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Massolt E.T.,Reinier Of Graaf Group Of Hospitals | van Haard P.M.,Reinier Of Graaf Group Of Hospitals | Rehfeld J.F.,Rigshospitalet | Posthuma E.F.,Reinier Of Graaf Group Of Hospitals | And 2 more authors.
Regulatory Peptides | Year: 2010

Cephalic effects on appetite are mediated by vagal tone and altered gastrointestinal hormones. The objective of this study is to explore the relationship between appetite and levels of gastrointestinal hormones after smelling chocolate and after melt-and-swallow 30g chocolate (1.059oz, 85% cocoa, 12.5g of sugar per 100g product). Twelve female residents (BMI between 18 and 25kg/m2) all participated in two 60-minute study sessions. In the first session, all 12 women ate chocolate; for the second session, they were randomized either to smell chocolate (n=6) or to serve as a control (no eating or smelling; n=6). At the start of the sessions, levels of insulin, glucagon-like peptide-1 (GLP-1) and cholecystokinin (CCK), but not glucose, correlated with appetite scored on a visual analogue scale (VAS). In contrast, ghrelin levels correlated inversely with scored appetite. Chocolate eating and smelling both induced a similar appetite suppression with a disappearance of correlations between VAS scores and insulin, GLP-1 and CCK levels. However, while the correlation between VAS score and ghrelin disappeared completely after chocolate eating, it reversed after chocolate smelling, that is, olfactory stimulation with dark chocolate (85%) resulted in a satiation response that correlated inversely with ghrelin levels. © 2010 Elsevier B.V.


Dolfing J.G.,Twente Group of Hospitals | Stassen C.M.,Twente Group of Hospitals | Van Haard P.M.M.,Reinier Of Graaf Group Of Hospitals | Wolffenbuttel B.H.R.,University of Groningen | Schweitzer D.H.,Reinier Of Graaf Group Of Hospitals
Human Reproduction | Year: 2011

BACKGROUND: Polycystic ovary syndrome (PCOS) is a heterogeneous disorder. However, PCOS has a strong resemblance to the metabolic syndrome, including preponderance of visceral fat deposition. The aim of this study is to compare fat distribution between lean women with PCOS and controls matched for body composition but with regular menstrual cycles and proven fertility. Methods In this prospective cross-sectional study in a fertility outpatient clinic, 10 Caucasian women with PCOS and 10 controls, all with a BMI between 19 and 25 kg/m2, were included. Fasting glucose, insulin and C-peptide concentrations, homeostasis model assessment (HOMA), hormonal levels and bioelectrical impedance analysis (BIA) variables were assessed and fat content and ovarian volume determinations were obtained with magnetic resonance imaging (MRI). Multiple axial cross-sections were calculated. Results The age of the PCOS and control groups were [mean (SD)] 28.2 years (2.6) versus 33.7 years (2.3) P < 0.0001, respectively, and both groups were matched for BMI: 21.6 kg/m2 (1.1) versus 21.8 kg/m2 (2.1) (ns), fasting glucose, insulin, C-peptide, HOMA-insulin resistance (IR) levels and BIA parameters. PCOS cases had higher ovarian volumes and less visceral fat compared with controls. CONCLUSIONS Lean women with PCOS have higher MRI-determined ovarian volumes and less visceral fat content when compared with control women. © The Author 2011. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved.


Van Der Weerd K.,Erasmus Medical Center | Dik W.A.,Erasmus Medical Center | Schrijver B.,Erasmus Medical Center | Schweitzer D.H.,Reinier Of Graaf Group Of Hospitals | And 8 more authors.
Diabetes | Year: 2012

