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Biomedical subjects

J Sugar

Publications and source records attributed to J Sugar.

At least 55 records · Page 3Linked to original sources

Outcome of penetrating keratoplasty after ocular trauma in children.

OBJECTIVE: To characterize the outcome of penetrating keratoplasty in children for the visual rehabilitation of corneal injury. DESIGN: Multicenter retrospective study of the outcome of penetrating keratoplasty for ocular trauma in children. PATIENTS: All children aged 12 years and younger who underwent penetrating keratoplasty between January 1975 and May 1993 for penetrating corneal (n = 18) or corneoscleral (n = 3) trauma and nonpenetrating corneal trauma (n = 1). MAIN OUTCOME MEASURES: Graft survival and postoperative visual acuity improvement. RESULTS: Twenty-two children underwent 25 penetrating keratoplasties during the study period. Graft survival was 84% at 1 year and 70% at 2 years after surgery. Visual acuity improved in 15 (83%) of the 18 children with measurable preoperative and postoperative vision. Children with posterior segment injury before keratoplasty were less likely to maintain a clear graft (P = .04) and less likely to have improved vision postoperatively (P = .06). Children who received amblyopia treatment and appropriate optical correction postoperatively were more likely to have visual improvement than those who did not (P = .02). CONCLUSIONS: Penetrating keratoplasty for corneal trauma is generally a successful operation in the pediatric age group, with visual improvement seen in more than four fifths of cases. Graft survival and visual outcome are best in patients with trauma limited to the anterior segment. Aggressive postoperative refractive correction and amblyopia management also appear to contribute to a better visual outcome in pediatric keratoplasty.

Child↗

The indications for and outcome in pediatric keratoplasty. A multicenter study.

PURPOSE: A multicenter study was undertaken to delineate the indications for and outcome of pediatric keratoplasty. METHODS: The authors retrospectively studied 164 grafts in 131 eyes of 108 children younger than 12 years of age, with an average follow-up of 45 months. Multivariate linear and logistic regression was performed to evaluate potential risk factors for poor visual outcome and graft failure. Graft survival was depicted in terms of the Kaplan-Meier survival curve. RESULTS: Corneal opacities were grouped into three diagnostic categories: congenital (64%), traumatic (17%), and acquired nontraumatic (19%) opacities. Overall graft survival was 80% at 12 months and 67% at 24 months postoperatively. There was no significant difference in retention of clarity among diagnostic groups. Vitrectomy-lensectomy, regrafts, and postoperative complications were associated significantly with poor allograft survival. Eighteen percent of all eyes had worse vision at the time of the last visit than preoperatively. Amblyopia treatment was the only independently significant prognosticator for visual improvement after surgery. Timing of keratoplasty was not demonstrated to be associated with visual outcome. Visual acuity in 33% of eyes that could be quantified was better than 20/200 at the last visit, whereas 62% of eyes retained full graft clarity. CONCLUSION: The authors conclude that keratoplasty can be successful in most children, especially when combined with appropriate amblyopia management.

Amblyopia↗

Ocular manifestations of leprosy in a noninstitutionalized community in the United States.

