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Biomedical subjects

R J Whitley

Publications and source records attributed to R J Whitley.

At least 145 records · Page 8Linked to original sources
PubMed1989

Diseases that mimic herpes simplex encephalitis. Diagnosis, presentation, and outcome. NIAD Collaborative Antiviral Study Group.

A total of 432 patients underwent brain biopsy for presumptive herpes simplex encephalitis. Three patient groups were identified. The first group, 195 patients (45%), had herpes simplex encephalitis confirmed by the isolation of herpes simplex virus from brain tissue at biopsy (193 patients) or autopsy (2 patients). The second group, 95 patients (22%), had diseases that were identified but that were not caused by herpes simplex virus. Three subgroups were recognized: (1) 38 patients (9%) with treatable disease, (2) 40 patients (9%) with nontreatable but diagnosed viral infection, and (3) 17 patients (4%) with identified diseases neither of viral etiology nor treatable. The third group, 142 patients (33%), remained without a diagnosis. Clinical presentation of patients in the second group was similar to that of those with herpes simplex encephalitis and those without a diagnosis. Patients in the subgroup with nontreatable but diagnosed viral infections had the greatest likelihood of returning to normal.

Adolescent↗
PubMed1989

Intrauterine herpes simplex virus infection.

Neonatal herpes simplex virus (HSV) infection usually is the consequence of intrapartum infection, with disease onset between 5 and 15 days of life. More recently, intrauterine HSV infection has been identified. Intrauterine infection is apparent within the first 24-48 hr of life and is associated with skin vesicles/scarring, chorioretinitis, and/or hydraencephaly. The recognition that babies with these findings can have disease caused by HSV should prompt enhanced physician awareness in the evaluation of newborns with suspected intrauterine infection. The frequency of intrauterine infection appears to be about 5% of all babies with neonatal HSV infection.

Female↗
PubMed1989

Immunological alterations associated with recurrent herpes simplex genitalis.

Immunological studies on 12 patients with culture-proven frequently recurrent herpes simplex genitalis were performed. All the patients were evaluated at three time intervals, initially without lesions and/or within 24 hr of lesion onset (acute illness); Days 5-7 from onset and after healing (convalescence); and between recurrences (quiescence). During the first 24 hr of lesions there was a decreased number of helper (CD4+) and an increased number of suppressor/cytotoxic (CD8+) cells with a resultant decrease in the CD4/CD8 ratio. An increased proportion of CD8+ cells coexpressing the CD11 marker (suppressor cells) was noted and correlated with a low proliferative response to HSV-2 antigens. Both the NK cells (CD16+) and the NK cell activity versus HSV-2-infected targets and the K562 cell line were decreased. Five to seven days after onset the number of CD8+ cells remained increased, although the expression of CD11 marker was decreased, indicating that the majority of CD8+ cells were cytotoxic (i.e., CD8+CD11-). At this time, the lymphoproliferative response to HSV-2 antigens and NK cell activity increased, correlating both with the number of CD16+ cells and with the expression of HLA-DR on this subset. In the interval between two recurrences, no significant alteration in any of the above immunological parameters was observed.

Adult↗
PubMed1989

Effect of recombinant hybrid human interferon on replication and morphogenesis of HSV-1 in monkey cells.

Human recombinant alpha interferon, A/D, significantly reduced the replication and cell fusion induced by herpes simplex virus type 1 in monkey cells. Thin-section electron microscopy of interferon-treated monkey cells showed distinct assembly of nucleocapsids within the nucleus. Analysis of virus-specific proteins by the immunoblot technique confirmed that A/D interferon had no significant effect on the expression of major nucleocapsid proteins, although the expression of glycoproteins B and D was reduced in interferon-treated cells. The possibility of an interferon-induced block at a late stage in virus morphogenesis is discussed.

Animals↗
PubMed1989

A role for herpes simplex virus type 1 glycoprotein E in induction of cell fusion.

The role of herpes simplex virus type 1 (HSV-1) glycoprotein E (gE) in the induction of multinucleate cell (syncytium) formation was investigated using monoclonal antibodies and a gE deletion mutant, R7023. We found that monoclonal antibodies directed against gE blocked HSV-1-induced syncytium formation in human cells. R7023 also failed to induce syncytium formation in tissue culture cells. The results indicate that gE, in addition to glycoproteins B, D, H and the gene sequence located between 0.732 and 0.745 map units, is involved in cell fusion. Thus, this important biological property appears to be regulated by several HSV-1 gene products.

