Edward L Peterson

Henry Ford Health System, Detroit, Michigan, United States

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Publications (227)1468.46 Total impact

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    ABSTRACT: Purpose: To describe the relationship between V[Combining Dot Above]O2 and surrogate markers of exercise intensity among patients with LVADs. Methods: Patients with continuous flow LVADS (n=24, 7 female) completed a symptom-limited graded exercise test on a treadmill. Heart rate and V[Combining Dot Above]O2 were measured continuously and averaged every 20 seconds. Regression equations were determined using a generalized estimating equation to predict %V[Combining Dot Above]O2R from %HRR, Borg rating of perceived exertion (RPE), and LVAD flow, overall and stratified by presence of pacing. Results: While the association between %HRR and %V[Combining Dot Above]O2R was good (R=0.75) the slope and y-intercept for %HRR versus %V[Combining Dot Above]O2R was different from the line of identity (p = 0.002). However, when paced subjects were excluded (n=8) from the analysis, there was no significant difference between the slope and y-intercept (%V[Combining Dot Above]O2R=0.036 + 0.937*%; SEE=2%; p=0.052). RPE showed a strong association with %V[Combining Dot Above]O2R (R=0.84) while LVAD flow showed a weak (albeit statistically significant) association (R=0.05). Both had slopes and y-intercepts that were different from the line of identity (p <0.05). Conclusions: In patients with LVADs who are not paced during exercise, the use of %HRR is a good predictor of %V[Combining Dot Above]O2R. However, for patients in this population who are also paced during exercise, RPE is a suitable surrogate measure of exercise intensity.
    Medicine and science in sports and exercise 09/2015; DOI:10.1249/MSS.0000000000000776 · 3.98 Impact Factor
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    ABSTRACT: Objective: Low birth weight (LBW) has been shown to be an independent risk factor for asthma. We hypothesized that LBW would have its greatest impact on early onset disease. Methods: A racially diverse cohort of children born from 1983 to 1985 at two hospitals, one urban and one suburban in the same metropolitan area, and oversampled for babies weighing ≤2500 g, was identified retrospectively when the children were 6 years of age and followed periodically. At the age 17 years study visit, cohort members and their parent/guardians were separately interviewed face-to-face regarding the subject's history of asthma using the standardized ISAAC questionnaire. We measured the cumulative incidence of asthma from birth through adolescence defined by age of diagnosis and persistence/remittance. Results: Six-hundred and eighty teens (82.6% of the original cohort) were included in the analyses, 387 with LBW and 293 of normal birth weight. The prevalence of physician-diagnosed "Current Asthma" was associated with LBW (p = 0.003 for trend), with patterns stronger in males and whites. LBW was associated most strongly with Late Onset Persistent asthma (current asthma that was diagnosed after 8 years); p for trend 0.032. This trend was again most evident in males and whites. None of the asthma categories classified as "remittent" were statistically associated with LBW. Conclusions: LBW was not associated with diagnosed asthma that remitted before age 17 years. LBW was associated with asthma diagnosis in mid-childhood that persisted through adolescence, suggesting that the asthmagenic effects of LBW can become evident post the early years of childhood and persist into adulthood.
    Journal of Asthma 09/2015; DOI:10.3109/02770903.2015.1054405 · 1.80 Impact Factor
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    ABSTRACT: N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) is a natural tetrapeptide with anti-inflammatory and antifibrotic properties. Its effect on salt-sensitive (SS) hypertension is unknown. We hypothesized that in Dahl SS rats on high-salt (HS) diet, Ac-SDKP prevents loss of nephrin expression and renal immune cell infiltration, leading to a decrease in albuminuria, renal inflammation, fibrosis, and glomerulosclerosis. To test this, Dahl SS rats and consomic SS13BN controls were fed either a low-salt (0.23% NaCl) or HS (4% NaCl) diet and treated for 6 weeks with vehicle or Ac-SDKP at either low or high dose (800 or 1600 µg/kg per day, respectively). HS increased systolic blood pressure in SS rats (HS+vehicle, 186±5 versus low salt+vehicle, 141±3 mm Hg; P<0.005) but not in SS13BN rats. Ac-SDKP did not affect blood pressure. Compared with low salt, HS-induced albuminuria, renal inflammation, fibrosis, and glomerulosclerosis in both strains, but the damages were higher in SS than in SS13BN. Interestingly, in SS13BN rats, Ac-SDKP prevented albuminuria induced by HS (HS+vehicle, 44±8 versus HS+low Ac-SDKP, 24±3 or HS+high Ac-SDKP, 8±1 mg/24 h; P<0.05), whereas in SS rats, only high Ac-SDKP dose significantly attenuated albuminuria (HS+vehicle, 94±10 versus HS+high Ac-SDKP, 57±7 mg/24 h; P<0.05). In both strains, Ac-SDKP prevented HS-induced inflammation, interstitial fibrosis, and glomerulosclerosis. In summary, in SS rats on HS diet, at low and high doses, Ac-SDKP prevented renal damage without affecting the blood pressure. Only the high dose of Ac-SDKP attenuated HS-induced albuminuria. Conversely, in SS13BN rats, both doses of Ac-SDKP prevented HS-induced renal damage and albuminuria. © 2015 American Heart Association, Inc.
