Aortic pulse wave velocity and carotid-femoral pulse wave velocity: similarities and discrepancies.

The objectives of this study were to determine the relationship between carotid-femoral (cfPWV) and aortic pulse wave velocity (aPWV) and to compare their modulators and association with coronary artery disease (CAD). We studied 107 consecutive patients (68 men) with a mean age of 60.49+/-8.31 years who had stable angina and had been referred for coronary angiography. cfPWV and aPWV were measured simultaneously during cardiac catheterization using the Complior device and aortic pressure waveform recordings, respectively. Based on the presence or absence of significant coronary artery stenosis (CAS) patients were subdivided into a CAS+ or CAS- group. The mean values of cfPWV and aPWV were 10.65+/-2.29 m/s and 8.78+/-2.24 m/s, respectively. They were significantly higher in the CAS+ (n=71) compared with the CAS- (n=36) group and predicted significant CAS independently of cardiovascular risk factors and mean or systolic aortic blood pressure. aPWV and cfPWV were significantly correlated (r=0.70; p<0.001) but the degree of correlation differed significantly (p<0.03) between the CAS+ (r=0.74, p<0.001) and CAS- group (r=0.46, p=0.003). Age and mean aortic blood pressure were independent predictors for aPWV as well as cfPWV. In the receiver operating characteristic (ROC) analysis, aPWV and cfPWV had similar accuracy in identification of significant CAS (AUC [area under the ROC curve]=0.76 and 0.69, respectively; p=0.13). However, neither cfPWV nor aPWV was effective at differentiating the extent of CAD. In conclusion, aPWV and cfPWV are highly correlated parameters with similar determinants and comparable accuracy in predicting significant CAS. The strength of correlation between these two indices differed significantly between subjects with and those without CAS.     

Patterns of nuclear proto-oncogene expression during induced differentiation and proliferation of human B chronic lymphocytic leukaemia cells.

Phorbol ester-induced differentiation of human B-chronic lymphocytic leukaemic cells was found to be preceded by a rapid transient induction in expression of the c-jun proto-oncogene, which paralleled that of c-fos. Induced expression of c-myc but not of c-fos/c-jun proto-oncogenes was markedly higher in a proliferating variant leukaemic cell population compared with that seen in typical lymphocytic leukaemia cells. These data suggest that the c-fos/c-jun nuclear oncogenes play a role in induced differentiation, whilst c-myc is more important in the proliferative response of B lymphocytes.     

The influence of high glucose on the aerobic metabolism of endothelial EA.hy926 cells

The endothelium is considered to be relatively independent of the mitochondrial energy supply. The goals of this study were to examine mitochondrial respiratory functions in endothelial cells and isolated mitochondria and to assess the influence of chronic high glucose exposure on the aerobic metabolism of these cells. A procedure to isolate of bioenergetically active endothelial mitochondria was elaborated. Human umbilical vein endothelial cells (EA.hy926 line) were grown in medium containing either 5.5 or 25?mM glucose. The respiratory response to elevated glucose was observed in cells grown in 25?mM glucose for at least 6?days or longer. In EA.hy926 cells, growth in high glucose induced considerably lower mitochondrial respiration with glycolytic fuels, less pronounced with glutamine, and higher respiration with palmitate. The Crabtree effect was observed in both types of cells. High glucose conditions produced elevated levels of cellular Q10, increased ROS generation, increased hexokinase I, lactate dehydrogenase, acyl-CoA dehydrogenase, uncoupling protein 2 (UCP2), and superoxide dismutase 2 expression, and decreased E3-binding protein of pyruvate dehydrogenase expression. In isolated mitochondria, hyperglycaemia induced an increase in the oxidation of palmitoylcarnitine and glycerol-3-phosphate (lipid-derived fuels) and a decrease in the oxidation of pyruvate (a mitochondrial fuel); in addition, increased UCP2 activity was observed. Our results demonstrate that primarily glycolytic endothelial cells possess highly active mitochondria with a functioning energy-dissipating pathway (UCP2). High-glucose exposure induces a shift of the endothelial aerobic metabolism towards the oxidation of lipids and amino acids.     

Small doses of droperidol do not present relevant torsadogenic actions: a double-blind,ondansetron-controlled study

AIM

Drugs used for postoperative nausea and vomiting prophylaxis are believed to provoke torsadogenic changes in cardiac repolarization. The aim of this study was to assess the effect of small doses of droperidol on the parameters of cardiac repolarization, including the QT_c interval and transmural dispersion of repolarization.

