Short-term memory impairment in an alert patient as a presentation of herpes simplex encephalitis.
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Adult↗
Biomedical subjects
G M Cleator
Publications and source records attributed to G M Cleator.
CSF pretreatment and the diagnosis of herpes encephalitis using the polymerase chain reaction.
A number of techniques for extraction of DNA prior to polymerase chain reaction (PCR) amplification of herpes simplex virus (HSV) DNA in cerebrospinal fluid (CSF) were compared to the use of "native" CSF in the PCR reaction. The results indicate that extraction of DNA (which allows efficient removal of inhibitors of Taq polymerase) is an essential pre-requisite of the PCR detection of CSF HSV DNA.
DNA, Viral↗
Obstacle to early diagnosis of herpes simplex encephalitis via CSF.
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Encephalitis↗
Diagnosis of herpes encephalitis via Southern blotting of cerebrospinal fluid DNA amplified by polymerase chain reaction.
Herpes simplex virus thymidine kinase gene specific polymerase chain reaction (PCR) amplification of DNA extracted from lumbar cerebrospinal fluid (CSF) and Southern blotting (SB) were evaluated as a method for the diagnosis of herpes simplex encephalitis (HSE). Positive PCR-SB results were obtained with CSF samples from 9 of 10 patients (11 of 12 CSF specimens) with proven herpes encephalitis as early as 2 days after onset of neurological illness. Our data support the suggestion that PCR techniques may provide a clinically relevant "non-invasive" method for the diagnosis of HSE.
Base Sequence↗
Immunoradiometric assay for cytomegalovirus-specific IgG antibodies: assay development and evaluation in blood transfusion practice.
An immunoradiometric assay (radio-immunosorbent test; RIST) for the detection of IgG antibodies to human herpesvirus 4 [human cytomegalovirus (CMV)] has been developed. The technique utilizes CMV antigen passively adsorbed to a polyvinyl microtitration plate and a radiolabelled murine monoclonal anti-human IgG antibody to detect binding of human antibody to the 'solid phase' reagent. The assay was optimized, and its specificity confirmed by testing paired acute and convalescent sera from patients with acute CMV or other human herpesvirus infections. To determine the assay's sensitivity 1433 blood donor sera were examined. The RIST was more sensitive than a standard complement fixation (CFT), in that 53% of these sera were positive by RIST and 48% positive by CFT. There were 1303 concordant results, 88 sera positive only by RIST and 19 sera were only positive by CFT. These discrepant results remained after an attempt to exclude false positive reactivity; their significance is discussed. Use of a monoclonal anti-human IgG antibody in the RIST reduced non-specific binding to the control uninfected cell antigen such that blood donor sera could be tested in the assay using only a CMV antigen without generating an unacceptable false positive rate.
Animals↗
Herpes virus in a corneal donor.
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Adult↗
Measurement of renal blood flow by 131I-labelled sodium iodohippurate imaging in a rat model of herpes encephalitis.
Renal blood flow was assessed qualitatively over a 30 min period in a rat model of herpes encephalitis by extra-renal scintigraphic imaging following the injection of 131I-labelled sodium iodohippurate. No significant differences were observed for renal blood flow in either kidney between (or within) infected and control groups. Our data suggest that kidney function is not compromised in this animal model of encephalitis. The results are discussed in the context of the development of a non-invasive protocol for the in vivo diagnosis of herpes encephalitis.
Animals↗
Altered in vitro uptake of the radiolabelled antiviral imaging "probe" E-5-(2-125iodovinyl)-2'-deoxyuridine following administration of acyclovir.
Current developments in the use of radiolabelled antiviral drugs as specific "probes" for virus-infected cells in vivo may allow the specific neuroradiological diagnosis of herpes encephalitis. As "blind therapy" with the antiviral drug acyclovir may precede specific neuroradiological diagnosis, the aim of the present study was to investigate whether or not acyclovir interferes with the uptake of the radioprobe E-5-(2-125Iodovinyl)-2'-deoxyuridine (rIVDU) by virus-infected cells in vitro. Acyclovir treatment (0.1 to 10 micrograms/ml) was shown to increase initial radioprobe uptake by virus-infected cells. However, with continued incubation in the presence of acyclovir, intracellular radioactivity decreased to a level not significantly different from that associated with noninfected cells. A mechanism to explain these results is proposed. It was concluded that concurrent acyclovir therapy could interfere with neuroradiological diagnosis using rIVDU, although this may not occur with all the candidate radioprobes currently under investigation.
Acyclovir↗
HM-PAO-imaging and herpes encephalitis.
Selective uptake of the cerebral blood-flow imaging agent 99mTc-hexamethylpropyleneamine oxime (HM-PAO) by Human Herpesvirus 1 (HSV-1) infected cells was investigated in vivo and in vitro. No specific uptake of HM-PAO was observed either in encephalitic rats (by brain scintigraphic imaging or by immunoperoxidase staining/autoradiography of brain sections) or in HSV-1 infected Vero cells.
