[show abstract][hide abstract] ABSTRACT: Helicobacter pylori infection causes lifelong gastritis and is associated with the development of peptic ulcer disease, MALT lymphoma and gastric cancer. Many patients benefit from H. pylori eradication therapy. PPI-triple therapy is recommended as initial therapy. Quadruple therapy, with a PPI, bismuth, and two antibiotics, used to be recommended as second-line therapy, but can no longer be prescribed because bismuth is no longer available. Therefore, there is an urgent need for new effective rescue therapies. Levofloxacin-based therapies were suggested as an alternative to quadruple therapy. The aim of this study is to examine the efficacy and tolerability of such a one-week therapy with levofloxacin and esomeprazole combined with either amoxicillin or clarithromycin in a Dutch population.
Between February 2005 and November 2006, 123 consecutive H. pylori positive patients were enrolled in this study. The first 59 patients were treated with esomeprazole, amoxicillin and levofloxacin (group I). The next 64 patients were treated with esomeprazole, clarithromycin, and levofloxacin (group II ). Both therapies were compared for efficacy and tolerability.
In group I the overall (ITT) cure rate was 96% and in group II it was 93%. Minor side effects occurred in 29% of patients in group I and in 41% of patients in group II. Major side effects that warranted discontinuation of therapy occurred in two patients in group II.
Seven-day triple therapy with esomeprazole, levofloxacin and either amoxicillin or clarithromycin for seven days is very effective and safe for H. pylori eradication. The combination with amoxicillin seems to be better tolerated than the combination with clarithromycin.
The Netherlands Journal of Medicine 04/2009; 67(3):96-101. · 2.38 Impact Factor
[show abstract][hide abstract] ABSTRACT: Antidepressants could be effective in the treatment of functional gastrointestinal disorders through their anticholinergic and pain-modulating effects. Previous studies with these drugs lacked sufficient power and were predominantly conducted in patients with irritable bowel syndrome. This study aimed to assess the effectiveness of the serotonin and norepinephrine reuptake inhibitor venlafaxine in patients with functional dyspepsia.
This was a multi-center, randomized, double-blind, placebo-controlled trial. Participants had persistent dyspeptic symptoms and underwent upper gastrointestinal endoscopy in a secondary care hospital to exclude organic abnormalities. They were randomly assigned to receive 8 weeks of treatment with either venlafaxine XR (2 weeks 75 mg once daily, 4 weeks 150 mg once daily, and 2 weeks 75 mg once daily) or placebo. Symptoms, health-related quality of life, anxiety, and depression were assessed before and at 4, 8, 12, and 20 weeks after inclusion.
One hundred sixty patients were randomized; 56% and 73% of participants completed treatment with venlafaxine or placebo, respectively, according to protocol. There was no difference in proportions of symptom-free patients after 8 weeks of treatment or at 20 weeks after inclusion, with venlafaxine in comparison to placebo (37% and 39%, respectively; odds ratio [OR], 0.8; 95% confidence interval [CI], 0.3-2.1; and 42% and 41%, respectively; OR, 3.1; 95% CI, 0.9-12.6). Per-protocol analysis did not reveal any differences between venlafaxine and placebo either (38% and 39% symptom-free, respectively; OR, 1.0; 95% CI, 0.4-2.4 at 8 weeks).
Treatment with the selective serotonin and norepinephrine reuptake inhibitor venlafaxine is not more effective than placebo in patients with functional dyspepsia.
Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association 07/2008; 6(7):746-52; quiz 718. · 5.64 Impact Factor
[show abstract][hide abstract] ABSTRACT: Spray formation from diesel fuel injection through a realistic heavy-duty multi-hole common rail injector is studied in a newly devel-oped high pressure, high temperature cell, using digital high speed shadowgraphy at 4500 frames per second. Care is taken to establish accurate synchronisation between camera and injection system and because of the relatively large exposure time, an effective camera image time is calculated for every frame. Further emphasis is given to determining the actual start of fuel mass injection by comparing (for each injection) a predetermined, rail pressure dependent needle relaxation distance to the actual needle lift signal. The spatiotem-poral evolution of the spray is found to reproduce well in general, but often sprays suffer from short-lived, small, laterally moving anom-alies, which influence axial motion and the spray cone angle. High speed shadowgraphy allows this to be observed and taken into account. After an overview of methods found in the literature, an algorithm for geometrical analysis is presented, which is based on an extension of a combination of those methods. In this algorithm, a local spray angle # i (x) is determined from lateral cross-sections at 80% of the shadow level in order to encompass most of the spray without being too sensitive to background noise. The macroscopic cone angle # cone is derived from the approximate constancy of # i (x) over a relatively long axial distance. Spray penetration is obtained by lateral integration of the spray shadow. A procedure for accurate correlation of spray growth with time shows that the growth is pro-portional to t b with b = 0.57 ± 0.02 for a common rail pressure of 150 MPa and a gas density 33 kg/m 3 (N 2 at room temperature). The exact value of b is very sensitive to uncertainties in synchronisation and the start of injection determination. The spray cone angle # cone is not constant, but varies with time during an injection, mainly as a result of spray shape changes.
[show abstract][hide abstract] ABSTRACT: To compare the accuracy and reaction time of a new dry rapid urease test (GUT test) with the CLO test and an independent gold standard in the diagnosis of Helicobacter pylori infection. To determine whether this new test can replace the CLO test in routine clinical practice.
We included consecutive patients in whom normal-sized gastric biopsies were taken in routine practice. six antral and three corpus biopsies were taken for determination of H. pylori infection. results of the GUT test were monitored after 15, 60 and 120 minutes of incubation. Results were compared with the standard CLO test and an independent gold standard (bacterial culture and histology). The results of the CLO test were also compared with the gold standard.
116 patients were recruited in the study: 60 were males and 56 females. The mean age was 59.3 years (range 14-89 years). Compared with the CLO test, the GUT test had a sensitivity of 76.7% and a specificity of 100% in 15 minutes. After 60 minutes the sensitivity of the GUT test increased to 95.3%, the specificity remained 100%. All positive results of the GUT test occurred before 60 minutes of incubation. Compared with the gold standard, the GUT test had a sensitivity and specificity of 97.4 and 96.1% respectively. The CLO test had a sensitivity of 97.4% and a specificity of 93.5%, when compared with the gold standard.
The GUT test appeared to be a good and reliable alternative for the widely used Clo test in diagnosing H. pylori infection. The GUT test results were not yet reliable after 15 minutes, but all positive results occurred before 60 minutes of incubation. The test can best be read 60 to 120 minutes after endoscopy.
The Netherlands Journal of Medicine 11/2006; 64(9):329-33. · 2.38 Impact Factor
[show abstract][hide abstract] ABSTRACT: Most patients treated for H. pylori infection receive empirical therapy based on epidemiological data of antibiotic resistance. However, previous European studies indicate that resistance patterns may be changing. Therefore, the aim of this study was to investigate the prevalence of primary clarithromycin and/or metronidazole resistant H. pylori strains over a six-year period (1997-2002) in a regional hospital.
All patients visiting Slingeland Hospital in Doetinchem, the Netherlands between 1997 and 2002 with a positive H. pylori culture were included in this study. Susceptibility to metronidazole and clarithromycin was determined by disk diffusion.
Of the 1355 patients with an H. pylori positive culture, 1127 did not have a history of H. pylori eradication, 58 did, and for 170 this information was not available. Mean rates of primary resistance to metronidazole and clarithromycin were 14.4% (162/1125) and 1.0% (11/1123), respectively. Primary metronidazole resistance was stable throughout the study period and primary clarithromycin resistance showed a decreasing trend. Patients of foreign descent and from secondary care had a higher chance of harbouring primary metronidazole-resistant H. pylori (adjusted OR (95% CI) 1.75 (1.1 to 2.8), and 1.60 (1.1 to 2.2), respectively). Patients with failed H. pylori eradication had a higher chance of harbouring metronidazole-resistant H. pylori (43 vs 14%, p<0.0001) and clarithromycin-resistantH. pylori (5.3 vs 1.0%, p=0.004) than untreated patients.
