19 results on '"Anthony P. Leonard"'
Search Results
2. Sex Differences in Cardiovascular Outcomes in Patients With Kidney Failure
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Silvi Shah, Annette L. Christianson, Karthikeyan Meganathan, Anthony C. Leonard, Deidra C. Crews, Jack Rubinstein, Mark M. Mitsnefes, Daniel P. Schauer, and Charuhas V. Thakar
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cardiovascular events ,death ,dialysis ,disparities ,sex ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Background Cardiovascular disease is the leading cause of mortality in patients with kidney failure, and their risk of cardiovascular events is 10 to 20 times higher as compared with the general population. Methods and Results We evaluated 508 822 patients who initiated dialysis between January 1, 2005 and December 31, 2014 using the United States Renal Data System with linked Medicare claims. We determined hospitalization rates for cardiovascular events, defined by acute coronary syndrome, heart failure, and stroke. We examined the association of sex with outcome of cardiovascular events, cardiovascular death, and all‐cause death using adjusted time‐to‐event models. The mean age was 70±12 years and 44.7% were women. The cardiovascular event rate was 232 per thousand person‐years (95% CI, 231–233), with a higher rate in women than in men (248 per thousand person‐years [95% CI, 247–250] versus 219 per thousand person‐years [95% CI, 217–220]). Women had a 14% higher risk of cardiovascular events than men (hazard ratio [HR], 1.14 [95% CI, 1.13–1.16]). Women had a 16% higher risk of heart failure (HR, 1.16 [95% CI, 1.15–1.18]), a 31% higher risk of stroke (HR, 1.31 [95% CI, 1.28–1.34]), and no difference in risk of acute coronary syndrome (HR, 1.01 [95% CI, 0.99–1.03]). Women had a lower risk of cardiovascular death (HR, 0.89 [95% CI, 0.88–0.90]) and a lower risk of all‐cause death than men (HR, 0.96 [95% CI, 0.95–0.97]). Conclusions Among patients undergoing dialysis, women have a higher risk of cardiovascular events of heart failure and stroke than men. Women have a lower adjusted risk of cardiovascular mortality and all‐cause mortality.
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- 2024
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3. Solitary fibrous tumor of pleura presenting as respiratory failure: unusual presentation of a rare tumor
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Layek, Avishek, Anthony, Michael Leonard, Darbari, Anshuman, and Mishra, Mayank
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- 2023
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4. Granulomatous cheilitis of Miescher: a rare entity
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Tummidi, Santosh, Nagendran, Prabhakaran, Anthony, Michael Leonard, Ramani, Rupa Jami, Shankaralingappa, Arundhathi, and Gopinath, Hima
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- 2023
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5. Racial and sex differences in optimizing anticoagulation therapy for patients with atrial fibrillation
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Mark H. Eckman, Ruth Wise, Anthony C. Leonard, Pete Baker, Rob Ireton, Brett M. Harnett, Estrelita Dixon, Bi Awosika, Chika Ezigbo, Matthew L. Flaherty, Adeboye Adejare, Carol Knochelmann, Rachael Mardis, Sharon Wright, Ashish Gummadi, Richard Becker, Daniel P. Schauer, Alexandru Costea, Dawn Kleindorfer, Heidi Sucharew, Amy Costanzo, Lora Anderson, and John Kues
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Racial disparities ,Gender disparities ,Atrial fibrillation ,Anticoagulation therapy ,Stroke prevention ,Decision sciences ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Study objective: Atrial fibrillation (AF) is the most common cardiac rhythm disorder, responsible for 15 % of strokes in the United States. Studies continue to document underuse of anticoagulation therapy in minority populations and women. Our objective was to compare the proportion of AF patients by race and sex who were receiving non-optimal anticoagulation as determined by an Atrial Fibrillation Decision Support Tool (AFDST). Design, setting, and participants: Retrospective cohort study including 14,942 patients within University of Cincinnati Health Care system. Data were analyzed between November 18, 2020, and November 20, 2021. Main outcomes and measures: Discordance between current therapy and that recommended by the AFDST. Results: In our two-category analysis 6107 (41 %) received non-optimal anticoagulation therapy, defined as current treatment category ≠ AFDST-recommended treatment category. Non-optimal therapy was highest in Black (42 % [n = 712]) and women (42 % [n = 2668]) and lower in White (39 % [n = 4748]) and male (40 % [n = 3439]) patients. Compared with White patients, unadjusted and adjusted odds ratios of receiving non-optimal anticoagulant therapy for Black patients were 1.13; 95 % CI, 1.02–1.30, p = 0.02; and 1.17; 95%CI, 1.04–1.31, p = 0.01; respectively, and 1.10; 95 % CI 1.03–1.18, p = 0.005; and 1.36; 95 % CI, 1.25–1.47, p
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- 2022
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6. Contraceptive Use Among Women With End-Stage Kidney Disease on Dialysis in the United StatesPlain-Language Summary
