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1/5. Progressive outer retinal necrosis caused by herpes simplex virus type 1 in a patient with acquired immunodeficiency syndrome.

    OBJECTIVE/BACKGROUND: To identify the etiologic agent of rapidly progressive outer retinal necrosis (PORN) in a 32-year-old man with acquired immunodeficiency syndrome (AIDS), who had retinitis developed from cytomegalovirus (CMV). Multiple yellowish spots appeared in the deep retina without evidence of intraocular inflammation or retinal vasculitis, diagnosed clinically as PORN. death occurred after failure of multiple organs. DESIGN: Case report. methods: Both globes were taken at autopsy, fixed in formalin, and examined histopathologically and immunohistochemically to identify causative agents in the retinal lesions. MAIN OUTCOME MEASURE: immunohistochemistry. RESULTS: All layers of the retina were severely damaged and contained focal calcification. Cytomegalic inclusion bodies were found in cells in the damaged retina of the right eye. Immunohistochemical studies for herpesviruses revealed the presence of CMV antigens in the right retina at the posterior pole and herpes simplex virus type 1 (HSV-1)-specific antigen in the periphery of both retinas. No varicella-zoster virus (VZV) antigen was detected in either retina. CONCLUSIONS: PORN has been described as a variant of necrotizing herpetic retinopathy, occurring particularly in patients with AIDS. Although the etiologic agent has been reported to be VZV, HSV-1 can be an etiologic agent.
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2/5. Detection of varicella zoster virus dna and viral antigen in the late stage of bilateral acute retinal necrosis syndrome.

    We describe the clinicopathologic and virologic findings in the right, blind eye of an immunocompetent 61-year-old woman. The eye was enucleated 32 months after the clinical onset of a bilateral acute retinal necrosis syndrome. Histopathologic study showed a diffuse, full-thickness, necrotizing retinitis with replacement of sensory retinal structures by glial tissue, occlusive retinal arteritis, granulomatous choroiditis, and optic neuritis with ischemic optic atrophy. Varicella zoster virus could be identified as the causative agent by dna in situ hybridization and by immunohistochemical stains in mononuclear cells with eosinophilic intracytoplasmic inclusions. Virus was detected only within the choroid and the choriocapillaris. We conclude that these histopathologic and virologic features are consistent with a "burned-out phase" of a varicella zoster virus-induced acute retinal necrosis syndrome.
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3/5. Acute retinal necrosis six years after herpes simplex encephalitis: an elusive immune deficit suggested by insufficient test sensitivity.

    A patient presented with acute retinal necrosis of the left eye. Demonstration of herpes simplex virus (HSV) dna in the aqueous humour confirmed the diagnosis. Negative results of HSV type-specific antibody tests based on gG antigens suggested a primary HSV infection. However, the patient had a past history of laboratory-confirmed herpes simplex encephalitis 6 years ago. Using antibody tests based on whole viral lysate antigens, he was seropositive from the onset, and immunoblot testing confirmed a lack of anti-gG reactivity. To be able to assess whether this might be related to the apparent inability of his immune system to suppress clinically symptomatic HSV infection, serial samples were tested by an HSV neutralisation test and a whole-blood flow cytometric assay to determine the frequency of HSV-specific CD4 lymphocytes. However, this did not yield evidence of obvious immunodeficiency; the patient reacted similarly to known positive controls by both assays. Although type-specific HSV serological tests based on gG are generally more specific than those based on whole viral lysate antigens, they have a somewhat lower sensitivity, as a certain percentage of HSV-infected individuals do not develop antibodies against gG, and others may suffer a secondary loss of anti-gG reactivity. Thus there is a risk of missing individual infected patients. Unless this potential problem is recognised, serious consequences might possibly result. We therefore urge virologists and clinicians to exercise great care if highly specific antibody assays based on recombinant proteins are employed.
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4/5. Intrathecal antibody production against viruses of the herpesvirus family in acute retinal necrosis syndrome.

    viruses of the herpesvirus family cause acute retinal necrosis syndrome, a devastating necrotic retinitis in immunocompetent individuals. Direct proof of the viral origin of this disease may be obtained by demonstration of the virus, viral antigens, or viral dna in biopsy specimens of retinas. In search of alternative diagnostic methods, we analyzed cerebrospinal fluid and serum with enzyme-linked immunosorbent assays for virus-specific antibody activity. Intrathecally produced viral antibodies were found in three consecutive patients with acute retinal necrosis syndrome: herpes simplex type 2 in a 30-year-old woman with a history of suspected neonatal herpes encephalitis, herpes simplex type 1 in a 35-year-old man, and varicella-zoster virus activity in a 62-year-old woman. None of the patients had clinical signs indicating an acute disorder in the central nervous system. This serologic approach seems to be of value for the diagnosis of an associated intracerebral viral infection in cases of acute retinal necrosis syndrome.
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5/5. Necrotizing herpetic retinopathies. A spectrum of herpes virus-induced diseases determined by the immune state of the host.

    PURPOSE: Necrotizing herpetic retinopathies (NHR), a new spectrum of diseases induced by viruses of the herpes family (herpes simplex virus, varicella-zoster virus and cytomegalovirus), includes acute retinal necrosis (ARN) occurring in apparently immunocompetent patients and progressive outer retinal necrosis (PORN) described in severely immuno-compromised patients. Signs of impaired cellular immunity were seen in 16% of ARN patients in a review of 216 reported cases, indicating that immune dysfunction is not only at the origin of PORN but might also be at the origin of ARN. The aim of this study was to correlate clinical findings in NHR patients with their immunologic parameters. methods: charts from patients with the diagnosis of ARN or PORN seen from 1990 to 1995 were reviewed. Clinical characteristics and disease patterns were correlated with immunological parameters taking into account CD4 lymphocyte rate in AIDS patients and blood-lymphocyte subpopulation determination by flow cytometry, cutaneous delayed type hypersensitivity testing and lymphocytic proliferation rate to seven antigens in hiv-negative patients. RESULTS: During the period considered, 11 patients and 7 patients fulfilled the criteria of ARN and PORN respectively. Immune dysfunctions were identified in most patients. Mild type of ARN and classical ARN were associated with discrete immune dysfunctions, ARN with features of PORN was seen in more immunodepressed patients and classical PORN was always seen in severely immunodepressed hiv patients. CONCLUSION: Our findings suggest that NHR is a continuous spectrum of diseases induced by herpes viruses, whose clinical expression depends on the immune state of the host going from mild or classical ARN at one end in patients with non-detectable or slight immune dysfunction to PORN in severely immunodepressed patients at the other end and with intermediary forms between these extremes.
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