In vitro and in vivo removal efficacy of insoluble Prussian blue in combination with calcium polystyrene sulfonate for thallium.

The similarities between thallium and potassium have suggested the use of calcium polystyrene sulfonate (CPS), an oral ion exchange resin, as a potential agent against thallium intoxication. Therefore, the study was an attempt to evaluate the efficacy of CPS and Prussian blue when given alone or in combination against thallium toxicity. The effect on binding capacity was investigated in terms of contact time, amount of CPS, influence of pH, simulated physiological solutions and interference of potassium ions. Also, rats were given single dose of thallium chloride (20 mg kg-1) and the treatment with PB and CPS was given for 28 days as CPS 30 g kg-1, orally, twice a day, PB 3 g kg-1, orally, twice a day and their combination. The effect of antidotal treatment was evaluated by calculating the thallium levels in various organs, blood, urine and feces. The results of the in vitro study indicated exceedingly quick binding in the combination of CPS and PB as compared to PB alone. Also, it was found that the binding capacity at pH 2.0 was considerably increased for PB with CPS (184.656 mg g-1) as compared to PB (37.771 mg g-1). Furthermore, statistically significant results were obtained in the in vivo study as after 7th day, thallium levels in blood of rats treated with combination were reduced by 64% as compared to control group and 52% as compared to alone PB treated group. Also, Tl retention in liver, kidney, stomach, colon and small intestine of combination treated rats was significantly reduced to 46%, 28%, 41%, 32% and 33% respectively, as compared to alone PB treated group. These findings demonstrate this as a good antidotal option against thallium intoxication.

A Review of Corneal Biomechanics and Scleral Stiffness in Topical Prostaglandin Analog Therapy for Glaucoma.

PURPOSE: The mechanism of action underlying prostaglandin analog (PGA) therapy involves changes in the expression of different metalloproteases to increase permeability of the sclera and allow increased aqueous humor outflow through this alternative drainage pathway. This alteration of structure impacts cornea/scleral biomechanics and may introduce artifact into the measurement of intraocular pressure (IOP) in the clinical setting. METHODS: A literature search reviewing the impact of PGA therapy on corneal and scleral biomechanics was conducted including basic studies, clinical studies with treatment naïve patients, and a clinical study examining the cessation of PGA therapy. Additional literature including engineering texts was added for greater clarity of the concepts underlying ocular biomechanics. RESULTS: One study with an animal model reported significant corneal stiffening with PGA treatment. Most longitudinal clinical studies examining the effects of initiation of PGA therapy in PGA naïve subjects failed to report biomechanical parameters associated with stiffness using the Corvis ST and only included those parameters strongly influenced by IOP. One study reported a significant reduction in scleral stiffness with IOP as a co-variate, highlighting the need to account for the effects of IOP lowering when assessing clinical biomechanics. The report of cessation of PGA therapy on corneal biomechanics showed no change in corneal compensated IOP after 6 weeks, raising the question of reversibility of the PGA-induced structural alteration. CONCLUSIONS: Given that the findings in several clinical studies may merely reflect a reduction in IOP, further studies are warranted using Corvis ST parameters associated with corneal and scleral stiffness. The gold standard for IOP measurement in the clinical setting is Goldmann applanation tonometry, a technique previously shown to be affected by corneal stiffness. Since PGA therapy has been reported to alter not only scleral biomechanics, but also corneal biomechanics, it is essential to consider alternative tonometry technologies in the clinic.

Evaluating the Relationship of Intraocular Pressure and Anterior Chamber Volume With Use of Prostaglandin Analogues.

PRCIS: In this prospective study, naive prostaglandin use in primary open-angle glaucoma was associated with scleral biomechanical alteration and intraocular pressure (IOP) measuring errors. PURPOSE: The purpose of this study is to determine the effects of naïve use of prostaglandin analogues (PGA) on IOP and anterior chamber volume (ACV), as well as investigate how PGAs might affect corneal and scleral stiffness and their impact on ocular rigidity. MATERIALS AND METHODS: This study was a prospective study of 21 recently diagnosed open-angle glaucoma patients (33 eyes) initiating medical therapy with a topical prostaglandin eye drop. Corneal morphologic and biomechanical parameters as well as IOP were measured at 3 visits over a 4-month period with the following equipment: Pentacam, Corvis ST, Ocular Response Analyzer, Goldmann applanation tonometry (GAT) and Pascal dynamic contour tonometry. RESULTS: The study demonstrated a significant decrease in mean IOP with initiation of PGA in all 4 tonometers (P<0.0001). The greatest change in IOP occurred in the first 4 weeks of treatment (P<0.0001). The mean ACV showed a significant decrease at visit 2 (P<0.02) and visit 3 (P<0.04) compared with baseline visit 1. However, there was a paradoxical increase in ACV in 37% of eyes at visit 2, despite a significant mean reduction in IOP by GAT and dynamic contour tonometry.The IOP/ACV ratio at visit 1 significantly predicted the reduction in respective measures of IOP, as well as scleral stiffness measured by stiffness parameter-highest concavity. CONCLUSION: In clinical practice, GAT may not be the most appropriate tonometer for measuring IOP in PGA treated eyes due the measurement errors from ocular biomechanical alteration. The IOP/ACV ratio could potentially serve as a new diagnostic parameter to determine the likelihood of PGA treatment success.