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Silvi Shah, Annette L. Christianson, Charuhas V. Thakar, Samantha Kramer, Karthikeyan Meganathan, and Anthony C. Leonard
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Rates ,contraception ,dialysis ,race/ethnicity ,end-stage kidney disease ,Diseases of the genitourinary system. Urology ,RC870-923 - Abstract
Rationale & Objective: Although end-stage kidney disease (ESKD) adversely affects fertility, pregnancies can occur among women receiving dialysis. ESKD increases the risk for adverse pregnancy outcomes and little is known about contraceptive use in women undergoing dialysis. Study Design: Retrospective cohort study. Setting & Participants: Using the US Renal Data System covering January 1, 2005, through December 31, 2014, we evaluated for each calendar year women who for the entire year were aged 15 to 44 years, receiving dialysis, and with Medicare as the primary payer. Predictors: Age, race/ethnicity, and calendar year of prevalent ESKD. Outcome: Contraceptive use. Analytic Approach: We determined rates of contraceptive use and used multivariable logistic regression to identify factors associated with contraceptive use. Results: The study cohort included 35,732 women and represented 115,713 person-years. The rate of contraceptive use was 5.30% of person-years (95% CI, 5.17%-5.42%). Overall, contraceptive use increased from 2005 to 2014 (4.21%; 95% CI, 3.84%-4.59% vs 6.54%, 95% CI, 6.10%-6.99%). Compared with women aged 25 to 29 years, contraceptive use was higher in women aged 15 to 24 years (OR, 1.30; 95% CI, 1.18-1.43) and lower in women aged 30 to 34 years (OR, 0.74; 95% CI, 0.68-0.81), 35 to 39 years (OR, 0.46; 95% CI, 0.42-0.50), and 40 to 44 years (OR, 0.30; 95% CI, 0.27-0.34). Compared with White women, contraceptive use was higher in Black (OR, 1.12; 95% CI, 1.02-1.24) and Native American women (OR, 1.60; 95% CI, 1.25-2.05). Women with ESKD due to glomerulonephritis had a higher likelihood of contraceptive use than women with ESKD due to diabetes (OR, 1.22; 95% CI, 1.06-1.42). Women receiving peritoneal dialysis had a lower likelihood of contraceptive use than women receiving hemodialysis (OR, 0.85; 95% CI, 0.78-0.93). Compared with women without predialysis nephrology care, contraceptive use was higher in women who received predialysis nephrology care for 12 or fewer months (OR, 1.22; 95% CI, 1.09-1.37) and more than 12 months (OR, 1.33; 95% CI, 1.20-1.47). Limitations: Retrospective design and use of administrative data. Conclusions: Among women with ESKD undergoing dialysis, contraceptive use remains low at 5.30%. Younger age, Native American and Black race/ethnicity, ESKD due to glomerulonephritis, hemodialysis, and predialysis nephrology care are associated with a higher likelihood of contraceptive use. The study highlights the importance of prepregnancy counseling for contraceptive use in women receiving dialysis.
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- 2020
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7. Functional status, pre-dialysis health and clinical outcomes among elderly dialysis patients
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Silvi Shah, Anthony C. Leonard, and Charuhas V. Thakar
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Functional status ,Elderly ,Mortality ,Vascular access ,and Dialysis ,Diseases of the genitourinary system. Urology ,RC870-923 - Abstract
Abstract Background Elderly patients comprise the fastest growing population initiating dialysis in United States. The impact of poor functional status and pre-dialysis health status on clinical outcomes in elderly dialysis patients is not well studied. Methods We studied a retrospective cohort of 49,645 incident end stage renal disease patients that initiated dialysis between January 1, 2008 and December 31, 2008 from the United States Renal Data System with linked Medicare data covering at least 2 years prior to dialysis initiation. Using logistic regression models adjusted for pre-dialysis health status and other cofounders, we examined the impact of poor functional status as defined from form 2728 on 1-year all-cause mortality as primary outcome, type of dialysis modality (hemodialysis vs. peritoneal dialysis), and type of initial vascular access (arteriovenous access vs. central venous catheter) among hemodialysis patients as secondary outcomes. Results Mean age was 72 ± 11 years. At dialysis initiation, 18.7% reported poor functional status, 88.9% had at least 1 pre-dialysis hospitalization, and 27.8% did not receive pre-dialysis nephrology care. In adjusted analyses, 1-year mortality was higher in patients with poor functional status (OR, 1.48; 95% CI, 1.40–1.57). Adjusted odds of being initiated on hemodialysis than peritoneal dialysis (odds ratio [OR], 1.39; 95% confidence interval [CI], 1.16–1.66) were higher in patients with poor functional status. Poor functional status decreased the adjusted odds of starting hemodialysis with arteriovenous access as compared to central venous catheter (OR, 0.79; 95% CI, 0.72–0.86). Conclusion Poor functional status in elderly patients with end stage renal disease is associated with higher odds of initiating hemodialysis; increases the risk of central venous catheter use, and is an independent predictor of 1-year mortality.
