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Biomedical subjects

O Parodi

Publications and source records attributed to O Parodi.

136 records · Page 8Linked to original sources

Correlation between extent of myocardial dysfunction and markers of irreversible damage in failing hearts.

BACKGROUND: The structural correlates of 201Tl uptake in patients with advanced postischemic pump dysfunction are unclear. There are no good experimental models adequately reflecting the mixture of normal, dysfunctional but viable, and necrotic regions characteristic of chronic ischemic heart disease in human beings. METHODS AND RESULTS: Four heart transplant candidates with idiopathic dilated cardiomyopathy and seven with ischemic heart disease underwent rest-injection 4-hour redistribution 201Tl single-photon emission computed tomography before surgery. Delayed tracer uptake was categorized into severely reduced (<50%), mildly or moderately reduced (50% to 74%), and normal (> or =75%) and related to echocardiographic wall motion and histologic findings in the hearts excised at transplantation. In idiopathic dilated cardiomyopathy, despite severe wall motion impairment, minimal or mild myocardial damage and homogeneously high 201Tl uptake were found. In ischemic heart disease, wall motion did not discriminate extensive from mild structural damage. 201Tl activity was inversely related to myocardial fibrosis (r = -0.50, p = 0.0001). Severe defects in 201Tl uptake (<50%) predicted extensive (>30%) fibrosis with 83% sensitivity and 63% specificity. Segmental akinesis and apical location resulted in loss of sensitivity (74% and 58%, respectively). No histologic or wall motion abnormality accounted for poor specificity. In the individual patient, more than nine segments determined viable by imaging criteria predicted left ventricular fibrosis of less than 15% with 86% accuracy. CONCLUSIONS: This histopathologic-clinical correlative study supports current evidence of good sensitivity but limited specificity of 201Tl rest-redistribution tomographic imaging in the evaluation of viable myocardium. In the individual patient, more than nine viable segments reliably predicted a limited extension of fibrosis.

Adult↗

Myocardial blood flow and perfusion reserve in infarcted patients with stress-induced normalization of previously negative T waves: a positron emission tomography study.

BACKGROUND: The clinical correlations between stress-induced normalization of previously negative T waves (NTW) and regional myocardial blood flow (MBF) regulation and tissue viability remain debatable. METHODS AND RESULTS: To confirm these correlations, 14 patients with previous anterior myocardial infarction (13 Q waves) and NTW on baseline electrocardiographic precordial leads and 10 healthy subjects were studied by means of positron emission tomography (PET). The MBF values were obtained in the anterior infarcted myocardial regions in either resting condition or during dipyridamole infusion, using N-13 ammonia as a flow tracer. Seven subjects had normalization of NTW (Group 1) and 7 had persistent NTW (Group 2) during dipyridamole infusion. The resting MBF values were similar for both Group 1 and Group 2 (0.43+/-0.13 versus 0.51+/-0.15 mL.min(-1).g(-1), respectively; P = not significant) and were significantly lower than in the anterior myocardial regions of healthy subjects (1.03+/-0.23 mL.min(-1).g(-1), P < .001). After administration of dipyridamole, the MBF was significantly higher in Group 1 than in Group 2 (0.88 +/- 0.37 versus 0.55 +/- 0.17 mL.min(-1).g(-1), respectively; P < .05) and markedly lower than in healthy subjects (3.78+/-0.64 mL.min(-1).g(-1), P < .001). Coronary reserves (dipyridamole/resting MBF) were 2.03+/-0.40 and 1.14+/-0.44 in Group 1 and Group 2, respectively (P < .002). CONCLUSION: Despite similar values of resting perfusion, infarcted dysfunctional areas with or without NTW during stress may present different regional MBF responses; normalization of NTW demonstrates higher coronary flow reserve than persistent NTW, suggesting a better preserved coronary microcirculatory function in the former, indicative of the presence of myocardial viability.

Adult↗

[Endothelial dysfunction and oxidative stress in sepsis].

