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Biomedical subjects

L Degen

Publications and source records attributed to L Degen.

At least 19 recordsLinked to original sources
PubMed2005

Adaptive regulation of the ileal apical sodium dependent bile acid transporter (ASBT) in patients with obstructive cholestasis.

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.

Adaptation, Physiological↗
PubMed2005

Effect of tegaserod on gut transit in male and female subjects.

Tegaserod is a novel selective serotonin receptor type-4 (5-HT(4)) 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.

Cross-Over Studies↗
PubMed2005

Ecological components and evolution of selfing in the freshwater snail Galba truncatula.

The reproductive assurance hypothesis emphasizes that self-fertilization should evolve in species with reduced dispersal capability, low population size or experiencing recurrent bottlenecks. Our work investigates the ecological components of the habitats colonized by the snail, Galba truncatula, that may influence the evolution of selfing. Galba truncatula is a preferential selfer inhabiting freshwater habitats, which vary with respect to the degree of permanence. We considered with a population genetic approach the spatial and the temporal degree of isolation of populations of G. truncatula. We showed that patches at distances of only a few meters are highly structured. The effective population sizes appear quite low, in the order of 10 individuals or less. This study indicates that individuals of the species G. truncatula are likely to be alone in a site and have a low probability of finding a partner from a nearby site to reproduce. These results emphasize the advantage of selfing in this species.

Animals↗
PubMed2004

Ileocecal reservoir reconstruction after total mesorectal excision: functional results of the long-term follow-up.

BACKGROUND: The aim of this study is to obtain functional results of the long-term follow-up after TME and ileocecal interposition as rectal replacement. METHODS: The study included patients operated on between March 1993 and August 1997 who received an ileocecal interposition as rectal replacement. Follow-up was carried out 3 and 5 years postoperatively. For statistical analysis, the paired t-test, rank test (Wilcoxon), and chi-square or Fisher's exact test were applied; level of significance, P<0.05. RESULTS: Forty-four patients were included in the studies. Of these, five were not available and four patients could not be evaluated (dementia 1, radiation proctitis 1, fistula 1, pouchitis 1). Seventeen patients died during the observation period; 12 died of the disease. Recurrence of the disorder occurred in 2 of 35 patients (5.7%); 26 and 18 patients, 3 and 5 years postoperatively, respectively remained in the study. At 5 years, 78% of the patients were continent; mean stool frequency was 2.5+/-1.6 per day. CONCLUSIONS: Functional results and subjective assessment of ileocecal interposition were constant at 3 and 5 years postoperatively. If construction of a colonic J-pouch is not possible due to lack of colonic length, especially after prior colonic resections, the ileocecal interpositional reservoir may offer an alternative to rectal replacement.

Anastomosis, Surgical↗
PubMed2003

Evolutionary implications of a high selfing rate in the freshwater snail Lymnaea truncatula.

Self-compatible hermaphroditic organisms that mix self-fertilization and outcrossing are of great interest for investigating the evolution of mating systems. We investigate the evolution of selfing in Lymnaea truncatula, a self-compatible hermaphroditic freshwater snail. We first analyze the consequences of selfing in terms of genetic variability within and among populations and then investigate how these consequences along with the species ecology (harshness of the habitat and parasitism) might govern the evolution of selfing. Snails from 13 localities (classified as temporary or permanent depending on their water availability) were sampled in western Switzerland and genotyped for seven microsatellite loci. F(IS) (estimated on adults) and progeny array analyses (on hatchlings) provided similar selfing rate estimates of 80%. Populations presented a low polymorphism and were highly differentiated (F(ST) = 0.58). Although the reproductive assurance hypothesis would predict higher selfing rate in temporary populations, no difference in selfing level was observed between temporary and permanent populations. However, allelic richness and gene diversity declined in temporary habitats, presumably reflecting drift. Infection levels varied but were not simply related to either estimated population selfing rate or to differences in heterozygosity. These findings and the similar selfing rates estimated for hatchlings and adults suggest that within-population inbreeding depression is low in L. truncatula.

Alleles↗
PubMed2002

Colonic involvement in non-necrotizing acute pancreatitis: correlation of CT findings with the clinical course of affected patients.

