Biomedical subjects
L A Levin
Publications and source records attributed to L A Levin.
Apoptosis of retinal ganglion cells in anterior ischemic optic neuropathy.
We identified retinal ganglion cells undergoing apoptosis, a form of programmed cell death, in an eye of a 70-year-old man with anterior ischemic optic neuropathy. The TUNEL (terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin end nick labeling) staining and the presence of condensed, fragmented nuclear bodies were used to identify apoptotic cells. Examination of TUNEL-stained retinal sections revealed occasional cells in the ganglion cell layer with pyknotic nuclei and brown reaction product, representing positive staining for chromosomal DNA breaks. Positive cells were sparsely distributed, consistent with the limited time in which apoptotic cells are identifiable before they are removed. The most likely explanation for these results is that injury to the retinal ganglion cell axon induces apoptosis. To our knowledge, this is the first report of human retinal ganglion cell apoptosis in an acute optic neuropathy.
The case report. When small is beautiful.
Explore the source record for details and available documents.
Traumatic optic neuropathy. A meta-analysis.
BACKGROUND: The management of traumatic optic neuropathy remains controversial. Reports of improvement have been published after observation alone, treatment with corticosteroids and surgical decompressions. OBJECTIVE: To systematically review the published literature about traumatic optic neuropathy using a meta-analysis. METHODS: We performed a retrospective literature review of case series and case reports of traumatic optic neuropathy. They include all English language cases and selected non-English language cases for which patient data were available. The cases were organized into four grades based on visual acuity and the locations and type of fracture. Grade 1 included patients with visual acuity greater than 20/200 in the affected eye and without a posterior orbit fracture; grade 2, patients with visual acuity between 20/200 and light perception; grade 3, patients without light perception or with a nondisplaced posterior orbital fracture and remaining vision; and grade 4, patients with no light perception and a displaced posterior orbital fracture. A meta-analysis was performed, analyzing for each case the recovery of visual acuity for treatment, fracture pattern, and grade. RESULTS: The recovery of vision in treated patients was significantly better than the recovery in patients receiving no treatment. No significant difference in improvement was found among patients treated with corticosteroids alone, with surgical decompression alone, or with corticosteroids and surgical decompression. Recovery was related to the severity of initial injury, as reflected in the grading system. A trend was noted for better improvement of visual acuity in patients without orbital fractures than those with orbital fractures, and also in patients with anterior orbital fractures than in patients with posterior fractures. CONCLUSIONS: Treatment with corticosteroids, extracranial decompression, or both, is better than no treatment of traumatic optic neuropathy. Because the data are insufficient to determine whether corticosteroids, surgery, or the use of both treatments is most effective, the findings of the ongoing International Optic Nerve Trauma Study should prove valuable. The standardized grading system we developed is a useful tool for comparing studies and treatment protocols.
Penetrating trauma with a meat thermometer.
Explore the source record for details and available documents.
Neural network differentiation of optic neuritis and anterior ischaemic optic neuropathy.
AIMS: The efficacy of an artificial intelligence technique, neural network analysis, was examined in differentiating two optic neuropathies with overlapping clinical profiles-idiopathic optic neuritis (ON) and non-arteritic anterior ischaemic optic neuropathy (AION). METHODS: A neural network was trained with data from 116 patients with 'gold standard' diagnoses of ON or AION. It was then tested with data from 128 patients with presumed ON or AION, and the correlation of the network's diagnosis with that of expert clinicians tabulated. RESULTS: The network agreed with the clinicians on 97.8% (88 of 90) of the patients with presumed ON and 94.7% (36 of 38) of the patients with presumed AION. Youth, female sex, better initial acuity, a central scotoma, subsequent improvement in acuity, or progressive disease biased the network towards a diagnosis of ON, while advanced age, male sex, presence of hypertension, poor initial acuity, an altitudinal field defect, disc oedema, or less improvement in acuity biased the network towards a diagnosis of AION. CONCLUSION: Neural network analysis is a useful technique for classification of optic neuropathies, particularly where there is overlap of clinical findings.
Clinical signs and symptoms requiring computed tomography and magnetic resonance imaging evaluation.
A summary of some of the clinically important symptoms and signs relating to disease of the afferent visual pathways, motility, and the orbit are presented. Common disorders are discussed in the context of choosing a neuroimaging study. Specific findings (e.g., pupillary abnormalities, types of nystagmus, visual field patterns) that may affect the type of study and the anatomic area that is imaged are emphasized.
Effect of lipid peroxidation inhibition on retinal ganglion cell death.
