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The practice of sedation, including monitoring practice for digestive endoscopy, continues to evolve throughout the world. In many countries, including Switzerland, there is a trend towards increased utilization of sedation during both routine and advanced endoscopic procedures. Sedation improves patient satisfaction with endoscopy and also improves the quality of the examination. In addition, a trend can be observed towards an increasing use of propofol as the preferred sedative drug. Here we review the latest published data from surveys describing sedation and monitoring practice in different countries and compare them with our own data from successive nationwide surveys among Swiss gastroenterologists over a period of 20 years. This development between these socioeconomically very similar Western industrialized countries, however, shows some unique and surprising differences. In Germany and Switzerland, propofol use has become increasingly widespread, in Switzerland even to the extent that during the last few years propofol has overtaken benzodiazepine sedation, with an absolute majority of Swiss gastroenterologists using it without the assistance of an anesthesiologist. In addition, the change in Switzerland reflects a successful generalization of nonanesthesiologist- administered propofol (NAAP) sedation from the hospital setting to private practice. [ABSTRACT FROM AUTHOR]

The availability of new topical preparations for the treatment of left sided ulcerative colitis ulcerosa offers a therapy optimization for many patients. Rectal application of steroids and 5- aminosalicylic acid (5-ASA) is associated with fewer side effects and has a higher therapeutic efficacy in mild to moderate-active left-sided colitis as compared to a systemic therapy. Often it is argued that the patients' compliance is insufficient with a rectal therapy. However, with sufficient information on the proven advantages this is usually not the case. The rectal application of drugs in distal ulcerative colitis is suitable also for themaintenance of remission. Therefore the new therapy guidelines recommend topical therapymore than in former times. Subsequently, these manuscripts focussed specifically on the topical therapy of distal colitis, to elucidate that clear treatment advantages are present in daily practice. [ABSTRACT FROM AUTHOR]

This proof-of-concept study was performed in order to establish the pharmacokinetics and pharmacodynamics of increasing oral doses of the satiety peptides glucagon-like peptide-1 (GLP-1) and peptide YY3-36 (PYY3-36). Six healthy male subjects were given oral doses of either a placebo or GLP-1 in a dose-escalating schedule (doses of 0.5, 1.0, 2.0, and 4.0 mg). Next, another group of six healthy male subjects were given oral doses of either a placebo or PYY3-36 in the same pattern of escalating doses (doses of 0.25, 0.5, 1.0, 2.0, and 4.0 mg). In healthy male volunteers, (i) oral administration of either of the peptides induced a rapid and dose-dependent increase in plasma drug concentrations; (ii) oral administration of GLP-1 induced a potent effect on insulin release; and (iii) both peptides suppressed ghrelin secretion. In conclusion, this study showed, for the first time, that satiety peptides such as GLP-1 and PYY3-36 can be orally delivered safely and effectively in humans.Clinical Pharmacology & Therapeutics (2008); 84, 4, 468–474 doi:10.1038/clpt.2008.35 [ABSTRACT FROM AUTHOR]

Aim: Lectins, carbohydrate-specific proteins without enzymatic activity on the ligand, are daily ingested plant proteins which survive the passage through the gastrointestinal tract in a biologically active form. Their binding to glycan determinants of natural glycoconjugates can trigger biological effects. The lectin phytohaemagglutinin (PHA) is abundantly present in red kidney beans and induces cholecystokinin (CCK) release in rats. The aim of the study was to investigate the effect of intraduodenal administration of PHA on plasma CCK levels and gallbladder contraction in humans and to elucidate potential mechanisms of action. Methods: Five healthy volunteers underwent four studies. After a basal intraduodenal saline infusion for 30 min, PHA or heat-inactivated PHA was infused in increasing doses: 150 μg, 1.5 mg and 15 mg for 30 min each. Intravenous saline, CCK1 receptor antagonist dexloxiglumide or atropine were administered in random order. Gallbladder volumes were measured by ultrasonography and plasma CCK levels by radioimmunoassay. Results: Intraduodenal PHA induced gallbladder contraction in a dose-dependent fashion starting with the lowest dose. The highest dose reduced the gallbladder volume to 65.3 ± 9.4% of basal volume ( P < 0.001) whereas heat-inactivated PHA did not have any effect. Blocking CCK1 or muscarinic receptors completely abolished PHA-stimulated gallbladder contraction (dexloxiglumide 208.7 ± 23.7%; atropine 104 ± 7.0% of basal volume) while none of the treatments affected CCK levels. Conclusion: Duodenal administration of PHA potently stimulates gallbladder contraction in humans. This contraction is mediated via cholinergic pathway. [ABSTRACT FROM AUTHOR]

