Insights for crystal mush storage utilizing mafic enclaves from the 2011-12 Cordón Caulle eruption.

Two distinct types of rare crystal-rich mafic enclaves have been identified in the rhyolite lava flow from the 2011-12 Cordón Caulle eruption (Southern Andean Volcanic Zone, SVZ). The majority of mafic enclaves are coarsely crystalline with interlocking olivine-clinopyroxene-plagioclase textures and irregular shaped vesicles filling the crystal framework. These enclaves are interpreted as pieces of crystal-rich magma mush underlying a crystal-poor rhyolitic magma body that has fed recent silicic eruptions at Cordón Caulle. A second type of porphyritic enclaves, with restricted mineral chemistry and spherical vesicles, represents small-volume injections into the rhyolite magma. Both types of enclaves are basaltic end-members (up to 9.3 wt% MgO and 50-53 wt% SiO2) in comparison to enclaves erupted globally. The Cordón Caulle enclaves also have one of the largest compositional gaps on record between the basaltic enclaves and the rhyolite host at 17 wt% SiO2. Interstitial melt in the coarsely-crystalline enclaves is compositionally identical to their rhyolitic host, suggesting that the crystal-poor rhyolite magma was derived directly from the underlying basaltic magma mush through efficient melt extraction. We suggest the 2011-12 rhyolitic eruption was generated from a primitive basaltic crystal-rich mush that short-circuited the typical full range of magmatic differentiation in a single step.

Optical coherence tomography in multiple sclerosis.

We do not have currently satisfactory clinical and anatomical correlates to gauge disability in multiple sclerosis. Structural biomarkers (such as MRI) are hindered because they cannot precisely segregate demyelination from axonal elements of tissue injury within the CNS. Axonal degeneration in multiple sclerosis is related to irreversible disability, which suggests that the confirmation of neuroprotective strategies needs highly quantifiable measures of axon loss that can be correlated with reliable measures of physiological function. The coupling of quantifiable measures of visual function with ocular imaging techniques, such as optical coherence tomography, enables us to begin to understand how structural changes in the visual system influence function in patients with multiple sclerosis. In this review, we consider the usefulness of optical imaging of the retina as a biomarker for neurodegeneration in multiple-sclerosis.

Sympathomimetic-induced kaleidoscopic visual illusion associated with a reversible splenium lesion.

BACKGROUND: Sympathomimetic-induced metabolic derangements within the central nervous system can result in conspicuous changes in neurological functioning and corresponding radiographic abnormalities that can be reversible. OBJECTIVE: To describe a patient with a "kaleidoscopic" visual illusion who was found by magnetic resonance imaging to have a transient lesion in the splenium of the corpus callosum. DESIGN: Case report. SETTING: The University of Texas Southwestern Medical Center, Dallas. PATIENT: A 17-year-old adolescent girl who developed an episode of kaleidoscopic vision while using sympathomimetic-containing diet pills that was associated with a reversible lesion of the splenium of the corpus callosum. Her brother has a history of migraine and experienced a similar episode while using illicit stimulant agents. INTERVENTION: Withdrawal of the medication resulted in the cessation of the episodes and normalization of the magnetic resonance image. MAIN OUTCOME MEASURES: Clinical and radiographic improvement. RESULTS: Sympathomimetic-induced metabolic derangements can be associated with reversible lesions within the brain. CONCLUSIONS: We hypothesize that the visual fragmentation was a manifestation of a migraine triggered by sympathomimetic-containing diet pills, and that the transient lesion in the corpus callosum was a manifestation of a reversible metabolic derangement. Both the visual fragmentation and the lesion in the corpus callosum resolved once the patient stopped receiving diet pills.

Relation of visual function to retinal nerve fiber layer thickness in multiple sclerosis.