    Hypertension 08/2015; 66(4). DOI:10.1161/HYPERTENSIONAHA.115.05970 · 6.48 Impact Factor
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    ABSTRACT: Elevated interleukin-4 (IL-4) levels are associated with cardiac fibrosis in hypertension and heart failure in both patients and experimental animals. We hypothesized that chronically elevated IL-4 induces cardiac fibrosis, resulting in a predisposition of the heart to angiotensin II-induced damage. Wild-type Balb/c (WT, high circulating IL-4) and IL-4-deficient Balb/c mice (IL-4(-/-)) were used. WT mice exhibited cardiac fibrosis (evidenced by an increase in expression of procollagen genes/interstitial collagen fraction), enlarged left ventricle chamber, and declined cardiac function associated with a greater number of mast cells and macrophages in the heart compared with IL-4(-/-). In contrast, IL-4(-/-) mice had normal cardiac architecture/function while showing a 57.9% reduction in heart interstitial collagen compared with WT, despite elevated proinflammatory cytokines in heart tissue. In response to angiotensin II administration, IL-4(-/-) had reduced interstitial myocardial fibrosis and were protected from developing dilated cardiomyopathy, which was seen in WT mice. This was associated with increased macrophage infiltration into the hearts of WT mice, despite a similar degree of hypertension and increased cardiac transforming growth factor-β1 in both groups. In vitro data demonstrated that IL-4 upregulates procollagen genes and stimulates collagen production in mouse cardiac fibroblasts. This process is mediated by signal transducer and activator of transcription 6 signaling pathway via IL-4 receptor alpha. This study not only establishes a causal relationship between IL-4 and cardiac fibrosis/dysfunction, but also reveals a critical role for IL-4 in angiotensin II-induced cardiac damage. IL-4 could serve as an additional target for the treatment of cardiac fibrosis.
    Hypertension 08/2015; 66(3):582-9. DOI:10.1161/HYPERTENSIONAHA.115.05627 · 6.48 Impact Factor

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    ABSTRACT: Angiotensin II type 2 receptor (AT2) and angiotensin I-converting enzyme 2 (ACE2) are important components of the renin-angiotensin system (RAS). Activation of AT2 and ACE2 reportedly counteract pro-inflammatory effects of angiotensin II. However, the possible interaction between AT2 and ACE2 has never been established. We hypothesized that activation of AT2 increases ACE2 activity, thereby preventing tumor necrosis factor-alpha (TNF-α) stimulated intercellular adhesion molecule-1 (ICAM-1) expression via inhibition of NF-κB signaling. Human coronary artery endothelial cells (HCAECs) were pretreated with AT2 antagonist PD123319 or ACE2 inhibitor DX600, and then stimulated with TNF-α in the presence or absence of AT2 agonist CGP42112 (CGP). We found that AT2 agonist CGP increased both ACE2 protein expression and activity. This effect was blunted by AT2 antagonist PD123319. ICAM-1 expression was very low in untreated cells but greatly increased by TNF-α. Activation of AT2 with agonist CGP or with angiotensin II under concomitant AT1 antagonist reduced TNF-α-induced ICAM-1 expression, which was reversed by AT2 antagonist PD123319 or ACE2 inhibitor DX600 or knockdown of ACE2 with siRNA. AT2 activation also suppressed TNF-α-stimulated phosphorylation of inhibitory κB (IκB) and NF-κB activity. Inhibition of ACE2 reversed the inhibitory effect of AT2 on TNFα-stimulated IκB phosphorylation and NF-κB activity. Our findings suggest that stimulation of AT2 reduces TNF-α-stimulated ICAM-1 expression, which is partly through ACE2-mediated inhibition of NF-κB signaling. Copyright © 2014, American Journal of Physiology - Heart and Circulatory Physiology.
