Restless legs syndrome: an underappreciated and distressing problem for haemodialysis patients.

Restless legs syndrome is a distressing condition that is more common in patients with end-stage renal failure. Despite the significant impact it has on quality of life and the documented association between restless legs syndrome and increased mortality, limited data regarding the epidemiology of restless legs syndrome in Australian dialysis patients are available. We report a prospective study that assessed the prevalence and factors associated with restless legs syndrome in an in-centre haemodialysis population.

Five-year decline in estimated glomerular filtration rate associated with a higher risk of renal disease and atherosclerotic vascular disease clinical events in elderly women.

BACKGROUND: Estimated glomerular filtration rate (eGFR) has been demonstrated to predict atherosclerotic vascular disease (ASVD)-associated clinical events independent of traditional vascular risk factors. Recent studies have demonstrated that eGFR decline over time may improve prediction of ASVD-associated mortality risk in chronic kidney disease (CKD) patients. AIM: The aim of this study is to evaluate the association between 5-year change in eGFR with renal disease and ASVD-associated clinical events. DESIGN: Prospective observational study. METHODS: A total of 1012 women over the age of 70 years from the Calcium Intake Fracture Outcome Study were included. Baseline characteristics including baseline and 5-year creatinine, participants' comorbidities and complete verified 10-year records for ASVD and renal disease-associated hospitalization and/or mortality were obtained using the Western Australian Data Linkage System. RESULTS: Participants were stratified according to annual rate of eGFR change in quartiles [≤-1.2 (first quartile), >-1.2 to 0.1 (second quartile), >0.1-1.7 (third quartile) and >1.7 ml/min/1.73 m(2)/year (fourth quartile)]. In the adjusted model, compared with participants in the fourth quartile, those in the first and/or second quartiles of annual eGFR change had significantly higher risk of renal disease and/or ASVD-associated clinical events. However, the association with renal clinical events was more pparent in participants with baseline eGFR of <60 ml/min/1.73 m(2). CONCLUSION: The results of this study suggest that the inclusion of long-term eGFR change over time might augment prognostication for renal disease and ASVD-associated clinical events in elderly women.

Hypercoagulability in chronic kidney disease is associated with coagulation activation but not endothelial function.

INTRODUCTION: Patients with chronic kidney disease exhibit features of a hypercoagulable state and have endothelial dysfunction, which may contribute to their increased cardiovascular risk. We examined the relationship between coagulation activation and vascular function in patients with chronic kidney disease. MATERIALS AND METHODS: We measured parameters of the tissue factor pathway of blood coagulation (tissue factor, factor VIIc and factor X); natural inhibitors (tissue factor pathway inhibitor, protein C, free and total protein S, antithrombin III) and markers of coagulation activation (thrombin-antithrombin complexes, prothrombin fragment 1+2) in 66 stage 4&5 chronic kidney disease patients and 36 healthy controls. Their relationship with markers of vascular function (flow mediated dilatation, soluble E-selectin and thrombomodulin) and a mediator of inflammation (interleukin-6) was determined. RESULTS: Up-regulation of the tissue factor pathway (increased tissue factor and factor VIIc), increased prothrombin fragment 1+2 and significant reductions in antithrombin III and the ratio of free protein S: total protein S were found in patients compared to healthy controls. Increased tissue factor antigen was significantly and independently correlated with creatinine and interleukin-6 (P<0.001). Factor X and antithrombin III were both reduced in chronic kidney disease and correlated (r=0.58; P<0.001). Changes in coagulation and anti-coagulation were independent of all measures of endothelial function. CONCLUSIONS: Significant activation of the TF pathway of coagulation and depletion or reduction of some natural anticoagulants in chronic kidney disease was correlated with the degree of renal dysfunction, but not correlated with the abnormalities of vascular function. These data are consistent with a hypercoagulable state in chronic kidney disease that may be independent of endothelial based regulation but associated with an inflammatory state.

Statin therapy improves brachial artery vasodilator function in patients with Type 1 diabetes and microalbuminuria.

