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Michael Estep - One of the best experts on this subject based on the ideXlab platform.
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hepatic sonic hedgehog protein expression measured by computer assisted morphometry significantly correlates with features of non alcoholic steatohepatitis
BMC Gastroenterology, 2019Co-Authors: Michael Estep, Rohini Mehta, Gary Bratthauer, Lakshmi Alaparthi, Fanny Monge, Simon AliAbstract:Hepatic expression of Sonic Hedgehog (SHH) is associated with Non-alcoholic fatty liver disease (NAFLD) and development of Non-alcoholic steatohepatitis (NASH). Hepatic SHH detection increases with the diagnosis of NASH. This pilot study was designed to confirm that staining for SHH is useful in NASH diagnosis and determine whether quantification of staining by computer assisted morphometry (CAM) can be used to assess severity of ballooning degeneration. SHH was detected by immunohistochemistry (IHC) on paraffin-embedded liver sections in subjects (N = 69) with biopsy proven NAFLD and no liver disease (control). Serum samples were also available for these subjects. Post-staining, a Digitized Image of the section was acquired and an area quantification algorithm was used to quantify the degree of SHH expression. Additionally, circulating M30, M65, and SHH were measured by ELISA. Notably, hepatic SHH expression correlated with histologic ballooning degeneration (rho = 0.62, p 2: OR = 1.986, p = 0.01, and OR = 3.280, p = 0.03, respectively). Thus, our findings show quantitation of SHH expression by CAM can provide a tool for quantifying changes in hepatocyte injury and assist in unambiguous staging/grading of NASH. Our study showed minimal interobserver variability using CAM based quantification. Once validated, CAM assessment of hepatic SHH could benefit clinical trials or long term outcomes studies of NASH subjects.
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Hepatic sonic hedgehog protein expression measured by computer assisted morphometry significantly correlates with features of non-alcoholic steatohepatitis
BMC, 2019Co-Authors: Michael Estep, Rohini Mehta, Gary Bratthauer, Lakshmi Alaparthi, Fanny Monge, Simon Ali, Dinan Abdelatif, Zahra Younoszai, Maria Stepanova, Zachary D. GoodmanAbstract:Abstract Background Hepatic expression of Sonic Hedgehog (SHH) is associated with Non-alcoholic fatty liver disease (NAFLD) and development of Non-alcoholic steatohepatitis (NASH). Hepatic SHH detection increases with the diagnosis of NASH. This pilot study was designed to confirm that staining for SHH is useful in NASH diagnosis and determine whether quantification of staining by computer assisted morphometry (CAM) can be used to assess severity of ballooning degeneration. Methods SHH was detected by immunohistochemistry (IHC) on paraffin-embedded liver sections in subjects (N = 69) with biopsy proven NAFLD and no liver disease (control). Serum samples were also available for these subjects. Post-staining, a Digitized Image of the section was acquired and an area quantification algorithm was used to quantify the degree of SHH expression. Additionally, circulating M30, M65, and SHH were measured by ELISA. Results Notably, hepatic SHH expression correlated with histologic ballooning degeneration (rho = 0.62, p
Claude F. Burgoyne - One of the best experts on this subject based on the ideXlab platform.
