Venkatachalam M.A.,University of Texas Health Science Center at San Antonio |
Weinberg J.M.,University of Michigan |
Kriz W.,University of Heidelberg |
Bidani A.K.,Hines Veterans Administration Hospital
Journal of the American Society of Nephrology | Year: 2015
The transition of AKI to CKDhasmajor clinical significance. As reviewed here, recent studies show that a subpopulation of dedifferentiated, proliferating tubules recovering from AKI undergo pathologic growth arrest, fail to redifferentiate, and become atrophic. These abnormal tubules exhibit persistent, unregulated, and progressively increasing profibrotic signaling along multiple pathways. Paracrine products derived therefrom perturb normal interactions between peritubular capillary endothelium and pericyte-like fibroblasts, leading to myofibroblast transformation, proliferation, and fibrosis as well as capillary disintegration and rarefaction. Although signals from injured endothelium and inflammatory/immune cells also contribute, tubule injury alone is sufficient to produce the interstitial pathology required for fibrosis. Localized hypoxia produced by microvascular pathology may also prevent tubule recovery. However, fibrosis is not intrinsically progressive, and microvascular pathology develops strictly around damaged tubules; thus, additional deterioration of kidney structure after the transition of AKI to CKD requires new acute injury or other mechanisms of progression. Indeed, experiments using an acute-on-chronic injury model suggest that additional loss of parenchyma caused by failed repair of AKI in kidneys with prior renal mass reduction triggers hemodynamically mediated processes that damage glomeruli to cause progression. Continued investigation of these pathologic mechanisms should reveal options for preventing renal disease progression after AKI. © 2015 by the American Society of Nephrology.
Hayward R.A.,Veterans Affairs Center for Clinical Management Research |
Reaven P.D.,Phoenix VA Health Care System |
Wiitala W.L.,Veterans Affairs Center for Clinical Management Research |
Bahn G.D.,Hines Veterans Administration Hospital |
And 5 more authors.
New England Journal of Medicine | Year: 2015
BACKGROUND: The Veterans Affairs Diabetes Trial previously showed that intensive glucose lowering, as compared with standard therapy, did not significantly reduce the rate of major cardiovascular events among 1791 military veterans (median follow-up, 5.6 years). We report the extended follow-up of the study participants. METHODS: After the conclusion of the clinical trial, we followed participants, using central databases to identify procedures, hospitalizations, and deaths (complete cohort, with follow-up data for 92.4% of participants). Most participants agreed to additional data collection by means of annual surveys and periodic chart reviews (survey cohort, with 77.7% follow-up). The primary outcome was the time to the first major cardiovascular event (heart attack, stroke, new or worsening congestive heart failure, amputation for ischemic gangrene, or cardiovascular-related death). Secondary outcomes were cardiovascular mortality and all-cause mortality. RESULTS: The difference in glycated hemoglobin levels between the intensive-therapy group and the standard-therapy group averaged 1.5 percentage points during the trial (median level, 6.9% vs. 8.4%) and declined to 0.2 to 0.3 percentage points by 3 years after the trial ended. Over a median follow-up of 9.8 years, the intensive-therapy group had a significantly lower risk of the primary outcome than did the standardtherapy group (hazard ratio, 0.83; 95% confidence interval [CI], 0.70 to 0.99; P = 0.04), with an absolute reduction in risk of 8.6 major cardiovascular events per 1000 person-years, but did not have reduced cardiovascular mortality (hazard ratio, 0.88; 95% CI, 0.64 to 1.20; P = 0.42). No reduction in total mortality was evident (hazard ratio in the intensive-therapy group, 1.05; 95% CI, 0.89 to 1.25; P = 0.54; median follow-up, 11.8 years). CONCLUSIONS: After nearly 10 years of follow-up, patients with type 2 diabetes who had been randomly assigned to intensive glucose control for 5.6 years had 8.6 fewer major cardiovascular events per 1000 person-years than those assigned to standard therapy, but no improvement was seen in the rate of overall survival. (Funded by the VA Cooperative Studies Program and others; VADT ClinicalTrials.gov number, NCT00032487.) Copyright © 2015 Massachusetts Medical Society. All rights reserved.
Gerding D.N.,Hines Veterans Administration Hospital |
Gerding D.N.,Loyola University Chicago
Infection Control and Hospital Epidemiology | Year: 2010
The past decade has been characterized by an epidemic of Clostridium difficile infection in North America and Europe that threatens to extend to the rest of the world. The epidemic is due in part to the emergence of a previously rare and now more lethal C. difficile strain variously named group BI, ribotype 027, and North American pulsed-field gel electrophoresis type 1. © 2010 by The 5th Decennial on Healthcare-Associated Infections, LLC. All rights reserved.
