Nora Laver - Academia.edu (original) (raw)

Papers by Nora Laver

Ophthalmology

To examine the immunohistochemical and ultrastructural features of the rare pleomorphic adenocarc... more To examine the immunohistochemical and ultrastructural features of the rare pleomorphic adenocarcinomas of the ciliary epithelium (CE). Retrospective case series. The study materials included 12 cases of adenocarcinoma of the ciliary epithelium: 9 cases of CE hyperplasia and 3 cases of CE adenomas. Histologic sections were stained with hematoxylin-eosin, alcian blue, periodic acid-Schiff, and occasionally with Masson trichrome. Additionally, the following immunohistochemical markers were used: Kermix (ae1/ae3 + ck1), cytokeratin 7 (CK7), cytokeratin 20 (CK20), epithelial membrane antigen, CAM 5.2, S-100 protein, neuron-specific enolase, glial fibrillary acid protein, smooth muscle actin, and vimentin. Five lesions were studied ultrastructurally. Clinical data were available in all cases, and follow-up was obtained in 9 of the 12 patients. Nine tumors occurred in phthisical eyes in adults. The tumor cells were arranged in tubular and solid patterns and surrounded by thick basement membrane (BM) material and fibrous stroma. Immunohistochemistry (IM) of adenocarcinomas showed positivity with kermix (8 of 12 lesions), CAM 5.2 (7 of 12), and CK7 (5 of 12). Ultrastructurally, the tumor cells were surrounded by a thick, homogeneous, and/or multilaminar BM and attached to each other by junctional complexes. Clinically, this intraocular neoplasm should be considered in adults with a longstanding blind eye with an epibulbar mass and/or proptosis of recent duration. Fatal cases only occurred in tumors with extraocular extension. Adenocarcinomas of CE should be differentiated from amelanotic melanoma and metastatic lesions by the presence of a thick BM material around the tumor cells and intraocular fibrosis. Immunohistochemistry is helpful in differentiating from melanomas but not helpful in cases of metastatic carcinomas.

Investigative Ophthalmology &amp Visual Science

The earliest histopathologic signs of diabetic retinopathy include selective loss of intramural p... more The earliest histopathologic signs of diabetic retinopathy include selective loss of intramural pericytes and thickening of capillary basement membranes. Previous evidence from animal models indicated that aldose reductase inhibitors could prevent these capillary wall lesions, but only recently have aldose reductase inhibitors been tested for prevention of the subsequent retinal complications of diabetes, such as microaneurysms. In the present study, Sprague-Dawley rats were fed diets containing 50% galactose with or without an aldose reductase inhibitor (tolrestat). After 28 months of galactose feeding, the retinal capillaries in whole mounts exhibited a marked increase in periodic acid-Schiff (PAS) staining, extensive pericyte loss, endothelial cell proliferation, acellularity, diffuse dilation, occluded lumens, microaneurysms, and complex microvascular abnormalities including gross dilation and formation of multiple shunt networks. The PAS hyperchromaticity of basement membrane material and pericyte loss occurred throughout the retinal vasculature, while the microaneurysms and complex lesions were limited to the capillaries of the central and paracentral retina. The changes were associated with both the arterial and venous portions of the capillary plexus. Treatment with orally administered tolrestat prevented essentially all of the vessel abnormalities. Thus, longterm galactose feeding of rats induced microvascular lesions simulating those occurring in background diabetic retinopathy in humans, and these lesions were prevented by treatment with an aldose reductase inhibitor. Invest Ophthalmol Vis

Investigative Ophthalmology &amp Visual Science

To improve the 30-year-old "trypsin digestion" procedure for isolation of the c... more To improve the 30-year-old "trypsin digestion" procedure for isolation of the complete retinal vasculature, which, in its time, was a revolutionary advance that allowed important discoveries about diabetic retinopathy; to provide a method that will yield more consistent results when applied to retinas representing a wide range of ages, species, and severity of vascular disease, such as that occurring in diabetes. Because the Difco trypsin preparation (Difco Laboratories, Detroit, MI) is a crude pancreatic extract, containing variable amounts of chymotrypsin, elastase, amylase, lipase, ribonuclease, collagenase, and other contaminants, an attempt was made to determine which of the major enzymes alone (using purified preparations), or what combination of enzymes, might be most effective in providing consistently clean yet intact retinal vasculatures from eyes of different origins. Purified elastase alone (40 U/ml) in 100 mmol/l sodium phosphate buffer with 150 mmol/l sodium chloride and 5 mmol/l EDTA at pH 6.5 and 37 degrees C gave better results than various concentrations of purified trypsin or chymotrypsin alone, or mixtures of trypsin/chymotrypsin, trypsin/elastase, chymotrypsin/elastase, or the crude trypsin preparation. Elastase, which exhibits broad protease activity, and not trypsin, is the most important enzyme of the standard, crude trypsin digestion procedure for removal of the nonvascular tissues of the retina.

