A personalized, web-based breast cancer decision making application: a pre-post survey.

BACKGROUND: Every case of breast cancer is unique, and treatment must be personalized to incorporate a woman's values and preferences. We developed an individually-tailored mobile patient education application for women with breast cancer. METHODS: Pre-post surveys were completed by 255 women who used the tool. RESULTS: Patients thought the application included helpful information (N = 184, 72%) and was easy to navigate (N = 156, 61%). Most patients thought the amount of information in the tool was "about right" (N = 193, 87%). Decision making confidence increased by an average of 0.8 points (10-point scale) following a consultation and use of the tool (p < 0.001). CONCLUSIONS: Tailored mobile applications may optimize care by facilitating shared decision making and knowledge transfer, and they may also enhance the experience of patients as they navigate through their breast cancer journey.

Frequency of radiologic procedures in patients with rheumatoid arthritis.

BACKGROUND: Patients with rheumatoid arthritis (RA) undergo radiologic investigations for disease and comorbidity evaluation. The actual use of radiologic imaging in RA is unknown. METHODS: Using the Rochester Epidemiology Project medical record linkage system, adult patients from previously assembled population-based cohorts of Olmsted County, Minnesota, residents who fulfilled the 1987 American College of Rheumatology criteria for RA in 1988 to 2007 and comparator subjects without RA of similar age and gender were studied. Data on all radiologic procedures performed were collected. RESULTS: The study included 650 patients with RA and 650 patients without RA. Patients with RA had significantly more radiographs of the chest (rate ratio [RR], 1.33; 95% confidence interval [CI], 1.28-31.38), upper extremity (RR, 2.97; 95% CI, 2.80-83.17), lower extremity (RR, 2.05; 95% CI, 1.94-102.16), spine (RR, 1.46; 95% CI, 1.35-41.59), and hip, pelvis, or sacroiliac joints (RR, 1.14; 95% CI, 1.03-11.26), as well as bone radionuclide (RR, 1.90; 95% CI, 1.50-52.44) and dual-energy x-ray absorptiometry imaging (RR, 1.77; 95% CI, 1.59-61.98) compared with patients without RA. Among patients with RA, having a positive rheumatoid factor was associated with an increased likelihood of undergoing radiologic procedures (RR, 1.05; 95% CI, 1.02-11.07). Women with RA underwent more imaging procedures than men (RR, 1.20; 95% CI, 1.16-21.23). CONCLUSIONS: Patients with RA undergo more radiologic procedures than patients without RA. Among patients with RA, women and patients with a positive rheumatoid factor have more radiologic procedures. The utilization of radiography is likely a reflection of overall disease burden. Despite some guidelines, routine hand wrist radiographs were not obtained with regularity; "overuse" is unlikely.

Hypertension in an experimental model of systemic lupus erythematosus occurs independently of the renal nerves.

Systemic lupus erythematosus (SLE) is a chronic inflammatory disorder with prevalent hypertension and renal injury. In this study, we tested whether the renal nerves contribute to the development of hypertension in an established mouse model of SLE (NZBWF1). Female SLE and control (NZW/LacJ) mice were subjected to either bilateral renal denervation or a sham procedure at 32 wk of age. Two weeks later, blood pressure was assessed in conscious mice using carotid artery catheters. Blood pressure was higher in SLE mice compared with controls, as previously reported; however, blood pressure was not altered in the denervated SLE or control mice. The development of albuminuria was markedly blunted in denervated SLE mice; however, glomerulosclerosis was increased. Renal denervation reduced renal cortical expression of monocyte-chemoattractant protein in SLE mice but did not significantly alter renal monocyte/macrophage infiltration. Renal cortical TNF-α expression was also increased in sham SLE mice, but this was not impacted by denervation. This study suggests that the renal nerves do not have a significant role in the pathogenesis of hypertension, but have a complex effect on the associated renal inflammation and renal injury.

Blood pressure in a hypertensive mouse model of SLE is not salt-sensitive.

