies and one from each duodenal quadrant were taken. A rapid urease test was carried out on one of the antral biopsies; the others were examined for Helicobacter pylori, gastritis, duodenitis and duodenal gastric metaplasia.

The difference in diet-associated prevalence persisted. No differences in smoking, Helicobacter pylori infection or duodenal gastric metaplasia were found between the two regions, but all three were more common in DU than in non-ulcer dyspeptic patients from both dietary areas.

The dietary differences between the regions remain the only factor to account for the differences in DU prevalence. A strong interrelationship between duodenal gastric metaplasia and cigarette smoking is demonstrated.

The gastric biopsy urease test is the most frequently used test for the diagnosis of Helicobacter pylori infection in routine gastrointestinal endoscopy practice. In Malaysia up to recently, only one commercial biopsy urease test was available: the CLO test (Ballard Medical Products, Draper, Utah, USA). Large endoscopy units use their own 'homemade' unbuffered ultra rapid urease test for diagnosis of H. pylori infection.

To compare the accuracy and reaction time of a new biopsy urease test, Pronto Dry (Medical Instruments Corporation, Solothurn, Switzerland) and the CLO test in the diagnosis of H. pylori infection.

Consecutive patients presenting with dyspepsia to the endoscopy unit, University of Malaya Medical Centre were recruited for the study. Patients who were previously treated for H. pylori infection or who had received antibiotics, proton pump inhibitors or bismuth compounds in the preceding 4 weeks were excluded. H. pylori diagnosis was made based on the ultra rapid urease test and histological examination of gastric biopsies. Four antral and four corpus biopsies were taken for this purpose from all patients. A diagnosis of H. pylori infection was made when both the ultra rapid urease test and histology were positive in either the antral or corpus biopsies. A negative diagnosis of H. pylori was made when both tests from antral and corpus biopsies were all negative. Another four antral and four corpus biopsies (two each) were taken for the Pronto Dry and CLO tests. The Pronto Dry and CLO tests were stored and performed according to the manufacturer's instruction.

Two hundred and eight patients were recruited in the study. Eighty-six of the patients were males and 122 were females. The mean age was 46.3 years with a range of 15-82 years. The results for both the Pronto Dry and the CLO tests were completely concordant with sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy of 98.1%, 100%, 100%, 98.1% and 99%, respectively. The Pronto Dry test showed a faster reaction time to positive compared with the CLO test, with 96.2% positive reaction by 30 min versus 70.8% and 100% positive reaction time by 55 min versus 83%. The colorimetric change was also more distinct with the Pronto Dry test compared with the CLO test.

Both the Pronto Dry and the CLO tests were highly accurate for the diagnosis of H. pylori infection. The Pronto Dry test showed a quicker positive reaction time and the positive colour change was more distinct.

Furazolidone-based regimens for the eradication of Helicobacter pylori are low cost and effective. Unfortunately, the usual dose of furazolidone is not tolerable in many patients. Lower doses of furazolidone are expected to cause fewer adverse effects.

To investigate the efficacy of low-dose furazolidone in the eradication of H. pylori.

One hundred and fifty patients with duodenal ulcer and H. pylori infection were randomly assigned to one of three treatment groups: omeprazole 20 mg b.d., amoxicillin 1000 mg b.d. and furazolidone 100 mg b.d. for 14 days (OAF); omeprazole 20 mg b.d., amoxicillin 1000 mg b.d., furazolidone 100 mg b.d. and bismuth subcitrate 240 mg b.d. for 14 days (OABF1); or omeprazole 20 mg b.d., amoxicillin 1000 mg b.d., furazolidone 200 mg b.d. and bismuth subcitrate 240 mg b.d. for 14 days (OABF2).

Of the 150 patients, 145 completed treatment. The intention-to-treat and per protocol eradication rates were 54% (27/50), 72% (36/50) and 92% (46/50) for the OAF, OABF1 and OABF2 groups, respectively. The OAF and OABF1 groups showed significantly lower eradication rates than the OABF2 group (P<0.001 and P<0.01, respectively).

Triple and quadruple furazolidone-based H. pylori eradication regimens do not yield acceptable success rates when a low dose of furazolidone (100 mg b.d.) is used.