Primary metronidazole resistance is stableat a low level, while primary clarithromycin resistance isvirtually absent in the eastern part of the Netherlands.Therefore, triple therapy with a proton pump inhibitor,clarithromycin and amoxicillin can remain the empiricaltreatment of choice in the Netherlands.
The Netherlands Journal of Medicine 07/2006; 64(6):191-5. · 2.38 Impact Factor
[show abstract][hide abstract] ABSTRACT: To measure the prevalence of metronidazole- or clarithromycin-resistant Helicobacter pylori. DESIGN. Retrospective.
All positive H. pylori cultures with known susceptibility to metronidazole or clarithromycin between 1998 and 2003 were selected from the database of the Microbiology Laboratory in 's-Hertogenbosch, the Netherlands. Resistance to clarithromycin and metronidazole was determined using the E-test with cut-off minimum inhibitory concentrations of > or = 2 microg/ml and > or = 8 microg/ml, respectively.
Of the 960 cultures with known metronidazole susceptibility, 135 (14%) were resistant. Of the 959 cultures with known clarithromycin susceptibility, 26 (3%) were resistant. The percentages of resistant cultures were higher in women than in men (17% versus 12% and 4% versus 2%, respectively). There was no relationship between age and resistance. Over the course of the study period, resistance to metronidazole decreased slightly, whereas resistance to clarithromycin increased slightly.
Prevalence of metronidazole- and clarithromycin-resistant H. pylori strains in the 's-Hertogenbosch region was so low that the combination of a proton pump inhibitor, clarithromycin and amoxicillin can be used in patients with H. pylori infection without first determining susceptibility.
Nederlands tijdschrift voor geneeskunde 10/2005; 149(39):2175-7.
[show abstract][hide abstract] ABSTRACT: The aim of this study was to determine whether an antral biopsy alone represents an adequate tissue sample to diagnose the presence of Helicobacter pylori on the mucosa. Furthermore, we explored the conditions associated with the presence of H. pylori in the corpus.
Consecutive patients who underwent an upper gastrointestinal endoscopy at a single centre between January 1995 and May 1997 were studied. Biopsies were taken at each endoscopy to assess the presence of H. pylori: two antral and two corpus biopsies for histological examination and one antral and one corpus biopsy for the CLO test.
A total of 620 patients underwent an upper gastrointestinal endoscopy, 307 (50%) were H. pylori infected. In 80% of the endoscopies there was total agreement between the performed biopsy tests. The addition of corpus biopsies increases the diagnostic yield by 10% in H. pylori-positive patients. Patients with only corpus infection more often showed atrophy and intestinal metaplasia compared with patients with both antral and corpus infection, 37 vs 20%, respectively (OR 2.2, 95% CI 1.1-4.4).
One biopsy from the antrum or corpus seems to be inadequate to diagnose the presence of H. pylori on the mucosa. Patients with an infection exclusively in the corpus more often had worse mucosa pathology.
The Netherlands Journal of Medicine 05/2005; 63(4):141-5. · 2.38 Impact Factor
[show abstract][hide abstract] ABSTRACT: There is much debate about the influence of pre-treatment with a proton pump inhibitor on Helicobacter pylori eradication. The few studies investigating the influence of pre-treatment on triple and quadruple therapies did not find differences in eradication rates. However, the high eradication rates make it difficult to study factors associated with therapy failure in small populations. In order to overcome this problem we performed a meta-analysis.
The literature was searched in order to identify randomized clinical trials comparing modern triple/quadruple therapies for H. pylori eradication without pre-treatment with a proton pump inhibitor with exactly the same regimen with pre-treatment. The overall risk difference (with - without pre-treatment) was calculated by pooling the risk differences of the individual studies weighted by the inverse of their variances.
Nine studies, investigating a total of 773 patients, were identified. There was considerable variation regarding therapy regimen and duration. Pooled eradication rates were 81.3% (312 of 384) for patients with pre-treatment and 81.2% (316 of 389) for patients without pre-treatment. The (weighted) overall risk difference was 0.1% (95% CI: -5%; 5%).
Pre-treatment with a proton pump inhibitor does not influence H. pylori eradication.