The purpose of this study was to describe CT findings of colonic involvement in acute non-necrotizing pancreatitis and to analyze the correlation between colonic wall thickening at CT and the clinical course of these patients. The CT examinations of 19 consecutive patients with acute non-necrotizing pancreatitis who were not treated with antibiotics initially were analyzed retrospectively. The severity of acute pancreatitis was categorized according to the CT severity index (CTSI) and the presence of colonic wall thickening at the initial CT was compared with the clinical course of all patients. Seven of 11 patients with a CTSI of 4 showed a colonic wall thickening, whereas the remaining patients with a CTSI of 4 (n=4), CTSI of 3 (n=5), and CTSI of 2 (n=3) showed no colonic abnormalities at CT. Patients with colonic wall thickening presented more often with fever, showed higher levels of infectious parameters, needed more often antibiotic therapy, and had more requests for additional CT examinations and CT-guided fluid aspirations as well as a longer duration of hospital stay as compared with patients without colonic wall involvement, even if the latter presented with the same CTSI initially. It is well known that translocation of the colonic flora may significantly influence the clinical course of patients with acute pancreatitis, and our results indicate that patients with acute pancreatitis who present with colonic wall thickening at CT have an increased risk for a complicated clinical course regarding systemic infection.

Acute Disease↗
PubMed2002

Subjective and functional results after replacement of the stomach with an ileocecal segment: a prospective study of 20 patients.

BACKGROUND AND AIMS: The optimal reconstruction procedure after gastrectomy is still a matter of debate. The ileocecal interpositional graft offers an excellent reservoir capacity, the preservation of duodenal passage, and a natural antireflux barrier (ileocecal sphincter). PATIENTS AND METHODS: We prospectively analyzed the quality-of-life outcome in 20 patients undergoing ileocecal interpositional graft (13 subdiaphragmatic reconstruction, 7 intrathoracic reconstruction) after gastrectomy in a University Hospital and a Canton Hospital (mean follow-up 6 months), operative and postoperative morbidity, body weight, reflux, and dumping symptoms. In a smaller series of nine patients we performed functional tests such as gastric emptying measurements, glucose tolerance tests, and manometry of the gastric substitute. RESULTS: The mean gastrointestinal quality-of-life index in the subdiaphragmatic reconstruction group 114, and that in the intrathoracic reconstruction group was 106. Mild reflux and dumping symptoms were noted by no patients in the former group and by two of seven patients in the latter. In the smaller series of nine patients gastric emptying time was faster in the intrathoracic group, but no difference in plasma glucose level was found between the two groups. CONCLUSIONS: Reconstruction after gastrectomy with an ileocecal interpositional graft achieves good quality of life with an acceptable morbidity. The technique seems to reduce the occurrence of postoperative reflux and dumping symptoms.

Anastomosis, Roux-en-Y↗
PubMed2002

Role of thyrotrophin releasing hormone and corticotrophin releasing factor in stress related alterations of gastrointestinal motor function.

There is a growing body of experimental and clinical evidence to indicate that stress influences gastrointestinal motility. The most common pattern of gastrointestinal motor alterations induced by a variety of different stress factors is that of delayed gastric emptying and accelerated colonic transit. Central administration of corticotrophin releasing factor mimics both of these effects. This review focuses on the effects of two centrally acting peptides known to influence gastrointestinal motility and transit in experimental animals: thyrotrophin releasing hormone and corticotrophin releasing factor. The biological actions of these peptides are discussed in relation to the motility changes and pathways involved in their actions.

Animals↗
PubMed2001

The effect of cholecystokinin in controlling appetite and food intake in humans.

The present review of the satiating effect of cholecystokinin in humans has revealed that cholecystokinin is a physiological satiety factor in humans. The results demonstrate the efficacy of the satiating actions of exogenous and endogenous CCK in humans. The therapeutic potential of CCK analogues cannot be estimated until further studies are performed that demonstrate the efficacy of CCK analogues for decreasing body weight, and the safety of CCK when administered repetitively for prolonged periods.

Animals↗
PubMed2001

[Diagnostic procedures in esophageal diseases].

The algorithms for diagnosis of esophageal diseases largely depend on the patient's symptoms. The most important diagnostic procedure is flexible upper gastrointestinal endoscopy which allows inspection and assessment of the entire esophagus with the possibility to take biopsies for histological examination. Radiographic tests are indicated for special indications only. Finally, the role of functional tests (manometry, 24-hour pH-metry) and their indications are discussed.

