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Grisouard J.,University of Basel | Bouillet E.,University of Basel | Timper K.,University of Basel | Radimerski T.,University of Basel | And 7 more authors.
Innate Immunity | Year: 2012

High fat diet-induced endotoxaemia triggers low-grade inflammation and lipid release from adipose tissue. This study aims to unravel the cellular mechanisms leading to the lipopolysaccharide (LPS) effects in human adipocytes. Subcutaneous pre-adipocytes surgically isolated from patients were differentiated into mature adipocytes in vitro. Lipolysis was assessed by measurement of glycerol release and mRNA expression of pro-inflammatory cytokines were evaluated by real-time PCR. Treatment with LPS for 24 h induced a dose-dependent increase in interleukin (IL)-6 and IL-8 mRNA expression. At 1 μg/ml LPS, IL-6 and IL-8 were induced to 19.5 ± 1.8-fold and 662.7 ± 91.5-fold (P < 0.01 vs basal), respectively. From 100 ng/ml to 1 μg/ml, LPS-induced lipolysis increased to a plateau of 3.1-fold above basal level (P < 0.001 vs basal). Co-treatment with inhibitors of inhibitory kappa B kinase kinase beta (IKKβ) or NF-κB inhibited LPS-induced glycerol release. Co-treatment with the protein kinase A (PKA) inhibitor H-89, the lipase inhibitor orlistat or the hormone-sensitive lipase (HSL) inhibitor CAY10499 abolished the lipolytic effects of LPS. Co-treatment with the MAPK inhibitor, U0126 also reduced LPS-induced glycerol release. Inhibition of lipolysis by orlistat or CAY10499 reduced LPS-induced IL-6 and IL-8 mRNA expression. Induction of lipolysis by the synthetic catecholamine isoproterenol or the phosphodiesterase type III inhibitor milrinone did not alter basal IL-6 and IL-8 mRNA expression after 24 treatments whereas these compounds enhanced LPS-induced IL-6 and IL-8 mRNA expression. Both the inflammatory IKKβ/NF-κB pathway and the lipolytic PKA/HSL pathways mediate LPS-induced lipolysis. In turn, LPS-induced lipolysis reinforces the expression of pro-inflammatory cytokines and, thereby, triggers its own lipolytic activity. © The Author(s) 2010 Reprints and permissions: sagepub.co.uk/ journalsPermissions.nav.


Businger A.,St. Claraspital Basel | Villiger P.,Kantonsspital Graubunden | Sommer C.,Kantonsspital Graubunden | Furrer M.,Kantonsspital Graubunden
Annals of Surgery | Year: 2010

Objective: To evaluate arguments given by board-certified surgeons in Switzerland for and against a career in surgery. Background data: Currently, the surgical profession in most Western countries is experiencing a labor shortage because of a declining interest in a surgical career among new graduates, a changed public opinion of medicine and its representatives, and as a consequence of the increasing influence of health economists and politicians on the professional independence of surgeons. Reports that focus primarily on the reasons that board-certified surgeons remain within the surgical profession are rare. Methods: Surgeons were asked to answer 2 questions concerning arguments for and against a career in surgery. Of 749 surgeons the arguments of 334 (44.6%) were analyzed using Mayring's content analysis. The surgeons were also asked whether they would choose medicine as a career path again. Results: The 334 participating surgeons provided 790 statements for and 981 statements against a career in surgery. Fifty-nine surgeons (17.7%) would not choose medicine as a career again. Mayring's content analysis of the statements yielded 10 categories with arguments both for and against a career in surgery. "Personal Experience in Daily Professional Life" (18.7%) was the top-ranked category in favor of a career in surgery, and "Specific Training Conditions" (20%) was the top-ranked category against the choice of such a career. Ordinal logistic regression showed that the category "Personal Experience in Daily Professional Life" (OR, 2.39; 95%CI, 1.13-5.07) was independently associated with again studying medicine, and the category "Work-life Balance" (OR, 0.37; 95%CI, 0.20-0.70) was associated with not studying medicine again. Conclusion: This qualitative study revealed unfavorable working conditions and regulations as surgeons' main complaints. It is concluded that new organizational frameworks and professional perspectives are required to retain qualified and motivated surgeons in the surgical profession. Copyright © 2010 by Lippincott Williams & Wilkins.


