BACKGROUND: In the current study, the authors attempted to describe the incidence, most common sites, and mortality of second primary malignancies among survivors of common cancers. METHODS: The authors identified patients aged ≥18 years who were diagnosed with a primary malignancy from the 10 most common cancer sites (prostate, breast, lung, colon, rectum, bladder, uterus, kidney, melanoma, and non-Hodgkin lymphoma) between 1992 and 2008 from Surveillance, Epidemiology, and End Results data. Factors associated with the incidence of second primary malignancies were explored using bivariable and multivariable models, and mortality attributable to first and second primary malignancies was examined. RESULTS: A cohort of 2,116,163 patients was identified, 170,865 of whom (8.1%) developed a second primary malignancy. Survivors of bladder cancer had the highest risk of developing a second cancer. In a multivariable model controlling for age, race, tumor grade, stage of disease, marital status, educational level, and income, a history of non-Hodgkin lymphoma (hazard ratios of 2.70 and 2.88, respectively, for men and women) and bladder cancer (hazard ratios of 1.88 and 1.66, respectively, for men and women) predicted the highest risk of developing a second cancer. For patients with 2 incident cancers, 13% died of their initial cancer, but greater than one-half (55%) died of their second primary malignancy. Lung cancer was the cause of death in 12% of patients with 2 incident cancers. CONCLUSIONS: Nearly 1 in 12 patients diagnosed with a common cancer developed a second malignancy, the most common of which was lung cancer. Greater than one-half of patients with 2 incident cancers died of their secondary malignancy. The findings from the current study may inform care strategies among cancer survivors.

. In one group of dogs (n ϭ 10), tempol infusion alone for 30 min before NLA infusion did not cause any significant changes in renal blood flow (RBF; 5.2 Ϯ 0.4 to 5.0 Ϯ 0.4 ml ⅐ min Ϫ1 ⅐ g Ϫ1 ), glomerular filtration rate (GFR; 0.79 Ϯ 0.04 to 0.77 Ϯ 0.04 ml ⅐ min Ϫ1 ⅐ g Ϫ1 ), urine flow (V; 13.6 Ϯ 2.1 to 13.9 Ϯ 2.5 l ⅐ minInterestingly, when tempol was infused in another group of dogs (n ϭ 12) pretreated with NLA, it caused increases in V (4.4 Ϯ 0.4 to 9.7 Ϯ 1.4 l⅐min Ϫ1 ⅐g Ϫ1) and in UNaV (0.7 Ϯ 0.1 to 1.3 Ϯ 0.2 mol⅐min Ϫ1 ⅐g Ϫ1 ) without affecting RBF or GFR. Although NO inhibition caused usual qualitative responses in both groups of dogs, the antidiuretic (47 Ϯ 5 vs. 26 Ϯ 4%) and antinatriuretic (67 Ϯ 4 vs. 45 Ϯ 11%) responses to NLA were seen much less in dogs pretreated with tempol. NLA infusion alone increased urinary excretion of 8-isoprostane (13.9 Ϯ 2.7 to 22.8 Ϯ 3.6 pg ⅐ min Ϫ1 ⅐ g Ϫ1

BackgroundNeurotropic arboviral infections are an important cause of encephalitis. A zoonotic, vector-borne alphavirus, Madariaga virus (MADV; formerly known as South American eastern equine encephalitis virus), caused its first documented human outbreak in 2010 in Darien, Panama, where the genetically similar Venezuelan equine encephalitis virus (VEEV) is endemic. We report the results of a seroprevalence survey of animals and humans, illustrating contrasting features of MADV and VEEV ecology and epidemiology.MethodsSmall mammals were trapped in 42 sites in Darien, Panama, using Sherman traps, Tomahawk traps, and mist nets for bats. Blood was tested for the presence of neutralizing antibodies to MADV and VEEV. In addition, bird sera collected in 2007 in Chagres, Panama, were tested for MADV and VEEV neutralizing antibodies. Viremia was ascertained by RT-PCR. Human exposure to these two viruses was determined by IgG ELISA, followed by plaque reduction neutralization tests. To identify relevant risk factors for MADV or VEEV exposure, logistic regression analysis was performed, and the most parsimonious model was selected based on the Akaike information criterion.ResultsThe animal survey yielded 32 bats (16 species), 556 rodents (12 species), and 20 opossums (4 species). The short-tailed cane mouse (Zygodontomys brevicauda) found abundantly in pasture and farms, had the highest MADV seroprevalence (8.3%). For VEEV, the shrub and forest-dwelling long-whiskered rice rat (Transandinomys bolivaris) had the highest seroprevalence (19.0%). Viremia was detected in one animal (Z. brevicauda). Of the 159 bird sera (50 species) tested, none were positive for either virus. In humans (n = 770), neutralizing antibodies to MADV and VEEV were present in 4.8% and 31.5%, respectively. MADV seropositivity was positively associated with cattle ranching, farming, and fishing. Having VEEV antibodies and shrubs near the house diminished risk. Age, forest work, farming and fishing were risk factors for VEEV, while having MADV antibodies, glazed windows, waste pick-up and piped water were protective.ConclusionOur findings suggest that the short-tailed cane mouse and the long-whiskered rice rat serve as hosts for MADV and VEEV, respectively. The preferred habitat of these rodent species coincides with areas associated with human infection risk. Our findings also indicate that MADV emerged recently in humans, and that the transmission cycles of these two sympatric alphaviruses differ spatially and in host utilization.

