24 research outputs found

    Taal en veiligheid: een groeiend nieuw werkveld [Language and security: a growing new field of work]

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    Language issues cause safety problems at work. This study presents an inventory of scientific studies in the economic sectors and assesses which level of risk management they address. Complications with language have not been investigated comprehensively across sectors as a causal factor in accidents. This leaves language related risks partially unknown, hence uncontrolled. There is lack of insight in both the nature and magnitude of this danger in healthcare, agricultural, transport and construction sectors. Healthcare is especially troublesome since patients might be victims of language related accidents due to their presence and interaction. The same may occur to members of the public in traffic accidents. In transport and agricultural sectors safety measures were taken without any analysis of language related risks. This study shows that scientific research on ‘language and safety’ is in its infancy and requires priority on the research agenda

    The Pathophysiology ofProtein-Overload Proteinur a

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    Alterations in glomerular function and structure were studied in protein-overload nephrosis in the rat induced by intraperitoneal administration of bovine serum albumin (BSA). Fractional clearance (C/GFR) studies using inulin and tracer proteins of different molecular size and charge revealed in proteinuric rats 1) unchanged glomerular filtration rate and renal plasma flow; 2) a 34-fold increase in C/GFR of rat serum albumin, reaching values similar to BSA; 3) a 2-fold increase in C/GFR for anionic horse radish peroxidase (HRP), but normal values for neutral and cationic HRP, and 4) an 11-and 3-fold increase for heter-THE GLOMERULAR capillary wall (GCW) constitutes a semipermeable, size-and charge-selective filter between the glomerular capillary lumen and the urinary space." 2 Under normal conditions, the ultrafiltrate is virtually devoid ofproteins. Increased permeability to plasma proteins may be caused by a number ofimmunopathologic, toxic, or hemodynamic events leading to damage ofthe endothelial and/or epithelial cells and disruption of the glomerular basement membrane (GBM).3'4 Increased passage of proteins from the capillary lumen to the urinary space has also been observed in man and in laboratory animals after parenteral administration of high amounts of proteins.5-26 Studies on experimental models of proteinoverload proteinuria have shown that increased transcapillary movement of proteins causes degenerative changes ofglomerular epithelial cells characterized by swelling, vacuolization, increased reabsorption droplets, loss of foot processes, and lifting from the underlying GBM.'1"220 Recent studies have reported on functional and structural glomerular alterations in rat models of protein-overload proteinuria, providing conflicting evidence with regard to changes in sizeand charge-selective properties ofthe GCW. In BSAinduced proteinuria sieving curves of neutral dextrans were found to be normal, suggestive ofan intact sieving filter.23 In contrast, in the same model inFrom the Departments ofPathology and Nephrology, State University ofLeiden, Leiden, The Netherlands ologous IgG and IgM, respectively. Glomerular epithelial cells showed degenerative changes, but the distribution of anionic sites in the glomerular basement membrane was found to be unaltered, as determined by polyethyleneimine binding studies. In summary, an elevation of serum albumin concentration resulted in an increased transcapillary albumin transport. This was found to lead to degenerative changes of glomerular epithelial cells with development of large pore defects, which were completely reversible. (Am J Pathol 1987, 129:64-73) creased filtration ofIgG24 and ofanionic ferritin22 was found, and morphologic studies revealed detachment of glomerular epithelium from the underlying GBM,20,26 a lesion which is usually associated with a large pore defect.27-29 Immunoelectrophoresis of urinary proteins revealed that albumin constitutes the majority of filtered proteins, but a considerable proportion of the globulin fraction also reaches the urine. 13"16,19'20 In addition, the role of hemodynamic factors, such as possibly increased flows and pressures, has not been studied in detail. This article describes pathophysiologic mechanisms in protein-overload proteinuria in female Wistar rats rendered proteinuric by daily administration ofbovine serum albumin (BSA). Hematocrits, serum total protein, rat serum albumin (RSA), and BSA concentrations were monitored during and after BSA administration. Alterations in charge-and size-selective properties of the GCW after two doses of BSA were studied by measuring proteinuria and fractiona

    Homocysteine, S-adenosylmethionine and S-adenosylhomocysteine are associated with retinal microvascular abnormalities: the Hoorn Study

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    The aim of the present study was to investigate the relationship between homocysteine and homocysteine metabolism components and retinal microvascular disorders in subjects with and without Type 2 diabetes. In this population-based study of 256 participants, aged 60-85 years, we determined total plasma homocysteine, SAM (S-adenosylmethionine) and SAH (S-adenosylhomocysteine) in plasma and erythrocytes, total folate in serum and erythrocytes, 5-MTHF (5-methyltetrahydrofolate), and vitamins B12 and B6. Participants were examined ophthalmologically by means of indirect funduscopy and two-field 45° fundus photography, and were graded for retinopathy and retinal sclerotic vessel abnormalities. A computer-assisted method was used to measure retinal vessel diameters. Total plasma homocysteine was inversely associated with retinal arteriolar diameters {standardized β, -0.20 [95% CI (confidence interval), -0.33 to - 0.07]} or a decrease of 3.78 μm CRAEs (central retinal arteriolar equivalents) per 1 S.D. increase in homocysteine level (= 4.6 μmol/l). In addition, the SAM/SAH ratio in plasma was inversely associated with retinal sclerotic vessel abnormalities and retinopathy [odds ratios, 0.61 (95% CI, 0.39-0.96) and 0.50 (95% CI, 0.30-0.83) per 1 S.D. respectively]. The associations were independent of age, sex, glucose tolerance status, other homocysteine metabolism components and cardiovascular risk factors. In conclusion, the results of the present study support the concept that total plasma homocysteine and a low SAM/SAH ratio in plasma, which may reflect reduced transmethylation reactions, may contribute to the pathogenesis of (retinal) microangiopathy. © The Authors

