Anti-(apolipoprotein A-1) IgGs are associated with high levels of oxidized low-density lipoprotein in acute coronary syndrome.

ApoA-1 (apolipoprotein A-1) is the main component of HDL (high-density lipoprotein) and stabilizes PON-1 (paraoxonase-1), which prevents lipid peroxidation and oxLDL (oxidized low-density lipoprotein) formation. Autoantibodies against apoA-1 [anti-(apoA-1) IgG] have been found in antiphospholipid syndrome and systemic lupus erythematosous, two diseases with an increased risk of thrombotic events, as well as in ACS (acute coronary syndrome). OxLDL levels are also elevated in these diseases. Whether anti-(apoA-1) IgGs exist in other prothrombotic conditions, such as APE (acute pulmonary embolism) and stroke, has not been studied and their potential association with oxLDL and PON-1 activity is not known. In the present study, we determined prospectively the prevalence of anti-(apoA-1) IgG in patients with ACS (n=127), APE (n=58) and stroke (n=34), and, when present, we tested their association with oxLDL levels. The prevalance of anti-(apoA-1) IgG was 11% in the ACS group, 2% in the control group and 0% in the APE and stroke groups. The ACS group had significantly higher median anti-(apoA-1) IgG titres than the other groups of patients. Patients with ACS positive for anti-(apoA-1) IgG had significantly higher median oxLDL values than those who tested negative (226.5 compared with 47.7 units/l; P<0.00001) and controls. The Spearman ranked test revealed a significant correlation between anti-(apoA-1) IgG titres and serum oxLDL levels (r=0.28, P<0.05). No association was found between PON-1 activity and oxLDL or anti-(apoA-1) IgG levels. In conclusion, anti-(apoA-1) IgG levels are positive in ACS, but not in stroke or APE. In ACS, their presence is associated with higher levels of oxLDL and is directly proportional to the serum concentration of oxLDL. These results emphasize the role of humoral autoimmunity as a mediator of inflammation and coronary atherogenesis.

Value of brain natriuretic peptide in the perioperative follow-up of children with valvular disease.

OBJECTIVE: To characterize N-terminal pro-brain natriuretic peptide (N-proBNP) and troponin I (TnI) profile following mitral and/or aortic valve surgery and to evaluate correlations with echocardiography measures and outcome criteria. DESIGN AND SETTING: Prospective cross-controlled study in a university children's hospital. PATIENTS: Twenty children with acquired valvular disease requiring valvular surgery. INTERVENTIONS: We prospectively studied clinical, biochemical, and echocardiographic characteristics at baseline and 6, 12, 24 h and 3-4 weeks postoperatively. RESULTS: TnI peaked 6 h after surgery and remained elevated during the first 24 h. N-proBNP was significantly lower 3-4 weeks after surgery than during the perioperative period. Overall, N-proBNP was correlated with the Pediatric Heart Failure Index, left ventricle shortening fraction, left atrium to aorta ratio, left ventricle mass index, end-systolic wall stress, and with outcome measures such as inotropic score, duration of inotropic support, and ICU length of stay. Preoperative N-proBNP was significantly more elevated in patients with complicated outcome than in patients with uneventful postoperative course. CONCLUSIONS: In pediatric valvular patients, perioperative N-proBNP is a promising risk stratification predicting factor. It is correlated with evolutive echocardiographic measures, need for inotropic support, and ICU length of stay.

Correlation between cardiac biomarkers and right ventricular enlargement on chest CT in non massive pulmonary embolism.