Investigative Ophthalmology &amp Visual Science

Normally, direct contacts between pericytes and endothelial cells occur frequently in both retina... more Normally, direct contacts between pericytes and endothelial cells occur frequently in both retinal and optic nerve capillaries. The contacts are made through fenestrae in the thick basement membranes which separate the plasma membranes of the two cell types over most of their juxtaposed surfaces. This study was initiated to determine if there was any change in the number of pericyte-endothelial cell contact regions in retinal or optic nerve capillaries of the galactose-fed rat model for polyol-related complications of diabetes. Sprague-Dawley rats were fed for 28 months a 50% galactose diet, with or without an aldose reductase inhibitor (tolrestat), or a normal diet. Electron micrographs of transected capillaries were taken from defined regions of the central retina and nearby portions of the optic nerve. The optic nerve capillaries showed no differences in the numbers of pericyte-endothelial cell contact regions nor in basement membrane thickness in the galactose-fed rats. In contrast, the retinal capillaries exhibited a 70% decrease in the numbers of contact regions and a 2.4-fold increase in basement membrane thickness in galactosemic rats. Both loss of cell contact regions and basement membrane thickening were prevented with tolrestat. The results are consistent with the proposed involvement of the polyol pathway in diabetic retinopathy and with the greater involvement of retinal versus optic nerve vessels in diabetic microangiopathy. Invest Ophthalmol Vis

Journal of Anatomy

The purpose of the present study was to determine if prolonged systemic arterial administration o... more The purpose of the present study was to determine if prolonged systemic arterial administration of basic fibroblast growth factor (bFGF) at a dose sufficient to enhance collateral vessel formation in the ischaemic hearts of dogs would produce retinal neovascularisation in these same animals. Adult dogs (15-25 kg) were subjected to gradual occlusion of a coronary artery and randomised to receive 1 of 3 treatments via an indwelling left atrial catheter: (1) bFGF 1.74 mg/d, 5 d/wk for 63 d (n = 7); (2) bFGF 1.74 mg/d, 5 d/wk, for 35 d followed by physiological saline, 5 d/wk, for 28 d (n = 10); or (3) physiological saline, 5 d/wk, for 63 d (n = 10). After 63 d the retinal vasculatures from these dogs were isolated and examined for capillary varicosity, neovascularisation and other histopathological signs of angiopathy. All data were collected under masked conditions. The results suggest that chronic, systemic arterial administration of bFGF stimulates neovascularisation in the ischemic...

Investigative Ophthalmology &amp Visual Science

To determine if the retinal microangiopathies of the galactose-fed rat model of diabetic retinopa... more To determine if the retinal microangiopathies of the galactose-fed rat model of diabetic retinopathy can be prevented with the aldose reductase inhibitor sorbinil. Sprague-Dawley rats were fed 50% d-galactose with or without sorbinil (0.05% wt/wt), mixed biweekly with fresh diet. Rats in each group were examined frequently by slit lamp and were killed after 8, 16, and 24 months. Computer-assisted morphometry was performed on wholemounts of elastase retinal digest preparations. Cataracts developed in all galactose-fed untreated rats within 3 weeks but not in the sorbinil-treated rats even after 24 months. At 8 months, the galactose-fed untreated rats exhibited statistically significant increases in the mean capillary width, the percent of retinal area occupied by capillaries (capillary density), and the percent of microvascular area with capillaries > 20 microns wide (dilated channels), compared to controls. At 16 months, the galactose-fed untreated rats showed statistically signi...