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measurement of optic disc compliance by Digitized Image analysis in the normal monkey eye
Ophthalmology, 1995Co-Authors: Claude F. Burgoyne, Susan Vitale, Harry A Quigley, Hilary W Thompson, Rohit VarmaAbstract:Abstract Purpose: To characterize the compliance of the normal monkey optic disc under conditions of induced short-term fluctuations in intraocular pressure (IOP). Methods: In 10 monkeys, one eye was compliance tested on three separate days followed by a single test of the contralateral eye (40 compliance tests). In a testing session, the optic disc was Imaged at 2 and 47 minutes (baseline time point) after IOP was lowered to 10 mmHg; then at 2, 17, 32, and 47 minutes after IOP was elevated to 45 mmHg; then at 2, 47, and, in some cases, 92 minutes after IOP was lowered back to 10 mmHg. Eight Digitized Images were analyzed at each time point, yielding two parameters to characterize the position of the disc: the Mean Position of the Disc (MPD) and the Change from MPD Baseline (the value of MPD at a given time point minus the value for MPD at the baseline time point of that testing session). Analysis of variance (ANOVA) testing was used to evaluate the overall effect of IOP on both parameters while taking into account the effects of variability due to different monkeys and repetitions of the test as well as differences between the two eyes of an individual monkey. With the addition of data from 11 compliance tests performed on eight additional monkeys, the overall results were calculated in terms of the mean Change from MPD Baseline at each time point for a total of 51 compliance testing sessions. Results: The mean Change from MPD Baseline was -28 μm (95% confidence interval, -23 to -33 μm) 47 minutes after elevation of IOP. The disc surface returned to its baseline position 92 minutes after IOP was lowered back to 10 mmHg. Elevation of IOP within a compliance test had a significant effect on the position of the optic disc surface ( P = 0.0002, ANOVA), as characterized by the parameter Change from MPD Baseline -Neither the difference in the amount of movement between -the two eyes of an individual monkey nor the variability within the three repetitions of the test in a given eye was statistically significant. Conclusion: Small, reversible (elastic) posterior deformations of the optic disc surface follow acute elevations of IOP in the normal monkey eye. Detection of acute IOP-induced deformations of the optic disc surface may represent a means by which to mechanically test the deeper load-bearing tissues of the optic nerve head.
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comparison of clinician judgment with Digitized Image analysis in the detection of induced optic disk change in monkey eyes
American Journal of Ophthalmology, 1995Co-Authors: Claude F. Burgoyne, Harry A Quigley, Rohit VarmaAbstract:Purpose To compare the ability of clinicians to detect change in the photographic appearance of the optic disk with the performance of a system for Digitized Image analysis. Methods In 11 monkey eyes, a Topcon Imagenet System was used to acquire eight Digitized Image pairs and four stereoscopic photographs at an intraocular pressure of 10 mm Hg, and then, again, 45 minutes after intraocular pressure was increased to 45 mm Hg. We recently reported detection of global (ten of 11 eyes) and regional (11 of 11 eyes) change in the Digitized Images of these eyes by using two new statistical strategies for optic disk analysis. For the current study, we evaluated the ability of three clinicians (the authors) to detect a change within the stereoscopic photographs of these 11 optic disks. For each eye, the eight stereoscopic photographs (four at intraocular pressure of 10 mm Hg and four at intraocular pressure of 45 mm Hg) were developed as stereoscopic slides and arranged into four pairs (10/10, 45/45, 10/45, and 45/10 mm Hg). Thus, two pairs represented no change in intraocular pressure (10/10 and 45/45 mm Hg) and the other two pairs represented either an increase or a decrease in intraocular pressure (10/45 and 45/10 mm Hg). The 44 pairs of stereoscopic slides (four pairs for each of 11 eyes) were masked then randomly mixed. On two separate occasions, each clinician evaluated each pair of stereoscopic slides for the presence or absence of optic disk change. Results Reproducibility between the two readings of each clinician ranged from .50 to .64 (kappa statistic). Clinicians correctly detected change (as detected by Image analysis) within 45% to 64% of the 10/45 and 45/10 pairs of stereoscopic slides. Clinicians correctly identified no change within 86% to 100% of the 10/10- and 45/45-mm Hg pairs of stereoscopic slides. Clinicians correctly identified no change significantly more often than change (P 2 test). Change was not detected consistently by all three clinicians in any of the 11 eyes. Conclusion In a controlled experimental setting, Digitized Image acquisition with extensive secondary statistical analysis more sensitively detected small short-term changes in the surface of the optic disks of monkeys than did three masked clinicians.
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Global and regional detection of induced optic disc change by Digitized Image analysis.
Archives of Ophthalmology, 1994Co-Authors: Claude F. Burgoyne, Susan Vitale, Mary Ellen Pease, Rohit Varma, Harry A Quigley, Patricia L. LenaneAbstract:Objective: To evaluate two new strategies for the detection of optic disc change within individual eyes by Digitized Image analysis. Methods: Eleven normal optic discs of 11 monkeys were Imaged with a digital imaging system (Topcon Imagenet, Topcon Instrument Corporation of America, Paramus, NJ) at two intraocular pressures (10 and 45 mm Hg). To detect global change in the disc, we compared conventional optic disc parameters with a new optic disc parameter: mean position of the disc. To detect regional change, the 95% confidence interval for change was calculated for each data point and mapped for each disc. Results: Posterior deformation of the disc surface was detected in seven of 11 eyes using conventional parameters and in 10 of 11 eyes using mean position of the disc. Regions of posterior deformation were detected by 95% confidence interval for change mapping in all 11 discs as localized areas of confluent, posteriorly displaced points. Conclusions: Mean position of the disc outperformed conventional measurements in the detection of global optic disc change. Ninety-five percent confidence interval for change mapping may allow individual data point-based focal and regional analysis of the disc.