    AJP Heart and Circulatory Physiology 07/2015; 309(5):ajpheart.00814.2014. DOI:10.1152/ajpheart.00814.2014 · 3.84 Impact Factor

  • Journal of Vascular Surgery 06/2015; 61(6):193S. DOI:10.1016/j.jvs.2015.04.366 · 3.02 Impact Factor
  • Xiaosong Gu · Jiang Xu · Xiao-Ping Yang · Edward Peterson · Pamela Harding ·
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    ABSTRACT: Levels of the chemokine fractalkine (FKN) are increased in patients with chronic heart failure (HF) and our studies show that aged mice lacking the prostaglandin E2 EP4 receptor subtype (EP4-KO) have increased cardiac FKN with a phenotype of dilated cardiomyopathy. However, how FKN participates in the pathogenesis of heart failure has rarely been studied. We therefore hypothesized that FKN contributes to the pathogenesis of heart failure and anti-FKN treatment prevents heart failure induced by myocardial infarction (MI) more effectively in EP4-KO mice. Male EP4-KO mice and wild type littermates underwent sham or MI surgery and were treated with an anti-FKN antibody or control IgG. At 2 wks post MI, echocardiography was performed and hearts excised for infarct size determination, immunohistochemistry and Western blot of signaling molecules. Since FKN protein levels in the left ventricle were increased similarly in both strains after MI and anti-FKN treatment improved survival and cardiac function in both strains; we subsequently used only WT mice to examine the mechanisms whereby anti-FKN is cardioprotective. Myocyte cross-sectional area (MCSA) and interstitial collagen fraction (ICF) were reduced after anti-FKN treatment, as were macrophage migration and gelatinase activity. Finally, activation of ERK 1/2 and p38MAPK were reduced after neutralization of FKN. In vitro, FKN increased fibroblast proliferation. In conclusion, increased FKN contributes to heart failure after MI. This effect is not exacerbated in EP4-KO mice, suggesting no link between FKN and lack of EP4. Overall, inhibition of FKN may be important to preserve cardiac function post MI. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Experimental physiology 05/2015; 100(7). DOI:10.1113/EP085104 · 2.67 Impact Factor
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    ABSTRACT: Systemic lupus erythematosus is an autoimmune disease characterized by the development of auto antibodies against a variety of self-antigens and deposition of immune complexes that lead to inflammation, fibrosis and end organ damage. Up to 60% of lupus patients develop nephritis and renal dysfunction leading to kidney failure. N-acetyl-seryl-aspartyl-lysyl-proline, i.e. Ac-SDKP, is a natural tetrapeptide that in hypertension prevents inflammation and fibrosis in heart, kidney, and vasculature. In experimental autoimmune myocarditis Ac-SDKP prevents cardiac dysfunction by decreasing innate and adaptive immunity. It has also been reported that Ac-SDKP ameliorates lupus nephritis in mice. We hypothesize that Ac-SDKP prevents lupus nephritis in mice by decreasing complement C5-9, proinflammatory cytokines, and immune cell infiltration. Lupus mice treated with Ac-SDKP for 20 weeks had significantly lower renal levels of macrophage and T cell infiltration and proinflammatory chemokine/cytokines. In addition, our data demonstrate for the first time that in lupus mouse Ac-SDKP prevented the increase in complement C5-9, RANTES, MCP-5 and ICAM-1 kidney expression and it prevented the decline of glomerular filtration rate. Ac-SDKP treated lupus mice had a significant improvement in renal function and lower levels of glomerular damage. Ac-SDKP had no effect on the production of autoantibodies. The protective Ac-SDKP effect is most likely achieved by targeting the expression of proinflammatory chemokines/cytokines, ICAM-1 and immune cell infiltration in the kidney, either directly or via C5-9 proinflammatory arm of complement system. Copyright © 2015, American Journal of Physiology - Renal Physiology.
