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Notes: Background: Phenolphthalein is widely used as a safe and effective laxative. After oral administration, phenolphthalein is absorbed in the small bowel and is conjugated in the liver to phenolphthalein glucuronide which passes into the colon where it is deconjugated and the active compound, phenolphthalein, is released. Since phenolphthalein glucuronide does not undergo enterohepatic circulation it should theoretically have a more rapid onset of action and a lower threshold dose for taxation. The present study was designed to examine this issue.Methods: Ten normal healthy subjects volunteered for the study. All subjects were administered placebo, phenolphthalein (at doses of 15, 30, 45, 60, 75 and 90 mg) or phenolphthalein glucuronide (at equivalent doses of 24, 48, 72, 96, 120 and 144 mg) in a random order. Stool weight, the frequency and consistency of stools, and the development of symptoms were recorded at 12-h intervals for 84 h.Results: There was a significant increase in the mean stool weight obtained within the first 24 h of administration of a 30 mg dose of phenolphthalein and its glucuronide equivalent compared to the values obtained with placebo. A further increase in the dose did not improve the therapeutic response. There was no difference between phenolphthalein and phenolphthalein glucuronide with respect to the rapidity of action, the threshold dose, effectiveness of taxation, or the frequency of adverse effects.Conclusions: The therapeutic response and side effect profile of the different doses favoured 30 mg phenolphthalein as the optimum laxative dose. Although theoretically superior, phenolphthalein glucuronide was not found to be a more effective laxative compared to phenolphthalein in normal subjects.

Notes: Background: More convenient therapies are needed to treat Helicobacter pylori infection successfully. Clarithromycin and amoxycillin are effective against H. pylori both in vivo and in vitro. Recent success with a high dose amoxycillin-metronidazole combination therapy led us to evaluate clarithromycin-amoxycillin dual therapy for H. pylori infection.Methods: We tested the combination of clarithromycin 500 mg t.d.s. with meals plus amoxycillin 750 mg t.d.s. with meals for 10 days for its effect on H. pylori infection in 29 patients with documented H. pylori peptic ulcers. There were 27 men and 2 women, ranging in age from 23 to 77 years. H. pylori and ulcer status were evaluated at entry and at least 4 weeks after ending antimicrobial therapy. For ulcer healing, ranitidine 300 mg was given each evening for 6 weeks. H. pylori status was determined by CLOtest and histology. Results: H. pylori infection was cured in 86% (95% CI = 78–99%). Compliance averaged 93% by pill count. Ten patients (34%) experienced mild side effects: eight reported dysgeusia and two had mild diarrhoea; none discontinued therapy because of side effects.Conclusion: We conclude that dual therapy with clarithromycin and amoxycillin is a safe and effective alternative regimen for the successful treatment of H. pylori infections.

Notes: Helicobacter pylori infection has proven to be extraordinarily difficult to eradicate. Antimicrobial monotherapies have been particularly disappointing, with most eradication rates in the range of 0 to 15%. We evaluated cefprozil (250 mg q.d.s. for 14 days) in 12 H. pylori-infected subjects. The 13C-urea breath test was used to evaluate effectiveness of therapy. Eradication was defined as a negative urea breath test 4 to 6 weeks after the end of treatment. Suppression of H. pylori was demonstrated in 4 of 12 (33%) by a negative urea breath test two days after start of treatment. H. pylori infection was not eradicated in any subject (0%). Adverse events were intermittent and mild. Cefprozil does not appear to offer promise as monotherapy for the eradication of H. pylori.

Notes: H. pylori infection is a major risk factor in gastric cancer development. The availability of cDNA microarrays creates the unprecedented opportunity to examine simultaneously dynamic changes of multiple pathways affected by H. pylori infection.〈section xml:id="abs1-2"〉〈title type="main"〉Aim:In this study we examined broad patterns of gene expression induced by H. pylori in the gastric cancer cell line 1739-CRL AGS cells in culture using the U95A microarray.〈section xml:id="abs1-3"〉〈title type="main"〉Methods: H. pylori were cocultured with AGS cells for 4, 12, 24 and 48 h. Total RNA was extracted and after labelling was used for detection of genes represented in the human U95A microarray set. Data analyses were performed using GeneChip and CLUSFAVOR software.〈section xml:id="abs1-4"〉〈title type="main"〉Results:Nearly 6000 genes present in the array were expressed by AGS cells. We report approximately 200 genes that showed the most marked changes. Our studies confirm the up-regulation of c-jun, jun-B, c-fos and cyclin D1 by H. pylori. We report for the first time the induction of the serine threonine kinase pim-1 and ATF3 by H. pylori infection of AGS cells.〈section xml:id="abs1-5"〉〈title type="main"〉Conclusions:In this microarray analysis of gene expression induced by H. pylori in gastric epithelial cells, we identified a large number of unsuspected genes affected by H. pylori. Further, we show that unsupervised hierarchical cluster analysis can provide useful insight into the possible contribution of genes in specific pathways, based on their profile of expression.

