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1.  Effects of Phosphate Binder Therapy on Vascular Stiffness in Early Stage Chronic Kidney Disease 
American journal of nephrology  2013;38(2):10.1159/000353569.
Cardiovascular disease (CVD) is increased in chronic kidney disease (CKD), and contributed to by the CKD-mineral bone disorder (CKD-MBD). The CKD-MBD begins in early CKD and its vascular manifestations begin with vascular stiffness proceeding to increased carotid artery intima-media thickness (cIMT) and vascular calcification (VC). Phosphorus is associated with this progression and is considered a CVD risk factor in CKD. We hypothesized that modifying phosphorus balance with lanthanum carbonate (LaCO3) in early CKD would not produce hypophosphatemia and may affect vascular manifestations of the CKD-MBD.
We randomized 38 subjects with normophosphatemic stage 3 CKD to a fixed dose of LaCO3 or matching placebo without adjusting dietary phosphorus in a 12-month randomized, double-blind, pilot and feasibility study. The primary outcome was the change in serum phosphorus. Secondary outcomes were changes in measures of phosphate homeostasis and vascular stiffness assessed by carotid-femoral pulse wave velocity (PWV), cIMT and VC over 12 months.
There were no statistically significant differences between LaCO3 and placebo with respect to the change in serum phosphorus, urinary phosphorus, tubular reabsorption of phosphorus, PWV, cIMT, or VC. Biomarkers of the early CKD-MBD such as plasma fibroblast growth factor-23 (FGF23), Dickkopf-related protein 1 (DKK1), and sclerostin were increased 2–3-fold at baseline but were not affected by LaCO3.
12 months of LaCO3 had no effect on serum phosphorus and did not alter phosphate homeostasis, PWV, cIMT, VC, or biomarkers of the CKD-MBD.
PMCID: PMC3874122  PMID: 23941761
Cardiovascular disease; chronic kidney disease; phosphate binders; vascular calcification; randomized controlled trials
2.  The St. Louis African American health-heart study: methodology for the study of cardiovascular disease and depression in young-old African Americans 
Coronary artery disease (CAD) is a major cause of death and disability worldwide. Depression has complex bidirectional adverse associations with CAD, although the mechanisms mediating these relationships remain unclear. Compared to European Americans, African Americans (AAs) have higher rates of morbidity and mortality from CAD. Although depression is common in AAs, its role in the development and features of CAD in this group has not been well examined. This project hypothesizes that the relationships between depression and CAD can be explained by common physiological pathways and gene-environment interactions. Thus, the primary aims of this ongoing project are to: a) determine the prevalence of CAD and depression phenotypes in a population-based sample of community-dwelling older AAs; b) examine the relationships between CAD and depression phenotypes in this population; and c) evaluate genetic variants from serotoninP and inflammatory pathways to discover potential gene-depression interactions that contribute significantly to the presence of CAD in AAs.
The St. Louis African American Health (AAH) cohort is a population-based panel study of community-dwelling AAs born in 1936–1950 (inclusive) who have been followed from 2000/2001 through 2010. The AAH-Heart study group is a subset of AAH participants recruited in 2009–11 to examine the inter-relationships between depression and CAD in this population. State-of-the-art CAD phenotyping is based on cardiovascular characterizations (coronary artery calcium, carotid intima-media thickness, cardiac structure and function, and autonomic function). Depression phenotyping is based on standardized questionnaires and detailed interviews. Single nucleotide polymorphisms of selected genes in inflammatory and serotonin-signaling pathways are being examined to provide information for investigating potential gene-depression interactions as modifiers of CAD traits. Information from the parent AAH study is being used to provide population-based prevalence estimates. Inflammatory and other biomarkers provide information about potential pathways.
This population-based investigation will provide valuable information on the prevalence of both depression and CAD phenotypes in this population. The study will examine interactions between depression and genetic variants as modulators of CAD, with the intent of detecting mechanistic pathways linking these diseases to identify potential therapeutic targets. Analytic results will be reported as they become available.
