Urinary connective tissue growth factor excretion correlates with clinical markers of renal disease in a large population of type 1 diabetic patients with diabetic nephropathy

OBJECTIVE: Levels of connective tissue growth factor (CTGF; CCN-2) in plasma are increased in various fibrotic disorders, including diabetic nephropathy. Recently, several articles have reported a strong increase of urinary CTGF excretion (U-CTGF) in patients with diabetic nephropathy. However, these studies addressed too small a number of patients to allow general conclusions to be drawn. Therefore, we evaluated U-CTGF in a large cross-sectional study of patients with type 1 diabetes. RESEARCH DESIGN AND METHODS: Subjects were 318 type 1 diabetic patients and 29 normoglycemic control subjects. U-CTGF was measured by sandwich enzyme-linked immunosorbent assay. Groups were compared by Kruskal-Wallis and Mann-Whitney analysis. The relation between U-CTGF and markers of diabetic nephropathy was determined by regression analysis. RESULTS: U-CTGF in patients with diabetic nephropathy (n = 89, median 155 pmol/24 h [interquartile range 96-258]) was significantly higher than in microalbuminuric (n = 79, 100 [65-78]) and normoalbuminuric (n = 150, 85 [48-127]) patients and control subjects (n = 29, 100 [78-114]). U-CTGF correlated with urinary albumin excretion (UAE) (R = 0.31) and glomerular filtration rate (R = -0.38) in patients with diabetic nephropathy. A standardized increase in U-CTGF was associated with diabetic nephropathy (odds ratio 2.3 [95% CI 1.7-3.1]), which was comparable with the odds ratios for diabetic nephropathy of increased HbA(1c) (2.0 [1.5-2.7]), and blood pressure (2.0 [1.5-2.6]). CONCLUSIONS: This is the first large cross-sectional study addressing U-CTGF in human type 1 diabetes. The observed association of U-CTGF with UAE and glomerular filtration rate might reflect a role of CTGF as progression promoter in diabetic nephropathy.     

Practical issues in the evaluation of methods for the prediction of shock outcome success in out-of-hospital cardiac arrest patients

There is a need for robust, effective predictors of the outcome from shock for out-of-hospital cardiac arrest patients. Such technology would enable the emergency responder to provide a therapy tailored to the patient's needs. Here we report our most recent findings while dwelling intentionally on the rationale behind the decisions taken during system development. Specifically, we illustrate the need for sensible data selection, fully cross-validated results and the care necessary when evaluating system performance. We analyze 878 pre-shock ECG traces, all of at least 10 s duration from 110 patients with cardiac arrest of cardiac aetiology. The continuous wavelet transform was applied to preshock segments of ECG trace. Time-frequency markers are extracted from the transform and a linear threshold derived from a training set to provide high sensitivity prediction of successful defibrillation. These systems are then evaluated on a withheld test set. All experiments are cross-validated. When compared to popular Fourier-based techniques our wavelet transform method, COP (Cardioversion Outcome Predictor), provides a 10-20% improvement in performance with values of 66 +/- 4 specificity at 95 +/- 4 sensitivity, 61 +/- 4 specificity at 97 +/- 2 sensitivity and 56 +/- 1 specificity at 98 +/- 2 sensitivity achieved for datasets limited to 3, 6, and 9 shocks per patient, respectively. Thus, the assessment of the wavelet marker was associated with a high specificity value at or above 95% sensitivity in comparison to previously reported methods. Therefore, COP could provide an optimal index for the identification of patients for whom shocking would be futile, and for whom an alternative therapy could be considered.     

Effect of acidosis on IL-8 and MCP-1 during hypoxia and reoxygenation in human NT2-N neurons

Inflammation probably plays a significant role in perinatal brain injury. To study the contribution of locally produced cytokines, the effect on cell death of addition of IL-8 and MCP-1 or antibodies to these, and the impact of acidosis, human postmitotic NT2-N neurons were exposed to 3 h of hypoxia and glucose deprivation and reoxygenated for 21 h. After 3 h of hypoxia with neutral medium, IL-8 was significantly increased compared to controls (150 (100-250)% vs. 100 (85-115)%, p=0.023). After 21 h of neutral reoxygenation, both IL-8 (380 (110-710)% vs. 150 (85-260)%, p=0.041) and monocyte chemoattractant protein-1 (MCP-1) (650 (440-2000)% vs. 310 (230-340)%, p=0.007) were significantly increased compared to controls. After 3 h of hypoxia, both IL-8 (p=0.002) and MCP-1 (p=0.008) were significantly lower in cells with acidotic compared with cells with neutral medium. Acidosis during reoxygenation, however, significantly increased IL-8 release, whereas MCP-1 release was diminished. Similar effects of acidosis were seen in normoxic controls. The cells also secreted RANTES and IP-10, but not 8 other cytokines tested. We found no effect on cell death, measured by MTT assay, of addition of IL-8, MCP-1 or antibodies to these. We conclude that human NT2-N neurons release IL-8 and MCP-1 during 21 h of reoxygenation after 3 h of hypoxia. Acidosis led to a differential effect on IL-8 and MCP-1, with increased IL-8 and decreased MCP-1, both during reoxygenation and in normoxic controls. IL-8 and MCP-1 had no effect on cell death.