Biomedical subjects

Myron J Levin

Publications and source records attributed to Myron J Levin.

28 records · Page 2Linked to original sources

PubMed2004

Development of a measure of the burden of pain due to herpes zoster and postherpetic neuralgia for prevention trials: adaptation of the brief pain inventory.

UNLABELLED: In preparation for clinical trials of a vaccine against herpes zoster (HZ), we conducted a prospective, observational study to evaluate (1) the Zoster Brief Pain Inventory (ZBPI), an HZ-specific questionnaire to quantify HZ pain and discomfort, (2) an operational definition of postherpetic neuralgia (PHN), and (3) a severity-duration measure of the burden of illness caused by HZ. HZ patients aged 60 years or older (n = 121) were enrolled within 14 days of rash onset and completed ZBPI, McGill Pain Questionnaire Present Pain Intensity (PPI), quality of life (QoL), and activities of daily living (ADL) questionnaires on a predetermined schedule. Reliability, measured by intraclass correlation coefficients within 14 days of rash onset, ranged between 0.63 and 0.78. ZBPI pain scores were strongly correlated with other pain measures, interference with ADL, and worsening QoL. The operational definition of PHN, a ZBPI pain score of 3 or greater occurring 90 or more days after rash onset, had high agreement with pain worse than mild on the PPI (kappa = 0.72). The ZBPI pain severity-duration measure had high correlations with severity-duration measures of ADL interference, worsening QoL, and other pain scales. These findings support the validity and utility of the ZBPI, the definition of PHN, and the severity-duration measure of the burden of HZ illness. PERSPECTIVE: Herpes zoster pain, as measured by the ZBPI severity-duration measure, is associated with impairment in daily living activities and quality of life. The ZBPI measure appears useful for quantifying herpes zoster pain, postherpetic neuralgia, and impairment in daily living activities for clinical trials of herpes zoster prevention.

Ambulatory Care↗

PubMed2003

Decline in varicella-zoster virus (VZV)-specific cell-mediated immunity with increasing age and boosting with a high-dose VZV vaccine.

The safety and immunogenecity of a booster dose of live attenuated varicella-zoster virus (VZV) vaccine was evaluated in 196 healthy subjects, >or=60 years old, who had already received a VZV vaccine >5 years before. This repeat booster dose was well tolerated. Cell-mediated immunity (CMI) to VZV was measured by an interferon-gamma (IFN-gamma) enzyme-linked immunosorbent spot-forming cell (ELISPOT) assay and a limiting dilution responder cell frequency (RCF) assay. Prevaccination responses decreased as a function of increasing age but were detectable in all subjects by use of the IFN-gamma ELISPOT assay. In most subjects, VZV-specific CMI was increased at 6 weeks postvaccination. The magnitude of the vaccine-induced IFN-gamma ELISPOT response was inversely related to prevaccination values. Although there was a significant correlation between the IFN-gamma ELISPOT and RCF assays, the ELISPOT assay had greater sensitivity and a wider dynamic range. A live attenuated VZV vaccine is safe and immunogenic in an elderly population, and the vaccine-induced immunity may be monitored by the IFN-gamma ELISPOT assay.

Age Factors↗

PubMed2003

Phase I/II trial of intravenous recombinant interleukin-2 in HIV-infected children.

OBJECTIVES: To define the tolerated dose of recombinant interleukin-2 (rIL-2) in HIV-infected children (part A), and to determine the safety and immunologic effects of the tolerated rIL-2 dose in a cohort of HIV-infected children (part B). DESIGN: Open-label, dose-escalation. SETTING: Multiple center study. SUBJECTS: Twenty HIV-infected children, aged 3-12 years. INTERVENTION: In part A six subjects received 1 x 10(6) IU/m2 and four subjects received 4 x 10(6) IU/m2 rIL-2 by continuous intravenous infusion for 5 days every 8 weeks for three cycles. In part B 10 different subjects received 1 x 10(6) IU/m2 for 5 days every 8 weeks for six cycles. MAIN OUTCOME MEASURES: Toxicity, CD4 cell count and percentage, and viral load. RESULTS: The tolerated dose of rIL-2 was 1 x 10(6) IU/m2. The most common side effects were fever and vomiting. Of 10 subjects enrolled in part B of the study, five discontinued rIL-2 therapy for a variety of reasons, most related to administration of study drug. Comparable rises in CD4 cell count and percentage were observed in each of the treatment arms. Six cycles of rIL-2 therapy did not appear to be better than three cycles with respect to improvement of CD4 parameters. Transient rises in plasma HIV-1 RNA levels were detected in some subjects. CONCLUSIONS: These results suggest that rIL-2 therapy can raise CD4 cell counts and percentages in some HIV-infected children, although a high proportion of HIV-infected children may have to discontinue intravenous therapy because of drug- or administration-related toxicity. Controlled trials of rIL-2 in this patient population are warranted.