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- 2018
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8. Racial disparities and factors associated with pregnancy in kidney transplant recipients in the United States.
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Silvi Shah, Annette L Christianson, Prasoon Verma, Karthikeyan Meganathan, Anthony C Leonard, Daniel P Schauer, and Charuhas V Thakar
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Medicine ,Science - Abstract
BackgroundAlthough kidney transplant improves reproductive function in women with end-stage kidney disease (ESKD), pregnancy in kidney transplant recipients' remains challenging due to the risk of adverse maternal and fetal outcomes.MethodsWe evaluated a retrospective cohort of 7,966 women who were aged 15-45 years and received a kidney transplant between January 1, 2005 and December 31, 2011 from the United States Renal Data System with Medicare as the primary payer for the entire three years after the date of transplantation. Unadjusted and adjusted rates of pregnancy in the first three post-transplant years were calculated, using Poisson regression for the adjustment. Factors associated with pregnancy, including race, were examined using logistic regression.ResultsOverall, 293 pregnancies were identified in 7966 women. The unadjusted pregnancy rate was 13.8 per thousand person-years (PTPY) (95% confidence interval (CI), 12.3-15.5). Pregnancy rates were roughly constant in the years 2005-2011 except in 2005 and 2010. The rate of pregnancy was highest in Hispanic women (21.4 PTPY; 95% CI, 17.2-26.4) and Hispanic women had a higher likelihood of pregnancy as compared to white women (OR, 1.56; CI, 1.12-2.16). Pregnancy rates were lowest in women aged 30-34 years and 35-45 years at transplant, and women aged 30-34 years and 35-45 years at transplant were less likely to ever become pregnant during the follow-up (odds ratio [OR], 0.69; CI, 0.49-0.98 and OR, 0.14; CI 0.09-0.21 respectively) as compared to women aged 25-29 years at time of transplant. Women had higher rates of pregnancy in the second and third-year post-transplant (16.0 PTPY, CI 13.2-19.2 and 16.9 PTPY, CI 14.0-20.4) than in the first-year post-transplant (9.0 PTPY, CI 7.0-11.4). In transplant recipients, pregnancy was more likely in women with ESKD due to cystic disease (OR, 2.42; CI, 1.02-5.74) or glomerulonephritis (OR, 2.14; CI, 1.07-4.31) as compared to women with ESKD due to diabetes.ConclusionHispanic race, younger age, and ESKD cause due to cystic disease or glomerulonephritis are significant factors associated with a higher likelihood of pregnancy. Pregnancy rates have been fairly constant over the last decade. This study improves our understanding of factors associated with pregnancy in kidney transplant recipients.
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- 2019
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9. Pre-dialysis acute care hospitalizations and clinical outcomes in dialysis patients.
