Search Results - (Author, Cooperation:P. Malfertheiner)

2016-01-09

American Association for the Advancement of Science (AAAS)

0036-8075

1095-9203

Biology

Chemistry and Pharmacology

Computer Science

Medicine

Natural Sciences in General

Physics

Asia ; Chromosome Mapping ; DNA, Bacterial/genetics/isolation & purification ; Europe ; Genome, Bacterial/*genetics ; Helicobacter Infections/*microbiology ; Helicobacter pylori/*genetics/isolation & purification ; Human Migration ; Humans ; *Hybridization, Genetic ; Ice Cover/microbiology ; Mummies/microbiology ; Phylogeny ; Phylogeography ; Sequence Analysis, DNA ; Stomach/*microbiology

2018-01-10

BMJ Publishing Group

0017-5749

1468-3288

Medicine

1523-5378

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

Background. One week of quadruple therapy including metronidazole is recommended for Helicobacter pylori treatment failures after first line therapy regardless of resistance status. This study investigated whether a quadruple regimen containing furazolidone could be effective as a third-line (salvage) therapy.Methods. All patients with previous H. pylori treatment failure after a clarithromycin-metronidazole ± amoxicillin combination plus acid suppression were given lansoprazole 30 mg twice a day (bid), tripotassiumdicitratobismuthate 240 mg bid, tetracycline 1 g bid, metronidazole 400 mg (PPI-B-T-M) three times a day (tid) for 1 week. In the case of treatment failure with this second-line therapy, the same regimen was applied for 1 week except for using furazolidone 200 mg bid (PPI-B-T-F) instead of metronidazole (sequential study design).Results. Eighteen consecutive patients were treated with PPI-B-T-M. Eleven of those 18 remained H. pylori positive (38.9% cured). Pretherapeutic metronidazole resistance was associated with a lower probability of eradication success (10% vs. 75%, p= .04). Ten of these 11 patients agreed to be retreated by PPI-B-T-F. Final cure of H. pylori with PPI-B-T-F was achieved in 9/10 patients (90%) nonresponsive to PPI-B-T-M.Conclusions. In the presence of metronidazole resistance, PPI-B-T-M as a recommended second-line therapy by the Maastricht consensus conference achieved unacceptable low cure rates in our metronidazole pretreated population. In this population, metronidazole based second-line quadruple therapy may be best suited in case of a metronidazole-free first line-regimen (e.g. PPI-clarithromycin-amoxicillin) or a low prevalence of metronidazole resistance. Furazolidone in the PPI-B-T-F combination does not have a cross-resistance potential to metronidazole and is a promising salvage option after a failed PPI-B-T-M regimen.

Electronic Resource

1365-2036

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

Aim : To study the efficacy of three pantoprazole-based triple therapy regimens for the eradication of Helicobacter pylori infection and gastric ulcer healing.Methods : In an open, multi-centre, randomized study, 519 H. pylori-positive patients with active gastric ulcer were randomized to receive pantoprazole (40 mg) (P) and two of three antibiotics: clarithromycin (500 mg) (C), metronidazole (500 mg) (M) or amoxicillin (1000 mg) (A). Triple therapy (PAC, PCM, PAM) was administered twice daily for 7 days, followed by pantoprazole until the ulcer had healed. Antrum and corpus biopsies were taken to determine the pattern of gastritis, to assess the H. pylori status and to determine the strain susceptibility to antibiotics, and from the ulcer margins and base to exclude malignancy. Scores based on the Sydney system were used to categorize the gastritis phenotypically.Results : The H. pylori eradication rates for the per protocol (intention-to-treat) analysis were 89% (67%) for PAC, 83% (68%) for PCM and 76% (60%) for PAM, with a significant difference between PAC and PAM. Healing rates after 4 weeks were 91% for PAM, 90% for PCM and 88% for PAC (per protocol analysis). The eradication rates were lower in patients in whom strains resistant to any antibiotic used in the triple therapies were detected. Successful eradication [odds ratio, 5.2 (3.3; 8.3)] and the ulcer size (〈 15 mm) were significant predictors for healing after 4 weeks. The regimens showed a comparable safety profile and compliance.Conclusions : Pantoprazole-based triple therapies are effective in the eradication of H. pylori infection in gastric ulcer patients, as reported in previous similar sized studies in duodenal ulcer patients. Successful eradication and an ulcer size of 〈 15 mm are the best predictors of gastric ulcer healing after 4 weeks.

