Air pollution and cardiovascular disease: a statement for healthcare professionals from the Expert Panel on Population and Prevention Science of the American Heart Association

Air pollution is a heterogeneous, complex mixture of gases, liquids, and particulate matter. Epidemiological studies have demonstrated a consistent increased risk for cardiovascular events in relation to both short- and long-term exposure to present-day concentrations of ambient particulate matter. Several plausible mechanistic pathways have been described, including enhanced coagulation/thrombosis, a propensity for arrhythmias, acute arterial vasoconstriction, systemic inflammatory responses, and the chronic promotion of atherosclerosis. The purpose of this statement is to provide healthcare professionals and regulatory agencies with a comprehensive review of the literature on air pollution and cardiovascular disease. In addition, the implications of these findings in relation to public health and regulatory policies are addressed. Practical recommendations for healthcare providers and their patients are outlined. In the final section, suggestions for future research are made to address a number of remaining scientific questions.     

Invasive strategy following fibrinolysis in ST-elevation acute myocardial infarction.

BACKGROUND: A recognized drawback of ST-elevation acute myocardial infarction (STEMI) after fibrinolysis is persistent coronary occlusion or a less than TIMI 3 flow. The present study describes the results of systematic pre-discharge coronary angiography and revascularization, whenever indicated, following fibrinolytic therapy for STEMI. METHODS: Consecutive patients admitted with the diagnosis of STEMI between April 1, 2000 and April 30, 2002 were included in the study. Patients with contraindications to thrombolytic therapy and/or patients not eligible for angiography were excluded. All patients received "accelerated" treatment with alteplase and had a coronary angiography at least 24 hours later, in order to perform, if anatomically feasible, angioplasty with stenting. Angioplasty of non-infarct-related coronary arteries was allowed. The mortality, reinfarction and new revascularization rates were evaluated during index hospitalization and up to 30 days and 6 months. RESULTS: Eighty patients underwent cardiac catheterization at a median of 6.5 days following admission; in 86.3% of cases a patent infarct-related artery was found; in 71% of patients a coronary angioplasty was performed, with stenting in 88% of cases. Procedure-related complications were infrequent. No deaths occurred during hospitalization and at 30 days; at 6 months the mortality rate was 1.3%. In-hospital reinfarction occurred in 3.8% of patients, in 4% at 30 days and in 5.3% at 6 months. The rate of any new revascularization was 2.6% at 30 days and 11% at 6 months. CONCLUSIONS: Although obtained in a small observational study, our data, unlike those from previous studies, suggest that an invasive strategy after fibrinolysis in STEMI is safe and associated with low mortality and morbidity rates in the short and medium-terms.     

Identification and management of invasive mycoses in internal medicine: a road-map for physicians

Invasive mycoses are a rising problem, not only in traditional categories of patients like hematologic or neutropenic ones, but also in elderly non-neutropenic patients admitted to internal medicine wards. Patients being admitted to medical wards are usually older, have multiple comorbidities, e.g., liver cirrhosis or chronic obstructive respiratory disease, may be malnourished or receive peripheral or total parenteral nutrition, and frequently are undergoing chronic corticosteroid therapy, chemotherapy for cancer or monoclonal antibodies for autoimmune diseases. Such risk factors may be contemporarily present in a single patient increasing the risk for the development of invasive mycoses. Diagnosis of candidemia and invasive aspergillosis is particularly difficult in patients hospitalized on medical wards, since symptoms and signs have low specificity, and most diagnostic tests have been only validated in neutropenic hematologic patients, but not in those without neutropenia. Both candidemia and invasive aspergillosis carry significant morbidity and mortality. The aim of this paper is to provide a simple guide to physicians for a prompt identification and treatment of patients with possible or suspected invasive mycoses.     

Correlates of the shift in heart rate variability with an active postural change in a healthy population sample: The Atherosclerosis Risk In Communities study