[show abstract][hide abstract] ABSTRACT: Many patients treated for H. pylori infection have been taking a proton pump inhibitor beforehand. There is conflicting evidence whether pretreatment influences the efficacy of H. pylori eradication. The aim of this study was to investigate the influence of pretreatment on cure rates of H. pylori eradication.
Patients with H. pylori positive peptic ulcer disease or functional dyspepsia were treated with two-day quadruple therapy (lansoprazole 30 mg twice daily, and colloidal bismuth subcitrate 120 mg, tetracycline 250 mg and metronidazole 250 mg, all eight times a day). Patients were randomised to receive either three-day pretreatment with lansoprazole 30 mg twice daily or no pretreatment. H. pylori was diagnosed using CLO, histology and culture.
Twenty-five (66%) of 38 patients with pretreatment and 32 (84%) of 38 patients without pretreatment were cured (p=0.06). After adjustment for diagnosis, smoking status and metronidazole resistance the influence of pretreatment became slightly less pronounced (OR 0.44, 95% CI 0.1-1.7). Nonsmokers and patients with peptic ulcer disease were more likely to achieve H. pylori eradication than smokers and patients with functional dyspepsia, respectively (adjusted odds ratios: 4.79 (1.2-19) and 4.32 (1.0-18)).
This two-day quadruple therapy reached an overall cure rate of 75%. Nonsmokers and patients with peptic ulcer disease were more likely to achieve H. pylori eradication. Three-day pretreatment with a proton pump inhibitor may decrease cure rates of this two-day quadruple therapy.
The Netherlands Journal of Medicine 07/2004; 62(6):192-6. · 2.38 Impact Factor
[show abstract][hide abstract] ABSTRACT: The discovery of Helicobacter pylori has had a major clinical impact. Clinical research is now focused on the role of H. pylori and H. pylori eradication in the treatment of several upper gastrointestinal disorders such as non-ulcer dyspepsia, ulceration during therapy with aspirin or other anti-inflammatory drugs, the treatment of precancerous conditions of the stomach, and the prevention of gastric cancer. Triple and quadruple therapies have become the standard for H. pylori eradication. The expansion of knowledge and the development of new therapeutic modalities are likely to lead to a further implementation of H. pylori-related methods in strategies for the prevention and treatment of upper gastrointestinal disorders.
Current Opinion in Pharmacology 11/2003; 3(5):480-5. · 5.44 Impact Factor
[show abstract][hide abstract] ABSTRACT: H. pylori eradication is usually performed with three or four drugs for at least seven days. Recently four reports have shown a cure rate of approximately 90% using a four-day quadruple therapy. The objectives of this prospective study were: 1) to evaluate the efficacy of pantoprazole-based quadruple therapy, and 2) to compare the efficacy and tolerability of four-day with seven-day quadruple therapy.
The study was performed in a single centre. The first 56 consecutive patients with nonulcer dyspepsia or peptic ulcer disease and proven H. pylori infection received seven days of quadruple therapy (pantoprazole, bismuth, tetracycline and metronidazole). At least six weeks after treatment, endoscopy was repeated with six biopsies of the antrum and corpus for histology, urease test and culture. The next 59 consecutive patients followed the same protocol but received four-day quadruple therapy.
Using an intention-to-treat analysis, the cure rate in the seven-day treatment group was 54/56 (96.4%, 95% confidence interval (CI) 87.7-99.6%). In the per protocol analysis the cure rate was 53/55 (96.3%, 95% CI 87.5-99.6%). Primary metronidazole resistance was observed in seven patients. All were cured. Using an intention-to-treat analysis, the cure rate in the four-day treatment group was 51/59 (86.4%, 95% CI 75.0-94.0%). In the per protocol analysis the cure rate was 50/58 (86.2%, 95% CI 74.6-93.8%). Primary metronidazole resistance was observed in seven patients, four of whom were cured. In three out of eight patients in whom four-day treatment failed, secondary metronidazole resistance was induced. Both treatment regimens were well tolerated. The difference between cure rates of both regimens did not reach statistical significance (p=0.0585).