Obesity is associated with local T-cell abnormalities in adipose tissue. Systemic obesity-related abnormalities in the peripheral blood T-cell compartment are not well defined. In this study, we investigated the peripheral blood T-cell compartment of morbidly obese and lean subjects. We determined all major T-cell sub-populations via six-color flow cytometry, including CD8 + and CD4 + T cells, CD4 + T-helper (Th) subpopulations, and natural CD4 +CD25 +FoxP3 + T-regulatory (Treg) cells. Moreover, molecular analyses to assess thymic output, T-cell proliferation (T-cell receptor excision circle analysis), and T-cell receptor-β (TCRB) repertoire (GeneScan analysis) were performed. In addition, we determined plasma levels of proinflammatory cytokines and cytokines associated with Th subpopulations and T-cell proliferation. Morbidly obese subjects had a selective increase in peripheral blood CD4 + naive, memory, natural CD4 +CD25 +FoxP3 + Treg, and Th2 T cells, whereas CD8 + T cells were normal. CD4 + and CD8 + T-cell proliferation was increased, whereas the TCRB repertoire was not significantly altered. Plasma levels of cytokines CCL5 and IL-7 were elevated. CD4 + T-cell numbers correlated positively with fasting insulin levels. The peripheral blood T-cell compartment of morbidly obese subjects is characterized by increased homeostatic T-cell proliferation to which cytokines IL-7 and CCL5, among others, might contribute. This is associated with increased CD4 + T cells, with skewing toward a Treg- and Th2-dominated phenotype, suggesting a more anti-inflammatory set point. © 2012 by the American Diabetes Association.


Jans G.,Unit Pregnancy | Voets W.,Jessa Hospital | Galjaard S.,Unit Pregnancy | Galjaard S.,University Hospitals Leuven | And 3 more authors.
Surgery for Obesity and Related Diseases | Year: 2014

Background: Neonatal intracranial bleedings and birth defects have been reported, possibly related to maternal vitamin K1 deficiency during pregnancy after bariatric surgery. The objective of this study was to investigate the effects of screening and supplementation on K1 serum levels in pregnant women with bariatric surgery, and to compare K1 levels and prothrombin time (PT %) in the first trimester with pregnant women without bariatric surgery. Methods: A prospective cohort study including 49 pregnant women with bariatric surgery. Nutritional deficiencies were prospectively screened. In case of observed low K1 serum levels, supplementation was provided. K1 serum levels and PT (%) during the first trimester were compared with a nonsurgical control group of 27 women. Results: During the first trimester, most women had low K1 serum levels (< 0.8 nmol/l). Mean vitamin K1 levels were significantly lower in the surgical group compared to the nonsurgical control group (.44 versus .64 nmol/l; P = .016). PT (%) remained in the normal range, The surgery group showed a higher mean PT compared to the controls (111.3 versus 98.9%; P < .001) Mean K1 serum levels in the study group were higher during the third than during the first trimester (P = .014). PT (%) was significantly higher during the second and third than during the first trimester (P = .004). Most of the coagulation factors, including II, V, VII, IX, and X, remained within normal ranges. Conclusion: Low circulating K1 appears to be common in pregnant women with and without bariatric surgery. Supplementation during pregnancy can restore vitamin K1 in women with bariatric surgery, potentially protecting the fetus and newborn against intracranial hemorrhage. © 2014 American Society for Metabolic and Bariatric Surgery. All rights reserved.


PubMed | Unit Pregnancy, Reinier Of Graaf Group Of Hospitals, Jessa Hospital Hasselt and University Hospitals Leuven
Type: Journal Article | Journal: Surgery for obesity and related diseases : official journal of the American Society for Bariatric Surgery | Year: 2014

Neonatal intracranial bleedings and birth defects have been reported, possibly related to maternal vitamin K1 deficiency during pregnancy after bariatric surgery. The objective of this study was to investigate the effects of screening and supplementation on K1 serum levels in pregnant women with bariatric surgery, and to compare K1 levels and prothrombin time (PT %) in the first trimester with pregnant women without bariatric surgery.A prospective cohort study including 49 pregnant women with bariatric surgery. Nutritional deficiencies were prospectively screened. In case of observed low K1 serum levels, supplementation was provided. K1 serum levels and PT (%) during the first trimester were compared with a nonsurgical control group of 27 women.During the first trimester, most women had low K1 serum levels (<0.8 nmol/l). Mean vitamin K1 levels were significantly lower in the surgical group compared to the nonsurgical control group (.44 versus .64 nmol/l; P = .016). PT (%) remained in the normal range, The surgery group showed a higher mean PT compared to the controls (111.3 versus 98.9%; P<.001) Mean K1 serum levels in the study group were higher during the third than during the first trimester (P = .014). PT (%) was significantly higher during the second and third than during the first trimester (P = .004). Most of the coagulation factors, including II, V, VII, IX, and X, remained within normal ranges.Low circulating K1 appears to be common in pregnant women with and without bariatric surgery. Supplementation during pregnancy can restore vitamin K1 in women with bariatric surgery, potentially protecting the fetus and newborn against intracranial hemorrhage.