Simon Ali - One of the best experts on this subject based on the ideXlab platform.
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hepatic sonic hedgehog protein expression measured by computer assisted morphometry significantly correlates with features of non alcoholic steatohepatitis
BMC Gastroenterology, 2019Co-Authors: Michael Estep, Rohini Mehta, Gary Bratthauer, Lakshmi Alaparthi, Fanny Monge, Simon AliAbstract:Hepatic expression of Sonic Hedgehog (SHH) is associated with Non-alcoholic fatty liver disease (NAFLD) and development of Non-alcoholic steatohepatitis (NASH). Hepatic SHH detection increases with the diagnosis of NASH. This pilot study was designed to confirm that staining for SHH is useful in NASH diagnosis and determine whether quantification of staining by computer assisted morphometry (CAM) can be used to assess severity of ballooning degeneration. SHH was detected by immunohistochemistry (IHC) on paraffin-embedded liver sections in subjects (N = 69) with biopsy proven NAFLD and no liver disease (control). Serum samples were also available for these subjects. Post-staining, a Digitized Image of the section was acquired and an area quantification algorithm was used to quantify the degree of SHH expression. Additionally, circulating M30, M65, and SHH were measured by ELISA. Notably, hepatic SHH expression correlated with histologic ballooning degeneration (rho = 0.62, p 2: OR = 1.986, p = 0.01, and OR = 3.280, p = 0.03, respectively). Thus, our findings show quantitation of SHH expression by CAM can provide a tool for quantifying changes in hepatocyte injury and assist in unambiguous staging/grading of NASH. Our study showed minimal interobserver variability using CAM based quantification. Once validated, CAM assessment of hepatic SHH could benefit clinical trials or long term outcomes studies of NASH subjects.
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Hepatic sonic hedgehog protein expression measured by computer assisted morphometry significantly correlates with features of non-alcoholic steatohepatitis
BMC, 2019Co-Authors: Michael Estep, Rohini Mehta, Gary Bratthauer, Lakshmi Alaparthi, Fanny Monge, Simon Ali, Dinan Abdelatif, Zahra Younoszai, Maria Stepanova, Zachary D. GoodmanAbstract:Abstract Background Hepatic expression of Sonic Hedgehog (SHH) is associated with Non-alcoholic fatty liver disease (NAFLD) and development of Non-alcoholic steatohepatitis (NASH). Hepatic SHH detection increases with the diagnosis of NASH. This pilot study was designed to confirm that staining for SHH is useful in NASH diagnosis and determine whether quantification of staining by computer assisted morphometry (CAM) can be used to assess severity of ballooning degeneration. Methods SHH was detected by immunohistochemistry (IHC) on paraffin-embedded liver sections in subjects (N = 69) with biopsy proven NAFLD and no liver disease (control). Serum samples were also available for these subjects. Post-staining, a Digitized Image of the section was acquired and an area quantification algorithm was used to quantify the degree of SHH expression. Additionally, circulating M30, M65, and SHH were measured by ELISA. Results Notably, hepatic SHH expression correlated with histologic ballooning degeneration (rho = 0.62, p
Rohit Varma - One of the best experts on this subject based on the ideXlab platform.