Routine use of both four-day and seven-day pantoprazole-based quadruple anti-H. pylori treatment is effective and well tolerated. The results of both regimens reach the required eradication standard, but results with the seven-day regimen were slightly but not significantly better. Seven-day treatment may be superior, especially in case of metronidazole resistance, and should be preferred.
The Netherlands Journal of Medicine 07/2003; 61(6):218-22. · 2.38 Impact Factor
[show abstract][hide abstract] ABSTRACT: The high prevalence of Helicobacter pylori resistance to metronidazole demands treatments more effective than standard bismuth-based triple therapy against these strains.
To evaluate the H. pylori eradication rate in both metronidazole-sensitive and -resistant strains following quadruple therapy using single-triple capsules of bismuth biskalcitrate, metronidazole and tetracycline, given with omeprazole.
One hundred and seventy valid patients with duodenal ulcer, gastric ulcer or non-ulcer dyspepsia were treated in eight centres located in five countries. H. pylori was confirmed at baseline using 13C-urea breath test, histology and/or culture. Patients received three single-triple capsules q.i.d. and omeprazole, 20 mg b.d., for 10 days. Each capsule contained bismuth biskalcitrate, 140 mg (as 40 mg Bi2O3 equivalent), metronidazole, 125 mg, and tetracycline, 125 mg. 13C-Urea breath test was repeated at least 4 and 8 weeks post-treatment.
Overall eradication rates were 93% (158/170) by modified intention-to-treat analysis and 97% (142/146) by per protocol analysis. Eradication rates were 93% (40/43) and 95% (38/40) for strains resistant to metronidazole and 95% (82/86) and 99% (75/76) for strains sensitive to metronidazole by modified intention-to-treat and per protocol analysis, respectively.
This omeprazole-bismuth biskalcitrate-metronidazole-tetracycline 10-day regimen is a very effective and well-tolerated treatment, which overcomes metronidazole resistance.
[show abstract][hide abstract] ABSTRACT: A high level of gastric acid secretion is considered to be a risk factor for reflux oesophagitis or Barrett's oesophagus. Corpus gastritis may have a protective effect on the oesophagus, because of decreased gastric acid output.
To determine if corpus gastritis is associated with reflux oesophagitis or Barrett's oesophagus.
Three antral and two corpus biopsies were taken from consecutive patients in whom Helicobacter pylori testing was requested during endoscopy at a single centre between January 1995 and May 1997. Antral and corpus gastritis was studied by histology; H. pylori was studied by histology, culture and CLO test. A regression model was used to test for correlation between reflux oesophagitis, Barrett's oesophagus and risk factors.
During the study period, 676 patients had biopsies taken during upper gastrointestinal endoscopy. Endoscopic signs of reflux oesophagitis and Barrett's oesophagus were observed in 125 and 23 patients, respectively. Corpus gastritis was found in 59% of patients without reflux oesophagitis or Barrett's oesophagus, 45% of patients with reflux oesophagitis and 30% of patients with Barrett's oesophagus. Two hundred and fifty-seven patients underwent follow-up endoscopy after H. pylori therapy. During a mean follow-up of 3 months, the incidence of reflux oesophagitis was not statistically different for patients with healing of corpus gastritis (10/98; 10%) and patients with persistent gastritis (8/97; 8%).
Corpus gastritis was less common in patients with an endoscopic diagnosis of reflux oesophagitis or Barrett's oesophagus.
