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Articles by A Prasad
Total Records ( 5 ) for A Prasad
  A Sekulic , S. Y Kim , G Hostetter , S Savage , J. G Einspahr , A Prasad , P Sagerman , C Curiel Lewandrowski , R Krouse , G. T Bowden , J Warneke , D. S Alberts , M. R Pittelkow , D DiCaudo , B. J Nickoloff , J. M Trent and M. Bittner
 

Cutaneous squamous cell carcinoma (SCC) occurs commonly and can metastasize. Identification of specific molecular aberrations and mechanisms underlying the development and progression of cutaneous SCC may lead to better prognostic and therapeutic approaches and more effective chemoprevention strategies. To identify genetic changes associated with early stages of cutaneous SCC development, we analyzed a series of 40 archived skin tissues ranging from normal skin to invasive SCC. Using high-resolution array-based comparative genomic hybridization, we identified deletions of a region on chromosome 10q harboring the INPP5A gene in 24% of examined SCC tumors. Subsequent validation by immunohistochemistry on an independent sample set of 71 SCC tissues showed reduced INPP5A protein levels in 72% of primary SCC tumors. Decrease in INPP5A protein levels seems to be an early event in SCC development, as it also is observed in 9 of 26 (35%) examined actinic keratoses, the earliest stage in SCC development. Importantly, further reduction of INPP5A levels is seen in a subset of SCC patients as the tumor progresses from primary to metastatic stage. The observed frequency and pattern of loss indicate that INPP5A, a negative regulator of inositol signaling, may play a role in development and progression of cutaneous SCC tumors. Cancer Prev Res; 3(10); 1277–83. ©2010 AACR.

  A Cassar , P Chareonthaitawee , C. S Rihal , A Prasad , R. J Lennon , L. O Lerman and A. Lerman
 

Background— Despite a nonobstructive coronary angiogram, many patients may still have an abnormal coronary vasomotor response to provocation and to myocardial demand during stress. The ability of noninvasive stress tests to predict coronary vasomotor dysfunction in patients with nonobstructive coronary artery disease is unknown.

Methods and Results— All patients with nonobstructive coronary artery disease who had invasive coronary vasomotor assessment and a noninvasive stress test (exercise ECG, stress echocardiography, or stress nuclear imaging) within 6 months of the cardiac catheterization with provocation at our institution were identified (n=376). Coronary vasomotor dysfunction was defined as a percentage increase in coronary blood flow of ≤50% to intracoronary acetylcholine (endothelium-dependent dysfunction) and/or a coronary flow reserve ratio of ≤2.5 to intracoronary adenosine (endothelium-independent dysfunction). We determined the sensitivity and specificity of various noninvasive stress tests to predict coronary vasomotor dysfunction in these patients. On invasive testing, 233 patients (63%) had coronary vasomotor dysfunction, of which 187 patients (51%) had endothelium-dependent dysfunction, 109 patients (29%) had endothelium-independent dysfunction, and 63 patients (17%) had both. On noninvasive stress testing, 157 (42%) had a positive imaging study and 56 (15%) a positive ECG stress test. The noninvasive stress tests had limited diagnostic accuracy for predicting coronary vasomotor dysfunction (41% sensitivity [95% CI, 34 to 47] and 57% specificity [95% CI, 49 to 66]), endothelium-dependent dysfunction (41% sensitivity [95% CI, 34 to 49] and 58% specificity [95% CI, 50 to 65]), or endothelium-independent dysfunction (46% sensitivity [95% CI, 37 to 56] and 61% specificity [95% CI, 54 to 67]). The exercise ECG test was more specific but less sensitive than the imaging tests.

Conclusion— This study suggests that a negative noninvasive stress test does not rule out coronary vasomotor dysfunction in symptomatic patients with nonobstructive coronary artery disease. This underscores the need for invasive assessment or novel more sensitive noninvasive imaging for these patients.

  M. H Drazner , A Prasad , C Ayers , D. W Markham , J Hastings , P. S Bhella , S Shibata and B. D. Levine
 

Background— Although right-sided filling pressures often mirror left-sided filling pressures in systolic heart failure, it is not known whether a similar relationship exists in heart failure with preserved ejection fraction.

