Uremic cardiomyopathy is characterised by loss of the cardioprotective effects of insulin

Chronic kidney disease is associated with a unique cardiomyopathy, characterised by a combination of structural and cellular remodelling, and an enhanced susceptibility to ischaemia-reperfusion injury. This may represent dysfunction of the reperfusion injury salvage kinase pathway, due to insulin resistance. Aims: The susceptibility of the uraemic heart to ischaemia-reperfusion injury and the cardioprotective effects of insulin and rosiglitazone were investigated. Methods and Results: Uraemia was induced in Sprague-Dawley rats by subtotal nephrectomy. Functional recovery from ischaemia was investigated in vitro in control and uraemic hearts ±insulin ±rosiglitazone. The response of myocardial oxidative metabolism to insulin was determined by 13C NMR spectroscopy. Activation of reperfusion injury salvage kinase pathway intermediates (Akt and GSK3β) were assessed by SDS-PAGE and immuno-precipitation. Insulin improved post-ischaemic rate pressure product in control but not uraemic hearts, (recovered rate pressure product (%), control 59.6±10.7 vs 88.9±8.5, p<0.05; uraemic 19.3±4.6 vs 28.5±10.4, p=ns). Rosiglitazone resensitised uraemic hearts to insulin-mediated cardio-protection (recovered rate pressure product (%) 12.7±7.0 vs. 61.8±15.9, p<0.05). Myocardial carbohydrate metabolism remained responsive to insulin in uraemic hearts. Uraemia was associated with increased phosphorylation of Akt (1.00±0.08 vs. 1.31±0.11, p<0.05) in normoxia, but no change in post-ischaemic phosphorylation of Akt or GSK3β. Akt2 isoform expression was decreased post-ischaemia in uraemic hearts (p<0.05). Conclusion: Uraemia is associated with enhanced susceptibility to ischaemia-reperfusion injury and a loss of insulin-mediated cardio-protection, which can be restored by administration of rosiglitazone. Altered Akt2 expression in uraemic hearts post ischaemia-reperfusion and impaired activation of reperfusion injury salvage kinase pathway may underlie these findings

Artificial Neural Network Inference (ANNI): A Study on Gene-Gene Interaction for Biomarkers in Childhood Sarcomas

Objective: To model the potential interaction between previously identified biomarkers in children sarcomas using artificial neural network inference (ANNI). Method: To concisely demonstrate the biological interactions between correlated genes in an interaction network map, only 2 types of sarcomas in the children small round blue cell tumors (SRBCTs) dataset are discussed in this paper. A backpropagation neural network was used to model the potential interaction between genes. The prediction weights and signal directions were used to model the strengths of the interaction signals and the direction of the interaction link between genes. The ANN model was validated using Monte Carlo cross-validation to minimize the risk of over-fitting and to optimize generalization ability of the model. Results: Strong connection links on certain genes (TNNT1 and FNDC5 in rhabdomyosarcoma (RMS); FCGRT and OLFM1 in Ewing’s sarcoma (EWS)) suggested their potency as central hubs in the interconnection of genes with different functionalities. The results showed that the RMS patients in this dataset are likely to be congenital and at low risk of cardiomyopathy development. The EWS patients are likely to be complicated by EWS-FLI fusion and deficiency in various signaling pathways, including Wnt, Fas/Rho and intracellular oxygen. Conclusions: The ANN network inference approach and the examination of identified genes in the published literature within the context of the disease highlights the substantial influence of certain genes in sarcomas

Clinical Features of Cardio-Renal Syndrome in a Cohort of Consecutive Patients Admitted to an Internal Medicine Ward