BACKGROUND: Troponin I (cTnI), myoglobin, heart-type fatty acid binding protein (H-FABP), and natriuretic peptides (BNP, NTproBNP) were all reported to be elevated in patients with pulmonary embolism (PE). METHODS: To assess the correlation between the aforementioned markers and helical computed tomography (hCT) right ventricular dysfunction (RVD) in non massive PE, we performed this prospective pilot study on 50 patients. RESULTS: Patients with RVD had significant higher natriuretic peptides prevalence than cardiomyocytes damage-related markers (48% vs 20%, P=0.006). Significant prevalence differences were observed only for natriuretic peptides when patients with RVD and those without were compared (74% vs 33% for NT-pro BNP, P=0.005 and 65% vs 22% for BNP, P=0.003). Patients with RVD had significant higher biomarkers median plasmatic values than those without (BNP: 170 vs 36 pg/ml, P=0.0027; NT-proBNP: 1369 vs 170.7 pg/ml, P=0.0024; cTnI: 0.032 vs 0 ng/ml, P=0.0034; H-FABP: 4.32 vs 2.23 ng/ml, P=0.0032; myoglobin: 36.7 vs 28.2 ng/ml, P=0.03). Significant correlations were only obtained between RV/LV index and plasmatic natriuretic peptides (NT-proBNP: r=0.36, P=0.009; BNP r=0.28; P=0.047). CONCLUSIONS: Natriuretic peptides prevalence elevation and median values are significantly higher when RVD is present and significantly correlate with hCT RVD.

Nutrition status in patients younger and older than 60 y at hospital admission: a controlled population study in 995 subjects.

OBJECTIVE: Body weight and body mass index are easily obtainable indicators of nutrition status but do not provide information on changes in fat-free mass (FFM) and fat mass with age. In this prospective controlled study, we investigated whether body composition measurements were useful in identifying moderately or severely depleted patients, as judged by the Subjective Global Assessment at hospital admission. In addition, the subjects were grouped by age (< or =60 and >60 y) to determine whether there was an effect of aging on the prevalence of malnutrition. METHODS: Nine hundred ninety-five consecutive patients were evaluated for malnutrition by body mass index, serum albumin, Subjective Global Assessment, and 50-kHz bioelectrical impedance analysis and compared with 995 age- and height-matched healthy volunteers for FFM and fat mass. RESULTS: A body mass index less than 20 kg/m(2) was found in 17.3% of patients. Low albumin (< or =34.9 g/L) was found in 14.9% of all patients and 23.7% of those older than 60 y. In contrast, 23.1% and 38.3% of all patients were severely and moderately depleted, respectively, according to the Subjective Global Assessment. FFM was significantly lower in severely depleted men and women and moderately depleted women (P < or = 0.001), and fat mass was significantly higher (P < or = 0.05) in well-nourished patients than in volunteers. Patients older than 60 y had lower FFM and higher fat mass than did patients 60 y or younger or volunteers (P < or = 0.001). CONCLUSION: The prevalence of malnutrition was greater in patients older than 60 y than in those 60 y and younger. Patients classified as severely depleted according to the Subjective Global Assessment were depleted of FFM. Body composition measurement can help to identify patients with low FFM and high fat mass.

Comparison of classifications for heart failure in children undergoing valvular surgery.

OBJECTIVES: To characterize correlations between clinical classifications of heart failure and diagnostic workup. STUDY DESIGN: Pre- and postoperative characteristics of 20 children with heart failure secondary to valvular rheumatic disease were studied. RESULTS: Both scoring systems correlated with N-terminal pro-brain natriuretic peptide (N-proBNP) but not with troponin I (TnI). The PHFI correlated with N-proBNP, end-systolic wall stress, left ventricular mass index and left atrium to aorta diameter ratio. No correlation could be established between modified Ross score, or the New York Heart Association (NYHA) grade and echocardiographic measurements. Cardiothoracic and Sokolow indexes were correlated with the PHFI as well as to the NYHA classification. CONCLUSION: In this study, PHFI seems better correlated with radiologic, electrocardiographic, echocardiographic, and biologic assessment of heart failure in children. Clinical severity was correlated with N-proBNP but not with TnI.

Inducible expression of Snail selectively increases paracellular ion permeability and differentially modulates tight junction proteins.