Electronic Resource

1365-2036

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

Background : Helicobacter pylori infection has been proposed as a protective factor against the development of gastro-oesophageal reflux disease.Aim : To study heartburn and endoscopic findings before and after H. pylori eradication therapy in patients with peptic ulcer disease.Methods : In a multicentre trial programme, patients (n = 1497) were randomized to the omeprazole triple therapy group or to the control group, and were followed for 1–6 months after treatment. Patients in whom the infection was eradicated were compared with those in whom infection persisted. The severity of heartburn was measured at baseline and at each return visit. Endoscopy was performed 6 months after therapy in two of the five studies.Results : In patients with duodenal ulcer, there was a significantly lower prevalence of heartburn after successful eradication of H. pylori relative to that after failed eradication (estimated odds ratio, 0.48). The reduction in the prevalence of heartburn in patients with gastric ulcer was independent of the post-treatment H. pylori status. In studies in which ulcer relapse was included in the model, this factor emerged as a significant factor for heartburn. The observed incidence of oesophagitis at the last visit was not influenced by H. pylori status.Conclusions : Eradication of H. pylori in patients with peptic ulcer disease was associated with a reduced prevalence of heartburn. Prevention of ulcer relapse could be the true cause of this reduction.

Electronic Resource

1365-2036

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

Gastric cancer remains a great clinical challenge despite its decreasing incidence. While major progress has been achieved in the understanding of the pathogenesis and molecular biology of sporadic gastric cancer, only recently has the role of familial aggregation of gastric cancers been rediscovered. The genetic changes underlying sporadic and familial gastric cancer have been revealed, and recent studies indicate that this familial aggregation combines genetic and microbiological aspects. Thus, for the prevention of gastric cancers these findings might be helpful for the early diagnosis and for the screening of risk groups and family members.

Electronic Resource

1365-2036

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

The prevalence of Helicobacter pylori infection increases with age world-wide, reaching levels of 40–60% in asymptomatic elderly subjects and over 70% in elderly patients with gastroduodenal diseases. However, the percentage of H. pylori-positive elderly patients who are treated for their infection remains very low.Data are now available that demonstrate the benefit of curing H. pylori infection in elderly patients with H. pylori-associated peptic ulcer disease and severe chronic gastritis. Furthermore, the cure of H. pylori may prevent the progression of intestinal metaplasia and gastric atrophy. New studies are needed to clarify the role of eradication in elderly patients with non-ulcer dyspepsia and gastro-oesophageal reflux disease and in those who use non-steroidal anti-inflammatory drugs. H. pylori infection may be easily diagnosed by histological evaluation, rapid urease test or culture performed on gastric biopsies taken during endoscopy. However, the biopsy site must be carefully selected in elderly patients. For non-invasive monitoring of H. pylori infection after treatment, the 13C-urea breath test has significantly higher accuracy than serology in the elderly; further studies are needed to clarify the role of the H. pylori stool antigen test in old age.One-week proton pump inhibitor-based triple therapy regimens, including clarithromycin, amoxicillin and/or nitroimidazoles, are highly effective and well tolerated in elderly patients. Low doses of both proton pump inhibitors and clarithromycin (in combination with standard doses of amoxicillin or nitroimidazoles) are sufficient. Low compliance and antibiotic resistance are the main factors related to treatment failure in old age.