METHODS

A total of 75 patients were randomly allocated to receive 0.625 or 1.25 mg droperidol or 8 mg ondansetron. The QT_c interval was calculated using Bazett''s formula and the Framingham correction. The transmural dispersion of repolarization was determined as T_peak–T_end time.

RESULTS

Transient QT prolongation, corrected with both formulae, followed 1.25 mg of droperidol 10 min after administration. No change in the QT_c value was observed in the other groups. When corrected with Bazett''s formula, QT_c was prolonged above 480 ms in two patients receiving 1.25 mg droperidol (at the 10^th and 20^th minute of the study) and in one receiving ondansetron. No patients developed a QT_cB prolongation over 500 ms. No increase above 480 ms was observed relative to the Framingham correction method. There were no significant differences in the T_peak–T_end time either between or within the groups.

CONCLUSION

In men without cardiovascular disorders small doses (1.25 mg) of droperidol prophylaxis induced transient QT_c prolongation without changes in transmural dispersion of repolarization. The apparently low risk of the drug applies only in low risk male patients with a low pro-QT_c score.     

Assessment of flow changes in the circle of Willis after stenting for severe internal carotid artery stenosis.

PURPOSE: To assess flow velocities in the cerebral arteries after carotid artery stenting (CAS) in patients with unilateral versus bilateral lesions and analyze velocities in patients with neurological complications after CAS. METHODS: Ninety-two patients (68 men; mean age 63.2 +/- 8.4 years, range 44-82) with internal carotid artery (ICA) stenoses were divided according to unilateral (group I, n = 72) or bilateral (group II, n = 20) disease. Fifty age- and gender-matched patients without lesions in the extra- or intracranial arteries served as a control group. Transcranial color-coded Doppler ultrasound was performed prior to and within 24 hours after CAS in the test groups; systolic velocities were assessed ipsilateral (i) and contralateral (c) to the CAS site in the middle cerebral artery (MCA) and anterior cerebral artery (ACA). RESULTS: Collateral flow via the anterior communicating artery (ACoA) was found in all group-II patients and 90% of group-I patients. After CAS, collateral flow through the ACoA ceased, and the velocity increased by 26% in the iMCA in group I compared to controls (p < 0.001). In group II, iMCA flow increased by 30% (p < 0.001) and flow via the ACoA (p < 0.001) increased, resulting in normalization of cMCA velocities (p = 0.928). In 89 (96.7%) subjects, CAS was uncomplicated. Hyperperfusion syndrome occurred in 2 (2.2%) patients, both with bilateral ICA stenoses; 1 (1.1%) transient ischemic attack was seen in a patient with unilateral disease. In the patients with hyperperfusion syndrome, the MCA velocities were 2.7- and 7.4-fold higher, respectively, versus before CAS and 2-fold higher than in controls. CONCLUSION: Uncomplicated CAS results in an iMCA velocity increase >25% compared to controls. MCA velocities in hyperperfusion syndrome were greatly increased versus before CAS and in controls.     

Reversed blood flow during internal carotid artery stenting using Parodi Anti-Emboli System--progress in protection against cerebral stroke

Carotid artery stenosis is one of the main causes of stroke. Nowadays two techniques for treating carotid stenosis are available - surgical endarterectomy and percutaneous angioplasty combined with stent implantation at the site of stenosis. Cerebral protection devices during internal carotid stenting significantly decrease the incidence of periprocedural complications, however, during the introduction of protective devices the cerebral blood flow remains unprotected. Therefore, the quest for a system specifically protecting cerebral flow during the whole procedure is still underway. Temporary reversal of carotid flow during the procedure using the Parodi Anti-Emboli System seems a viable solution. The present study describes the first two patients who underwent internal carotid artery stenting using this technique in our institution.     