Central to the pathophysiology of sepsis and septic shock is an alteration in endothelial cell function and oxidative stress. Highly complex, integrated responses that include the activation of a number of cell types, inflammatory mediators and the hemostatic system are involved in endothelial dysfunction. On the other hand, the imbalance between the excessive production of reactive oxygen species and/or inadequate antioxidative defenses characterizes the oxidative stress. The overview of all these mechanisms suggests clinical biochemical markers as a possible therapeutic target together with correct intervention timing.

Biomarkers↗

[Polymyxin-B direct hemoperfusion (PMX-DHP) in gram negative sepsis].

UNLABELLED: Severe sepsis and septic shock have a mortality rate that may range between 28 and 50%. It is estimated that approximately 200,000 patients die per annum in the USA as a consequence of sepsis. The reduction of plasma endotoxin levels to achieve a favourable outcome for septic patients has been previously demonstrated but the effectiveness of treatments targeting single inflammatory mediators during established sepsis has been disappointing. Furthermore,some clinical study clinically showed valuable reduction in cytokine levels by hemofiltration alone. The prompt removal of endotoxins could be an effective way to reduce the immunological activation and the amount of NO produced by endotoxin-activated inducible NO-synthase in many tissues and cells. The polymyxin B cartridge is an extracorporeal hemoperfusion device (PMX-DHP) known to remove circulating endotoxins. Open-label clinical trials testing PMX-DHP have demonstrated its safety in the septic shock treatment while the overall survival rate significantly improved in comparison with the control groups. The purpose of this study was to investigate the effects of PMX-DHP on redox status, inflammatory cytokine profile, monocytes and PMN leukocyte activation in Gram-negative sepsis. Prospective study: six patients, 2 males and 4 females 60.5+/-24.5 years old, in ICU for severe Gram-negative sepsis (emergency surgery for intra abdominal infection). Two PMX-DHP runs, at T0 and T1; 2 hours each; the first within 24 hours from sepsis diagnosis or 12 hours after emergency surgery, the first PMX-DHP at T0, the second after 24 hours.; APACHE II score at T0: 20.1+/-3.7; SOFA score 14.2+/-2.5; organ failure: 3+/-1.5; norepinephrine(Ne) in 1 patient; Ne + dopamine (DA) in 4 patients; DA in 1 patient only. Mean dosage: Ne 0.24 mcg/kg/min; DA 8.9 mcg/kg/min. Four patients in CRRT (continuous veno-venous hemofiltration, AN69 hemofilter) for the entire length of the study. QB 100+/-10 ml/min. Pre and post PMX-DHP, plasma endotoxins as well as anti-IL 1-beta, IL2, IL4, IL5, IL6, IL8, IL10, TNF-alpha, GM-CSF, IFN-gamma levels were measured. Expression of CD64 on monocytes and PMN leukocytes and I -2r CD25 on CD4+ T cells by flow cytometry. Total and reduced plasma cysteine, homocysteine, glutathione (GSH); plasma glutathione peroxidase (GSH-Px) and reductase (GSH-Rx); erythrocyte GSH (eGSH), eGSH-Px and eGSH-Rx; NADP and NADPH and their ratio assessed pre and post PMX-DHP, all compared with 15 age and gender-matched healthy subjects for complete REDOX characterization. RESULTS: We observed a significant reduction of endotoxin levels post PMX-DHP; CD64 monocytes and PMN leukocytes overexpression returned to normal; pro-inflammatory cytokines Il6, Il 10 and TNF-alpha were significantly reduced. We detected no differences in plasma levels of anti-IL 1-beta, IL2, IL4, IL5, IL8, GM-CSF, IFN-gamma pre versus post PMX-DHP. SOFA score from 14.2+/-2.5 to 8.9+/-2.1 post PMX-DHP runs. Four out of six patients survived and were discharged; mortality was 33% versus the anticipated 51%. CONCLUSION: PMX-DHP reduces circulating endotoxins, down-activates monocytes and PMN leukocytes, reduces pro-Inflammatory cytokines and corrects the redox environment imbalance preventing oxidative damage to endothelial cells and the metabolic and functional microvascular derangements that usually lead to multi-organ failure and septic shock.

Adult↗