To evaluate the 2-year outcomes of uveitic macular edema.
Longitudinal follow-up of a randomized cohort.
At baseline, 148 eyes of 117 patients enrolled in the Multicenter Uveitis Steroid Treatment ...(MUST) Trial had macular edema, and 134 eyes of 108 patients completed 2-year follow-up.
Patients enrolled in the study were randomized to either systemic immunosuppression or intravitreal fluocinolone acetonide implant therapy. Macular edema was defined as thickening of the retina (center point thickness≥240 μm) on time-domain optical coherence tomography (OCT) of macula.
Improvement in macular edema (≥20% reduction in central point thickness on OCT), resolution of macular edema (normalization of thickness on OCT), and best-corrected visual acuity (BCVA).
Between randomization and 2-years' follow-up, 62% and 25% of eyes in the systemic and implant groups, respectively, received at least 1 supplemental regional corticosteroid injection. By 2-years' follow-up, macular edema improved in 71% of eyes and resolved in 60%. There were no differences between treatment groups in the proportion of eyes with macular edema improving (systemic therapy vs. implant, 65% vs. 77%; P=0.20) and resolving (52% vs. 68%; P=0.28), but eyes randomized to implant had more improvement in macular thickness (median decrease of 180 vs. 109 μm in the systemic therapy group; P=0.04). Eyes with baseline fluorescein angiographic leakage were more likely to improve than those without (76% vs. 58%; P=0.03). Overall, there was a mean 5-letter (1 line) improvement in BCVA at 2 years. Mean changes in BCVA from baseline at 2 years by macular edema response status were: resolution, +10 letters; improvement without resolution, +10 letters (P=0.92); little to no change, 6 letters (P=0.19); and worsening, -16 letters (worsening acuity; P=0.0003).
About two thirds of eyes with uveitic macular edema were observed to experience improvement in the edema and visual acuity with implant or systemic treatment. Fluocinolone acetonide implant therapy was associated with a greater quantitative improvement in thickness. Fluorescein angiography leakage was associated with a greater likelihood of improvement in macular edema.
Background: The initiation and acceleration of atherosclerosis is hypothesized as a physiologic mechanism underlying associations between air pollution and cardiovascular effects. Despite toxicologic ...evidence, epidemiologic data are limited. Methods: In this cross-sectional analysis we investigated exposure to fine particulate matter ( $\text{PM}_{2.5}$ ) and residential proximity to major roads in relation to abdominal aortic calcification, a sensitive indicator of systemic atherosclerosis. Aortic calcification was measured by computed tomography among 1147 persons, in 5 US metropolitan areas, enrolled in the Multi-Ethnic Study of Atherosclerosis. The presence and quantity of aortic calcification were modeled using relative risk regression and linear regression, respectively, with adjustment for potential confounders. Results: We observed a slightly elevated risk of arotic calcification (RR = 1.06; 95% confidence interval = 0.96-1.16) with a 10 μg/m³ contrast in $\text{PM}_{2.5}$ . The $\text{PM}_{2.5}-\text{associated}$ risk of aortic calcification was stronger among participants with long-term residence near a $\text{PM}_{2.5}$ monitor (RR = 1.11; 1.00-1.24) and among participants not recently employed outside the home (RR = 1.10; 1.00-1.22). $\text{PM}_{2.5}$ was not associated with an increase in the quantity of aortic calcification (Agatston score) and no roadway proximity effects were noted. There was indication of $\text{PM}_{2.5}$ effect modification by lipid-lowering medication use, with greater effects among users, and $\text{PM}_{2.5}$ associations were observed most consistently among Hispanics. Conclusions: Although we did not find persuasive associations across our full study population, associations were stronger among participants with less exposure misclassification. These findings support the hypothesis of a relationship between particulate air pollution and systemic atherosclerosis.