Electronic Resource

1365-2036

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

The optimal second-line treatment after failed Helicobacter pylori therapy has not been established.〈section xml:id="abs1-2"〉〈title type="main"〉Aims:To ascertain whether quadruple therapy or triple therapy with omeprazole, clarithromycin and amoxicillin is the superior re-treatment after triple therapy containing a macrolide and a nitroimidazole, and to determine the impact of microbial in vitro resistance.〈section xml:id="abs1-3"〉〈title type="main"〉Methods:Patients after failed triple therapy were randomly allocated to one of two 1-week second-line treatments: omeprazole, 40 mg, clarithromycin, 500 mg, and amoxicillin, 1 g, all b.d.; or omeprazole, 20 mg b.d., bismuth subsalicylate, 600 mg q.d.s., metronidazole, 400 mg t.d.s., and tetracycline, 500 mg q.d.s. Post-therapeutic Helicobacter pylori status was assessed by 13C-urea breath test at least 4 weeks after treatment.〈section xml:id="abs1-4"〉〈title type="main"〉Results:The study was terminated after including 84 patients. H. pylori cure rates differed significantly: omeprazole–clarithromycin–amoxicillin: intention-to-treat, 43%; per protocol, 50%; omeprazole–bismuth subsalicylate–metronidazole–tetracycline: intention-to-treat, 68%; per protocol, 69%. The frequencies of resistance after first-line therapy were: metronidazole, 90%; clarithromycin, 71%; both combined, 68%. For clarithromycin resistance, H. pylori cure with omeprazole–clarithromycin–amoxicillin was 30% vs. 83% for clarithromycin susceptibility.〈section xml:id="abs1-5"〉〈title type="main"〉Conclusions:Omeprazole–bismuth subsalicylate–metron- idazole–tetracycline was superior to omeprazole–clarithromycin–amoxicillin, but both therapies yielded unsatisfactory results. The high rate of post-therapeutic dual resistance has a negative impact on omepraz- ole–clarithromycin–amoxicillin, and probably also on omeprazole–bismuth subsalicylate–metronidazole–tetracycline, and limits the choice for second-line treatment.

Electronic Resource

1365-2036

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

A double-blind, randomized, placebo-controlled crossover study was performed to assess the influence of one week of selective M1-muscarinic receptor blockade on pancreatic exocrine secretion in man. Ten healthy subjects received telenzepine (3 mg p.o.) and placebo each for 8 days, with a 6-day drug-free washout interval between treatment sequences. On Day 8 of each sequence, pancreatic secretion was stimulated for 2 h by infusion of submaximal secretin (0.2 U.kg/h) followed by maximal stimulation with secretin (1.0 U.kg/h) and ceruletide (120 ng.kg/h). Telenzepine had no significant effect on secretory parameters during submaximal stimulation with secretin. During maximal stimulation, total protein, secretory volume, and output of amylase, trypsin and bicarbonate were unexpectedly increased by telenzepine. These findings might be partially explained by removal of the inhibitory influence of pancreatic polypeptide, which was depressed by telenzepine. Acute studies have shown that M1-receptor antagonists inhibit exocrine secretion. Our results suggest that adaptation of physiological mechanisms governing the exocrine pancreas may occur after one week of receptor blockade by a therapeutic dosage of telenzepine, to the extent that M1-blockade no longer inhibits secretion.

Electronic Resource

1365-2036

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

Gastric cancer can be divided into intestinal type and diffuse type that differ substantially in epidemiology and pathogenesis. The most important aetiological factor associated both with intestinal and diffuse gastric cancer, is Helicobacter pylori.Exposure of gastric epithelial cells to H. pylori results in an inflammatory reaction with the production of reactive oxygen species and nitric oxide that, in turn, deaminates DNA causing mutations. The complex interplay between H. pylori strain, inflammation and host characteristics may directly promote diffuse type gastric cancer or induce a cascade of morphological events, i.e. atrophy, intestinal metaplasia and dysplasia, finally leading to intestinal type gastric cancer. Two mechanisms, genetic and epigenetic have been held to play a role in the molecular alterations underlying gastric carcinogenesis. The former, comprising changes in the DNA sequence, is irreversible; the latter, involving DNA methylation, is potentially reversible by eliminating the triggering agents. If H. pylori is eradicated before development of stable mutations, the risk of gastric cancer will likely be prevented. Thus, eradication of H. pylori might immediately reduce the risk of diffuse type gastric cancer, whereas prevention of intestinal type gastric cancer may be less effective if patients are treated later in the evolution of the carcinogenic process.

Electronic Resource

1365-2036

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

Aim : To assess whether the eradication of Helicobacter pylori leads to long-term relief of symptoms in functional dyspepsia.Methods : Eight hundred patients with functional dyspepsia were randomized to receive double-blind treatment with twice-daily 30 mg lansoprazole, 1000 mg amoxicillin and 500 mg clarithromycin for 7 days (L30AC), twice-daily 15 mg lansoprazole, 1000 mg amoxicillin and 500 mg clarithromycin for 7 days (L15AC), or once-daily 15 mg lansoprazole for 14 days (LP). Dyspepsia and reflux symptoms were monitored for 12 months.Results : In intention-to-treat analysis, the non-ulcer dyspepsia sum score showed a statistically significant benefit in terms of symptom relief in the L30AC group (P = 0.0068) compared with the LP group, but there was no significant difference between the L15AC and LP groups (P = 0.2). When all patients in the two eradication therapy arms were considered together, successful eradication had a significant benefit with regard to the complete absence of symptoms (P 〈 0.04). H. pylori eradication did not lead to an increase in reflux symptoms.Conclusion : This study suggests that H. pylori infection causes dyspeptic symptoms in a subset of patients with functional dyspepsia, and that these patients may obtain long-term symptomatic benefit following H. pylori eradication.