Notes: Non-invasive methods to detect the presence of H. pylori infection continue to be refined.〈section xml:id="abs1-2"〉〈title type="main"〉Aim:To evaluate a new 20-min immunochromatography method (RAPIRUN H. pylori Antibody) for the presence of anti-H. pylori IgG in urine.〈section xml:id="abs1-3"〉〈title type="main"〉Methods:We used the 13C-urea breath test to establish H. pylori status. We evaluated the urine test among 104 subjects including 43 with H. pylori infection confirmed by repeatedly positive urea breath tests and 61 H. pylori-negative subjects with repeatedly negative urea breath tests. Forty-one of the 43 subjects with H. pylori infection had a positive rapid urine test with two false negative tests. There were two false positive tests among the 61 with repeatedly negative urea breath tests. The sensitivity, specificity, positive and negative predictive values for the rapid urine test were 95.3%, 96.7%, 95.3%, and 96.7%, respectively. The kit was easy to use and required no special equipment.〈section xml:id="abs1-4"〉〈title type="main"〉Conclusions:The rapid immunochromatography method for determination of anti-H. pylori IgG proved to be reliable with excellent sensitivity and specificity and is likely to be useful for both clinical and epidemiological studies.

Notes: In a previous study, the use of a citric acid test meal produced a rapid dose-dependent increase in urease activity that was significantly greater than that resulting from a pudding meal, ascorbic acid or sodium citrate. The mechanism was hypothesized to be related to the ability of citric acid to delay gastric emptying and possibly to enhance intragastric distribution of the urea.〈section xml:id="abs1-2"〉〈title type="main"〉Objective:To compare the effects of sodium citrate, two doses of citric acid and a pudding meal on gastric motor function.〈section xml:id="abs1-3"〉〈title type="main"〉Method:Eleven normal healthy volunteers were investigated using non-invasive techniques to measure gastric emptying and gastric motility. We evaluated gastric emptying using the Meretek 13Ceebiscuit solid phase gastric emptying breath test, which employs a 340-calorie biscuit containing 200 mg of the edible 13C-blue–green alga Spirulina platensis, after the administration of test meals of pudding, 2 g and 4 g of citric acid and 2 g of sodium citrate. Electrogastrograms (Digitrapper EGG) were also recorded for 30 min before and 180 min after the test meal.〈section xml:id="abs1-4"〉〈title type="main"〉Results:Gastric emptying, as assessed by the half-time (T1/2), was delayed similarly with the pudding (136.8 ± 9 min) and with 4 g of citric acid (144.5 ± 7 min) (P 〉 0.7). Sodium citrate (108.7 ± 6 min) and 2 g of citric acid (110.1 ± 6 min) had similar effects on gastric emptying (P=0.986), and were significantly less effective in delaying gastric emptying (P 〈 0.01) compared to pudding or 4 g of citric acid. The electrogastrograms remained normal and there were no differences among meals and no relation with the gastric emptying results.〈section xml:id="abs1-5"〉〈title type="main"〉Conclusions:The increased intragastric urea hydrolysis associated with citric acid test meals cannot be attributed to delayed gastric emptying. Changes in the intragastric distribution of urea or a direct effect of citric acid on the bacteria (e.g. via the cytoplasmic protein, UreI) are more likely to be responsible.

Notes: Effective anti-Helicobacter pylori therapies with few side-effects are needed. We studied the effectiveness of a low-dose combination of metronidazole, amoxycillin and omeprazole for treatment of ulcer patients in Seoul, Korea.〈section xml:id="abs1-2"〉〈title type="main"〉Methods:Patients with gastric or duodenal ulcer received metronidazole (125 mg b.d.), amoxycillin (500 mg b.d.) and omeprazole (20 mg at bedtime) for 2 weeks. Endoscopic examinations were performed before treatment and at least 6 weeks after completion of antimicrobial therapy. H. pylori status was confirmed by histological examination of two gastric biopsies using the Genta stain.〈section xml:id="abs1-3"〉〈title type="main"〉Results:Seventy-nine patients (64 men, 15 women, mean age 46 years) with peptic ulcer were enrolled. H. pylori infection was cured in 56 (71%, 95% CI: 60–81%). The cure rate in non-smokers was significantly higher than in smokers (88% vs. 65%, P=0.035). Twelve pre-treatment isolates were available and metronidazole resistance was noted in all; H. pylori infection was cured in 10. Thirty-six patients cured of H. pylori have been followed for 1 year (mean of 361 days) and 2 cases became reinfected (5.5%, 95% CI: 1–18%).〈section xml:id="abs1-4"〉〈title type="main"〉Conclusions:The low-dose combination of metronidazole, amoxycillin and omeprazole was effective even in the face of metronidazole resistance. Recurrence of H. pylori infection is infrequent even in countries with a high prevalence of H. pylori infection.