    American journal of physiology. Renal physiology 03/2015; 308(10):ajprenal.00039.2015. DOI:10.1152/ajprenal.00039.2015 · 3.25 Impact Factor
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    ABSTRACT: Afferent (Af-Art) and efferent arterioles (Ef-Art) resistance regulate glomerular capillary pressure (GCP). The nephron regulates Af-Art resistance via: 1) vasoconstrictor tubuloglomerular feedback (TGF), initiated in the macula densa via Na/K/2Cl cotransporters (NKCC2); and 2) vasodilator connecting tubuloglomerular feedback (CTGF), initiated in connecting tubules (CT) via epithelial Na channels (ENaC). Furosemide inhibits NKCC2 and TGF. Benzamil inhibits ENaC and CTGF. In vitro, CTGF dilates preconstricted Af-Arts. In vivo, benzamil decreases stop-flow pressure (PSF), suggesting that CTGF antagonizes TGF; however, even when TGF is blocked, CTGF does not increase PSF, suggesting there is another mechanism antagonizing CTGF. We hypothesize that in addition to NKCC2, activation of Na/H exchanger (NHE) antagonizes CTGF, and when both are blocked CTGF dilates Af-Arts and this effect is blocked by a CTGF inhibitor benzamil. Using micropuncture, we studied the effects of transport inhibitors on TGF responses by measuring PSF while increasing nephron perfusion from 0 to 40 nL/min. Control TGF response (-7.9±0.2 mmHg) was blocked by furosemide (-0.4±0.2 mm Hg; P<0.001). Benzamil restored TGF in the presence of furosemide (furosemide: -0.2±0.1 vs furosemide+benzamil: -4.3±0.3 mmHg, P<0.001). With furosemide and NHE inhibitor, dimethylamiloride (DMA), increase in tubular flow increased PSF (furosemide+DMA: 2.7±0.5 mmHg, n=6), and benzamil blocked this (furosemide+DMA+benzamil: -1.1±0.2 mmHg, P<0.01, n=6). We conclude that NHE in the nephron decreases PSF (Af-Art constriction) when NKCC2 and ENaC are inhibited, suggesting that in the absence of NKCC2, NHE causes a TGF response and that CTGF dilates the Af-Art when TGF is blocked with NKCC2 and NHE inhibitors. Copyright © 2014, American Journal of Physiology - Renal Physiology.
    American journal of physiology. Renal physiology 02/2015; 308(9):ajprenal.00605.2014. DOI:10.1152/ajprenal.00605.2014 · 3.25 Impact Factor
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    ABSTRACT: Glucagon-like peptide-1 (GLP-1) agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors (GLP-1 agents) may be protective in heart failure (HF). We set out to determine whether GLP-1 agent use is associated with HF risk in diabetics. Retrospective cohort study of members of a large health system. We identified >19,000 adult diabetics from January 1, 2000-July 1, 2012. GLP-1 agent users were matched 1:2 to controls using propensity matching based on age, race, gender, coronary disease, HF, diabetes duration, and number of anti-diabetic medications. The association of GLP-1 agents with time to HF hospitalization was tested with multivariable Cox regression. All-cause hospitalization and mortality were secondary endpoints. We identified 1,426 users of GLP-1 agents and 2,798 controls. Both were similar except for angiotensin-converting enzyme inhibitors/angiotensin receptor blocker (ACEi/ARB) use, number of anti-diabetic medications and age. There were 199 hospitalizations, of which 128 were for HF, and 114 deaths. GLP-1 agents were associated with reduced risk of HF hospitalization (adjusted hazard ratio [aHR] 0.51; 95% confidence interval [CI] 0.34-0.77, p=0.002), all-cause hospitalization (aHR 0.54; 95% CI 0.38-0.74, p=0.001), and death (aHR 0.31; 95% CI 0.18-0.53, p=0.001). GLP-1 agents may reduce the risk of HF events in diabetics. Copyright © 2014 Elsevier Inc. All rights reserved.