PURPOSE: To examine the relation of visual function to retinal nerve fiber layer (RNFL) thickness as a structural biomarker for axonal loss in multiple sclerosis (MS), and to compare RNFL thickness among MS eyes with a history of acute optic neuritis (MS ON eyes), MS eyes without an optic neuritis history (MS non-ON eyes), and disease-free control eyes. DESIGN: Cross-sectional study. PARTICIPANTS: Patients with MS (n = 90; 180 eyes) and disease-free controls (n = 36; 72 eyes). METHODS: Retinal never fiber layer thickness was measured using optical coherence tomography (OCT; fast RNFL thickness software protocol). Vision testing was performed for each eye and binocularly before OCT scanning using measures previously shown to capture dysfunction in MS patients: (1) low-contrast letter acuity (Sloan charts, 2.5% and 1.25% contrast levels at 2 m) and (2) contrast sensitivity (Pelli-Robson chart at 1 m). Visual acuity (retroilluminated Early Treatment Diabetic Retinopathy charts at 3.2 m) was also measured, and protocol refractions were performed. MAIN OUTCOME MEASURES: Retinal nerve fiber layer thickness measured by OCT, and visual function test results. RESULTS: Although median Snellen acuity equivalents were better than 20/20 in both groups, RNFL thickness was reduced significantly among eyes of MS patients (92 mum) versus controls (105 mum) (P<0.001) and particularly was reduced in MS ON eyes (85 mum; P<0.001; accounting for age and adjusting for within-patient intereye correlations). Lower visual function scores were associated with reduced average overall RNFL thickness in MS eyes; for every 1-line decrease in low-contrast letter acuity or contrast sensitivity score, the mean RNFL thickness decreased by 4 mum. CONCLUSIONS: Scores for low-contrast letter acuity and contrast sensitivity correlate well with RNFL thickness as a structural biomarker, supporting validity for these visual function tests as secondary clinical outcome measures for MS trials. These results also suggest a role for ocular imaging techniques such as OCT in trials that examine neuroprotective and other disease-modifying therapies. Although eyes with a history of acute optic neuritis demonstrate the greatest reductions in RNFL thickness, MS non-ON eyes have less RNFL thickness than controls, suggesting the occurrence of chronic axonal loss separate from acute attacks in MS patients.

Metal-dependent inhibition of HIV-1 integrase.

Human immunodeficiency virus type 1 integrase (HIV-1 IN) is an essential enzyme for effective viral replication. Therefore, IN inhibitors are being sought for chemotherapy against AIDS. We had previously identified a series of salicylhydrazides as potent inhibitors of IN in vitro (Neamati, N.; et al. J. Med. Chem. 1998, 41, 3202-3209.). Herein, we report the design, synthesis, and antiviral activity of three novel mercaptosalicylhydrazide (MSH) derivatives. MSHs were effective against the IN catalytic core domain and inhibited IN binding to HIV LTR DNA. They also inhibited catalytic activities of IN in IN-DNA preassembled complexes. Site-directed mutagenesis and molecular modeling studies suggest that MSHs bind to cysteine 65 and chelate Mg(2+) at the active site of HIV-1 IN. Contrary to salicylhydrazides, the MSHs are 300-fold less cytotoxic and exhibit antiviral activity. They are also active in Mg(2+)-based assays, while IN inhibition by salicylhydrazides is strictly Mn(2+)-dependent. Additionally, in target and cell-based assays, the MSHs have no detectable effect on other retroviral targets, including reverse transcriptase, protease, and virus attachment, and exhibit no detectable activity against human topoisomerases I and II at concentrations that effectively inhibit IN. These data suggest that MSHs are selective inhibitors of HIV-1 IN and may serve as leads for antiviral therapeutics.

Validation of Najjar-Awwad cataract surgery risk score for resident phacoemulsification surgery.

PURPOSE: To validate the Najjar-Awwad cataract surgery risk score for residents, which has been proposed to predict surgical complexity and risk. SETTING: Two urban public county hospitals. DESIGN: Case series. METHODS: Phacoemulsification cataract surgeries performed by residents between January 2005 and April 2008 were retrospectively reviewed. The cataract risk score was calculated retrospectively. Intraoperative complications included posterior and anterior capsular tears, vitreous prolapse, dropped nucleus, and conversion to manual extracapsular cataract extraction. RESULTS: Of the cases performed by 33 residents, 1833 met the inclusion criteria. There were 120 complications (6.5%); the rate of complications involving vitreous prolapse or loss (including dropped nucleus) was 3.2%. Significant risk factors in the risk score associated with intraoperative complications were dense nuclear sclerosis (odds ratio [OR], 2.08; 95% confidence interval [CI], 1.32-3.26; P = .004) and poor red reflex (OR, 2.10; 95% CI, 1.45-3.06; P = .00007). Cataract risk scores ranged from 3 to 16. The score was less than 5 in 85 cases (4.6%) and less than 7 in 885 cases (48.3%). The OR for complications increased significantly when the risk score was higher than 6 (OR, 2.11; 95% CI, 1.42-3.14; P = .0002). CONCLUSIONS: Although the Najjar-Awwad cataract surgery risk score can be used to predict intraoperative complications at the time of cataract surgery, the complication rate did not significantly increase until the score reached 7. There were few cases with scores lower than 5 in these county hospital populations. Beginning surgeons should be given cases with a risk score of less than 7.