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Federal Way, WA, United States

Mata I.F.,Veterans Affairs Puget Sound Health Care System
Movement disorders : official journal of the Movement Disorder Society | Year: 2012

Common variants in the LRRK2 gene influence the risk of Parkinson's disease (PD) in Asians, but whether the same is true in European-derived populations is less clear. We genotyped 66 LRRK2 tagging single-nucleotide polymorphisms (SNPs) in 575 PD patients and 689 controls from the northwestern United States (tier 1). PD-associated SNPs (P < .05) were then genotyped in an independent sample of 3617 cases and 2512 controls from the United States and Spain (tier 2). Logistic regression was used to model additive SNP genotype effects adjusted for age and sex among white individuals. Two regions showed independent association with PD in tier 1, and SNPs in both regions were successfully replicated in tier 2 (rs10878226, combined odds ratio [OR], 1.20; 95% confidence interval [CI], 1.08-1.33; P = 6.3 × 10(-4); rs11176013, OR, 0.89; CI, 0.83-0.95; P = 4.6 × 10(-4)). Our data suggest that common variation within LRRK2 conveys susceptibility for PD in individuals of European ancestry. Copyright © 2012 Movement Disorder Society. Source

Lankford H.V.,8001 Riverside Drive | Swenson E.R.,Veterans Affairs Puget Sound Health Care System
High Altitude Medicine and Biology | Year: 2014

Lankford, Harvey V, Erik R Swenson. Dilated hearts at high altitude: Words from on high. High Alt Med Biol 15:511-519, 2014. - From the time of the turn of the twentieth century, dilated hearts and presumed cardiac fatigue in expeditionary climbers and scientists have been the subject of much commentary in the medical and mountaineering literature. Although largely attributed by most, but not all, to left heart strain, the description of dilated hearts in these accounts is clearly that of right heart dilation as a consequence of high and sustained hypoxic pulmonary vasoconstriction with hypertensive remodeling. This essay will feature quotations from the writings of high altitude pioneers about dilated, strained, or enlarged hearts. It will give some brief physiology of the right side of the heart as background, but will focus on the words of mountaineers and mountaineering physicians as color commentary. Copyright © 2014, Mary Ann Liebert, Inc. 2014. Source

Rowhani-Rahbar A.,University of Washington | Zatzick D.,University of Washington | Wang J.,University of Washington | Mills B.M.,University of Washington | And 3 more authors.
Annals of Internal Medicine | Year: 2015

Background: Risk for violent victimization or crime perpetration after firearm-related hospitalization (FRH) must be determined to inform the need for future interventions. Objective: To compare the risk for subsequent violent injury, death, or crime perpetration among patients with an FRH, those hospitalized for noninjury reasons, and the general population. Design: Retrospective cohort study. Setting: All hospitals in Washington. Patients: Patients with an FRH and a random sample of those with a non-injury-related hospitalization in 2006 to 2007 (index hospitalization). Measurements: Primary outcomes included subsequent FRH, firearm-related death, and the combined outcome of firearm- or violence-related arrest ascertained through 2011. Results: Among patients with an index FRH (n = 613), rates of subsequent FRH, firearm-related death, and firearm- or violencerelated arrest were 329 (95% CI, 142 to 649), 100 (CI, 21 to 293), and 4221 (CI, 3352 to 5246) per 100 000 person-years, respectively. Compared with the general population, standardized incidence ratios among patients with an index FRH were 30.1 (CI, 14.9 to 61.0) for a subsequent FRH and 7.3 (CI, 2.4 to 22.9) for firearm-related death. In survival analyses that accounted for competing risks, patients with an index FRH were at greater risk for subsequent FRH (subhazard ratio [sHR], 21.2 [CI, 7.0 to 64.0]), firearm-related death (sHR, 4.3 [CI, 1.3 to 14.1]), and firearm- or violence-related arrest (sHR, 2.7 [CI, 2.0 to 3.5]) than those with a non-injury-related index hospitalization. Limitation: Lack of information on whether patients continued to reside in Washington during follow-up may have introduced outcome misclassification. Conclusion: Hospitalization for a firearm-related injury is associated with a heightened risk for subsequent violent victimization or crime perpetration. Further research at the intersection of clinical care, the criminal justice system, and public health to evaluate the effectiveness of interventions delivered to survivors of firearm-related injury is warranted. Primary Funding Source: Seattle City Council and University of Washington Royalty Research Fund. © 2015 American College of Physicians. Source