To assess the role of superoxide (O2-) and nitric oxide (NO) interaction in mediating the renal actions of ANG II, we examined the renal responses to intra-arterial infusion of ANG II (0.5 ng x kg(-1) x min(-1)) before and during administration of a superoxide dismutase mimetic, tempol (0.5 mg x kg(-1) x min(-1)), in the presence or absence of NO synthase inhibitor, nitro-L-arginine (NLA; 50 microg x kg(-1) x min(-1)), in anesthetized dogs pretreated with enalaprilat (33 microg x kg(-1) x min(-1)). In one group of dogs (n = 7), ANG II infusion before tempol infusion caused decreases of 24 +/- 4% in renal blood flow (RBF), 55 +/- 7% in urine flow (V), and 53 +/- 8% in urinary sodium excretion (U(Na)V) with a slight decrease in glomerular filtration rate (GFR; -7.8 +/- 3.4%). Tempol infusion alone did not cause significant alterations in RBF, GFR, V, or U(Na)V; however, ANG II in the presence of tempol caused a smaller degree of decreases in RBF (-12 +/- 2%), in V (-16 +/- 5%), and in U(Na)V (-27 +/- 10%) with a slight increase in GFR (6.6 +/- 2.8%) than the responses observed before tempol. In another group of NLA-treated dogs (n = 6), tempol infusion also caused significant attenuation in the ANG II-induced responses on RBF (-13 +/- 3% vs. -22 +/- 7%), GFR (-19 +/- 5% vs. -33 +/- 3), V (-15 +/- 12% vs. -28 +/- 4%), and U(Na)V (-11 +/- 14% vs. -32 +/- 7%). These data demonstrate that renal responses to ANG II are partly mediated by O2- generation and its interaction with NO. The sodium-retaining effect of ANG II is greatly influenced by O2- generation, particularly in the condition of NO deficiency.

This study was performed to examine the role of superoxide formation in the regulation of renal hemodynamic and excretory function and to assess its contribution in the pathogenesis of ANG II-dependent hypertension. Renal responses to acute intra-arterial infusion of the O2(-) scavenger tempol (50 microg x min(-1) x 100 g body wt(-1)) with or without catalase (1,500 U x min(-1) x 100 g(-1); both native and polyethylene glycol-catalase), which reduces H2O2, were evaluated in anesthetized male Sprague-Dawley rats treated chronically with ANG II (65 ng/min) for 2 wk and compared with nontreated control rats. In ANG II-treated hypertensive rats, tempol caused increases in medullary (13 +/- 2%), cortical (5 +/- 2%), and total renal blood flow (9 +/- 2%) without altering systemic arterial pressure. There were also increases in glomerular filtration rate (9 +/- 2%), urine flow (17 +/- 4%), and sodium excretion (26 +/- 5%). However, tempol infusion in nontreated normotensive rats did not cause significant changes in any of these renal parameters. Coinfusion of catalase with tempol did not alter the responses observed with tempol alone, indicating that the observed renal responses to tempol in ANG II-treated rats were attributed to its O2(-) scavenging effects without the involvement of H2O2. Tempol infusion also significantly decreased 8-isoprostane excretion in ANG II-treated rats (39 +/- 6%) without changes in H2O2 excretion. However, coinfusion of catalase reduced H2O2 excretion in both ANG II-treated (41 +/- 6%) and nontreated rats (28 +/- 5%). These data demonstrate that enhanced generation of O2(-) modulates renal hemodynamic and tubular reabsorptive function, possibly leading to sodium retention and thus contributing to the pathogenesis of ANG II-induced hypertension.