The mechanisms responsible for the persistence of HIV-1 after many years of suppressive antiretroviral therapy (ART) have been only partially elucidated. Most of the studies investigating HIV-1 persistence have been performed with blood, although it is well known that germinal centers (GCs) within lymph nodes (LNs) serve as primary sites for HIV-1 replication. We sought to identify the memory CD4 T cell populations in blood and LNs that are responsible for the production of replication-competent and infectious HIV-1, as well as for active and persistent virus transcription in ART-treated (for 1.5-14.0 years), aviremic (<50 HIV RNA copies/ml) HIV-infected individuals. We demonstrate that LN CD4 T cells that express programmed cell death 1 (PDCD1; also known as PD-1), which are composed of about 65% T follicular helper cells as defined by the expression of the cell surface receptors CXCR5 and PD-1, are the major source of replication-competent HIV-1 and of infectious virus, as compared to any other (CXCR5(-)PD-1(-) and CXCR5(+)PD-1(-)) blood or LN memory CD4 T cell populations. LN PD-1(+) cells accounted for 46% and 96% of the total pools of memory CD4 T cells containing inducible replication-competent or infectious virus, respectively. Notably, higher levels of cell-associated HIV-1 RNA were present in LN PD-1(+) cells after long-term (up to 12 years) ART than in other memory CD4 T cell subpopulations. These results indicate that LN PD-1(+) cells are the major CD4 T cell compartment in the blood and LNs for the production of replication-competent and infectious HIV-1, and for active and persistent virus transcription in long-term-ART-treated aviremic individuals. Thus, these cells may represent a major obstacle to finding a functional cure for HIV-1 infection.
The increased circumferential stress resulting from the flow-mediated dilatation rather than the elevation of blood pressure appears to represent the main contributing factor to the eccentric hypertrophy of the venous limb of Brescia-Cimino haemodialysis access.
Objective: Fish oil (FO) may attenuate the inflammatory response after major surgery such as abdominal aortic aneurysm (AAA) surgery. We aimed at evaluating the clinical impact and safety aspects of a FO containing parenteral nutrition (PN) after AAA surgery. Methods: Intervention consisted in 4 days of either standard (STD: Lipofundin medium-chain triglyceride (MCT): long-chain triglyceride (LCT)50%-MCT50%) or FO containing PN (FO: Lipoplus: LCT40%-MCT50%-FO10%). Energy target were set at 1.3 times the preoperative resting energy expenditure by indirect calorimetry. Blood sampling on days 0, 2, 3 and 4. Glucose turnover by the 2 H 2 -glucose method. Muscle microdialysis. Clinical data: maximal daily T1, intensive care unit (ICU) and hospital stay. Results: Both solutions were clinically well tolerated, without any differences in laboratory safety parameters, inflammatory, metabolic data, or in organ failures. Plasma tocopherol increased similarly; with FO, docosahexaenoic and eicosapentaenoic acid increased significantly by day 4 versus baseline or STD. To increased postoperatively, with a trend to lower values in FO group (P ¼ 0.09). After FO, a trend toward shorter ICU stay (1.670.4 versus 2.370.4), and hospital stay (9.972.4 versus 11.372.7 days: P ¼ 0.19) was observed. Conclusions: Both lipid emulsions were well tolerated. FO-PN enhanced the plasma n-3 polyunsaturated fatty acid content, and was associated with trends to lower body temperature and shorter length of stay.
The long-term kinetics of T cell production following highly active antiretroviral therapy (HAART) were investigated in blood and lymph node in a group of HIV-infected subjects at early stage of established infection and prospectively studied for 72 wk. Before HAART, CD4 and CD8 T cell turnover was increased. However, the total number of proliferating CD4 ؉ T lymphocytes, i.e., CD4 ؉ Ki67 ؉ T lymphocytes, was not significantly different in HIV-infected (n ؍ 73) and HIV-negative (n ؍ 15) subjects, whereas proliferating CD8 ؉ Ki67 ؉ T lymphocytes were significantly higher in HIV-infected subjects. After HAART, the total body number of proliferating CD4 ؉ Ki67 ؉ T lymphocytes increased over time and was associated with an increase of both naive and memory CD4 ؉ T cells. The maximal increase (2-fold) was observed at week 36, whereas at week 72 the number of proliferating CD4 ؉ T cells dropped to baseline levels, i.e., before HAART. The kinetics of the fraction of proliferating CD4 and CD8 T cells were significantly correlated with the changes in the total body number of these T cell subsets. These results demonstrate a direct relationship between ex vivo measures of T cell production and quantitative changes in total body T lymphocyte populations. This study provides advances in the delineation of the kinetics of T cell production in HIV infection in the presence and͞or in the absence of HAART.
Blood flow <120 mL has a good predictive value for early failure in RCAVF. During the procedure, this cut-off value may be used to select appropriately which RCAVF should be investigated in the operation theatre in order to correct in real time any abnormality.
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