Cataract surgery in sympathetic ophthalmia

PURPOSE: To analyze the results of cataract surgery in patients with sympathetic ophthalmia. SETTING: Sankara Nethralaya, Medical Research Foundation, Chennai, India. METHODS: This study comprised 66 patients (132 eyes) with sympathetic ophthalmia seen at the uveitis referral clinic between January 1990 and July 2001; 42 eyes (31.8%) had cataract. Cataract surgery was performed in 17 sympathizing eyes and 1 exciting eye (17 patients). The records of these 18 eyes were retrospectively analyzed. Three eyes had extracapsular cataract extraction (ECCE) with intraocular lens (IOL) implantation, 6 eyes had ECCE without IOL implantation, and 9 eyes had phacoemulsification with IOL implantation. The mean follow-up was 28.7 months (range 3 to 60 months). RESULTS: The causes of sympathetic ophthalmia were penetrating trauma (n = 8 eyes), ocular surgery (n = 6), perforated corneal ulcer (n = 2), and cyclocryotherapy (n = 1). The most common cataract type, present in 7 eyes (38.8%), was mixed (posterior subcapsular and posterior polar). Visual acuity improved after surgery in 13 eyes (72.2%). The main factors impairing visual recovery were submacular scar and optic atrophy, which were sequelae of the sympathetic ophthalmia. Posterior capsule opacification was noted in 14 eyes (77.7%); it was visually significant in 6 eyes. There was no significant difference in postoperative inflammation or disease reactivation between the 3 types of surgery. CONCLUSIONS: Cataract extraction in cases of sympathetic ophthalmia can be safely and successfully performed with vigilant preoperative and postoperative control of inflammation, careful surgical planning, and meticulous surgical technique. The final visual outcome, however, depends on the posterior segment complications of the disease.     

Adsorbed proteins influence the biological activity and molecular targeting of nanomaterials.

The possible combination of specific physicochemical properties operating at unique sites of action within cells and tissues has led to considerable uncertainty surrounding nanomaterial toxic potential. We have investigated the importance of proteins adsorbed onto the surface of two distinct classes of nanomaterials (single-walled carbon nanotubes [SWCNTs]; 10-nm amorphous silica) in guiding nanomaterial uptake or toxicity in the RAW 264.7 macrophage-like model. Albumin was identified as the major fetal bovine or human serum/plasma protein adsorbed onto SWCNTs, while a distinct protein adsorption profile was observed when plasma from the Nagase analbuminemic rat was used. Damaged or structurally altered albumin is rapidly cleared from systemic circulation by scavenger receptors. We observed that SWCNTs inhibited the induction of cyclooxygenase-2 (Cox-2) by lipopolysaccharide (LPS; 1 ng/ml, 6 h) and this anti-inflammatory response was inhibited by fucoidan (scavenger receptor antagonist). Fucoidan also reduced the uptake of fluorescent SWCNTs (Alexa647). Precoating SWCNTs with a nonionic surfactant (Pluronic F127) inhibited albumin adsorption and anti-inflammatory properties. Albumin-coated SWCNTs reduced LPS-mediated Cox-2 induction under serum-free conditions. SWCNTs did not reduce binding of LPS(Alexa488) to RAW 264.7 cells. The profile of proteins adsorbed onto amorphous silica particles (50-1000 nm) was qualitatively different, relative to SWCNTs, and precoating amorphous silica with Pluronic F127 dramatically reduced the adsorption of serum proteins and toxicity. Collectively, these observations suggest an important role for adsorbed proteins in modulating the uptake and toxicity of SWCNTs and nano-sized amorphous silica.     