PMCID: PMC3847628  PMID: 24011389
Coronary artery disease; Depression; Genetic analyses; African Americans; Inflammatory biomarkers; Inflammatory pathway; Serotonin-signaling pathway; Heart rate variability; Built environment; Bayesian analysis
3.  Stereotactic body radiation therapy for the treatment of early-stage minimally invasive adenocarcinoma or adenocarcnioma in situ (formerly bronchioloalveolar carcinoma): a patterns of failure analysis 
Ongoing prospective trials exploring stereotactic body radiation therapy (SBRT) for early stage non-small cell lung cancer (NSCLC) often exclude minimally invasive adenocarcinoma or adenocarcnioma in situ, formerly bronchioloalveolar carcinoma (BAC), due to concerns for accurate target delineation on CT. We performed a patterns of failure analysis to compare outcomes between BAC and other NSCLC subtypes.
One hundred twenty patients with early stage NSCLC were treated with SBRT from 2004–2009. Pathologic confirmation of NSCLC was obtained in 97 patients. Radiotherapy was delivered according to RTOG guidelines. The log-rank test was used to compare outcomes between BAC and other NSCLC.
Median follow-up was 29 months. The median SBRT dose was 5400 cGy. Thirteen patients had radiographically diagnosed BAC and five patients had biopsy confirmed BAC, of which two had both. The three-year local control was 100% for biopsy-proven or radiographically diagnosed BAC (n = 18) and 86% for all other NSCLC subtypes (n = 102) (p = 0.13). Likewise, no significant difference was detected between BAC and other NSCLC for 3-year regional failure (12% vs. 20%, p = 0.45), progression-free survival (57.6% vs. 53.5%, p = 0.84) or overall survival (35% vs. 47%, p = 0.66). There was a trend towards lower three-year rates of freedom from distant failure in patients with any diagnosis of BAC compared to those without (26% vs. 38%, p = 0.053).
Compared to other NSCLC subtypes, BAC appears to have similar patterns of failure and survival after treatment with SBRT, however there may be an increased risk of distant metastases with BAC. RTOG guideline-based target delineation provides encouraging local control rates for patients with BAC.
PMCID: PMC3552761  PMID: 23286648
SBRT; Bronchioloalveolar carcinoma; Adenocarcinoma in situ; Minimally invasive adenocarcinoma; BAC; SABR
4.  Effects of Sodium Thiosulfate on Vascular Calcification in End-Stage Renal Disease: A Pilot Study of Feasibility, Safety and Efficacy 
American Journal of Nephrology  2011;33(2):131-138.
Background and Objectives
Vascular calcification is a major contributor to morbidity and mortality in hemodialysis. The objective of this pilot study was to determine the feasibility, safety and efficacy of sodium thiosulfate (STS) in the progression of vascular calcification in hemodialysis patients.
Chronic hemodialysis patients underwent a battery of cardiovascular tests. Those with coronary artery calcium (Agatston scores >50) received intravenous STS after each dialysis for 5 months (n = 22) and the tests were repeated. Changes in MDCT-determined calcification were assessed as the mean annualized rate of change in 3 vascular beds (coronary, thoracic and carotid arteries) and in L1-L2 vertebral bone density.
Although individual analyses showed coronary artery calcification progression in 14/22 subjects, there was no progression in the mean annualized rate of change of vascular calcification in the entire group. The L1-L2 vertebral bone density showed no changes. There were no correlations between rates of progression of vascular calcification and phosphorus, fetuin or C-reactive protein levels. Changes in coronary artery calcification scores correlated with those of the thoracic aorta.
STS treatment is feasible, appears safe and may decrease the rate of progression of vascular calcification in hemodialysis patients. A large, randomized, controlled trial is warranted.
PMCID: PMC3064860  PMID: 21242673
Hemodialysis; Sodium thiosulfate; Vascular calcification
5.  Emphysema Quantification in Inflation-Fixed Lungs Using Low-Dose CT and 3He MR Imaging 
To evaluate the use of inflation-fixed lung tissue for emphysema quantification with CT and 3He MR diffusion imaging.
Fourteen subjects representing a range of chronic obstructive pulmonary disease severity who underwent complete or lobar lung resection were studied. CT measurements of lung attenuation and MR measurements of the hyperpolarized 3He apparent diffusion coefficient (ADC) in resected specimens fixed in inflation with heated formalin vapor were compared with measurements obtained before fixation.
