Ankyrin is the major oxidised protein in erythrocyte membranes from end-stage renal disease patients on chronic haemodialysis and oxidation is decreased by dialysis and vitamin C supplementation

Chronically haemodialysed end-stage renal disease patients are at high risk of morbidity arising from complications of dialysis, the underlying pathology that has led to renal disease and the complex pathology of chronic kidney disease. Anaemia is commonplace and its origins are multifactorial, involving reduced renal erythropoietin production, accumulation of uremic toxins and an increase in erythrocyte fragility. Oxidative damage is a common risk factor in renal disease and its co-morbidities and is known to cause erythrocyte fragility. Therefore, we have investigated the hypothesis that specific erythrocyte membrane proteins are more oxidised in end-stage renal disease patients and that vitamin C supplementation can ameliorate membrane protein oxidation. Eleven patients and 15 control subjects were recruited to the study. Patients were supplemented with 2 × 500 mg vitamin C per day for 4 weeks. Erythrocyte membrane proteins were prepared pre- and post-vitamin C supplementation for determination of protein oxidation. Total protein carbonyls were reduced by vitamin C supplementation but not by dialysis when investigated by enzyme linked immunosorbent assay. Using a western blot to detect oxidised proteins, one protein band, later identified as containing ankyrin, was found to be oxidised in patients but not controls and was reduced significantly by 60% in all patients after dialysis and by 20% after vitamin C treatment pre-dialysis. Ankyrin oxidation analysis may be useful in a stratified medicines approach as a possible marker to identify requirements for intervention in dialysis patients

Venous gas embolism as a predictive tool for improving CNS decompression safety

A key process in the pathophysiological steps leading to decompression sickness (DCS) is the formation of inert gas bubbles. The adverse effects of decompression are still not fully understood, but it seems reasonable to suggest that the formation of venous gas emboli (VGE) and their effects on the endothelium may be the central mechanism leading to central nervous system (CNS) damage. Hence, VGE might also have impact on the long-term health effects of diving. In the present review, we highlight the findings from our laboratory related to the hypothesis that VGE formation is the main mechanism behind serious decompression injuries. In recent studies, we have determined the impact of VGE on endothelial function in both laboratory animals and in humans. We observed that the damage to the endothelium due to VGE was dose dependent, and that the amount of VGE can be affected both by aerobic exercise and exogenous nitric oxide (NO) intervention prior to a dive. We observed that NO reduced VGE during decompression, and pharmacological blocking of NO production increased VGE formation following a dive. The importance of micro-nuclei for the formation of VGE and how it can be possible to manipulate the formation of VGE are discussed together with the effects of VGE on the organism. In the last part of the review we introduce our thoughts for the future, and how the enigma of DCS should be approached

How unstable? Volatility and the genuinely new parties in Eastern Europe

Measuring of party system stability in Eastern Europe during the first decade of democratic elections presents problems. The traditional quantitative measure - volatility - does not distinguish between the dynamics among incumbent parties and the rise of genuinely new ones. I propose a new additional measure - success of genuinely new parties - and compare it to volatility. The subsequent performance of initially successful genuinely new parties is analysed. While volatility has been remarkably high in East European countries, the genuinely new parties have, in general, not been very successful. Instability of party systems in the region stems rather from the inner dynamics of incumbent actors than from the rise of new contenders

Confusion assessment method for the intensive care unit (CAM-ICU): translation, retranslation and validation into Swedish intensive care settings