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Silvi Shah, Karthikeyan Meganathan, Annette L Christianson, Anthony C Leonard, and Charuhas V Thakar
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Medicine ,Science - Abstract
BackgroundPatients with chronic kidney disease (CKD), a precursor of end stage renal disease (ESRD), face an increasing burden of hospitalizations. Although mortality on dialysis is highest during the first year, the impact of pre-dialysis acute hospitalizations on clinical outcomes in dialysis patients remains unknown.MethodsWe evaluated 170,897 adult patients who initiated dialysis between 1/1/2010 and 12/31/2014 with linked Medicare claims from the United States Renal Data System. Using logistic regression models, we examined the association of 2-year pre-dialysis hospitalization on the primary outcome of 1-year all-cause mortality. Secondary outcomes included 90-day mortality, type of initial dialysis modality and type of vascular access at hemodialysis initiation.ResultsMean age was 72.7 ± 11.0 years. In the study sample, 76.0% of patients had at least one pre-dialysis hospitalization. Compared to patients with no pre-dialysis hospitalization, the adjusted 1-year mortality was higher with pre-dialysis cardiovascular related hospitalization (odds ratio [OR], 1.63; 95% confidence interval [CI], 1.57-1.68), infection related hospitalization (OR, 1.51; CI, 1.45-1.57), both cardiovascular and infection hospitalization (OR, 1.91; CI, 1.83-1.99), and neither-cardiovascular nor-infection hospitalization (OR, 1.23; CI, 1.19-1.27). Additionally, the adjusted odds of hemodialysis vs. peritoneal dialysis as the initial dialysis modality were higher, whereas adjusted odds to initiate hemodialysis with an arteriovenous access vs. central venous catheter were lower in patients with any type of hospitalization.ConclusionPre-dialysis hospitalization is an independent predictor of 1-year mortality in dialysis patients. Reducing the risk of pre-dialysis hospitalization may provide opportunities to improve quality of care in ESRD.
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- 2019
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10. Contrast-Induced Nephropathy in Renal Transplant Recipients: A Single Center Experience
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Bassam G. Abu Jawdeh, Anthony C. Leonard, Yuvraj Sharma, Swapna Katipally, Adele R. Shields, Rita R. Alloway, E. Steve Woodle, and Charuhas V. Thakar
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contrast nephropathy ,transplant ,AKI ,calcineurin inhibitors ,kidney ,Medicine (General) ,R5-920 - Abstract
BackgroundContrast-induced nephropathy (CIN) in native kidneys is associated with a significant increase in mortality and morbidity. Data regarding CIN in renal allografts are limited, however. We retrospectively studied CIN in renal allografts at our institution: its incidence, risk factors, and effect on long-term outcomes including allograft loss and death.MethodsOne hundred thirty-five renal transplant recipients undergoing 161 contrast-enhanced computed tomography (CT) scans or coronary angiograms (Cath) between years 2000 and 2014 were identified. Contrast agents were iso- or low osmolar. CIN was defined as a rise in serum creatinine (SCr) by >0.3 mg/dl or 25% from baseline within 4 days of contrast exposure. After excluding 85 contrast exposures where patients had no SCr within 4 days of contrast administration, 76 exposures (CT: n = 45; Cath: n = 31) in 50 eligible patients were analyzed. Risk factors assessed included demographics, comorbid conditions, type/volume of contrast agent used, IV fluids, N-acetylcysteine administration, and calcineurin inhibitor use. Bivariate and multivariable analyses were used to assess the risk of CIN.ResultsIncidence of CIN was 13% following both, CT (6 out of 45) and Cath (4 out of 31). Significant bivariate predictors of CIN were IV fluid administration (p = 0.05), lower hemoglobin (p = 0.03), and lower albumin (p = 0.02). In a multivariable model, CIN was predicted by N-acetylcysteine (p = 0.03) and lower hemoglobin (p = 0.01). Calcineurin inhibitor use was not associated with CIN. At last follow-up, CIN did not affect allograft or patient survival.ConclusionCIN is common in kidney transplant recipients, and there is room for quality improvement with regards to careful renal function monitoring post-contrast exposure. In our study, N-acetylcysteine exposure and lower hemoglobin were associated with CIN. Calcineurin inhibitor use was not associated with CIN. Our sample size is small, however, and larger prospective studies of CIN in renal allografts are needed.