AIMS: Type 1 diabetes mellitus patients with microalbuminuria have endothelial dysfunction associated with the degree of albuminuria but not with LDL-cholesterol levels. Lipid-lowering agents such as statins may still be of benefit as they can correct endothelial dysfunction by both lipid and non-lipid mechanisms. We therefore examined the effects of atorvastatin on brachial artery endothelial dysfunction in these patients. METHODS: In a double-blind, randomized crossover study, 16 Type 1 diabetes mellitus patients with microalbuminuria received 6 weeks of atorvastatin 40 mg/day or placebo, separated by a 4-week washout. Brachial artery, endothelium-dependent, flow-mediated dilatation (FMD) and endothelium-independent, glyceryl trinitrate-mediated dilatation (GTNMD) were measured. RESULTS: Compared with placebo, atorvastatin produced a significant decrease in apolipoprotein B (34.2%), LDL-cholesterol (44.1%) (all P < 0.001), and oxidized-LDL (35.7%, P = 0.03). There was a non-significant increase in plasma cGMP (P = 0.13) on atorvastatin. FMD and GTNMD increased significantly on atorvastatin (FMD: atorvastatin +1.8 +/- 0.4%; placebo +0.2 +/- 0.4%, P = 0.007); (GTNMD: atorvastatin +1.3 +/- 0.9%; placebo -1.2 +/- 0.6%, P = 0.04). An increase in cGMP was independently correlated with an increase in FMD on atorvastatin (adjusted (R2) 0.41, P = 0.02). CONCLUSION: Atorvastatin improves endothelium-dependent and independent vasodilator function of the brachial artery in Type 1 diabetes mellitus patients with microalbuminuria. This may relate to pleiotropic effects of statins, in particular reduced oxidative stress and increased availability of nitric oxide.

Oxidant stress in nephrotic syndrome: comparison of F(2)-isoprostanes and plasma antioxidant potential.

BACKGROUND: The nephrotic syndrome (NS) is associated with an increased risk of coronary heart disease. Increased oxidant stress may contribute to this by means of hyperlipidaemia and/or hypoalbuminaemia. In this study we assessed the contributory role of oxidant stress, as measured by F(2)-isoprostanes and plasma oxygen radical absorbance capacity (ORAC), in subjects with NS. METHODS: We studied 14 subjects with NS and 17 age- and sex-matched healthy non-proteinuric controls. Measurement of plasma and urinary F(2)-isoprostanes was carried out using a combination of silica and reverse-phase cartridges, high-performance liquid chromatography, and gas chromatography mass spectrometry using electron-capture negative ionization. The plasma ORAC assay measured the decrease in fluorescence of phycoerythrin added to plasma in the presence of a free-radical generator. The ORAC value (microM) was calculated as the ratio of the area under the fluorescence decay curve for plasma to the area under the fluorescence decay curve for a Trolox standard. RESULTS: Plasma ORAC was significantly lower in NS patients compared with controls: mean (standard error) NS patients 3306 microM (286); controls 4882 microM (496), P=0.011. In univariate linear regression analysis, plasma albumin was significantly positively correlated with plasma ORAC (r=0.40, P=0.03). Plasma and urinary F(2)-isoprostanes did not differ significantly between NS and control groups. CONCLUSIONS: This study demonstrates that in the NS there is decreased free-radical trapping capacity of plasma that is inversely correlated with hypoalbuminaemia, but no increase in plasma and urinary F(2)-isoprostanes. Decreased total plasma antioxidant potential in combination with hyperlipidaemia may contribute to the increased risk of cardiovascular disease seen in NS.

Vascular function of the peripheral circulation in patients with nephrosis.

