Common genetic variation in the Estrogen Receptor Beta (ESR2) gene and osteoarthritis: results of a meta-analysis

Background: The objective of this study was to examine the relationship between common genetic variation of the ESR2 gene and osteoarthritis.Methods: In the discovery study, the Rotterdam Study-I, 7 single nucleotide polymorphisms (SNPs) were genotyped and tested for association with hip (284 cases, 2772 controls), knee (665 cases, 2075 controls), and hand OA (874 cases, 2184 controls) using an additive model. In the replication stage one SNP (rs1256031) was tested in an additional 2080 hip, 1318 knee and 557 hand OA cases and 4001, 2631 and 1699 controls respectively. Fixed- and random-effects meta-analyses were performed over the complete dataset including 2364 hip, 1983 knee and 1431 hand OA cases and approximately 6000 controls.Results: The C allele of rs1256031 was associated with a 36% increased odds of hip OA in women of the Rotterdam Study-I (OR 1.36, 95% CI 1.08-1.70, p = 0.009). Haplotype analysis and analysis of knee- and hand OA did not give additional information. With the replication studies, the meta-analysis did not show a significant effect of this SNP on hip OA in the total population (OR 1.06, 95% CI 0.99-1.15, p = 0.10). Stratification according to gender did not change the results. In this study, we had 80% power to detect an odds ratio of at least 1.14 for hip OA (α = 0.05).Conclusion: This study showed that common genetic variation in the ESR2 gene is not likely to influence the risk of osteoarthritis with effects smaller than a 13% increase

Dutch guideline on total hip prosthesis

Contains fulltext : 97840.pdf (publisher's version ) (Open Access

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Guideline for the Diagnostic Pathway in Patients with Acute Abdominal Pain

Introduction: Diagnostic practice for acute abdominal pain at the Emergency Department varies widely and is mostly based on doctor's preferences. We aimed at developing an evidence-based guideline for the diagnostic pathway of patients with abdominal pain of non-traumatic origin. Methods: All available international literature on patients with acute abdominal pain was identified and graded according to their methodological quality by members of the multidisciplinary steering group. A guideline was synthetized, providing evidence-based recommendations together with considerations based on expertise of group members, patient preferences, costs, availability of facilities, and organizational aspects. Conclusions and Recommendations: Definition: Uniform terminology is needed in patients with acute abdominal pain to avoid difficulty in interpretation and ease comparison of findings between studies. We propose the use of the following definition for acute abdominal pain: pain of nontraumatic origin with a maximum duration of 5 days. Clinical diagnosis: Clinical evaluation is advised to differentiate between urgent and nonurgent causes. The diagnostic accuracy of clinical assessment is insufficient to identify the correct diagnosis but can discriminate between urgent and nonurgent causes. Patients suspected of nonurgent diagnoses can safely be reevaluated the next day. Based on current literature, no conclusions can be drawn on the differences in accuracy between residents and specialists. No conclusions can be drawn on the influence of a gynecological consultation. In patients suspected of an urgent condition, additional imaging is justified. CRP and WBC count alone are insufficient to discriminate urgent from nonurgent diagnoses. Diagnostic imaging: There is no place for conventional radiography in the work-up of patients with acute abdominal pain due to the lack of added value on top of clinical assessment. Computed tomography leads to the highest sensitivity and specificity in patients with acute abdominal pain. Positive predictive value of ultrasound is comparable with CT and therefore preferred as the first imaging modality due to the downsides of computed tomography; negative or inconclusive ultrasound is followed by CT. Based on current literature, no conclusions can be drawn on the added value of a diagnostic laparoscopy in the work-up of patients with acute abdominal pain. Antibiotic treatment should be started within the first hour after recognition of sepsis. Administration of opioids (analgesics) decreases the intensity of the pain and does not affect the accuracy of physical examination. (C) 2015 S. Karger AG, Base

Richtlijn 'Diagnostiek acute buikpijn bij volwassenen'

The interdisciplinary, evidence-based guideline 'Diagnostics in acute abdominal pain in adults' describes the optimal in-hospital diagnostic work-up of patients with acute abdominal pain. Amongst other recommendations, the guideline advises the use of C-reactive protein and white blood cell count to differentiate urgent from non-urgent causes in an adult with acute abdominal pain presenting at the Emergency Department. If there is clinical suspicion of an urgent condition the guideline advises that additional imaging be performed. The guideline states that conventional imaging (plain abdominal - or chest x-ray) is unnecessary as this is of no benefit. Additionally the guideline recommends that patients with acute abdominal pain and severe sepsis or septic shock are started on antibiotic treatment within an hour at the Emergency Department and not to wait for the diagnostic procedures to be complete

6-Mercaptopurine Inhibits Atherosclerosis in Apolipoprotein E*3-Leiden Transgenic Mice Through Atheroprotective Actions on Monocytes and Macrophages

Objective-6-Mercaptopurine (6-MP), the active metabolite of the immunosuppressive prodrug azathioprine, is commonly used in autoimmune diseases and transplant recipients, who are at high risk for cardiovascular disease. Here, we aimed to gain knowledge on the action of 6-MP in atherosclerosis, with a focus on monocytes and macrophages. Methods and Results-We demonstrate that 6-MP induces apoptosis of THP-1 monocytes, involving decreased expression of the intrinsic antiapoptotic factors B-cell CLL/Lymphoma-2 (Bcl-2) and Bcl2-like 1 (Bcl-xL). In addition, we show that 6-MP decreases expression of the monocyte adhesion molecules platelet endothelial adhesion molecule-1 (PECAM-1) and very late antigen-4 (VLA-4) and inhibits monocyte adhesion. Screening of a panel of cytokines relevant to atherosclerosis revealed that 6-MP robustly inhibits monocyte chemoattractant chemokine-1 (MCP-1) expression in macrophages stimulated with lipopolysaccharide (LPS). Finally, local delivery of 6-MP to the vessel wall, using a drug-eluting cuff, attenuates atherosclerosis in hypercholesterolemic apolipoprotein E*3-Leiden transgenic mice (P <0.05). In line with our in vitro data, this inhibition of atherosclerosis by 6-MP was accompanied with decreased lesion monocyte chemoattractant chemokine-1 levels, enhanced vascular apoptosis, and reduced macrophage content. Conclusion-We report novel, previously unrecognized atheroprotective actions of 6-MP in cultured monocytes/macrophages and in a mouse model of atherosclerosis, providing further insight into the effect of the immunosuppressive drug azathioprine in atherosclerosis. (Arterioscler Thromb Vasc Biol. 2010;30:1591-1597.