Genetic glucocorticoid receptor variants differ between ethnic groups but do not explain variation in age of diabetes onset, metabolic and inflammation parameters in patients with type 2 diabetes

AimsThe effect of excess glucocorticoid receptor (GR) stimulation through glucocorticoid medication or cortisol on glucose metabolism is well established. There are genetic GR variants that result in increased or decreased GR stimulation. We aimed to determine the prevalence of genetic GR variants in different ethnic groups in a cohort of patients with type 2 diabetes, and we aimed to determine their association with age of diabetes onset and metabolic and inflammation parameters.MethodsA cross-sectional analysis was performed in a multiethnic cohort (n = 602) of patients with established type 2 diabetes. Polymorphisms in the GR gene that have previously been associated with altered glucocorticoid sensitivity (TthIIII, ER22/23EK N363S, BclI and 9β) were determined and combined into 6 haplotypes. Associations with age of diabetes onset, HbA1c, hs-CRP and lipid values were evaluated in multivariate regression models.ResultsThe prevalence of the SNPs of N363S and BclI was higher in Dutch than in non-Dutch patients. We observed a lower prevalence of the SNP 9β in Dutch, South(East) Asian and Black African patients versus Turkish and Moroccan patients. We did not detect an association between SNPs and diabetes age of onset or metabolic parameters. We only found a trend for lower age of onset and higher HbA1c in patients with 1 or 2 copies of haplotype 3 (TthIIII + 9β).ConclusionsThe prevalence of genetic GR variants differs between patients of different ethnic origins. We did not find a clear association between genetic GR variants and age of diabetes onset or metabolic and inflammation parameters. This indicates that the clinical relevance of GR variants in patients with established type 2 diabetes is limited

N-acetylcysteine reduces oxidative stress in sickle cell patients

Oxidative stress is of importance in the pathophysiology of sickle cell disease (SCD). In this open label randomized pilot study the effects of oral N-acetylcysteine (NAC) on phosphatidylserine (PS) expression as marker of cellular oxidative damage (primary end point), and markers of hemolysis, coagulation and endothelial activation and NAC tolerability (secondary end points) were studied. Eleven consecutive patients (ten homozygous [HbSS] sickle cell patients, one HbSβ0-thalassemia patient) were randomly assigned to treatment with either 1,200 or 2,400 mg NAC daily during 6 weeks. The data indicate an increment in whole blood glutathione levels and a decrease in erythrocyte outer membrane phosphatidylserine exposure, plasma levels of advanced glycation end-products (AGEs) and cell-free hemoglobin after 6 weeks of NAC treatment in both dose groups. One patient did not tolerate the 2,400 mg dose and continued with the 1,200 mg dose. During the study period, none of the patients experienced painful crises or other significant SCD or NAC related complications. These data indicate that N-acetylcysteine treatment of sickle cell patients may reduce SCD related oxidative stress

Differential Gene Expression Changes in Children with Severe Dengue Virus Infections

Dengue virus infection is an impressively emerging disease that can be fatal in severe cases. It is not precisely clear why some patients progress to severe disease whereas most patients only suffer from a mild infection. In severe disease, a “cytokine storm” is induced, which indicates the release of a great number of inflammatory mediators (“cytokines”). Evidence suggested that a balance could be involved between protective and pathologic cytokine release patterns. We studied this concept in a cohort of Indonesian children with severe dengue disease using a gene expression profiling method

Dichotomal Effect of the Coumadin Derivative Warfarin on Inflammatory Signal Transduction

Warfarin, a widely prescribed drug for preventing thrombosis, is thought to act solely through inhibition of vitamin K-dependent coagulation factors. Low concentrations of warfarin inhibit interleukin-6 production and phosphorylation of I-κB but not activation of p38 mitogen-activated protein kinase. Thus, warfarin inhibits inflammatory signal transduction, and this may contribute to clinical effects of warfarin

The Significance of Attachment Representations for Quality of Life One Year Following Gastric Bypass Surgery: A Longitudinal Analysis

Background: Quality of life after bariatric surgery may, among other things, depend on patients' attachment representations such as anxiety about rejection and abandonment (attachment anxiety) and avoidance of intimacy and interdependence (attachment avoidance). The aim of this study was to examine whether attachment representations, independent of body mass index (BMI), are associated with the level and course of physical functioning and mental well-being after gastric bypass surgery. Method: A total of 131 patients applying for a Roux-en-Y gastric bypass operation agreed to participate in this longitudinal study. Patients' attachment representations (ECR-R) were measured before surgery, and quality of life dimensions (physical functioning and mental well-being, SF-36) were measured before surgery and 1, 3, 6, and 12 months following surgery. Linear mixed effect models were used in analyses. Results: Physical functioning (p <0.001) improved, and mental well-being worsened (p = 0.002) in the postoperative interval. Both attachment anxiety (p = 0.005) and attachment avoidance (p <0.001) were associated with a lower level of mental well-being, but not with the postoperative course of quality of life. Conclusions: Our study suggests that bariatric surgery leads to improvement in physical functioning but not mental well-being. Results highlight that patients with insecure attachment representations should be protected against unrealistic expectations regarding improvement of mental well-being after surgery

