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Biomedical subjects

A G Lewis

Publications and source records attributed to A G Lewis.

13 recordsLinked to original sources

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

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

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

Common forefoot deformities. How to treat, when to refer.

Initial assessment of common forefoot deformities by the primary care physician is quite feasible. A thorough history, examination of the foot with the patient standing and seated, assessment of the patient's footwear, and radiographic evaluation can often lead to gratifying relief with use of simple office measures. Even in cases that require referral to an orthopedic surgeon, interim relief of symptoms and the patient's increased awareness of the problem and its cause enhance the patient's understanding and the final outcome as well.

Arthritis

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

Altered renal function in chronically hyperprolactinaemic rats.

1. Standard renal clearance techniques were used to investigate the effects of chronic hyperprolactinaemia on kidney function in male, female and ovariectomized female rats. 2. All hyperprolactinaemic rats showed a significantly increased glomerular filtration rate (G.F.R.) compared to controls. Values were (microliter min-1) 2738 +/- 146 vs. 2299 +/- 99 for males (P less than 0.05), 2236 +/- 79 vs. 1865 +/- 74 for females (P less than 0.01) and 2200 +/- 76 vs. 1941 +/- 62 for ovariectomized females (P less than 0.05). 3. Hyperprolactinaemic rats in all groups also showed a significant increase in absolute tubular reabsorption of water, sodium and chloride compared to their respective controls. Increases here averaged 19%. 4. There was a significantly greater fractional tubular reabsorption of fluid and solutes in hyperprolactinaemic male rats compared to controls. Values were (%) 92.9 +/- 0.6 vs. 90.3 +/- 0.7 for water, 93.0 +/- 0.4 vs. 91.0 +/- 0.6 for sodium and 89.9 +/- 0.7 vs. 86.5 +/- 0.9 for chloride. In each case P less than 0.05. 5. These results imply an osmoregulatory role for prolactin which is not specific to pregnancy or related female reproductive states.

Absorption

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