Barium Compounds↗
PubMed2001

Tegaserod, a 5-HT4 receptor partial agonist, accelerates gastric emptying and gastrointestinal transit in healthy male subjects.

BACKGROUND: Serotonin and its type-4 (5-hydroxytryptamine4) receptor play a major role in the physiology of the gastrointestinal tract. The effect of intravenous and/or oral tegaserod, a 5-hydroxytryptamine4 receptor partial agonist, on gastric emptying, small bowel transit and colonic transit has not been studied in detail in humans. AIM: To assess the pharmacodynamic effects of repeated oral and intravenous administration of tegaserod on gastric emptying and small intestine and colonic transit. METHODS: A randomized, placebo-controlled, double-blind, three-way, crossover study of 6 mg oral and 0.6 mg intravenous tegaserod in 12 healthy male subjects was performed. Each treatment arm of the study involved 3 days of twice-daily administration and 1 day of daily administration of the study drugs. RESULTS: In comparison with placebo, oral and intravenous tegaserod significantly increased the gastric emptying rate (P < 0.01), accelerated colonic filling (P < 0.01) and shortened colonic transit at 48 h (P < 0.05). Tegaserod shortened the small intestine transit time by 30% after oral and by 37% after intravenous administration. CONCLUSIONS: In healthy subjects, tegaserod markedly accelerated gastric emptying and small intestinal transit, and induced a small but significant acceleration of colonic transit. Tegaserod can act as a promotile agent throughout the gastrointestinal tract.

Administration, Oral↗
PubMed2001

Loxiglumide, a CCK-A receptor antagonist, stimulates calorie intake and hunger feelings in humans.

Exogenous cholecystokinin (CCK) induces early satiety when infused into humans. Whether alimentary CCK (CCK-A) receptor blockade stimulates food intake in humans is, however, uncertain. The aim of the present investigation was, therefore, to establish the effect of CCK-A receptor blockade on satiety and eating behavior in healthy volunteers. To further explore the role of endogenous CCK, the effects of the specific CCK-A receptor antagonist loxiglumide (Lox; 22 micromol. kg(-1). h(-1)) on satiety and eating behavior were investigated in healthy men and compared with saline infusions (as placebo) in a series of randomized, double-blind, placebo-controlled, crossover studies. Lox produced a slight (7%), but not significant (P = 0.104), increase in food intake that was accompanied by a modest (10%), but significant (P < 0.004), increase in calorie intake. Fluid ingestion was not affected by Lox. Subjects experienced more hunger and delayed fullness during Lox infusion than during saline infusion (P < 0.05). This study provides further evidence that CCK is an endogenous physiological satiety signal acting through CCK-A receptor-mediated mechanisms. Repeated-dose studies comparing hunger and satiety responses after CCK-A receptor blockade in healthy subjects and patients with eating disorders may help clarify the possible involvement of endogenous CCK in these conditions.

Adult↗
PubMed2000

The role of long chain fatty acids in regulating food intake and cholecystokinin release in humans.

BACKGROUND AND AIMS: The mechanism of intraduodenal fat induced inhibition of food intake is still unclear. Therefore, we tested the ability of duodenal fatty acids to suppress food intake at a lunchtime meal; in addition, we were interested to test if these effects were mediated by cholecystokinin (CCK) A receptors. SUBJECTS AND METHODS: Three sequential double blind, three period crossover studies were performed in 12 healthy males each: (1) subjects received intraduodenal fat with or without 120 mg of tetrahydrolipstatin, an inhibitor of gastrointestinal lipases, or saline; (2) volunteers received intraduodenal long chain fatty acids, medium chain fatty acids, or saline; (3) subjects received long chain fatty acids or saline together with concomitant intravenous infusions of saline or loxiglumide, a specific CCK-A receptor antagonist. The effect of these treatments on food intake and feelings of hunger was quantified. RESULTS: Intraduodenal fat perfusion significantly (p<0.05) reduced calorie intake. Inhibition of fat hydrolysis abolished this effect. Only long chain fatty acids significantly (p<0.05) decreased calorie intake, whereas medium chain fatty acids were ineffective. Infusion of loxiglumide abolished the effect of long chain fatty acids. CONCLUSIONS: Generation of long chain fatty acids through hydrolysis of fat is a critical step for fat induced inhibition of food intake; the signal is mediated via CCK-A receptors.

Adult↗