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Biomedical subjects

H A Rotbart

Publications and source records attributed to H A Rotbart.

At least 19 recordsLinked to original sources
PubMed2001

Treatment of potentially life-threatening enterovirus infections with pleconaril.

Enteroviruses usually cause self-limited disease that, although associated with high morbidity, is rarely fatal. In certain patient populations, however, the enteroviruses may cause potentially life-threatening infections. Pleconaril is a novel compound that integrates into the capsid of picornaviruses, including enteroviruses and rhinoviruses, preventing the virus from attaching to cellular receptors and uncoating to release RNA into the cell. Pleconaril was used on a compassionate-release basis to treat patients with potentially life-threatening enterovirus infections, and for 38 of these patients sufficient follow-up data were available for determining responses to therapy. Response was evaluated in 4 categories: clinical, virological, laboratory, and radiological. Most patients (28 [78%] of 36), including 12 of 16 with chronic enterovirus meningoencephalitis, were judged to have a clinical response temporally associated with pleconaril therapy. Similarly, nearly all patients whose virological responses (12 [92%] of 13), laboratory responses (14 [88%] of 16), and radiological responses (3 [60%] of 5) could be evaluated were judged to have responded favorably to a course of pleconaril treatment. Adverse effects were minimal and the drug was generally well-tolerated.

Adolescent↗
PubMed2000

Stable enterovirus 5' nontranslated region over a 7-year period in a patient with agammaglobulinemia and chronic infection.

Cerebrospinal fluid samples obtained 7 years apart from a patient with chronic meningoencephalitis and underlying agammaglobulinemia were examined to determine enteroviral genotypic variability. From each sample, amplicons spanning 496 nucleotides within the 5' nontranslated region were generated directly from the cerebrospinal fluid and analyzed. A consensus sequence derived from 3 clones of each amplicon revealed only 7 nucleotide changes over the 7-year period within the region studied. The observed 5' nontranslated region mutation rate in this patient ( approximately 0.2% per year) was significantly lower than mutation rates reported for the poliovirus genome.

5' Untranslated Regions↗
PubMed2000

Viral meningitis.

Enteroviruses account for 85 to 95% of all cases of aseptic meningitis, but the arboviruses and herpes simplex virus are also important etiologic agents. Mumps, lymphocytic choriomeningitis virus, herpes zoster, human herpesvirus type 6, and influenza viruses are rare causes of meningitis. The virology, pathogenesis, epidemiology, clinical manifestations, diagnostic studies, and established and potential antiviral therapies for viral meningitis are discussed. A differential diagnosis of the aseptic meningitis syndrome is provided.

Humans↗
PubMed2000

Antiviral therapy for enteroviruses and rhinoviruses.

The picornaviruses are a diverse group of viral pathogens that together comprise the most common causes of infection of humans in the developed world. Within the picornavirus family are three well-known groups of human pathogens--the rhinoviruses, the enteroviruses (including polioviruses, coxsackieviruses and echoviruses) and the hepatoviruses (including hepatitis A virus). This article will focus on the rhinoviruses and enteroviruses, agents for which substantial effort has been expended, and recent successes reported, toward the development of safe and effective antiviral therapy.

3C Viral Proteases↗
PubMed1999

Enteroviral meningoencephalitis as a complication of X-linked hyper IgM syndrome.

We describe 5 children from 2 families with mutations in the CD40 ligand (CD40L) gene leading to absent expression of CD40L on activated CD4 cells. All subjects presented with interstitial pneumonia with low serum IgG and normal serum IgM. One child had normal and one child had elevated serum IgA. Four had confirmed Pneumocystis carinii pneumonia. In spite of intravenous immunoglobulin treatment yielding therapeutic serum immunoglobulin levels, 3 children had enteroviral encephalitis. When assessed by flow cytometry, the 3 surviving affected male children had absent CD40L expression on activated CD4(+) T cells. The affected children from both families were shown to have the same single nucleotide insertion (codon 131) resulting in frameshift and early termination within exon 4 (extracellular domain). This observation demonstrates that persistent enteroviral infection is not only observed in X-linked agammaglobulinemia but may also occur in patients with X-linked hyper IgM syndrome.

CD4-Positive T-Lymphocytes↗
PubMed1999

Clinical significance of enteroviruses in serious summer febrile illnesses of children.