Notes: Background : The mechanism of citric acid-enhanced Helicobacter pylori urease activity remains unclear.Aim : To compare ascorbic, citric and malic acid given at the same concentration and pH on intragastric urease activity.Methods : Volunteers received 40 mg of famotidine the evening prior to breath testing. After an overnight fast volunteers were randomized to receive 100 mL of water or 100 mm citric, malic, or ascorbic acid, pH 2.3 containing 75 mg of 13C-urea. At 15 min a second 100 mL solution of one of the test solutions was taken without added urea.Results : Twelve volunteers were studied (eight men, four women, age 19–57, median 50.7) in a randomized-crossover study. The mean breath test result at 30 min with ascorbic (17.5 ± 5), malic (25.8 ± 5) and citric acid (29.5 ± 5) were all significantly greater than with water (9.5 ± 3). Citric and malic acid were similar (P = 0.699) and significantly greater than ascorbic acid (P 〈 0.02). When the ascorbic acid was followed by citric acid, the result was similar to that with citrate alone (25.8 ± 4) and greater than with ascorbic then ascorbic (P = 0.026).Conclusions : Enhancement of H. pylori urease activity is not strictly a function of the pH. We propose the effect is related to differential effects of the availability of nickel, which is required for urease activity. Citric acid and malic acid were essentially equivalent such that malic acid could substitute for citric acid in the UBT; ascorbic acid would be a poor choice.

Notes: Background : Currently available colon cleansing preparations are often poorly tolerated.Aim : To evaluate the efficacy of a low-volume, low-salt preparation for colonoscopy.Methods : This was a pilot study in patients scheduled for colonoscopy. The preparation consisted of 34 g of magnesium citrate and four bisacodyl tablets the day before the procedure, and one bisacodyl suppository on the morning of the procedure.Results : Twenty patients (age range, 49–81 years; all males) were entered into the study. There were no significant side-effects associated with the preparation. All rated the taste as ‘tolerable or better’. The examination was considered to be adequate, with no limitations, in 17 patients (85%), and was scored as good to excellent (no solid stool) in 11 (55%), acceptable (small amounts of solid stool) in six (30%) and poor in three (15%: two in-patients and one out-patient). Importantly, two of the failures then received a standard polyethylene glycol preparation and again failed to show adequate colon preparation.Conclusions : This pilot study showed that the low-salt colon cleansing preparation was an effective alternative preparation for colonoscopy.

Notes: Significant progress and new insights have been gained in the 4 years since the first Maastricht Consensus Report, necessitating an update of the original guidelines. To achieve this, the European Helicobacter Pylori Study Group organized a meeting of specialists and experts from around the world, representatives from National Gastroenterology Societies and general practitioners from Europe to establish updated guidelines on the current management of Helicobacter pylori infection. The meeting took place on 21–22 September 2000.A ‘test and treat’ approach is recommended in adult patients under the age of 45 years (the age cut-off may vary locally) presenting in primary care with persistent dyspepsia, having excluded those with predominantly gastro-oesophageal reflux disease symptoms, non-steroidal anti-inflammatory drug users and those with alarm symptoms. Diagnosis of infection should be by urea breath test or stool antigen test.As in the previous guidelines, the eradication of H. pylori is strongly recommended in all patients with peptic ulcer, including those with complications, in those with low-grade gastric mucosa-associated lymphoid tissue lymphoma, in those with atrophic gastritis and following gastric cancer resection. It is also strongly recommended in patients who are first-degree relatives of gastric cancer patients and according to patients’ wishes after full consultation.It is advised that H. pylori eradication is considered to be an appropriate option in infected patients with functional dyspepsia, as it leads to long-term symptom improvement in a subset of patients. There was consensus that the eradication of H. pylori is not associated with the development of gastro-oesophageal reflux disease in most cases, and does not exacerbate existing gastro-oesophageal reflux disease. It was agreed that the eradication of H. pylori prior to the use of non-steroidal anti-inflammatory drugs reduces the incidence of peptic ulcer, but does not enhance the healing of gastric or duodenal ulcer in patients receiving antisecretory therapy who continue to take non-steroidal anti-inflammatory drugs.Treatment should be thought of as a package which considers first- and second-line eradication therapies together. First-line therapy should be with triple therapy using a proton pump inhibitor or ranitidine bismuth citrate, combined with clarithromycin and amoxicillin or metronidazole. Second-line therapy should use quadruple therapy with a proton pump inhibitor, bismuth, metronidazole and tetracycline. Where bismuth is not available, second-line therapy should be with proton pump inhibitor-based triple therapy. If second-line quadruple therapy fails in primary care, patients should be referred to a specialist. Subsequent failures should be handled on a case-by-case basis by the specialist. In patients with uncomplicated duodenal ulcer, eradication therapy does not need to be followed by further antisecretory treatment. Successful eradica- tion should always be confirmed by urea breath test or an endoscopy-based test if endoscopy is clinically indicated. Stool antigen test is the alternative if urea breath test is not available.