Background: Becoming critical ill or severely injured leads to a process of worry, anxiety and pain. Patients in intensive care sometimes have strange and frightening experiences and may show symptoms of acute confusion or delirium. CAM-ICU, the confusion assessment method for the intensive care unit, was based on the DSM IV, the Diagnostic and Statistic Manual of Mental Disorders IV, and today, healthcare professionals and researchers are increasingly accepting this concept of diagnosing ICU delirium. In Sweden, there is no commonly used, single instrument or method to test the development of ICU delirium. The aim of this study was to translate, retranslate and validate CAM-ICU for use in Swedish ICU settings. Methods: The translation of the instrument was done according to the guidelines suggested by The Translation and Cultural Adaptation group which includes preparation, forward translation/reconciliation, back translation, back translation review, harmonization, cognitive debriefing and validation. In the validation process, the applicability of the Swedish version of the instruments was tested in a Swedish intensive care unit. Results: Fourteen adult patients were included in the study, 40 paired tests were carried out, and 80 CAM-ICU instruments were completed. The participating patients were given CAM-ICU ratings using independent paired evaluations by two nurses, specialized in intensive care, at least twice during the patients' stay in the ICU. Interrater reliability was calculated using kappa statistics. In the 40 paired observations, interrater reliability was 'very good' (kappa statistics > 0.81). In our material, we recognized a delirium rate of 48%, which is in accordance with previous studies. Conclusion: The translation of the instrument CAM-ICU showed good correlation with the original version and could therefore be applicable in a Swedish ICU setting. In the 40 paired observations, interrater reliability was very good. Although there are limitations in using CAM-ICU, previous studies reveal a need for a homogeneous screening instrument making it possible to detect and determine ICU delirium; and from this basis are able to implement and make the necessary decisions required in medical and nursing care practice preventing ICU delirium

Decreases in myocardial glucose and increases in pyruvate but not ischaemia are observed during porcine endotoxaemia.

Myocardial dysfunction occurs commonly in septic shock. It is not known whether this is due to local ischaemia and metabolic disturbances. Our hypothesis was that endotoxaemic myocardial dysfunction may be associated with interstitial ischaemic and metabolic changes, measured using interstitial microdialysis (MD). Methods: Eighteen pigs were randomized to control (n=6) or endotoxin infusion (n=12). MD catheters were inserted into the myocardium for measurement of interstitial glucose, pyruvate and lactate concentrations. Plasma glucose and lactate concentrations and systemic haemodynamic parameters were measured simultaneously. Results: Compared with the control group, the endotoxaemic animals had significantly decreased left ventricular stroke work and venous oxygen saturation (SvO2), and increased mean pulmonary artery pressure and plasma lactate. In the endotoxaemic group, decreases in interstitial glucose were observed, occurring simultaneously with increases in interstitial pruvate. Interstitial lactate : pyruvate ratios decreased with time in all animals. Conclusions: Despite severe systemic and pulmonary haemodynamic changes, interstitial MD measurements revealed no evidence of anaerobic metabolism in the myocardium of endotoxaemic pigs. There were, however, changes in glucose and pyruvate concentrations, suggesting local energy metabolic disturbances

Feasibility of endovascular and surface cooling strategies in acute stroke

Background Therapeutic hypothermia (TH) is a promising treatment of stroke, but limited data are available regarding the safety and effectiveness of cooling methodology. We investigated the safety of TH and compared the cooling capacity of two widely used cooling strategies endovascular and surface cooling. Methods COOLAID Oresund is a bicentre randomized trial in Copenhagen (Denmark) and Malmo (Sweden). Patients were randomized to either TH (33 degrees C for 24h) in a general intensive care unit (ICU) or standardized stroke unit care (control). Cooling was induced by a surface or endovascular-based strategy. Results Thirty-one patients were randomized. Seven were cooled using endovascular and 10 using surface-based cooling methods and 14 patients received standard care (controls). 14 (45%) patients received thrombolysis. Pneumonia was recorded in 6 (35%) TH patients and in 1 (7%) control. 4 TH patients and 1 control developed massive infarction. 1 TH patient and 2 control suffered asymptomatic haemorrhagic transformation. Mortality was comparable with 2 (12%) in the TH group and 1 (7%) among controls. Mean (SD) duration of hospital stay was 25.0days (24, 9) in TH and 22.5days (20.6) in control patients (P=0.767). Mean (SD) induction period (cooling onset to target temperature) was 126.3min (80.6) with endovascular cooling and 196.3min (76.3) with surface cooling (P=0.025). Conclusions Therapeutic hypothermia with general anaesthesia is feasible in stroke patients. We noticed increased rates of pneumonia, while the length of hospital stay remained comparable. The endovascular cooling strategy provides a faster induction period than surface cooling