A 96-well surrogate survival assay coupled with a special short interfering RNA vector for assessing cancer gene targets with enhanced signal/noise ratio and its utility in HTS for cancer therapeutic targets

Transient transfection of short interfering RNAs to inactivate cancer therapeutic genes in cancer cells is an important method to induce therapeutic phenotypes (cell apoptosis, growth arrest, etc.) for cancer target validation. These phenotypes can be initially assessed by cell survival via colorimetric/fluorescence readings, e.g., alamarBlue (Trek Diagnostic Systems, Cleveland, OH) and WST-1. However, intrinsic problems exist for transient transfection-varying toxicity, inconsistent transfection efficiency, as well as other cell-specific determinants-which contribute to a low signal:noise ratio of the assays, rendering of the assay ineffective particularly when applied in high-throughput screening (HTS) multiplexed for different cells. This report describes a method using reporter as a "normalized surrogate" for the conventional survival readout in a 96-well format. In this approach, only the transfected surviving cells produce reporter activities, and many variables associated with transient transfection are excluded. A constitutively expressed reporter gene (luciferase or LacZ) expression cassette is co-transfected into cells along with a specially designed RNA interference (RNAi) vector (or a transgene for that matter). The reporter activity in either liquid cultures or in soft agar cultures in 96-well formats is then quantitated in situ. The RNAi vector construction is simplified so that it can be adapted to a 96-well format. Our data demonstrated that the relative reporter readings for survival are independent of both transfection efficiency and cellular toxicity. The signal:noise ratio is markedly increased, particularly for cells with low transfection efficiency. The assay is versatile and robust and can be applied in multiplexed HTS for cancer target identification and validation.     

Heterotopic ossification: a review

Heterotopic ossification is the formation of bone in the soft tissues. Soft tissue bone deposition may range from the minimal and inconsequential to massive and clinically significant. In some clinical settings it is a predictable finding with an unpredictable course and in other settings it may be diagnostically confounding. Heterotopic ossification may be encountered in clinically disparate disease processes and circumstances. We review the genetic, neurogenic, post-traumatic, post-surgical and reactive causes of heterotopic ossification and discuss some current concepts of its pathogenesis.     

The advanced age deceased kidney donor: current outcomes and future opportunities

BaCKGROUND: Due to the aging general population, deceased donors > or =55 years will form an increasingly larger proportion of the deceased kidney donor pool. METHODS: Using data from the United States Renal Data System, we determined the change in graft survival between 1996 and 2000 among 32,557 recipients of donors aged <55 years and > or =55 years in univariate and multivariate survival analyses. We identified donor risk factors for graft loss that might influence the decision to accept or reject donors <55 and > or =55 years. The initial glomerular filtration rate established 6 months after transplantation (initial GFR), and the stability of GFR in the first post-transplant year (GFR at 12 months post-transplantation-GFR at six months post-transplantation) were compared between recipients of donors <55 and > or =55 years and the association of these factors with graft survival was determined. RESULTS: In 2000, one-year graft survival in donors > or =55 years was 86.7%. Between 1996 and 1999 the projected graft half life improved from 11.4 to 14.5 years for recipients of donors <55 years (P < 0.01); however, there was no improvement for recipients of donors > or =55 years (8.2 to 9.2 year, P= 0.46). Among donor factors studied, only cold ischemic time >24 hours identified recipients of donors > or =55 years at risk for graft loss. Compared to recipients of donors <55 years, recipients of donors > or =55 years established a lower initial GFR (42 vs. 56 mL/min/1.73 m(2), P < 0.0001), and had less stable GFR in the first post-transplant year (-1.5 vs. -0.6 mL/min/1.73 m(2), P <.0001). Recipients from donors > or =55 years with initial GFR > or =50 mL/min/1.73 m(2) and no drop GFR during the first post-transplant year had graft survival that was superior to that of donors <55 years with either initial GFR <50 mL/min/1.73 m(2) or a drop in GFR during the first post-transplant year. CONCLUSION: Donors > or =55 years are a valuable resource. Despite improvements in immunosuppression, rejection, and delayed graft function, the projected increase in long-term graft survival among recipients of donors <55 years was not shared among recipients of donors > or =55 years. Recipients of donors > or =55 years had lower initial GFR, and less stable GFR during the first post-transplant year. Limiting cold ischemic time to <24 hours may improve outcomes among recipients of donors > or =55 years. Future studies to maximize initial GFR and minimize early loss of GFR in recipients of donors > or =55 years may lead to improved outcomes from deceased donors > or =55 years.