Electronic Resource

1365-2036

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

Proton pump inhibitor-based therapy including two antibiotics is the treatment of choice for Helicobacter pylori infection. Oral antibiotic treatment can lead to intestinal overgrowth of potentially pathogenic bacteria.〈section xml:id="abs1-2"〉〈title type="main"〉Aim:To investigate the intestinal microflora before and at different times after H. pylori treatment with omeprazole, clarithromycin and metronidazole.〈section xml:id="abs1-3"〉〈title type="main"〉Methods:Bacterial growth in faecal samples from 51 patients infected with H. pylori was determined qualitatively and quantitatively. During the same period of time, stool samples from 27 H. pylori-negative controls were taken and investigated at the same intervals.〈section xml:id="abs1-4"〉〈title type="main"〉Results:The microflora of H. pylori-infected patients was different from that in H. pylori negative controls. It was characterized by a high concentration of lactobacilli, mainly Lactobacillus acidophilus. Immediately after therapy there was an increased colonization with yeasts, while the growth of lactobacilli and other species was inhibited. Clostridium difficile was cultured from three cases, but without clinical manifestations of pseudomembranous colitis. After 4 weeks of therapy, the microflora returned to normal and was not different from that of the H. pylori-negative control group.〈section xml:id="abs1-5"〉〈title type="main"〉Conclusions:In H. pylori-positive patients the intestinal flora is characterized by an increase in growth of acid-tolerant L. acidophilus. Eradication therapy exerts only a short-term influence on intestinal flora, whereas in the long term, the intestinal microflora is restored to a pattern similar to that of the control group.

Electronic Resource

1365-2036

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

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.

Electronic Resource

1365-2036

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

: To study the efficacy of omeprazole triple therapy in the eradication of Helicobacter pylori in patients with active gastric ulcer, and to assess healing and relapse of gastric ulcer.〈section xml:id="abs1-2"〉〈title type="main"〉Methods: A double-blind, randomized study was carried out in 18 centres in Germany, Hungary and Poland. Patients (n = 160) with gastric ulcer and a positive H. pylori screening test were randomized to a 7-day twice daily treatment with omeprazole 20 mg, clarithromycin 500 mg and amoxycillin 1000 mg (OAC) or omeprazole 20 mg, clarithromycin 250 mg and metronidazole 400 mg (OMC), or with omeprazole 20 mg once daily (O). After completion of this 1-week treatment, patients were treated with omeprazole until healing (maximum 12 weeks), and followed for 6 months. H. pylori was assessed by urea breath test (UBT) and histology.〈section xml:id="abs1-3"〉〈title type="main"〉Results: Eradication rates ITT were OAC 79% (95% CI: 65–90%), OMC 86% (95% CI: 73–94%) and O 4% (95% CI: 0–14%). Eradication rates PP were OAC 83% (95% CI: 68–93%), OMC 93% (95% CI: 80–98%) and O 3% (95% CI: 0–13%). Gastric ulcer relapses occurred in 5, 0 and 11 patients in the groups, respectively.〈section xml:id="abs1-4"〉〈title type="main"〉Conclusions: The results from the study demonstrate that OMC and OAC 1-week regimens are safe and effective for eradication of H. pylori in gastric ulcer patients, and that ulcer relapse is infrequent after successful eradication.