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- 2017
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11. Health care utilization history, GOLD guidelines, and respiratory medication prescriptions in patients with COPD
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Joseph Seaman, Anthony C Leonard, and Ralph J Panos
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Diseases of the respiratory system ,RC705-779 - Abstract
Joseph Seaman1,2, Anthony C Leonard3, Ralph J Panos1,21Pulmonary, Critical Care, and Sleep Division, Cincinnati Veterans Affairs Medical Center, Cincinnati, OH, USA; 2Pulmonary, Critical Care, and Sleep Division, University of Cincinnati School of Medicine, Cincinnati, OH, USA; 3Department of Public Health Sciences, University of Cincinnati School of Medicine, Cincinnati, OH, USABackground: The relationship between prior health care utilization and respiratory medication prescriptions in an unselected population of patients with COPD is not known.Methods: We determined the prescribed respiratory medications and respiratory and nonrespiratory health care encounters in 523 Veterans with COPD at the Cincinnati Veterans Affairs Medical Center between 2000 and 2005. Prescribed treatments were compared with the GOLD guidelines and each patient was classified as receiving less medications than recommended in the guidelines (G).Results: Respiratory medications were G for 14% of the patients studied. For GOLD stages 1 and 2, G patients the most prior respiratory encounters during a 12 month period (0.31 ± 0.073 (0.21, 0.47), 0.75 ± 0.5 (0.37, 1.5), 1.1 ± 0.27 (0.74, 1.6) visits/person/year, G, respectively, mean + standard error of mean (SEM) (95% confidence limits) 2 degrees of freedom (df) ANOVA P < 0.001 for prescription effect). For GOLD stages 3 and 4, G respectively, 2 df ANOVA P = 0.096) or for GOLD stages 3 and 4 (3.6 ± 0.25 (3.2, 4.1) and 4.0 ± 0.44 (3.3, 4.9) visits/ person/year,
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- 2010
12. Outcomes and Practice Preferences After Endophthalmitis Following Anti-VEGF Intravitreal Injection
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Ryan J. Whitted, Tavé van Zyl, Kevin J. Blinder, Ananda Kalevar, Carl D. Regillo, John S. Pollack, Asheesh Tewari, Gaurav K. Shah, Lawrence J. Singerman, Abdallah Jeroudi, Jonathan Hu, Charles C. Wykoff, Dean Eliott, Mahdi Rostamizadeh, J. Michael Jumper, Anthony Joseph, Brett M. Weinstock, Musa Abdelaziz, Anthony P. Leonard, Marina Gilca, John W. Kitchens, Yicheng Chen, Vaishali Shah, Rui Wang, Bobeck S. Modjtahedi, Gregory D. Lee, and Jeffrey S. Heier
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Anti vegf ,medicine.medical_specialty ,business.industry ,Growth factor ,medicine.medical_treatment ,Diabetic macular edema ,Vitreoretinal surgery ,medicine.disease ,03 medical and health sciences ,Retinal neovascularization ,0302 clinical medicine ,Endophthalmitis ,Choroidal neovascularization ,Central retinal vein occlusion ,Ophthalmology ,030221 ophthalmology & optometry ,medicine ,030212 general & internal medicine ,medicine.symptom ,business - Abstract
Purpose:This study examines treatment-based outcomes of endophthalmitis due to antivascular endothelial growth factor (anti-VEGF) intravitreal injection and its effect on subsequent management of neovascular disease.Methods:A retrospective multicenter study was conducted of 157 patients with a diagnosis of endophthalmitis following anti-VEGF intravitreal injection at 10 major ophthalmic centers.Results:The median number of injections before endophthalmitis was 10 (range, 1 to 84 injections). Initial treatment with tap and inject with or without subsequent vitrectomy trended toward smaller visual acuity changes from baseline (4 ETDRS [Early Treatment Diabetic Retinopathy Study] letter difference vs 19 ETDRS letter difference) compared with initial vitrectomy, but the difference was not statistically significant. There was no significant change in medication choice among injections after endophthalmitis. There was a statistically significant shift away from regular interval (1- to 2-month) injections and a shift toward treat-and-extend and as-needed injection algorithms.Conclusions:The visual outcomes were not significantly different between patients who initially underwent tap and injection of antibiotics and those who underwent vitrectomy. There was no significant change in medication choice before and after endophthalmitis but there was a shift toward lower-frequency injection algorithms after postintravitreal injection endophthalmitis compared with prior.
