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Biomedical subjects

L A Levin

Publications and source records attributed to L A Levin.

At least 19 recordsLinked to original sources
PubMed1999

Ethambutol is toxic to retinal ganglion cells via an excitotoxic pathway.

PURPOSE: Ethambutol is an essential medication in the management of tuberculosis. However, it can cause an optic neuropathy of uncertain etiology. Ethambutol toxicity was therefore studied in rodent retinal cells, and agents that might block its toxicity were considered. METHODS: The toxicity of ethambutol and related agents was evaluated in rodent retinal dissociated cell preparations and whole eyes. Calcium fluxes and mitochondrial function were evaluated by fluorescent and staining techniques. For in vivo assays, adult rats were administered oral ethambutol over a 3-month period. Cell survival was assessed by stereology. RESULTS: Ethambutol is specifically toxic to retinal ganglion cells in vitro and in vivo. Endogenous glutamate is necessary for the full expression of ethambutol toxicity, and glutamate antagonists prevent ethambutol-mediated cell loss. Ethambutol causes a decrease in cytosolic calcium, an increase in mitochondrial calcium, and an increase in the mitochondrial membrane potential. CONCLUSIONS: The visual loss associated with ethambutol may be mediated through an excitotoxic pathway, inasmuch as ganglion cells are rendered sensitive to normally tolerated levels of extracellular glutamate. Ethambutol perturbs mitochondrial function. Its toxicity may depend on decreased ATPase activity and mitochondrial energy homeostasis. Glutamate antagonists may be useful in limiting the side effects seen with ethambutol.

Animals↗
PubMed1998

Economic evaluation of general childhood vaccination against Haemophilus influenzae type b in Sweden.

The objective of the study was to evaluate the economic consequences of a general childhood vaccination programme against Haemophilus influenzae type b (Hib) in Sweden. A retrospective pre-vaccination annual cohort of 0-4-y-old children was compared with an annual cohort of the same age group after a complete implemented vaccination program against Hib. The cost analysis shows that vaccination against Hib is cost saving when indirect costs are included in the analysis. In the cost-benefit analysis it is shown that society will gain approximately 88 million Swedish Crowns (SEK) annually when Hib vaccination is totally implemented. In conclusion, general childhood Hib vaccination is a cost-effective public health intervention in Swedish society.

Child, Preschool↗
PubMed1998

Domiciliary liquid oxygen versus concentrator treatment in chronic hypoxaemia: a cost-utility analysis.

Whether long-term oxygen therapy (LTOT) improves quality of life in chronic hypoxaemia has been questioned. LTOT with an oxygen concentrator (C/C) and gas cylinders for ambulation is considered cumbersome compared to mobile liquid oxygen equipment (L). The hypothesis for this study was that LTOT with liquid oxygen treatment (L) improves patients' health-related quality of life, but that it is also more expensive compared to concentrator (C/C) treatment. A prospective, randomized multicentre trial comparing C/C with L for LTOT was conducted during a six-month period. Fifty-one patients (29 on L and 22 on C/C) with chronic hypoxaemia, regularly active outside the home, participated in the study initially. Costs for oxygen were obtained from the pharmacies. Patient diaries and telephone contacts with members of the healthcare sector were used to estimate costs. Health-related quality of life was measured by the Sickness Impact Profile (SIP) and the EuroQol, instruments at the start and after 6 months. The average total cost per patient for group C/C for the six-month period was US$1,310, and for group L it was US$4,950. Health-related quality of life measured by the SIP instrument showed significant differences in favour of group L in the categories/dimensions of physical function, body care, ambulation, social interaction and total SIP score. In conclusion, liquid-oxygen treatment was more expensive compared to concentrator treatment. However, treatment effects showed that liquid oxygen had a better impact on quality of life.

Chronic Disease↗
PubMed1998

Expression of ceruloplasmin in the retina: induction after optic nerve crush.

PURPOSE: To better understand the molecular program of neuronal cell death induced by axotomy, the authors attempted to identify retinal genes differentially expressed by optic nerve crush. METHODS: Total RNA isolated from rat retinas at 1 and 4 days after intraorbital optic nerve crush was used in a modification of the differential display technique. After several rounds of screening, a single reproducibly upregulated band was reamplified and cloned, and differential expression was confirmed by Northern analysis. RESULTS: Sequencing of the differentially expressed band revealed identity to the ferroxidase ceruloplasmin. Reverse transcription-polymerase chain reaction demonstrated high levels of ceruloplasmin expression in retina and liver, but minimal or no expression in brain, lung, spleen, kidney, or thymus of adult rats. The retina mRNA transcript was the same size as that of the liver, as measured by Northern blotting. In situ hybridization identified ceruloplasmin expression in the inner nuclear and ganglion cell layers of the retina, which increased after optic nerve crush. Immunoblotting confirmed expression of the same size protein product in the retina and the liver, and ceruloplasmin could be identified in the retina by immunofluorescence, which increased after optic nerve crush. CONCLUSIONS: Ceruloplasmin was expressed in the retina, and was induced by optic nerve crush. The possible role of ceruloplasmin in inhibiting reaction oxygen species in the retina after injury is discussed.