Animals↗
PubMed1988

Herpes simplex virus infections of the central nervous system. A review.

Herpes simplex virus (HSV) infections of the central nervous system are a significant cause of mortality and morbidity. The introduction of antiviral therapy has improved the outcome for patients with life-threatening disease. Neonatal HSV infection is usually acquired at the time of delivery by contact of the fetus with infected maternal genital secretions resulting in disease that can be localized to the skin, eye, and mouth, and can lead to encephalitis or become disseminated. A total of 291 babies with neonatal HSV infection have been evaluated over a period of 14 years with mortality and morbidity rates determined at one year. Vidarabine therapy decreased the incidence of mortality and improved morbidity rates; however, further improvement in mortality rates with acyclovir therapy has not been apparent. No significant clinical toxicity appeared in either treatment group. In order to improve outcome, earlier intervention and prophylactic strategies must be developed. For patients with herpes simplex encephalitis, acyclovir therapy is superior to vidarabine therapy for biopsy-proven disease. When outcome is compared for 136 vidarabine- and 46 acyclovir-treated, biopsy-proven patients, mortality rates are decreased to 20 percent with acyclovir, and approximately 40 percent of survivors are evaluated as normal at one year after therapy. Despite better outcome with antiviral therapy for the treatment of biopsy-proven herpes simplex encephalitis, further improvement is required.

Acyclovir↗
PubMed1988

Neurovirulence in an experimental focal herpes encephalitis: relationship to observed seizures.

An animal model of focal herpes simplex encephalitis was used to study several strains of type-1 herpes simplex virus. Rabbits were inoculated in the olfactory bulb by a standardized technique. Virus strains resulting in mortality of greater than 70% produced seizures of 3 types, and all animals that seized became moribund or died. In contrast, a virus strain resulting in a 20% mortality produced no seizures. Administration of 60 mg phenobarbital intramuscularly daily reduced mortality significantly in animals given the epileptogenic viruses. Cultures from temporal and frontal lobes showed viral growth more frequently than did cultures of other brain areas. Microscopic examination of routine and immunoperoxidase-stained brain sections confirmed the focal nature of the infection. Clinical syndromes such as seizures arising from viral brain disease may influence mortality in animal model systems.

Animals↗
PubMed1988

An isoelectric focusing study in herpes simplex virus encephalitis.

To establish an early reliable diagnostic test for herpes simplex virus (HSV) type 1 encephalitis (HSVE), we used isoelectric focusing (IEF) and an IEF-overlay technique with radiolabeled HSV glycoprotein B (gB) to study 7 serum and 12 cerebrospinal fluid (CSF) samples from 12 patients with presumed or biopsy-proved HSVE. Blood-brain barrier damage and increased intra-blood-brain barrier IgG synthesis were detected in 5 of the 7 patients with HSVE. CSF oligoclonal bands were found in 6 of 11 patients. Using an IEF-overlay technique, we detected anti-gB antibody in all serum (7 of 7) and in 10 of 12 CSF samples. Anti-gB antibody was found in 4 of 6 CSF specimens obtained within the first week of disease (days 3 to 5) and in all samples collected later in the disease. The pH range of anti-gB antibody activity was broad (4.5 to 9.5), indicating a heterogeneous immune response to HSV. A hematogenous origin of the CSF antibody was suggested because anti-gB antibody appeared in serum before matched CSF and because both serum and matched CSF had a similar antibody IEF pattern. Local production of anti-gB antibody was suggested in some cases because of a greater prominence of anti-gB antibody in CSF than in matched sera and because CSF oligoclonal bands had anti-gB antibody activity. In contrast, only one of 6 CSF samples from patients with multiple sclerosis had gB antibody activity; in this case, anti-gB antibody activity did not correspond in isoelectric point location to oligoclonal bands.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1988

Intravenous acyclovir therapy of first episodes of genital herpes: a multicenter double-blind, placebo-controlled trial.