The mean CT emphysema index was 56% ± 17% before and 58% ± 19% after fixation (P=0.77; R=0.76). Index differences correlated with differences in lung volume (R2=0.47). The mean 3He ADC was 0.40 ± 0.15 cm2/sec before and 0.39 ± 0.14 cm2/sec after fixation (P=0.03, R=0.98). The CT emphysema index and the 3He ADC were correlated before (R=0.89) and after fixation (R=0.79).
Concordance of CT and 3He MR imaging measurements in unfixed and inflation-fixed lungs supports the use of inflation-fixed lungs for quantitative imaging studies in emphysema.
PMCID: PMC2946251  PMID: 20861785
6.  Effects of CT Section Thickness and Reconstruction Kernel on Emphysema Quantification: Relationship to the Magnitude of the CT Emphysema Index 
Academic radiology  2010;17(2):146.
Rationale and Objectives
CT section thickness and reconstruction kernel each influence CT measurements of emphysema. This study was performed to assess whether their effects are related to the magnitude of the measurement.
Materials and Methods
Low-radiation-dose multidetector CT was performed in 21 subjects representing a wide range of emphysema severity. Images were reconstructed using 20 different combinations of section thickness and reconstruction kernel. Emphysema index values were determined as the percentage of lung pixels having attenuation lower than multiple thresholds ranging from −960 HU to −890 HU. The index values obtained from the different thickness-kernel combinations were compared by repeated measures ANOVA and Bland-Altman plots of mean vs. difference, and correlated with quantitative histology (mean linear intercept, Lm) in a subset of resected lung specimens.
The effects of section thickness and reconstruction kernel on the emphysema index were significant (p<0.001) and diminished as the index threshold was raised. The changes in index values due to changing the thickness-kernel combination were largest for subjects with intermediate index values (10–30%), and became progressively smaller for those with lower and higher index values. This pattern was consistent regardless of the thickness-kernel combinations compared and the HU threshold used. Correlations between the emphysema index values obtained with each thickness-kernel combination and Lm ranged from r=0.55–0.68 (p=0.007–0.03).
The effects of CT section thickness and kernel on emphysema index values varied systematically with the magnitude of the emphysema index. All reconstruction techniques provided significant correlations with quantitative histology.
PMCID: PMC2818169  PMID: 19931472
Emphysema; computed tomography; histology
7.  Effects of Diffusion Time on Short-Range Hyperpolarized 3He Diffusivity Measurements in Emphysema 
To characterize the effect of diffusion time on short-range hyperpolarized 3He MR diffusion measurements across a wide range of emphysema severity.
Materials and Methods
3He diffusion MR imaging was performed on 19 lungs or lobes resected from 18 subjects with varying degrees of emphysema using 3 diffusion times (1.6 msec, 5 msec, and 10 msec) at constant b value. Emphysema severity was quantified as the mean apparent diffusion coefficient (ADC) and as the percentage of pixels with ADC higher than multiple thresholds from 0.30–0.55 cm2/sec (ADC index). Quantitative histology (mean linear intercept) was obtained in 10 of the lung specimens from 10 of the subjects.
The mean ADCs with diffusion times of 1.6, 5.0, and 10.0 msec were 0.46, 0.40, and 0.37 cm2/sec, respectively (P <0.0001, ANOVA). There was no relationship between the ADC magnitude and the effect of diffusion time on ADC values. Mean linear intercept correlated with ADC (r=0.91–0.94, P<0.001) and ADC index (r=0.78–0.92, P<0.01) at all diffusion times.
Decreases in ADC with longer diffusion time were unrelated to emphysema severity. The strong correlations between the ADC at all diffusion times tested and quantitative histology demonstrate that the ADC is a robust measure of emphysema.
PMCID: PMC2844435  PMID: 19787725
Helium-3; diffusivity; emphysema
8.  Accuracy of Emphysema Quantification Performed With Reduced Numbers of CT Sections 
The purpose of this study was to assess the accuracy of emphysema measurements obtained from systematic samples of evenly spaced CT images compared with measurements obtained from the entire scan.
