Non-invasive assessment of coronary artery bypass graft with retrospectively ECG-gated four-row multi-detector spiral computed tomography

The purpose of this study was to assess the accuracy of four-row multi-detector CT (MDCT) in the evaluation of coronary artery bypass graft (CABG) in patients with at least a left internal mammary artery (LIMA) grafted to the left anterior descending artery (LAD), because of the conduit of choice in bypass surgery and the greater difficulty of evaluation with non-invasive diagnostic tools. Included in the study were 57 patients with a total of 122 grafts (95 arterial and 27 venous) who underwent MDCT (4×2.5-mm detector-collimation, 3-mm slice width, 1.5-mm reconstruction increment) with retrospective ECG gating. Twelve patients (21%) with high heart rates were given beta-blockers in order to obtain a heart rate 70 bpm in all patients. The ECG-synchronized axial images, reconstructed in the mid-diastole, MPR, MIP and 3D-VR images were independently and blindly assessed by two radiologists for graft patency and presence of high grade stenosis. Conventional angiography was the standard of reference. MDCT correctly classified 92/94 patent grafts and 26/28 occluded grafts (sensitivity/specificity 93%/97.8%); sensitivity and specificity of MDCT for assessment of arterial grafts were 100 and 98.7% (77/78 patent grafts and 17/17 occluded grafts). Image quality was considered adequate for assessment of significant stenoses in 62/92 (67%) patent grafts, with a significant differences between LIMA and non-LIMA conduits (44/57 vs. 18/65; P=0.002), according to the coronary vessel area supplied (anterior>lateral>posterior-inferior wall; P=0.002). In the remaining 30 patent grafts (33%), the assessment of stenoses was hampered by surgical clips, calcifications and motion artifacts. Sensitivity and specificity of MDCT for detection of significant graft stenoses were 80 and 96%, respectively. Inter-observer agreement was good (K=0.73). MDCT seems to be a valuable diagnostic tool for non-invasive assessment of patency of both venous and arterial grafts. An accurate evaluation of distal anastomoses and native coronary arteries may still represent a limitation of four-row MDCT, which will improve with the newest MDCT scanner.     

The effects of nitric oxide on striatal serotoninergic transmission involve multiple targets: an in vivo microdialysis study in the awake rat

The role of endogenous nitric oxide (NO) in N-methyl-D-aspartate (NMDA)-induced modulation of serotonin (5-HT) release in the striatum of freely moving rats has been studied using microdialysis technique. NMDA-induced increase in 5-HT release was significantly inhibited by selective nitric oxide synthase (nNOS) inhibitor S-methylthiocitrulline (S-Me-TC), ONOO- scavenger L-cysteine (L-cys), and guanylate cyclase (GC) inhibitor 1H[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ). These data suggest that modulation of 5-HT levels is linked to the formation of NO produced by NMDA receptor activation and that endogenously produced NO increases 5-HT concentrations both by stimulating formation of 3'-5'-cyclic monophosphate (cGMP) and conversion of ONOO-.     

Markers of endothelial function in pediatric stem cell transplantation for acute leukemia

BACKGROUND: Endothelial cells and leukocytes intimately interact in inflammation and coagulation processes, so that dysregulation of their function may lead to both cellular damage and thrombosis, which may occur as complications of bone marrow transplantation (BMT). Partially conflicting evidence about endothelial markers and their relationships with clinical complications after BMT has been reported in the literature. Since almost all studies were carried out in adults, we evaluated some recent available markers of endothelial cell function in pediatric patients undergoing stem cell transplantation (SCT) for acute leukemia. PROCEDURE: We studied the variation in circulating serum endothelial-selectin (ES), leukocyte-selectin (LS), thrombomodulin (TM), von Willebrand factor (vWF), nitrate + nitrite (NO(2) (-)/NO(3) (-)), endothelin-1 (EN), and tissue factor (TF) in 21 pediatric patients undergoing SCT for acute leukemia. RESULTS: ES and LS significantly lowered following SCT and returned to pre-SCT levels 4 weeks after the procedure. NO(2) (-)/NO(3) (-) markedly increased following SCT. Also, TM and vWF increased, although such changes did not reach statistical significance. EN and TF did not appreciably change. A strong correlation was observed between white blood cell (WBC) count and both ES and LS, as well as between such selectins. TM significantly correlated with both selectins and NO(2) (-)/NO(3) (-). The pre-conditioning levels of TM and vWF in patients undergoing major complications, considered altogether, were significantly lower and higher, respectively, than in uncomplicated patients. NO(2) (-)/NO(3) (-) levels 3 and 4 weeks post-SCT were significantly lower in patients suffering from veno occlusive disease. Both selectins were significantly higher in allo- than in auto-transplanted patients 4 weeks after SCT. CONCLUSIONS: Our data support the hypothesis of severe endothelial damage after conditioning and SCT, particularly allogeneic. However, the increase in TM, which has strong anticoagulant properties, and metabolites of NO, involved also in protective actions, may reflect regeneration of the anti-thrombotic endothelial function. This could take place after transitory functional impairment, rather than pure endothelial damage.     