De Graaff L.C.G.,Reinier Of Graaf Group Of Hospitals | Van Essen M.,Reinier Of Graaf Group Of Hospitals | Schipper E.M.,Reinier Of Graaf Group Of Hospitals | Boom H.,Reinier Of Graaf Group Of Hospitals | Duschek E.J.J.,Reinier Of Graaf Group Of Hospitals
American Journal of Emergency Medicine | Year: 2012

Acute abdominal pain is the reason for 5% to 10% of all emergency department visits. In 1 in every 9 patients, operated on for an acute abdomen, laparotomy is negative. In a minority of patients, the acute abdomen is caused by side effects of medication. We present a case of unnecessary abdominal surgery in a patient with acute abdominal pain caused by intestinal angioedema (AE), which was eventually due to angiotensin-converting enzyme inhibitor (ACE-i) use. We hope that this case report increases awareness of this underdiagnosed side effect. Emergency department physicians, surgeons, internists, and family physicians should always consider ACE-i in the differential diagnosis of unexplained abdominal pain. Since early withdrawal of the medication causing intestinal AE can prevent further complications and, in some cases, needless surgery, we propose an altered version of the known diagnostic algorithm, in which ACE-i and nonsteroidal anti-inflammatory drugs-induced AE is excluded at an early stage. © 2012 Elsevier Inc. All rights reserved.


Van De Giessen E.,University of Amsterdam | Celik F.,Slotervaart Hospital | Schweitzer D.H.,Reinier Of Graaf Group Of Hospitals | Van Den Brink W.,University of Amsterdam | Booij J.,University of Amsterdam
Journal of Psychopharmacology | Year: 2014

Introduction: The neurotransmitter dopamine is important in the regulation of food intake. It is hypothesised that obese people experience less reward from food due to lower striatal dopamine release, which consequently leads to overeating. This study is the first to assess whether obese subjects have blunted striatal dopamine release. Method: We measured striatal dopamine D 2/3 receptor (DRD2/3) availability and amphetamine-induced striatal dopamine release in 15 obese and 15 age-matched, normal-weight women using [123I]iodobenzamide single photon emission computed tomography (SPECT) imaging. In addition, correlations with food craving were examined. Results: Baseline striatal DRD2/3 availability was lower in obese subjects (0.91±0.16) compared to controls (1.09±0.16; p=0.006). Amphetamineinduced dopamine release was significant in controls (7.5%±9.2; p=0.007) and not in obese subjects (1.2%±17.7; p=0.802), although the difference in release between groups (d=0.45) was not significant. Dopamine release positively correlated with the trait food craving in obese subjects. Conclusion: This study replicates previous findings of lower striatal DRD2/3 availability in obesity and provides preliminary data that obesity is associated with blunted dopamine release. The positive correlation between dopamine release and food craving in obesity may seem contradictory with the latter finding but is presumably related to heterogeneity within the obese subjects. © The Author(s) 2014.


De Graaff L.C.G.,Reinier Of Graaf Group Of Hospitals | Ten Broek M.R.J.,Reinier Of Graaf Group Of Hospitals | Schweitzer D.H.,Reinier Of Graaf Group Of Hospitals
Rheumatology International | Year: 2012

Adult-onset Still's disease (AOSD) is known as a systemic inflammatory disease of unknown etiology and pathogenesis, characterized by fever, skin eruptions, systemic organ involvement, and arthralgias. AOSD is difficult to diagnose because of its heterogeneous clinical manifestations and prevalence (although more prevalent in the young, onset of AOSD after the age of 60 has also been described), and absence of pathognomonic clinical features. The disease also lacks a specific diagnostic test. To date, association studies between AOSD and HLA loci have failed to indentify a genetic predisposition. The recent publication of entirely different PET-CT manifestations found in three patients who were supposed to have the same disease (AOSD), as well as the surprisingly different PET-CT images of our AOSD patient (accumulation in the carotids and large vessels of the legs), raises our suspicion that AOSD is actually not one entity but a constellation of disorders whose varying underlying pathologies are now being revealed by new imaging techniques. © Springer-Verlag 2011.