Background and purpose:P-glycoprotein (P-gp) is an important efflux transporter that supports the barrier function of the gut against invading antigens and against administered drugs. Since glucocorticoids, such as budesonide, are frequently used during inflammatory bowel disease we investigated how budesonide influences P-gp expression in different intestinal cell lines.Experimental approach:LS180 and Caco-2 cells were incubated with budesonide and changes in P-gp expression were determined on mRNA, protein and functional level. The mRNA expression levels of glucocorticoid receptor (GR) and pregnane X receptor (PXR) were determined in these cell lines. PXR receptor was transiently transfected into Caco-2 cells.Key results:Budesonide showed an induction of P-gp in LS180 cells and a down-regulation in Caco-2 cells. Expression levels of nuclear receptors revealed high expression of PXR only in LS180 cells and exclusive expression of GR in Caco-2 cells. Mifepristone, an anti-glucocorticoid, could not reverse the down-regulation of P-gp by budesonide in Caco-2 cells. In PXR-transfected Caco-2 cells the budesonide-mediated down-regulation of P-gp was abolished. Furthermore the expression of cytochrome P450 3A4 (CYP3A4), another PXR target gene, was induced in PXR-transfected Caco-2 cells after budesonide treatment.Conclusions and Implications:Budesonide has the potential to influence MDR1 expression in vitro. In LS180 cells, the induction of MDR1 by budesonide probably is mediated via PXR. The mechanism of the down-regulation in Caco-2 cells still remains unclear, but GR does not seem to be involved. Further studies are required to evaluate how budesonide alters P-gp expression in vivo.British Journal of Pharmacology (2007) 150, 361–368. doi:10.1038/sj.bjp.0706992; published online 18 December 2006 [ABSTRACT FROM AUTHOR]

The article focuses on the consensus on the diagnosis and management of Crohn's disease, attained by the European Crohn's and Colitis Organisation at a meeting held on September 24, 2004 in Prague, Czech Republic. The group's general agreement is classified into three parts including definitions and diagnosis, current management and instruction for special conditions.

Background/aims: The apical sodium dependent bile acid transporter ASBT (SLC10A2) contributes substantially to the enterohepatic circulation of bile acids by their reabsorption from the intestine. In the rat, its adaptive regulation was observed in the kidneys, cholangiocytes, and terminal ileum after bile duct ligation. Whether adaptive regulation of the human intestinal ASBT exists during obstructive cholestasis is not known. Methods: Human ASBT mRNA expression along the intestinal tract was analysed by real time polymerase chain reaction in biopsies of 14 control subjects undergoing both gastroscopy and colonoscopy. Their duodenal ASBT mRNA expression was compared with 20 patients with obstructive cholestasis. Additionally, in four patients with obstructive cholestasis, duodenal ASBT mRNA expression was measured after reconstitution of bile flow. Results: Normalised ASBT expression in control subjects was highest (mean arbitrary units (SEM)) in the terminal ileum (1010 (330)). Low ASBT expression was found in colonic segments (8.3 (5), 4.9 (0.9), 4.8 (1.7), and 1.1 (0.2) in the ascending, transverse, descending, and sigmoid colon, respectively). Duodenal ASBT expression in control subjects (171.8 (20.3)) was found to be approximately fourfold higher compared with patients with obstructive cholestasis (37.9 (6.5); p<0.0001). Individual ASBT mRNA expression was inversely correlated with bile acid and bilirubin plasma concentrations. In four cholestatic patients, average ASBT mRNA increased from 76 (18) before to 113 (18) after relief of cholestasis (NS). Immunohistochemical assessment indicated that ASBT protein was expressed on the apical surface of duodenal epithelial cells. Conclusion: Obstructive cholestasis in humans leads to downregulation of ASBT mRNA expression in the distal part of the human duodenum. [ABSTRACT FROM AUTHOR]