Investigative Ophthalmology &amp Visual Science

To determine whether the diabeticlike retinal microangiopathies of the galactose-fed rat model co... more To determine whether the diabeticlike retinal microangiopathies of the galactose-fed rat model could be ameliorated if intervention by withdrawal of the galactose diet or treatment with the aldose reductase inhibitor AL-3152 was initiated after quantifiable microangiopathies had occurred. Weanling male Sprague-Dawley rats were randomized into five groups and fed for up to 24 months Purina laboratory chow (#5001) plus 50% starch (control [CON]), 50% D-galactose (galactose [GAL]), 50% D-galactose with AL-3152 (approximately 14 mg/kg per day) (prevention [PRV]), 50% D-galactose for 6 months followed by intervention with the inhibitor (intervention [INT]), or 50% D-galactose for 6 months followed by replacement with the 50% starch diet (withdrawal [GWD]). In rats on experimental diets and killed after 6, 18, and 24 months, one retina was prepared for transmission electron microscopy; the other was used for vessel wholemounts using elastase digestion. Capillary images were analyzed by co...

Purpose. To evaluate the efficacy of WAY-121,509, a potent new aldose reductase inhibitor (ARI), ... more Purpose. To evaluate the efficacy of WAY-121,509, a potent new aldose reductase inhibitor (ARI), in preventing the retinopathy that develops in the galactose-fed rat model of diabetic ocular complications. Methods. Sprague-Dawley rats were randomized into treatment and duration groups and fed diets with either 50% starch or 50% galactose with or without WAY-121,509 (25 mg/kg body weight per day). Progression

Ophthalmic Surgery, Lasers and Imaging Retina, 2014

Retinal pigment epithelium (RPE) neoplasms are extraordinarily rare and have been infrequently de... more Retinal pigment epithelium (RPE) neoplasms are extraordinarily rare and have been infrequently described in the literature. Most RPE tumors are pigmented and may simulate choroidal melanoma. The best management of RPE tumors has not yet been elucidated. In the current case, a 36-year-old man presenting with visual disturbance is found to have biopsy-proven RPE adenocarcinoma with subfoveal fluid. He is treated with grid laser over the lesion with complete resolution of fluid. RPE adenocarcinoma can present as an amelanotic mass, and grid laser over the lesion may represent a novel approach for treating associated subretinal fluid.

Cancer and Clinical Oncology, 2014

Journal of biophotonics, 2013

The first study interpreting B-lymphocyte activation in normal lymph nodes using vibrational micr... more The first study interpreting B-lymphocyte activation in normal lymph nodes using vibrational micro-spectral imaging is reported. Lymphocyte activation indicates the presence and response against a pathogen, regardless of the inciting pathogen's etiology, whether a benign, reactive or malignant process. Understanding the biochemical makeup of lymphocyte activation during early stages of disease and immune response may offer significant aid in determining a tumor's origin without the presence of malignant metastatic cells but within lymph nodes that are reactive and displaying regions of hyperplasia. Infrared and Raman data scrutinized via unsupervised multivariate methods may provide a physical and reproducible method to determine the biochemical components and variances therein of activated lymph nodes with distinguishing characteristics depending on the malignancy present in the region or elsewhere in the body. The results reported here provide a proof-of-concept study that...

Infrared and Raman Spectroscopic Imaging, 2009

... ä us , Tatyana Chernenko , Melissa J. Romeo , Milo š Miljkovi c , Benjamin Bird , Jennifer Sc... more ... ä us , Tatyana Chernenko , Melissa J. Romeo , Milo š Miljkovi c , Benjamin Bird , Jennifer Schubert ,Kostas Papamarkakis , and Nora Laver 173 5 5.1 Introduction Since the introduction of the first cytological cancer screening methods in 1941 by Papanicolaou ( ' Pap ' for short ...

Archives of pathology & laboratory medicine, 2010

Intraocular melanoma of the ciliary body and choroid is the most common primary ocular malignant ... more Intraocular melanoma of the ciliary body and choroid is the most common primary ocular malignant tumor in adults and the most common noncutaneous melanoma. To describe the most salient clinical features, histopathologic findings, and treatment modalities of intraocular melanoma, as well as the novel therapies currently being tested. Clinically, it is important to determine which lesions carry a worse prognosis so as to offer patients the best treatment modalities available. Tumor location, size, histopathology, cytogenetic abnormalities, and tumor profiling are all used in determining the risk of death from metastatic disease of uveal melanocytic lesions. Despite successful local tumor control, up to 50% of patients have metastatic disease within 15 years of diagnosis; there is no effective treatment for metastatic disease. Pathologists should be aware of the importance of tumor gross description, cellular histopathology classification, the use of fine-needle aspiration biopsy coupl...

