{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T22:36:24Z","timestamp":1790375784787,"version":"4.1.0"},"reference-count":38,"publisher":"Archives of Pathology and Laboratory Medicine","issue":"7","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2012,7]]},"abstract":"\n Context<\/jats:italic>\n .\u2014Assessing the amount of globotriaosylceramide inclusions in renal peritubular capillaries by a semiquantitative approach is a standard and useful measure of therapeutic efficacy in Fabry disease, achievable by light microscopy analysis.\n <\/jats:p>\n \n Objective<\/jats:italic>\n .\u2014To describe a novel virtual microscopy quantitative method to measure globotriaosylceramide inclusions (Barisoni Lipid Inclusion Scoring System [BLISS]) in renal biopsies from patients with Fabry disease.\n <\/jats:p>\n \n Design<\/jats:italic>\n .\u2014Plastic embedded 1-\u00b5m-thick sections from kidney biopsies from 17 patients enrolled in a Fabry disease clinical trial were evaluated using a standard semiquantitative methodology and BLISS to compare sensitivity. We also tested intrareader and interreader variability of BLISS and compared results from conventional light microscopy analysis with a virtual microscopy-based methodology. Peritubular capillaries were first annotated on digital images of whole slides by 1 pathologist and then scored for globotriaosylceramide inclusions by 2 additional pathologists.\n <\/jats:p>\n \n Results<\/jats:italic>\n .\u2014We demonstrated that (1) quantitative analysis by BLISS results in detection of small amount of globotriaosylceramide inclusions even when by semiquantitative analysis the score is 0, (2) application of BLISS combined with conventional light microscopy results in low intrareader and interreader variability, and (3) BLISS combined with virtual microscopy results in significant reduction of intrareader and interreader variability compared with BLISS\u2013light microscopy.\n <\/jats:p>\n \n Conclusions<\/jats:italic>\n .\u2014BLISS is a simpler and more sensitive scoring system compared to the semiquantitative approach. The virtual microscopy\u2013based methodology increases accuracy and reproducibility; moreover, it provides a permanent record of retrievable data with full transparency in clinical trials.\n <\/jats:p>","DOI":"10.5858\/arpa.2011-0350-oa","type":"journal-article","created":{"date-parts":[[2012,6,28]],"date-time":"2012-06-28T15:53:59Z","timestamp":1340898839000},"page":"816-824","source":"Crossref","is-referenced-by-count":20,"title":["Novel Quantitative Method to Evaluate Globotriaosylceramide Inclusions in Renal Peritubular Capillaries by Virtual Microscopy in Patients With Fabry Disease"],"prefix":"10.5858","volume":"136","author":[{"given":"Laura","family":"Barisoni","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Charles","family":"Jennette","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Colvin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheela","family":"Sitaraman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Bragat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeff","family":"Castelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Walker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pol","family":"Boudes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"3906","reference":[{"issue":"3","key":"arpa-136-07-816-824-b01","series-title":"Mol Genet Metab","first-page":"207","article-title":"Response of women with Fabry disease to enzyme replacement therapy; comparison with men, using data from FOS\u2014the Fabry Outcome Survey","volume":"103","author":"Hughes\n DA,","year":"2011","unstructured":"Hughes\n DA, \n \n Barba Romero\n M\u00c1, \n \n Hollak\n CE, \n \n Giugliani\n R, \n \n Deegan\n PB\n \n . 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Kidney Int. 2002;62(6):1933\u20131946."},{"issue":"16","key":"arpa-136-07-816-824-b03","series-title":"Drugs","first-page":"2179","article-title":"Enzyme replacement therapy for Fabry disease: a systematic review of available evidence","volume":"69","author":"Schaefer\n RM,","year":"2009","unstructured":"Schaefer\n RM, \n \n Tylki-Szymanska\n A, \n \n Hilz\n MJ\n \n . Enzyme replacement therapy for Fabry disease: a systematic review of available evidence. Drugs. 2009;69(16):2179\u20132205."