Detection of clinical and subclinical retinal abnormalities in neurosarcoidosis with optical coherence tomography

The aim of this work was to determine if neurosarcoidosis (NS) patients exhibit quantitative and/or qualitative in vivo evidence of retinal abnormalities on optical coherence tomography (OCT). Retinal imaging was performed using spectral-domain Cirrus HD-OCT in 20 NS patients (40 eyes) and 24 age-matched healthy controls (48 eyes). Study participants also underwent magnetic resonance imaging of the brain and spine, cerebrospinal fluid (CSF) analysis, and detailed neurological and ophthalmological evaluation. Quantitative OCT abnormalities of average macular thickness (AMT), peri-papillary retinal nerve fiber layer (RNFL) thickness, or both, were detectable in 60% of NS patients. Of NS patients with ocular symptomatology, 75% demonstrated quantitative OCT abnormalities, while only 25% had detectable abnormalities on detailed ophthalmological assessment. Furthermore, 33% of NS patients without ocular symptoms had quantitative OCT changes, while only 8% had abnormal ophthalmologic examination. RNFL and macular thinning and swelling were significant in the NS cohort compared to healthy controls (variance ratio testing; RNFL: p = 0.02, AMT: p = 0.006). AMT also correlated inversely with disease duration (r (s) = -0.65, p = 0.002). Patient proportions with OCT abnormalities did not differ according to NS subtype (myelopathic, meningeal, or encephalitic NS), CSF findings, or immunotherapy exposure. No qualitative OCT abnormalities were detected. Retinal abnormalities occur in all NS subtypes, and may be clinical or subclinical. Our findings suggest OCT may enable greater detection of retinal abnormalities in NS than ophthalmological assessment alone, and have implications for the assessment of ocular involvement in NS, and sarcoidosis in general. Longitudinal NS studies utilizing OCT are warranted.     

Ventricular restoration by linear endoventricular patchplasty and linear repair

Surgical ventricular restoration improves cardiac function in patients with large left ventricular aneurysms. Aneurysm repair techniques have evolved to geometric repair by exclusion of the aneurysmal area with a circular patch. But even circular endoventricular patchplasty may result in a less elliptical ventricle. We modified the techniques of both linear and geometric repair. The early and intermediate outcomes in 102 patients with post-infarction left ventricular aneurysm, treated between 2001 and 2004, were analyzed. Concomitant procedures included coronary artery bypass grafting in 73 patients, mitral valve repair in 29, cryoablation in 3, and post-infarction ventricular septal rupture repair in 3. Overall mortality was 12.7%. Left ventricular ejection fraction increased significantly postoperatively, from 31.5% +/- 6.5% to 34.2% +/- 5.9%. There were significant decreases in end-diastolic volumes from 140.3 +/- 38.3 to 100.8 +/- 33.5 mL, and end-systolic volumes from 95.1 +/- 26.1 to 66.0 +/- 21.7 mL. These benefits continued at the 12- to 52-month follow-up. Our modified technique restores a near physiological left ventricular geometry and has a favorable clinical outcome.     

A retrospective analysis of the first Indian experience on Artisan phakic intraocular lens

PURPOSE: To evaluate the efficacy, safety, predictability and stability of implanting a polymethylmethacrylate phakic intraocular lens (PIOL) in high myopia. MATERIALS AND METHODS: A retrospective analysis of the data of patients who underwent Artisan phakic IOL implantation between 2002 and 2003 with a follow-up of at least 24 months. RESULTS: An Artisan myopia lens was implanted in 60 eyes of 36 patients with preoperative myopia ranging from -5.0 to -24.0 D. Mean patient age was 22.6 years. Mean spherical equivalent of manifest refraction stabilized by the first postoperative week. At three months follow-up, 54 eyes (90%) had a postoperative refraction within +/- 1D emmetropia and 45 eyes (75%) had uncorrected visual acuity of 20/40 or better. Seven eyes (11.6%) had loss of one Snellen line and none had loss of two Snellen lines or more at three months. The mean endothelial cell loss was 3.8% at three months, 5.2% at six months, 5.25% at 12 months and 6.38% at two years, which was not significant. Postoperative complications included anterior chamber reaction in two eyes (3.3%), rise in intraocular pressure in six eyes (10%) and dislocation of PIOL in two eyes (3.3%). CONCLUSION: Implantation of Artisan myopia lens to correct high myopia resulted in a stable and fairly predictable refractive outcome with few complications. Significant endothelial damage was not detected in two years of follow-up.     

Gene expression signature-based chemical genomic prediction identifies a novel class of HSP90 pathway modulators

Although androgen receptor (AR)-mediated signaling is central to prostate cancer, the ability to modulate AR signaling states is limited. Here we establish a chemical genomic approach for discovery and target prediction of modulators of cancer phenotypes, as exemplified by AR signaling. We first identify AR activation inhibitors, including a group of structurally related compounds comprising celastrol, gedunin, and derivatives. To develop an in silico approach for target pathway identification, we apply a gene expression-based analysis that classifies HSP90 inhibitors as having similar activity to celastrol and gedunin. Validating this prediction, we demonstrate that celastrol and gedunin inhibit HSP90 activity and HSP90 clients, including AR. Broadly, this work identifies new modes of HSP90 modulation through a gene expression-based strategy.     

Synthesis and anti-mycobacterial activity of 4-(4-phenyl-1<Emphasis Type="Italic">H</Emphasis>-1,2,3-triazol-1-yl)salicylhydrazones: revitalizing an old drug

The antitubercular drug; para-aminosalicylic acid (PAS) was used as the core scaffold for the design of a series of 1H-1,2,3-triazolylsalicylhydrazones upon coupling with triazole and arylhydrazone moietis to furnish a single molecular architecture. The obtained derivatives were screened against Mycobacterium tuberculosis H37Rv revealing good to high activity for the active compounds (MIC values of 0.39–1.5 μg/mL) compared to the marketed drugs isoniazid, rifampicin and ethambutol. Moreover, the most active analogue N-(1-(4-chlorobenzyl)-2-oxoindolin-3-ylidene)-2-hydroxy-4-(4-phenyl-1H-1,2,3-triazol-1-yl)-benzohydrazide (20) was found to be ten-fold more potent than PAS and equipotent to rifampicin (MIC 0.39 µg/mL), while exhibiting low cytotoxicity with a selectivity index of >128. In addition, this compound was shown to be active against persistent forms of mycobacteria comparable to standard drugs in nutrient starvation model. Accordingly, we introduce compound 20 as a valuable lead for further development. A 3D-QSAR study was also conducted to help in explaining the observed activity and to serve as a tool for further development.