Journal of pathology informatics, 2011

Cytology poses different obstacles in whole slide imaging compared to surgical pathology slides. ... more Cytology poses different obstacles in whole slide imaging compared to surgical pathology slides. A single focal plane suffices for most of the latter, but cytology slides are thicker, potentially requiring multiple focal planes for adequate diagnostic information. Multiple focal planes adversely impact scanning time per slide, evaluation times, and file sizes. In this pilot study, we evaluated and compared the multilayer stack method to the extended focus algorithm as an alternative which collapses multiple focal planes into a single image, retaining only focused areas from each plane. 10 SurePath(®) cervical cytology slides were scanned at three thickness settings: 18, 24, and 30 μm. Three scanners were used: (1) Hamamatsu Nanozoomer 2.0-HT, (2) 3DHISTECH Mirax scan, and (3) Bioimagene iScan Coreo Au. The Nanozoomer and iScan utilized multilayer stacking, while the Mirax files were composited by extended focus. Scan times and file sizes were recorded, and image quality compared. Th...

Case Reports in Ophthalmology, 2013

This is an Open Access article licensed under the terms of the Creative Commons Attribution-NonCo... more This is an Open Access article licensed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs 3.0 License (www.karger.com/OA-license), applicable to the online version of the article only. Distribution for non-commercial purposes only.

Journal of Biophotonics, 2009

The first detection of breast cancer micrometastases in lymph nodes by infrared spectral imaging ... more The first detection of breast cancer micrometastases in lymph nodes by infrared spectral imaging and methods of multivariate analysis is reported. Micrometastases are indicators of early spread of cancer from the organ originally affected by disease, and their detection is of prime importance for the staging and treatment of cancer. Infrared spectral imaging, at a spatial resolution of ca. 10-12 μm, can detect small metastases down to the level of a few cancerous cells. The results presented here add to a rapidly growing database of infrared spectral imaging results for cancer diagnostics.

Spectroscopy: An International Journal, 2012

This paper summarizes the progress achieved over the past fifteen years in applying vibrational (... more This paper summarizes the progress achieved over the past fifteen years in applying vibrational (Raman and IR) spectroscopy to problems of medical diagnostics and cellular biology. During this time, a number of research groups have verified the enormous information content of vibrational spectra; in fact, genomic, proteomic, and metabolomic information can be deduced by decoding the observed vibrational spectra. This decoding process is aided enormously by the availability of high-power computer workstations and advanced algorithms for data analysis. Furthermore, commercial instrumentation for the fast collection of both Raman and infrared microspectral data has rendered practical the collection of images based solely on spectral data. The progress in the field has been manifested by a steady increase in the number and quality of publications submitted by established and new research groups in vibrational biological and biomedical arenas.

Ophthalmic Surgery, Lasers, and Imaging, 2010

A 72-year-old woman presented with a 3-day history of focal pain and swelling of the left upper e... more A 72-year-old woman presented with a 3-day history of focal pain and swelling of the left upper eyelid. A cystic lesion had been present in this area for longer than 7 years, and a lesion consistent with an epidermal inclusion cyst was present on the contralateral upper eyelid. An erythematous, tender, fluctuant mass was noted on the left upper eyelid consistent with abscess. It was drained and cultured, and the infection resolved with oral amoxicillin/clavulanate potassium followed by surgical excision. Histopathologic examination demonstrated an epidermal inclusion cyst and cultures grew anaerobic gram-positive cocci. Epidermal inclusion cysts are common eyelid lesions, yet infection is rare and may result from the spread of normal flora through the pore often found on the anterior surface of these lesions.

Vibrational Spectroscopy, 2008

We report microscopically collected infrared spectra of cells found in human urine in an effort t... more We report microscopically collected infrared spectra of cells found in human urine in an effort to develop automatic methods for bladder cancer screening. Unsupervised multivariate analysis of the observed spectral patterns reveals distinct spectral classes, which correlated very well with visual cytology. Therefore, we believe that spectral analysis of individual cells can aid cytology in rendering reliable diagnoses based on objective measurements and discriminant algorithms.