Comparison between rules-based human immunodeficiency virus type 1 genotype interpretations and real or virtual phenotype: concordance analysis and correlation with clinical outcome in heavily treated patients

We compared 2 rules-based genotype interpretation systems and real or virtual phenotype through a retrospective analysis of a prospective trial. Genotypes were determined with VircoGEN II (VIRCO) and were interpreted with either RetroGram 1.4 or TRUGENE HIV-1 (guidelines 3.0) or original virtual phenotype (Virtual Phenotype; VIRCO), as available in the year 2000. Among 188 human immunodeficiency virus (HIV) type 1 isolates, overall concordance (kappa agreement) was observed for the 2 rules-based systems, whereas striking discordances were noted between them and real and virtual phenotype interpretations for stavudine, didanosine, zalcitabine, abacavir, and amprenavir (kappa<0.4). Clinical evaluation of a subset of 173 patients showed that both rules-based sensitivity scores were independently associated with HIV RNA loads <400 copies/mL at week 16 of during-treatment analysis (TRUGENE: odds ratio [OR], 2.90; 95% confidence interval [CI], 1.52-5.52; P=.001; RetroGram: OR, 2.34; 95% CI, 1.21-4.55; P=.012), whereas, in contrast to real or virtual phenotype, interpretations according to biological cut-offs were not (OR, 1.91; 95% CI, 0.77-4.76; P=.162).     

Lymphatic drainage and CTV in breast cancer

Conformal radiotherapy has improved the technique and favored the solution of the problem of limiting cardiac and pulmonary irradiation. However new uncertainties have arisen especially with regard to treatment reproducibility. Passing from the clinical concept of CTV to the geometric concept of PTV, the anatomic identification of the different structure becomes of major importance together with the knowledge of the clinical evolution of breast cancer. The irradiation of breast lymph nodes now requires, if possible, 3D conformal processing of the treatment. Treatment parameters should be selected as to ensure adequate irradiation of target volumes while sparing healthy tissues as much as possible. In a near future, IMRT should be able to markedly improve the dose homogeneity to target with consequent lower cardiopulmonary toxicity.     

The psychosocial approach to the planning and implementation of vaccine trials for HIV infection

The production of an effective vaccine for HIV infection is one of the major challenges for the third millennium public health. Here we review published studies addressing the issue of incentives and barriers influencing the choice to participate in a vaccine trial. Currently available literature clearly indicates the need to include psychosocial dimensions in the preparation and implementation of vaccine trials. The underestimation of participants' satisfaction about information communication may lead to non-adherence and to drop-out from the trials. Proper attention to communication skills of professionals involved in participants' enrollment and follow-up is essential to ensure trial success.     

p46, a Novel Natural Killer Cell–specific Surface Molecule That Mediates Cell Activation

Limited information is available on the surface molecules that are involved in natural killer (NK) cell triggering. In this study, we selected the BAB281 monoclonal antibody (mAb) on the basis of its ability to trigger NK-mediated target cell lysis. BAB281 identified a novel NK cell–specific surface molecule of 46 kD (p46) that is expressed by all resting or activated NK cells. Importantly, unlike the NK cell antigens identified so far, the expression of p46 was strictly confined to NK cells. Upon mAb-mediated cross-linking, p46 molecules induced strong cell triggering leading to [Ca²⁺]i increases, lymphokine production, and cytolytic activity both in resting NK cells and NK cell clones. The p46-mediated induction of Ca²⁺ increases or triggering of cytolytic activity was downregulated by the simultaneous engagement of inhibitory receptors including p58, p70, and CD94/NKG2A. Both the unique cellular distribution and functional capability of p46 molecules suggest a possible role in the mechanisms of non-major histocompatibility complex–restricted cytolysis mediated by human NK cells.