The relationship between Helicobacter pylori infection and gastric carcinoma remains controversial, especially in the African setting where infection is common, while gastric cancer is perceived to be uncommon, the basis of the so called 'African enigma'. This discrepancy between infection and the development of disease is commonly attributed to differences in host, environment and bacterial factors. Interest in the bacterial factors has focused on heterogeneity in the so-called 'virulence genes'.

The aim of this prospective, case-controlled study was to establish whether H. pylori infection is significantly associated with gastric cancer and to investigate whether gastric cancer is associated with genotypically distinct (as it relates to the candidate virulence genes) organisms in this population.

Patients with histologically confirmed gastric cancer were matched with nonulcer dyspeptic controls for age (within 5 years), gender and ethnicity. Helicobacter pylori status was determined by RUT, histology, culture and serology (locally validated and used as default determinant of H. pylori status). Tumors were classified according to the Lauren classification. The 'virulence genotype' of 17 paired culture samples was determined by previously described and validated molecular techniques (cagA presence, vacA alleles, structure of the cag pathogenicity island and analysis of the iceA alleles). Categorical variables were analysed by the chi2 test.

Forty-eight patients (median age 59 years) could be adequately matched to controls. 39/48 (81%) cases and 43/48 (90%) controls were H. pylori positive (NS). Significant differences in the virulence genotypes of infecting strains were noted: vacAs2-controls 24%, cases 0%, p < .00001; vacAs1 present - cases 100%, controls 76%, p < .05; cagA-3'-length > 650 bp - cases 47%, controls 0%, p < .002; cag pathogenicity island intact - cases 82%, controls 43%, p < .04; iceA1 - cases 53%, controls 6%, p < .005. cagA was found in all subjects.

This study indicates that, in this African population at least, there is no difference in the prevalence of H. pylori infection when comparing gastric cancer cases with matched controls. However, the findings suggest that gastric cancer may be associated with infection by organisms that are genotypically different from those not associated with disease.

One of the major problems when evaluating dyspeptic patients at public hospitals is the large interval between the consultation and the endoscopy, leading to the prescription of antisecretory drugs, what can be responsible for false results on examinations.

To evaluate changes in ultrarapid urease test and histopathological examination for Helicobacter pylori by antisecretory drugs.

In a prospective double-blind study, 50 patients with dyspeptic complaints and endoscopic diagnosis of peptic ulcer, erosive gastritis, esophagitis or duodenitis with a positive urease test, were randomized to a 7-day course of treatment with either omeprazole 20 mg or ranitidine 300 mg a day. Before and after treatment, two biopsy specimens each were obtained from the antrum and corpus and an ultrarapid urease test and a histopathological examination for Helicobacter pylori were performed.

There were no significant changes in the results of ultrarapid urease test and histopathological examination for Helicobacter pylori after treatment with ranitidine. With omeprazole, we observed a decrease in positive results in ultrarapid urease test and histopathological examination for Helicobacter pylori in the antrum, but not in the corpus.

Omeprazole, used for 7 days can lead to negative results in ultrarapid urease test and histopathological examination for Helicobacter pylori in the antrum, and should not be employed in patients before the endoscopy is performed.

Unbuffered rapid urease test (RUT) is an accurate, rapid, and inexpensive method of detecting Helicobacter pylori. However, it is generally recommended to prepare the reagent daily. This prospective study was undertaken to evaluate the shelf-life of our unbuffered RUT at -20 degrees C. Two sets of antral biopsies (X2) and body biopsies (X1) were taken from all patients. They were subjected to histologic examination and RUT stored at -20 degrees C. We studied 303 patients. One hundred seventy-nine (59%) were infected as defined by histologic examination. The reagent was classified according to the storage time (group I, 0-30 days [n = 109]; group II, 31-60 days [n = 63]; group III, 61-90 days [n = 80]; and group IV, tau91 days [n = 51]). There was an excellent agreement between the histologic examination and the RUT of the four groups (kappa coefficient: group I, 0.88; group III, 0.80; group III, 0.87; group IV, 0.88). The sensitivity of our RUT in groups I, II, III, and IV were 92%, 92%, 91%, and 89%, respectively. The corresponding specificity were 97%, 88%, 97%, and 100%. Our RUT remains highly sensitive and specific when it is stored at -20 degrees C for 4 months.