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- 2019
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13. Double-Pass Retina Point Imaging for the Evaluation of Optical Light Scatter, Retinal Image Quality, and Staging of Keratoconus
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Karolinne Maia Rocha, Scott D Gardner, Evan R Zeldin, David M Tremblay, George O. Waring, and Anthony P. Leonard
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Adult ,Diagnostic Imaging ,Male ,Point spread function ,Keratoconus ,medicine.medical_specialty ,Light ,genetic structures ,Population ,Diagnostic Techniques, Ophthalmological ,Sensitivity and Specificity ,Retina ,Article ,Cornea ,03 medical and health sciences ,0302 clinical medicine ,Ophthalmology ,medicine ,Humans ,Scattering, Radiation ,Stage (cooking) ,education ,Retinoscopy ,education.field_of_study ,medicine.diagnostic_test ,business.industry ,Corneal Topography ,medicine.disease ,Corneal topography ,eye diseases ,medicine.anatomical_structure ,ROC Curve ,Area Under Curve ,030221 ophthalmology & optometry ,Optometry ,Female ,Surgery ,sense organs ,Tomography ,business ,030217 neurology & neurosurgery - Abstract
PURPOSE: To measure retinal image quality using point spread function (PSF) analysis by double-pass retina point imaging in patients with keratoconus and to correlate visual quality with disease severity. METHODS: Patients diagnosed as having keratoconus by clinical examination, topography, and tomography and normal eyes were included in this study. A commercially available double-pass retina point imaging instrument (OQAS 108 II AcuTarget HD; Visiometrics S.L., Terrassa, Spain) was used to collect Objective Scatter Index (OSI) values in 21 keratoconic and 22 normal eyes. Eyes were also subjected to corneal topography and tomography, and staged using the Keratoconus Severity Score (KSS) and Amsler–Krumeich (AK) scales. RESULTS: The OSI was increased in keratoconic eyes (5.85 ± 0.98) versus control eyes (0.83 ± 0.12; mean ± SEM), in AK stages 1 to 4, and KSS stages 3 and 4. Receiver-operator characteristic analysis obtained an area under the curve (AUC) of 0.859 when evaluating the OSI as a unimodal diagnostic indicator for any KSS stage and 0.993 for KSS stages 3 and higher. An AUC of 0.949 was obtained in comparing eyes with lower severity topographic aberrations (KSS 1 and 2) versus mild to moderate keratoconus (KSS 3 and 4). Increasing corneal steepening patterns on tomography and topography were associated with PSF broadening and increased OSI. CONCLUSIONS: Double-pass retina point imaging is useful in correlating retinal image quality with keratoconus severity. The OSI may represent a clinically significant parameter for staging keratoconus with a unique ability to directly evaluate quality of vision in this population. [ J Refract Surg. 2016;32(11):760–765.]
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- 2016
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14. A high-content, live-cell, and real-time approach to the quantitation of ligand-induced β-Arrestin2 and Class A/Class B GPCR mobilization
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Louis M. Luttrell, Yuri K. Peterson, Anthony P. Leonard, and Kathryn M. Appleton
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Agonist ,medicine.drug_class ,Endosome ,Arrestins ,Time-Lapse Imaging ,Article ,Cell Line ,Automation ,Arrestin ,medicine ,Humans ,Receptor ,Instrumentation ,beta-Arrestins ,G protein-coupled receptor ,Receptor, Parathyroid Hormone, Type 1 ,Parathyroid hormone receptor ,Chemistry ,Colocalization ,Ligand (biochemistry) ,Kinetics ,Biochemistry ,Microscopy, Fluorescence ,Biophysics ,Receptors, Adrenergic, beta-1 ,Protein Binding - Abstract
We report the development of a method to analyze receptor and β-arrestin2 mobilization between Class A and B GPCRs via time-resolved fluorescent microscopy coupled with semiautomated high-content multiparametric analysis. Using transiently expressed, tagged β2-adrenergic receptor (β2-AR) or parathyroid hormone receptor type 1 (PTH1R), we quantified trafficking of the receptors along with the mobilization and colocalization of coexpressed tagged β-arrestin2. This classification system allows for exclusion of cells with nonoptimal characteristics and calculation of multiple morphological and spatial parameters including receptor endosome formation, β-arrestin mobilization, colocalization, areas, and shape. Stimulated Class A and B receptors demonstrate dramatically different patterns with regard to β-arrestin interactions. The method provides high kinetic resolution measurement of receptor translocation, which allows for the identification of the fleeting β-arrestin interaction found with β2-AR agonist stimulation, in contrast to stronger mobilization and receptor colocalization with agonist stimulation of the PTH1R. Though especially appropriate for receptor kinetic studies, this method is generalizable to any dual fluorescence probe system in which quantification of object formation and movement is desired. These methodologies allow for quantitative, unbiased measurement of microscopy data and are further enhanced by providing real-time kinetics.