Animals↗
PubMed1998

[Acute appendicitis in patients with salmonellosis and dysentery].

Results of 214 appendectomies in patients with acute intestinal diseases were analyzed. The clinical course and results of treatment of acute appendicitis against the background of salmonellosis and dysentery were discussed. It was shown that the theory of infectious nature of acute appendicitis is rightful and that valuable etiotropic therapy is necessary for prevention of chronicity of the intestinal infection.

Acute Disease↗
PubMed1997

Ophthalmology.

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Cytomegalovirus Retinitis↗
PubMed1997

Expression of endothelin-B receptors by glia in vivo is increased after CNS injury in rats, rabbits, and humans.

Previous studies have demonstrated that neonatal cultures of astrocytes express functional endothelin (ET) receptors. To determine if similar ET receptors are expressed by adult glia we used 125I-ET-1 to examine the expression of ET receptors both in vivo in the normal and transected optic nerves of the rabbit and rat and in vitro in cultures of astrocytes, microglia, or oligodendrocytes. Additionally, we examined the expression of ET receptors in the human optic nerve. Moderate levels of ET(B) receptors were identified in the rabbit and rat forebrain, whereas in the normal rabbit, rat, and human optic nerves a low density of ET(B) receptors was observed, mainly in association with glial fibrillary acidic protein + (GFAP+) astrocytes. After unilateral optic nerve transection, or damage to the retina, the density of glial ET(B) receptors in the optic nerve is significantly increased in all species examined. Thus, at 7 days posttransection there is a significant increase in ET(B) receptors, and by 90 days posttransection the density of ET(B) receptors in the rabbit or rat optic nerve was among the highest of any area in the central nervous system (CNS). Primary cultures of astrocytes or microglia, but not oligodendrocytes, express 125I-ET-1 binding sites. These data demonstrate that in the normal CNS, astrocytes express low but detectable levels of ET(B) receptors, and, after CNS injury, both astrocytes and microglia express high levels of ET(B) receptors. ET(B) receptors provide a therapeutic target for regulating glial proliferation and the release of neurotrophic factors from glia that occur in response to neuronal injury.

Aged↗
PubMed1997

Postprandial transient visual loss. A symptom of critical carotid stenosis.

PURPOSE: The authors report the association of transient visual loss after eating meals with severe carotid occlusive disease, and propose a hypothesis for its pathophysiology. METHODS: Description of clinical history and examination, radiologic and other studies in two patients with postprandial transient visual loss, and review of the literature for three related cases. RESULTS: Two women, 59 and 65 years of age, presented with splotchy visual loss lasting up to more than 1 hour in the left and both eyes, respectively. In both patients, the visual loss was precipitated by eating a meal. Radiologic investigations revealed 90% stenosis of the left internal carotid artery in the first patient and occlusion of the right internal carotid artery and 40% to 70% stenosis of the left internal carotid artery in the second patient. CONCLUSIONS: Visual loss after eating a meal may result from hypoperfusion of the retinal and choroidal circulations and is suggestive of severe carotid occlusive disease.

Aged↗
PubMed1997

Identification of the bcl-2 family of genes in the rat retina.

PURPOSE: Retinal ganglion cells die by apoptosis after axotomy, and this process may reflect altered expression of cell-death genes. Several of these genes, including bcl-2, bcl-x, and bax, share homology at the amino acid level in the BH1 and BH2 domains, through which they also interact. To understand their role in the neuronal response to axotomy, the authors studied their expression in the adult rat retina and after optic nerve crush. METHODS: An initial survey was conducted with reverse transcription-polymerase chain reaction (RT-PCR), using oligonucleotides against identified members of this family and against the conserved BH1 and BH2 domains. Retinal bcl-xl expression at the messenger RNA (mRNA) and protein level was studied by RT-PCR, Northern blotting, RNase protection analysis, in situ hybridization, Western blotting, and immunofluorescence staining. The effect of retinal ganglion cell axotomy on the steady-state level of bcl-x mRNA was investigated. RESULTS: RT-PCR results indicated that rat retinal cells predominantly express the long form of bcl-x. Both clonal analysis and quantitative measurements using RNase protection assays demonstrated that bcl-xL message was at least 16 times more abundant than that of bcl-2. In situ hybridization and indirect immunofluorescence demonstrated that nearly all neuronal cells of the retina express bcl-x. Northern and RNase protection analyses showed a moderate decrease in bcl-xL message shortly after optic nerve crush. CONCLUSIONS: These findings suggest that the antideath gene bcl-xL is the predominant member of the bcl-2 family in the adult retina, and that its level decreases after optic nerve crush. Changes in bcl-xL expression may correlate with increased retinal ganglion cell apoptosis after axotomy.

Animals↗
PubMed1996

Ophthalmology.

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Cataract Extraction↗
PubMed1996

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.

Aged↗
PubMed1996

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.

Adrenal Cortex Hormones↗
PubMed1996

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.

Adult↗
PubMed1996

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.

Diagnosis, Differential↗
PubMed1996

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.

Animals↗
PubMed1995

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.

Animals↗