Vascular complications in kidney disease

The main objectives of this thesis were to investigate the association between kidney disease and venous and arterial thrombosis and to provide insight in the mechanism of the association between kidney disease and thrombosis. Furthermore, the mortality risks for hemodialysis patients with catheter, fistula and graft vascular accesses were investigated. Our studies showed that kidney disease was associated with an increased risk of venous thrombosis. We showed that patients with chronic kidney disease stages 1__3 (early stages) had an almost 2-fold increased risk of venous thrombosis as compared with subjects without chronic kidney disease. We also showed that patients with a severely decreased kidney function (estimated glomerular filtration rate <30 ml/min) had a 6-fold increased risk of venous thrombosis as compared with persons with a normal kidney function. Furthermore, it was shown that dialysis patients have increased risks of myocardial infarction and ischemic stroke. Dialysis patients with a catheter had increased mortality risks as compared with dialysis patients with an arteriovenous access (fistula or graft). An important mechanism for the increased thrombosis risk in patients with a kidney disease could be hypercoagulability (increased factor VIII and von Willebrand factor levels).UBL - phd migration 201

Attitudes towards psychopharmacology and psychotherapy in psychiatric patients with and without migration background

Background: Sociodemographic factors, attitude towards treatment and acculturation may be important factors influencing the decision of immigrants to seek and maintain psychiatric treatment. A better understanding of these factors may significantly improve treatment adherence and outcome in these patients. Therefore, we investigated factors associated the attitude towards psychotherapy and medication in a sample of psychiatric outpatients with and without migration background. Methods: N = 381 patients in a psychiatric outpatient unit offering specialized treatment for migrants were included in this study. Attitude towards psychotherapy was assessed using the Questionnaire on Attitudes Toward Psychotherapeutic Treatment, attitude towards medication with the Drug Attitude Inventory-10. Acculturation, symptom load and sociodemographic variables were assessed in a general questionnaire. Statistical analyses included analyses of covariance and hierarchical regression. Results: Patients of Turkish and Eastern European origin reported a significantly more positive attitude towards medication than patients without migration background. When controlling for sociodemographic and clinical variables, we did not observe any significant differences in attitude towards psychotherapy. Acculturation neither influenced the attitude towards psychotherapy nor towards medication. Conclusion: Our study indicates that sociodemographic and clinical factors may be more relevant for patients´ attitudes towards treatment than acculturation. Considering these factors in psychiatric treatment of patients with migration background may improve treatment outcome and adherence

Validation of risk scores for ischaemic stroke in atrial fibrillation across the spectrumof kidney function

Aims The increasing prevalence of ischaemic stroke (IS) can partly be explained by the likewise growing number of patients with chronic kidney disease (CKD). Risk scores have been developed to identify high-risk patients, allowing for personalized anticoagulation therapy. However, predictive performance in CKD is unclear. The aim of this study is to validate six commonly used risk scores for IS in atrial fibrillation (AF) patients across the spectrum of kidney function.Methods and results Overall, 36 004 subjects with newly diagnosed AF from SCREAM (Stockholm CREAtinine Measurements), a healthcare utilization cohort of Stockholm residents, were included. Predictive performance of the AFI, CHADS(2), Modified CHADS(2), CHA(2)DS(2)-VASc, ATRIA, and GARFIELD-AF risk scores was evaluated across three strata of kidney function: normal kidney function [estimated glomerular filtration rate (eGFR) >60 mL/min/1.73 m(2)], mild CKD (eGFR 30-60 mL/min/1.73 m(2)), and advanced CKD (eGFR <30 mL/min/1.73 m(2)). Predictive performance was assessed by discrimination and calibration. During 1.9 years, 3069 (8.5%) patients suffered an IS. Discrimination was dependent on eGFR: the median c-statistic in normal eGFR was 0.75 (range 0.68-0.78), but decreased to 0.68 (0.58-0.73) and 0.68 (0.55-0.74) for mild and advanced CKD, respectively. Calibration was reasonable and largely independent of eGFR. The Modified CHADS(2) score showed good performance across kidney function strata, both for discrimination [c-statistic: 0.78 (95% confidence interval 0.77-0.79), 0.73 (0.71-0.74) and 0.74 (0.69-0.79), respectively] and calibration.Conclusion In the most clinically relevant stages of CKD, predictive performance of the majority of risk scores was poor, increasing the risk of misclassification and thus of over- or undertreatment. The Modified CHADS2 score performed good and consistently across all kidney function strata, and should therefore be preferred for risk estimation in AF patients.Clinical epidemiolog