[show abstract][hide abstract] ABSTRACT: Glutathione S-transferases (GST) and glutathione peroxidases (GPO) are important in detoxification. GST activity in the mucosa of the gastrointestinal tract is inversely correlated with the development of gastrointestinal cancer. Helicobacter pylori (H. pylori) infection has been associated with gastric cancer. We studied GST activity and the substrate glutathione (GSH) in patients with H. pylori-associated gastritis. GST activity and isoenzyme levels, GPO activity and GSH levels were studied in antral biopsies of 38 H. pylori-positive patients, before and after eradication treatment. In 31 patients in whom H. pylori was successfully eradicated, antral GST enzyme activity before therapy was 532 (465 - 598) nmol / mg protein. min (mean and 95% confidence interval) and that after therapy was 759 (682 - 836) nmol / mg protein. min (P < 0.0001). Correspondingly, levels of GST alpha and GST-P1 were higher after eradication (P < 0.001). GSH concentration significantly increased: 21.2 (16.2 - 26.2) nmol / mg protein before and 27.1 (23.6 - 30.6) nmol / mg protein after therapy (P < 0.05). In 7 patients in whom H. pylori was not eradicated, GST activity was 671 (520 - 823) nmol / mg protein. min and 599 (348 - 850) nmol / mg protein before and after treatment respectively (P = 0.32). GSH levels were 17.4 (9.0 - 25.7) nmol / mg protein and 18.2 (9.1 - 27.3) nmol / mg protein, respectively (P = 0.84). No differences in antral GPO enzyme activity, both of selenium (Se)-dependent and total GPO, before and after successful treatment were found. Eradication of H. pylori infection increases GST activity and GSH levels in antral mucosa. Low GST activity and GSH concentration due to H. pylori infection might play a role in gastric carcinogenesis.
Japanese journal of cancer research: Gann 12/2001; 92(12):1329-34.
[show abstract][hide abstract] ABSTRACT: Physicians should try to reach an optimal cure rate with initial anti-Helicobacter therapy. Helicobacter pylori infection in patients with peptic ulcer disease (PUD) is more likely to be cured then in patients with 'functional' dyspepsia (FD). Differences in cure rates of 5-15% are usually reported, which is considered to be clinically relevant. Different strains (virulent v. non-virulent) in PUD and FD may induce different alterations in the gastric mucosa, and thereby either facilitate or impair antimicrobial efficacy. A study in this journal showed that triple therapy with ranitidine bismuth citrate (RBC) was superior to triple therapy with a proton pump inhibitor (PPI), but only in the more-difficult-to-cure FD patients. Clinicians should be aware that most published treatment studies have included only PUD patients. This means that in clinical practice the cure rates obtained in patients with FD or even uninvestigated dyspepsia will usually be lower then those reported in the literature. One way to deal with this is to consider prolonging the duration of an initial anti-Helicobacter therapy from 7 to 10 or 14 days in patients without ulcers.
European Journal of Gastroenterology & Hepatology 12/2001; 13(11):1281-4. · 1.92 Impact Factor
[show abstract][hide abstract] ABSTRACT: Glutathione S-transferases (GST) and glutathione peroxidases (GPO) are important in detoxification. GST activity in the mucosa of the gastrointestinal tract is inversely correlated with the development of gastrointestinal cancer. Helicobacter pylori (H. pylori) infection has been associated with gastric cancer. We studied GST activity and the substrate glutathione (GSH) in patients with H. pylori-associated gastritis. GST activity and isoenzyme levels, GPO activity and GSH levels were studied in antral biopsies of 38 H./pyfori-positive patients, before and after eradication treatment. In 31 patients in whom H. pylori was successfully eradicated, antral GST enzyme activity before therapy was 532 (465–598) nmol/mg protein-min (mean and 95% confidence interval) and that after therapy was 759 (682–836) nmol/mg protein-min (P<0.0001). Correspondingly, levels of GST α and GST-P1 were higher after eradication (P<0.001). GSH concentration significantly increased: 21.2 (16.2–26.2) nmol/mg protein before and 27.1 (23.6–30.6) nmol/mg protein after therapy (P<0.05). In 7 patients in whom H. pylori was not eradicated, GST activity was 671 (520–823) nmol/mg protein min and 599 (348–850) nmol/mg protein before and after treatment respectively (P=0.32). GSH levels were 17.4 (9.0–25.7) nmol/mg protein and 18.2 (9.1–27.3) nmol/mg protein, respectively (P=0.84). No differences in antral GPO enzyme activity, both of selenium (Se)-dependent and total GPO, before and after successful treatment were found. Eradication of H. pylori infection increases GST activity and GSH levels in antral mucosa. Low GST activity and GSH concentration due to H. pylori infection might play a role in gastric carcinogenesis.
Cancer Science 11/2001; 92(12):1329 - 1334. · 3.48 Impact Factor