Furazolidone, an old but cheap antibiotic, was shown to be a good alternative to metronidazole in triple therapy for Helicobacter pylori eradication in areas where metronidazole resistant bacteria are common, but randomized studies are lacking.

A randomized controlled trial to determine the efficacy and safety of furazolidone compared to metronidazole in classic quadruple therapy for eradication of H. pylori infection in duodenal ulcer patients.

Patients with endoscopically proven duodenal ulcer and positive urease test were randomized to receive ranitidine 300 mg, amoxycillin 1000 mg and bismuth subcitrate 240 mg b.d, with either furazolidone 200 mg b.d (RABF), or metronidazole 500 mg b.d. (RABM) for 2 weeks. Compliance and side-effects were monitored and recorded by table diary. H. pylori eradication was assessed at least 4 weeks after the completion of therapy with 14C-urea breath test.

A total of 106 patients were enrolled and 101 (59 male, 42 female, mean age=40 +/- 11 years) completed the study. Endoscopic findings and demographic data were comparable in both groups. Intention-to-treat eradication rates were 75% and 55% (P=0.03) and per protocol eradication rates were 82 and 56% (P=0. 006) in the RABF and RABM groups, respectively. Side-effects were reported by 13 patients (27%) in the RABF group (one stopped treatment) compared to five patients (10%) in the RABM group (P=0. 04).

Quadruple therapy containing furazolidone, instead of metronidazole, results in a significantly higher H. pylori eradication rate in Iranian duodenal ulcer patients.

'Home made' ultra-rapid urease tests are used extensively in the Asia Pacific region. Data on the reliability of these 'home made' tests are limited.

To evaluate the effect of test duration on the sensitivity and specificity of a self-prepared biopsy urease test for the detection of Helicobacter pylori.

Using histology as the 'gold standard', the effect of test duration on the sensitivity and specificity of a self prepared urease test for the detection of H. pylori was evaluated in 411 consecutive patients undergoing upper gastrointestinal endoscopy.

Histology was positive for H. pylori in 217 of the 411 patients (52.8%). Within 24 hours of retrieving the specimen, 189 (87.1%) of the histology positives and 174 (89.7%) of the histology negatives were correctly identified by the urease test. Of the H. pylori positives, 72.0%, 81.0%, 89.9% and 100% were detected by the urease test within one minute, five minutes, three hours and 24 hours respectively. Thus, sensitivities of the urease test at one minute, five minutes, three hours and 24 hours were 62.7%, 70.5%, 78.3% and 87.1% respectively. Corresponding figures for the specificity were 93.8%, 93.3%, 92.3% and 89.7% respectively. Using a receiver-operating characteristic curve, an optimal combination of sensitivity and specificity was obtained when the urease test was read at 24 hours.

While the biopsy urease test was positive in most cases within a minute, better results could be obtained if the test continued to be read over a 24 hour period.

Controversy surrounds the optimal composition, dosage, and duration of therapies for eradication of Helicobacter pylori. We prospectively compared omeprazole-based dual and triple therapies in the eradication of H. pylori in a randomized manner.

Between June 1995 and March 1997, 1000 consecutive patients with acid-peptic disease associated with H. pylori infection (duodenal ulcer, 388 patients, gastric ulcer, 179 patients; duodenitis, 173 patients; gastritis, 260 patients) were prospectively recruited. They were randomized to either a 2-wk (OA) course of omeprazole 20 mg and amoxicillin 1 g, both given twice daily, or treatment for 1 wk (OCM) with omeprazole 20 mg once daily, clarithromycin 500 mg twice daily, and metronidazole 400 mg twice daily.