Bleeding risk of haemodialysis and peritoneal dialysis patients

Background. Dialysis patients have an increased bleeding risk as compared with the general population. However, there is limited information whether bleeding risks are different for patients treated with haemodialysis (HD) or peritoneal dialysis (PD). From a clinical point of view, this information could influence therapy choice. Therefore the aim of this study was to investigate the association between dialysis modality and bleeding risk.Methods. Incident dialysis patients from the Netherlands Cooperative Study on the Adequacy of Dialysis were prospectively followed for major bleeding events over 3years. Hazard ratios with 95% confidence intervals (CIs) were calculated for HD compared with PD using a time-dependent Cox regression analysis, with updates on dialysis modality.Results. In total, 1745 patients started dialysis, of whom 1211 (69.4%) received HD and 534 (30.6%) PD. The bleeding rate was 60.8/1000 person-years for HD patients and 34.6/1000 person-years for PD patients. The time-dependent Cox regression analysis showed that after adjustment for age, sex, primary kidney disease, prior bleeding, cardiovascular disease, antiplatelet drug use, vitamin K antagonist use, erythropoietin use, arterial hypertension, residual glomerular filtratin rate, haemoglobin and albumin levels, bleeding risk for HD patients compared with PD increased 1.5-fold (95% CI 1.0-2.2).Conclusions. In this large prospective cohort of incident dialysis patients, HD patients had an increased bleeding risk compared with PD patients. In particular, HD patients with a history of prior bleeding had an increased bleeding risk.Clinical epidemiolog

The HLA Class II Allele Allele DRB1*15 is over-represented in patients with Idiopathic Pulmonary Fibrosis

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive and medically refractory lung disease with a grim prognosis. Although the etiology of IPF remains perplexing, abnormal adaptive immune responses are evident in many afflicted patients. We hypothesized that perturbations of human leukocyte antigen (HLA) allele frequencies, which are often seen among patients with immunologic diseases, may also be present in IPF patients. METHODS/PRINCIPAL FINDINGS: HLA alleles were determined in subpopulations of IPF and normal subjects using molecular typing methods. HLA-DRB1*15 was over-represented in a discovery cohort of 79 Caucasian IPF subjects who had lung transplantations at the University of Pittsburgh (36.7%) compared to normal reference populations. These findings were prospectively replicated in a validation cohort of 196 additional IPF subjects from four other U.S. medical centers that included both ambulatory patients and lung transplantation recipients. High-resolution typing was used to further define specific HLA-DRB1*15 alleles. DRB1*1501 prevalence in IPF subjects was similar among the 143 ambulatory patients and 132 transplant recipients (31.5% and 34.8%, respectively, p = 0.55). The aggregate prevalence of DRB1*1501 in IPF patients was significantly greater than among 285 healthy controls (33.1% vs. 20.0%, respectively, OR 2.0; 95%CI 1.3-2.9, p = 0.0004). IPF patients with DRB1*1501 (n = 91) tended to have decreased diffusing capacities for carbon monoxide (DL(CO)) compared to the 184 disease subjects who lacked this allele (37.8±1.7% vs. 42.8±1.4%, p = 0.036). CONCLUSIONS/SIGNIFICANCE: DRB1*1501 is more prevalent among IPF patients than normal subjects, and may be associated with greater impairment of gas exchange. These data are novel evidence that immunogenetic processes can play a role in the susceptibility to and/or manifestations of IPF. Findings here of a disease association at the HLA-DR locus have broad pathogenic implications, illustrate a specific chromosomal area for incremental, targeted genomic study, and may identify a distinct clinical phenotype among patients with this enigmatic, morbid lung disease