Materials and Methods
Evenly spaced transverse sections from the CT studies of 136 heavy smokers who underwent screening for lung cancer in the National Lung Screening Trial and of 112 subjects who underwent imaging before lung volume reduction surgery were sampled retrospectively. The samples were acquired both by selection of specific numbers of evenly spaced images and by selection of images at specific distance intervals. The percentage of lung pixels with attenuation below specific thresholds was used as an emphysema index. The image sample error was determined as the difference in emphysema index between the image samples and the entire scan.
The largest absolute image sample errors in the National Lung Screening Trial cohort with image sample sizes of five, 10, and 20 were 2.2, 0.8, and 0.5 index percentage points, respectively, at 1-mm section thickness (−960 HU threshold), and 2.6, 1.1, and 0.5 index percentage points at 5-mm section thickness (−930 HU threshold). The largest errors in the lung volume reduction surgery cohort for image sample sizes of five and 10 were 5.6 and 2.3 index percentage points at 8- to 10-mm section thickness (−900 HU threshold). Image sample errors were equivalent for the two sampling methods.
Systematic sampling resulted in very small errors in emphysema quantification and may be useful for decreasing radiation exposure in clinical research studies of emphysema.
PMCID: PMC2838241  PMID: 20173132
emphysema; quantitative CT
9.  Relation of Serum Fetuin-A Levels to Coronary Artery Calcium in African-American Patients on Chronic Hemodialysis 
Vascular calcium deposition in end-stage renal disease occurs commonly, however its relationship to cardiovascular risk factors and fetuin-A levels in African-Americans is not known. Compliant African-American HD patients (n=17) agreed to undergo a 64-slice multidetector computed tomography for the assessment of coronary artery calcium score (CACS). The relationship between traditional cardiovascular risk factors (i.e., age, gender, dialysis vintage, history of diabetes, means of the previous 3 years of the weekly pre-dialysis blood pressure and hemoglobin, means of monthly values of calcium, phosphorus, alkaline phosphatase, uric acid and albumin, and means of quarterly measures of parathyroid hormone and lipids), and fetuin-A levels and CACS was explored by univariate analyses. Serum phosphorus levels over the previous 3 years were well controlled. The CACS range was 0-3,877 Agatston units (mean: 996; median :196). Among the tested variables, only fetuin-A was significantly and inversely associated with CACS (standardized β = -0.64 [95% confidence limits [CL]: -18.09, -3.62], p=0.006). There was no association between age and fetuin-A level (standardized β = -0.02 [95%CL: -0.10, 0.23]). In conclusion, African-American patients on long-term HD and with good phosphorus control exhibit a strong inverse correlation between fetuin-A levels and CACS which is independent of age.
PMCID: PMC2631229  PMID: 19101228
Fetuin-A; Hemodialysis; Coronary artery calcium score; African-American
10.  Conditioning Injuries Associated with Artificial Turf in Two Preseason Football Training Programs 
Journal of Athletic Training  1997;32(4):304-308.
To compare the occurrence of preseason football conditioning injuries in traditional and crossover conditioning programs over five preseasons.
Design and Setting:
The turf group performed all preseason conditioning by running or sprinting on artificial turf, and the turf and swim group alternated all preseason conditioning by running and sprinting on artificial turf or kickboard swimming.
Subjects were 519 NCAA Division III physically active football players.
Previous conditioning injuries, preseason conditioning injuries, missed practices, and missed conditioning sessions were recorded. Exact numbers and areas of injury for each year and each group were tabulated. A chi-square statistic compared the two groups and a logistic regression model was used to estimate the risk of becoming injured and the types of conditioning injuries experienced in the two groups.
Prevalence of injury was significantly different in the two groups. In the turf group, 35% of subjects developed a conditioning injury; in the turf and swim group, 13% developed a conditioning injury (x 2= 33.16, p <.0001). No significant difference in missed practices or missed conditioning sessions was found.
The turf and swim group experienced significantly fewer football preseason conditioning injuries than the turf group. The crossover effects of a running and swimming program may decrease the number of overuse injuries associated with repetitive running on artificial turf in traditional preseason conditioning programs.
PMCID: PMC1320345  PMID: 16558463
Omni turf; running; swimming; overuse injuries; crossover effect

Results 1-10 (10)