The age of these 1000 patients ranged from 16 to 90 yr, with a mean of 54.9 yr. Side effects occurred in 29.6% (95% confidence interval [CI] 25.6-33.8%) and 10.6% (95% CI 8.0-13.6%) of patients taking OCM and OA, respectively (p < 0.0001). Apart from taste disturbance, however, there were no significant differences in the incidences of side effects between the two groups. One patient in the OA group and four patients of the OCM group could not tolerate the medications, and therefore did not complete treatment (p = 0.37). Seven and 13 patients in the OA and OCM groups, respectively, refused a second endoscopy (p = 0.25). The remaining 975 patients underwent a second endoscopy. Positive endoscopic findings were significantly more common in the OA group (51/492; 10.4%; 95% CI 7.8-13.4%) than in the OCM group (25/483; 5.2%; 95% CI 3.4-7.5%) in the per-protocol (PP) analysis (p = 0.004). On intent-to-treat (ITT) analysis, the overall eradication rates in the OA and OCM groups were 73.6% (95% CI 69.5-77.4%) and 92% (95% CI 89.3-94.2%), respectively (p < 0.0001). On PP analysis, the corresponding rates were 74.8% (95% CI 70.7-78.6%) and 95.2% (95% CI 92.9-97.0%), respectively (p < 0.0001).

A course of omeprazole, clarithromycin, and metronidazole for 1 wk is a safe, well-tolerated, efficacious, and cost-effective treatment for H. pylori infection.

A number of noncommercial preparations of urease test have been described. The present prospective study evaluated the accuracy of one such preparation for the diagnosis of Helicobacter pylori infection.

From February 1996 to November 1996, all patients undergoing elective upper endoscopy in a single endoscopy facility were included. Three antral biopsy specimens were taken. Two specimens were subjected to histologic examination, and one specimen was placed into a "locally made rapid urease test" (LRUT). Results of histologic examinations were taken as standards for comparison. The final result of LRUT was obtained on scrutiny of color changes at 4 hours after the start of the test.

Two thousand three hundred sixteen patients (male/female = 1.5:1) with a mean age of 56.7 +/- 0.4 years were included. Five hundred sixty-two patients (24.3%) had a history of eradication treatment for H. pylori. Nine hundred fifty-three patients (41.1%) were found to be positive for H. pylori on histologic examination. In patients in whom a history of eradication therapy was absent, the sensitivity, specificity, and positive and negative predictive values of the LRUT were 92.8%, 97.6%, 97.5%, and 93.0%, respectively. In patients with a history of eradication treatment, the corresponding figures were 76.1%, 99.6%, 96.2%, and 96.9%.

The locally made rapid urease test provides a simple, safe, rapid, inexpensive, and accurate test for the diagnosis of H. pylori infection.

In view of its potential risk for the development of gastrointestinal disease or even gastric cancer at a later age, the study of Helicobacter pylori infection in childhood is gaining increasing importance and H. pylori infection is being considered a major issue of public health. H. pylori infection can be detected by a variety of methods. Because of its easy use, affordability, and overall availability, serology is the preferred diagnostic test, especially for large epidemiological studies. Based on our results, one might consider treating a child with recurrent abdominal pain and positive serology for H. pylori without further work-up, and only perform additional investigations when an anti-H. pylori therapy fails to resolve the complaints. According to this proposition, endoscopy of the upper gastrointestinal tract remains indicated in children if the noninvasive tests for Helicobacter pylori are negative in the absence of a diagnosis, or if symptomatology persists despite treatment.

Antibody titres (IgA and IgG) for Helicobacter pylori were assayed in 69 insulin-dependent diabetes mellitus patients (42 males, age 1-20 years) and 310 healthy controls (171 males, age 1-20 years). A positive antibody titre for Helicobacter pylori was found in 18/69 diabetic subjects compared to 17/310 controls (p < 0.001). There was no difference between Helicobacter pylori positive and negative diabetic subjects as regards age, sex, duration of diabetes, diabetic control, insulin dose and SDS for weight and height. Gastroduodenoscopy revealed presence of Helicobacter pylori and evidence of gastric inflammation in 7/8 symptomatic diabetic children. There was a significant association in the diabetic subjects between positivity for anti-cow's milk protein and anti-Helicobacter antibodies, compared to the control group. Seven of the 17 diabetics studied within 3 months of the onset of diabetes had positive antibody titres for Helicobacter. Of these seven patients, five were positive for anti-cow's milk protein antibodies. In our study the prevalence of Helicobacter pylori infection was significantly higher in diabetic subjects than in controls, but the infection was asymptomatic and there was no correlation with diabetes control. In diabetic subjects Helicobacter pylori infection was associated with a humoral response to cow's milk proteins and was often present from the onset of diabetes.

