Background-Structural and electrophysiological changes of the atria occur with prolonged rapid rates; however, the effects of sustained atrial fibrillation (AF) on autonomic innervation of the atria are unknown. We hypothesized that electrophysiological remodeling from rapid atrial rates is accompanied by altered atrial autonomic innervation. Methods and Results-Six dogs (paced group) underwent atrial pacing at 600 bpm; 9 dogs (control animals) were not paced. All paced dogs developed sustained AF by week 4 of pacing. All 15 animals underwent positron emission tomography imaging of the atria with [C-11] hydroxyephedrine (HED) to label sympathetic nerve terminals. HED retention in the atria was significantly greater in paced dogs compared with control animals (Pϭ0.03). Tissue samples from the atrial appendages had a greater concentration of norepinephrine in paced animals than in control animals (Pϭ0.01). The coefficient of variation of HED retention was also greater in paced animals (Pϭ0.05) and was greater in the right atrium than in the left atrium (Pϭ0.004). Epicardial activation maps of AF were obtained in the paced animals at baseline and with autonomic manipulation. Mean AF cycle length was longer in the right atrium (109.2Ϯ5 ms) than in the left atrium (85.8Ϯ5.5 ms) at baseline (Pϭ0.005). AF cycle length did not vary significantly from baseline (97.6Ϯ13.4 ms) with stellate stimulation (100.5Ϯ6 ms) but lengthened with propranolol (107.5Ϯ6.1 ms, Pϭ0.03). Conclusions-Rapid rates of AF produce a heterogeneous increase in atrial sympathetic innervation. These changes parallel disparate effects of rapid pacing-induced AF on atrial electrophysiology.

Atrial flutter involving either clockwise or counterclockwise rotation around the tricuspid annulus utilizing the subeustachian isthmus has been well described. However, macroreentrant atrial circuits in atypical atrial flutter in patients who have not undergone previous surgery or without atrial disease are not well defined. We describe a patient without structural heart disease who presented with an atrial macroreentrant rhythm. Entrainment mapping demonstrated a critical isthmus within the coronary sinus. Activation mapping demonstrated double potential throughout the length of the coronary sinus with disparate activation sequences. A circuit involving the myocardium of the coronary sinus, exiting in the lateral left atrium, down the interatrial septum, and reentering into the coronary sinus was identified. Successful ablation of the rhythm was accomplished by a circumferential radiofrequency application within the coronary sinus.

Background-Heterogeneous electrophysiological properties, which may be due in part to autonomic innervation, are important in the maintenance of atrial fibrillation (AF). We hypothesized that heterogeneous sympathetic denervation with phenol would create a milieu for sustained AF. Methods and Results-After the determination of baseline inducibility, 15 dogs underwent atrial epicardial phenol application and 11 underwent a sham procedure. After 2 weeks of recovery, the animals had repeat attempts at inducing AF and effective refractory period (ERP) testing. Epicardial maps were obtained to determine local AF cycle lengths. ERPs were determined at baseline and during sympathetic, vagal, and simultaneous vagal/sympathetic stimulation.

A wide array of biomarkers is being investigated as predictors of prostate cancer (PCa) diagnosis and recurrence. We compared the expression of a small panel of these biomarkers as a function of race among men undergoing radical prostatectomy (RP). Prostate needle biopsy specimens from 131 patients treated with RP at the Durham Veterans Affairs Medical Center were hematoxylin and eosin stained and immunofluorescent assayed for α-methylacyl CoA racemase (AMACR), androgen receptor (AR) and Ki67. Proprietary image analysis was used to identify six biometric feature combinations that were significantly associated with progression in a previous study. Analysis of population characteristics, stratified by race, was performed using rank-sum and χ(2)-test. The effect of race on expression of these biomarker profiles was analyzed using multivariate linear regression. All six biomarker features were expressed at higher levels in black men than white men, with Norm AR (P=0.006) and Ki67 (P=0.02) attaining statistical significance. On multivariate analysis, all markers were expressed at higher levels in black men, with Norm AR (P=0.001), Ki67 (P=0.007) and Ki67/lum (P=0.022) reaching significance. These data support the hypothesis that PCa may be biologically more aggressive among black men.