OBJECTIVE: Our goal was to delineate the epidemiologic and clinical patterns of ocular leprosy in an outpatient setting in the United States. DESIGN: Examinations were performed in 61 consecutive outpatients seen in a Midwestern leprosy clinic. PATIENTS: Forty-three male and 18 female patients were examined. The patients' origins included Southeast Asia (24 patients [39%]), Latin America (23 patients [38%]), India (nine patients [15%]), Europe or North America (two patients [3%]), Africa (two patients [3%]), and the Middle East (one patient [2%]). RESULTS: Thirty-nine percent of patients were classified as having polar lepromatous leprosy; 18%, borderline lepromatous leprosy; 3%, borderline borderline leprosy; 36%, borderline tuberculoid leprosy; 2%, polar tuberculoid leprosy; and 2%, indeterminate leprosy. Ninety-six percent of patients had a best-corrected visual acuity of 20/40 or better. Ocular findings included madarosis (28 patients [46%]), subconjunctival fibrosis (18 patients [30%]), punctate epithelial keratopathy (17 patients [28%]), posterior subcapsular cataract (10 patients [16%]), corneal hypesthesia (10 patients [16%]), lagophthalmos (seven patients [11%]), corneal pannus (six patients [10%]), entropion (five patients [8%]), prominent or beaded corneal nerves (four patients [7%]), iridocyclitis (four patients [7%]), focal avascular keratitis (three patients [5%]), scleritis (three patients [5%]), interstitial keratitis (two patients [3%]), iris pearls (two patients [3%]), and ocular clofazimine crystals (two patients [3%]). Madarosis, corneal hypesthesia, and posterior subcapsular cataracts were significantly associated with disease duration (P < .05). CONCLUSION: We report herein a relatively low frequency of visual impairment attributable to leprosy in our series compared with that seen among institutionalized leprous patients. However, since 48% of subjects had one or more sight-threatening complications as a result of their disease, a program of regular ophthalmic follow-up is strongly advocated for all patients with leprosy.

Adolescent↗

Lysosomal enzyme activities in conjunctival tissues of patients with keratoconus.

OBJECTIVE: To examine the lysosomal enzyme activities in the conjunctival tissues of patients with keratoconus. METHODS: Tissues collected from 11 patients with keratoconus, eight patients with senile cataract, three patients with Fuchs' corneal dystrophy, and 11 normal control subjects were processed for histochemical staining for two lysosomal hydrolases, acid esterase and acid phosphatase. RESULTS: The epithelium of all conjunctival specimens stained positively for the two enzymes. The staining in the conjunctival tissues of patients with keratoconus was more prominent than that seen in specimens from either normal control subjects or patients with other diseases. CONCLUSION: Our results suggest that the conjunctival epithelium may be altered in keratoconus. Elevation of lysosomal enzyme levels has been demonstrated in the epithelium of corneas with keratoconus, implicating a role of this layer in the disease. The conjunctival abnormality seems to corroborate the corneal epithelial theory. It also adds one dimension to the pathogenesis of keratoconus.

Acetylesterase↗

Herpetic Eye Disease Study. A controlled trial of oral acyclovir for herpes simplex stromal keratitis.

PURPOSE: To evaluate the efficacy of oral acyclovir in treating stromal keratitis caused by herpes simplex virus (HSV) in patients receiving concomitant topical corticosteroids and trifluridine. METHODS: The authors performed a randomized, double-masked, placebo-controlled, multicenter trial in 104 patients with HSV stromal keratitis without accompanying HSV epithelial keratitis. Sample size was chosen so that a 5%, one-tailed test would have an 80% chance of detecting a doubling of the median time to treatment failure. Patients were randomized to receive a 10-week course of either oral acyclovir (400 mg 5 times daily, n = 51) or placebo (n = 53). All patients also received a standard regimen of topical prednisolone phosphate and trifluridine. Ophthalmologic examinations were performed weekly during the 10-week treatment period, every 2 weeks for an additional 6 weeks, and at 6 months after entry into the trial. RESULTS: The median time to treatment failure (defined as worsening or no improvement of stromal keratitis or an adverse event) was 84 days (95% confidence interval, 69-93 days) for the acyclovir group and 62 days (95% confidence interval, 57-90 days) for the placebo group. By 16 weeks, 38 patients (75%) in the acyclovir group and 39 patients (74%) in the placebo group had failed treatment. Also by that time, the keratitis had resolved with trial medications, and there was no subsequent worsening in nine patients (18%) in the acyclovir group and ten (19%) in the placebo group. None of these results were significantly different between the two groups. However, visual acuity improved over 6 months in significantly more patients in the acyclovir group than in the placebo group. CONCLUSION: There was no statistically or clinically significant beneficial effect of oral acyclovir in treating HSV stromal keratitis in patients receiving concomitant topical corticosteroids and trifluridine with regard to time to treatment failure, proportion of patients who failed treatment, proportion of patients whose keratitis resolved, time to resolution, or 6-month best-corrected visual acuity. Visual acuity improved over 6 months in more patients in the acyclovir group than in the placebo group.

