Head C.A.,Georgia Regents University |
Swerdlow P.,Wayne State University |
McDade W.A.,University of Chicago |
Joshi R.M.,Dean McGee Eye Institute |
And 3 more authors.
American Journal of Hematology | Year: 2010
Pain from vaso-occlusive crisis (VOC) is the major cause of hospitalization in patients with sickle cell disease (SCD). The beneficial therapeutic effects of inhaled nitric oxide (NO) on the pathophysiology of SCD have been reported. A double-blind, randomized, placebo-controlled clinical trial was conducted to determine whether NO breathing reduces acute VOC pain in adult patients and to study the safety of inhaled NO. Twenty-three patients experiencing acute VOC were enrolled. After randomization but before treatment, five were found to not meet final eligibility criteria. Nine patients were assigned to inhaled NO (80 ppm) and nine to placebo (21% O2). Primary outcome was the mean change in pain scores after 4 hr of inhalation, measured on a 10-cm visual analog scale (VAS). Both groups had similar baseline VAS pain scores but inhaled NO significantly reduced pain scores compared with placebo (P = 0.02) at the end of NO inhalation. Secondary outcome was parenteral morphine use at baseline, 4, and 6 hr. Parenteral morphine use was lower in the inhaled NO group, but the difference was not statistically significant. Safety assessments included systolic blood pressure measurements, pulse oximetry readings, concentration of delivered nitrogen dioxide, and concentration of methemoglobin (metHb). None of these NO toxicities was observed.
Agbaga M.-P.,The University of Oklahoma Health Sciences Center |
Agbaga M.-P.,Dean McGee Eye Institute |
Tam B.M.,University of British Columbia |
Wong J.S.,University of British Columbia |
And 4 more authors.
Investigative Ophthalmology and Visual Science | Year: 2014
Purpose. Autosomal dominant Stargardt macular dystrophy caused by mutations in the Elongation of Very Long Chain fatty acids (ELOVL4) gene results in macular degeneration, leading to early childhood blindness. Transgenic mice and pigs expressing mutant ELOVL4 develop progressive photoreceptor degeneration. The mechanism by which these mutations cause macular degeneration remains unclear, but have been hypothesized to involve the loss of an ER-retention dilysine motif located in the extreme C-terminus. Dominant negative mechanisms and reduction in retinal polyunsaturated fatty acids also have been suggested. To understand the molecular mechanisms involved in disease progression in vivo, we addressed the hypothesis that the disease-linked C-terminal truncation mutant of ELOVL4 exerts a dominant negative effect on wild-type (WT) ELOVL4, altering its subcellular localization and function, which subsequently induces retinal degeneration and loss of vision. Methods. We generated transgenic Xenopus laevis that overexpress HA-tagged murine ELOVL4 variants in rod photoreceptors. Results. Tagged or untagged WT ELOVL4 localized primarily to inner segments. However, the mutant protein lacking the dilysine motif was mislocalized to post-Golgi compartments and outer segment disks. Coexpression of mutant and WT ELOVL4 in rods did not result in mislocalization of the WT protein to outer segments or in the formation of aggregates. Fulllength HA-tagged ELOVL4 lacking the dilysine motif (K308R/K310R) necessary for targeting the WT ELOVL4 protein to the endoplasmic reticulum was similarly mislocalized to outer segments. Conclusions. We propose that expression and outer segment mislocalization of the diseaselinked 5-base-pair deletion mutant ELOVL4 protein alters photoreceptor structure and function,which subsequently results in retinal degeneration, and suggest three possible mechanisms by which mutant ELOVL4 may induce retinal degeneration in STGD3. © 2014 The Association for Research in Vision and Ophthalmology, Inc.
Zhang Q.,Emory University |
Randleman J.B.,Emory University |
Stulting R.D.,Emory University |
Lee W.B.,Eye Consultants of Atlanta |
And 4 more authors.