Background In a recent multicenter randomized trial comparing unfractionated heparin (UFH) with low-molecular-weight heparin (dalteparin) for thromboprophylaxis in 3,746 critically ill patients, 17 ...patients (0.5%) developed heparin-induced thrombocytopenia (HIT) based on serotonin-release assay-positive (SRA+) status. A trend to a lower frequency of HIT with dalteparin vs UFH was observed in the intention-to-treat analysis (five vs 12 patients, P = .14), which was statistically significant (three vs 12 patients, P = .046) in a prespecified per-protocol analysis that excluded patients with DVT at study entry. We sought to characterize HIT outcomes and to determine how dalteparin thromboprophylaxis may reduce HIT frequency in patients in the ICU. Methods In 17 patients with HIT, we analyzed platelet counts and thrombotic events in relation to the study drug and other open-label heparin, to determine whether the study drug plausibly explained seroconversion to SRA+ status and/or breakthrough of thrombocytopenia/thrombosis. We also compared antibody frequencies (dalteparin vs UFH) in 409 patients serologically investigated for HIT. Results HIT-associated thrombosis occurred in 10 of 17 patients (58.8%) (8:1:1 venous:arterial:both). Dalteparin was associated with fewer study drug-attributable HIT-related events ( P = .020), including less seroconversion ( P = .058) and less breakthrough of thrombocytopenia/thrombosis ( P = .032). Antiplatelet factor 4/heparin IgG antibodies by enzyme-linked immunosorbent assay were less frequent among patients receiving dalteparin vs UFH (13.5% vs 27.3%, P < .001). One patient with HIT-associated DVT died after UFH bolus (anaphylactoid reaction), whereas platelet counts recovered in two others with HIT-associated VTE despite continuation of therapeutic-dose UFH. Conclusions The lower risk of HIT in patients in the ICU receiving dalteparin appears related to both decreased antibody formation and decreased clinical breakthrough of HIT among patients forming antibodies.
Little is known about patterns of tuberculosis (TB) transmission among populations in developing countries with high rates of TB and human immunodeficiency virus (HIV) infection. To examine patterns ...of TB transmission in such a setting, we performed a population-based DNA fingerprinting study among TB patients in Botswana. Between January 1997 and July 1998, TB patients from four communities in Botswana were interviewed and offered HIV testing. Their Mycobacterium tuberculosis isolates underwent DNA fingerprinting using IS6110 restriction fragment length polymorphism, and those with matching fingerprints were reinterviewed. DNA fingerprints with >5 bands were considered clustered if they were either identical or differed by at most one band, while DNA fingerprints with < or =5 bands were considered clustered only if they were identical. TB isolates of 125 (42%) of the 301 patients with completed interviews and DNA fingerprints fell into 20 different clusters of 2 to 16 patients. HIV status was not associated with clustering. Prior imprisonment was the only statistically significant risk factor for clustering (risk ratio, 1.5; 95% confidence interval, 1.1 to 2.0). In three communities where the majority of eligible patients were enrolled, 26 (11%) of 243 patients overall and 26 (25%) of 104 clustered patients shared both a DNA fingerprint and strong antecedent epidemiologic link. Most of the increasing TB burden in Botswana may be attributable to reactivation of latent infection, but steps should be taken to control ongoing transmission in congregate settings. DNA fingerprinting helps determine loci of TB transmission in the community.
We hypothesized that fibrosis detected by late gadolinium enhancement (LGE) cardiovascular magnetic resonance predicts outcomes in patients with transposition of the great arteries post atrial ...redirection surgery. These patients have a systemic right ventricle (RV) and are at risk of arrhythmia, premature RV failure, and sudden death.
Fifty-five patients (aged 27±7 years) underwent LGE cardiovascular magnetic resonance and were followed for a median 7.8 (interquartile range, 3.8-9.6) years in a prospective single-center cohort study. RV LGE was present in 31 (56%) patients. The prespecified composite clinical end point comprised new-onset sustained tachyarrhythmia (atrial/ventricular) or decompensated heart failure admission/transplantation/death. Univariate predictors of the composite end point (n=22 patients; 19 atrial/2 ventricular tachyarrhythmia, 1 death) included RV LGE presence and extent, RV volumes/mass/ejection fraction, right atrial area, peak Vo(2), and age at repair. In bivariate analysis, RV LGE presence was independently associated with the composite end point (hazard ratio, 4.95 95% confidence interval, 1.60-15.28; P=0.005), and only percent predicted peak Vo(2) remained significantly associated with cardiac events after controlling for RV LGE (hazard ratio, 0.80 95% confidence interval, 0.68-0.95; P=0.009/5%). In 8 of 9 patients with >1 event, atrial tachyarrhythmia, itself a known risk factor for mortality, occurred first. There was agreement between location and extent of RV LGE at in vivo cardiovascular magnetic resonance and histologically documented focal RV fibrosis in an explanted heart. There was RV LGE progression in a different case restudied for clinical indications.