Systemic lupus erythematosus (SLE) is a risk factor for hypertension. Previously, we demonstrated that an established mouse model of SLE (female NZBWF1 mice) develops hypertension with renal inflammation and oxidative stress, both characteristics known as contributing mechanisms to the development of salt-sensitive hypertension. On the basis of this model, we hypothesized that blood pressure in SLE mice would be salt-sensitive. Thirty-week-old female SLE and control mice (NZW/LacJ) were fed 8% high-salt (HS) diet or normal diet (0.4% salt) for 4 wk. Plasma levels of double-stranded DNA (dsDNA) autoantibodies, a marker of SLE disease activity, were increased in SLE mice compared with controls (472 ± 148 vs. 57 ± 17 U/ml × 1,000, P < 0.001). HS did not alter dsDNA autoantibody levels in SLE or control mice. Mean arterial pressure was increased in SLE mice compared with controls (132 ± 3 vs. 118 ± 2 mmHg, P < 0.001) and was not significantly altered by the HS diet in either group. Similarly, albuminuria was higher in SLE mice compared with controls (10.7 ± 9.0 vs. 0.3 ± 0.1 mg/day) but was not significantly increased in SLE or control mice fed a HS diet. In summary, blood pressure during SLE is not salt-sensitive, and the HS diet did not adversely affect SLE disease activity or significantly augment albuminuria. These data suggest that renal inflammation and oxidative stress, characteristics common to both SLE and models of salt-sensitive hypertension, may have diverging mechanistic roles in the development of hypertension.

Blood pressure and renal hemodynamic responses to acute angiotensin II infusion are enhanced in a female mouse model of systemic lupus erythematosus.

Inflammation and immune system dysfunction contributes to the development of cardiovascular and renal disease. Systemic lupus erythematosus (SLE) is a chronic autoimmune inflammatory disorder that carries a high risk for both renal and cardiovascular disease. While hemodynamic changes that may contribute to increased cardiovascular risk have been reported in humans and animal models of SLE, renal hemodynamics have not been widely studied. The renin-angiotensin system (RAS) plays a central role in renal hemodynamic control, and although RAS blockade is a common therapeutic strategy, the role of RAS in hemodynamic function during SLE is not clear. This study tested whether mean arterial pressure (MAP) and renal hemodynamic responses to acute infusions of ANG II in anesthetized animals were enhanced in an established female mouse model of SLE (NZBWF1). Baseline MAP was not different between anesthetized SLE and control (NZWLacJ) mice, while renal blood flow (RBF) was significantly lower in mice with SLE. SLE mice exhibited an enhanced pressor response and greater reduction in RBF after ANG II infusion. An acute infusion of the ANG II receptor blocker losartan increased RBF in control mice but not in mice with SLE. Renin and ANG II type 1 receptor expression was significantly lower, and ANG II type 2 receptor expression was increased in the renal cortex from SLE mice compared with controls. These data suggest that there are fewer ANG II receptors in the kidneys from mice with SLE but that the existing receptors exhibit an enhanced sensitivity to ANG II.

Assessing Biomarkers of Breast Cancer Risk in Underserved Women in a Midwestern County.

OBJECTIVE: The primary aim of this study was to evaluate the feasibility of collecting risk factor information and accessing digitized mammographic data in a medically marginalized population. A secondary aim was to examine the association between vitamin D status and mammographic density. METHODS: Breast-screening examinations were provided for age-appropriate patients, and a referral for no-cost screening mammography was offered. Study participants were asked to undergo 25-hydroxyvitamin D testing at mammography and 1-year follow-up. RESULTS: Of 62 women approached, 35 (56%) consented to participate. Of 32 participants who had baseline mammography, the median mammographic density measured by VolparaDensity (Volpara Solutions Limited) was 5.7%. After 1 year, 9 women obtained follow-up mammograms, with a median density of 5.7%. Vitamin D status was measured for 31 participants at baseline and 13 participants in the following year. Insufficient vitamin D status (<30 ng/mL) was noted in 77% at each time point. Mammographic density was not significantly correlated with vitamin D status (P = .06). CONCLUSIONS: On the basis of this small pilot study, vitamin D insufficiency is common in this study population. Owing to the small sample size, an association between vitamin D insufficiency and breast density was not clear. Additional unexpected findings included substantial barriers in initial access to care and longitudinal follow-up in this population. Further study of these issues is needed.