},{"issue":"5","key":"arpa-136-07-816-824-b04","series-title":"Drugs","first-page":"733","article-title":"New prospects for the treatment of lysosomal storage diseases","volume":"62","author":"Schiffmann\n R,","year":"2002","unstructured":"Schiffmann\n R, \n \n Brady\n RO\n \n . New prospects for the treatment of lysosomal storage diseases. Drugs. 2002;62(5):733\u2013742."},{"issue":"3","key":"arpa-136-07-816-824-b05","series-title":"Mol Genet Metab","first-page":"207","article-title":"Response of women with Fabry disease to enzyme replacement therapy: comparison with men, using data from FOS\u2014the Fabry Outcome Survey","volume":"103","author":"Hughes\n DA,","year":"2011","unstructured":"Hughes\n DA, \n \n Barba Romero\n MA, \n \n Hollak\n CE, \n \n Giugliani\n R, \n \n Deegan\n PB\n \n . Response of women with Fabry disease to enzyme replacement therapy: comparison with men, using data from FOS\u2014the Fabry Outcome Survey. Mol Genet Metab. 2011;103(3):207\u2013214."},{"issue":"6","key":"arpa-136-07-816-824-b06","series-title":"Kidney Int","first-page":"663","article-title":"Progressive podocyte injury and globotriaosylceramide (GL-3) accumulation in young patients with Fabry disease","volume":"79","author":"Najafian\n B,","year":"2011","unstructured":"Najafian\n B, \n \n Svarstad\n E, \n \n Bostad\n L\n , et al. \n Progressive podocyte injury and globotriaosylceramide (GL-3) accumulation in young patients with Fabry disease. 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A virtual microscopy system to scan, evaluate and archive biomarker enhanced cervical cytology slides. Cell Oncol. 2010;32(12):109\u2013119."},{"issue":"8","key":"arpa-136-07-816-824-b18","series-title":"Hum Pathol","first-page":"1082","article-title":"Virtual slide telepathology enables an innovative telehealth rapid breast care clinic","volume":"40","author":"Lopez\n AM,","year":"2009","unstructured":"Lopez\n AM, \n \n Graham\n AR, \n \n Barker\n GP\n , et al. \n Virtual slide telepathology enables an innovative telehealth rapid breast care clinic. 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Mol Genet Metab. 2011;103(3):207\u2013214."},{"issue":"6","key":"arpa-136-07-816-824-b02","series-title":"Kidney Int","first-page":"1933","article-title":"Globotriaosylceramide accumulation in the Fabry kidney is cleared from multiple cell types after enzyme replacement therapy","volume":"62","author":"Thurberg\n BL,","year":"2002","unstructured":"Thurberg\n BL, \n \n Rennke\n H, \n \n Colvin\n RB\n , et al. \n Globotriaosylceramide accumulation in the Fabry kidney is cleared from multiple cell types after enzyme replacement therapy. Kidney Int. 2002;62(6):1933\u20131946."},{"issue":"16","key":"arpa-136-07-816-824-b03","series-title":"Drugs","first-page":"2179","article-title":"Enzyme replacement therapy for Fabry disease: a systematic review of available evidence","volume":"69","author":"Schaefer\n RM,","year":"2009","unstructured":"Schaefer\n RM, \n \n Tylki-Szymanska\n A, \n \n Hilz\n MJ\n \n . Enzyme replacement therapy for Fabry disease: a systematic review of available evidence. Drugs. 2009;69(16):2179\u20132205."},{"issue":"5","key":"arpa-136-07-816-824-b04","series-title":"Drugs","first-page":"733","article-title":"New prospects for the treatment of lysosomal storage diseases","volume":"62","author":"Schiffmann\n R,","year":"2002","unstructured":"Schiffmann\n R, \n \n Brady\n RO\n \n . New prospects for the treatment of lysosomal storage diseases. Drugs. 2002;62(5):733\u2013742."},{"issue":"3","key":"arpa-136-07-816-824-b05","series-title":"Mol Genet Metab","first-page":"207","article-title":"Response of women with Fabry disease to enzyme replacement therapy: comparison with men, using data from FOS\u2014the Fabry Outcome Survey","volume":"103","author":"Hughes\n DA,","year":"2011","unstructured":"Hughes\n DA, \n \n Barba Romero\n MA, \n \n Hollak\n CE, \n \n Giugliani\n R, \n \n Deegan\n PB\n \n . Response of women with Fabry disease to enzyme replacement therapy: comparison with men, using data from FOS\u2014the Fabry Outcome Survey. Mol Genet Metab. 2011;103(3):207\u2013214."},{"issue":"6","key":"arpa-136-07-816-824-b06","series-title":"Kidney Int","first-page":"663","article-title":"Progressive podocyte injury and globotriaosylceramide (GL-3) accumulation in young patients with Fabry disease","volume":"79","author":"Najafian\n B,","year":"2011","unstructured":"Najafian\n B, \n \n Svarstad\n E, \n \n Bostad\n L\n , et al. \n Progressive podocyte injury and globotriaosylceramide (GL-3) accumulation in young patients with Fabry disease. Kidney Int. 2011;79(6):663\u2013670."