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measurement of optic disc compliance by Digitized Image analysis in the normal monkey eye
Ophthalmology, 1995Co-Authors: Claude F. Burgoyne, Susan Vitale, Harry A Quigley, Hilary W Thompson, Rohit VarmaAbstract:Abstract Purpose: To characterize the compliance of the normal monkey optic disc under conditions of induced short-term fluctuations in intraocular pressure (IOP). Methods: In 10 monkeys, one eye was compliance tested on three separate days followed by a single test of the contralateral eye (40 compliance tests). In a testing session, the optic disc was Imaged at 2 and 47 minutes (baseline time point) after IOP was lowered to 10 mmHg; then at 2, 17, 32, and 47 minutes after IOP was elevated to 45 mmHg; then at 2, 47, and, in some cases, 92 minutes after IOP was lowered back to 10 mmHg. Eight Digitized Images were analyzed at each time point, yielding two parameters to characterize the position of the disc: the Mean Position of the Disc (MPD) and the Change from MPD Baseline (the value of MPD at a given time point minus the value for MPD at the baseline time point of that testing session). Analysis of variance (ANOVA) testing was used to evaluate the overall effect of IOP on both parameters while taking into account the effects of variability due to different monkeys and repetitions of the test as well as differences between the two eyes of an individual monkey. With the addition of data from 11 compliance tests performed on eight additional monkeys, the overall results were calculated in terms of the mean Change from MPD Baseline at each time point for a total of 51 compliance testing sessions. Results: The mean Change from MPD Baseline was -28 μm (95% confidence interval, -23 to -33 μm) 47 minutes after elevation of IOP. The disc surface returned to its baseline position 92 minutes after IOP was lowered back to 10 mmHg. Elevation of IOP within a compliance test had a significant effect on the position of the optic disc surface ( P = 0.0002, ANOVA), as characterized by the parameter Change from MPD Baseline -Neither the difference in the amount of movement between -the two eyes of an individual monkey nor the variability within the three repetitions of the test in a given eye was statistically significant. Conclusion: Small, reversible (elastic) posterior deformations of the optic disc surface follow acute elevations of IOP in the normal monkey eye. Detection of acute IOP-induced deformations of the optic disc surface may represent a means by which to mechanically test the deeper load-bearing tissues of the optic nerve head.
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comparison of clinician judgment with Digitized Image analysis in the detection of induced optic disk change in monkey eyes
American Journal of Ophthalmology, 1995Co-Authors: Claude F. Burgoyne, Harry A Quigley, Rohit VarmaAbstract:Purpose To compare the ability of clinicians to detect change in the photographic appearance of the optic disk with the performance of a system for Digitized Image analysis. Methods In 11 monkey eyes, a Topcon Imagenet System was used to acquire eight Digitized Image pairs and four stereoscopic photographs at an intraocular pressure of 10 mm Hg, and then, again, 45 minutes after intraocular pressure was increased to 45 mm Hg. We recently reported detection of global (ten of 11 eyes) and regional (11 of 11 eyes) change in the Digitized Images of these eyes by using two new statistical strategies for optic disk analysis. For the current study, we evaluated the ability of three clinicians (the authors) to detect a change within the stereoscopic photographs of these 11 optic disks. For each eye, the eight stereoscopic photographs (four at intraocular pressure of 10 mm Hg and four at intraocular pressure of 45 mm Hg) were developed as stereoscopic slides and arranged into four pairs (10/10, 45/45, 10/45, and 45/10 mm Hg). Thus, two pairs represented no change in intraocular pressure (10/10 and 45/45 mm Hg) and the other two pairs represented either an increase or a decrease in intraocular pressure (10/45 and 45/10 mm Hg). The 44 pairs of stereoscopic slides (four pairs for each of 11 eyes) were masked then randomly mixed. On two separate occasions, each clinician evaluated each pair of stereoscopic slides for the presence or absence of optic disk change. Results Reproducibility between the two readings of each clinician ranged from .50 to .64 (kappa statistic). Clinicians correctly detected change (as detected by Image analysis) within 45% to 64% of the 10/45 and 45/10 pairs of stereoscopic slides. Clinicians correctly identified no change within 86% to 100% of the 10/10- and 45/45-mm Hg pairs of stereoscopic slides. Clinicians correctly identified no change significantly more often than change (P 2 test). Change was not detected consistently by all three clinicians in any of the 11 eyes. Conclusion In a controlled experimental setting, Digitized Image acquisition with extensive secondary statistical analysis more sensitively detected small short-term changes in the surface of the optic disks of monkeys than did three masked clinicians.
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Global and regional detection of induced optic disc change by Digitized Image analysis.