Acyclovir↗

Herpetic Eye Disease Study. A controlled trial of topical corticosteroids for herpes simplex stromal keratitis.

PURPOSE: To evaluate the efficacy of topical corticosteroids in treating herpes simplex stromal keratitis. METHODS: The authors performed a randomized, double-masked, placebo-controlled, multicenter clinical trial of 106 patients with active herpes simplex stromal keratitis who had not received any corticosteroids for at least 10 days before study enrollment. Patients were assigned to the placebo group (n = 49) or the steroid group (topical prednisolone phosphate; n = 57); both regimens were tapered over 10 weeks. Both groups received topical trifluridine. Visual acuity assessment and slit-lamp biomicroscopy were performed weekly for 10 weeks, every other week for an additional 6 weeks or until removal from the trial, and at 6 months after randomization. RESULTS: The time to treatment failure (defined by specific criteria as persistent or progressive stromal keratouveitis or an adverse event) was significantly longer in the steroid group compared with the placebo group. Compared with placebo, corticosteroid therapy reduced the risk of persistent or progressive stromal keratouveitis by 68%. The time from randomization to resolution of stromal keratitis and uveitis was significantly shorter in the steroid group compared with the placebo group even though both groups included patients who were removed from the study and treated with topical corticosteroids according to best medical judgment. Nineteen (33%) of the steroid-treated patients and 11 (22%) of the placebo-treated patients completed the 10 weeks of protocol therapy and had stable, noninflamed corneas after 16 weeks. At 6 months after randomization, no clinically or statistically significant differences in visual outcome or recurrent herpetic eye disease were identified between the steroid and placebo groups. CONCLUSIONS: The topical corticosteroid regimen used in this study was significantly better than placebo in reducing persistence or progression of stromal inflammation and in shortening the duration of herpes simplex stromal keratitis. Postponing steroids during careful observation for a few weeks delayed resolution of stromal keratitis but had no detrimental effect as assessed by visual outcome at 6 months.

Administration, Topical↗

Alpha 2-macroglobulin levels in normal human and keratoconus corneas.

PURPOSE: To compare the levels of alpha 2-macroglobulin, one of the major proteinase inhibitors, in corneas with keratoconus to those in normal human corneas and corneas with other diseases. METHODS: An immunoperoxidase technique was used to visualize the presence of alpha 2-macroglobulin in the corneas. Western blot analysis was performed, and the levels of this inhibitor in extracts of keratoconus and normal human corneas were subsequently analyzed by a dot blot assay. RESULTS: alpha 2-Macroglobulin was demonstrated immunohistochemically in the epithelium, stroma, and endothelium of all corneal sections. Compared with normal human control specimens, the staining intensity in the epithelium of keratoconus corneas was markedly reduced. The majority of scarred and other diseased corneas exhibited normal staining intensity for alpha 2-macroglobulin. Dot blot assays showed that the alpha 2-macroglobulin levels in the epithelial and stromal extracts of keratoconus corneas were lower than those found in normal human control counterparts. CONCLUSION: Keratoconus corneas contained a reduced level of alpha 2-macroglobulin. This result lends further support to the hypothesis that degradation processes may be aberrant in keratoconus.

Adolescent↗

Microbial keratitis following penetrating keratoplasty.

A retrospective study of 36 cases of infectious keratitis in the graft following 885 consecutive penetrating keratoplasties was conducted to evaluate the spectrum of pathogens and the factors affecting graft survival. Gram positive cocci and gram negative rods were equally responsible (47% in both cases) for 94% of the infections. Epithelial defects were responsible for 64% of the ulcers; suture-related infections, for 36%. After the infectious keratitis resolved, only 50% of the patients had a clear graft. Because the visual prognosis is poor once infectious keratitis develops, aggressive treatment is essential as soon as any sign of infiltration appears.

