Background: HIV-infected subjects have increased risk for atherosclerosis. Both carotid artery intima-media thickness (IMT) assessed by ultrasound and coronary artery calcium (CAC) detected by comp...
We applied a new test statistic for linkage that removes the traditional assumption of equal female (theta f) and male (theta m) recombination fractions by testing Ho: theta f + theta m = 1 vs. HA: theta f + theta m < 1 to GAW10 Problem 1. Specifically we reanalyzed the reported possible linkage between a suggested susceptibility locus for bipolar affective disorder and marker D18S41 on chromosome 18 [Stine et al., 1995]. We used penetrance functions fitting the description of those used by Stine et al. [1995] assuming a continuous age-dependent logistic distribution. Maximum likelihood marker allele frequencies were estimated assuming Hardy-Weinberg equilibrium. Results from the traditional lod-score analyses do not strongly support the existence of linkage between the disease locus and marker D18S41. Similarly, the new test statistic for linkage failed to provide evidence in support of linkage. This was true whether dominant or recessive models of inheritance were assumed, and whether the analyses included all available pedigrees or were confined to paternally transmitted pedigrees. The appreciable difference found between our lod scores and those obtained by Stine et al. [1995] can be attributed to differences in the assumptions made regarding the age-dependent penetrance function, the marker allele frequencies, or both.
PURPOSE STUDY In cardiovascular tissue engineering, tissue is constructed from its cellular components. Fibrin gel can be produced of the patients blood and be used as an autologous scaffold for the seeded fibroblasts to form a 3-dimensional tissue. However the contraction of tissue during the culture period causes a major problem for the creation of functional tissue. The fixation with microstructured culture plates in comparison with a poly-L-lysine fixation was investigated in this study. METHODS To preserve tissue from shrinking a small border (2–3 mm) of the wells were precoated with a 0.01% solution of poly-L-lysine (group L). 3-D microstructured tissue culture polysterene plates (3D-TCPS)(Integra Bioscience Inc., Switzerland) were used in group S. A suspension of fibrin and myofibroblast (∼ 1.75±106 cells per well) was placed in each well. Cells were cultured with medium supplemented with 1 mM L-ascorbic acid 2-phosphate and aprotinin (20 μg/ml) for 25 days. The macroscopic Tissue detachment was evaluated twice a week and tissue development were investigated by light microscopy. Hydroxyproline assay was performed as a marker of collagen production. SUMMARIZE RESULTS In group S. 2 of 12 partial and 4 of 12 complete tissue detachments were observed vs no detachment in group L. Light microscopy of the cellular sheets showed myofibroblasts surrounded by extracellular matrix. The concentration of hydroxyproline was significantly higher (p < 0.05) in group L (7.1 μg/mg ± 1.78) than in the non detached group S (4.8 μg/mg ± 0.6) and particularly significantly higher (p < 0.01) in comparison with the detached group S (3.1 μg/mg ± 0.57). The 3D-TCPS is principly able to prevent the shrinking of the fibrin gel although not as efficient as poly-L-lysine. The elimination of the non structured border of the 3D-TCPS may lead to lower detachment rates.
Excess risk of cardiovascular disease occurs in effectively treated individuals with human immunodeficiency virus (HIV) infection. Although elevated plasma D-dimer levels are associated with increased morbidity and mortality, the impact of HIV infection on coagulation in vivo has not been well studied.We measured D-dimers, antithrombin, endogenous thrombin potential (ETP; a functional measure of thrombin generation in vitro), thrombin/antithrombin complexes (TAT; a measure of thrombin generation in vivo), tissue factor, prothrombin fragment 1 + 2 (F1+2), and normalized APC sensitivity ratio (nAPCsr) in 199 HIV-positive men who were receiving antiretroviral therapy and had an undetectable HIV RNA level, in 79 HIV-positive untreated men, and in 39 uninfected controls.Median antithrombin levels were higher while the ETP was lower among HIV-infected adults (treated and untreated), compared with controls. There were few differences between coagulation markers in the 2 HIV groups. Compared with controls, the nAPCsr was lower in treated men and the TAT level was lower in untreated individuals. We observed little difference among measured levels of D-dimer, tissue factor, or F1+2 between HIV-infected individuals and controls. Antiretroviral therapy exposure was associated with a lower antithrombin level, a lower nAPCsr, and a lower ETP, while history of opportunistic infection was associated with a higher nAPCsr.HIV infection is associated with decreased thrombin generation, as measured by the ETP, and an increased antithrombin level. These data suggest that HIV infection may not be associated with increased propensity toward clotting, as has been suggested on the basis of isolated measures of D-dimer levels.
Purpose HIV-associated morbidity and mortality have decreased following the introduction of highly active antiretroviral therapy. Previous studies have shown that HIV-infected patients are at increased risk for atherosclerosis, independent of other risk factors. Measurement of carotid artery intima media thickness (IMT) is a noninvasive method of assessing atherosclerosis that predicts myocardial infarction and stroke even after adjustment for traditional risk factors. Wherease some studies of HIV patients have shown increased carotid IMT measurements, others have not. We hypothesized that the disparity between these studies may result from different methods used to measure carotid IMT, namely, either including or excluding the bifurcation region. Methods Carotid IMT data were available from 230 HIV-infected individuals. Measurements were taken on both right and left sides at a total of 12 sites per subject. These included the near and far walls of the common carotid artery (CCA), the bifurcation (BIF), and the internal carotid artery (ICA). A carotid plaque was defined as IMT ≥ 1.5 mm. Results The mean IMT of all sites (0.97 mm ± 0.40) was significantly higher than the mean taken from only the CCA (0.74 mm ± 0.30; p Conclusion These data suggest that the different results from recent carotid IMT studies in HIV patients may result from important differences in IMT measurement protocols, some of which exclude the most common sites for plaque formation. A standard procedure should be established to be able to compare the results from different centers. As the majority of disease in our HIV patients was found at the BIF region, we recommend a measurement protocol that includes this specific region.
