Allergen-induced synthesis of F(2)-isoprostanes in atopic asthmatics. Evidence for oxidant stress

It is thought that reactive oxygen species (ROS) participate in the inflammation which characterizes asthma, but the evidence supporting this contention is incomplete. F(2)-isoprostanes (F(2)-IsoPs) are arachidonate products formed on membrane phospholipids by the action of ROS and thereby represent a quantitative measure of oxidant stress in vivo. Using a mass spectrometric assay we measured urinary release of F(2)-IsoPs in 11 patients with mild atopic asthma after inhaled allergen challenge. The excretion of F(2)-IsoPs increased at 2 h after allergen (1.5 +/- 0.2 versus 2.6 +/- 0.3 ng/mg creatinine) and remained significantly elevated in all urine collections for the 8-h period of the study (analysis of variance [ANOVA]). The measured compounds were of noncyclooxygenase origin because neither aspirin nor indomethacin given before challenge suppressed them. Urinary F(2)-IsoPs remained unchanged after inhaled methacholine challenge. In nine atopic asthmatics, F(2)-IsoPs were quantified in bronchoalveolar lavage fluid (BALF) at baseline values and in a separate segment 24 h after allergen instillation. F(2)-IsoPs were elevated late in the BALF (0.9 +/- 0.2 versus 11.4 +/- 3.0 pg /ml, baseline versus allergen, respectively, p = 0.007). The increase was inhibited by pretreatment of the subjects with inhaled corticosteroids. These findings provide a new evidence for a role for ROS and lipid peroxidation in allergen-induced airway inflammation.     

Infection by the retrovirus associated with the acquired immunodeficiency syndrome. Clinical, biological, and molecular features

Peripheral mononuclear cells from more than 160 persons from groups at risk for the acquired immunodeficiency syndrome (AIDS) have yielded AIDS-associated retroviruses (ARV). Antibodies to ARV can also be found in these risk groups. Antibody-negative, virus-positive persons have been identified with early infection or possible viremia with immune complex formation. Established lines of human T and B cells, monocytes, and promyelocytes have been infected with ARV. Moreover, infectious virus has been recovered from macrophages cultured from the blood of some persons with AIDS. The cytopathic effects of ARV in T cells is associated with the accumulation of unintegrated viral forms in the infected cells. The ARV has also been isolated from plasma, serum, saliva, semen, urine, cerebrospinal fluid, and brain tissue. All these results reflect the wide host range of ARV and support its role in neurologic abnormalities seen in some patients. Molecular studies of independent ARV isolates indicate a polymorphism of nucleotide sequences, particularly in the viral envelope region. All these features place ARV in the lentivirus subfamily of human retroviruses.     

Predictors of the rise in vWF after ST elevation myocardial infarction: implications for treatment strategies and clinical outcome: An ENTIRE-TIMI 23 substudy.

AIMS: Prior studies suggest that acute coronary syndromes (ACSs) are associated with endothelial activation and that this is of prognostic significance. We hypothesized that endothelial activation, as measured by a rise in von Willebrand Factor (DeltavWF), was influenced by the thrombolysis in myocardial infarction flow grade (TFG), the corrected TIMI frame count (CTFC) and the choice of anticoagulant therapy after fibrinolysis in ST elevation myocardial infarction (STEMI). METHODS AND RESULTS: Data were drawn from the enoxaparin and tenecteplase tissue plasminogen activator (TNK-tpa) with or without GPIIb/IIIa inhibitor as the reperfusion strategy in the STEMI trial (ENTIRE-TIMI 23). Three hundred and fourteen patients had serial measurements of vWF (baseline and 48-72 h) and angiographic data available. TFG<3 (P=0.0042) or CTFC>/=40 at 60 min (P=0.0035) were associated with a higher DeltavWF. DeltavWF >/=75th percentile was associated with a higher incidence of death or myocardial infarction (MI) at 30 days, compared with <75th percentile (11.2 vs. 4.1%, P=0.027). Enoxaparin independently reduced the DeltavWF (P=0.019) and also the composite of death or MI (OR 0.33, 95% CI 0.12-0.91, P=0.03) compared with unfractionated heparin. CONCLUSION: In STEMI treated by fibrinolysis, coronary flow at 60 min and choice of adjunctive anticoagulant appear to be independent determinants of DeltavWF. Enoxaparin is independently associated with a reduction in DeltavWF and a reduction in death or MI. The clinical benefits of enoxaparin as an adjunctive treatment in STEMI may be mediated in part by a reduction in vWF release.     

Safety and Effectiveness of Transvenous Lead Extraction in Octogenarians

Transvenous Lead Extraction . Introduction: As the population ages, the number of elderly patients with implantable cardiac devices referred for transvenous lead extraction will dramatically increase in Western countries. The safety and effectiveness of lead extraction in elderly patients has not been well evaluated. We report the safety and effectiveness of transvenous lead extraction in octogenarians. Methods and Results: From January 2005 to January 2011, we reviewed data from consecutive patients ≥ 80 years referred to our institutions for transvenous lead extraction because of cardiac device infection or lead malfunction. Clinical characteristics, procedural features, and periprocedural major and minor complications were compared between octogenarians and younger patients. Out of 849 patients undergoing lead extraction in the participating institutions during the study period, 150 (18%) patients were octogenarians (mean age 84 years; range 80–96; 64% males). A significantly higher percentage of octogenarians presented with chronic renal failure (55% vs 26%; P < 0.001), history of malignancy (22% vs 6%; P < 0.001), and chronic obstructive pulmonary disease (46% vs 19%; P < 0.001). Complete lead extraction rates were similar in the 2 age groups (97% in octogenarians vs 96% in patients <80 years; P = 0.39). Periprocedural death occurred in 2 (1.3%) patients ≥80 years and in 5 (0.72%) patients <80 years (P = 0.45 for comparison). No differences in terms of other periprocedural major and minor complications were found between the 2 age groups. Conclusion: Despite presenting with a significantly higher rate of comorbidities, transvenous lead extraction can be performed safely and successfully in octogenarians. (J Cardiovasc Electrophysiol, Vol. 23 pp. 1103‐1108, October 2012)