Ophthalmology

To examine the immunohistochemical and ultrastructural features of the rare pleomorphic adenocarc... more To examine the immunohistochemical and ultrastructural features of the rare pleomorphic adenocarcinomas of the ciliary epithelium (CE). Retrospective case series. The study materials included 12 cases of adenocarcinoma of the ciliary epithelium: 9 cases of CE hyperplasia and 3 cases of CE adenomas. Histologic sections were stained with hematoxylin-eosin, alcian blue, periodic acid-Schiff, and occasionally with Masson trichrome. Additionally, the following immunohistochemical markers were used: Kermix (ae1/ae3 + ck1), cytokeratin 7 (CK7), cytokeratin 20 (CK20), epithelial membrane antigen, CAM 5.2, S-100 protein, neuron-specific enolase, glial fibrillary acid protein, smooth muscle actin, and vimentin. Five lesions were studied ultrastructurally. Clinical data were available in all cases, and follow-up was obtained in 9 of the 12 patients. Nine tumors occurred in phthisical eyes in adults. The tumor cells were arranged in tubular and solid patterns and surrounded by thick basement membrane (BM) material and fibrous stroma. Immunohistochemistry (IM) of adenocarcinomas showed positivity with kermix (8 of 12 lesions), CAM 5.2 (7 of 12), and CK7 (5 of 12). Ultrastructurally, the tumor cells were surrounded by a thick, homogeneous, and/or multilaminar BM and attached to each other by junctional complexes. Clinically, this intraocular neoplasm should be considered in adults with a longstanding blind eye with an epibulbar mass and/or proptosis of recent duration. Fatal cases only occurred in tumors with extraocular extension. Adenocarcinomas of CE should be differentiated from amelanotic melanoma and metastatic lesions by the presence of a thick BM material around the tumor cells and intraocular fibrosis. Immunohistochemistry is helpful in differentiating from melanomas but not helpful in cases of metastatic carcinomas.

Investigative Ophthalmology &amp Visual Science

The earliest histopathologic signs of diabetic retinopathy include selective loss of intramural p... more The earliest histopathologic signs of diabetic retinopathy include selective loss of intramural pericytes and thickening of capillary basement membranes. Previous evidence from animal models indicated that aldose reductase inhibitors could prevent these capillary wall lesions, but only recently have aldose reductase inhibitors been tested for prevention of the subsequent retinal complications of diabetes, such as microaneurysms. In the present study, Sprague-Dawley rats were fed diets containing 50% galactose with or without an aldose reductase inhibitor (tolrestat). After 28 months of galactose feeding, the retinal capillaries in whole mounts exhibited a marked increase in periodic acid-Schiff (PAS) staining, extensive pericyte loss, endothelial cell proliferation, acellularity, diffuse dilation, occluded lumens, microaneurysms, and complex microvascular abnormalities including gross dilation and formation of multiple shunt networks. The PAS hyperchromaticity of basement membrane material and pericyte loss occurred throughout the retinal vasculature, while the microaneurysms and complex lesions were limited to the capillaries of the central and paracentral retina. The changes were associated with both the arterial and venous portions of the capillary plexus. Treatment with orally administered tolrestat prevented essentially all of the vessel abnormalities. Thus, longterm galactose feeding of rats induced microvascular lesions simulating those occurring in background diabetic retinopathy in humans, and these lesions were prevented by treatment with an aldose reductase inhibitor. Invest Ophthalmol Vis

Investigative Ophthalmology &amp Visual Science

To improve the 30-year-old "trypsin digestion" procedure for isolation of the c... more To improve the 30-year-old "trypsin digestion" procedure for isolation of the complete retinal vasculature, which, in its time, was a revolutionary advance that allowed important discoveries about diabetic retinopathy; to provide a method that will yield more consistent results when applied to retinas representing a wide range of ages, species, and severity of vascular disease, such as that occurring in diabetes. Because the Difco trypsin preparation (Difco Laboratories, Detroit, MI) is a crude pancreatic extract, containing variable amounts of chymotrypsin, elastase, amylase, lipase, ribonuclease, collagenase, and other contaminants, an attempt was made to determine which of the major enzymes alone (using purified preparations), or what combination of enzymes, might be most effective in providing consistently clean yet intact retinal vasculatures from eyes of different origins. Purified elastase alone (40 U/ml) in 100 mmol/l sodium phosphate buffer with 150 mmol/l sodium chloride and 5 mmol/l EDTA at pH 6.5 and 37 degrees C gave better results than various concentrations of purified trypsin or chymotrypsin alone, or mixtures of trypsin/chymotrypsin, trypsin/elastase, chymotrypsin/elastase, or the crude trypsin preparation. Elastase, which exhibits broad protease activity, and not trypsin, is the most important enzyme of the standard, crude trypsin digestion procedure for removal of the nonvascular tissues of the retina.