Animals↗
Specific neuro-radiological diagnosis of herpes encephalitis in an animal model.
The potential of utilizing a radio-labelled derivative of the antiviral drug (E)-5-(2-iodovinyl)-2'-deoxyuridine (IVDU) for the specific, non-invasive, in vivo diagnosis of Herpes simplex virus encephalitis (HSVE) was investigated in a rat model of the disease. Following pharmacological disruption of the blood brain barrier radiolabelled IVDU was administered by intra-carotid injection. Brain radioactivity was compared between control and infected animals via gamma camera scintigraphy. After clearance of non-metabolized drug, markedly higher levels of activity were found in infected brain. Post-mortem studies of cryostat sections of brain examined by autoradiography and immunochemical staining showed the radioactivity selectively accumulated in areas of virus infection. These results indicate that radio-labelled derivatives of antiviral drugs may allow the specific neuro-radiological diagnosis of HSVE.
Animals↗
Penetration of the blood-brain barrier by the antiviral drug (E)-5-(2-iodovinyl)-2'-deoxyuridine in a rat model of herpes encephalitis.
The blood-brain barrier penetration of a radiohalogenated (125I) derivative of the antiviral drug (E)-5-(2-iodovinyl)-2'-deoxyuridine (IVDU) was investigated in a rat model of herpes encephalitis. CNS delivery was assessed by external gamma camera scintigraphic imaging in vivo, a technique which may have general application in evaluating brain specific delivery of drugs, and by autoradiography of cryostat sections of rat brain. Radiohalogenated IVDU was found to be almost totally excluded from the CNS. These findings may be explained in terms of the poor lipid solubility of IVDU (in vitro oil/aqueous salt solution partition coefficient 0.012). Since IVDU appears in CSF after carotid artery administration, our results stress the necessity, in the design of compounds for the treatment of CNS infections, of distinguishing blood-brain, blood-CSF, and CSF-brain drug barriers. The significance of our data both in relation to the development of neuro-radiological diagnosis and antiviral chemotherapy of CNS infection is discussed.
Animals↗
A rat model of herpes encephalitis with special reference to its potential for the development of diagnostic brain imaging.
A rat model of herpes encephalitis using intraocular inoculation of herpes simplex virus strain SC16 was investigated. Virus distribution in the brain was examined by virus isolation and immunocytochemical staining using immuno-gold silver and peroxidase-anti-peroxidase. At 5 days post-infection virus was found in the thalamus, hypothalamus, septum, colliculus, geniculate bodies, the pons, trapezoidium and medulla oblongata, but less frequently, in the cerebellum and occipital lobes. Possible routes of spread of virus and the potential of this model in neuro-radiological scanning procedures are discussed.
Animals↗
Immuno-gold silver staining in the diagnosis of herpes encephalitis.
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Brain↗
Herpesvirus simplex in chronic human stromal keratitis.
A method is described for the isolation of Herpesvirus simplex (HSV) from corneal discs of patients suffering from chronic stromal keratitis. The discs were removed during penetrating keratoplasty. Virus was successfully isolated from 2 out of 8 discs maintained in vitro.
Cornea↗
Altered in vitro uptake of E-5-2-125iodovinyl-2'-deoxyuridine following administration of the antineoplastic agent etoposide.
The semi-synthetic epipodophyllotoxin derivative, etoposide (VP-16-213), has been shown to inhibit nucleoside uptake in mammalian cells. The present study examined whether etoposide (or the solvent in which it is usually supplied) affected the uptake of the radioiodinated antiviral nucleoside analogue E-5-2-125Iodovinyl-2'-deoxyuridine (125IVDU) by HSV1-infected cells (human herpesvirus 1; herpesvirus simplex type 1). Etoposide was found to significantly reduce 125IVDU sequestration, although some of this effect could be attributed to the solvent. The results are discussed in relation to the use of etoposide in the development of a specific, scintigraphic brain imaging technique to enable early diagnosis of herpes encephalitis.
Animals↗
Effects of the anti-cancer agent etoposide on human herpesvirus 1 replication in vitro.
The anti-human herpesvirus type 1 (herpes simplex virus 1; HSV1) activity of etoposide (VP-16-213, a semi-synthetic derivative of epipodophyllotoxin) was investigated in vitro. Etoposide (but not the proprietary solvent in which the compound is usually formulated) demonstrated a significant antiviral action, probably through an effect on virus replication. Etoposide, at 3 micrograms/ml, induced a 50% reduction of HSV1-plaque formation in Vero cells. These findings are considered in the context of the use of etoposide in an in vivo procedure for the diagnosis of herpes encephalitis through virus-specific scintigraphic brain imaging.
Animals↗