Furazolidone is an inexpensive antibiotic that has considerable anti-Helicobacter pylori activity in vitro.

Twenty-three patients with culture-proven H. pylori infection were treated for one week with a dual therapy containing omeprazole and furazolidone.

Eradication succeeded in 10 of the first 20 evaluable patients (50%; 95% CI: 27.2-72.8%). This percentage was regarded as too low, and the study was terminated. Side-effects were mild.

With the possible increase in resistance to metronidazole and clarithromycin world-wide, furazolidone may be useful alternative in the treatment of H. pylori infection. Dual therapy for one week, however, is not sufficient.

We aimed to determine the frequency of portal hypertensive gastropathy (PHG) in children with extrahepatic portal venous obstruction (EHPVO) and to find out the role of esophageal variceal obliteration by endoscopic injection sclerotherapy (EIS) and Helicobacter pylori (H. pylori) infection in the pathogenesis of PHG. Twenty consecutive children were studied before EIS and 20 after esophageal varices obliteration. Diagnosis of PHG was established by endoscopic assessment. Helicobacter pylori infection was diagnosed by rapid urease test, H. pylori culture, smear, and histopathologic examination of antral biopsy specimens. Portal hypertensive gastropathy was characterized and graded by endoscopy according to previously established criteria. In the pre-EIS group, eight (40%) had PHG (mild in all) compared with 16 (80%; mild in eight, severe in eight) in the post-EIS group (p < 0.05). Portal hypertensive gastropathy was more extensive in the post-EIS group. There was no significant difference between frequency of gastric varices and H. pylori infection in the pre-EIS and post-EIS groups. We conclude that PHG is common in children with EHPVO; its frequency, extent, and severity increase after esophageal variceal obliteration by EIS, and H. pylori infection does not play any role in its development.

Current tests used to detect Helicobacter pylori are either invasive (histological detection, culture, the polymerase chain reaction (PCR), smear examination) or non-invasive (serology, 13C-urea breath test). These tests vary in their sensitivity and specificity, and the choice of test will depend on the situation, for example, whether the test is to detect infection or the success of eradication treatment. The accuracy of histological tests depends, to a large degree, on the expertise of the pathologist, while the accuracy of culture can depend on the conditions in which the specimen is transported and processed. When performed under optimal conditions, both techniques give very good results. The PCR test has similar sensitivity and specificity to histological and culture tests but a strict protocol must be followed to avoid contamination with H. pylori DNA. The rapid urease test (with a reading taken 1 hour later) is suitable for diagnosis before treatment but its sensitivity decreases after treatment. Smear examination has limited sensitivity. The urea breath test and serology (specific IgG detected by enzyme-linked immunosorbent assay with purified antigens) have sensitivities close to those using the best of the biopsy methods. Other points to consider when selecting a test are its availability, the rapidity of the results (which can range from a few minutes to 2 weeks), possibilities for retrospective analysis, quantification and the detection of pathogenic properties, the globality of certain tests that present an overall picture of the stomach, thus avoiding errors in sampling, and the cost of the test. Important added value can be gained from certain tests: histology allows evaluation of the status of the mucosa, culture allows strain typing and tests for antibiotic susceptibility, and the breath test can confirm successful eradication without endoscopy. When the diagnostic tests are performed correctly, most of them are highly accurate.