    Homocysteine and blood pressure

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    Several studies, some population-based, have linked plasma homocysteine levels to blood pressure, especially systolic pressure. The strength of this association is weak, but may be underestimated due to inaccurate blood pressure measurements. In addition, the association may be confounded by renal function. Observations that homocysteine-lowering therapies with folic acid-based treatments have been followed by decreases in blood pressure, however, raise the possibility that the link between homocysteine and blood pressure is real, which is important as homocysteine levels can easily be lowered by folic acid-based regimens. Mechanisms that could explain the relationship between homocysteine and blood pressure include increased arterial stiffness, endothelial dysfunction with decreased availability of nitric oxide, low folate status, and insulin resistance. So far, however, no evidence has been provided that these mechanisms are operative in humans. Ongoing large intervention studies with homocysteine-lowering vitamins may indicate whether blood pressure is indeed lowered by these vitamins, whether the blood pressure decrease, if any, is explained by the decrease in homocysteine levels, and whether a vitamin treatment-associated decrease in cardiovascular morbidity (if any) is explained by the decrease in blood pressure

    Homocysteine and asymmetric dimethylarginine (ADMA): Biochemically linked but differently related to vascular disease in chronic kidney disease

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    Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, is formed by methylation of arginine residues in proteins and released after proteolysis. In this reaction, S-adenosylmethionine is methyldonor and S-adenosylhomocysteine the demethylated product. ADMA and homocysteine are thus biochemically linked. Both plasma homocysteine and ADMA concentrations are increased in patients with renal dysfunction, probably as a result of an impairment in their metabolic, but not urinary, clearance. Hyperhomocysteinemia has been associated with an increased risk of cardiovascular disease in end-stage renal disease, especially in patients without malnutrition and inflammation. Also, plasma ADMA levels have been associated with cardiovascular disease in renal failure patients. Both homocysteine and ADMA are thought to mediate their adverse vascular effects by impairing endothelial, nitric oxide-dependent function resulting in decreased vasodilatation, increased smooth muscle cell proliferation, platelet dysfunction and increased monocyte adhesion. At the same time, it has been shown that the correlation between plasma ADMA and homocysteine is weak and that, in renal patients, the association of plasma ADMA carotid intima-media thickness, cardiovascular events and overall mortality is independent of homocysteine. This indicates that the negative vascular effects of ADMA and homocysteine have a different etiology. Treatment with folic acid substantially lowers homocysteine, but not ADMA concentration. So far, homocysteine-lowering therapy has not been very successful in decreasing cardiovascular disease. In patients with renal failure, ADMA reduction may be an interesting new goal in the prevention of cardiovascular disease

    Effect of a treatment strategy consisting of pravastatin, vitamin E, and homocysteine lowering on carotid intima-media thickness, endothelial function, and renal function in patients with mild to moderate chronic kidney disease: Results from the anti-oxidant therapy in chronic renal insufficiency (ATIC) study

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    Background: Patients with chronic kidney disease have an increased risk of cardiovascular disease. Oxidative stress has been proposed to play a role in the development of cardiovascular disease among these patients. Methods:Weconducted a randomized, double-blind trial in 93 patients (Cockcroft-Gault equation: creatinine clearance, 38±15 [mean±SD] mL/min per 1.73 m 2 [0.63±0.25 mL/s per m2]) to investigate the effect of a treatment strategy designed primarily to achieve stepwise oxidative stress reduction oncommoncarotid intima-media thickness (CC-IMT), brachial artery flow-mediated dilatation (BA-FMD), albuminuria, and renal function. The treatment group received a regimen of pravastatin to which vitamin E supplementation was added after 6 months and homocysteine-lowering therapy after another 6 months. Blood pressure in both groups was managed according to a standard protocol. The placebo group received matching placebos. Measurement of CC-IMT and BA-FMD was performed at randomization after 6, 12, and 18 months. Patients were followed up for 2 years. Generalized estimating equations were used for analysis. Results: Compared with placebo, active treatment was associated with a decrease in CC-IMT (after 18 months: from 0.68 to 0.63 mm in the treatment group and from 0.65 to 0.71 mm in the placebo group; P<.001), an increase in BA-FMD (after 18 months: from 4.66% to 7.56% in the treatment group and from 6.21% to 4.73% in the placebo group; P<.001), and an attenuated increase in urinary albumin excretion over time (P=.04 for between-group difference after 24 months), but no effect was observed on renal function. Conclusion: In patients with mild to moderate chronic kidney disease, 18 months of a treatment strategy along with well-controlled blood pressure reduced CC-IMT and urinary albumin excretion and increased BA-FMD. Trial Registration: clinicaltrials.gov Identifier: NCT00384618

    Taal en veiligheid: een groeiend nieuw werkveld

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    Taalproblemen veroorzaken onveiligheid op het werk. Deze studie inventariseert welk wetenschappelijk onderzoek in een aantal economische sectoren is gedaan. Deze studie laat zien dat wetenschappelijk onderzoek naar 'taal en veiligheid' nog pril is en meer aandacht op de wetenschappelijke onderzoeksagenda verdient
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