Background The heart rate variability (HRV) response to postural change is a sensitive measure of the shift in autonomic balance from parasympathetic to sympathetic predominance that, when attenuated or absent, has been correlated with prevalent disease in patient populations. In a healthy population sample, we evaluated whether the shift in HRV with postural change differed by demographic characteristics as well as whether it differed between participants with established coronary heart disease (CHD) risk factors and their counterparts. Methods HRV was measured for 2 minutes in the supine and standing positions in a biracial sample of men and women (aged 45-64 years) without clinical CHD from the Atherosclerosis Risk In Communities Study (n = 7686). Mean differences among supine and standing mean R-R interval lengths, the SD of R-R intervals, and high-frequency power (HF) were compared by demographic characteristics (age, race, and sex) and CHD risk factors (smoking, obesity, physical activity, hypertension, and diabetes). Multivariable linear regression models were used to adjust for demographic characteristics. Results Smaller changes in R-R intervals and larger changes in SD of R-R intervals with standing were found among participants who were obese, less physically active than their counterparts, hypertensive, and diabetic. Smaller changes in HF were identified in male and white participants, but there were no differences in HF by CHD risk factors once models were adjusted for demographic characteristics. Conclusions These simple noninvasive measures can be used to detect differences in cardiac autonomic balance that may be markers for autonomic impairment in healthy adults. (Am Heart J 2002;143:808-13.)     

开通闭塞冠状动脉策略的全球性研究 GUSTO—Ⅱb（亚组研究）

病人资料 3 289例因急性冠脉综合征而接受溶栓治疗的患者,2274例接受t－PA治疗,1015例接受链激酶治疗。     

Interleukin-8 induces rapid mobilization of hematopoietic stem cells with radioprotective capacity and long-term myelolymphoid repopulating ability

Interleukin-8 (IL-8) belongs to a family of chemoattractant cytokines involved in chemotaxis and activation of neutrophils. As in vivo administration of IL-8 induces granulocytosis and the release of immature white blood cells into the circulation, we assessed a possible mobilizing effect of IL-8 on myeloid progenitor cells. IL-8 was administered at intraperitoneal doses ranging from 0.1 to 100 micrograms per mouse to female Balb/C mice (aged 8 to 12 weeks; weight, 20 to 25 g). Animals were killed at time intervals ranging from 1 to 240 minutes after IL-8 administration, and blood, bone marrow, and spleen cells were harvested. Injection of 30 micrograms IL-8 resulted in an increment from 25 +/- 9 to 418 +/- 299 granulocyte-macrophage colony-forming units (CFU-GM) per milliliter blood at 15 minutes after a single intraperitoneal injection. Sixty minutes after the injection of IL-8, the numbers of circulating CFU-GM per milliliter blood had almost returned to pretreatment values (82 +/- 39 CFU-GM per milliliter). A dose of 100 micrograms IL-8 per animal did not result in a further increment in the number of circulating CFU-GM. Transplantation of 5 x 10(5) blood-derived mononuclear cells (MNC) obtained at 30 minutes after IL-8 injection (30 micrograms) resulted in 69% survival of lethally irradiated (8.5 Gy) recipients at 60 days versus 22% for animals transplanted with an equal number of nonprimed blood-derived MNC. Transplantation of 1.5 x 10(6) MNC obtained from IL- 8-treated donors resulted in 100% survival. Six months after transplantation, female recipients of MNC derived from IL-8-treated male donors were killed, and chimerism was determined in bone marrow, spleen, and thymus using a Y chromosome-specific probe and fluorescent in situ hybridization (FISH). The majority of bone marrow, spleen, and thymus cells (83% +/- 25%, 89% +/- 5%, and 64 +/- 28%, respectively) consisted of Y chromosome-positive cells, showing that the IL-8- mobilized cells had myelolymphoid repopulating ability. We conclude that IL-8 is a cytokine that induces rapid mobilization of progenitor cells and pluripotent stem cells that are able to rescue lethally irradiated mice and that are able to completely and permanently repopulate host hematopoietic tissues.     

The functional characterization of interleukin-10 receptor expression on human natural killer cells

