Purpose-To compare optic disc and retinal nerve fiber layer (RNFL) imaging methods to discriminate eyes with early glaucoma from normal eyes.Design-Retrospective, cross-sectional study. Methods-Setting:Tertiary care academic glaucoma center. Ninety-two eyes of 92 subjects (46 with early perimetric open-angle glaucoma and 46 controls) were studied. Diagnostic performance of optical coherence tomography (StratusOCT), scanning laser polarimetry (GDx-VCC), confocal laser ophthalmoscopy (Heidelberg Retinal Tomograph III), and qualitative assessment of stereoscopic optic disc photographs were compared. Outcome measures were areas under receiver operator characteristic curves (AUC) and sensitivities at fixed specificities. Classification and Regression Trees (CART) analysis was used to evaluate combinations of quantitative parameters.Results-The average (±SD) visual field mean deviation for glaucomatous eyes was −4.0±2.5 dB. Parameters with largest AUCs (±SE) were: average RNFL thickness for StratusOCT (0.96±0.02), nerve fiber indicator for GDx-VCC (0.92±0.03), FSM discriminant function for HRT III (0.91±0.03), and 0.97±0.02 for disc photograph evaluation. At 95% specificity, sensitivity of disc photograph evaluation (90%) was greater than GDx-VCC (p=0.05) and HRT III (p=0.002), but not significantly different than that of StratusOCT (p>0.05). Combination of StratusOCT average RNFL thickness and HRT III cup/disc area with CART produced a sensitivity of 91% and specificity of 96% Conclusions-StratusOCT, GDx-VCC, and HRT III performed as well as, but not better than, qualitative evaluation of optic disc stereophotographs for detection of early perimetric glaucoma. The combination of StratusOCT average RNFL thickness and HRT III cup/disc area ratio provided a high diagnostic precision.
Ubiquitin-dependent proteolysis of cyclins plays a critical role in cell cycle progression and tumorigenesis. We examined the expression of ubiquitin-conjugating enzyme E2C (UBE2C) during progression from Barrett's metaplasia to esophageal adenocarcinoma (EA) and the effects of targeting this enzyme on EA-derived cell lines. Using oligonucleotide microarrays UBE2C expression was elevated in 73% (11 of 15) of EAs relative to Barrett's metaplasia. Tissue microarray showed elevated UBE2C in 70% (7 of 10) of dysplastic samples and in 87% (58 of 67) of tumors relative to metaplastic samples. Transfection of dominant-negative UBE2C into Seg-1 cells decreased proliferation (P = .04) and increased mitotic arrest compared to vector controls (63.5% vs 6.8%; P < .001). Transfection of UBE2C small interfering RNA also caused inhibiton of cell proliferation and distortion of the cell cycle, with maximal increase of G(2) cells (155% of mock cells) at 72 hours and of S-phase cells (308% of mock cells) at 24 hours. Treatment of Seg-1 cells with the proteasome inhibitor MG-262 (1 nM-1 microM) showed decreased proliferation (P = .02). EA-derived cells expressing UBE2C are sensitive to treatment with MG-262 and to silencing of UBE2C, suggesting that patients with EAs overexpressing UBE2C may benefit from agents targeting this ubiquitin-conjugating enzyme.
The L-type amino acid transporter-1 (LAT-1) has been associated with tumor growth. Using cDNA microarrays, overexpression of LAT-1 was found in 87.5% (7/8) of esophageal adenocarcinomas relative to 12 Barrett's samples (33% metaplasia and 66% dysplasia) and was confirmed in 100% (28/28) of Barrett's adenocarcinomas by quantitative reverse transcription polymerase chain reaction. Immunohistochemistry revealed LAT-1 staining in 37.5% (24/64) of esophageal adenocarcinomas on tissue microarray. LAT-1 also transports the amino acid-related chemotherapeutic agent, melphalan. Two esophageal adenocarcinoma and one esophageal squamous cell line, expressing LAT-1 on Western blot analysis, were sensitive to therapeutic doses of melphalan (P <.001). Simultaneous treatment with the competitive inhibitor, BCH [2-aminobicyclo-(2,1,1)-heptane-2-carboxylic acid], decreased sensitivity to melphalan (P <.05). In addition, confluent esophageal squamous cultures were less sensitive to melphalan (P <.001) and had a decrease in LAT-1 protein expression. Tumors from two esophageal adenocarcinoma cell lines grown in nude mice retained LAT-1 mRNA expression. These results demonstrate that LAT-1 is highly expressed in a subset of esophageal adenocarcinomas and that Barrett's adenocarcinoma cell lines expressing LAT-1 are sensitive to melphalan. LAT-1 expression is also retained in cell lines grown in nude mice providing a model to evaluate melphalan as a chemotherapeutic agent against esophageal adenocarcinomas expressing LAT-1.
Laser-assisted in-situ keratomileusis (LASIK) is one of the most commonly performed refractive procedures with excellent visual outcomes. Dry eye syndrome is one of the most frequently seen complications after LASIK, with most patients developing at least some mild dry eye symptoms postoperatively. To achieve improved visual outcomes and greater patient satisfaction, it is essential to identify patients prone to dry eyes preoperatively, and initiate treatment early in the course. Enhanced understanding of the pathophysiology of post-LASIK dry eye will help advance our approach to its management.
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