http://repub.eur.nl/res/aut/17130/ List of Publications en http://repub.eur.nl/static-eur/img/logo.png http://repub.eur.nl http://repub.eur.nl/res/pub/34437/ 2011-11-01T00:00:00Z http://repub.eur.nl/res/pub/25639/ 2011-06-23T00:00:00Z Background: Minimally invasive parathyroidectomy is the treatment of choice for single-gland primary hyperparathyroidism. However, the exact location of the abnormal gland has to be established. Sestamibi scintigraphy, computed tomography and ultrasound (US) are commonly used modalities. We describe our experience in a non-academic center with surgeon-performed US (S-US) of the neck as preoperative localization study in patients with primary hyperparathyroidism (PHPT). Methods: Patients with a biochemically proven diagnosis of PHPT and preoperative S-US were included. Data were recorded prospectively. Perioperative gland location was compared to the preoperative S-US to determine sensitivity, specificity and accuracy rates. Results: Two of the 50 patients who underwent S-US were not subjected to surgery. In 85% of the patients analyzed by S-US, the appropriate abnormal gland(s) were identified. In 11%, no gland was identified, but abnormal glands were found during surgery. Sensitivity of S-US in our hospital is 85%, with a positive predictive value of 97%. Conclusions: We achieved a satisfactory sensitivity rate. S-US provides anatomic information to the surgeon which enables a more detailed operation planning, and it is a valuable diagnostic modality for patients with PHPT in our opinion. We hope that our data encourage other centers to implement this technique as well. Copyright http://repub.eur.nl/res/pub/26235/ 2011-06-01T00:00:00Z We show that brief periods of fasting induce functional changes similar to those induced by long-term dietary restriction in mice, and these changes include protection from ischemia/reperfusion (I/R) injury. In this study, we investigated the mechanisms of protection induced by fasting, and we determined the effect on liver regeneration after partial hepatectomy. Partial hepatic ischemia (75 minutes) was induced in ad libitum fed mice and in 1- to 3-day-fasted mice, and one-third or two-thirds hepatectomy was performed in ad libitum fed mice and 3-day-fasted mice. Preoperative fasting for 2 or 3 days significantly decreased hepatocellular I/R injury. Hepatic gene expression of heme oxygenase 1 (HO-1), superoxide dismutase 2 (SOD2), glutathione peroxidase 1 (Gpx1), and glutathione reductase (GSR) was significantly up-regulated in 3-day-fasted mice at the baseline and 6 hours after reperfusion. After reperfusion, p-selectin and interleukin-6 (IL-6) levels were significantly lower, and superoxide radical generation, lipid peroxidation, and neutrophil influx were significantly attenuated in 3-day-fasted mice. Preoperative fasting did not affect liver regeneration after one-third hepatectomy. Hepatic gene expression of IL-6 and transforming growth factor β1 was significantly higher in 3-day-fasted mice before and after one-third hepatectomy. Tumor necrosis factor α expression significantly increased after one-third hepatectomy in 3-day-fasted mice. After a 3-day fast and two-thirds hepatectomy, liver regeneration and subsequent postoperative recovery were compromised. In conclusion, up-regulation of the stress response gene HO-1 and the antioxidant enzymes SOD2, Gpx1, and GSR at the baseline and a better response after reperfusion likely underlie the protection induced by fasting against hepatic I/R injury. Preoperative fasting may be a promising new strategy for protecting the liver against I/R injury during liver transplantation and minor liver resections, although its effect on extended hepatectomy warrants further exploration. Liver Transpl 17:695-704, 2011. © 2011 AASLD. http://repub.eur.nl/res/pub/34074/ 2011-05-01T00:00:00Z Dietary restriction (DR), defined as reduced energy intake without malnutrition, confers protection against renal ischemia and reperfusion injury in animal models. This pilot study investigates for the first time the feasibility of pre-operative DR in the clinical setting. Live-kidney donors were randomized between pre-operative DR or ad libitum intake. Seventeen participants were instructed to follow a 30% calorie-restricted diet, followed by one day of water-only fasting prior to surgery. Thirteen participants were allowed to eat ad libitum pre-operatively. Ninety-four percent of the donors adhered to the diet, 31.4% reduction in caloric intake was achieved. Post-operative well-being, appetite and ability to perform daily tasks were not different between both groups. There was no difference in post-transplant graft function of kidneys obtained from DR donors or control donors as determined by serum creatinine levels during the first post-operative month and renograms at post-operative day one. This study shows that mild dietary restriction is feasible in the setting of live-kidney donation. No effect was observed regarding post-operative graft function. Additional studies are warranted to investigate the appropriate regimen of dietary restriction to protecting against ischemia and reperfusion injury, such as increasing the magnitude and/or duration of the reduction in