Oxidative stress promotes hypertension and albuminuria during the autoimmune disease systemic lupus erythematosus.

Several lines of evidence suggest that essential hypertension originates from an autoimmune-mediated mechanism. One consequence of chronic immune activation is the generation of oxygen-derived free radicals, resulting in oxidative stress. Renal oxidative stress has direct prohypertensive actions on renal microvascular and tubular function. Whether oxidative stress contributes to the prevalent hypertension associated with autoimmune disease is not clear. We showed previously that female NZBWF1 mice, an established model of the autoimmune disease systemic lupus erythematosus (SLE), develop hypertension associated with renal oxidative stress. In the present study we tested the hypothesis that oxidative stress contributes to autoimmune-mediated hypertension by treating SLE and control (NZW/LacJ) mice with tempol (2.0 mmol/L) and apocynin (1.5 mmol/L) in the drinking water for 4 weeks. Although the treatment did not alter SLE disease activity (assessed by plasma double-stranded DNA autoantibodies), blood pressure and renal injury (urinary albumin) were reduced in the treated SLE mice. Tempol plus apocynin-treated SLE mice had reduced expression of nitrosylated proteins in the renal cortex, as well as reduced urinary and renal cortical hydrogen peroxide, suggesting that treatment reduced renal markers of oxidative stress. These data suggest that renal oxidative stress plays an important mechanistic role in the development of autoimmune-mediated hypertension.

Can estrogens promote hypertension during systemic lupus erythematosus?

SLE is a chronic autoimmune inflammatory disorder that predominantly affects young women. Based on this observation, it has been speculated that sex steroids, particularly estrogens, contribute to SLE disease progression. Young women with SLE are at an increased risk for the development of hypertension yet the reasons for this are unclear. One potential mechanism for the increased risk of hypertension during SLE is the chronic inflammation caused by immune complex mediated tissue injury. Estrogens are known to have an immunomodulatory role that can lead to the production of characteristic autoantibodies important for immune complex formation. Therefore, it is conceivable that during SLE estrogens contribute to tissue injury, increased inflammation and hypertension. This brief review discusses the increased risk for hypertension during SLE, the role of estrogens in immune system function, evidence for estrogens in SLE, and a possible link between estrogens and SLE hypertension.

Sexual dimorphism in the blood pressure response to angiotensin II in mice after angiotensin-converting enzyme blockade.

BACKGROUND: The incidence of hypertension and progression of renal disease are greater in men than in women. Data suggest that there is a dimorphic response to angiotensin II (Ang II) in rats, with male rats exhibiting a greater increase in mean arterial pressure (MAP) than females. However, during endogenous renin-angiotensin system (RAS) blockade with angiotensin-converting enzyme (ACE) inhibition, female rats have a greater MAP response to Ang II. We tested whether female mice exhibit a greater MAP response to chronic Ang II during ACE inhibition. METHODS: Twenty-week-old male and female C57BL/6J mice (n > or = 6/group), treated with enalapril (40 mg/kg/day in drinking water), were assigned to groups receiving either Ang II (800 ng/kg/min) or saline for 2 weeks. Enalapril treatment began 4 days before and continued throughout the experiment. RESULTS: MAP was higher in male mice than female mice treated with enalapril and Ang II (male: 144 +/- 3 vs. female: 121 +/- 6 mm Hg, P < 0.05) and was not different between mice treated with enalapril alone (male: 99 +/- 3 vs. female: 100 +/- 3 mm Hg). F2-isoprostanes were not increased by Ang II; however, female mice had significantly higher levels than males. Renal cortical expression of catalase and Cu/Zn-superoxide dismutase (SOD) was not different between experimental groups. Urinary protein was higher in male mice when compared to females, but was not changed after treatment with Ang II in either group. CONCLUSIONS: These data suggest that there are species and sex-specific differences in the mechanism of the blood pressure response to Ang II, even during ACE inhibition.