BACKGROUND: Nephrotic syndrome is associated with abnormal lipoprotein metabolism and increased risk of coronary heart disease. Endothelial dysfunction, an early phase of atherogenesis that manifests as impaired flow-mediated dilation (FMD) of the peripheral circulation, may link these associations. METHODS: We examined endothelial function of the brachial artery and forearm resistance arteries in 15 patients with nephrosis (NP), 15 patients with primary hyperlipidemia (HL) alone, and 15 normolipidemic, nonproteinuric subjects (NC) matched for age, sex, and weight. The NP and HL groups had similar serum cholesterol and triglyceride concentrations. Post-ischemic FMD (endothelium-dependent) and glyceryl trinitrate-mediated dilation (GTNMD; endothelium-independent) of the brachial artery were studied using ultrasonography and computerized edge detection software. Postischemic forearm blood flow was also measured using plethysmography. RESULTS: Postischemic FMD of the brachial artery was significantly lower in the NP and HL groups compared with NC group (mean +/- SE): NP 4.91 +/- 0.8%, HL 4.53 +/- 0.6%, NC 8.45 +/- 0.5% (P < 0.001). There were no significant differences among the groups in baseline diameter and GTNMD of the brachial artery, nor in maximal forearm blood flow and flow debt repayment of the forearm microcirculation. Significant differences in FMD among the groups were principally related to differences in serum low-density lipoprotein cholesterol. CONCLUSIONS: Patients with NP have abnormal endothelium-dependent but preserved endothelium-independent dilation of the brachial artery following an ischemic stimulus. Postischemic forearm microcirculatory function is unimpaired. Dyslipoproteinemia is probably the principal cause of endothelial dysfunction of conduit arteries in patients with NP and the basis for their increased risk of cardiovascular disease.

Endothelium-dependent and independent vasodilation studies at normoglycaemia in type I diabetes mellitus with and without microalbuminuria.

AIMS/HYPOTHESIS: We examined whether endothelial function is impaired in patients with Type I (insulin-dependent) diabetes mellitus under conditions of near-normoglycaemia compared with age-matched healthy control subjects. Our aim was to determine whether microalbuminuria is associated with endothelial dysfunction in Type I diabetes. METHODS: Endothelial function, measured as post-ischaemic flow-mediated dilatation of the brachial artery using ultrasound, was compared among 17 microalbuminuric and 17 normoalbuminuric diabetic patients, and 17 control subjects. Glyceryl trinitrate-mediated dilatation of the brachial artery was used to measure endothelium-independent function. All diabetic patients were studied at near-normoglycaemia, using insulin and 5 % dextrose infusions to maintain blood glucose between 3.5 and 8.0 mmol/l. RESULTS: Flow-mediated dilatation was significantly lower in microalbuminuric diabetic patients (3.2 +/- 0.3%) compared with normoalbuminuric diabetic patients (5.4 +/- 0.6%) and control subjects (7.9 +/- 0.6%, p < 0.001). Normoalbuminuric diabetic patients also had significantly lower flow-mediated dilatation than control subjects (p = 0.01). Glyceryl trinitrate mediated dilatation was significantly lower in the microalbuminuric patients compared with the control subjects (11.9 +/- 1.1% vs 20.0 +/- 1.2%, p = 0.001). Albumin excretion rate and glycated haemoglobin showed a significant negative independent correlation with flow-mediated dilatation (both p < 0.05). CONCLUSION/INTERPRETATION: Type I diabetic patients show endothelial dysfunction at near-normoglycaemia compared with the control subjects, and this abnormality is more marked in diabetic patients with microalbuminuria. Endothelial dysfunction in Type I diabetes is related to the albumin excretion rate and glycaemic control. The presence of endothelial dysfunction in normoalbuminuric diabetic patients suggests it could precede microalbuminuria as an early risk marker for cardiovascular disease.

Morphological and histological studies on the neuroendocrine system of the sugarcane leaf hopper, Pyrilla perpusilla Wlk. (Fulgoridae: Hemoptera).

Neuroendocrine system of the sugarcane leaf hopper, Pyrilla perpusilla, has been studied by employing PAVB and AF techniques in situ and on sections. There are four groups of NS cells in the brain, a medial of 14--17 cells, lateral and an antero-ventral of 2 cells each and a latero-ventral of a single cell. The cells are of A and B types: tinctorially the A-cells are further subdivided into A1, A2 and A3 subtypes. Suboesophageal and thoracic ganglions have 2 groups of 2 and 3 cells, each of A and B types. Axons of the cells of cerebral groups converge to form a common pathway which emerge from the protocerebrum as NCC. NSM transports both inter and intracellularly. In CC stained colloids accumulate at the commissuris, the gland has two--A and B--types of intrinsic cells. CA is devoid of NSM. Though considerably small in size and have new NS cells, its NS pathways are easily demonstrated in situ. It is emphasized that size and number of neurosecretory axons is not a limitation of the in situ technique but the demonstration of the tract depends upon the physiological state of the animal at the time of fixation.