Archives of Ophthalmology, 1994Co-Authors: Claude F. Burgoyne, Susan Vitale, Mary Ellen Pease, Rohit Varma, Harry A Quigley, Patricia L. LenaneAbstract:Objective: To evaluate two new strategies for the detection of optic disc change within individual eyes by Digitized Image analysis. Methods: Eleven normal optic discs of 11 monkeys were Imaged with a digital imaging system (Topcon Imagenet, Topcon Instrument Corporation of America, Paramus, NJ) at two intraocular pressures (10 and 45 mm Hg). To detect global change in the disc, we compared conventional optic disc parameters with a new optic disc parameter: mean position of the disc. To detect regional change, the 95% confidence interval for change was calculated for each data point and mapped for each disc. Results: Posterior deformation of the disc surface was detected in seven of 11 eyes using conventional parameters and in 10 of 11 eyes using mean position of the disc. Regions of posterior deformation were detected by 95% confidence interval for change mapping in all 11 discs as localized areas of confluent, posteriorly displaced points. Conclusions: Mean position of the disc outperformed conventional measurements in the detection of global optic disc change. Ninety-five percent confidence interval for change mapping may allow individual data point-based focal and regional analysis of the disc.
Fanny Monge - One of the best experts on this subject based on the ideXlab platform.
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hepatic sonic hedgehog protein expression measured by computer assisted morphometry significantly correlates with features of non alcoholic steatohepatitis
BMC Gastroenterology, 2019Co-Authors: Michael Estep, Rohini Mehta, Gary Bratthauer, Lakshmi Alaparthi, Fanny Monge, Simon AliAbstract:Hepatic expression of Sonic Hedgehog (SHH) is associated with Non-alcoholic fatty liver disease (NAFLD) and development of Non-alcoholic steatohepatitis (NASH). Hepatic SHH detection increases with the diagnosis of NASH. This pilot study was designed to confirm that staining for SHH is useful in NASH diagnosis and determine whether quantification of staining by computer assisted morphometry (CAM) can be used to assess severity of ballooning degeneration. SHH was detected by immunohistochemistry (IHC) on paraffin-embedded liver sections in subjects (N = 69) with biopsy proven NAFLD and no liver disease (control). Serum samples were also available for these subjects. Post-staining, a Digitized Image of the section was acquired and an area quantification algorithm was used to quantify the degree of SHH expression. Additionally, circulating M30, M65, and SHH were measured by ELISA. Notably, hepatic SHH expression correlated with histologic ballooning degeneration (rho = 0.62, p 2: OR = 1.986, p = 0.01, and OR = 3.280, p = 0.03, respectively). Thus, our findings show quantitation of SHH expression by CAM can provide a tool for quantifying changes in hepatocyte injury and assist in unambiguous staging/grading of NASH. Our study showed minimal interobserver variability using CAM based quantification. Once validated, CAM assessment of hepatic SHH could benefit clinical trials or long term outcomes studies of NASH subjects.
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Hepatic sonic hedgehog protein expression measured by computer assisted morphometry significantly correlates with features of non-alcoholic steatohepatitis
BMC, 2019Co-Authors: Michael Estep, Rohini Mehta, Gary Bratthauer, Lakshmi Alaparthi, Fanny Monge, Simon Ali, Dinan Abdelatif, Zahra Younoszai, Maria Stepanova, Zachary D. GoodmanAbstract:Abstract Background Hepatic expression of Sonic Hedgehog (SHH) is associated with Non-alcoholic fatty liver disease (NAFLD) and development of Non-alcoholic steatohepatitis (NASH). Hepatic SHH detection increases with the diagnosis of NASH. This pilot study was designed to confirm that staining for SHH is useful in NASH diagnosis and determine whether quantification of staining by computer assisted morphometry (CAM) can be used to assess severity of ballooning degeneration. Methods SHH was detected by immunohistochemistry (IHC) on paraffin-embedded liver sections in subjects (N = 69) with biopsy proven NAFLD and no liver disease (control). Serum samples were also available for these subjects. Post-staining, a Digitized Image of the section was acquired and an area quantification algorithm was used to quantify the degree of SHH expression. Additionally, circulating M30, M65, and SHH were measured by ELISA. Results Notably, hepatic SHH expression correlated with histologic ballooning degeneration (rho = 0.62, p