Timper K.,University of Basel | Grisouard J.,University of Basel | Radimerski T.,University of Basel | Dembinski K.,University of Basel | And 6 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2011

Context: Increased plasma levels of glucose-dependent insulinotropic polypeptide (GIP), calcitonin CT gene-related peptide (CGRP)-I, and procalcitonin (Pro-CT) are associated with obesity. Adipocytes express functional GIP receptors and the CT peptides Pro-CT and CGRP-I. However, a link between GIP and CT peptides has not been studied yet. Objective: The objective of the study was the assessment of the GIP effect on the expression and secretion of CGRP-I and Pro-CT in human adipocytes, CGRP-I and CT gene expression in adipose tissue (AT) from obese vs. lean subjects, and plasma levels of CGRP-I and Pro-CT after a high-fat meal in obese patients. Design and Participants: Human preadipocyte-derived adipocytes, differentiated in vitro, were treated with GIP. mRNA expression and protein secretion of CGRP-I and Pro-CT were measured. Human CGRP-I and CT mRNA expression in AT and CGRP-I and Pro-CT plasma concentrations were assessed. Results: Treatment with 1 nM GIP induced CGRP-I mRNA expression 6.9 ± 1.0-fold (P < 0.001 vs. control) after 2 h and CT gene expression 14.0 ± 1.7-fold (P < 0.001 vs. control) after 6 h. GIP stimulated CGRP-I secretion 1.7 ± 0.2-fold (P < 0.05 vs. control) after 1 h. In AT samples of obese subjects, CGRP-I mRNA expression was higher in sc AT (P < 0.05 vs. lean subjects), whereas CT expression was higher in visceral AT (P<0.05 vs. lean subjects). CGRP-I plasma levels increased after a high-fat meal in obese patients. Conclusion: GIP induces CGRP-I and CT expression in human adipocytes. Therefore, elevated Pro-CT and CGRP-I levels in obesity might result from GIP-induced Pro-CT and CGRP-I release in AT and might be triggered by a high-fat diet. How these findings relate to the metabolic complications of obesity warrants further investigations. Copyright © 2011 by The Endocrine Society.


Gass M.,St. Claraspital Basel | Beglinger C.,University of Basel | Peterli R.,St. Claraspital Basel
Langenbeck's Archives of Surgery | Year: 2011

Introduction: In the almost six decades of bariatric surgery, a variety of surgical approaches to treating morbid obesity have been developed. History and evolution: Rather than prior techniques being continually superseded by new ones, a broad choice of surgical solutions based on restrictive, malabsorptive, humoral effects, or combinations thereof, is now available. In fact, in recent years, the advent of surgically modifying human metabolism promises new approaches to ameliorate traditionally medically treated metabolic entities, i.e., diabetes, even in the non-obese. The understanding of the various metabolic effects have led to a paradigm shift from bariatric surgery as a solely weight-reducing procedure to metabolic surgery affecting whole body metabolism. Conclusion: The bariatric surgeon now faces the challenge and opportunity of selecting the most suitable technique for each individual case. To assist in such decision-making, this review, Metabolic surgery-principles and current concepts, is presented, tracing the historical development; describing the various surgical techniques; elucidating the mechanisms by which glycemic control can be achieved that involve favorable changes in insulin secretion and insulin sensitivity, gut hormones, adipokines, energy expenditure, appetite, and preference for low glycemic index foods; as well as exploring the fascinating future potential of this new interdisciplinary field. © 2011 Springer-Verlag.


Grisouard J.,University of Basel | Timper K.,University of Basel | Bouillet E.,University of Basel | Radimerski T.,University of Basel | And 7 more authors.
Archives of Physiology and Biochemistry | Year: 2011

Objective: To study the effects of metformin on lipolysis and hormone sensitive lipase (HSL) phosphorylation in human adipocytes treated with lipolytic and inflammatory agents. Methods: Lipolysis and phosphorylation status of HSL were assessed in subcutaneous pre-adipocytes surgically isolated from patients and differentiated into mature adipocytes in vitro. Results: Stimulation for 1h with forskolin, isoproterenol and IBMX or stimulation for 24h with LPS, IL-1β and TNF-α increased lipolysis (p<0.05 vs. basal). The phosphorylation of HSL at Ser-554 was decreased while the Ser-552 phosphorylation was increased. Pre-incubation with metformin (24h, 1mM) inhibited forskolin-, isoproterenol-, IBMX-, LPS-, IL-1β-and TNF-α-induced glycerol release and prevented p(Ser554)HSL decrease and p(Ser-552)HSL increase due to lipolytic and inflammatory agents. AMPKα1 is involved in metformin-induced HSL phosphorylation at Ser-552. Conclusion: Phosphorylation of HSL at Ser-554 inversely correlates with lipolysis and HSL phosphorylation at Ser552 in human adipocytes. © 2011 Informa UK, Ltd.


Manz M.,St. Claraspital Basel | Michetti P.,University of Lausanne | Rogler G.,University of Zürich | Beglinger C.,University of Basel
Swiss Medical Weekly | Year: 2011

The care for a patient with ulcerative colitis (UC) remains challenging despite the fact that morbidity and mortality rates have been considerably reduced during the last 30 years. The traditional management with intravenous corticosteroids was modified by the introduction of ciclosporin and infliximab. In this review, we focus on the treatment of patients with moderate to severe UC. Four typical clinical scenarios are defined and discussed in detail. The treatment recommendations are based on current literature, published guidelines and reviews, and were discussed at a consensus meeting of Swiss experts in the field. Comprehensive treatment algorithms were developed, aimed for daily clinical practice.


