Summary
Aim : The gastrointestinal transit of sequentially administered capsules was investigated in relation to the availability of fluid along the intestinal lumen by magnetic resonance imaging.
...Methods : Water‐sensitive magnetic resonance imaging was performed on 12 healthy subjects during fasting and 1 h after a meal. Specifiable non‐disintegrating capsules were administered at 7, 4 and 1 h prior to imaging.
Results : While food intake reduced the mean fluid volumes in the small intestine (105 ± 72 mL vs. 54 ± 41 mL, P < 0.01) it had no significant effect on the mean fluid volumes in the colon (13 ± 12 mL vs. 18 ± 26 mL). The mean number of separated fluid pockets increased in both organs after meal (small intestine: 4 vs. 6, P < 0.05; large intestine: 4 vs. 6, P < 0.05). The distribution of capsules between the small and large intestine was strongly influenced by food (colon: 3 vs. 17 capsules, P < 0.01).
Conclusions : The results show that fluid is not homogeneously distributed along the gut, which likely contributes to the individual variability of drug absorption. Furthermore, transport of fluid and solids through the ileocaecal valve is obviously initiated by a meal‐induced gastro‐ileocaecal reflex.
Summary
Background
Gastro‐oesophageal reflux disease (GERD), functional dyspepsia (FD) and irritable bowel syndrome (IBS) are highly prevalent gastrointestinal conditions with accumulating evidence ...of overlap in patients. Despite availability of a vast body of research related to individual disorders, major pharmacological breakthrough in treatment of the overlap condition is still lacking.
Aim
To assess sustainability of GERD healing and whether known beneficial effects of proton pump inhibitor treatment on GERD also extend to symptoms suggestive of FD and IBS.
Methods
A total of 626 patients with reflux oesophagitis were treated with pantoprazole for up to 16 weeks depending on healing of GERD, followed by an observational phase of up to 6 months without treatment. Rates of patients suffering from GERD, FD or IBS were assessed at baseline, and at last visits of treatment and observational phase.
Results
Rates of patients with reflux oesophagitis and concomitantly with reflux symptoms, FD or IBS were each significantly lower after pantoprazole treatment (P < 0.0001). While rates of patients with reflux signs or symptoms increased again during observational phase, rates of FD and IBS were maintained at the low level after cessation of medication (P < 0.0001).
Conclusions
Pantoprazole is efficacious in the treatment of patients suffering from signs and symptoms suggesting an overlap of GERD, FD and/or IBS, providing a sustained response post‐treatment in FD and IBS symptom categories. Mechanisms underlying the beneficial effects of improvement in reflux oesophagitis on symptoms suggestive of FD or IBS still need to be determined.
Gastro-oesophageal reflux disease (GERD) is highly prevalent in Western countries. Because the majority of patients do not present with endoscopic abnormalities, the assessment of the symptom ...severity and quality of life, and their response to treatment, has become increasingly important. Self-assessed symptom questionnaires are now key instruments in clinical trials.
To evaluate the validity of available GERD measurement tools.
An ideal GERD symptom assessment instrument, suitable as a primary end-point for clinical trials, should possess the following characteristics: (i) be sensitive in patients with GERD; (ii) cover the frequency and intensity of typical and atypical GERD symptoms; (iii) be multidimensional (cover all symptom dimensions); (iv) have proven psychometric properties (validity, reliability and responsiveness); (v) be practical and economical; (vi) be self-assessed; (vii) use 'word pictures' which are easy to understand for patients; (viii) respond rapidly to changes (responsiveness over short time intervals); (ix) be used daily to assess changes during and after therapy; and (x) be valid in different languages for international use.
A literature review revealed five scales that met some of the above characteristics, but did not fulfil all criteria.
There is a need for a new evaluative tool for the assessment of GERD symptoms and their response to therapy.