Long-term outcome of coronary balloon angioplasty in diabetic patients

Diabetes is recognised to increase morbidity and mortality after coronary revascularization. We compared clinical outcomes in mean 5-year-long follow-up of coronary balloon angioplasty in diabetic and non-diabetic patients. We studied 621 patients undergoing elective angioplasty from 1987 to 1996. There were 60 (9.7%) patients with diabetes who were compared with 561 non-diabetic patients. Diabetics were older, more often obese, less frequently were current smokers, and less frequently had hypercholesterolaemia. Diabetic patients in comparison with non-diabetics had lower ejection fraction and more frequently had angioplasty of complex (B2 or C) lesions, but there were no differences between both groups in the other clinical and angiographic risk factors. Clinical success of angioplasty, as well as complications rate were similar in both groups. In follow-up restenosis occurred more frequently in diabetics (46.3 vs. 32.2%, P=0.03), resulting in significantly higher re-intervention rate (50.0 vs. 35.4%, P=0.03). Especially diabetic patients were more frequently referred to CABG (20.4 vs. 9. 9%, P=0.02). There were no significant differences in deaths (1.9 vs. 2.8%) and myocardial infarction (3.7 vs. 4.4%). Diabetics presented worse CCS status at the end of observation (Class 0 and I - 61.1 vs. 74.4%, P=0.037). Angioplasty proved to be a safe procedure in diabetic patients. Despite higher restenosis and re-intervention rate in diabetics, mortality as well as myocardial infarction rate was the same in both groups during mean 5-year follow-up.     

Distinct roles of CSF family cytokines in macrophage infiltration and activation in glioma progression and injury response

Gliomas attract brain‐resident (microglia) and peripheral macrophages and reprogram these cells into immunosuppressive, pro‐invasive cells. M‐CSF (macrophage colony‐stimulating factor, encoded by the CSF1 gene) has been implicated in the control of recruitment and polarization of macrophages in several cancers. We found that murine GL261 glioma cells overexpress GM‐CSF (granulocyte–macrophage colony‐stimulating factor encoded by the CSF2 gene) but not M‐CSF when compared to normal astrocytes. Knockdown of GM‐CSF in GL261 glioma cells strongly reduced microglia‐dependent invasion in organotypical brain slices and growth of intracranial gliomas and extended animal survival. The number of infiltrating microglia/macrophages (Iba1⁺ cells) and intratumoural angiogenesis were reduced in murine gliomas depleted of GM‐CSF. M1/M2 gene profiling in sorted microglia/macrophages suggests impairment of their pro‐invasive activation in GM‐CSF‐depleted gliomas. Deficiency of M‐CSF (op/op mice) did not affect glioma growth in vivo and the accumulation of Iba1⁺ cells, but impaired accumulation of Iba1⁺ cells in response to demyelination. These results suggest that distinct cytokines of the CSF family contribute to macrophage infiltration of tumours and in response to injury. The expression of CSF2 (but not CSF1) was highly up‐regulated in glioblastoma patients and we found an inverse correlation between CSF2 expression and patient survival. Therefore we propose that GM‐CSF triggers and drives the alternative activation of tumour‐infiltrating microglia/macrophages in which these cells support tumour growth and angiogenesis and shape the immune microenvironment of gliomas. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Reduced clot permeability and susceptibility to lysis in patients with acute coronary syndrome: effects of inflammation and oxidative stress

BackgroundStable angina is associated with unfavorable fibrin structure/function. It is not known how acute coronary syndromes (ACS) affect fibrin architecture.ObjectiveWe investigated fibrin clot properties and their determinants in ACS patients.Patients and methodsClot permeability, turbidity and fibrinolysis were assessed in 40 patients with ACS versus 40 controls with stable angina matched for age, sex, and risk factors.ResultsPatients with ACS had lower clot permeability (p = 0.001), faster fibrin polymerization (p = 0.008), and prolonged fibrinolysis time (p < 0.0001) than controls. C-reactive protein (CRP) and 8-epi-prostaglandin F_2α, a marker of oxidative stress, were the only independent predictors of clot permeability (R² = ?0.74; p < 0.0001 and R² = ?0.65; p < 0.0001, respectively) and fibrinolysis time in ACS patients (R² = 0.60; p < 0.0001 and R² = 0.59; p = 0.0002, respectively). In angina patients, fibrinogen and CRP predicted permeability (R² = ?0.71; p < 0.0001 and R² = ?0.62; p < 0.0001), and D-dimer predicted lysis time (R² = 0.54; p = 0.0005). In regression analysis models incorporating all patients, the only independent predictor of all clot variables was being an ACS patient (R² 0.51 to 0.85; p < 0.001).ConclusionsThis first study of clot properties in patients during an ACS demonstrated that compared with stable angina patients, their clots are composed of dense networks that are more resistant to lysis and these features are correlated with raised CRP and oxidative stress.