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- 2013
15. Targeting Hyaluronan Interactions in Spinal Cord Astrocytomas and Diffuse Pontine Gliomas
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Mark G. Slomiany, Anthony P. Leonard, Bernard L. Maria, John T. Lucas, Anne G. Gilg, May Abdel-Wahab, Bryan P. Toole, William G. Wheeler, Lauren B. Tolliver, Michael A. Babcock, and Nalin Gupta
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Pathology ,medicine.medical_specialty ,Central nervous system ,Brain Stem Neoplasm ,Spinal Cord Neoplasm ,Biology ,Astrocytoma ,Article ,chemistry.chemical_compound ,Glioma ,Hyaluronic acid ,medicine ,ATP Binding Cassette Transporter, Subfamily G, Member 2 ,Animals ,Brain Stem Neoplasms ,Humans ,Spinal Cord Neoplasms ,Hyaluronic Acid ,Child ,neoplasms ,Medulloblastoma ,medicine.disease ,Spinal cord ,nervous system diseases ,Neoplasm Proteins ,Rats ,Disease Models, Animal ,medicine.anatomical_structure ,Hyaluronan Receptors ,chemistry ,Drug Resistance, Neoplasm ,Pediatrics, Perinatology and Child Health ,Basigin ,ATP-Binding Cassette Transporters ,Neurology (clinical) - Abstract
Although significant advances have been made in treating malignant pediatric central nervous system tumors such as medulloblastoma, no effective therapy exists for diffuse pontine glioma or intramedullary spinal astrocytoma. Biology of these 2 tumors is poorly understood, in part because diffuse pontine gliomas are not treated surgically, and tumor specimens from intramedullary spinal astrocytomas are rare and minuscule. At the 2007 Neurobiology of Disease in Children Symposium, we presented evidence that malignant glioma behaviors, including antiapoptosis, invasiveness, and treatment resistance, are enhanced by hyaluronan, an extracellular glycosaminoglycan. We review the clinical course of pediatric intramedullary spinal astrocytoma and diffuse pontine glioma, and show expression of membrane proteins that interact with hyaluronan: CD44, extracellular matrix metalloproteinase inducer, and breast cancer resistance protein (BCRP/ABCG2). Furthermore, we describe novel animal models of these tumors for preclinical studies. These findings suggest that hyaluronan antagonism has potential therapeutic value in malignant central nervous system tumors.
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- 2008
16. In vitro and in vivo imaging studies of a new endohedral metallofullerene nanoparticle
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Harry C. Dorn, Zhongxin Ge, Jennifer L. Russ, James C. Duchamp, Panos P. Fatouros, Harry W. Gibson, Birgit Kettenmann, William C. Broaddus, Anthony P. Leonard, Zhi-Jian Chen, James L. Tatum, and Frank D. Corwin
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Biodistribution ,business.industry ,Gadodiamide ,Radiochemistry ,Nanoparticle ,Brain ,Magnetic Resonance Imaging ,Rats, Inbred F344 ,Nanostructures ,Rats ,chemistry.chemical_compound ,Nuclear magnetic resonance ,chemistry ,In vivo ,Metallofullerene ,medicine ,Agarose ,Animals ,Radiology, Nuclear Medicine and imaging ,Female ,Fullerenes ,business ,Ethylene glycol ,Preclinical imaging ,medicine.drug - Abstract
To evaluate the effectiveness of a functionalized trimetallic nitride endohedral metallofullerene nanoparticle as a magnetic resonance (MR) imaging proton relaxation agent and to follow its distribution for in vitro agarose gel infusions and in vivo infusions in rat brain.The animal study was approved by the animal care and use committee. Gd(3)N@C(80) was functionalized with poly(ethylene glycol) units, and the carbon cage was hydroxylated to provide improved water solubility and biodistribution. Relaxation rate measurements (R1 = 1/T1 and R2 = 1/T2) of water solutions of this contrast agent were conducted at 0.35-, 2.4-, and 9.4-T MR imaging. Images of contrast agent distributions were produced following infusions in six agarose gel samples at 2.4 T and from direct brain infusions into normal and tumor-bearing rat brain at 2.4 T. The relaxivity of a control functionalized lutetium agent, Lu(3)N@C(80), was also determined.Water hydrogen MR imaging relaxivity (r1) for this metallofullerene nanoparticle was markedly higher than that for commercial agents (eg, gadodiamide); r1 values of 102, 143, and 32 L . mmol(-1) . sec(-1) were measured at 0.35, 2.4, and 9.4 T, respectively. In studies of in vitro agarose gel infusion, the use of functionalized Gd(3)N@C(80) at concentrations an order of magnitude lower resulted in equivalent visualization in comparison with commercial agents. Comparable contrast enhancement was obtained with direct infusions of 0.013 mmol/L of Gd(3)N@C(80) and 0.50 mmol/L of gadodiamide in live normal rat brain. Elapsed-time studies demonstrated lower diffusion rates for Gd(3)N@C(80) relative to gadodiamide in live normal rat brain tissue. Functionalized metallofullerenes directly infused into a tumor-bearing brain provided an improved tumor delineation in comparison with the intravenously injected conventional Gd(3+) chelate. A control lutetium functionalized Lu(3)N@C(80) nanoparticle exhibited very low MR imaging relaxivity.The new functionalized trimetallic nitride endohedral metallofullerene species Gd(3)N@C(80)[DiPEG5000(OH)(x)] is an effective proton relaxation agent, as demonstrated with in vitro relaxivity and MR imaging studies, in infusion experiments with agarose gel and in vivo rat brain studies simulating clinical conditions of direct intraparenchymal drug delivery for the treatment of brain tumors.