Tegaserod is a novel selective serotonin receptor type-4 (5-HT4) partial agonist that stimulates gastrointestinal (GI) motility. Tegaserod has proven efficacy in irritable bowel syndrome with constipation in women and in men and women with chronic idiopathic constipation. The effects on gastric emptying, small bowel transit and colonic transit have not been studied in detail in male and female subjects. This study aimed therefore to assess the effect of gender on GI transit with and without tegaserod. A randomized, placebo-controlled, double-blind, crossover study was performed in 40 healthy subjects (23 males, 17 females). Each treatment period involved three and a half days of bid treatment with either 6 mg tegaserod or an identical placebo. Transit parameters were assessed by a scintigraphy. Tegaserod significantly accelerated gastric emptying, small bowel and colonic transit times ( P < 0.05–0.0001). The effect was more apparent in male subjects than in females ( P = 0.044 to P < 0.0001). The most striking prokinetic effects were observed in the upper GI tract (stomach and small intestine). In both healthy male and female subjects, tegaserod markedly accelerated small intestinal transit, and induced a significant increase in gastric emptying time and colonic transit. The results imply that tegaserod is a potent prokinetic agent throughout the GI in both sexes. [ABSTRACT FROM AUTHOR]

: In industrialized countries, colorectal cancer is a leading cause of morbidity and mortality. Decisions on colorectal cancer screening are based on cost-effectiveness analyses that rely on colorectal cancer cost studies. Additionally, the study of the resource utilization pattern may lead to cost-saving strategies in the care of colorectal cancer.: To estimate hospital resource utilization, the use of various therapy modalities and costs of colorectal cancer cases undergoing surgery during the first 3 years following the diagnosis at a Swiss university hospital.: Consecutive colorectal cancer patients from 1997 to 1998 were identified using the surgery database of the University Hospital of Basel and followed for a period of 3 years. In-hospital resource utilization and costs were retrieved from the computerized administrative records. Treatment outside of the hospital during the study period constituted an exclusion criterion.: Eighty-three (94%) of 89 patients undergoing surgery for colorectal cancer were included in the study, 58 with colon cancer and 25 with rectal cancer. The average ages were 70.3 and 63.6 years, respectively. Overall, 59% of the patients were treated with surgery alone, 27% also had chemotherapy and 15% received additional chemoradiotherapy. These percentages and resource utilization varied broadly between the two colorectal cancer groups. On average, patients were admitted to the hospital 2.7 times and the hospital length of stay amounted to 35 days. They were visited by doctors 69 times, and examined with colonoscopy, ultrasonography and computerized tomography 2.7, 3.2 and 2.4 times, respectively. Mean costs incurred for rectal cancer ($40 230) were about 22% higher than for colon cancer patients ($33 079). Hospitalization and surgical therapy generated the greatest costs. Expenses were highest for the first year and with more severe disease stages at diagnosis.: Colorectal cancer is an expensive disease. Economic analyses on screening should take into account the large resource utilization and cost variability by performing sensitivity analysis on broad cost ranges. Furthermore, they should consider stage shifting at diagnosis and include stage-specific costs. [ABSTRACT FROM AUTHOR]