daily caloric intake. http://repub.eur.nl/res/pub/33698/ 2011-04-01T00:00:00Z Background & Aims:99mTc-mebrofenin hepatobiliary scintigraphy (HBS) and the indocyanine green (ICG) clearance test are used for the assessment of hepatic function before and after liver surgery. The hepatic uptake of99mTc-mebrofenin and ICG is considered similar to the uptake of organic anions such as bilirubin and bile acids. Little is known about hepatic uptake mechanisms of both compounds and recent evidence suggests that the hepatic transporters for ICG and99mTc-mebrofenin are distinct. The aim of this study was to identify the specific human hepatic transporters of99mTc-mebrofenin and ICG. Methods: The uptake of99mTc-mebrofenin was investigated in cRNA-injected Xenopus laevis oocytes expressing human OATP1B1, OATP1B3, OATP2B1, or NTCP. Chinese hamster ovary (CHO) cells stably expressing OATP1B1, OATP1B3, OATP2B1, or NTCP were used as a mammalian expression system. ICG transport into CHO cells was additionally imaged with confocal microscopy. Results: We demonstrated that OATP1B1 and OATP1B3 are involved in the transport of99mTc-mebrofenin. OATP1B1 showed an approximately 1.5-fold higher affinity for99mTc-mebrofenin compared to OATP1B3. ICG is transported by OATP1B3 and NTCP. Conclusions: The transporter specificity of99mTc-mebrofenin and ICG partially overlaps as both compounds are transported by OATP1B3.99mTc- mebrofenin is also taken up by OATP1B1, whereas ICG is additionally transported by NTCP. http://repub.eur.nl/res/pub/22970/ 2011-02-02T00:00:00Z People have always been searching for methods to stay young and live longer. For example, in the European middle ages alchemists were looking for the “potion of life”. This elixir, also known as the elixir of immortality and sometimes equated with the philosopher’s stone, is a legendary potion, or drink, that grants the drinker eternal life or eternal youth. So far no elixir has been found. The same holds for the fountain of youth, a legendary spring that reputedly restores the youth of anyone who drinks of its waters. Despite all these efforts it was not until the beginning of the twentieth century that a non-invasive way to prolong life-, and healthspan was found: dietary restriction. http://repub.eur.nl/res/pub/27847/ 2010-12-01T00:00:00Z One of the factors negatively influencing the outcome after kidney transplantation is ischemia-reperfusion (I/R) injury. Preoperative fasting is able to confer protection against I/R injury. We hypothesized that the protection imposed by preoperative fasting is mediated by increased levels of acylated ghrelin. Male C57BL/6 mice, 10 to 12 weeks old, were fasted for 1, 2, or 3 days, after which, acylated ghrelin levels were determined. Ad libitum fed mice were injected with acylated ghrelin or phosphate-buffered saline before renal I/R injury. Furthermore, mice were fasted for 3 days during which they were injected with a growth hormone secretagogue receptor antagonist, to block the effects of ghrelin, or a vehiculum. Bilateral renal I/R injury was induced by clamping the artery and vein of the left and right kidney simultaneously for 37 minutes. Kidney function was assessed by means of serum urea values determined at 24 and 48 hours after reperfusion. Fasting significantly increased acylated ghrelin serum levels. Ghrelin suppletion in ad libitum fed animals or ghrelin receptor blockade in fasted animals did not affect renal function after I/R injury. Our data suggest that the increased levels of acylated ghrelin induced by fasting do not mediate its protection against renal I/R injury. http://repub.eur.nl/res/pub/21245/ 2010-11-01T00:00:00Z Three days of fasting protects mice against lethal renal ischemia-reperfusion (IR) injury. We hypothesize that the protection imposed by fasting is mediated by increased levels of corticosterone, induced by the stress of food deprivation. C57Bl6 mice were fasted for 3 days after which serum corticosterone levels were determined. Mice underwent a bilateral adrenalectomy (ADX). Ten days later, they were either fasted or given a corticosterone receptor antagonist while fasting. Bilateral renal IR injury was induced by clamping the artery and vein of the left and right kidney simultaneously for 37 min. Survival and kidney function were determined. Fasting significantly increased corticosterone levels. Only 8% of the ADX mice which were fasted prior to IR injury survived, whereas all sham-ADX operated mice survived IR injury after fasting. After ADX and fasting, 70% of the mice subjected to sham IR succumbed to the surgical procedure. After fasting with concomitant blockade of the glucocorticoid receptor all animals survived renal IR. Three days of fasting protects against IR injury and increases serum corticosterone levels. ADX renders mice incapable of withstanding subsequent abdominal surgery. Glucocorticoid receptor blockade does not interfere with the protective effects of fasting. Thus, the protection against renal IR injury induced by preoperative fasting is mediated by corticosterone-independent mechanisms. http://repub.eur.nl/res/pub/27695/ 2010-09-15T00:00:00Z Background: Inflammatory responses facilitate metastasis by increasing expression of