Alcohol consumption and coronary artery calcium in middle-aged Japanese men

Epidemiologic studies have investigated the relation between alcohol intake and coronary calcification, with controversial results. Furthermore, the influence of heavy drinking has not been well elucidated. In the present study, a random sample of community-based Japanese men aged 40 to 49 years without a history of cardiovascular disease (n=245) were examined for coronary artery calcium (CAC) determined by electron-beam computed tomography and drinking status. There was a J-shaped association between alcohol intake and CAC. There was an increase of CAC in heavy drinkers (>or=46 g/day), and participants who were drinking>or=69 g/day showed a significant increase in CAC compared with never drinkers after adjusting for other cardiovascular risk factors.     

Biologic pathways associated with relapse in childhood acute lymphoblastic leukemia: a Children's Oncology Group study

Outcome for children with childhood acute lymphoblastic leukemia (ALL) who relapse is poor. To gain insight into the mechanisms of relapse, we analyzed gene-expression profiles in 35 matched diagnosis/relapse pairs as well as 60 uniformly treated children at relapse using the Affymetrix platform. Matched-pair analyses revealed significant differences in the expression of genes involved in cell-cycle regulation, DNA repair, and apoptosis between diagnostic and early-relapse samples. Many of these pathways have been implicated in tumorigenesis previously and are attractive targets for intervention strategies. In contrast, no common pattern of changes was observed among late-relapse pairs. Early-relapse samples were more likely to be similar to their respective diagnostic sample while we noted greater divergence in gene-expression patterns among late-relapse pairs. Comparison of expression profiles of early- versus late-relapse samples indicated that early-relapse clones were characterized by overexpression of biologic pathways associated with cell-cycle regulation. These results suggest that early-relapse results from the emergence of a related clone, characterized by the up-regulation of genes mediating cell proliferation. In contrast, late relapse appears to be mediated by diverse pathways.     

RNAIII-inhibiting peptide significantly reduces bacterial load and enhances the effect of antibiotics in the treatment of central venous catheter-associated Staphylococcus aureus infections

BACKGROUND: Medical devices used in clinical practice are often associated with biofilm-associated staphylococcal infections. METHODS: An in vitro antibiotic susceptibility assay of Staphylococcus aureus biofilms using 96-well polystyrene tissue-culture plates was performed to test the effects of RNAIII-inhibiting peptide (RIP), ciprofloxacin, imipenem, and vancomycin. Efficacy studies were performed using a rat model of central venous catheter (CVC)-associated infection. Twenty-four hours after implantation, the catheters were filled with RIP (1 mg/mL). Thirty minutes later, rats were challenged, via the CVC, with 1.0 x 10(6) cfu of S. aureus strain Smith diffuse. The antibiotic-lock technique was begun 24 h later. RESULTS: Minimum inhibitory concentrations of antibiotics in biofilms were at least 4-fold higher than those against the freely growing planktonic cells. When they were first treated with RIP, the cells in biofilms became as susceptible to antibiotics as did planktonic cells. These data were confirmed by the in vivo studies. In particular, when CVCs were treated with both RIP and antibiotics, the biofilm bacterial load was further reduced to 1 x 10(1) cfu/mL, and bacteremia was not detected, suggesting that there was 100% elimination of bacteremia and a 6 log10 reduction in biofilm bacterial load. CONCLUSION: RIP significantly reduces bacterial load and enhances the effect of antibiotics in the treatment of CVC-associated S. aureus infections.     

Towards an acoustic model-based poroelastic imaging method: II. experimental investigation

Soft biological tissue contains mobile fluid. The volume fraction of this fluid and the ease with which it may be displaced through the tissue could be of diagnostic significance and may also have consequences for the validity with which strain images can be interpreted according to the traditional idealizations of elastography. In a previous paper, under the assumption of frictionless boundary conditions, the spatio-temporal behavior of the strain field inside a compressed cylindrical poroelastic sample was predicted (Berry et al. 2006). In this current paper, experimental evidence is provided to confirm these predictions. Finite element modeling was first used to extend the previous predictions to allow for the existence of contact friction between the sample and the compressor plates. Elastographic techniques were then applied to image the time-evolution of the strain inside cylindrical samples of tofu (a suitable poroelastic material) during sustained unconfined compression. The observed experimental strain behavior was found to be consistent with the theoretical predictions. In particular, every sample studied confirmed that reduced values of radial strain advance with time from the curved cylindrical surface inwards towards the axis of symmetry. Furthermore, by fitting the predictions of an analytical model to a time sequence of strain images, parametric images of two quantities, each related to one or more of three poroelastic material constants were produced. The two parametric images depicted the Poisson's ratio (nu(s)) of the solid matrix and the product of the aggregate modulus (H(A)) of the solid matrix with the permeability (k) of the solid matrix to the pore fluid. The means of the pixel values in these images, nu(s) = 0.088 (standard deviation 0.023) and H(A)k = 1.449 (standard deviation 0.269) x 10(-7) m(2) s(-1), were in agreement with values derived from previously published data for tofu (Righetti et al. 2005). The results provide the first experimental detection of the fluid-flow-induced characteristic diffusion-like behavior of the strain in a compressed poroelastic material and allow parameters related to the above material constants to be determined. We conclude that it may eventually be possible to use strain data to detect and measure characteristics of diffusely distributed mobile fluid in tissue spaces that are too small to be imaged directly.     

Leukocyte-endothelium interactions after hemorrhagic shock/reperfusion and cecal ligation/puncture: an intravital microscopic study in rat mesentery

Hemorrhagic shock/reperfusion (HS/R) followed by sepsis triggers systemic microcirculatory disturbances that may induce multiple organ failure. The present study evaluated the effects of HS/R and cecal ligation and puncture, followed by necrotic cecal resection/peritoneal lavage (REL) on leukocyte-endothelium interactions at the mesentery. Eighty-one anesthetized Wistar rats (200-250 g) were randomly assigned to a first injury: (1) control-HS-no hemorrhagic shock/no reperfusion group, (2) HS/blood-HS/R with 25% shed blood, and (3) HS/blood + LR-HS/R with 25% of the shed blood + lactated Ringer's solution, 3x shed blood volume. Twenty-four hours post-HS/R, animals were submitted to cecal ligation and puncture and, 24 h thereafter, to REL. Leukocyte-endothelium interactions were assessed by intravital microscopy and intercellular adhesion molecule (ICAM) 1 and P-selectin expression by immunohistochemistry. Lungs were observed for ICAM-1 expression and neutrophil infiltration. Single and double injury induced significant increases in rolling (approximately 2-fold), adherent (approximately 5-fold), and migrated leukocytes (approximately 7-fold); ICAM-1 expression (approximately 1/2-fold), and P-selectin expression (approximately 1/2-fold) at the mesentery compared with control-HS group. REL normalized leukocyte-endothelium interactions at the mesentery in single-injured animals. However, in double-injured rats, adherence and migration of leukocytes decreased but did not normalize. Similar results were observed on ICAM-1 expression and neutrophil infiltration in the lungs from these animals. In conclusion, the current in vivo observation of the mesenteric microcirculation after a double injury followed by REL is a suitable model for the systematic evaluation of the inflammatory reaction at local and distant sites. In addition, data presented herein emphasized the importance of surgical removal of the septic focus in controlling the otherwise lethal sepsis-induced multiple organ dysfunction syndrome.