BACKGROUND: Enteroviruses are common causes of aseptic meningitis and nonspecific febrile illnesses in young children. During the summer-fall months, enterovirus-infected children are frequently evaluated in emergency room settings to rule out bacterial sepsis and/or meningitis. OBJECTIVES: We sought to determine the clinical significance of enterovirus infections in children evaluated for serious febrile illnesses in pediatric emergency rooms during the summer-fall season. METHODS: Children admitted to emergency rooms at four university teaching hospitals during a single summer-fall season who required blood culture and/or lumbar puncture to rule out bacterial sepsis/meningitis were prospectively studied. An extensive questionnaire was administered, and specimens of cerebrospinal fluid, serum, urine and throat were tested for enteroviruses by viral culture and PCR. Patients were followed to determine the duration, management and outcome of their illnesses. RESULTS: Of 203 patients studied 173 had no apparent explanation for their illness (e.g. bacterial sepsis, bacterial urinary tract infection, etc.). Of those 173 patients 79 (46%) were infected with enteroviruses, including 33 of 47 (70%) patients with aseptic meningitis, 13 of 25 (52%) patients with nonspecific febrile episodes and 33 of 101 (33%) patients with fever and focal findings (P < 0.0001 for aseptic meningitis vs. fever and focal findings; P = 0.0001 for aseptic meningitis vs. combined nonspecific febrile episodes and fever/focal patients). Among 119 hospitalized patients 65 (55%) were enterovirus-infected. Children < or =90 days of age were more likely to be enterovirus-infected (66 of 122; 54%) than children older than 90 days (13 of 51; 25%) (P = 0.0001). Enterovirus-infected children were more likely to be hospitalized as a result of the current emergency room visit (65 of 79 vs. 54 of 94; P = 0.0005) and were more likely to have had an additional hospitalization for the same illness (10 of 79 vs. 1 of 94; P = 0.003). Enterovirus-infected patients also had a shorter period from illness onset to presentation. Enterovirus-infected children were indistinguishable from those without enterovirus infection in their symptoms at onset, signs at presentation and total duration of illness (>7 days in both groups). Enterovirus-infected children were almost all treated with antibiotics (78 of 79; 99%), with 74 of 79 (94%) receiving parenteral antibiotics for a mean of 3.6 days. CONCLUSIONS: During the summer-fall months, 39% (79 of 203) of children for whom blood cultures and/or lumbar punctures were performed for suspected bacterial infection had enterovirus infection identified as the only explanation for their illness. Of those patients with no alternative diagnosis, enterovirus infection was confirmed in 46% (79 of 179). The majority of those patients requiring hospitalization were infected with enteroviruses. The use of PCR increases the number of children for whom a specific etiology of illness can be determined and may in the future reduce the hospitalization and use of unnecessary antibiotics in patients with enterovirus infections.

Emergency Service, Hospital↗
PubMed1998

Clinical and economic impact of enterovirus illness in private pediatric practice.

OBJECTIVE: To characterize the acute clinical course and economic burden of nonpolio enteroviral (NPEV) illness in the summer/fall season as seen in private pediatric practice. METHODS: We prospectively studied 380 children aged 4 to 18 years with systemic NPEV syndromes presenting to private suburban pediatric practices. Seventy-three asymptomatic controls were concurrently enrolled. Clinical diagnosis of NPEV illness was based on the presence of fever plus at least one of the following: headache and stiff neck (n = 2); myalgia and malaise (n = 105); nonpuritic maculopapular rash (n = 10); papulovesicular stomatitis (n = 214); papular rash of the hands, feet, and mouth (H/F/M) (n = 30); or pleurodynia (n = 11). Study participants were enrolled during a 4-month time span (July-October, 1994) and followed daily for 14 days. A parent symptom diary card and twice weekly phone contacts by study nurses characterized the illness to include the frequency of health care contacts, the necessity for laboratory tests, medication use, and school/work absenteeism. RESULTS: Three hundred seventy-two (98%) children completed the study; 122 (33%) of the patients were confirmed to be infected with NPEV. Confirmed NPEV infection was more frequently observed in Rochester, NY (85/147 = 58%) than in Scottsdale, AZ (32/224 = 14%). The age group 4 to 12 years comprised 79% to 90% of the enrollees, depending on the syndrome. Median duration of illness and median number of missed days of school/summer camp/work for the enrolled patients was: meningitis (7 days ill, 2 days missed), myalgia/malaise (9 days ill, 3 days missed), rash (6 days ill, 4 days missed), stomatitis (7 days ill, 2 days missed), H/F/M (7 days ill, 1 day missed), and pleurodynia (8 days ill, 3 days missed). Direct medical costs varied from $69 per case to $771 per case and indirect costs, attributable primarily to parent missed work and/or sick-child care, varied from $63 per case to $422 per case for H/F/M and meningitis, respectively. In households, H/F/M spread to 50% of siblings and 25% of parents. CONCLUSIONS: In our study population, NPEV infection: 1) caused sufficient illness to prompt physician visits in summer and fall; 2) occurred more frequently in 4 to 12 year olds than in adolescents; 3) produced various clinical syndromes concurrently during the same months in the same season of a given year; 4) varied in occurrence geographically; 5) was characterized by numerous symptoms of longer duration than previously recognized; and 6) produced a significant economic impact by generating both direct and indirect costs.

