Background & Aims: 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. Methods: 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. Results: 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). Conclusions: Treatment with the selective serotonin and norepinephrine reuptake inhibitor venlafaxine is not more effective than placebo in patients with functional dyspepsia.
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.
Background
We classified non‐demented European Prevention of Alzheimer's Dementia (EPAD) participants through the amyloid/tau/neurodegeneration (ATN) scheme and assessed their neuropsychological and ...imaging profiles.
Materials and methods
From 1500 EPAD participants, 312 were excluded. Cerebrospinal fluid cut‐offs of 1000 pg/mL for amyloid beta (Aß)1‐42 and 27 pg/mL for p‐tau181 were validated using Gaussian mixture models. Given strong correlation of p‐tau and t‐tau (R2 = 0.98, P < 0.001), neurodegeneration was defined by age‐adjusted hippocampal volume. Multinomial regressions were used to test whether neuropsychological tests and regional brain volumes could distinguish ATN stages.
Results
Age was 65 ± 7 years, with 58% females and 38% apolipoprotein E (APOE) ε4 carriers; 57.1% were A–T–N–, 32.5% were in the Alzheimer's disease (AD) continuum, and 10.4% suspected non‐Alzheimer's pathology. Age and cerebrovascular burden progressed with biomarker positivity (P < 0.001). Cognitive dysfunction appeared with T+. Paradoxically higher regional gray matter volumes were observed in A+T–N– compared to A–T–N– (P < 0.001).
Discussion
In non‐demented individuals along the AD continuum, p‐tau drives cognitive dysfunction. Memory and language domains are affected in the earliest stages.
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.
In this pilot study we investigated the efficacy and tolerability of a new monocapsule that contains a bismuth compound, tetracycline, and metronidazole. If proven to be effective, this monotherapy ...would turn the well-accepted multidrug regimen of standard bismuth-based triple therapy into an easy and more patient-friendly regimen. It can be used in patients allergic to penicillin.
A total of 53 consecutive H. pylori-infected patients (30 with proven ulcer disease, 23 with gastritis only) from a single center were prescribed two monocapsules q.i.d. after the three meals and after an evening snack during 10 days. Each capsule contained 60 mg colloidal bismuth subcitrate (as Bi2O3 equivalent), 125 mg tetracycline, and 125 mg metronidazole. Repeat endoscopy with biopsies for urease test, Giemsa stain, and culture was carried out > or =5 wk later. Side effect data were collected.
One patient was lost to follow-up, two failed to respond, and 50 were cured. The intention-to-treat cure rate was 50 of 53 (94.4%, 95% CI 88.1-100%). Antibiotic sensitivity was available from 51 isolates. The cure rate in the metronidazole sensitive strains was 44 of 45 (97.8%, 95% CI: 93.5-100%), whereas it was four of five in the resistant strains. The regimen was well tolerated, with only two drop-outs (4%) because of side effects.
The new monocapsule is an inexpensive, well tolerated, and patient-friendly formulation of a bismuth based triple therapy. A 10-day course with this multidrug capsule reached a very high cure rate in metronidazole-sensitive strains. The number of cases with resistant strains was insufficient to allow firm conclusions about its efficacy in case of resistance. The results are in agreement with previous data with bismuth triple therapy using separate drugs. From the high cure rate, we can conclude that the new capsule dissolves adequately, with proper delivery of its ingredients at the site of action.
Endoscopic biopsy-based tests are considered to be the reference method for diagnosing
Helicobacter pylori infection and monitoring antibiotic treatment, but unbiased data on their diagnostic ...performance is lacking. In this study we evaluated the diagnostic performance of culture, histology and rapid urease testing of antral biopsies separately and in combination. Antral biopsies were taken from consecutive patients undergoing upper gastrointestinal endoscopies at a single center between January 1995 and May 1997. The biopsies were examined for culture, histology, and CLOtest. The diagnostic performance, i.e., the sensitivity and specificity of the tests was estimated with 7 non-linear equations in 7 unknowns. To determine sources of heterogeneity that may have biased the results, data were stratified for age, gender, and whether they were taken before or after anti-
Helicobacter antibiotic treatment. During the study period 631 patients underwent 869 upper gastrointestinal endoscopies. In 122 (14%) of the antral specimens the test results of culture, histology and CLOtest differed. Based on the nonlinear regression techniques we estimated that in 347 tests (40%)
H. pylori infection was present. Overall sensitivity, specificity, positive and negative predictive value for each test were as follows: culture 91.4%, 96.3%, 94.2%, 94.4%, respectively; histology 90.3%, 97.8%, 96.4%, 93.8%, respectively; CLOtest 94.9%, 96.7%, 95.0%, 96.6%, respectively. In combination, the three tests provided the definitive diagnosis, either non-infected or infected, in 862 out of the 869 tests. Sensitivity of gastric antral histology was 64.9% (95% CI: 38-86) in females who did and 84.5% (95% CI: 77-90) in females who did not have had recent antibiotic therapy to cure the infection. Approximately 5–10% of
H. pylori infected patients, were mis-diagnosed with a single biopsy-based test taken from the gastric antrum. Only a combination of bacterial culture, histological examination and the CLOtest represents an appropriate reference standard for research purposes to identify infected patients.
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.
To assess the efficacy and side-effect profile of two currently advocated treatment regimens for eradicating Helicobacter pylori.
A randomized, controlled, open, single-centre study.
A community ...hospital in The Netherlands.
Seventy-six consecutive patients with (chronic) ulcer disease and biopsy-proven H. pylori infection, but without active ulceration at the time of inclusion.
Patients were randomly allocated to 1 week of quadruple therapy with omeprazole, bismuth, tetracycline and metronidazole (group 1) or 2 weeks of dual therapy with omeprazole and amoxicillin (group 2). Group 1 patients were pretreated with omeprazole for 3 days.
Cure was confirmed by obtaining 10 endoscopic biopsies for urease testing, histology and culture 6 weeks after treatment. Side-effects were scored on a standard questionnaire.
Three patients were lost to follow-up. In the 'intention to treat' analysis 37 (92.5%) of 40 patients in group 1 were cured compared with 20 (55.6%) of 36 patients in group 2 (P < 0.001). The difference in efficacy was 36.9% (95% confidence interval 18.7-55.1%). Side-effects were fewer and milder in group 2, but all patients in both groups were able to complete the course of treatment.
Dual therapy is significantly less effective in curing H. pylori infection in peptic ulcer patients than quadruple therapy. No patients were intolerant to either treatment. On the basis of the low efficacy of dual therapy, we believe that this therapy should not be used as a first-line treatment strategy. We confirmed our previous finding that 1 week of quadruple therapy is tolerated well and that it is highly effective against metronidazole-sensitive as well as metronidazole-resistant strains of H. pylori.
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