An in vitro experiment and an in vivo clinical trial were both performed in order to assess the efficacy of four biopsy urease test systems, including one commercial kit, Temmler CUT test (Temmler Pharma, Marburg, Germany), for the rapid detection of Helicobacter pylori. We first evaluated four rapid urease test systems by inoculating bacterial suspensions of different concentrations into urea-containing media and observing the color change at room temperature. We found that the CUT test was superior in vitro to the other three urease test systems. As was expected, the lower the concentration of the inoculum, the slower was the color change and the fewer were the positive results noted. The minimal concentration of H. pylori for a positive urease test at 24 h was 1000-10,000 colony-forming units/ml in 1 drop of bacterial suspension inoculated. We then evaluated four biopsy urease test systems for the rapid diagnosis of H. pylori infection in antral and fundal mucosa biopsy specimens of 37 patients undergoing upper gastrointestinal endoscopy. All four test systems were 100% specific when compared with culture. In 69 culture-positive biopsy specimens, the CUT test was not only more sensitive (72%) than the other three systems (42%, 51%, and 45%, respectively), but also gave the fastest reaction by detecting more culture-positive biopsy specimens after 3 h of incubation at room temperature. The differences were statistically significant.

Forty-two gastric biopsies, in two transport media, were homogenized and cultured on three media under micro-aerophilic conditions. Brain-heart infusion agar with a commercial antibiotic supplement (giving 10 mg vancomycin, 5 mg trimethoprim and 2500 i.u. polymixin per litre) yielded the best results. Ordinary chocolate (heated) human blood agar could be used in laboratories with limited resources. Growth was obtained in 4-6 days at 37 degrees C. All isolates were sensitive to metronidazole. The resistance to nalidixic acid and rapid urease production of Helicobacter pylori could be used to differentiate this species from Campylobacter spp. Indicator medium (brain-heart infusion broth with 7% human blood and 40 mg 2,3,5-triphenyletetrazolium chloride agar/litre) also proved useful in identification.

We used Japanese monkeys (Macaca fuscata) to establish an experimental model in order to clarify the pathogenicity of Helicobacter pylori in gastric and duodenal disorders. A suspension (5 ml; 10(9) CFU/ml) of H. pylori cells isolated from humans was sprayed around the antrum of the stomach of each of 12 of 17 animals with an endoscope. The remaining five animals were not inoculated; they served as a control group. On days 7, 14, and 28 after inoculation, the gastric mucosa samples were examined grossly and were biopsied for microscopic examination with an endoscope. H. pylori was recovered from 7 of the 12 inoculated animals (58%), and infiltration by neutrophils and monocytes was observed histologically. Macroscopic gastritis with erythema and erosions were noted for five of these animals. On day 28 after inoculation, five animals in the infected group were treated with ampicillin. In two infected but untreated animals, the bacteria persisted for more than 6 months. The result of the gastritis scoring of the antral mucosa and the ammonia concentration in the gastric secretion were significantly higher (P < 0.01 to 0.001) for the infected group than for the control group; however, these values decreased to levels comparable to those for the control group after treatment with ampicillin. Urease activity was positive in gastric biopsy specimens from five of the seven animals in the infected group after 7 days and from four of these animals after 14 days but was negative in all specimens from animals in the control group. The level of antibody (immunoglobulin G) in serum for the infected group was elevated but changed very little for the control group. These results suggest that this M. fuscata model can be used to study H. pylori infection and that H. pylori can induce gastritis.

A modified rapid urease test (MRU test) for the detection of Helicobacter pylori was evaluated under field conditions during an endoscopic survey in rural India and compared with a commercially available urease test (CLO test) and with histology. Of 195 consecutive subjects who underwent upper gastrointestinal endoscopy, 153 (78.5%) were positive for Helicobacter pylori when tested by the CLO test and/or histology. The sensitivity and specificity of the MRU test relative to this was 97.4 and 95.2%, respectively when the test was read over a 3 h period. The MRU test was positive in 77.4, 89.0, 93.8 and 96.6% of cases at 1, 5, 20 and 60 min, respectively, compared with 2.7, 14.4, 48.6 and 71.2% of cases for the CLO test at the same time. The accuracy of the MRU test was thus similar to that of other methods for the detection of Helicobacter pylori. Furthermore, it gave a positive diagnosis more rapidly than other tests, in most cases before the subject had left the endoscopy suite. The MRU test is extremely simple to prepare and read and costs less than 0.05 pounds per test compared with 2.26 pounds for a CLO test. It is suitable for use in clinical or epidemiological work and especially where cost factors are critical.