Anti-HIV Agents↗

PubMed2003

Development of resistance to acyclovir during chronic infection with the Oka vaccine strain of varicella-zoster virus, in an immunosuppressed child.

A 1-year-old boy was vaccinated with the Oka strain of varicella just prior to the discovery of a tumor that required intensive antitumor therapy. Three months later he developed herpes zoster, which developed into chronic verrucous lesions that were refractory to treatment with acyclovir and which subsequently disseminated. DNA from a biopsy specimen of a chronic herpes-zoster lesion indicated that the Oka vaccine strain of the the virus caused this severe complication. Analysis of this viral DNA demonstrated a mutation in the viral thymidine kinase gene. Plasmids containing this altered gene were unable to produce functional thymidine kinase in an in vitro translation system. The presence of this mutation would explain the clinical resistance to acyclovir. This is the first report of Oka-strain varicella virus causing severe disease after reactivation and of resistance to acyclovir during an infection caused by this virus.

Abdominal Neoplasms↗

PubMed2003

Susceptibility of herpes simplex virus isolates to nucleoside analogues and the proportion of nucleoside-resistant variants after repeated topical application of penciclovir to recurrent herpes labialis.

Subjects received topical penciclovir for 4 days during successive episodes of recurrent herpes labialis. Isolation of herpes simplex virus (HSV) was attempted from lesions obtained before initiation of treatment and on each day of therapy. Isolates remained sensitive to penciclovir when tested by a plaque reduction assay, and there was no significant change in sensitivity during any treatment course or between successive treatments. The proportion of nucleoside-resistant variants present within a subset of these isolates was further investigated using a more-sensitive plating efficiency assay. Although the proportion of antiviral-resistant HSV variants increased on successive days, it invariably remained a minor subpopulation. Moreover, isolates from successive episodes obtained before treatment showed no change in the proportion of resistant HSV variants. We conclude that antiviral-resistant variants, which are readily detected in HSV isolates from peripheral lesions, do not accumulate in the sensory ganglia of immunocompetent patients receiving multiple courses of nucleoside analogues.

Acyclovir↗

PubMed2003

Herpes simplex virus resistance to acyclovir and penciclovir after two decades of antiviral therapy.

Acyclovir, penciclovir, and their prodrugs have been widely used during the past two decades for the treatment of herpesvirus infections. In spite of the distribution of over 2.3 x 10(6) kg of these nucleoside analogues, the prevalence of acyclovir resistance in herpes simplex virus isolates from immunocompetent hosts has remained stable at approximately 0.3%. In immuncompromised patients, in whom the risk for developing resistance is much greater, the prevalence of resistant virus has also remained stable but at a higher level, typically 4 to 7%. These observations are examined in the light of characteristics of the virus, the drugs, and host factors.

Acyclovir↗

PubMed2003

Varicella-zoster virus DNA in cells isolated from human trigeminal ganglia.

To determine the type of cell(s) that contain latent varicella-zoster virus (VZV) DNA, we prepared pure populations of neurons and satellite cells from trigeminal ganglia of 18 humans who had previously had a VZV infection. VZV DNA was present in 34 of 2,226 neurons (1.5%) and in none of 20,700 satellite cells. There was an average of 4.7 (range of 2 to 9) copies of VZV DNA per latently infected neuron. Latent VZV DNA was primarily present in large neurons, whereas the size distribution of herpes simplex virus DNA was markedly different.

