The ßLys66Tyr Variant of Human Hemoglobin as a Component of a Blood Substitute.

It has been proposed that introducing tyrosine residues into human hemoglobin (e.g. ßPhe41Tyr) may be able to reduce the toxicity of the ferryl heme species in extracellular hemoglobin-based oxygen carriers (HBOC) by facilitating long-range electron transfer from endogenous and exogenous antioxidants. Surface-exposed residues lying close to the solvent exposed heme edge may be good candidates for mutations. We therefore studied the properties of the ßLys66Tyr mutation. Hydrogen peroxide (H2O2) was added to generate the ferryl protein. The ferryl state in ßLys66Tyr was more rapidly reduced to ferric (met) by ascorbate than recombinant wild type (rwt) or ßPhe41Tyr. However, ßLys66Tyr suffered more heme and globin damage following H2O2 addition as measured by UV/visible spectroscopy and HPLC analysis. ßLys66Tyr differed notably from the rwt protein in other ways. In the ferrous state the ßLys66Tyr forms oxy, CO, and NO bound heme complexes similar to rwt. However, the kinetics of CO binding to the mutant was faster than rwt, suggesting a more open heme crevice. In the ferric (met) form the typical met Hb acid-alkaline transition (H2O to -OH) appeared absent in the mutant protein. A biphasicity of cyanide binding was also evident. Expression in E. coli of the ßLys66Tyr mutant was lower than the rwt protein, and purification included significant protein heterogeneity. Whilst, ßLys66Tyr and rwt autoxidised (oxy to met) at similar rates, the oxygen p50 for ßLys66Tyr was very low. Therefore, despite the apparent introduction of a new electron transfer pathway in the ßLys66Tyr mutant, the heterogeneity, and susceptibility to oxidative damage argue against this mutant as a suitable starting material for a HBOC.

Severe retinal injuries from paintball projectiles.

BACKGROUND: To determine the outcomes and circumstances of retinal injuries caused by blunt trauma from paintball pellet projectiles. METHODS: Retrospective case series of all patients who presented with retinal injuries due to paintball-related trauma to 2 retina specialists in a clinical setting from 2004 to 2005. Patients were followed for a mean of 7.3 months, and retinal trauma was documented with retinal photographs and ocular coherence tomography as needed. Best corrected visual acuity (BCVA) was the main outcome measure. RESULTS: Three eyes of 3 patients suffered severe retinal injuries after blunt trauma from a paintball pellet. Together, the 3 eyes demonstrated extensive retinal findings, including commotio retinae, choroidal rupture, and macular hole. BCVA at last follow-up ranged from 20/80 to hand motions. INTERPRETATION: Our small case series indicates that retinal trauma from paintball injuries is not uncommon and results in severe long-term visual morbidity. The sale of paintball guns and pellets should be strictly prohibited for minors, and adults should be educated about the need for appropriate ocular protection and the potentially serious consequences of the use of these guns outside of commercial settings.

Safety profile of intravitreal triamcinolone acetonide.

BACKGROUND: There is currently a widespread use of intravitreal triamcinolone acetonide (IVTA) for age-related macular degeneration, diabetic macular edema, cystoid macular edema secondary to retinal vein occlusions, and uveitis. The aim of this investigation was to assess the rates of various complications associated with this treatment and to determine which factors are associated with the development of these complications. METHODS: A retrospective interventional case series of all patients from one retina specialist undergoing IVTA was conducted in a clinical setting from 2002 to 2005. All disease entities were included. Patients were followed for a mean of 9.5 months after receiving 4 mg (0.1 mL) of nonfiltered triamcinolone acetonide (TA). All complications associated with the injection procedure or with the TA were noted. RESULTS: Two hundred and twenty-three (223) eyes of 192 patients received a total of 336 IVTA injections between 2002 and 2005. The mean age was 73.3 years and mean follow-up was 9.5 months. A single injection was performed in 144 eyes (64.6%); 2 IVTAs in 55 eyes (24.7%); 3 IVTAs in 16 eyes (7.2%), and 3.6% of eyes had more than 3 injections at a minimal interval of 3 months. The only immediate complication was a single injection (0.3%) associated with a temporary occlusion of the central retinal artery, which opened immediately following anterior paracentesis. Late complications included endophthalmitis in 1 of 336 (0.3%) injections and a steroid response requiring glaucoma medication in 60 of 192 patients (31.3%). In patients with preexisting glaucoma, 58.8% required additional glaucoma medication. Glaucoma-filtering surgery was required in 2 of 192 patients (1.0%). CONCLUSIONS: In the study center, the IVTA is extremely safe in patients without a history of glaucoma. However, patients with preexisting glaucoma with progressive optic neuropathy must be treated with great caution.