    Journal of Cardiac Failure 10/2014; 21(1). DOI:10.1016/j.cardfail.2014.10.012 · 3.05 Impact Factor
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    ABSTRACT: Objective: Inflammation has been proposed as a key component in the development of hypertension and cardiac remodeling associated with different cardiovascular diseases. However, the role of the proinflammatory cytokine interleukin-6 in the chronic stage of hypertension is not well defined. Here, we tested the hypothesis that deletion of interleukin-6 protects against the development of hypertension, cardiac inflammation, fibrosis, remodeling and dysfunction induced by high salt diet and angiotensin II (Ang II). Methods: Male C57BL/6J and interleukin-6-knock out (KO) mice were implanted with telemetry devices for blood pressure (BP) measurements, fed a 4% NaCl diet, and infused with either vehicle or Ang II (90 ng/min per mouse subcutaneously) for 8 weeks. We studied BP and cardiac function by echocardiography at baseline, 4 and 8 weeks. Results: Myocyte cross-sectional area (MCSA), macrophage infiltration, and myocardial fibrosis were also assessed. BP increased similarly in both strains when treated with Ang II and high salt (Ang II-high salt); however, C57BL/6J mice developed a more severe decrease in left ventricle ejection fraction, fibrosis, and macrophage infiltration compared with interleukin-6-KO mice. No differences between strains were observed in MCSA, capillary density and MCSA to capillary density ratio. Conclusion: In conclusion, absence of interleukin -6 did not alter the development of Ang II-high salt-induced hypertension and cardiac hypertrophy, but it prevented the development of cardiac dysfunction, myocardial inflammation, and fibrosis. This indicates that interleukin-6 plays an important role in hypertensive heart damage but not in the development of hypertension.
    Journal of Hypertension 10/2014; 33(1). DOI:10.1097/HJH.0000000000000358 · 4.72 Impact Factor
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    ABSTRACT: Prostaglandin E2 (PGE2) is elevated during cardiac injury and we have previously shown that mice lacking the PGE2 EP4 receptor display dilated cardiomyopathy (DCM) with increased expression of the membrane type matrix metalloproteinase, MMP-14. We thus hypothesized that PGE2 regulates expression of MMP-14 and also affects fibroblast migration. Primary cultures of neonatal rat ventricular fibroblasts (NVFs) were used to test the effects of PGE2. Gene and protein expression was assessed by real time RT-PCR and Western blot, MMP activity was determined by zymography and migration of NVF was assessed by motility in a transwell system. PGE2 reduced expression of MMP-14 and these effects were antagonized by an EP4 antagonist. An EP4 agonist mimicked the effect of PGE2. PGE2 also increased mRNA and protein levels of plasminogen activator inhibitor-1 (PAI-1), an inhibitor of MMP activation. However, PGE2-stimulation of PAI-1 was mediated by the EP1/EP3 receptor and not EP4. Migration of NVF was assessed by motility in a transwell system. Treatment of NVFs with PGE2 reduced the number of cells migrating toward 10% FCS. Treatment with the EP2 agonist also reduced migration but did not affect MMP-14 expression or PAI-1. Our results suggest that PGE2 utilizes different receptors and mechanisms to ultimately decrease MMP expression and NVF migration.
    Prostaglandins & other lipid mediators 09/2014; 113. DOI:10.1016/j.prostaglandins.2014.09.002 · 2.38 Impact Factor
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    ABSTRACT: Thymosin β4 (Tβ4) promotes cell survival, angiogenesis, tissue regeneration and reduces inflammation. Cardiac rupture after myocardial infarction (MI) is mainly the consequence of excessive regional inflammation, whereas cardiac dysfunction after MI results from a massive cardiomyocyte loss and cardiac fibrosis. It is possible that Tβ4 reduces incidence of cardiac rupture post-MI via anti-inflammatory actions and that it decreases adverse cardiac remodeling and improves cardiac function by promoting cardiac cell survival and cardiac repair. C57BL/6 mice were subjected to MI and treated with either vehicle or Tβ4 (1.6 mg/kg/day i.p. via osmotic minipump) for 7 days or 5 weeks. Mice were assessed for 1) cardiac remodeling and function by echocardiography; 2) inflammatory cell infiltration, capillary density, myocyte apoptosis and interstitial collagen fraction (ICF) histopathologically; 3) gelatinolytic activity by in situ zymography; and 4) expression of intercellular adhesion molecule-1 (ICAM-1) and p53 by immunoblot. Tβ4 reduced cardiac rupture that was associated with decrease in the numbers of infiltrating inflammatory cells and apoptotic myocytes, decrease in gelatinolytic activity and ICAM-1 and p53 expression, as well as the increase in the numbers of CD31-positive cells. Five-week treatment with Tβ4 ameliorated left ventricular dilation, improved cardiac function, and markedly reduced ICF and increased capillary density. In murine model of acute MI, Tβ4 not only decreased mortality rate as a result of cardiac rupture but also significantly improved cardiac function after MI. Thus the use of Tβ4 could be explored as an alternative therapy in preventing cardiac rupture and restoring cardiac function in patients with MI.