Adult↗

PubMed2002

Fractionation of neurons and satellite cells from human sensory ganglia in order to study herpesvirus latency.

A method is described for fractionating human trigeminal ganglia into highly purified populations of neurons and satellite cells in order to study alpha-herpesvirus latency. The method was validated by microscopy of the separated populations and by the observation that only the neuronal population, not the satellite cells, contained herpes simplex virus (HSV) DNA. The frequency of detecting HSV in neurons from ganglia was 3% (43 of 1440 neurons). HSV DNA was not detected in approximately 17,500 satellite cells. The HSV DNA genome copy number in single cells ranged from 2 to 50. These data on the frequency and cellular location of latent HSV indicate that our mechanical fractionation of cell types results in low levels of cross-contamination and provides samples from which cells infected latently can be studied at the single cell level.

Adult↗

PubMed2002

Susceptibilities of herpes simplex viruses to penciclovir and acyclovir in eight cell lines.

The commonly used antiviral drugs acyclovir (ACV) and penciclovir (PCV) possess similarly potent antiviral activities in vivo against herpes simplex virus (HSV). Assay methods for sensitivity to ACV are not necessarily transferable to PCV, even though the two drugs have similar in vivo potencies and mechanisms of action. We determined by plaque reduction assay the relative activities of ACV and PCV against five laboratory-adapted strains of HSV types 1 and 2 (including sensitive and resistant strains) in seven human cell lines and one nonhuman primate cell line. Seven characteristics were used to evaluate the cell lines. All cell lines were similar in their plating efficiencies and abilities to discriminate between sensitive and resistant HSV isolates. Vero and MRC-5 cells yielded the most discordant 50% inhibitory concentrations (IC50s) for the two HSV types, while Vero and WI-38 VA-13 cells yielded large differences in the IC50s of ACV and PCV. The limited life spans and poor plaque morphologies of the fibroblast lines were undesirable characteristics. Among the transformed cell lines producing well-defined plaques, A549 cells provided the best concordance between IC50s for the two HSV types and two antiherpes drugs. Comparison experiments with a yield reduction format indicated that the use of assays of this type might allow some of the cell-specific properties observed in plaque reduction assays to be avoided.

Acyclovir↗

PubMed2001

Sabin attenuated LSc/2ab strain of poliovirus spreads to the spinal cord from a peripheral nerve in bonnet monkeys (Macaca radiata).

Vaccine-associated paralytic poliomyelitis is a serious concern while using the live attenuated oral polio vaccine for the eradication of poliomyelitis. The bonnet monkey model of poliovirus central nervous system (CNS) infection following experimental inoculation into the ulnar nerve allows the comparative study of wild-type and attenuated poliovirus invasiveness. Dosages >/=10(4) TCID(50) of Mahoney strain of poliovirus type 1 [PV1(M)] result in paralysis. In contrast, even with 10(7) TCID(50) of Sabin attenuated strain of poliovirus type 1 (LSc/2ab), no paralysis occurs, but virus spreads into the CNS where viral RNA is found in spinal cord neurons. While wild-type PV1(M) viral RNA replicates in neurons (and possibly in glial cells) and in cells around vessel walls, which may be mononuclear or endothelial cells, attenuated viral RNA is detected only in neurons. Systemic viraemia and gastrointestinal virus shedding occurs only in PV1(M)-infected animals. While a systemic serologic response is detected in both groups of animals, cerebrospinal fluid antibodies are detected only in animals infected with PV1(M). Both the PV1(M) and LSc/2ab strains spread to the cervical spinal cord and then to the lumbar spinal cord following ulnar nerve inoculation. Neuronophagia and neuronal loss are only seen in PV1(M)-infected monkeys in whom clinical paralysis is observed. Infection with LSc/2ab does not result in neuronophagia, neuronal loss or clinical paralysis. Spread of attenuated poliovirus in spinal cord neurons without causing paralysis following inoculation into the ulnar nerve is an important finding.

Animals↗