Ioannou G.N.,Veterans Affairs Puget Sound Health Care System
Annals of Internal Medicine | Year: 2011

Background: Up-to-date estimates of the prevalence of hepatitis B virus (HBV) infection, exposure, and immunity are necessary to assess the effectiveness of ongoing programs aimed at preventing HBV transmission. Objective: To determine the prevalence and associations of chronic HBV infection, past exposure, and immunity in the United States from 1999 to 2008. Design: Nationally representative, cross-sectional household survey. Setting: U.S. civilian, noninstitutionalized population. Participants: 39 787 participants in the National Health and Nutrition Examination Survey (1999 to 2008) aged 2 years or older. Measurements: Chronic HBV infection was defined by presence of serum HBV surface antigen and past exposure by serum antibody to hepatitis B core antigen among persons aged 6 years or older. Infant immunity was defined by presence of serum antibody to hepatitis B surface antigen among children aged 2 years. Results: Among persons aged 6 years or older, 0.27% (95% CI, 0.20% to 0.34%) had chronic HBV infection (corresponding to approximately 704 000 persons nationwide), and 4.6% (CI, 4.1% to 5.0%) had been exposed to HBV (approximately 11 993 000 persons). These estimates are lower (P < 0.001) than estimates of HBV infection (0.42%) and exposure (5.1%) in the United States reported from 1988 to 1994. Infection and past exposure were very uncommon among persons aged 6 to 19 years. Children aged 2 years have high rates of immunity (68.6% [CI, 64.1% to 73.2%]). Adults, including those at high risk for infection, have much lower rates of immunity. Limitations: Incarcerated and homeless persons were not sampled. Categorization of race or ethnicity did not identify high-risk groups, such as persons of Asian and Pacific Islander descent. Conclusion: A cohort of children and adolescents is growing up in the United States with high rates of immunity against HBV and very low rates of infection. Vaccination of high-risk adults should continue to be emphasized. Primary Funding Source: The veterans affairs research enhancement award program. © 2011 American College of Physicians. Source

Van Rooyen D.M.,Liver Research Group | Larter C.Z.,Liver Research Group | Haigh W.G.,University of Washington | Yeh M.M.,University of Washington | And 5 more authors.
Gastroenterology | Year: 2011

Background & Aims: Type 2 diabetes and nonalcoholic steatohepatitis (NASH) are associated with insulin resistance and disordered cholesterol homeostasis. We investigated the basis for hepatic cholesterol accumulation with insulin resistance and its relevance to the pathogenesis of NASH. Methods: Alms1 mutant (foz/foz) and wild-type NOD.B10 mice were fed high-fat diets that contained varying percentages of cholesterol; hepatic lipid pools and pathways of cholesterol turnover were determined. Hepatocytes were exposed to insulin concentrations that circulate in diabetic foz/foz mice. Results: Hepatic cholesterol accumulation was attributed to up-regulation of low-density lipoprotein receptor via activation of sterol regulatory element binding protein 2 (SREBP-2), reduced biotransformation to bile acids, and suppression of canalicular pathways for cholesterol and bile acid excretion in bile. Exposing primary hepatocytes to concentrations of insulin that circulate in diabetic Alms1 mice replicated the increases in SREBP-2 and low-density lipoprotein receptor and suppression of bile salt export pump. Removing cholesterol from diet prevented hepatic accumulation of free cholesterol and NASH; increasing dietary cholesterol levels exacerbated hepatic accumulation of free cholesterol, hepatocyte injury or apoptosis, macrophage recruitment, and liver fibrosis. Conclusions: In obese, diabetic mice, hyperinsulinemia alters nuclear transcriptional regulators of cholesterol homeostasis, leading to hepatic accumulation of free cholesterol; the resulting cytotoxicity mediates transition of steatosis to NASH. © 2011 AGA Institute. Source

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