    AJP Heart and Circulatory Physiology 07/2014; 307(5). DOI:10.1152/ajpheart.00129.2014 · 3.84 Impact Factor
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    ABSTRACT: The afferent arteriole (Af-Art) controls glomerular capillary pressure, an important determinant of glomerular injury. Af-Art myogenic response is mediated by ATP, and ATP signaling is in turn mediated by 20-HETE. Dahl salt-sensitive rats (Dahl SS) have decreased renal 20-HETE production. We hypothesized that Dahl SS have an impaired myogenic response and constrictor response to ATP, due to decreased 20-HETE. Af-Arts from Dahl SS or Dahl salt resistant rats (Dahl SR) were microdissected and perfused. When myogenic response was induced by increasing Af-Art perfusion pressure from 60 to 140 mmHg, luminal Af-Art diameter decreased in Dahl SR but not in Dahl SS (-3.1±0.8 vs. 0.5±0.8 µm, P<0.01). The 20-HETE antagonist 20-HEDE (10(-6)M) blocked the myogenic response in Dahl SR but had no effect in Dahl SS. Addition of a subconstrictor concentration of 20-HETE (but not a subconstrictor concentration of norepinephrine) restored the myogenic response in Dahl SS. We then perfused Af-Arts at 60 mmHg and tested the effects of the ATP analog α,β-methylene-ATP (10-6M). Maximum ATP-induced constriction was attenuated in Dahl SS compared to Dahl SR (1.5±0.5 vs. 7.4±0.8 µm, P<0.001). 20-HEDE attenuated ATP-induced Af-Art constriction in Dahl SR but not in Dahl SS, and consequently, ATP-induced constriction was no longer different between strains. In conclusion, Dahl SS have an impaired myogenic response and ATP-induced Af-Art constriction due to a decrease in Af-Art 20-HETE. The impaired myogenic responses may contribute to the nephrosclerosis that develops in Dahl SS.
    American journal of physiology. Renal physiology 07/2014; 307(5). DOI:10.1152/ajprenal.00283.2014 · 3.25 Impact Factor
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    ABSTRACT: Background and objectives: Infection is the second leading cause of death in hemodialysis patients. Catheter-related bloodstream infection and infection-related mortality have not improved in this population over the past two decades. This study evaluated the impact of a prophylactic antibiotic lock solution on the incidence of catheter-related bloodstream infection and mortality. Design, setting, participants, & measurements: This prospective, multicenter, observational cohort study compared the effectiveness of two catheter locking solutions (gentamicin/citrate versus heparin) in 555 hemodialysis patients dialyzing with a tunneled cuffed catheter between 2008 and 2011. The groups were not mutually exclusive. Rates of catheter-related bloodstream infection and mortality hazards were compared between groups. Results: The study population (n=555 and 1350 catheters) had a median age of 62 years (interquartile range=41-83 years), with 50% men and 71% black. There were 427 patients evaluable in the heparin period (84,326 days) and 322 patients evaluable in the antibiotic lock period (71,192 days). Catheter-related bloodstream infection in the antibiotic lock period (0.45/1000 catheter days) was 73% lower than the heparin period (1.68/1000 catheter days; P=0.001). Antibiotic lock use was associated with a decreased risk of catheter-related bloodstream infection compared with heparin (risk ratio, 0.23; 95% confidence interval, 0.13 to 0.38 after multivariate adjustment). Cox proportional hazards modeling found that antibiotic lock was associated with a reduction in mortality (hazard ratio, 0.36; 95% confidence interval, 0.22 to 0.58 in unadjusted analyses; hazard ratio, 0.32; 95% confidence interval, 0.14 to 0.75 after multivariate adjustment). The rate of gentamicin-resistant organisms decreased (0.40/1000 person-years to 0.22/1000 person-years) in the antibiotic lock period (P=0.01). Conclusions: The results of this study show that the use of a prophylactic, gentamicin/citrate lock was associated with a substantial reduction in catheter-related bloodstream infection and is the first to report a survival advantage of antibiotic lock in a population at high risk of infection-related morbidity and mortality.