Constitutive expression of the transcription factor Snail was previously shown to trigger complete epithelial-mesenchymal transition (EMT). The aim of this study was to determine whether inducible expression of Snail could modify epithelial properties without eliciting full mesenchymal conversion. For this purpose, we expressed mouse Snail (mSnail) cDNA in Madin-Darby canine kidney (MDCK) cells under the control of a doxycycline-repressible transactivator. Inducible expression of Snail did not result in overt EMT but induced a number of phenotypic alterations of MDCK cells, the most significant of which was the absence of fluid-filled blisterlike structures called "domes." To understand the mechanisms responsible for dome suppression, we assessed the effect of mSnail expression on epithelial barrier function. Although mSnail did not alter tight junction (TJ) organization and permeability to uncharged solutes, it markedly decreased transepithelial electrical resistance. In light of these findings, we evaluated the ability of MDCK cell monolayers to maintain ionic gradients and found that expression of mSnail selectively increases Na+ and Cl- permeability. Analysis of the expression of claudins, transmembrane proteins that regulate TJ ionic permeability, showed that mSnail induces a moderate decrease in claudin-2 and a substantial decrease in claudin-4 and -7 expression. Together, these results suggest that induction of mSnail selectively increases the ionic permeability of TJs by differentially modulating the expression of specific claudins.

MODULAR ANALYTICS: A New Approach to Automation in the Clinical Laboratory.

MODULAR ANALYTICS (Roche Diagnostics) (MODULAR ANALYTICS, Elecsys and Cobas Integra are trademarks of a member of the Roche Group) represents a new approach to automation for the clinical chemistry laboratory. It consists of a control unit, a core unit with a bidirectional multitrack rack transportation system, and three distinct kinds of analytical modules: an ISE module, a P800 module (44 photometric tests, throughput of up to 800 tests/h), and a D2400 module (16 photometric tests, throughput up to 2400 tests/h). MODULAR ANALYTICS allows customised configurations for various laboratory workloads. The performance and practicability of MODULAR ANALYTICS were evaluated in an international multicentre study at 16 sites. Studies included precision, accuracy, analytical range, carry-over, and workflow assessment. More than 700 000 results were obtained during the course of the study. Median between-day CVs were typically less than 3% for clinical chemistries and less than 6% for homogeneous immunoassays. Median recoveries for nearly all standardised reference materials were within 5% of assigned values. Method comparisons versus current existing routine instrumentation were clinically acceptable in all cases. During the workflow studies, the work from three to four single workstations was transferred to MODULAR ANALYTICS, which offered over 100 possible methods, with reduction in sample splitting, handling errors, and turnaround time. Typical sample processing time on MODULAR ANALYTICS was less than 30 minutes, an improvement from the current laboratory systems. By combining multiple analytic units in flexible ways, MODULAR ANALYTICS met diverse laboratory needs and offered improvement in workflow over current laboratory situations. It increased overall efficiency while maintaining (or improving) quality.

Inhibition of inducible nitric oxide synthase protects against liver injury induced by mycobacterial infection and endotoxins.

BACKGROUND/AIMS: Bacillus Calmette Guerin (BCG) infection causes hepatic injury following granuloma formation and secretion of cytokines which render mice highly sensitive to endotoxin-mediated hepatotoxicity. This work investigates the role of inducible nitric oxide synthase (iNOS) in liver damage induced by BCG and endotoxins in BCG-infected mice. METHODS: Liver injury and cytokine activation induced by BCG and by LPS upon BCG infection (BCG/LPS) were compared in wild-type and iNOS-/- mice. RESULTS: iNOS-/- mice infected with living BCG are protected from hepatic injury when compared to wild-type mice which express iNOS protein in macrophages forming hepatic granulomas. In addition, iNOS-/- mice show a decrease in BCG-induced IFN-gamma serum levels. LPS challenge in BCG-infected mice strongly activates iNOS in the liver and spleen of wild-type mice which show important liver damage associated with a dramatic increase in TNF and IL-6 and also Th1 type cytokines. In contrast, iNOS-/- mice are protected from liver injury after BCG/LPS challenge and their TNF, IL-6 and Th1 type cytokine serum levels raise moderately. CONCLUSIONS: These results demonstrate that nitric oxide (NO) from iNOS is involved in hepatotoxicity induced by both mycobacterial infection and endotoxin effects upon BCG infection and that inhibition of NO from iNOS protects from liver injuries.