Gerding D.N.,Hines Veterans Administration Hospital |
Johnson S.,Loyola University Chicago
Clinical Infectious Diseases | Year: 2010
Treatment of Clostridium difficile infection (CDI) has relied on 2 antimicrobial agents, metronidazole and vancomycin, since the recognition of this disease entity. While effective, these "inside the box" approaches to CDI management have the disadvantage of further microbial disruption of the host indigenous microflora. "Outside the box" therapies use non-antimicrobial approaches to management and are theoretically less prone to causing recurrent CDI episodes. Recent advances in understanding of "inside the box" approaches include appreciation of the decreased efficacy of metronidazole overall and the superior efficacy of vancomycin for treatment of severe CDI, as well as a new agent under development, fidaxomicin, which appears to be equal in efficacy to vancomycin but with less risk of subsequent CDI recurrences. Several "outside the box" approaches have also entered clinical development, including use of monoclonal antibodies, active vaccination, luminal toxin binders, and nontoxigenic C. difficile. These reports provide optimism that more-effective management of CDI is forthcoming. © 2010 by the Infectious Diseases Society of America. All rights reserved.
Picken M.,Hines Veterans Administration Hospital
Hypertension | Year: 2016
The relative contribution of self-perpetuating versus hemodynamic-induced fibrosis to the progression of chronic kidney disease (CKD) after acute kidney injury (AKI) is unclear. In the present study, male Sprague-Dawley rats underwent right uninephrectomy and were instrumented with a blood pressure radiotelemeter. Two weeks later, separate groups of rats were subjected to 40 minutes renal ischemia–reperfusion or sham surgery and followed up for 4 or 16 weeks to determine the extent to which glomerulosclerosis and tubulointerstitial fibrosis as a result of the AKI–CKD transition (ie, at 4 weeks post AKI) change over time during the progression of CKD (ie, at 16 weeks post AKI). On average, tubulointerstitial fibrosis was ≈3-fold lower (P<0.05), whereas glomerulosclerosis was ≈6-fold higher (P<0.05) at 16 versus 4 weeks post AKI. At 16 weeks post AKI, marked tubulointerstitial fibrosis was only observed in rats exhibiting marked glomerulosclerosis, proteinuria, and kidney hypertrophy consistent with a hemodynamic pathogenesis of renal injury. Moreover, quantitative analysis between blood pressure and renal injury revealed a clear and modest blood pressure threshold (average 16-week systolic blood pressure of ≈127 mm Hg) for the development of glomerulosclerosis. In summary, modest levels of blood pressure may be playing a substantial role in the progression of renal disease after AKI in settings of preexisting CKD associated with 50% loss of renal mass. In contrast, these data do not support a major role of self-perpetuating tubulointerstitial fibrosis in the progression CKD after AKI in such settings. © 2016 American Heart Association, Inc
Fortenbaugh F.C.,Hines Veterans Administration Hospital
Journal of vision | Year: 2012
Previous studies of localization of stationary targets in the peripheral visual field have found either underestimations (foveal biases) or overestimations (peripheral biases) of target eccentricity. In the present study, we help resolve this inconsistency by demonstrating the influence of visual boundaries on the type of localization bias. Using a Goldmann perimeter (an illuminated half-dome), we presented targets at different eccentricities across the visual field and asked participants to judge the target locations. In Experiments 1 and 2, participants reported target locations relative to their perceived visual field extent using either a manual or verbal response, with both response types producing a peripheral bias. This peripheral localization bias was a non-linear scaling of perceived location when the visual field was not bounded by external borders induced by facial features (i.e., the nose and brow), but location scaling was linear when visual boundaries were present. Experiment 3 added an external border (an aperture edge placed in the Goldmann perimeter) that resulted in a foveal bias and linear scaling. Our results show that boundaries that define a spatial region within the visual field determine both the direction of bias in localization errors for stationary objects and the scaling function of perceived location across visual space.
