Cytosine Arabinoside (CA) and Other Nucleosides in Herpes Virus Infections

Underwood, Gerald E.; Wisner, Carolyn A.; Weed, Sheldon D.

doi:10.1001/archopht.1964.00970020505014

Cited by 43 publications

(15 citation statements)

References 10 publications

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“…DISCUSSION Ara-C has potent in vitro activity against HSV (1), VZV (11), and CMV (R. W. Sidwell, G. Arnett, and F. M. Schabel, Jr., Chemotherapy, in press). Ara-C has the advantage over IUdR in vitro (1) and in vivo (13) in the lack of development of markedly resistant mutants in its presence. Mutants solidly resistant to IUdR develop rapidly (1).…”

Section: Methodsmentioning

confidence: 99%

Susceptibility of Herpesviruses to Cytosine Arabinoside: Standardization of Susceptibility Test Procedure and Relative Resistance of Herpes Simplex Type 2 Strains

Fiala

Chow

Guze

1972

Antimicrob Agents Chemother

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Susceptibility testing of herpes simplex type 1 (HSV-1) and type 2 viruses to cytosine arabinoside (Ara-C) has been standardized under conditions of optimal reproducibility, susceptibility, and simplicity. Standard Clinically useful antibiotics are usually found among those antibiotics which possess marked in vitro activity against pathogenic bacteria. Determination of antibiotic susceptibilities of bacterial isolates has great significance for rational therapy. At present, several drugs are useful in treatment of viral diseases: thiosemicarbazones in smallpox and vaccinia; 5-iodo-desoxyuridine (IUdR), cytosine arabinoside (Ara-C), and adenine arabinoside, (Ara-A) in herpesvirus infections. Virus isolates are routinely not tested for in vitro susceptibility to drugs. This paper describes a simple, standardized method for susceptibility testing of herpesviruses to Ara-C based on inhibition of cytopathic effect (CPE). This method can be modified to measure virus inhibitory titers (VIT) of body fluids. MATERIALS AND METHODSPreparation of drug solution. Ara-C (Cytarabine, The Upjohn Co.) was prepared every 2 days at a concentration of 2 mg/ml in distilled water, sterilized by membrane filtration (Millipore Corp.), and diluted to appropriate concentrations in Eagle minimum essential medium (MEM) with Earle's salt solution, 2% dialyzed fetal calf serum, 100 units of penicillin per ml, and 100 ,ug of streptomycin per ml (MEMFCa2).Viruses. Seven herpes simplex virus (HSV) type 1 (HSV-1) strains (X-2, X-119, X-334, E-377, E-515 S-39, and W-844) and seven HSV type 2 (HSV-2) strains (E-304, E-294, E-194, E-330, E-503, E-689, and Z-570) were kindly provided by A. Nahmias. Two HSV-2 strains (T.M. and T.A.P.) were isolated from neonates with HSV encephalitis. Varicella-zoster virus (VZV) strain N.R. was isolated from a patient with Hodgkin's disease and disseminated zoster. HSV stocks were prepared in strain WI-38 of human lung fibroblasts, harvested at time of about 90% CPE, and frozen in samples at -70 C.

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Section: Methodsmentioning

confidence: 99%

Susceptibility of Herpesviruses to Cytosine Arabinoside: Standardization of Susceptibility Test Procedure and Relative Resistance of Herpes Simplex Type 2 Strains

Fiala

Chow

Guze

1972

Antimicrob Agents Chemother

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“…Both these cytotoxic drugs are known to inhibit herpesvirus replication (Cohen et al, 1969;Underwood, 1962;Underwood et al, 1964), so that enhancement of herpetic infection in these patients is surprising, particularly as seven out of 18 patients who showed evidence of herpetic infection had received treatment with one of these drugs in the preceding month.…”

Section: Treatmentmentioning

confidence: 99%

Herpesvirus hominis Infection in Patients with Myeloproliferative and Lymphoproliferative Disorders

Aston¹,

Cohen²,

Spindler³

1972

BMJ

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SummaryInfection with Herpesvirus hominis, often associated with oral ulceration, was found to be more frequent in patients with myeloproliferative and lymphoproliferative disorders than in normal populations or patients with other diseases. This increased frequency was not associated with any deficiency of the humoral antibody response, suggesting a possible impairment of cellmediated immunity. The otherwise untreatable oral lesions appeared to respond effectively to local irradiation. IntroductionThe frequent occurrence of severe oral ulceration in patients suffering from various types of leukaemia and lymphoma prompted an investigation into the aetiology of the oral lesions. Clinical impressions suggested an herpetic origin and others have commented on the frequency of herpetic infections in patients with myeloproliferative and lymphoproliferative disorders (Stewart, 1950;Ultman et al., 1959;Muller et al., 1972) few patients, however, have been subjected to virological investigations. In the present study virological investigations were used to establish the aetiological role of Herpesvirus

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“…Firstly, the development of viral resistance to Ara-C in vitro has not been a problem as is the case with IUdR (3,26). Secondly, toxicities with Ara-C, given in low doses, are considerably less than conventional doses of IUdR (6).…”

Section: Discussionmentioning

confidence: 99%

Cytosine Arabinoside Therapy for Herpes Simplex Encephalitis—Clinical Experience with Six Patients

Chow

Ronald

Fiala

et al. 1973

Antimicrob Agents Chemother

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Two neonates and four adults with herpes simplex virus (HSV) encephalitis were treated with cytosine arabinoside (Ara-C). A low dose of 40 to 160 mg per m 2 per day was given for 4 to 6 days by continuous intravenous infusion and, except in two cases, by intrathecal administration. In one patient, idoxuridine (IUdR) at the dose of 1 g every 4 h was also administered after 4 days of Ara-C therapy. Both neonates and two of four adults survived. Their clinical improvement was closely related in time to the onset of therapy with Ara-C (cases 1, 2, 3) and with IUdR (case 4). In one adult who died on the 27th day of illness of a massive pulmonary embolus, postmortem examination of the brain did not disclose viral inclusions, and viral culture was negative. In the other patient who died, however, brain culture postmortem was still positive for HSV despite 4 days of Ara-C therapy. Ara-C, in addition to IUdR, may be effective in HSV encephalitis treatment, but double-blind, controlled studies appear to be necessary with these agents.

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Cytosine Arabinoside (CA) and Other Nucleosides in Herpes Virus Infections

Cited by 43 publications

References 10 publications

Susceptibility of Herpesviruses to Cytosine Arabinoside: Standardization of Susceptibility Test Procedure and Relative Resistance of Herpes Simplex Type 2 Strains

Susceptibility of Herpesviruses to Cytosine Arabinoside: Standardization of Susceptibility Test Procedure and Relative Resistance of Herpes Simplex Type 2 Strains

Herpesvirus hominis Infection in Patients with Myeloproliferative and Lymphoproliferative Disorders

Cytosine Arabinoside Therapy for Herpes Simplex Encephalitis—Clinical Experience with Six Patients

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