Human natural killer (NK) cells are large granular lymphocytes that constitutively express functional forms of the interleukin-2 receptor (IL-2R) and lyse tumor and virally infected cells without prior sensitization. NK cells with high density expression of CD56 (CD56bright) express the high affinity IL-2R and proliferate in response to low (picomolar) concentrations of IL-2. CD56dim NK cells express the intermediate affinity IL-2R and demonstrate enhanced cytotoxic activity without proliferation in response to high (nanomolar) concentrations of IL-2. In the present study, we characterized IL-10R expression on human NK cells and the functional consequences of IL-10 binding directly to highly purified subsets of CD56bright and CD56dim NK cells. Binding studies using 125I-IL-10 indicated that resting human NK cells constitutively express the IL-10 receptor protein at a surface density of approximately 90 receptor sites per cell, with a kd of approximately 1 nmol/L. Alone, IL-10 did not induce proliferation of CD56bright or CD56dim NK cell subsets. However, at low concentrations (0.5 to 5 ng/mL), IL-10 significantly augmented IL-2-induced proliferation of the CD56bright NK cell subset mediated via the high-affinity IL-2R. In the absence of IL-2, IL-10 was able to induce significant NK cytotoxic activity against NK-resistant tumor cell targets in both subsets of NK cells in a dose-dependent fashion. Furthermore, the combination of IL-10 and IL-2 had an additive effect on NK cytotoxic activity, whereas that of IL-10 and IL-12 did not. Production of interferon-gamma, tumor necrosis factor-alpha, and granulocyte-macrophage colony-stimulating factor by IL-2-activated NK cells was also significantly enhanced by IL-10. Neither resting nor activated human NK cells appear to produce human IL-10 protein. In summary, NK cells constitutively express the IL-10R protein in low density, and the functional consequences of IL-10 binding directly to human NK cell subsets appear to be stimulatory and dose-dependent. In contrast to its direct effects on human T cells and monocytes/macrophages, IL-10 potentiates cytokine production by human NK cells.     

Effects of troglitazone on in vitro oxidation of LDL and HDL induced by copper ions and endothelial cells

Summary Troglitazone is a new oral antidiabetic agent able to reduce lipid peroxidation. In this study we evaluated its effect on the susceptibility of LDL and HDL to in vitro oxidation induced by copper ions and endothelial cells. In Cu ⁺⁺ -induced LDL modification, different amounts of troglitazone were added to aliquots of the same pool of plasma with subsequent ultracentrifuge separation of LDL and HDL. Differences in LDL and HDL susceptibility to in vitro oxidation with Cu ⁺⁺ were studied by measuring the changes in fluorescence intensity (expressed as lag phase). LDL derived from plasma incubated with different amounts of troglitazone were also incubated with umbilical vein endothelial cells (HUVEC), the modification being monitored by LDL relative electrophoretic mobility and fluorescence. During Cu ⁺⁺ - and HUVEC-induced LDL oxidation, the decay rate of vitamin E, and the potency of troglitazone as a radical scavenger in comparison with vitamin E were also studied. Troglitazone determined a significant, dose-dependent decrease in Cu ⁺⁺ -induced LDL and HDL oxidation. Incubation with HUVEC was also followed by a progressive, significant decrease of LDL relative electrophoretic mobility and fluorescence intensity. During Cu ⁺⁺ - and HUVEC-induced-LDL modification, troglitazone significantly reduced the rate of vitamin E decay. In this study we also demonstrated that under the same oxidative stress, troglitazone was much more potent as a radical scavenger than vitamin E. In conclusion, the results demonstrate that troglitazone can reduce LDL and HDL in vitro oxidation and that, during this process, it can protect vitamin E. In addition to ensuring blood glucose control, the drug may therefore be useful in inhibiting lipoprotein peroxidation. [Diabetologia (1997) 40: 165–172] Received: 26 August 1996, and in revised form: 29 October 1996     

Recovery of contact hypersensitivity responses following murine bone marrow transplantation: comparison of gamma-irradiation and busulfan as preparative marrow-ablative agents

Bone marrow transplantation (BMT) is often followed by significant morbidity and mortality due to protracted immunodeficiency. We have hypothesized that the bone marrow-ablative regimen may delay the recovery of normal immune function following transplantation by impairing the interaction of host endothelial cells with circulating graft-derived lymphocytes. This report compares the relative effects of busulfan (an alkylating drug) and gamma-irradiation on the tissue- specific localization potential of lymphocytes and the eventual recovery of immune function within syngeneic murine transplant recipients. Localization of normal lymphocytes into peripheral lymph nodes of irradiated BMT recipients was markedly less (less than 50%) than in busulfan-treated or normal mice over the first 2 months post- BMT. This finding correlated with irradiation-induced endothelial cell edema and microvascular occlusions within lymphocyte-receptive areas of the nodal microvasculature. The effect of both preparative regimens on the recovery of contact hypersensitivity (CHS) was also analyzed. This response recovered more quickly (between 1 and 2 months) in busulfan- pretreated animals. Further experiments demonstrated that the decrease in CHS responsiveness appeared, in part, related to a depression in the capacity of lymphocytes to localize into skin sites of antigen deposition within irradiated mice. The impairment of tissue-specific lymphocyte localization may represent a novel mechanism by which whole body irradiation can contribute to delayed immunologic reconstitution following bone marrow transplantation.