Duodenal ulcer relapse rates after therapy with sucralfate or bismuth are lower than those after H2-receptor antagonist therapy. This may be mediated by an antibacterial effect of these drugs on Helicobacter pylori. Bismuth has become an integral part of 'triple therapy' because of its documented anti-H. pylori effect. In vitro and clinical data suggest that sucralfate may also have an anti-H. pylori effect. The aim of this randomized, prospective therapeutic trial was to compare the efficacy of triple therapy containing bismuth with that containing sucralfate and to determine the effect of therapy with these combinations on duodenal ulcer relapse. Forty H. pylori-positive duodenal ulcer patients were healed with omeprazole and randomized to receive either 1 g sucralfate four times daily or 120 mg bismuth compound four times daily. All patients received 400 mg metronidazole three times daily and either 250 or 500 mg tetracycline four times daily for 7-14 days. Thirty-five patients could be analysed. Overall eradication rates did not differ in the treatment groups (10 of 17 eradicated with sucralfate and 11 of 18 with bismuth). Relapse rates were significantly lower in the eradicated group (1 of 21 compared with 8 of 14 in the non-eradicated group) and did not differ between treatment groups in those patients not eradicated. A triple therapy regimen utilizing sucralfate appears to be as effective as the bismuth-containing regimen.

A study was undertaken to determine the role of Helicobacter pylori in non-ulcer dyspepsia (NUD) and to determine the efficacy of colloidal bismuth subcitrate (CBS) in the treatment of NUD. Seventy-one patients were randomly allocated (double blind) to CBS or placebo, two tablets twice daily for 4 weeks. The severity of dyspepsia was scored and endoscopies performed before and after treatment, and antral biopsy specimens were taken for bacteriologic and histologic examination. Forty patients had H. pylori infection, and all had changes of chronic active gastritis. H. pylori was cleared from 17 to 21 patients (81%) treated with CBS, whereas none of the 19 patients treated with placebo cleared the bacteria. Improvement in histology was noted in 15 of 21 patients (71.4%) treated with CBS, whereas no improvement was noted in any of the placebo controls. Thirty-one patients were negative for H. pylori. All had either normal gastric histology or minor degrees of inflammation. Seventeen of these patients received CBS, and 14 received placebo. All groups reported improvement in the symptom score; however, the H. pylori-positive, CBS-treated group recorded a significantly higher improvement than the other groups (p less than 0.001). Relapse of H. pylori infection after initial clearance of the bacteria was high. Twelve of 16 patients evaluated relapsed 1 month after withdrawal of CBS.

Twenty three children with coexistent duodenal ulcer and Helicobacter pylori infection were treated with either two weeks of amoxycillin (25 mg/kg/day) in addition to six weeks of cimetidine, or cimetidine alone. Endoscopy with antral and duodenal biopsies for urease test, microaerophilic culture, and histological studies were performed at entry, six weeks, 12 weeks, and at six months. Children with persistent H pylori infection at six weeks were given a further two weeks' course of amoxycillin. H pylori persisted in all children not receiving amoxycillin treatment but cleared in six of the 13 children (46%) treated with amoxycillin. With failure of H pylori clearance at six months, only two out of six (33%) ulcers had healed and 50% of patients had experienced ulcer recurrence. In contrast, when H pylori remained cleared all ulcers healed and no ulcer recurred. Persistent H pylori infection was associated with persistent gastritis and duodenitis despite endoscopic evidence of ulcer healing. Detection and eradication of H pylori deserves particular attention in the routine management of duodenal ulceration in children.

Antral biopsy specimens from 106 patients were examined by culture, Gram stain and silver stain for Campylobacter pylori. Biopsies were also examined by a urea test paper test (UTPT). Of 106 patients studied C. pylori was detected in 68 (64.2%) by Gram stain, silver stain and culture. The UTPT was positive in 63 (59.4%) specimens. Five had false negative results using the UTPT with no false positive subjects. Thus, UTPT has a sensitivity of 92.6% (63/68) and a specificity of 100%. Of the 63 specimens that were UTPT positive, 45 were positive within 1 min, 58 were positive within 5 min. The remainder became positive between 5 and 15 min. There was a negative correlation between the time required for positive UTPT and the number of C. pylori per pit as seen on silver stained sections (P less than 0.05). UTPT is a rapid and sensitive method for detecting C. pylori in gastric mucosa. This enables early therapy, if indicated, before discharge from hospital. Moreover, the urea test paper method is cheap and easily stored.