    Clinical Journal of the American Society of Nephrology 06/2014; 9(7). DOI:10.2215/CJN.11291113 · 4.61 Impact Factor
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    ABSTRACT: Increasing Na delivery to epithelial Na channels (ENaC) in the connecting tubule (CNT) dilates the afferent arteriole (Af-Art), a process we call connecting tubule glomerular feedback (CTGF). We hypothesize that aldosterone sensitizes CTGF via a nongenomic mechanism that stimulates CNT ENaC via the aldosterone receptor GPR30. Rabbit Af-Arts and their adherent CNTs were microdissected and simultaneously perfused. Two consecutive CTGF curves were elicited by increasing luminal NaCl in the CNT. During the control period, the concentration of NaCl that elicited a half-maximal response (EC50) was 37.0±2.0 mmol/L; addition of aldosterone 10-8 mol/L to the CNT lumen caused a left-shift (decrease) in EC50 to 19.3±1.3 mmol/L (P=0.001 vs. Control; n=6). Neither the transcription inhibitor actinomycin D (control EC50=34.7±1.9 mmol/L; aldosterone+actinomycin D EC50=22.6±1.6 mmol/L; n=6; P < 0.001) nor the translation inhibitor cycloheximide (control EC50=32.4±4.3 mmol/L; aldosterone+cycloheximide EC50=17.4±3.3 mmol/L; n=6; P < 0.001) prevented the effect of aldosterone. The aldosterone antagonist eplerenone prevented the sensitization of CTGF by aldosterone (control EC50=33.2±1.7 mmol/L; aldosterone+eplerenone EC50=33.5±1.3 mmol/L; n=7). The GPR30 receptor blocker G-36 blocked the sensitization of CTGF by aldosterone (aldosterone EC50=16.5±1.9 mmol/L; aldosterone+G-36 EC50=29.0±2.1 mmol/L; n=7; P < 0.001). Finally, we found that the sensitization of CTGF by aldosterone was mediated, at least in part, by the sodium/hydrogen exchanger (NHE). We conclude that aldosterone in the CNT lumen sensitizes CTGF via a nongenomic effect involving GPR30 receptors and NHE. Sensitized CTGF induced by aldosterone may contribute to renal damage by increasing Af-Art dilation and glomerular capillary pressure (glomerular barotrauma).
    American journal of physiology. Renal physiology 06/2014; 307(4). DOI:10.1152/ajprenal.00072.2014 · 3.25 Impact Factor
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    ABSTRACT: Context: Metformin is considered first-line treatment for type 2 diabetes mellitus. However, little is known about its effects in African American individuals. Objective: The objective of the study was to assess whether metformin's effect on glycemic control differs by race-ethnicity Design: Electronic health records were used to identify adults who had a diagnosis of diabetes, two or more fills of metformin, and two or more glycated hemoglobin (HbA1c) measurements. Pharmacy claims were used to estimate metformin exposure based on fill frequency and dose dispensed. Regression analyses modeled the relationship between metformin exposure and HbA1c levels. Analyses were stratified by race-ethnicity and baseline HbA1c values. Setting: The study was conducted at a large health system in southeast Michigan. Main Outcome Measure: Differences in HbA1c levels while on metformin were measured. Results: We identified 19ü672 patients with diabetes taking metformin; 7429 were African American and 8783 were European American. Baseline HbA1c values in these two groups were 7.81% (61.8 mmol/mol) and 7.38% (57.1 mmol/mol), respectively. Compared with no use, metformin was associated with a 0.62% (6.8 mmol/mol) reduction in HbA1c; however, there was a significant difference by race-ethnicity (P < .001). Among African American individuals, metformin use was associated with a 0.90% (9.8 mmol/mol) reduction in HbA1c levels, whereas among European Americans, metformin was associated with a 0.42% (4.6 mmol/mol) reduction. Irrespective of baseline HbA1c, metformin use was associated with lower HbA1c levels in African American individuals. Conclusions: African American individuals appear to have a better glycemic response to metformin when compared with European Americans. Further studies are needed to determine whether this translates to commensurate reductions in diabetes complications.