Investigative Ophthalmology &amp Visual Science

Normally, direct contacts between pericytes and endothelial cells occur frequently in both retina... more Normally, direct contacts between pericytes and endothelial cells occur frequently in both retinal and optic nerve capillaries. The contacts are made through fenestrae in the thick basement membranes which separate the plasma membranes of the two cell types over most of their juxtaposed surfaces. This study was initiated to determine if there was any change in the number of pericyte-endothelial cell contact regions in retinal or optic nerve capillaries of the galactose-fed rat model for polyol-related complications of diabetes. Sprague-Dawley rats were fed for 28 months a 50% galactose diet, with or without an aldose reductase inhibitor (tolrestat), or a normal diet. Electron micrographs of transected capillaries were taken from defined regions of the central retina and nearby portions of the optic nerve. The optic nerve capillaries showed no differences in the numbers of pericyte-endothelial cell contact regions nor in basement membrane thickness in the galactose-fed rats. In contrast, the retinal capillaries exhibited a 70% decrease in the numbers of contact regions and a 2.4-fold increase in basement membrane thickness in galactosemic rats. Both loss of cell contact regions and basement membrane thickening were prevented with tolrestat. The results are consistent with the proposed involvement of the polyol pathway in diabetic retinopathy and with the greater involvement of retinal versus optic nerve vessels in diabetic microangiopathy. Invest Ophthalmol Vis

Journal of Anatomy

The purpose of the present study was to determine if prolonged systemic arterial administration o... more The purpose of the present study was to determine if prolonged systemic arterial administration of basic fibroblast growth factor (bFGF) at a dose sufficient to enhance collateral vessel formation in the ischaemic hearts of dogs would produce retinal neovascularisation in these same animals. Adult dogs (15-25 kg) were subjected to gradual occlusion of a coronary artery and randomised to receive 1 of 3 treatments via an indwelling left atrial catheter: (1) bFGF 1.74 mg/d, 5 d/wk for 63 d (n = 7); (2) bFGF 1.74 mg/d, 5 d/wk, for 35 d followed by physiological saline, 5 d/wk, for 28 d (n = 10); or (3) physiological saline, 5 d/wk, for 63 d (n = 10). After 63 d the retinal vasculatures from these dogs were isolated and examined for capillary varicosity, neovascularisation and other histopathological signs of angiopathy. All data were collected under masked conditions. The results suggest that chronic, systemic arterial administration of bFGF stimulates neovascularisation in the ischemic...

Investigative Ophthalmology &amp Visual Science

To determine if the retinal microangiopathies of the galactose-fed rat model of diabetic retinopa... more To determine if the retinal microangiopathies of the galactose-fed rat model of diabetic retinopathy can be prevented with the aldose reductase inhibitor sorbinil. Sprague-Dawley rats were fed 50% d-galactose with or without sorbinil (0.05% wt/wt), mixed biweekly with fresh diet. Rats in each group were examined frequently by slit lamp and were killed after 8, 16, and 24 months. Computer-assisted morphometry was performed on wholemounts of elastase retinal digest preparations. Cataracts developed in all galactose-fed untreated rats within 3 weeks but not in the sorbinil-treated rats even after 24 months. At 8 months, the galactose-fed untreated rats exhibited statistically significant increases in the mean capillary width, the percent of retinal area occupied by capillaries (capillary density), and the percent of microvascular area with capillaries > 20 microns wide (dilated channels), compared to controls. At 16 months, the galactose-fed untreated rats showed statistically signi...