Over a 15-month period, 399 patients with dyspepsia were investigated for the presence of Campylobacter pylori infection. Half of the patients (50.6%) had Campylobacter organisms in the antrum of the stomach. C. pylori was found in 96.1% of patients with histological changes of chronic active gastritis in the antrum. Of patients with duodenal and gastric ulcers, 87.8% and 87.5%, respectively, had Campylobacter organisms, as did 39.3% of patients with non-ulcer dyspepsia. C. pylori infection was most commonly found in Chinese and Indians. Although the prevalence of infection appeared to increase with age, there was an equal distribution amongst the sexes.

One hundred fifty-five biopsy specimens from the gastric mucosa of 81 patients undergoing routine endoscopy procedures were tested for the presence of Campylobacter pylori by three methods: Gram stain, culture, and modified Minitek, a rapid urea disk test (BBL Microbiology Systems, Cockeysville, Md.). Twenty-nine patients were infected with C. pylori. Sensitivities and specificities of detection were 100 and 94% with the Minitek test and 93 and 100% with Gram stain, respectively. Rapid testing by the urea disk is a simple, cost-effective, and accurate method for detecting the presence of C. pylori in gastric biopsy specimens.

We developed a buffered azide-free urea medium which is sensitive, specific, and nontoxic for rapid detection of Campylobacter pylori in gastric biopsies. Detection of urease produced by the organism provides the basis for the test. The substrate is urea in monobasic sodium phosphate buffer, and phenol red provides indication of the pH change that results from urease activity. A rapid change from yellow to red occurs in the presence of C. pylori, even at low concentrations of the organism. A slower color change occurs with higher concentrations of other urease producers, such as Yersinia enterocolitica and Proteus mirabilis. Experience with 51 patients with our medium showed excellent results in detection of C. pylori in gastric mucosal biopsies. In clinical research and practice, a rapid bedside test will be helpful for rapid diagnosis of C. pylori-positive patients.

Campylobacter pylori infection was sought in 382 consecutive patients referred for upper gastrointestinal endoscopy. Five antral biopsy specimens were taken from each patient: one was inserted into a CLO-test to detect the urease activity of C pylori, two were sent for histological analysis where multiple sections were stained by the Warthin-Starry silver method, and two were sent for microbiological evaluation by Gram stain and culture. A patient was deemed to be infected when C pylori was cultured or seen in either the histological sections or the Gram stain of the biopsy smear. One hundred and seventy four (46%) patients were infected. Culture, Gram stain, histological examination and the CLO-test showed sensitivities of 92%, 87%, 93% and 90%, respectively. In 27 (15%) infected patients an uneven distribution of C pylori was seen between samples in the biopsy pair sent for histology. Examination of multiple sections stained with Warthin-Starry silver was more sensitive at detecting infection (93%) than examination of multiple sections from only one biopsy specimen (84%). Fifty seven of 80 patients, biopsied a median seven days (range 5 to 55) after completing colloidal bismuth subcitrate treatment, were still infected with C pylori. There was no decrease in the sensitivities of the above tests to detect infection after treatment. It is concluded that at least two antral biopsy specimens should be examined when attempting to diagnose C pylori infection by histological methods.

The accuracy of various staining techniques for immersion microscopy, of five media for culture and five urease test modalities for the detection of Campylobacter pylori infection is reported. It was found that 2% urea unbuffered gel preparation is the most accurate urease test (sensitivity: 89%, specificity: 98%) but a minimal amount of 10,000 CFU/ml is necessary to observe positivity and the sensitivity of urease tests drops to 52% in patients under antimicrobial treatment. For histological diagnosis, modified Giemsa staining was shown to be slightly superior to H&E. The most valuable diagnosis technique is culture when the biopsy specimen is transported and processed under appropriate conditions. A 94% sensitivity rate was observed with 'BCC agar', a new medium containing brain heart infusion, activated charcoal and horse serum.