Absenteeism↗
PubMed1997

Adverse effects of maternal enterovirus infection on the fetus and placenta.

Gestational outcome in a murine model of congenital enterovirus infection was evaluated. Pregnant mice were inoculated intravenously with Theiler's murine encephalomyelitis virus (TMEV), a murine enterovirus, or with BHK 21 cell lysate (control) at 6-7 days of gestation (early) and sacrificed 6 or 12 days later, and their placentas and fetuses were studied. High rates of gross and histologic abnormalities (50%-87%) were seen in placentas and fetuses from dams infected with TMEV and sacrificed 6 days later. TMEV-infected dams sacrificed 12 days after inoculation had lower rates of placental-fetal abnormalities (25%-57%) but an additional 42% rate of complete pregnancy loss. Pregnancy loss (9%) and placental-fetal abnormalities (4%-7%) were uncommon in control animals. Rates of fetal abnormalities and placental infection in infected dams exceeded fetal viral infection, suggesting that TMEV infection adversely affects pregnancy either directly by fetal damage or indirectly by placental compromise.

Abortion, Spontaneous↗
PubMed1997

Reproducibility of AMPLICOR enterovirus PCR test results.

The reproducibility of AMPLICOR enterovirus PCR test results was determined with clinical samples of cerebrospinal fluid, serum, urine, and throat and rectal swabs. Among 608 samples from which duplicate aliquots were run simultaneously, only seven pairs gave discordant results. Among 104 samples from which duplicate aliquots were run in separate assays, no discordance was seen. Overall, the reproducibility of test kit results was 99% (705 of 712).

Blood↗
PubMed1995

Diagnosis of neonatal enterovirus infection by polymerase chain reaction.

A 5-hour colorimetric polymerase chain reaction (PCR) assay was more sensitive than viral culture in identifying viral infection in initial serum (13/16 vs 5/16; p = 0.008) and urine (10/16 vs 5/16; p = 0.2) specimens from 16 enterovirus-infected newborn infants, and remained more sensitive throughout their illnesses. Combined sensitivity of serum and urine PCR was 14 of 16 (88%). Results of all acute-phase PCR assays of serum and urine from four neonates with cultures negative for enterovirus were also negative. PCR assay of serum and urine facilitates rapid, accurate diagnosis of neonatal enterovirus infections.

Enterovirus↗
PubMed1995

Direct and uninterrupted RNA amplification of enteroviruses with colorimetric microwell detection.

BACKGROUND: Enteroviruses (EV) cause a broad spectrum of human diseases, of which aseptic meningitis is among the most common and most clinically vexing. While the clinical symptoms of meningitis caused by bacteria, fungi and viruses are similar, the diagnosis, therapy and outcome of disease caused by these agents vary greatly. In order to appropriately manage meningitis patients, rapid and reliable diagnosis of EV meningitis impacts significantly on patient management. OBJECTIVE: To develop a direct and uninterrupted RNA amplification of enteroviruses using rTth DNA polymerase. STUDY DESIGN: Purified coxsackievirus B6 RNA of various concentrations was amplified by rTth DNA polymerase-mediated amplification to determine analytic sensitivity. The specificity of the EV amplification was examined with a panel of nucleic acids from 36 EV serotypes, 15 non-EV pathogens and 10 coded clinical specimens of cerebrospinal fluid (CSF). RESULTS: All EV serotypes tested were detected successfully by this method at a sensitivity of 1 TCID(50) with the exception of echoviruses 1, 5, 22 and 23. Echovirus 5 was detected at 10 TCID(50), and echovirus 1 was detected at 100 TCID(50). Echoviruses 22 and 23 were not detectable at 100 TCID(50). Cross-reactivity of EV RT-PCR assay with 15 known non-EV meningitis pathogens has not been observed. Results of 10 CSF tested with this system correlated well with tissue culture. CONCLUSIONS: We have developed an EV amplification assay which has several important advantages over previously reported methods. This assay employs rTth DNA polymerase which possesses both reverse transcriptase and DNA polymerase activities, simplifying RNA reverse transcription and DNA amplification to an uninterrupted reaction. Additionally, potential carryover contamination and enhanced amplification specificity is provided by substituting dUTP for dTTP and adding uracil N-glycosylase (UNG) in the amplification reaction. Finally, the detection of amplified product is via a colorimetric, microwell format permitting the use of readily available instrumentation.

Journal Article↗