PURPOSE: To determine whether the lipid peroxidation inhibitor tirilazad mesylate can block the death of retinal ganglion cells induced by the inhibition of oxidative phosphorylation and glycolysis. METHODS: Rat retinal ganglion cells were labeled retrogradely with the fluorescent tracer DiI, and mixed cultures were prepared. Cell death was induced with chemical hypoxia, hypoglycemia, or glycolysis inhibition, and the effect on cell survival of tirilazad mesylate was assessed. RESULTS: Tirilazad mesylate enhanced relative ganglion cell survival after plating, with detectable effects at 200 nM and a maximal increase above diluent control of 148% +/- 2% at 20 microM. Relative survival at 24 hours in the presence of the complex IV inhibitor sodium cyanide (3 mM) was significantly greater when it was co-incubated with tirilazad mesylate than with diluent control (91.8% +/- 4.6% versus 39.3% +/- 7.1%; P = 0.008). Enhanced relative survival with tirilazad mesylate also was seen in cultures containing reduced glucose media. CONCLUSIONS: The lipid peroxidation blocker tirilazad mesylate inhibits retinal ganglion cell death in vitro. Because irreversible loss of retinal ganglion cells is the final common pathway in a variety of optic neuropathies, this or similar agents may be useful in animal models of optic neuropathies.
An astrocytic binding site for neuronal Thy-1 and its effect on neurite outgrowth.
Thy-1, a member of the immunoglobulin superfamily, is one of the most abundant glycoproteins on mammalian neurons. Nevertheless, its role in the peripheral or central nervous system is poorly understood. Certain monoclonal antibodies to Thy-1 promote neurite outgrowth by rodent central nervous system neurons in vitro, suggesting that Thy-1 functions, in part, by modulating neurite outgrowth. We describe a binding site for Thy-1 on astrocytes. This Thy-1-binding protein has been characterized by immunofluroesence with specific anti-idiotype monoclonal antibodies and by three competitive binding assays using (i) anti-idiotype antibodies, (ii) purified Thy-1, and (iii) Thy-1-transfected cells. The Thy-1-binding protein may participate in axonal or dendritic development in the nervous system.
Ophthalmology.
Those in the highest 20th percentile of dietary intake of carotenoids had a 43% lower risk of age-related macular degeneration. Rifabutin was implicated as causing hypopyon uveitis. The National Eye Institute issued a Clinical Alert advising against the use of optic nerve decompression for nonarteritic anterior ischemic optic neuropathy.
Clarifying the treatment of nonarteritic anterior ischemic optic neuropathy.
Explore the source record for details and available documents.
Beta 2-adrenergic receptors are expressed by glia in vivo in the normal and injured central nervous system in the rat, rabbit, and human.
Previous studies have demonstrated that glial cells in culture express several subtypes of functional adrenergic receptors. To determine if similar receptors are expressed by glia in vivo, we examined the expression of adrenergic receptors in the normal, crushed, and transected optic nerves of the rabbit and rat using quantitative receptor autoradiography. Additionally, we examined the expression of adrenergic receptors in the normal and damaged human optic nerve. High levels of alpha 1-, alpha 2-, beta 1-, and beta 2-adrenergic receptors were identified in the rabbit and rat forebrain. In the normal rabbit, rat, and human optic nerves, only alpha 1 and beta 2 receptors were observed, and these were present in low to moderate densities. Combined immunohistochemistry and autoradiography suggests that the majority of beta 2-adrenergic receptors in the rabbit, rat, and human optic nerve are expressed by astrocytes. After unilateral optic nerve crush or transection, only beta 2- adrenergic receptors were significantly increased. This increase in beta 2 receptors was first detectable at days 7 and 28 post-transection in the rabbit and rat, respectively. The expression of beta 2 receptors in the transected optic nerve continued to increase with time, so that by 90 d post-transection the density of beta 2 receptors in both the rabbit and rat optic nerve was among the highest of any area in the forebrain. Taken together with previous studies, these results suggest that in vivo, beta 2-adrenergic receptors may provide a therapeutic target for regulation of astrocyte functions including glycogen metabolism, cytokine release, and the hypertrophy and proliferation that occurs in response to neuronal injury.
Optic canal decompression in indirect optic nerve trauma.
BACKGROUND: The proper management of neurogenic visual loss after blunt head trauma is controversial. Non-treatment, corticosteroids, and surgical decompression of the optic canal are all currently considered to be reasonable alternatives. The goal of this study was to identify factors affecting improvement in patients treated with canal decompression. METHODS: A retrospective analysis of 31 cases in which transethmoidal decompression of the optic canal had been performed for neurogenic visual loss after closed head trauma was conducted. Each patient was alert and free of injury to the globe when evaluated before surgery. Surgery was performed within 6 days of injury, and all were given perioperative steroids. RESULTS: Visual acuity improved in 22 (71%) patients, with 6 (19%) regaining visual acuity of 20/40 or better. The mean improvement from preoperative visual deficit was 42.0% +/- 6.6%, with a median improvement of 45.2%. Both univariate and multivariate analysis suggested that vision improved more in patients who were younger than 40 years of age than in patients who were 40 years of age or older. Interval between injury and surgery, preoperative visual acuity, and the presence of optic canal fracture did not affect outcome. CONCLUSION: Any future randomized trials of therapy should stratify patients based on age. Enrollment of patients with no light perception or who experienced delay between injury and treatment may be reasonably considered.