Investigative Ophthalmology &amp Visual Science

To determine whether the diabeticlike retinal microangiopathies of the galactose-fed rat model co... more To determine whether the diabeticlike retinal microangiopathies of the galactose-fed rat model could be ameliorated if intervention by withdrawal of the galactose diet or treatment with the aldose reductase inhibitor AL-3152 was initiated after quantifiable microangiopathies had occurred. Weanling male Sprague-Dawley rats were randomized into five groups and fed for up to 24 months Purina laboratory chow (#5001) plus 50% starch (control [CON]), 50% D-galactose (galactose [GAL]), 50% D-galactose with AL-3152 (approximately 14 mg/kg per day) (prevention [PRV]), 50% D-galactose for 6 months followed by intervention with the inhibitor (intervention [INT]), or 50% D-galactose for 6 months followed by replacement with the 50% starch diet (withdrawal [GWD]). In rats on experimental diets and killed after 6, 18, and 24 months, one retina was prepared for transmission electron microscopy; the other was used for vessel wholemounts using elastase digestion. Capillary images were analyzed by co...

Purpose. To evaluate the efficacy of WAY-121,509, a potent new aldose reductase inhibitor (ARI), ... more Purpose. To evaluate the efficacy of WAY-121,509, a potent new aldose reductase inhibitor (ARI), in preventing the retinopathy that develops in the galactose-fed rat model of diabetic ocular complications. Methods. Sprague-Dawley rats were randomized into treatment and duration groups and fed diets with either 50% starch or 50% galactose with or without WAY-121,509 (25 mg/kg body weight per day). Progression

Ophthalmic Surgery, Lasers and Imaging Retina, 2014

Retinal pigment epithelium (RPE) neoplasms are extraordinarily rare and have been infrequently de... more Retinal pigment epithelium (RPE) neoplasms are extraordinarily rare and have been infrequently described in the literature. Most RPE tumors are pigmented and may simulate choroidal melanoma. The best management of RPE tumors has not yet been elucidated. In the current case, a 36-year-old man presenting with visual disturbance is found to have biopsy-proven RPE adenocarcinoma with subfoveal fluid. He is treated with grid laser over the lesion with complete resolution of fluid. RPE adenocarcinoma can present as an amelanotic mass, and grid laser over the lesion may represent a novel approach for treating associated subretinal fluid.

Cancer and Clinical Oncology, 2014

Journal of biophotonics, 2013

The first study interpreting B-lymphocyte activation in normal lymph nodes using vibrational micr... more The first study interpreting B-lymphocyte activation in normal lymph nodes using vibrational micro-spectral imaging is reported. Lymphocyte activation indicates the presence and response against a pathogen, regardless of the inciting pathogen's etiology, whether a benign, reactive or malignant process. Understanding the biochemical makeup of lymphocyte activation during early stages of disease and immune response may offer significant aid in determining a tumor's origin without the presence of malignant metastatic cells but within lymph nodes that are reactive and displaying regions of hyperplasia. Infrared and Raman data scrutinized via unsupervised multivariate methods may provide a physical and reproducible method to determine the biochemical components and variances therein of activated lymph nodes with distinguishing characteristics depending on the malignancy present in the region or elsewhere in the body. The results reported here provide a proof-of-concept study that...

Infrared and Raman Spectroscopic Imaging, 2009

... ä us , Tatyana Chernenko , Melissa J. Romeo , Milo š Miljkovi c , Benjamin Bird , Jennifer Sc... more ... ä us , Tatyana Chernenko , Melissa J. Romeo , Milo š Miljkovi c , Benjamin Bird , Jennifer Schubert ,Kostas Papamarkakis , and Nora Laver 173 5 5.1 Introduction Since the introduction of the first cytological cancer screening methods in 1941 by Papanicolaou ( ' Pap ' for short ...

Archives of pathology & laboratory medicine, 2010

Intraocular melanoma of the ciliary body and choroid is the most common primary ocular malignant ... more Intraocular melanoma of the ciliary body and choroid is the most common primary ocular malignant tumor in adults and the most common noncutaneous melanoma. To describe the most salient clinical features, histopathologic findings, and treatment modalities of intraocular melanoma, as well as the novel therapies currently being tested. Clinically, it is important to determine which lesions carry a worse prognosis so as to offer patients the best treatment modalities available. Tumor location, size, histopathology, cytogenetic abnormalities, and tumor profiling are all used in determining the risk of death from metastatic disease of uveal melanocytic lesions. Despite successful local tumor control, up to 50% of patients have metastatic disease within 15 years of diagnosis; there is no effective treatment for metastatic disease. Pathologists should be aware of the importance of tumor gross description, cellular histopathology classification, the use of fine-needle aspiration biopsy coupl...