Vinzens F.,St Claraspital Basel | Zumstein V.,St Claraspital Basel | Bieg C.,St Claraspital Basel | Ackermann C.,St Claraspital Basel
BMJ Case Reports | Year: 2016

Patients presenting with abdominal pain and pneumoperitoneum in radiological examination usually require emergency explorative laparoscopy or laparotomy. Pneumoperitoneum mostly associates with gastrointestinal perforation. There are very few cases where surgery can be avoided. We present 2 cases of pneumoperitoneum with unknown origin and successful conservative treatment. Both patients were elderly women presenting to our emergency unit, with moderate abdominal pain. There was neither medical intervention nor trauma in their medical history. Physical examination revealed mild abdominal tenderness, but no clinical sign of peritonitis. Cardiopulmonary examination remained unremarkable. Blood studies showed only slight abnormalities, in particular, inflammation parameters were not significantly increased. Finally, obtained CTs showed free abdominal gas of unknown origin in both cases. We performed conservative management with nil per os, nasogastric tube, total parenteral nutrition and prophylactic antibiotics. After 2 weeks, both were discharged home. Copyright 2016 BMJ Publishing Group. All rights reserved.


Patients presenting with abdominal pain and pneumoperitoneum in radiological examination usually require emergency explorative laparoscopy or laparotomy. Pneumoperitoneum mostly associates with gastrointestinal perforation. There are very few cases where surgery can be avoided. We present 2 cases of pneumoperitoneum with unknown origin and successful conservative treatment. Both patients were elderly women presenting to our emergency unit, with moderate abdominal pain. There was neither medical intervention nor trauma in their medical history. Physical examination revealed mild abdominal tenderness, but no clinical sign of peritonitis. Cardiopulmonary examination remained unremarkable. Blood studies showed only slight abnormalities, in particular, inflammation parameters were not significantly increased. Finally, obtained CTs showed free abdominal gas of unknown origin in both cases. We performed conservative management with nil per os, nasogastric tube, total parenteral nutrition and prophylactic antibiotics. After 2weeks, both were discharged home.


PubMed | St. Claraspital Basel
Type: Journal Article | Journal: Langenbeck's archives of surgery | Year: 2011

In the almost six decades of bariatric surgery, a variety of surgical approaches to treating morbid obesity have been developed.Rather than prior techniques being continually superseded by new ones, a broad choice of surgical solutions based on restrictive, malabsorptive, humoral effects, or combinations thereof, is now available. In fact, in recent years, the advent of surgically modifying human metabolism promises new approaches to ameliorate traditionally medically treated metabolic entities, i.e., diabetes, even in the non-obese. The understanding of the various metabolic effects have led to a paradigm shift from bariatric surgery as a solely weight-reducing procedure to metabolic surgery affecting whole body metabolism.The bariatric surgeon now faces the challenge and opportunity of selecting the most suitable technique for each individual case. To assist in such decision-making, this review, Metabolic surgery-principles and current concepts, is presented, tracing the historical development; describing the various surgical techniques; elucidating the mechanisms by which glycemic control can be achieved that involve favorable changes in insulin secretion and insulin sensitivity, gut hormones, adipokines, energy expenditure, appetite, and preference for low glycemic index foods; as well as exploring the fascinating future potential of this new interdisciplinary field.


PubMed | St. Claraspital Basel
Type: Journal Article | Journal: Annals of surgery | Year: 2010

To evaluate arguments given by board-certified surgeons in Switzerland for and against a career in surgery.Currently, the surgical profession in most Western countries is experiencing a labor shortage because of a declining interest in a surgical career among new graduates, a changed public opinion of medicine and its representatives, and as a consequence of the increasing influence of health economists and politicians on the professional independence of surgeons. Reports that focus primarily on the reasons that board-certified surgeons remain within the surgical profession are rare.Surgeons were asked to answer 2 questions concerning arguments for and against a career in surgery. Of 749 surgeons the arguments of 334 (44.6%) were analyzed using Mayrings content analysis. The surgeons were also asked whether they would choose medicine as a career path again.The 334 participating surgeons provided 790 statements for and 981 statements against a career in surgery. Fifty-nine surgeons (17.7%) would not choose medicine as a career again. Mayrings content analysis of the statements yielded 10 categories with arguments both for and against a career in surgery. Personal Experience in Daily Professional Life (18.7%) was the top-ranked category in favor of a career in surgery, and Specific Training Conditions (20%) was the top-ranked category against the choice of such a career. Ordinal logistic regression showed that the category Personal Experience in Daily Professional Life (OR, 2.39; 95%CI, 1.13-5.07) was independently associated with again studying medicine, and the category Work-life Balance (OR, 0.37; 95%CI, 0.20-0.70) was associated with not studying medicine again.This qualitative study revealed unfavorable working conditions and regulations as surgeons main complaints. It is concluded that new organizational frameworks and professional perspectives are required to retain qualified and motivated surgeons in the surgical profession.

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