Adolescent↗

Amyloid precursor protein in the cerebral cortex is rapidly and persistently induced by loss of subcortical innervation.

Lesions of the cholinergic nucleus basalis of Meynert elevate the ex vivo synthesis of beta amyloid precursor protein (beta-APP) in the cerebral cortex, a major projection region. We have found that this elevation is reflected by increased levels of beta-APP mRNA. The induction is rapid (occurring 60 min after placement of the lesion) and persistent (remaining for at least 45 days after lesioning). Two other subcortical lesions, which result in reductions of cortical adrenergic and serotonergic innervation, similarly induced cortical beta-APP. The beta-APP induction is reversible and does not require loss of the subcortical neurons. Infusion of lidocaine, a calcium antagonist that disrupts neurotransmitter release, into the nucleus basalis of Meynert leads to the temporary reduction of released acetylcholine in the cortex. In this model, beta-APP mRNA levels are elevated shortly after the infusion of lidocaine (90 min) but return to preinfusion levels 7 days after the lidocaine treatment. However, metabolic stresses of the brain, including chronic physostigmine, glucocorticoid, and diabetogenic treatments, fail to induce the beta-APP response. These results suggest that the induction of beta-APP is a specific response to the loss of functional innervation in the cortex. Importantly, these studies show that cortical beta-APP is induced by lesions that mimic the neurochemical deficits most frequently observed in Alzheimer disease.

5,7-Dihydroxytryptamine↗

Diffuse corneal clouding in siblings with fetal alcohol syndrome.

Three of four siblings born to parents with a history of heavy alcohol abuse had bilateral diffusely cloudy corneas at birth. These three siblings, who had mild systemic features of fetal alcohol syndrome, underwent corneal transplantations, and their specimens were examined by light and electron microscopy. Histologically, the alterations in Bowman's layer ranged from thickening to total loss. There were varying degrees of corneal stromal edema. The unique pathologic feature in the corneas was the anomaly of the anterior banded zone of Descemet's membrane, which was either absent, poorly formed, or thinned in the central and peripheral cornea. The corneal endothelium was attenuated or multilayered. The diffuse clouding and the range of histologic abnormalities in the corneas might be related to the maternal alcohol abuse.

Child, Preschool↗

Reversible phosphorylation of tau to form A68 in heat-shocked neuronal PC12 cells.

A68, the primary protein constituent of Alzheimer's disease-associated neurofibrillary tangles, is an abnormally phosphorylated form of the microtubule-associated protein tau. We find that A68 is formed in neuronal PC12 cells when the cells are subjected to a heat shock (45 degrees C for 30 min). A68 was identified by immunoprecipitation with two different anti-tau antibodies (tau-2 and Alz50). Upon separation by SDS-polyacrylamide gel electrophoresis, the tau immunoprecipitates from heat-shocked cells exhibited an additional polypeptide of reduced electrophoretic mobility (approximately 68 kDa) when compared to control cells. A68 was formed with heat shock in the presence of cycloheximide, suggesting that its production occurred by post-translational modification of existing polypeptides. The tau/A68 polypeptides were identified as phosphoproteins by incorporation of 32P into the immunoprecipitates. The phosphorylation of tau to form A68 was reversed with recovery of the intact cells from the heat shock. Finally, immunoprecipitation of lysates from heat-shocked cells with antibodies to heat shock protein (hsp) 72/73 resulted in co-precipitation of tau with hsp 72, which indicates a stable complex formation between these two proteins. On the other hand, A68 remained unassociated with hsp during the heat shock. These results suggest that tau is reversibly phosphorylated to form A68 in neuronal PC12 cells under conditions of stress.

Animals↗