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Microbial keratitis is a severe, sight-threatening condition caused by various pathogens. Eyedrops are the standard delivery modality for treating these disorders; however, blinking reflex, elevated tear production, and nasolacrimal drainage eliminate much of the instilled dose within a few seconds. Therefore, eyedrops must be applied repeatedly for prolonged periods. The present study aimed to probe more effective ocular delivery of chlorhexidine based upon drug-loaded hydrogel contact lenses and β-cyclodextrin (β-CD), while also determining the effect of constant irrigation with simulated tear fluid (STF) in in vitro experiments. Chlorhexidine digluconate (as 0.2 and 2% solutions, β-CD inclusion complexes, and loaded hydrogel contact lenses) were applied to enucleated porcine eyes as single or multiple 10 μL doses, or as drug-loaded contact lenses, with and without β-CD. The corneas were then excised and drug-extracted quantified by high-performance liquid chromatography (HPLC). The effect of constant irrigation by STF was evaluated to test the effect of increased tear production on corneal delivery. Potential antimicrobial activity of the delivered drug was also assessed. Results showed that drug-loaded contact lenses delivered the greatest amount of chlorhexidine into the cornea over a 24 h period, while the eyedrop solution comparator delivered the least. The β-CD significantly enhanced chlorhexidine delivery to the cornea from eyedrop solution, although contact lenses loaded with chlorhexidine-β-CD failed to enhance delivery. β-CD within the hydrogel matrix impeded drug release. Constant irrigation with STF significantly reduced the amount of drug delivered to the cornea in all cases. Chlorhexidine retained antimicrobial activity in all delivery methods. Hydrogel contact lenses loaded with chlorhexidine delivered significantly higher levels to the cornea compared to eyedrops, either multiple hourly doses or a single dose. They also offer reduced application, in particular, to a nonulcerated corneal infection. Finally, the importance of fully accounting for tear production in in vitro ocular delivery experiments was highlighted.

Purpose: The purpose of our study was to determine the relative frequencies of causes of widespread ground-glass opacity (GGO) in an unselected, consecutive patient population and to identify any associated imaging findings that can narrow or reorganize the differential., Materials and Methods: The study was approved by the center's IRB and is HIPPA compliant. Cases with widespread GGO in the radiology report were identified by searching the Radiology Information System. Medical records and CT scan examinations were reviewed for the causes of widespread GGO. Associations between a less dominant imaging finding and a particular diagnosis were analyzed with the chi square test. Our study group consisted of 234 examinations with 124 women and 110 men and a mean age of 53.7 years., Results: A cause was established in 204 (87.2%) cases. Hydrostatic pulmonary edema was most common with 131 cases (56%). Interstitial lung diseases (ILD) were the next most common, most often hypersensitivity pneumonitis (HP) (n=12, 5%) and connective tissue disease related ILD (n=7, 3%). Infection accounted for 5% (12 cases). A few miscellaneous diseases accounted for 5 cases (2.1%). The combination of septal thickening and pleural effusions had a specificity of 0.91 for hydrostatic pulmonary edema (P<.001) while centrilobular nodules and air trapping had a specificity of 1.0 for HP. In 24 (10.2%) patients, increased opacification from expiration was incorrectly interpreted as representing widespread ground glass opacity. The relative frequency of disease dramatically changed according to the setting. In the inpatient setting, diffuse alveolar disease and diffuse infection accounted for all of the known diagnoses. Pulmonary edema accounted for 75% of the diagnoses and diffuse infection accounted for approximately 7%. In the outpatient setting, interstitial lung disease was the most common cause, accounting for 26 of 53 cases (49%). Regarding immunocompromised patients, hydrostatic pulmonary edema was still the most common cause (46%) with diffuse infection (24%) the next most likely diagnosis. For patients with bone marrow suppression, 80% of the cases were due to opportunistic viral infection., Conclusion: Widespread GGO is most commonly a manifestation of hydrostatic pulmonary edema. Outpatients will most often have HP or connective tissue disease related ILD. Associated findings are helpful for the diagnosis of hydrostatic pulmonary edema and HP., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Rationale: Multiple causes for air trapping as identified by expiratory computed tomography (CT) have been reported, but a unified evaluation schema has never been proposed., Objectives: It was our purpose to identify imaging features that would help distinguish etiologies of mosaic air trapping., Methods: Cases with the term "air trapping" in the radiology report in 2010 were identified by searching the Radiology Information System of an academic tertiary care center and associated community hospital. Medical records and CT examinations were reviewed for the causes of air trapping., Measurements and Main Results: Causes for moderate to severe air trapping could be identified in 201 of 230 (87.4%) cases and could be subdivided into those associated with bronchiectasis (76 of 201, 38%), those associated with interstitial lung disease (62 of 201, 31%), those associated with tree-in-bud opacities (5 of 201, 2%), and those with air trapping alone (58 of 201, 29%). When found with bronchiectasis, nontuberculous mycobacteria, cystic fibrosis, idiopathic bronchiectasis, and transplant-related bronchiolitis obliterans were the most common causes of air trapping. When found with interstitial lung disease, sarcoidosis, hypersensitivity pneumonitis, or unspecified interstitial lung disease were the most common cause of air trapping. When found in isolation, chronic bronchitis, asthma, bronchiolitis obliterans, and unspecified small airways disease were the most common causes of air trapping. Unusual conditions causing isolated air trapping included vasculitis and diffuse idiopathic neuroendocrine cell hyperplasia., Conclusion: A variety of conditions can cause air trapping. Associated imaging findings can narrow the differential diagnosis.