Electronic Resource

1365-2036

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

The new long-acting somatostatin analogue octreotide (SMS 201–995) was investigated for its influence on segretatagogue-stimulated human exocrine pancreatic secretion. Eighteen healthy volunteers participated in the study. During duodenal intubation with a background stimulation of either secretin 1 U.kg/h or secretin 1 U. kg/h + ceruletide, 120 ng.kg/h, octreotide was infused at doses of 5, 20 and 80 μg/h in a placebo-controlled randomized double-blind crossover trial. Duodenal juice samples were collected in 10-min intervals, and amylase, trypsin, chymotrypsin, and bicarbonate were measured in the individual fractions.During secretin stimulation, amylase was inhibited between 41 and 59%, trypsin between 28 and 72%, chymotrypsin between 55 and 70%, and bicarbonate between 0 and 31% with 5, 20 and 80 μg/h octreotide. During secretin and ceruletide stimulation, amylase was significantly inhibited by 84%, 78%, 81%, trypsin by 76%, 55%, 52%, chymotrypsin by 77%, 55%, 60%, and bicarbonate by 25%, 11%, 19% with 5, 20, and 80 μg/h octreotide, respectively (all decreases P 〈 0.05).The long-acting somatostatin analogue octreotide was confirmed to be a potent inhibitor of stimulated human exocrine pancreatic secretion. The near maximal inhibitory potency of octreotide was achieved at a dose of only 5 μg/h. This finding may be of value in the planning of therapeutic studies with octreotide.

Electronic Resource

1365-2036

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

Aims : To determine the impact of gastro-oesophageal reflux disease (GERD) on the quality of life, to assess changes in the quality of life during treatment with esomeprazole and to define factors that can predict these changes.Methods : Patients with GERD (n = 6215) were included in a prospective cohort study (ProGERD). All patients underwent endoscopy and received esomeprazole. At baseline and after 2 weeks of treatment, symptoms and quality of life were assessed. Factors that influenced changes in the quality of life were determined by multiple regression analyses.Results : At baseline, the quality of life in GERD patients was lower than that in the general population, and was similar to that in patients after acute coronary events. No differences in symptoms or quality of life were observed between the subgroups of patients with non-erosive GERD, erosive GERD and Barrett's oesophagus. After treatment with esomeprazole, the symptoms and quality of life were improved in all subscales within 2 weeks (P 〈 0.001). The mean score of the disease-specific quality of life instrument (Quality of Life in Reflux and Dyspepsia Patients) increased from 4.6 to 6.2 points, representing a highly relevant clinical improvement. The generic quality of life (SF-36) reached levels similar to those in the general population, but, again, no difference was found between the three different subgroups of GERD patients. The main factors associated with an improvement in the quality of life after treatment were symptom relief, severe erosive reflux disease, absence of extra-oesophageal disorders, avoidance of non-steroidal anti-inflammatory drug intake and positive Helicobacter pylori status.Conclusions : GERD causes a significant impairment in the quality of life that can be attenuated or normalized within a time period as short as 2 weeks by treatment with esomeprazole. These findings were similar across the whole GERD patient spectrum.

Electronic Resource

1365-2036

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

Aim : Non-invasive tests for the assessment of Helicobacter pylori status are now an integral part of the management strategies for patients with dyspepsia. The aim of this study was to evaluate a urine based antibody ELISA and a near patient urine test for the diagnosis of H. pylori infection in a European population.Methods : Urine samples were collected from 449 patients (240 females, 209 males, mean age 54 years), with dyspeptic symptoms but no previous H. pylori eradication therapy, at five centres in four European countries. All patients underwent GI endoscopy and biopsies were taken for H. pylori diagnosis. Urine samples were analysed using an IgG ELISA (URINELISA) and a near patient urine test (RAPIRUN). In addition, a serum IgG ELISA (Pyloriset-EIA-GIII), a whole blood test (Pyloriset-Screen) and a 13C-urea breath test were performed.Results : The sensitivity of the urine based ELISA and the near patient urine test was 90% and 82%, and the specificity 68% and 83%, respectively. The accuracy of the serum ELISA and the whole blood test was comparable with the urine based test.Conclusion : The urine based ELISA and the near patient urine test are just as accurate as the serological tests. This comparable accuracy and complete non-invasiveness of the former gives it an advantage over blood based tests. This limits the application of these tests in general practice.