- Published
- 2006
17. Quantitative analysis of mitochondrial morphology and membrane potential in living cells using high-content imaging, machine learning, and morphological binning
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Rick G. Schnellmann, Baerbel Rohrer, Jaime L. Speiser, Robert B. Cameron, Yuri K. Peterson, Anthony P. Leonard, Bethany J. Wolf, and Craig Beeson
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Carbonyl Cyanide m-Chlorophenyl Hydrazone ,Oligomycin ,Cell Survival ,Cell Respiration ,Antimycin A ,Biology ,Mitochondrion ,Carbonyl cyanide m-chlorophenyl hydrazone ,Image cytometry ,Ouabain ,Article ,Cell Line ,Electron Transport ,03 medical and health sciences ,chemistry.chemical_compound ,Mice ,0302 clinical medicine ,Imaging, Three-Dimensional ,tert-Butylhydroperoxide ,Artificial Intelligence ,Stress, Physiological ,High content microscopy ,Mitophagy ,medicine ,Fluorescence microscope ,Animals ,Molecular Biology ,030304 developmental biology ,Membrane potential ,Membrane Potential, Mitochondrial ,0303 health sciences ,Morphometry ,Cell Membrane ,Mitochondrial toxicology ,Cell Biology ,Oxidants ,Cell biology ,Mitochondria ,Phenotype ,chemistry ,Mitochondrial dynamics ,Sodium-Potassium-Exchanging ATPase ,Mitochondrial function ,030217 neurology & neurosurgery ,medicine.drug - Abstract
Understanding the processes of mitochondrial dynamics (fission, fusion, biogenesis, and mitophagy) has been hampered by the lack of automated, deterministic methods to measure mitochondrial morphology from microscopic images. A method to quantify mitochondrial morphology and function is presented here using a commercially available automated high-content wide-field fluorescent microscopy platform and R programming-language-based semi-automated data analysis to achieve high throughput morphological categorization (puncta, rod, network, and large & round) and quantification of mitochondrial membrane potential. In conjunction with cellular respirometry to measure mitochondrial respiratory capacity, this method detected that increasing concentrations of toxicants known to directly or indirectly affect mitochondria (t-butyl hydroperoxide [TBHP], rotenone, antimycin A, oligomycin, ouabain, and carbonyl cyanide-p-trifluoromethoxyphenylhydrazone [FCCP]), decreased mitochondrial networked areas in cultured 661w cells to 0.60–0.80 at concentrations that inhibited respiratory capacity to 0.20–0.70 (fold change compared to vehicle). Concomitantly, mitochondrial swelling was increased from 1.4- to 2.3-fold of vehicle as indicated by changes in large & round areas in response to TBHP, oligomycin, or ouabain. Finally, the automated identification of mitochondrial location enabled accurate quantification of mitochondrial membrane potential by measuring intramitochondrial tetramethylrhodamine methyl ester (TMRM) fluorescence intensity. Administration of FCCP depolarized and administration of oligomycin hyperpolarized mitochondria, as evidenced by changes in intramitochondrial TMRM fluorescence intensities to 0.33- or 5.25-fold of vehicle control values, respectively. In summary, this high-content imaging method accurately quantified mitochondrial morphology and membrane potential in hundreds of thousands of cells on a per-cell basis, with sufficient throughput for pharmacological or toxicological evaluation.
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18. Expression of Programmed Cell Death-1 (PD-1) and Its Ligand (PD-L1) in Breast Cancers and Its Association with Clinicopathological Parameters: A Study from North India
- Author
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Mehan, Anoushika, Anthony, Michael Leonard, Paul, Pranoy, Syed, Anjum, Chowdhury, Nilotpal, Rao, Shalinee, Hussain, Nuzhat, and Ravi, Bina
- Published
- 2021
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19. Immunoexpression of PD-L1 and PD-1 and Its Clinicopathological Correlation in Urothelial Carcinomas
- Author
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Kumar, Utpal, Anthony, Michael Leonard, Sahai, Rishabh, Mittal, Ankur, Durgapal, Prashant, and Kishore, Sanjeev
- Published
- 2021
- Full Text
- View/download PDF
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