Journal of pathology informatics, 2011

Cytology poses different obstacles in whole slide imaging compared to surgical pathology slides. ... more Cytology poses different obstacles in whole slide imaging compared to surgical pathology slides. A single focal plane suffices for most of the latter, but cytology slides are thicker, potentially requiring multiple focal planes for adequate diagnostic information. Multiple focal planes adversely impact scanning time per slide, evaluation times, and file sizes. In this pilot study, we evaluated and compared the multilayer stack method to the extended focus algorithm as an alternative which collapses multiple focal planes into a single image, retaining only focused areas from each plane. 10 SurePath(®) cervical cytology slides were scanned at three thickness settings: 18, 24, and 30 μm. Three scanners were used: (1) Hamamatsu Nanozoomer 2.0-HT, (2) 3DHISTECH Mirax scan, and (3) Bioimagene iScan Coreo Au. The Nanozoomer and iScan utilized multilayer stacking, while the Mirax files were composited by extended focus. Scan times and file sizes were recorded, and image quality compared. Th...

Case Reports in Ophthalmology, 2013

This is an Open Access article licensed under the terms of the Creative Commons Attribution-NonCo... more This is an Open Access article licensed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs 3.0 License (www.karger.com/OA-license), applicable to the online version of the article only. Distribution for non-commercial purposes only.

Journal of Biophotonics, 2009

The first detection of breast cancer micrometastases in lymph nodes by infrared spectral imaging ... more The first detection of breast cancer micrometastases in lymph nodes by infrared spectral imaging and methods of multivariate analysis is reported. Micrometastases are indicators of early spread of cancer from the organ originally affected by disease, and their detection is of prime importance for the staging and treatment of cancer. Infrared spectral imaging, at a spatial resolution of ca. 10-12 μm, can detect small metastases down to the level of a few cancerous cells. The results presented here add to a rapidly growing database of infrared spectral imaging results for cancer diagnostics.

Spectroscopy: An International Journal, 2012

This paper summarizes the progress achieved over the past fifteen years in applying vibrational (... more This paper summarizes the progress achieved over the past fifteen years in applying vibrational (Raman and IR) spectroscopy to problems of medical diagnostics and cellular biology. During this time, a number of research groups have verified the enormous information content of vibrational spectra; in fact, genomic, proteomic, and metabolomic information can be deduced by decoding the observed vibrational spectra. This decoding process is aided enormously by the availability of high-power computer workstations and advanced algorithms for data analysis. Furthermore, commercial instrumentation for the fast collection of both Raman and infrared microspectral data has rendered practical the collection of images based solely on spectral data. The progress in the field has been manifested by a steady increase in the number and quality of publications submitted by established and new research groups in vibrational biological and biomedical arenas.

Ophthalmic Surgery, Lasers, and Imaging, 2010

A 72-year-old woman presented with a 3-day history of focal pain and swelling of the left upper e... more A 72-year-old woman presented with a 3-day history of focal pain and swelling of the left upper eyelid. A cystic lesion had been present in this area for longer than 7 years, and a lesion consistent with an epidermal inclusion cyst was present on the contralateral upper eyelid. An erythematous, tender, fluctuant mass was noted on the left upper eyelid consistent with abscess. It was drained and cultured, and the infection resolved with oral amoxicillin/clavulanate potassium followed by surgical excision. Histopathologic examination demonstrated an epidermal inclusion cyst and cultures grew anaerobic gram-positive cocci. Epidermal inclusion cysts are common eyelid lesions, yet infection is rare and may result from the spread of normal flora through the pore often found on the anterior surface of these lesions.

Vibrational Spectroscopy, 2008

We report microscopically collected infrared spectra of cells found in human urine in an effort t... more We report microscopically collected infrared spectra of cells found in human urine in an effort to develop automatic methods for bladder cancer screening. Unsupervised multivariate analysis of the observed spectral patterns reveals distinct spectral classes, which correlated very well with visual cytology. Therefore, we believe that spectral analysis of individual cells can aid cytology in rendering reliable diagnoses based on objective measurements and discriminant algorithms.