Electronic Resource

1365-2036

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

Background : Carbonic anhydrase IX has been linked to cancer development and progression.Aim : To analyse carbonic anhydrase IX expression and anhydrase inhibition in pancreatic cancer and to correlate these findings with p53 expression and microvessel density.Materials and methods : Seventy-seven pancreatic cancers were examined (43 males, 34 females; mean age, 64 years). The anti-carbonic anhydrase IX M75 antibody was used for immunohistochemistry and Western blot analysis. Microvessels were visualized using the anti-CD34 antibody, and p53 expression in cancer cells was assessed with a specific anti-p53 antibody. Quantitative polymerase chain reaction was performed in order to assess carbonic anhydrase IX mRNA levels in the pancreas. Furthermore, pancreatic cancer cell lines were treated with acetazolamide, a carbonic anhydrase inhibitor.Results : In the normal pancreas, carbonic anhydrase IX immunoreactivity was observed at the basolateral membrane of ductal cells in 24 cases (31%). Carbonic anhydrase IX expression was found at the membrane and in the cytoplasm of pancreatic cancer cells in 16 pancreatic cancers (21%). Carbonic anhydrase IX expression was independent of the localization, stage, size, metastases and differentiation of the tumour. p53 expression was significantly more frequent in poorly differentiated cancers (P = 0.0323); however, p53 expression and microvessel density were independent of carbonic anhydrase IX expression. Overall, carbonic anhydrase IX expression was not altered in pancreatic cancers vs. adjacent normal pancreatic tissue as assessed by Western blot and quantitative polymerase chain reaction analysis. However, incubation of pancreatic cancer cell lines with acetazolamide led to a significant inhibition of cell proliferation in AsPC-1 and PANC-1 pancreatic cancer cells.Conclusion : Carbonic anhydrase IX expression is observed in both ductal epithelial and cancer cells of the pancreas. Although the expression of carbonic anhydrase IX in pancreatic cancer is not associated with angiogenesis or advanced disease, it may well be a target for carbo-anhydrase inhibitors in a subset of pancreatic cancers.

Electronic Resource

1365-2036

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

Background : Re-bleeding of Helicobacter pylori-associated peptic ulcer disease is reduced by H. pylori eradication.Aim : To validate a non-invasive test, the Premium Platinum HpSA™ stool test, in patients with upper gastrointestinal bleeding.Methods : Stool samples of consecutive patients with relevant bleeding from gastric or duodenal ulcers or erosions were collected at initial endoscopy and during the following week. Samples were assessed using the HpSA™ test. H. pylori status was defined by three biopsy-based reference methods: culture, rapid urease test and histology. It was positive if culture was positive or if rapid urease test and histology were positive.Results : One hundred and fourteen patients (mean age, 66 years) were included. In accordance with the definition, 56 (49%) were H. pylori positive. The sensitivity and specificity of the first stool sample were 84% and 90%, respectively. The respective values for two samples from consecutive days were 91% and 86%. In comparison with a serum immunoglobulin G antibody enzyme-linked immunoabsorbent assay, the HpSA™ test showed superior specificity.Conclusions : The diagnostic accuracy, in particular the sensitivity, of the HpSA™ stool test is reduced by upper gastrointestinal bleeding. The positive predictive value of 89%, however, justifies the initiation of eradication therapy on the basis of a positive stool test. A negative test result should be confirmed by a further diagnostic method.

Electronic Resource

1365-2036

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

Helicobacter pylori is a gastric pathogen that is a major cause of peptic ulcer disease, has a role in mucosa-associated lymphoid tissue (MALT) lymphoma and is associated with gastric cancer. Yet, in a large proportion of the human population, H. pylori infection has no apparent adverse clinical consequences. Furthermore, recent research suggests that H. pylori may even confer protection against gastroesophageal reflux disease.The conflicting evidence surrounding H. pylori infection was discussed at a sponsored symposium in Helsinki, introduced by Professor P. Malfertheiner, with papers presented by Dr H. J. O'Connor, Professor R. M. Genta, Dr P. Unge and Professor A. T. R. Axon. Emerging epidemiological and retrospective evidence suggests that the presence of H. pylori infection may provide some protection against gastroesophageal reflux disease, but there is other evidence that shows no benefit of H. pylori for the protection of the oesophagus. It was felt that prospective, multicentre studies are needed to explore the H. pylori–gastroesophageal disease relationship further, to avoid confusing potential benefits with known risks.Following the symposium, a discussion on the relative risks and benefits for H. pylori eradication was provided by Professor Axon and Professor Blaser.Eradication of H. pylori has been recommended in a series of management guidelines issued by consensus groups. However, accurate estimates of the relative risks and benefits of H. pylori infection in the general population, as well as in specific patient groups, is essential in order to develop a management strategy.

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