Tumor necrosis factor-alpha antagonist etanercept decreases blood pressure and protects the kidney in a mouse model of systemic lupus erythematosus.

Chronic inflammation has been implicated in the pathology of hypertension; however, the role for specific cytokines remains unclear. We tested whether tumor necrosis factor-α blockade with etanercept (Etan) reduces mean arterial pressure in a female mouse model of systemic lupus erythematosus (SLE). SLE is a chronic inflammatory disorder with prevalent hypertension. Thirty-week-old SLE (NZBWF1) and control mice (NZW/LacJ) received Etan (0.8 mg/kg SC weekly) for 4 weeks or vehicle. Mean arterial pressure (in millimeters of mercury) was increased in SLE mice (150±5 versus 113±5 in controls; P<0.05) and was lower in Etan-treated SLE mice (132±3) but not controls (117±5). Albuminuria (in micrograms per milligram of creatinine) was elevated in SLE mice (28 742±9032 versus 1075±883; P<0.05) and was lower in Etan-treated SLE mice (8154±3899) but not control animals (783±226). Glomerulosclerosis (in percentage of glomeruli) was evident in SLE mice (2.5±1.6 versus 0.0±0.0 in controls; P<0.05) and was ameliorated in Etan-treated SLE mice (0.1±0.1). Renal cortex CD68(+) cell staining (in percentage of area) was elevated in SLE mice (4.75±0.80 versus 0.79±0.12 in controls; P<0.05) and was lower in Etan-treated SLE mice (2.28±0.32) but not controls (1.43±0.25). Renal cortex NADPH oxidase activity (relative light units per milligram of protein) was higher in SLE mice compared with controls (10 718±1276 versus 7584±229; P<0.05) and lowered in Etan-treated SLE mice (6645±490). Renal cortex nuclear factor κB (phosphorylated and nonphosphorylated) was increased in SLE mice compared with controls and lower in Etan-treated SLE mice. These data suggest that TNF-α mechanistically contributes to the development of hypertension in a chronic inflammatory disease through increased renal nuclear factor κB, oxidative stress, and inflammation.

Rosiglitazone reduces blood pressure in female Dahl salt-sensitive rats.

Postmenopausal women (PMW) are at greater risk for salt-sensitive hypertension and insulin resistance than premenopausal women. Peroxisome-proliferator-activated receptor-gamma (PPARgamma) agonists reduce blood pressure (BP) and insulin resistance in humans. As in PMW, ovariectomy (OVX) increases salt sensitivity of BP and body weight in Dahl salt-sensitive (DS) rats. This study addressed whether rosiglitazone (ROSI), a PPARgamma agonist, attenuates salt-sensitive hypertension in intact (INT) and OVX DS rats, and if so, whether insulin resistance, nitric oxide (NO), oxidative stress, and/or renal inflammation were contributing mediators. Telemetric BP was similar in OVX and INT on low salt diet (0.3% NaCl), but was higher in OVX than INT on high salt (8% NaCl). ROSI reduced BP in OVX and INT on both low and high salt diet, but only attenuated salt sensitivity of BP in OVX. Nitrate/nitrite excretion (NO(x); index of NO) was similar in INT and OVX on low salt diet, and ROSI increased NO(x) in both groups. High salt diet increased NO(x) in all groups but ROSI only increased NO(x) in OVX rats. OVX females exhibited insulin resistance, increases in body weight, plasma leptin, cholesterol, numbers of renal cortical macrophages, and renal MCP-1 and osteopontin mRNA expression compared to INT. ROSI reduced cholesterol and macrophage infiltration in OVX, but not INT. In summary, PPARgamma activation reduces BP in INT and OVX females, but attenuates the salt sensitivity of BP in OVX only, likely due to increases in NO and in part to reductions in renal resident macrophages and inflammation.