Systemic RV LGE is strongly associated with adverse clinical outcome especially arrhythmia in transposition of the great arteries, thus LGE cardiovascular magnetic resonance should be incorporated in risk stratification of these patients.
The goal of this study was to develop a primary culture model of differentiated murine tracheal epithelium. When grown on semipermeable membranes at an air interface, dissociated murine tracheal ...epithelial cells formed confluent polarized epithelia with high transepithelial resistances ( approximately 12 kOmega. cm(2)) that remained viable for up to 80 days. Immunohistochemistry and light and electron microscopy demonstrated that the cells were epithelial in nature (cytokeratin positive, vimentin and alpha-smooth muscle actin negative) and differentiated to form ciliated and secretory cells from day 8 after seeding onward. With RT-PCR, expression of the cystic fibrosis transmembrane conductance regulator (Cftr) and murine beta-defensin (Defb) genes was detected (Defb-1 was constitutively expressed, whereas Defb-2 expression was induced by exposure to lipopolysaccharide). Finally, Ussing chamber experiments demonstrated an electrophysiological profile compatible with functional amiloride-sensitive sodium channels and cAMP-stimulated CFTR chloride channels. These data indicate that primary cultures of murine tracheal epithelium have many characteristics similar to those of murine tracheal epithelium in vivo. This method will facilitate the establishment of primary cultures of airway epithelium from transgenic mouse models of human diseases.
This study objectively compares efficacy of dexamethasone Na phosphate 0.1%, fluorometholone 0.1% (FML), loteprednol etabonate 0.5% (Lotemax LE; Bausch & Lomb Pharmaceuticals, Inc., Tampa, FL), ...prednisolone acetate 1% (Pred Forte PRED F; Allergan Pharmaceuticals, Irvine, CA), and generic prednisolone acetate 1% (PRED A). These steroids were administered for 24 hours or 72 hours to New Zealand white rabbits with endotoxin-induced uveitis. Intraocular pressure (IOP), slit-lamp examination, and confocal microscopy were performed daily. Internalization of the glucocorticoid receptor (GC) was assayed in iris tissue by Western blot, and protein in aqueous humor by Bradford assay. Only LE and PRED F treatments significantly internalized GC receptor after 72 hours of treatment. Only LE and PRED A reduced protein concentration between 24 hours and 72 hours of treatment. All drugs improved clinical signs after 24 hours of treatment. None of the steroids promoted return of the inflammation-induced corneal thickness to baseline. While none returned IOP to baseline, LE was most effective. Confocal microscopy indicated that only treatment with LE reverted the abnormal endothelial-cell shape to normal. In conclusion, all steroid treatments reduced uveitis to some degree but LE was consistently effective. A longer observation period may be required to document the return of IOP and corneal thickness to baseline values.
Pterygium, a sun-related eye disease, presents as wing-shaped ocular surface lesions that extend from the bulbar conjunctiva onto the cornea, most commonly on the nasal side. Pterygia show ...characteristic histological features that suggest that inflammation plays a prominent role in their initial pathogenesis and recurrence. Appropriate surgery is the key to successful treatment of pterygia, but there is also a rationale for the use of anti-inflammatory agents to reduce the rate of recurrence following surgery. Multiple surgical techniques have been developed over the last two millennia, but these initially had little success, due to high rates of recurrence. Current management strategies, associated with lower recurrence rates, include bare sclera excision and various types of grafts using tissue glues. Adjunctive therapies include mitomycin C and 5-fluorouracil, as well as the topical ocular steroid loteprednol etabonate, which has been shown to have a lower risk of elevated intraocular pressure than have the other topical ocular steroids. Here, the surgical management of pterygium is presented from a historical perspective, and current management techniques, including the appropriate use of various adjunctive therapies, are reviewed, along with an illustrative case presentation and a discussion of the conjunctival forceps designed to facilitate surgical management. Despite thousands of years of experience with this condition, there remains a need for a more thorough understanding of pterygium and interventions to reduce both its incidence and postsurgical recurrence. Until that time, the immediate goal is to optimize surgical practices to ensure the best possible outcomes. Loteprednol etabonate, especially the ointment formulation, appears to be a safe and effective component of the perioperative regimen for this complex ocular condition, although confirmatory prospective studies are needed.
PDF