Background: Diabetes is associated with lower prostate cancer risk. The association of diabetes with prostate cancer outcomes is less clear. We examined the association between diabetes and outcomes after radical prostatectomy and tested whether associations varied by race and/or obesity.Materials and Methods: This study is a retrospective analysis of 1,262 men treated with radical prostatectomy between 1988 and 2008 within the Shared Equal-Access Regional Cancer Hospital database. We examined the multivariate association between diabetes at surgery and adverse pathology, biochemical recurrence (BCR), and prostate-specific antigen doubling time at recurrence using logistic, proportional hazards, and linear regression, respectively. Data were examined as a whole and stratified by race and obesity.Results: Diabetes was more prevalent among black (22% versus 15%, P < 0.001) and more obese men (P < 0.001). Diabetes was associated with higher tumor grade (odds ratio, 1.73; P = 0.002), seminal vesicle invasion (odds ratio, 1.73; P = 0.04), but not BCR (P = 0.67) or PSADT at recurrence (P = 0.12). In the secondary analysis, among white obese men, diabetes was associated with 2.5-fold increased BCR risk (P = 0.002) and a trend toward shorter PSADT, whereas among all other men (nonobese white men and black men), diabetes was associated with 23% lower recurrence risk (P = 0.09) and longer PSADT (P = 0.04).Conclusion: In a radical prostatectomy cohort, diabetes was not associated with BCR. In the secondary analysis, diabetes was associated with more aggressive disease in obese white men and less aggressive disease for all other subsets. If externally validated, these findings suggest that among men with prostate cancer, the association between diabetes and prostate cancer aggressiveness may vary by race and obesity. Cancer

Activation of the NHE is one mechanism underlying short-term ER.

We hypothesized that factors beyond pathological stage, grade, PSA and margin status would be important predictors of biochemical recurrence (BCR) after radical prostatectomy (RP). A cohort of 3194 patients who underwent RP between 1988 and 2007 and who had neither neoadjuvant therapy nor postoperative adjuvant hormonal therapy was retrieved from the Duke Prostate Center database. Age, prostate-specific antigen (PSA), pathological Gleason score (pG), lymph node status, seminal vesicle invasion (SVI), extracapsular extension (ECE), positive surgical margin (PSM) status, year of surgery, race, adjuvant radiation therapy (XRT), percent tumor involvement in the RP specimen and prostate weight were evaluated as possible predictors of BCR in multivariate Cox regression analysis. BCR was defined as a PSA of 0.2 ng ml À1 or higher at least 30 days after surgery. A nomogram was developed from the Cox model. Predictive accuracy was obtained by calculating bias-corrected Harrell's c and by bootstrap calibration. In multivariate analysis, PSA (hazard ratio 1.39 (95% confidence interval 1.29-1.51)), ECE (1.22 (1.04-1.44)), pG score (1.38 (1.14-1.68), 2.23 (1.76-2.84), 2.69 (2.12-3.40) for pG 3 þ 4, 4 þ 3, 47, respectively), SVI (1.72 (1.40-2.12)), PSM (2.05 (1.73-2.42)), year of surgery (0.65 (0.54-0.77)), African-American race (1.37 (1.13-1.66)), adjuvant ) and prostate weight (0.83 (0.76-0.92)) were identified as independent predictors of BCR (Pp0.018 for all factors). Predictive accuracy of the nomogram was 0.75. Race and prostate weight were independent predictors for BCR after RP. By incorporating these variables, we developed a nomogram, which provides a highly accurate means for estimating risk of BCR after RP.

Purpose-Among men with either extracapsular disease or positive surgical margins after radical prostatectomy, immediate adjuvant therapy decreases the risk of biochemical recurrence at the cost of increased toxicity. We sought to further stratify these men into a low-risk group in whom watchful waiting after surgery may be preferred and a high-risk cohort in whom adjuvant therapy may be preferred. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Materials and Methods-We NIH Public Access NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptCox proportional hazards regression model, we generated tables to estimate the risk of recurrence at 1, 3 and 5 years after surgery.Results-After a median of 3 years of follow-up, 346 (39%) patients developed a biochemical recurrence. On multivariate analysis, the significant predictors of biochemical recurrence included age >60 years, PSA >10 ng/ml, Gleason score 4+3 and 8-10, 2 or more sites of positive surgical margins and prostate specimen weight ≤30 grams. The overall predictive accuracy of the model as determined by the Concordance Index C was 0.67, which compared to 0.60 for the post-operative "Kattan nomogram" for this patient population.Conclusions-We have developed a simple instrument, which once validated, may aid in the postoperative decision making process for men with intermediate risk of recurrence after prostatectomy.