The rate and extent of amoxicillin and clavulanic acid absorption from pharmacokinetically enhanced extended release (ER) tablets is strongly influenced by the intake conditions. In order to ...investigate the cause of the food effects, a pharmacokinetic study with simultaneous imaging of the in vivo behaviour of the ER tablets by magnetic marker monitoring (MMM) was performed. Under fasting conditions the amoxicillin AUC (1854
±
280
μg
min
ml
−1) was significantly lower than after intake at the beginning of the breakfast (2452
±
354
μg
min
ml
−1) or after the breakfast (2605
±
446
μg
min
ml
−1). In contrast, clavulanic acid AUC was well comparable after tablet intake under fasting conditions and intake at the beginning of a breakfast (191
±
46 and 189
±
44
μg
min
ml
−1, respectively) but significantly lower following a breakfast (126
±
71
μg
min
ml
−1). The localization data showed that the reduced bioavailability of amoxicillin under fasting conditions is due to early gastric emptying in combination with poor absorption from deeper parts of the small intestine. Prolonged gastric residence of clavulanic acid caused by intragastric tablet deposition in the proximal stomach was identified as the reason for the decreased bioavailability of clavulanic acid after tablet intake following the meal.
Background and aims: Ghrelin, the natural ligand of the growth hormone secretagogue receptor 1a, is the most powerful peripherally active orexigenic agent known. In rodents, ghrelin administration ...stimulates growth hormone release, food intake, and adiposity. Because of these effects, blocking of ghrelin has been widely discussed as a potential treatment for obesity. Spiegelmer NOX-B11 is a synthetic l-oligonucleotide, which was previously shown to bind ghrelin. We examined the effects of NOX-B11 on ghrelin induced neuronal activation and food intake in non-fasted rats. Methods: Animals received various doses of NOX-B11, inactive control Spiegelmer, or vehicle intravenously. Ghrelin or vehicle was administered intraperitoneally 12 hours later and food intake was measured over four hours. Neuronal activation was assessed as c-Fos-like immunoreactivity in the arcuate nucleus. Results: Treatment with NOX-B11 30 nmol suppressed ghrelin induced c-Fos-like immunoreactivity in the arcuate nucleus and blocked the ghrelin induced increase in food intake within the first half hour after ghrelin injection (mean 1.13 (SEM 0.59) g/kg body weight; 4.94 (0.63) g/kg body weight versus 0.58 (0.58) g/kg body weight; p<0.0001). Treatment with NOX-B11 1 nmol or control Spiegelmer had no effect whereas treatment with NOX-B11 10 nmol showed an intermediate effect on ghrelin induced food intake. Conclusions: Spiegelmer NOX-B11 suppresses ghrelin induced food intake and c-Fos induction in the arcuate nucleus in rats. The use of an anti-ghrelin Spiegelmer could be an innovative new approach to inhibit the biological action of circulating ghrelin. This may be of particular relevance to conditions associated with elevated plasma ghrelin, such as the Prader-Willi syndrome.
Summary
Background : Reflux Questionnaire (ReQuest), a newly developed gastro‐oesophageal reflux disease‐sensitive scale, can be used to reliably evaluate the effect of treatment on ...gastro‐oesophageal reflux disease symptoms.
Aim : International validation of this scale, in patients suffering from endoscopy‐negative gastro‐oesophageal reflux disease.
Methods : In this open, multicentre and multinational clinical trial 840 endoscopy‐negative gastro‐oesophageal reflux disease patients received pantoprazole 20 mg daily for 28 days. The long and short versions of ReQuest were completed both in the pre‐treatment and treatment phases. For scale development an item reduction analysis was performed. Internal consistency, test–retest reliability and responsiveness were calculated for psychometric analysis. Construct validity was evaluated by comparison with the Gastrointestinal Symptom Rating Scale and the Psychological General Well‐being questionnaire by means of correlation coefficients.
Results : Factor analyses confirmed the content validity of both long and short version of ReQuest. Psychometric calculations proved high internal consistency (Cronbach's alpha: 0.9), test–retest reliability Intraclass Correlation Coefficient: 0.9 (long vs. long) and 0.8 (short vs. short), and responsiveness (Responsiveness Index 320.3) of the scale, for which also good construct validity was achieved (correlation coefficient: Gastrointestinal Symptom Rating Scale –0.6; Psychological General Well‐being −0.4).