},{"key":"arpa-136-07-816-824-b07","series-title":"Nephrol Dial Transplant","article-title":"Renal outcomes of agalsidase beta treatment for Fabry disease: role of proteinuria and timing of treatment initiation [published online ahead of print July 29, 2011]","author":"Warnock\n DG,","unstructured":"Warnock\n DG, \n \n Ortiz\n A, \n \n Mauer\n M\n , et al. \n Renal outcomes of agalsidase beta treatment for Fabry disease: role of proteinuria and timing of treatment initiation [published online ahead of print July 29, 2011]. Nephrol Dial Transplant. doi: 10.1093\/ndt\/gfr420."},{"issue":"8476","key":"arpa-136-07-816-824-b08","series-title":"Lancet","first-page":"307","article-title":"Statistical methods for assessing agreement between two methods of clinical measurement","volume":"1","author":"Bland\n JM,","year":"1986","unstructured":"Bland\n JM, \n \n Altman\n DG\n \n . 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Proc AMIA Symp. 1998:912\u2013916."},{"issue":"suppl 1","key":"arpa-136-07-816-824-b12","series-title":"Hematology","first-page":"151","article-title":"Virtual microscopy: applications to hematology education and training","volume":"10","author":"Lee\n SH","year":"2005","unstructured":"Lee\n SH\n \n . Virtual microscopy: applications to hematology education and training. Hematology. 2005;10(suppl 1):151\u2013153."},{"issue":"6","key":"arpa-136-07-816-824-b13","series-title":"Ann Anat","first-page":"378","article-title":"Virtual microscopy\u2014the future of teaching histology in the medical curriculum","volume":"192","author":"Paulsen\n FP,","year":"2010","unstructured":"Paulsen\n FP, \n \n Eichhorn\n M, \n \n Brauer\n L\n \n . Virtual microscopy\u2014the future of teaching histology in the medical curriculum? Ann Anat. 2010;192(6):378\u2013382."},{"issue":"2","key":"arpa-136-07-816-824-b14","series-title":"J Clin Pathol","first-page":"139","article-title":"Expression of epidermal growth factor receptor in relation to BRCA1 status, basal-like markers and prognosis in breast cancer","volume":"62","author":"Arnes\n JB,","year":"2009","unstructured":"Arnes\n JB, \n \n Begin\n LR, \n \n Stefansson\n I\n , et al. \n Expression of epidermal growth factor receptor in relation to BRCA1 status, basal-like markers and prognosis in breast cancer. J Clin Pathol. 2009;62(2):139\u2013146."},{"issue":"2","key":"arpa-136-07-816-824-b15","series-title":"Histopathology","first-page":"266","article-title":"A randomized controlled trial of the diagnostic accuracy of internet-based telepathology compared with conventional microscopy","volume":"50","author":"Furness\n P","year":"2007","unstructured":"Furness\n P\n \n . A randomized controlled trial of the diagnostic accuracy of internet-based telepathology compared with conventional microscopy. Histopathology. 2007;50(2):266\u2013273."},{"issue":"2","key":"arpa-136-07-816-824-b16","series-title":"Histopathology","first-page":"182","article-title":"The virtual double-headed microscope: telepathology for all","volume":"36","author":"Furness\n P,","year":"2000","unstructured":"Furness\n P, \n \n Rashbass\n J\n \n . The virtual double-headed microscope: telepathology for all? Histopathology. 2000;36(2):182\u2013183."},{"issue":"12","key":"arpa-136-07-816-824-b17","series-title":"Cell Oncol","first-page":"109","article-title":"A virtual microscopy system to scan, evaluate and archive biomarker enhanced cervical cytology slides","volume":"32","author":"Grabe\n N,","year":"2010","unstructured":"Grabe\n N, \n \n Lahrmann\n B, \n \n Pommerencke\n T, \n \n von Knebel Doeberitz\n M, \n \n Reuschenbach\n M, \n \n Wentzensen\n N\n \n . A virtual microscopy system to scan, evaluate and archive biomarker enhanced cervical cytology slides. Cell Oncol. 2010;32(12):109\u2013119."},{"issue":"8","key":"arpa-136-07-816-824-b18","series-title":"Hum Pathol","first-page":"1082","article-title":"Virtual slide telepathology enables an innovative telehealth rapid breast care clinic","volume":"40","author":"Lopez\n AM,","year":"2009","unstructured":"Lopez\n AM, \n \n Graham\n AR, \n \n Barker\n GP\n , et al. \n Virtual slide telepathology enables an innovative telehealth rapid breast care clinic. 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