Introduction: Cardiorenal syndrome (CRS) is a disorder of the heart and kidney whereby interactions between the 2 organs can occur. We recorded the clinical features of CRS in patients consecutively admitted to an Internal Medicine ward. Patients and Methods: We retrospectively analyzed the anthropometric, history, clinical, biochemical and treatment characteristics in 438 out of 2,998 subjects (14.6%) admitted to our unit (from June 2007 to December 2009), diagnosed with CRS, according to Acute Dialysis Quality Initiative (ADQI) recommendations. Estimated glomerular filtration (eGFR) was calculated using several equations: MDRD (Modification of Diet in Renal Disease; 2 variations GFRMDRD186, GFRMDRD175), Mayo, Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and Cockroft-Gault. Results: Mean age was 80±8 years, 222 (50.6%) were males, 321 (73.2%) were smokers, 229 (52.2%) were diabetic, 207 (47.2%) had a history of acute myocardial infarction, 167 (38.1%) had angina, 135 (30.8%) were affected by cerebrovascular disease, 339 (77.3%) had peripheral arterial disease. CRS was type 1 in 211 cases (48.2%), type 2 in 96 (21.9%), type 3 in 88 (20.1%), type 4 in 29 (6.6%) and type 5 in 14 (3.2%). eGFR, calculated by different formulae, ranged between 31 and 36 ml/min/1.73 m2. GFR was lower in CRS type 3 than in the other types, and the values ranged between 24 and 27 ml/min/1.73 m2. Mean hospital length-of-stay (LOS) was 9.8±6.3 days. Diuretics were the most prescribed medication (78.7%); only 5 patients underwent haemodialysis. Conclusions: CRS is common, especially in the elderly. CRS Type 1 was the prevalent subset and patients had stage 3-4 renal insufficiency. Results obtained from the GFR equations were similar although the Mayo equation tended to overestimate the eGFR

Incidence of contrast-induced nephropathy with volume supplementation--insights from a large cohort

OBJECTIVE: The present study was performed to determine the effect of combined intravenous and oral volume supplementation on the incidence of contrast-induced nephropathy (CIN) in patients undergoing percutaneous coronary intervention (PCI). SUBJECTS AND METHODS: Consecutive patients (n = 958) receiving iomeprol 350 during PCI were evaluated prospectively for the development of CIN. All patients received protocol-defined intravenous and oral volume supplementation. CIN was defined as an increase in serum creatinine of at least 44 micromol/l within 48 h. RESULTS: Of the 958 patients enrolled in the study, 147 (15%) were diabetic and 107 (11%) had stage III renal disease. The average baseline glomerular filtration rate was 88 +/- 25 ml/min/1.73 m(2). During the intervention an average of 238 +/- 86 ml of contrast medium was administered. CIN developed in 13 of 958 (1.4%; 95% confidence interval 0.6-2.1%) patients. The incidence of CIN was low even in predefined risk subgroups (women: 2.4%, diabetics: 2.7%, patients with stage III kidney disease: 6.5%). CONCLUSIONS: The incidence of CIN is low when preprocedural fluid volume supplementation is used

Impact of body temperature on in-hospital and long-term mortality in patients with acute heart failure

OBJECTIVES: Body temperature (BT) was shown to have impact on outcome in several medical conditions. This study investigated the prognostic impact of BT in patients with acute heart failure (HF). DESIGN AND PATIENTS: The B-type natriuretic peptide for Acute Shortness of breath EvaLuation (BASEL) study prospectively enrolled 452 consecutive patients presenting with acute dyspnoea to the emergency department. Among these, 170 patients had a final discharge diagnosis of acute HF and a documented BT on presentation. The primary endpoint was cardiovascular mortality during long-term follow-up. Morbidity was documented as secondary endpoint. RESULTS: BT on presentation was 37.2 degrees C (SD 0.9) and ranged from 34.8-40.4 degrees C. Patients were divided into quartiles of BT. Initial morbidity as reflected by intensive care unit admission rate was significantly higher among patients in the highest quartile (38% versus 13% in the first quartile, p >0.05). Length of stay in hospital was significantly increased by 2.7 days per one degree rise in BT. A total of 64 cardiovascular deaths occurred (38%). Kaplan-Meier analysis showed no apparent difference in long-term cardiovascular mortality among quartiles of BT. Cardiovascular mortality rate was 47% in the first (>36.6 degrees C), 26% in the second (36.7-37.2 degrees C), 44% in the third (37.3-37.8 degrees C) and 35% in the fourth quartile ( 37.9 degrees C; P = 0.31) at 720 days. In addition, Cox regression analysis adjusted for age and sex showed no association between BT and either in-hospital (HR 0.59, 95% CI 0.26-1.35; P = 0.21) or long-term cardiovascular mortality (HR 0.91, 95% CI 0.67-1.24; P = 0.55). CONCLUSION: In patients with acute HF, BT on presentation is not associated with in-hospital or long-term cardiovascular mortality, but is associated with short-term morbidity. However, it is important to stress that our findings relate to central BT and do not negate the undisputed value of assessing peripheral BT which reflects peripheral hypoperfusion