Langert K.A.,Hines Veterans Administration Hospital
ASN neuro | Year: 2013
Recruitment and trafficking of autoreactive leucocytes across the BNB (blood-nerve barrier) is an early pathological insult in GBS (Guillain-Barré syndrome), an aggressive autoimmune disorder of the PNS (peripheral nervous system). Whereas the aetiology and pathogenesis of GBS remain unclear, pro-inflammatory cytokines, including TNFα (tumour necrosis factor α), are reported to be elevated early in the course of GBS and may initiate nerve injury by activating the BNB. Previously, we reported that disrupting leucocyte trafficking in vivo therapeutically attenuates the course of an established animal model of GBS. Here, PNMECs (peripheral nerve microvascular endothelial cells) that form the BNB were harvested from rat sciatic nerves, immortalized by SV40 (simian virus 40) large T antigen transduction and subsequently challenged with TNFα. Relative changes in CCL2 (chemokine ligand 2) and ICAM-1 (intercellular adhesion molecule 1) expression were determined. We report that TNFα elicits marked dose- and time-dependent increases in CCL2 and ICAM-1 mRNA and protein content and promotes secretion of functional CCL2 from immortalized and primary PNMEC cultures. TNFα-mediated secretion of CCL2 promotes, in vitro, the transendothelial migration of CCR2-expressing THP-1 monocytes. Increased CCL2 and ICAM-1 expression in response to TNFα may facilitate recruitment and trafficking of autoreactive leucocytes across the BNB in autoimmune disorders, including GBS.
Alhosaini M.,Hines Veterans Administration Hospital |
Leehey D.J.,Hines Veterans Administration Hospital
American Journal of Kidney Diseases | Year: 2015
Disorders of magnesium homeostasis are very common in dialysis patients but have received scant attention. In this review, we address measurement of plasma magnesium, magnesium balance and the factors that affect magnesium flux during dialysis, the prevalence of hypo- and hypermagnesemia in dialysis patients, and the potential clinical significance of hypo- and hypermagnesemia in dialysis patients. Many factors can affect plasma magnesium concentration, including diet, nutritional status (including plasma albumin level), medications (such as proton pump inhibitors), and dialysis prescription. Further interventional studies to determine the effect of normalization of plasma magnesium concentration on clinical outcomes are needed. At the present time, we recommend that predialysis plasma magnesium be measured on a regular basis, with the dialysate magnesium concentration adjusted to maintain plasma magnesium concentration within the normal range.
Jubran A.,Hines Veterans Administration Hospital |
Jubran A.,Loyola University Chicago
Critical Care | Year: 2015
Pulse oximetry is universally used for monitoring patients in the critical care setting. This article updates the review on pulse oximetry that was published in 1999 in Critical Care. A summary of the recently developed multiwavelength pulse oximeters and their ability in detecting dyshemoglobins is provided. The impact of the latest signal processing techniques and reflectance technology on improving the performance of pulse oximeters during motion artifact and low perfusion conditions is critically examined. Finally, data regarding the effect of pulse oximetry on patient outcome are discussed. © 2015 Jubran.
Humensky J.L.,Hines Veterans Administration Hospital
Substance Abuse: Treatment, Prevention, and Policy | Year: 2010
Background: Previous literature has shown a divergence by age in the relationship between socioeconomic status (SES) and substance use: adolescents with low SES are more likely to engage in substance use, as are adults with high SES. However, there is growing evidence that adolescents with high SES are also at high risk for substance abuse. The objective of this study is to examine this relationship longitudinally, that is, whether wealthier adolescents are more likely than those with lower SES to engage in substance use in early adulthood.Methods: The study analyzed data from the National Longitudinal Survey of Adolescent Health (AddHealth), a longitudinal, nationally-representative survey of secondary school students in the United States. Logistic regression models were analyzed examining the relationship between adolescent SES (measured by parental education and income) and substance use in adulthood, controlling for substance use in adolescence and other covariates.Results: Higher parental education is associated with higher rates of binge drinking, marijuana and cocaine use in early adulthood. Higher parental income is associated with higher rates of binge drinking and marijuana use. No statistically significant results are found for crystal methamphetamine or other drug use. Results are not sensitive to the inclusion of college attendance by young adulthood as a sensitivity analysis. However, when stratifying by race, results are consistent for white non-Hispanics, but no statistically significant results are found for non-whites. This may be a reflection of the smaller sample size of non-whites, but may also reflect that these trends are driven primarily by white non-Hispanics.Conclusions: Previous research shows numerous problems associated with substance use in young adults, including problems in school, decreased employment, increases in convictions of driving under the influence (DUI) and accidental deaths. Much of the previous literature is focused on lower SES populations. Therefore, it is possible that teachers, parents and school administrators in wealthier schools may not perceive as great to address substance abuse treatment in their schools. This study can inform teachers, parents, school administrators and program officials of the need for addressing drug abuse prevention activities to this population of students. © 2010 Humensky; licensee BioMed Central Ltd.