Archives of Ophthalmology | Year: 2010
Objective: To evaluate the clinical features of and histologic findings from failed Descemet stripping automated endothelial keratoplasty (DSAEK). Methods: This retrospective observational case series evaluated 47 consecutive corneal specimens from 42 patients who underwent either penetrating keratoplasty or repeated DSAEK for failed DSAEK. Clinical information was obtained for the cases. Sections of the specimenswere examined using light microscopy. Immunohistochemical staining was performed for cytokeratins AE1/AE3 and for the myogenic marker smooth-muscle actin when indicated. Transmission electron microscopic examination was performed in some cases. Results: Graft survival ranged from 0.5 to 34 months. Histologic examination showed that 94% of the specimens (44 of 47) had endothelial cell loss. Residual host Descemet membrane (19%; 9 of 47), fibrocellular tissue (19%; 9 of 47), epithelial implantation (15%; 7 of 47), and fungal infection (4%; 2 of 47) were also identified. Immunohistochemical stains were positive for AE1/AE3 in the epithelial implantations and for smooth-muscle actin in cells in the fibrocellular proliferations. Conclusions: The principal cause of failed DSAEK is endothelial cell loss. Residual host Descemet membrane, fibrocellular tissue at the edge of the lenticule, and epithelial implantation are common histologic findings. Fungal infection may occur in the setting of DSAEK. ©2010 American Medical Association. All rights reserved.
Allan E.J.,Dean McGee Eye Institute |
Khaimi M.A.,Dean McGee Eye Institute |
Jones J.M.,The University of Oklahoma Health Sciences Center |
Ding K.,The University of Oklahoma Health Sciences Center |
Skuta G.L.,Dean McGee Eye Institute
Ophthalmology | Year: 2015
Purpose To investigate the long-term surgical outcomes of the Baerveldt 250 mm2 versus Baerveldt 350 mm2 glaucoma drainage implants (GDIs) (Abbott Laboratories Inc., Abbott Park, IL) in the treatment of refractory glaucoma. Design Comparative case study. Participants A total of 89 consecutive eyes in 86 patients treated at Dean McGee Eye Institute between January 2006 and December 2008. Methods We retrospectively reviewed patient data from the following postoperative visits: 1 week, 1 month, 2 months, 3 months, 6 months, and every 3 months thereafter. Postoperative complications were also recorded. The mean follow-up time was 40 months (range, 2-78 months) for the Baerveldt 250 mm2 group and 31 months (range, 3-75 months) for the Baerveldt 350 mm2 group. Main Outcome Measures The primary outcome measure was surgical success. Secondary outcome measures included visual acuity (VA), intraocular pressure (IOP), and number of medications. Results There was no difference in surgical success (P = 0.98). No significant differences were observed in VA measured using the logarithm of the minimum angle of resolution (logMAR) scale, IOP, and number of medications at the last visit (P = 0.09, 0.23, and 0.82, respectively). Complication and failure rates were comparable (P = 0.82 and 0.64, respectively). Conclusions With a mean follow-up of 40 and 31 months, no differences in surgical success, VA, IOP, number of medications at the last visit, and complication/failure rates were noted between the Baerveldt 250 mm2 and 350 mm2 GDIs, respectively. The size of the GDI may not be associated with surgical outcomes. © 2015 American Academy of Ophthalmology.
Sluch I.M.,Dean McGee Eye Institute |
Siatkowski R.L.,Dean McGee Eye Institute |
Shah V.A.,Dean McGee Eye Institute
Cornea | Year: 2016
Purpose: To report a case of Mycobacterium chelonae scleral abscess after an intravitreal injection of ranibizumab. Methods: A 54-year-old female received an intravitreal ranibizumab injection for diabetic macular edema. Two weeks postinjection, a scleral abscess developed at the injection site. The patient was treated with incision and drainage of the abscess, subconjunctival injection of amikacin, topical clarithromycin and amikacin, and oral clarithromycin. Results: After 4 weeks of treatment, the inflammation and infection resolved, and the patient returned to best-corrected preinjection visual acuity. Conclusions: Injection-site scleral abscesses are very rare and serious complications of intravitreal injections. Once the abscess is drained, it is possible to identify the organism and treat the infection with appropriate combination antibiotic therapy. © 2016 Wolters Kluwer Health, Inc.