Asymmetric glaucoma in pseudoplateau iris syndrome.

A 39-year-old Caucasian man with bilateral narrow angles, a plateau-like iris configuration on gonioscopy and elevated intraocular pressure (IOP) presented with significant asymmetric glaucoma, left eye affected more than right. Initial management with topical medical therapy, laser iridoplasty and peripheral iridotomy in the left eye was ineffective in lowering the IOP or opening the anterior chamber angle. Ultrasound biomicroscopy demonstrated bilateral ciliary body cysts. The patient ultimately required surgical management, consisting of cataract extraction and endoscopic cyclophotocoagulation of ciliary body cysts in the left eye and trabeculectomy in the right eye, for persistent IOP control to prevent further optic nerve damage and subsequent visual field loss.

Role of GSK-3ß in Regulation of Canonical Wnt/ß-catenin Signaling and PI3-K/Akt Oncogenic Pathway in Colon Cancer.

Non-steroidal anti-inflammatory drugs (NSAIDs) are emerging as novel chemopreventive agents because of their ability in blocking cellular proliferation, and thereby tumor development, and also by promoting apoptosis. GSK-3ß, a serine threonine kinase and a negative regulator of the oncogenic Wnt/ß-catenin signaling pathway, plays a critical role in the regulation of oncogenesis. Celecoxib and etoricoxib, the two cyclooxygenase-2 (COX-2) selective NSAIDs, and Diclofenac, a preferential COX-2 inhibitory NSAID, had shown uniformly the chemopreventive and anti-neoplastic effects in the early stage of colon cancer by promoting apoptosis as well as an over-expression of GSK-3ß while down-regulating the PI3-K/Akt oncogenic pathway.

Chemoprevention of Colon Cancer through Inhibition of Angiogenesis and Induction of Apoptosis by Nonsteroidal Anti-Inflammatory Drugs.

Cancer cells require nourishment for the growth of the primary tumor mass and spread of the metastatic colony. These needs are fulfilled by tumor-associated neovasculature known as angiogenesis, which also favors the transition from hyperplasia to neoplasia, that is, from a state of cellular multiplication to uncontrolled proliferation. Therefore, targeting angiogenesis is profitable as a mechanism to inhibit tumor growth. Furthermore, it is important to understand the cross-communication between vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMPs) in the neoplastic and proinflammatory milieu. We studied the role of two important chemokines (monocyte chemoattractant protein-1 [MCP-1] and macrophage inflammatory protein-1ß [MIP-1ß]) along with VEGF and MMPs in nonsteroidal anti-inflammatory drug (NSAID)-induced chemopreventive effects in experimental colon cancer in rats. 1,2-Dimethylhydrazine dihydrochloride (DMH) was used as cancer-inducing agent and three NSAIDs (celecoxib, etoricoxib, and diclofenac) were given orally as chemopreventive agents. Analysis by immunofluorescence and western blotting shows that the expression of VEGF, MMP-2, and MMP-9 was found to be significantly elevated in the DMH- treated group and notably lowered by NSAID coadministration. The expression of MCP-1 was found to be markedly decreased, whereas that of MIP-1ß increased after NSAID coadministration. NSAID coadministration was also able to induce apoptosis, confirmed using studies by Hoechst/propidium iodide (PI) costaining and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. Results from the present study indicate the potential role of these chemokines along with VEGF and MMPs against angiogenesis in DMH-induced cancer. The inhibition of angiogenesis and induction of apoptosis by NSAIDs were found to be possible mechanisms in the chemoprevention of colon cancer.

Breaking bad news: A communication competency for ophthalmology training programs.

As the ophthalmology accreditation system undergoes major changes, training programs must evaluate residents in the 6 core competencies, including appropriately communicating bad news. Although the literature is replete with recommendations for breaking bad news across various non-ophthalmology specialties, no formal training programs exist for ophthalmology. There are many valuable lessons to be learned from our colleagues regarding this important skill. We examine the historic basis for breaking bad news, explore current recommendations among other specialties, and then evaluate a pilot study in breaking bad news for ophthalmology residents. The results of this study are limited by a small number of residents at a single academic center. Future studies from multiple training programs should be conducted to further evaluate the need and efficacy of formal communication skills training in this area, as well as the generalizability of our pilot training program. If validated, this work could serve as a template for future ophthalmology resident training and evaluation in this core competency.

