THE CHRYSANTHEMUM PHENOTYPE OF IDIOPATHIC MULTIFOCAL CHOROIDITIS.

PURPOSE: To describe the clinical characteristics and multimodal imaging features of a distinctive subtype of active idiopathic multifocal choroiditis (iMFC) lesions with grey-yellow chorioretinal lesions surrounded by smaller satellite dots, a presentation referred to as "chrysanthemum lesions." METHODS: Retrospective, observational, multicenter case series of eyes with active iMFC and chrysanthemum lesions. Multimodal imaging features were reviewed and presented. RESULTS: Twenty-five eyes from 20 patients (12 women and 8 men), with a mean age of 35.8 ± 17.0 years (range, 7-78 years) were included. Chrysanthemum lesions were equally located in the macula (48.0%) or the mid/far periphery (52.0%). The number of lesions per eye varied from 1 (16.0%) to more than 20 (56.0%). On optical coherence tomography, chrysanthemum lesions showed typical features of iMFC, including subretinal hyperreflective material splitting the retinal pigment epithelium/Bruch membrane. Chrysanthemum lesions were hypoautofluorescent on fundus autofluorescence imaging, hyperfluorescent on fluorescein angiography, hypofluorescent on indocyanine green angiography, and associated with choriocapillaris flow signal deficit on optical coherence tomography angiography. CONCLUSION: Active iMFC may present with findings resembling chrysanthemum lesions. The distinctive lesion morphology on ophthalmoscopic examination, the large number of lesions, and the high prevalence of exclusive midperipheral and far peripheral involvement may represent a distinctive phenotype of iMFC.

Orbital Inflammatory Syndrome and Anterior Uveitis: A Case Series.

PURPOSE: To describe four cases of orbital inflammatory syndrome (OIS) with associated anterior uveitis that have presented within 2 years to our practice. METHODS: Charts of patients diagnosed with OIS from June 2013 to May 2015 were reviewed. RESULTS: Four patients, three children and one adult, presented with orbital swelling, pain, and varying degrees of vision loss. Treatment with intravenous methylprednisolone resulted in significant symptomatic improvement in all cases initially; when symptoms recurred, the patients had evidence of anterior uveitis. With continued systemic therapy and the addition of topical prednisolone, the patients all achieved control of their uveitis and OIS and are well controlled with regular outpatient follow-up. CONCLUSIONS: Reports of OIS-associated with uveitis are relatively rare. The presentation of three pediatric patients and one adult patient to the same practice with OIS and secondary uveitis within a 2-year period may indicate that the association is underreported.

Comparing the conformational behavior of a series of diastereomeric cyclic urea HIV-1 inhibitors using the low mode:monte carlo conformational search method.

The conformational flexibility of a series of diastereomeric cyclic urea HIV-1 protease inhibitors has been examined using the Low Mode:Monte Carlo conformational search method. Force fields were validated by a comparison of the energetic ordering of the minimum energy structures on the AMBER/GBSA(water), OPLSAA/GBSA(water) and HF/6-311G/SCRF(water) surfaces. The energetic ordering of the minima on the OPLSAA /GBSA(water) surface was in better agreement with the quantum calculations than the ordering on the AMBER/GBSA(water) surface. An ensemble of low energy structures was generated using OPLSAA/GBSA(water) and used to compare the molecular shape and flexibility of each diastereomer to the experimentally determined binding affinities and crystal structures of closely related systems. The results indicate that diastereomeric solution-phase energetic stability, conformational rigidity and ability to adopt a chair conformation correlate strongly with experimental binding affinities. Rigid body docking suggests that all of the diastereomers adopt solution-phase conformations suitable for alignment with the HIV-1 protease; however, these results indicate that the binding affinities are dependent upon subtle differences in the P1/P1' and P2/P2' substituent orientations.

A comparison of the Low Mode and Monte Carlo conformational search methods.

The Low Mode (LM) and Monte Carlo (MC) conformational search methods were compared on three diverse molecular systems; (4R, 5S, 6S, 7R)-hexahydro-5,6-dihydroxy-1,3,4,7-tetrakis(phenylmethyl)-2H-1,3-diazapin-2-one (1), 2-methoxy-2-phenyl-2-triflouromethyl-N-alpha-methyl benzyl propanamide (2) and a trimeric 39-membered polyazamacrolide (3). We find that either method, or a combination of the methods, is equally efficient at searching the conformational space of the smaller molecular systems while a 50:50 hybrid of Low Mode and Monte Carlo is most efficient at searching the space of the larger molecular system.

Co-localization of mu opioid receptor and N-methyl-D-aspartate receptor in the trigeminal dorsal horn.

Antagonists acting at the N-methyl-D-aspartate (NMDA) receptor can block the development of tolerance to the analgesic effects of [mu ] opioid receptor (MOR) ligands, such as morphine, and can also enhance the analgesic efficacy of opioids. These findings have led to the hypothesis that interactions between NMDA receptor and MOR ligands may be due to the co-localization of these receptors on neurons in the dorsal horn. We used dual immunogold and immunoperoxidase immunocytochemistry for MOR1 and NMDAR1 to determine the degree of co-localization of these receptors in neurons of the trigeminal dorsal horn. By use of electron microscopy, we found that both receptors were primarily located in dendrites and to a lesser extent in perikarya, axons, axon terminals, and glia. With regard to the degree of co-localization in dendrites, 63% of MOR1-labeled dendrites also contained NMDAR1, whereas 61% of NMDAR1-labeled dendrites also contained MOR1. Most of the dual-labeled profiles (94%) were classified as dendrites, with the remainder being axons, axon terminals, or perikarya. These results suggest that direct interactions between MOR and NMDA receptor ligands are likely mediated through shared dendritic targets in the dorsal horn. Less frequently, we found evidence for modulation of afferents to MOR-containing neurons through presynaptic NMDA receptors.