adhesion molecules. Dietary restriction (30% reduction in daily calorie intake) reduces the expression of adhesion molecules and protects against surgically induced inflammation. DR might therefore beneficially interfere with surgery-induced inflammation and subsequent adhesion of circulating tumor cells. Methods: BALB/c mice were subjected to 2 weeks dietary restriction prior to inoculation with tumor cells. Intra-splenic injection of 5.0 × 104C26-colon carcinoma cells was followed by splenectomy. Hepatic tumor load was scored after 10 days as a percentage (tumor surface/total liver surface) on H&E stained sections. Liver mRNA expression of adhesion molecules was determined and the effect of serum from dietary restriction mice on in vitro tumor growth and adhesion capacity was assessed. Results: Preoperative dietary restriction significantly reduced mRNA expression levels of E-selectin (P = 0.0087) and hepatic tumor load (P = 0.036). Dietary restriction serum did not affect in vitro cell growth but reduced in vitro adhesion of C26 cells to endothelial cells (P = 0.0043). Conclusions: Preoperative dietary restriction reduces hepatic tumor load after injection with tumor cells. Reduced adhesion to endothelial cells and reduced mRNA expression of E-selectin suggest that dietary restriction reduces tumor load by lowering the adhesion of circulating tumor cells to hepatic vascular endothelium. http://repub.eur.nl/res/pub/27439/ 2010-06-10T00:00:00Z Background: Lifespan extension is achieved through long-term application of dietary restriction (DR), and benefits of short-term dietary restriction on acute stress and inflammation have been observed. So far, the effects of short-term DR in humans are relatively unknown. We hypothesized that short-term DR in humans reduces the acute phase response following a well defined surgical trauma. Methods: Thirty live kidney donors were randomized between 30% preoperative dietary restriction followed by 1 d of fasting (n = 17) or a 4 d ad libitum regimen (n = 13) prior to surgery. Leukocyte subsets and numbers and serum cytokine levels were determined. Whole blood was stimulated with lipopolysaccharide (LPS) and cytokine production was determined. Results: A clear trend towards lower numbers of postoperative circulating leukocytes was observed in the DR group. IL-8 serum levels were significantly higher in the DR group over the first 6 postoperative d (P = 0.018). After LPS stimulation, significantly less TNF-α (P = 0.001) was produced by blood obtained postoperatively compared with preoperative blood from the DR group. This was not observed in the control group. Conclusions: A relatively short preoperative dietary restriction regimen was able to modify certain aspects of the postoperative acute phase response. These data warrant further studies into the dietary conditions that improve stress resistance in humans. (Dutch Trial Registry number: NTR1875). http://repub.eur.nl/res/pub/26926/ 2009-10-01T00:00:00Z Preoperative fasting was introduced in the 19th century to reduce the risk of aspiration pneumonia while patients were under general anesthesia. During the last decades, the value of preoperative fasting has been questioned, and more liberal guidelines have been proposed, such as the use of preoperative carbohydrate-rich drinks. Here we review both old and new evidence supporting the view that fasting slightly longer than overnight is beneficial for an entirely different purpose: protection against certain types of stress, such as ischemia-reperfusion injury. We provide a framework to explain these benefits as well as future applications and alternatives that could be used to induce the protection afforded by nutritional interventions. http://repub.eur.nl/res/pub/14723/ 2008-10-01T00:00:00Z The treatment of intra-articular calcaneal fractures is controversial and randomised clinical trials are scarce. Moreover, the socio-economic cost remains unclear. The aim of this study was to estimate the incidence, treatment preferences and socio-economic cost of this complex fracture in the Netherlands. This data may aid in planning future clinical trials and support education. The method of study was of a cross-sectional survey design. A written survey was sent to one representative of both the traumatology and the orthopaedic staff in each hospital in the Netherlands. Data on incidence, treatment modalities, complications and follow-up strategies were recorded. The socio-economic cost was calculated. The average response rate was 70%. Fracture classifications, mostly by Sanders and Essex-Lopresti, were applied by 29%. Annually, 920 intra-articular calcaneal fractures (0.4% incidence rate) were treated, mainly with ORIF (46%), conservative (39%) and percutaneous (10%) treatment. The average non-weight-bearing mobilisation was 9 weeks (SD 2 weeks). An outcome score, mainly AOFAS, was documented by 7%. A secondary arthrodesis was performed in 21% of patients. The socio-economic cost was estimated to be €21.5-30.7 million. Dutch intra-articular calcaneal fracture incidence is at least 0.4% of all fractures presenting to hospitals. Better insight into treatment modalities currently employed and costs in the Netherlands was obtained.