ABSTRACT
Tamoxifen is a selective estrogen receptor modulator used mainly for the treatment of breast cancer. Based on the case reports and studies performed to date on the retinal toxicity of tamoxifen, retinopathy appears to occur in as many as 12% of patients taking 20 mg tamoxifen a day for over 2 years. Of this 12%, as many as half develop symptomatic changes in visual acuity. Retinal changes consist primarily of crystalline deposits, cystoid macular edema, hyperreflective deposits in the inner retinal layers, and telangiectasia. Tamoxifen retinopathy is currently managed by discontinuing tamoxifen therapy as the cancer prognosis permits; however, discontinuing therapy demonstrates little to no improvement in visual acuity once visual changes have taken place. Intravitreal injections of steroids or antivascular endothelial growth factor therapy have been performed, but require further studying before conclusions can be made. Until then, optical coherence tomography screening for retinal changes should be performed every 6 months for patients who have been on tamoxifen therapy for 2 years or more. This way, patients can become aware of retinal changes, and their physicians can consider adjusting tamoxifen therapy before they risk developing changes in visual acuity.
Subject(s)
Breast Neoplasms , Diabetic Retinopathy , Macular Edema , Retinal Diseases , Humans , Female , Retinal Diseases/chemically induced , Retinal Diseases/diagnosis , Retinal Diseases/drug therapy , Retina , Tamoxifen/adverse effects , Macular Edema/chemically induced , Macular Edema/diagnosis , Macular Edema/drug therapy , Breast Neoplasms/drug therapy , Intravitreal Injections , Tomography, Optical Coherence/methods , Retrospective Studies , Angiogenesis Inhibitors/therapeutic useABSTRACT
OBJECTIVES: To assess the repeatability and reproducibility of corneal measurements performed by the Galilei G6 and determine its agreement with the Pentacam® AXL. METHODS: 105 eyes underwent examination by both devices, measuring nine parameters. Paired t-tests, Deming Regression, and Bland-Altman plots were used to determine agreement. Analysis of Variance was used to determine repeatability and reproducibility. RESULTS: Measurements showed no clinically significant differences between the two devices. On average, the Galilei G6 measured axial length longer than the Pentacam® AXL by 0.05 mm ± 0.03 mm (p < 0.001), just 0.2% of the mean value and therefore clinically insignificant. It measured central corneal thickness and anterior chamber depth 3.77 µm ± 7.71 µm longer (p < 0.001) and 0.04 mm ± 0.07 µm shorter (p < 0.001), respectively. They are also clinically insignificant, constituting just 0.7% and 1% of the mean values. The results showed evidence of repeatability and reproducibility. Only measurements of corneal cylinder showed some clinically significant variance. CONCLUSIONS: The Galilei G6 and Pentacam® AXL measurements show evidence of repeatability, reproducibility, and agreement for examined parameters. Certain caution needs to be applied in cases with moderate or severe corneal cylinder, due to discrepancies in repeatability and reproducibility of corneal cylinder measurements with the Galilei G6.
Subject(s)
Cornea , Tomography, X-Ray Computed , Biometry , Cornea/diagnostic imaging , Corneal Pachymetry , Corneal Topography , Humans , Prospective Studies , Reproducibility of Results , Tomography, Optical CoherenceABSTRACT
Despite their clinical importance, drug resistance remains problematic for microtubule targeting drugs. D4-9-31, a novel microtubule destabilizing agent, has pharmacology that suggests it can overcome common resistance mechanisms and has been shown to remain efficacious in cell and animal models with acquired taxane resistance. To better understand resistance mechanisms and the breadth of cross-resistance with D4-9-31, this study examines the A2780 ovarian cancer cell line as it develops acquired resistance with continuous exposure to D4-9-31. Analyzing cellular responses to D4-9-31 reveals that D4-9-31 resistance is associated with increased mitochondrial respiration, but no cross-resistance to other microtubule targeting agents is observed. Sequencing of transcripts of parental cells and resistant counterparts reveals mutations and altered expression of microtubule-associated genes, but not in genes commonly associated with resistance to microtubule targeting drugs. Additionally, our findings suggest distinct mechanisms drive short- and long-term drug resistance.
Subject(s)
Amides/therapeutic use , Microtubules/drug effects , Polymerization/drug effects , Pyridines/therapeutic use , Pyrimidines/therapeutic use , Amides/pharmacology , Humans , Pyridines/pharmacology , Pyrimidines/pharmacologyABSTRACT
Signals collected by infrasound arrays require continuous analysis by skilled personnel or by automatic algorithms in order to extract useable information. Typical pieces of information gained by analysis of infrasonic signals collected by multiple sensor arrays are arrival time, line of bearing, amplitude, and duration. These can all be used, often with significant accuracy, to locate sources. A very important part of this chain is associating collected signals across multiple arrays. Here, a pairwise, cross-beam coherence method of signal association is described that allows rapid signal association for high signal-to-noise ratio events captured by multiple infrasound arrays at ranges exceeding 150 km. Methods, test cases, and results are described.