Methods and Results— Eleven subjects with heart failure with preserved ejection fraction underwent right heart catheterization at rest and under loading conditions manipulated by lower body negative pressure and saline infusion. Right atrial pressure (RAP) was classified as elevated when ≥10 mm Hg and pulmonary capillary wedge pressure (PCWP) when ≥22 mm Hg. If both the RAP and the PCWP were elevated or both not elevated, they were classified as concordant; otherwise, they were classified as discordant. Correlation of RAP and PCWP was determined by a repeated measures model. Among 66 paired measurements of RAP and PCWP, 44 (67%) had a low RAP and PCWP and 8 (12%) a high RAP and PCWP, yielding a concordance rate of 79%. In a sensitivity analysis performed by varying the definition of elevated RAP (from 8 to 12 mm Hg) and PCWP (from 15 to 25 mm Hg), the mean±SD concordance of RAP and PCWP was 76±10%. The correlation coefficient of RAP and PCWP for the overall cohort was r=0.86 (P<0.0001).

Conclusions— Right-sided filling pressures often reflect left-sided filling pressures in heart failure with preserved ejection fraction, supporting the role of estimation of jugular venous pressure to assess volume status in this condition.

  A Prasad , J. L Hastings , S Shibata , Z. B Popovic , A Arbab Zadeh , P. S Bhella , K Okazaki , Q Fu , M Berk , D Palmer , N. L Greenberg , M. J Garcia , J. D Thomas and B. D. Levine
  Background—

Congestive heart failure in the setting of a preserved left ventricular (LV) ejection fraction is increasing in prevalence among the senior population. The underlying pathophysiologic abnormalities in ventricular function and structure remain unclear for this disorder. We hypothesized that patients with heart failure with preserved ejection fraction (HFPEF) would have marked abnormalities in LV diastolic function with increased static diastolic stiffness and slowed myocardial relaxation compared with age-matched healthy controls.

Methods and Results—

Eleven highly screened patients (4 men, 7 women) aged 73±7 years with HFPEF were recruited to participate in this study. Thirteen sedentary healthy controls (7 men, 6 women) aged 70±4 years also were recruited. All subjects underwent pulmonary artery catheterization with measurement of cardiac output, end-diastolic volumes, and pulmonary capillary wedge pressures at baseline; cardiac unloading (lower-body negative pressure or upright tilt); and cardiac loading (rapid saline infusion). The data were used to define the Frank-Starling and LV end-diastolic pressure-volume relationships. Doppler echocardiographic data (tissue Doppler velocities, isovolumic relaxation time, propagation velocity of early mitral inflow , E/A-wave ratio) were obtained at each level of cardiac preload. Compared with healthy controls, patients with HFPEF had similar LV contractile function and static LV compliance but reduced LV chamber distensibility with elevated filling pressures and slower myocardial relaxation as assessed by tissue Doppler imaging.

Conclusions—

In this small, highly screened patient population with hemodynamically confirmed HFPEF, increased end-diastolic static ventricular stiffness relative to age-matched controls was not a universal finding. Nevertheless, patients with HFPEF, even when well compensated, had elevated filling pressures, reduced distensibility, and increased diastolic wall stress compared with controls. In contrast, LV relaxation as assessed by tissue Doppler variables appeared consistently impaired in patients with HFPEF.

  E Raichlin , A Prasad , W. K Kremers , B. S Edwards , C. S Rihal , A Lerman and S. S. Kushwaha
  Aims

The aim of this study was to evaluate coronary vasomotor function in cardiac transplant recipients maintained on sirolimus (SRL)- or cyclosporin (CyA)-based immunosuppression.

Methods and results

Endothelium-independent response to intracoronary nitroglycerin and adenosine and endothelium-dependent response to intracoronary acetylcholine (Ach) were assessed in 15 SRL- and 21 CyA- treated subjects with angiographically normal coronary arteries. Baseline mean blood pressure was lower in the SRL group (85.6 ± 10.3 vs. 105.2 ± 8.7 mmHg, P = 0.002). There was no difference between the groups in coronary flow reserve after adenosine administration in multivariable analysis (P = 0.34). Nitroglycerin administration resulted in increase in coronary artery diameter in the SRL compared with the CyA groups (2.79 ± 0.54 vs. 2.57 ± 0.61, P = 0.0036). In 13 SRL-treated subjects without evidence of cardiac allograft vasculopathy (CAV), Ach administration resulted in less epicardial vasoconstriction compared with CyA-treated subjects (2.7 ± 17.7 vs. –15.6 ± 17.2%, P = 0.005). Two SRL-treated subjects with three-dimensional intravascular ultrasound evidence of CAV developed coronary spasm in response to Ach 10–4. Microvascular endothelial function did not differ between the groups.

Conclusion

Sirolimus immunosuppression is associated with less pronounced coronary epicardial endothelial dysfunction compared with CyA immunosuppression. Improvement of coronary vasomotor function with SRL may be an important mechanism for the prevention of CAV.

 
 
 
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