Coping style as a mediator between attachment and mental and physical health in patients suffering from morbid obesity

The presence of mental health problems and limitations in physical functioning is high in patients suffering from morbid obesity. The purpose of the current study was to examine the mediating role of coping style in the relationship between attachment representations and mental health and physical functioning in a morbidly obese population. A total of 299 morbidly obese patients who were referred to the Slotervaart bariatric surgery unit in Amsterdam, the Netherlands, completed self-report questionnaires assessing adult attachment style (Experiences in Close Relationship-Revised Questionnaire), coping style (Utrecht Coping List), and patients physical functioning and mental health (Short Form-36). Attachment anxiety (beta = -.490, p <.001) and attachment avoidance (3 = -.387, p <.001) were both found to be related to mental health. In addition, attachment anxiety was also found to be related to physical functioning (beta = - .188,p <.001). Coping style partly mediated these associations. Findings suggest that coping mediates the association between attachment anxiety and attachment avoidance on the one hand and mental health and physical functioning in patients with morbid obesity on the other han

Psychologists' evaluation of bariatric surgery candidates influenced by patients' attachment representations and symptoms of depression and anxiety

This study examines whether patients self-reported attachment representations and levels of depression and anxiety influenced psychologists' evaluations of morbidly obese patients applying for bariatric surgery. A sample of 250 patients (mean age 44, 84 % female) who were referred for bariatric surgery completed questionnaires to measure adult attachment and levels of depression and anxiety. Psychologists rated patients' suitability for bariatric surgery using the Cleveland Clinic Behavioural Rating System (CCBRS), unaware of the results of the completed questionnaires. Attachment anxiety (OR = 2.50, p = .01) and attachment avoidance (OR = 3.13, p = .001) were found to be associated with less positive evaluations on the CCBRS by the psychologists, and symptoms of depression and anxiety mediated this association. This study strongly supports the notion that patients' attachment representations influence a psychologist's evaluation in an indirect way by influencing the symptoms of depression and anxiety patients report during an assessment interview. The clinical implications of these findings are discusse

Unusual presentation of Lemierre's syndrome: two cases and a review

Lemierre's syndrome is a potentially fatal disease that usually presents with oropharyngeal infection, followed by sepsis, thrombosis of the internal jugular vein and septic emboli. Most cases are caused by the Gram-negative, anaerobic Fusobacterium necrophorum. We present two patients with an atypical presentation of Lemierre's syndrome and a review. These cases illustrate that a positive blood culture for F necrophorum, even without the presence of clinical symptoms pointing towards thrombosis of the internal jugular vein, justifies further radiological testing for thrombophlebitis of the internal jugular vein. Blood Coagul Fibrinolysis 20:466-469 (C) 2009 Wolters Kluwer Health | Lippincott Williams & Wilkin

The effect of hyperthyroidism on procoagulant, anticoagulant and fibrinolytic factors

Several coagulation and fibrinolytic parameters appear to be affected by thyroid hormone excess; however, the net effect on the haemostatic system remains unclear. We aimed to update our previous review and systematically summarise and meta-analyse the data by assessing the effects of thyrotoxicosis on the coagulation and fibrinolytic system in vivo . Data sources included MEDLINE (2006-2012), EMBASE (2006-2012), and reference lists. The sources were combined with our previous search containing studies from 1980-2006. Eligible studies were all observational or experimental studies. Two investigators independently extracted data and rated study quality. Weighted mean proportion and 95% confidence intervals were calculated and pooled using a fixed and a random-effects model. A total of 29 articles consisting of 51 studies were included, as in several articles more than one study was described. We included four intervention (before and after treatment in hyperthyroid patients), five cross-sectional (hyperthyroid subjects and euthyroid controls), and four experimental (before and after use of thyroid hormone in euthyroid subjects) medium/high quality studies for meta-analysis. We found that thyrotoxicosis shifts the haemostatic balance towards a hypercoagulable and hypofibrinolytic state with a rise in factors VIII and IX, fibrinogen, von Willebrand factor, and plasminogen activator inhibitor-1. This was observed in endogenous and exogenous thyrotoxicosis, and in subclinical as well as overt hyperthyroidism. We conclude that both subclinical and overt hyperthyroidism induce a prothrombotic state, which is therefore likely to be a risk factor for venous thrombosi