    Journal of Clinical Endocrinology &amp Metabolism 06/2014; 99(9):jc20141539. DOI:10.1210/jc.2014-1539 · 6.21 Impact Factor
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    ABSTRACT: Purpose: Angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) have been established as a mainstay of heart failure treatment. Current data are limited and conflicting regarding the consistency of ACE/ARB benefit across race groups in heart failure. This study aims to clarify this point. Methods: This was a retrospective study of insured patients with a documented ejection fraction of less than 50%, hospitalized for heart failure between January 2000 and June 2008. Pharmacy claims data were used to estimate ACE/ARB exposure over 6-month rolling windows. The association between ACE/ARB exposure and all-cause hospitalization or death was assessed by proportional hazards regression, with adjustment for baseline covariates and β-blocker exposure. Further analyses were stratified by race, and included an ACE/ARB × Race interaction term. Results: A total of 1095 patients met inclusion criteria (619 African-American individuals). Median follow-up was 2.1 years. In adjusted models, ACE/ARB exposure was associated with lower risk of death or hospitalization in both groups (African-Americans hazard ratio 0.47, P < 0.001; whites hazard ratio 0.55, P < 0.001). A formal test for interaction was consistent with similar effects in each group (P = 0.861, β = 0.04). Conclusion: ACE/ARB exposure was equally associated with a protective effect in preventing death or rehospitalization among heart failure patients with systolic dysfunction in both African-American patients and whites.
    Journal of Cardiovascular Medicine 05/2014; Publish Ahead of Print(9). DOI:10.2459/JCM.0000000000000091 · 1.51 Impact Factor
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    ABSTRACT: Objective: This study investigates trends in opioid use and related adverse events among individuals with non-cancer pain before and after implementation of major national policies. Study Design: The study used a longitudinal prospective study design. The analysis was limited to adults (age ≥ 18 years) without a recorded cancer diagnosis. Pharmacy claims were used to assess rates of prescription opioid use, the strength of opioids dispensed, the proportion using opioids chronically, and related adverse events. Time trend analysis was used to identify changes in these rates over time. The study was Institutional Review Board approved. Setting: Study patients were members of a large, health maintenance organization in southeast Michigan, with longitudinal records of prescription opioid use. Results: The analysis comprised 523,623 individuals and 1,066,700 opioid pharmacy fills from January 1, 1997, to December 31, 2011. Contemporaneous with the implementation of health organization accreditation criteria requiring assessment and treatment of pain in all patients beginning January 2001, we observed a consistent and unabated increase in the rate of opioid fills and the proportion of chronic use. A parallel increase in the annual rate of adverse events was also observed. Similarly, we observed a continuous rise in the average strength of opioid fills following January 2001 with the exception of a single drop in December 2010, which was attributable to the withdrawal of propoxyphene from the U.S. market. Limitations: This was an observational study and not a trial. Other long-term opioid-related benefits or harms, including functional status, quality of life, and substance use disorder, were not assessed. Conclusions: This study provides temporal evidence for a rise in prescription opioid use after implementation of health organization accreditation criteria requiring standardized management of all individuals with pain.
    Pain physician 05/2014; 17(3):205-16. · 3.54 Impact Factor

Publication Stats

15k Citations
1,468.46 Total Impact Points


  • 1992-2015
    • Henry Ford Health System
      • • Department of Public Health Sciences
      • • Department of Psychiatry
      Detroit, Michigan, United States
  • 1989-2015
    • Henry Ford Hospital
      • • Hypertension and Vascular Research Division
      • • Department of Internal Medicine
      • • Surgery
      Detroit, Michigan, United States
  • 2007
    • Cancer Research and Biostatistics
      Seattle, Washington, United States
  • 2006
    • University of Wisconsin–Madison
      Madison, Wisconsin, United States
    • University of Chicago
      • Department of Molecular Genetics & Cell Biology
      Chicago, Illinois, United States
  • 2002-2006
    • Johns Hopkins University
      • Department of Medicine
      Baltimore, Maryland, United States
    • Georgia College
      Атина, Georgia, United States
  • 1993-2006
    • Wayne State University
      • Department of Neurology
      Detroit, Michigan, United States
  • 2004
    • Harvard Medical School
      Boston, Massachusetts, United States
    • Michigan State University
      • Department of Epidemiology
      Ист-Лансинг, Michigan, United States
  • 2000-2002
    • Georgia Health Sciences University
      • Department of Pediatrics
      Augusta, GA, United States
  • 2001
    • Case Western Reserve University
      • Department of Epidemiology and Biostatistics
      Cleveland, Ohio, United States