Rosiglitazone decreases blood pressure and renal injury in a female mouse model of systemic lupus erythematosus.

Women with systemic lupus erythematosus (SLE) exhibit a high prevalence of hypertension and renal injury. Rosiglitazone (Rosi), a peroxisome proliferator activator receptor gamma (PPARgamma) agonist, has renal protective and antihypertensive effects. We tested whether Rosi ameliorates hypertension and renal injury in a female mouse model of SLE (NZBWF1). Thirty-week-old SLE and control (NZW/LacJ) mice (n > or = 6/group) were fed Rosi (5 mg.kg(-1).day(-1) in standard chow) or standard chow for 4 wk. SLE mice had increased blood pressure (BP in mmHg) compared with controls (139 +/- 4 vs. 111 +/- 4, P < 0.05). Rosi treatment lowered BP in SLE mice (127 +/- 4, P < 0.05) but not in controls (111 +/- 4). Urinary albumin (mug/mg creatinine) was increased in SLE mice compared with controls (12,396 +/- 6,525 vs. 50 +/- 6) and reduced with Rosi treatment (148 +/- 117). Glomerulosclerosis (% of glomeruli with sclerosis) was reduced in Rosi-treated SLE mice (4.2 +/- 1.6 vs. 0.4 +/- 0.3, P < 0.05). Renal monocyte/macrophage numbers (cell number/1,320 points counted) were reduced in SLE mice treated with Rosi (32.6 +/- 11.0 vs. 10.6 +/- 3.6, P < 0.05) but unchanged in controls (3.7 +/- 1.6 vs. 3.7 +/- 2.0). Renal osteopontin expression, a cytokine-regulating macrophage recruitment, was reduced in Rosi-treated SLE mice. Urinary endothelin (in pg/mg creatinine) was increased in SLE mice compared with controls (1.9 +/- 0.59 vs. 0.6 +/- 0.04, P < 0.05) and reduced in SLE mice treated with Rosi (0.8 +/- 0.11, P < 0.05). PPARgamma protein expression in the renal cortex was significantly lower in SLE mice compared with controls and was unaffected by Rosi. These data suggest that Rosi may be an important therapeutic option for the treatment of SLE hypertension and renal injury.

Renal blood flow and dynamic autoregulation in conscious mice.

Autoregulation of renal blood flow (RBF) occurs via myogenic and tubuloglomerular feedback (TGF) mechanisms that are engaged by pressure changes within preglomerular arteries and by tubular flow and content, respectively. Our understanding of autoregulatory function in the kidney largely stems from experiments in anesthetized animals where renal perfusion pressure is precisely controlled. However, normally occurring variations in blood pressure are sufficient to engage both myogenic and TGF mechanisms, making the assessment of autoregulatory function in conscious animals of significant value. To our knowledge, no studies have evaluated the dynamics of RBF in conscious mice. Therefore, we used spectral analysis of blood pressure and RBF and identified dynamic operational characteristics of the myogenic and TGF mechanisms in conscious, freely moving mice instrumented with ultrasound flow probes and arterial catheters. The myogenic response generates a distinct resonance peak in transfer gain at 0.31 +/- 0.01 Hz. Myogenic-dependent attenuation of RBF oscillations, indicative of active autoregulation, is apparent as a trough in gain below 0.3 Hz (-6.5 +/- 1.3 dB) and a strong positive phase peak (93 +/- 9 deg), which are abolished by amlodipine infusion. Operation of TGF produces a local maximum in gain at 0.05 +/- 0.01 Hz and a positive phase peak (62.3 +/- 12.3 deg), both of which are eliminated by infusion of furosemide. Administration of amlodipine eliminated both myogenic and TGF signature peaks, whereas furosemide shifted the myogenic phase peak to a slower operational frequency. These data indicate that myogenic and TGF dynamics may be used to investigate the effectiveness of renal autoregulatory mechanisms in conscious mice.