Van Haaften C.,Leiden University | Duke C.C.,University of Sydney | Weerheim A.M.,Leiden University | Smit N.P.M.,Leiden University | And 3 more authors.
Journal of Experimental and Clinical Cancer Research | Year: 2011

Background: Ovarian cancer remains the leading cause of death from gynaecological malignancy. More than 60% of the patients are presenting the disease in stage III or IV. In spite of combination of chemotherapy and surgery the prognosis stays poor for therapy regimen. Methods. The leaves of a plant endemic to Australia, Calomeria amaranthoides, were extracted and then fractionated by column chromatography. In vitro cytotoxicity tests were performed with fractions of the plant extract and later with an isolated compound on ovarian cancer cell lines, as well as normal fibroblasts at concentrations of 1-100 g/mL (crude extract) and 1-10 g/mL (compound). Cytotoxicity was measured after 24, 48 and 72 hours by using a non-fluorescent substrate, Alamar blue. In vivo cytotoxicity was tested on ascites, developed in the abdomen of nude mice after inoculation with human OVCAR3cells intraperitoneally. The rate of change in abdomen size for the mice was determined by linear regression and statistically evaluated for significance by the unpaired t test. Results: Two compounds were isolated by chromatographic fractionation and identified by 1H-NMR, 13C-NMR and mass spectrometry analyses, EPD, an -methylene sesquiterpene lactone of the eremophilanolide subtype, and EPA, an -methylene carboxylic acid. Cytotoxicity of EPD for normal fibroblasts at all time points IC50was greater than 10 g/mL, whereas, for OVCAR3cells at 48 hours IC50was 5.3 g/mL (95% confidence interval 4.3 to 6.5 g/mL). Both, the crude plant extract as well as EPD killed the cancer cells at a final concentration of 10 g/mL and 5 g/mL respectively, while in normal cells only 20% cell killing effect was observed. EPA had no cytotoxic effects. Changes in abdomen size for control versus Cisplatin treated mice were significantly different, P = 0.023, as were control versus EPD treated mice, P = 0.025, whereas, EPD versus Cisplatin treated mice were not significantly different, P = 0.13. Conclusions: For the first time both crude plant extract from Calomeria amaranthoides and EPD have been shown to have potent anti-cancer effects against ovarian cancer. © 2011 van Haaften et al; licensee BioMed Central Ltd.


PubMed | Reinier Of Graaf Group Of Hospitals and Rijnstate Hospital
Type: Journal Article | Journal: Surgery for obesity and related diseases : official journal of the American Society for Bariatric Surgery | Year: 2016

After Roux-en-Y gastric bypass, calcium and vitamin D deficiencies are frequently reported. In the presence of adequate vitamin D levels, calcium deficiency is caused by a lower efficacy of the intestinal calcium transport.To investigate whether the use of a simple clinical score quantifying bowel habits (fecal score [FS]) correlates with the degree of secondary hyperparathyroidism that arises to compensate for calcium deficiency postsurgery.Large peripheral hospital.Seventy-five patients supplemented with calcium and vitamin D were prospectively studied before and 6 and 12 months after Roux-en-Y gastric bypass. FS, calcium (mmol/L), phosphate (mmol/L), magnesium (mmol/L), vitamin D (nmol/L), and parathyroid hormone (PTH; pmol/L) were measured in each patient.Mean body mass index was 44.75.4 kg/mFS is positively correlated with secondary hyperparathyroidism using vitamin D-adjusted PTH levels as a biochemical marker. The present study in humans confirms the relation reported in animal studies. These results emphasize that managing stool habits are important after bariatric surgery.

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