Citations

Abstract A number of mechanisms participate in virus-induced asthma. Previously, we described enhanced basophil histamine release (HR) during an experimentally induced rhinovirus infection and after in vitro incubation of peripheral blood mononuclear cells (PBMC) with influenza virus. This study extends our previous observations and examines the effect of influenza A virus on basophil leukotriene C4 (LTC4) release as well as the effect of T-cell depletion on virus-enhanced basophil HR. PBMC were isolated from ragweed-allergic subjects and incubated with live influenza A virus or control medium (allantoic fluid). After incubation with influenza A, ragweed antigen (AgE) stimulated LTC4 and HR were enhanced (P < 0.05). To further define the role of T cells in virus-enhanced basophil secretion, PBMC were isolated and divided into two aliquots. In one aliquot, T cells were removed by magnetic bead separation of mouse monoclonal anti-CD3-coated lymphocytes. T-cell-depleted and nontreated PBMC suspensions were incubated with influenza A or control medium, collected, and challenged with AgE to release histamine. Basophil HR was enhanced in the virus-treated group of PBMC that had not undergone T-cell depletion. In contrast, virus incubation did not enhance HR in the T-cell-depleted fraction. Finally, preliminary analysis of the supernate from virus-treated leukocytes indicates the presence of interferon-γ. These findings suggest that T cells, and their cytokine products, play an integral role in the process by which viruses enhance basophil HR.

External groups requiring measures now include public and private payers, regulators, accreditors and others that certify performance levels for consumers, patients and payers. Although benefits have accrued from the growth in quality measurement, the recent explosion in the number of measures threatens to shift resources from improving quality to cover a plethora of quality-performance metrics that may have a limited impact on the things that patients and payers want and need (ie, better outcomes, better care, and lower per capita costs). Here we propose a policy that quality measurement should be: balanced to meet the need of end users to judge quality and cost performance and the need of providers to continuously improve the quality, outcomes and costs of their services; and parsimonious to measure quality, outcomes and costs with appropriate metrics that are selected based on end-user needs.

Abstract Chronic obstructive pulmonary disease (COPD) is a strong risk factor for lung cancer. Published studies about variations of genes encoding glutathione metabolism, DNA repair, and inflammatory response pathways in susceptibility to COPD were inconclusive. We evaluated 470 single-nucleotide polymorphisms (SNP) from 56 genes of these three pathways in 620 cases and 893 controls to identify susceptibility markers for COPD risk, using existing resources. We assessed SNP- and gene-level effects adjusting for sex, age, and smoking status. Differential genetic effects on disease risk with and without lung cancer were also assessed; cumulative risk models were established. Twenty-one SNPs were found to be significantly associated with risk of COPD (P < 0.01); gene-based analyses confirmed two genes (GCLC and GSS) and identified three additional genes (GSTO2, ERCC1, and RRM1). Carrying 12 high-risk alleles may increase risk by 2.7-fold; eight SNPs altered COPD risk without lung cancer by 3.1-fold and 4 SNPs altered the risk with lung cancer by 2.3-fold. Our findings indicate that multiple genetic variations in the three selected pathways contribute to COPD risk through GCLC, GSS, GSTO2, ERCC1, and RRM1 genes. Functional studies are needed to elucidate the mechanisms of these genes in the development of COPD, lung cancer, or both. Cancer Prev Res; 5(3); 365–73. ©2011 AACR.

AbstractObjectivesThe objective of this study is to examine the impact of marital status on survival of patients with epithelial ovarian cancer (EOC).MethodsPatients with a diagnosis of EOC were identified from the Surveillance, Epidemiology, and End Results Program for the period 1988–2006 and divided into married and unmarried groups. Statistical analysis using Student's t‐test, Kaplan–Meier, and Cox regression proportional hazards was performed.ResultsIn 49,777 patients with EOC, 51.2% were married and 48.8% were unmarried. White women were likely to be married compared with African Americans (52.0% vs 32.4%, p < 0.05). Younger age (63.9% vs 43.4%, p < 0.001) and early stage disease (37.5% vs 33.8%, p < 0.001) were more prominent in married patients compared with unmarried patients. Staging lymphadenectomy was performed more frequently in married than unmarried patients (39.9% vs 29.8%, p < 0.001).Overall 5‐year survival was 45.0% for married patients and 33.1% for unmarried patients, p < 0.001. Married patients had a better survival compared with unmarried patients within each racial subgroup: 44.5% vs 33.3% for White women (p < 0.001), 36.9% vs 24.9% for African Americans (p < 0.001), and 53.7% vs 42.7% for others (p < 0.001), respectively. In a model that controlled for age, race, histology, stage, grade, and surgical treatment, married patients had a significantly improved survival compared with unmarried patients (HR 0.8, 95% CI 0.78–0.83, p < 0.001).ConclusionsIn this epidemiologic study, the social institution of marriage is associated with improved survival in women with ovarian cancer. Copyright © 2011 John Wiley & Sons, Ltd.

Abstract The contribution of emphysema to lung cancer risk has been recognized, but the effect size needs to be further defined. In this study, 565 primary lung cancer cases were enrolled though a prospective lung cancer cohort at Mayo Clinic, and 450 controls were smokers participating in a lung cancer screening study in the same institution using spiral computed tomography (CT). Cases and controls were frequency matched on age, gender, race, smoking status, and residential region. CT imaging using standard protocol at the time of lung cancer diagnosis (case) or during the study (control) was assessed for emphysema by visual scoring CT analysis as a percentage of lung tissue destroyed. The clinical definition of emphysema was the diagnosis recorded in the medical documentation. Using multiple logistic regression models, emphysema (≥5% on CT) was found to be associated with a 3.8-fold increased lung cancer risk in Caucasians, with higher risk in subgroups of younger (&lt;65 years old, OR = 4.64), heavy smokers (≥40 pack-years, OR = 4.46), and small-cell lung cancer (OR = 5.62). When using &gt;0% or ≥10% emphysema on CT, lung cancer risk was 2.79-fold or 3.33-fold higher than controls. Compared with CT evaluation (using criterion ≥5%), the sensitivity, specificity, positive and negative predictive values, and the accuracy of the clinical diagnosis for emphysema in controls were 19%, 98%, 73%, 84%, and 83%, respectively. These results imply that an accurate evaluation of emphysema could help reliably identify individuals at greater risk of lung cancer among smokers. Cancer Prev Res; 4(1); 43–50. ©2010 AACR.