Conclusion : ReQuest proved valid, reliable, and responsive in this multinational clinical trial to evaluate treatment response in endoscopy‐negative gastro‐oesophageal reflux disease patients.
Several endoscopic antireflux therapies have been marketed, but long-term data on their objective and clinical efficacy are sparse. This report presents prospective 1-year follow-up results, ...including technical, clinical, and functional success rates, for the first of these treatments to be developed, endoscopic gastroplication (EGP).
A total of 43 EGP procedures were carried out in 38 patients with gastroesophageal reflux disease (GERD). Two or three EndoCinch gastroplications were constructed at the level of the gastric cardia in each patient; five patients were treated twice within 6 - 12 months. Each endoscopic suture joined two gastric folds to each other as a double fold, known as a "gastroplication", in order to narrow the esophagogastric junction. Postprocedure data after 2 months and after 1 year were compared with preoperative data, focusing on symptoms, medication requirements, endoscopic findings, and pH-metry results.
In contrast to the findings at 2 months (which showed that 72 % of the sutures were present and that there was a reduction in the percentage of time when the esophageal pH was < 4 from 15.4 % to 8.7 %), the results 1 year after EGP were considered to indicate failure of the treatment in all 38 patients because none of them still had all of the initially placed gastroplications in situ (90 % of gastroplications were lost). The percentage of patients who did not require proton pump inhibitor medication decreased from 52 % at 2 months to only 20 % at 1 year and even more patients had evidence of reflux esophagitis at 1 year (56 %) than had initially demonstrated signs of this (41 %).
EGP has some short-term beneficial effects on clinical symptoms and pH-metry. However, mainly due to the loss of the endoscopically placed sutures, these effects were not maintained at the 1-year follow-up. EGP cannot therefore be recommended for routine clinical use. Better endoscopic methods need to be developed, and they should be adequately tested before being marketed.
Background: Dipeptidyl peptidase IV (DP IV, CD26), a serine protease with broad tissue distribution and known activity in serum, participates in T cell activation and promotes a Th1 cytokine ...response, a function in part attributable to its enzymatic activity. We hypothesized that the activity of DP IV in serum and expression of CD26/DP IV in lymphocytes may be altered in patients with inflammatory bowel disease (IBD). Methods: Serum DP IV activity and CD26 (DP IV)-positive peripheral blood lymphocytes were measured in 110 patients with IBD (Crohn disease (CD): n = 63, ulcerative colitis (UC): n = 47). Additionally, T cell activation antigens (CD25, CD95) and costimulatory molecules (CD28) were evaluated. The same analyses were carried out in healthy volunteers (HC, n = 28). Thirty-nine patients with CD and 28 patients with UC were reassessed 3-6 months after the first visit. Results:
Do we need gastric acid? Pohl, D; Fox, M; Fried, M ...
Digestion,
01/2008, Letnik:
77, Številka:
3-4
Journal Article
Recenzirano
Odprti dostop
Evidence from comparative anatomy and physiology studies indicates that gastric acid secretion developed during the evolution of vertebrates approximately 350 million years ago. The cellular ...mechanisms that produce gastric acid have been conserved over the millennia and therefore proton pump inhibitors have pharmacological effects in almost all relevant species. These observations suggest that gastric acid provides an important selective advantage; however, in modern-day humans the need for gastric acid can be questioned in light of the widespread use of safe and effective pharmacologic acid suppression. The Kandahar Working Group addressed questions concerning the need, production and effects of gastric acid, specifically: (1) motility in the upper gastrointestinal (GI) tract; (2) neuroendocrine factors; (3) digestive and mucosal processes; (4) microbiology, and (5) central processes and psychological involvement. We addressed each topic with the individual models available to answer our questions including animal versus human studies, pharmacologic, surgical as well as pathophysiologic states of acid suppression.
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