The HLA class II allele DRB1*1501 is over-represented in patients with idiopathic pulmonary fibrosis

Background: Idiopathic pulmonary fibrosis (IPF) is a progressive and medically refractory lung disease with a grim prognosis. Although the etiology of IPF remains perplexing, abnormal adaptive immune responses are evident in many afflicted patients. We hypothesized that perturbations of human leukocyte antigen (HLA) allele frequencies, which are often seen among patients with immunologic diseases, may also be present in IPF patients. Methods/Principal Findings: HLA alleles were determined in subpopulations of IPF and normal subjects using molecular typing methods. HLA-DRB1*15 was over-represented in a discovery cohort of 79 Caucasian IPF subjects who had lung transplantations at the University of Pittsburgh (36.7%) compared to normal reference populations. These findings were prospectively replicated in a validation cohort of 196 additional IPF subjects from four other U.S. medical centers that included both ambulatory patients and lung transplantation recipients. High-resolution typing was used to further define specific HLA-DRB1*15 alleles. DRB1*1501 prevalence in IPF subjects was similar among the 143 ambulatory patients and 132 transplant recipients (31.5% and 34.8%, respectively, p = 0.55). The aggregate prevalence of DRB1*1501 in IPF patients was significantly greater than among 285 healthy controls (33.1% vs. 20.0%, respectively, OR 2.0; 95%CI 1.3-2.9, p = 0.0004). IPF patients with DRB1*1501 (n = 91) tended to have decreased diffusing capacities for carbon monoxide (DLCO) compared to the 184 disease subjects who lacked this allele (37.8±1.7% vs. 42.8±1.4%, p = 0.036). Conclusions/Significance: DRB1*1501 is more prevalent among IPF patients than normal subjects, and may be associated with greater impairment of gas exchange. These data are novel evidence that immunogenetic processes can play a role in the susceptibility to and/or manifestations of IPF. Findings here of a disease association at the HLA-DR locus have broad pathogenic implications, illustrate a specific chromosomal area for incremental, targeted genomic study, and may identify a distinct clinical phenotype among patients with this enigmatic, morbid lung disease

Indoor air quality in a restaurant kitchen using margarine for deep-frying

Indoor air quality has a great impact on human health. Cooking, in particular frying, is one of the most important sources of indoor air pollution. Indoor air CO, CO2, particulate matter (PM), and volatile organic compound (VOC) concentrations, including aldehydes, were measured in the kitchen of a small establishment where a special deep-frying margarine was used. The objective was to assess occupational exposure concentrations for cooks of such restaurants. While individual VOC and PM2.5 concentrations were measured before, during, and after frying events using active sampling, TVOC, PM10, CO, CO2, temperature, and relative humidity were continuously monitored through the whole period. VOC and aldehyde concentrations did not increase to considerable levels with deep-frying compared to the background and public indoor environment levels, whereas PM10 increased significantly (1.85 to 6.6 folds). The average PM2.5 concentration of the whole period ranged between 76 and 249 μg/m3. Hence, considerable PM exposures could occur during deep-frying with the special margarine, which might be sufficiently high to cause health effects on cooks considering their chronic occupational exposures.Dokuz Eylul University (BAP-2011.KB.SAG.017

Synthesis of macrocyclic receptors with intrinsic fluorescence featuring quinizarin moieties

An unprecedented class of macrocycles with intrinsic fluorescence consisting of phenolic trimers and quinizarin is developed. Though they are lacking strong hydrogen bonds as observed in calixarenes, the two examples introduced here each adopt a vase-like conformation with all four aromatic units pointing in one direction (syn orientation). This “cone” conformation has been confirmed by NMR spectroscopy, molecular modeling, and X-ray crystallography. The laminar, electron-rich fluorophore as part of the macrocycle allows additional contacts to enclosed guest molecules