Chemopreventive action of non-steroidal anti-inflammatory drugs on the inflammatory pathways in colon cancer.

Non-steroidal anti-inflammatory drugs (NSAIDs) are emerging as novel chemopreventive agents against a variety of cancers owing to their capability in blocking the tumor development by cellular proliferation and by promoting apoptosis. Inflammation is principal cause of colon carcinogenesis. A missing link between inflammation and cancer could be the activation of NF-κB, which is a hallmark of inflammatory response, and is commonly detected in malignant tumors. Therefore, targeting pro-inflammatory cyclooxygenase enzymes and transcription factors will be profitable as a mechanism to inhibit tumor growth. In the present study, we have studied the role of various pro-inflammatory enzymes and transcription factors in the development of the 1,2-dimethylhydrazine dihydrochloride (DMH)-induced colorectal cancer and also observed the role of three NSAIDs, viz., Celecoxib, Etoricoxib and Diclofenac. Carcinogenic changes were observed in morphological and histopathological studies, whereas protein regulations of various biomolecules were identified by immunofluorescence analysis. Apoptotic studies was done by TUNEL assay and Hoechst/PI co-staining of the isolated colonocytes. It was found that DMH-treated animals were having an over-expression of pro-inflammatory enzymes, aberrant nuclear localization of activated cell survival transcription factor, NF-κB and suppression of anti-inflammatory transcription factor PPAR-γ, thereby suggesting a marked role of inflammation in the tumor progression. However, co-administration of NSAIDs has significantly reduced the inflammatory potential of the growing neoplasm.

Binocular visual field impairment in glaucoma and at-fault motor vehicle collisions.

PURPOSE: To evaluate the association between the binocular visual field defects in drivers with glaucoma and the risk of motor vehicle collision (MVC) involvement. METHODS: A retrospective cohort study was conducted on 438 drivers with glaucoma aged 55 years or older using data from 1994 through 2000. Demographic, clinical, and driving characteristics were obtained from chart abstractions and patient survey. Binocular field measures were generated by combining data from the monocular (central 24-degree radius) fields whereby the binocular field measure was defined as the more sensitive point at each monocular field location. Measures included threshold (TH), total deviation (TD), and pattern deviation (PD); severe impairment in these measures was defined as falling into the worst quartile. MVC data were obtained from police records. Rate ratios (RR) and 95% confidence intervals (CI) were calculated. RESULTS: Drivers with severely impaired PD measures were twice as likely to have an at-fault MVC compared with those not severely impaired (RR, 2.13; 95% CI, 1.21-3.75); those with severely impaired TH (RR, 1.49; 95% CI, 0.81-2.74) and TD (RR, 1.50; 95% CI, 0.82-2.74) also had an increased rate of at-fault MVCs, although these were not significant. When the binocular central visual field was stratified into 9 regions, drivers with impaired TH, TD, or PD had similarly elevated MVC rates in all regions compared with those not severely impaired, though not all reached statistical significance. CONCLUSIONS: On the basis of clinical measures of visual field routinely used in the management of glaucoma, drivers with glaucoma with severe PD field defects in the binocular field have a higher rate of at-fault MVC compared with those with less impaired or unimpaired binocular visual fields.

Intracameral triamcinolone acetonide in glaucoma surgery: a prospective randomized controlled trial.

PURPOSE: To evaluate the efficacy and safety of intracameral triamcinolone acetonide (TA) in glaucoma surgery. DESIGN: Prospective randomized clinical trial. SETTING: Institutional-Wills Eye Hospital. STUDY POPULATION: Patients undergoing trabeculectomy (with or without cataract surgery) or tube shunt surgery. INTERVENTION: Patients were randomized to receive intracameral TA or balanced salt solution at the end of surgery. Follow-up time was 6 months. MAIN OUTCOME MEASURES: Intraocular pressure, visual acuity, inflammation measured by slit-lamp examination and laser flare meter, cataract grading, bleb appearance, dry eye scores, use of supplemental medical therapy, surgical success, and rate of complications. RESULTS: Seventy-seven patients were enrolled in the study, including 37 in the TA group and 40 in the control group. There were no significant differences in success rates between the 2 groups (P=.60). Intraocular pressure and medication use were similar between the groups for each follow-up visit. Dry eye scores were lower in the TA group at month 1 (P=.042), while flare scores were higher in the TA group on day 1 (P=.015) but lower at month 1 (P=.044). The complication rates were higher in the TA group on day 1 (P=.04). All other outcome measures were similar for both groups. CONCLUSIONS: Intracameral TA did not affect the success rates or change the complication rates of glaucoma surgery.