Magnetic resonance angiography.
Explore the source record for details and available documents.
Nucleolar organizer regions in optic gliomas.
The biological nature of optic gliomas is controversial, with some considering them benign hamartomatous lesions, and others believing them to be true neoplasms. We evaluated the use of colloid silver impregnation of nucleolar organizer region-associated proteins (AgNORs) in making this distinction. Thirty-one optic gliomas, 14 optic nerve meningiomas, and a single case of giant cell glioblastoma multiforme (monstrocellular glioma) of the optic chiasm were stained for AgNORs and counted in a masked fashion. The optic gliomas contained 2.01 +/- 0.09 AgNORs per nucleus, similar to that of optic nerve meningiomas (2.15 +/- 0.15) and our previously reported counts for diffuse fibrillary astrocytoma (2.22 +/- 0.10), and significantly more than that of reactive astrocytosis (1.18 +/- 0.02). Six of the seven optic gliomas examined had compound AgNORs, a feature associated with malignancy in other tumour types. AgNOR counts did not correlate with clinical features, including those seen during the post-operation course. These data suggest that optic gliomas may be true neoplasms, and not benign hamartomas.
Mast cells in human optic nerve.
PURPOSE: Mast cells are classically found in ocular tissues within the conjunctiva, choroid, and iris. The aim of this study was to examine their distribution in the optic nerve and its meninges. METHODS: Sixty-six human optic nerves were studied from normal subjects at autopsy, fetuses aborted for chromosomal abnormalities, and from enucleation specimens of patients with a variety of inflammatory, traumatic, neoplastic, and vascular disorders. Mast cells were identified using a stain for the enzyme chloroacetate esterase, and confirmed using toluidine blue, revealing metachromatic cytoplasmic granules. RESULTS: Mast cells were found scattered in the meninges of almost all optic nerves examined, frequently in perivascular locations, with densities up to 2325 mast cells/mm3 (mean 269.7 +/- 64.1 cells/mm3 in normal nerves). Mast cells were found in the optic nerve parenchyma in nerves from four eyes that had severe abnormality, often associated with neovascularization. Normal nerves, as well as nerves from fetuses aborted for congenital defects, had significantly fewer meningeal mast cells than those from eyes with inflammatory or vascular diseases. Degranulation of mast cells was observed more often in eyes with recent severe trauma. CONCLUSIONS: Based on their work and the work of others suggesting an association between mast cells and nervous system autoimmune disorders, the authors hypothesize a role for optic nerve mast cells in certain ocular inflammatory conditions.
Astrocytes support mast cell viability in vitro.
Mast cells are normally found adjacent to blood vessels in the nervous system, and have been implicated in the development of inflammatory central nervous system (CNS) diseases such as experimental allergic encephalomyelitis. To further study mast cell-CNS interactions, we have developed a model in which viable rat peritoneal mast cells can be maintained in culture for up to 30 days on a monolayer of rat astrocytes. In this microenvironment, mast cells maintain their phenotype, morphology, and ability to degranulate in response to appropriate stimuli.
Cost-effectiveness of thrombolysis--a randomized study of intravenous rt-PA in suspected myocardial infarction.
The aim of this randomized placebo-controlled study is to ascertain the costs of intravenous thrombolytic therapy (rt-PA) in the first year after suspected myocardial infarction and to measure the treatment effect on quality of life. The main findings are that the direct costs (including all health care expenditure), on average were 9880 SEK higher in the rt-PA group (N = 153) than in the placebo group (N = 160). At the same time the indirect costs were 4200 SEK lower in the rt-PA group. The total cost of the first year after suspected myocardial infarction were on average 5680 SEK higher in the rt-PA group. The treatment gain in mean life expectancy calculated with a yearly mortality rate of 6% from the end of follow up was 1.25 years. Quality of life was measured using the Nottingham Health Profile and was classified according to NYHAs functional classification. The Nottingham Health Profile (NHP) results show that the rt-PA patients had a slightly higher (worse) score in all dimensions after one month with the exception of sleep. After 12 months the differences no longer exist and the rt-PA patients had even lower (better) scores in the sleep and energy dimensions. The calculated cost-effectiveness ratio varies from 3090 to 5970 SEK per life year saved and the calculated cost-utility ratio varies from 3260 SEK to 6310 SEK per QALY gained. In comparison with other heart disease treatments, intravenous thrombolysis is cost-effective.