PURPOSE: A collaborative multicenter double-blind, placebo-controlled trial of intravenous acyclovir treatment of first-episode genital herpes was performed in order to substantiate previous findings on the efficacy and safety of this drug, to evaluate the influence of parenteral therapy on recurrence frequency, and to obtain further data on the natural history of genital herpes. PATIENTS AND METHODS: Eighty-two patients with first episodes of genital herpes simplex virus (HSV) infection were randomly assigned in a double-blind fashion to treatment with intravenous acyclovir (5 mg/kg every eight hours) or placebo for five days. Before therapy, all lesions in the genital/perineal area and in extragenital sites were cultured. New lesions appearing in both areas after the onset of therapy were cultured separately. Lesions in all groups were cultured until completely healed. Sera were collected from all patients on entry to the study and on Day 21 to determine presence or absence of antibodies to HSV-1 and HSV-2. Time to healing, time to crusting, time to cessation of viral shedding, and appearance of new lesions during therapy were compared for each treatment group. RESULTS: Patients receiving acyclovir experienced a significant reduction in the median duration of pain (4.3 versus 4.8 days, p = 0.019), viral shedding (1.9 versus 8.4 days, p less than 0.001), and time to healing (8.4 versus 11.5 days, p = 0.02) compared with placebo recipients. These differences were largely attributable to the effect of therapy in the subset of patients with primary disease in whom acyclovir reduced the median duration of pain from 10.6 days to 4.2 days, the median duration of viral shedding from 17.1 days to 1.9 days, and the median time to healing from 14.2 days to 8.3 days. The rate of subsequent recurrence of genital herpes was not altered by acyclovir treatment: 24 of 32 acyclovir recipients (75 percent) experienced one or more recurrences during a mean follow-up of 14 months compared with 19 of 27 placebo recipients (70 percent). Among patients experiencing recurrences, the mean number of recurrences per month among acyclovir recipients was 0.25 compared with 0.19 for patients given placebo. CONCLUSION: This multicenter trial confirms the efficacy of intravenous acyclovir in the management of first-episode genital herpes, especially in patients with primary infection. However, therapy did not alter the frequency of recurrences.

Acyclovir↗
PubMed1988

Antiviral treatment of a serious herpes simplex infection: encephalitis.

Herpes simplex encephalitis is the most common cause of sporadic encephalitis in the western world. Patients usually have altered levels of consciousness, altered levels of mentation, fever, headache, and personality changes. These may progress to hemiparesis and seizures. Exact diagnosis must be established by brain biopsy and identification of the virus in biopsy material. There is a great need for a noninvasive test that is positive early in the disease. Without antiviral treatment the mortality rate is greater than 70%, and many survivors have serious disabilities. Both adenine arabinoside and acyclovir decrease death and morbidity, but acyclovir is the preferred drug. With acyclovir about 40% of patients will survive with normal development or minor levels of impairment but more than half of the patients will die or suffer significant impairment. It is essential to treat early; patients who are young and have not reached coma or impaired consciousness may show 65% recovery and return to normal function. Development of new antiviral drugs or other types of therapies is desirable. Herpetic skin lesions are likely to be more confusing than diagnostic because other types of encephalitis with fever often precipitate recurrent herpes that is unrelated to the encephalitis.

Acyclovir↗
PubMed1988

Changing presentation of herpes simplex virus infection in neonates.

We compared the clinical presentation of 95 newborns with herpes simplex virus (HSV) infection from 1973 through 1981 (first period) with data from 196 newborns evaluated from 1982 through 1987 (second period). There was a significant change in the presentation of infection in these infants. From the first to the second period, the frequency of disseminated disease decreased from 50.5% to 22.9%, whereas the frequency of skin, eye, and mouth (SEM) diseases increased from 17.9% to 43.4% (P less than .001). The frequency of infants with central nervous system (CNS) disease remained relatively unchanged--31.6% versus 33.7%. We also compared the demographic and clinical characteristics of the infants and their mothers. For neonates with CNS or disseminated infection, disease duration and frequency of prematurity were significantly decreased in the second period, as was the frequency of skin vesicles for newborns with SEM or disseminated infection. These changes are most likely the consequence of recognizing and treating SEM infection before its progression to more-severe disease.

Central Nervous System↗
PubMed1988

Antibody response of the newborn after herpes simplex virus infection.

Antibody responses to herpes simplex virus (HSV) types 1 and 2, as determined by enzyme-linked immunoabsorbent assay (ELISA), neutralization, and immunoblot, were assessed in sera from newborns with documented HSV infections. The antibody response of the newborns was defined by disease duration and correlated with disease classification and outcome. Three unique observations were made. First, the quantity of total antibodies at presentation, as determined by ELISA and neutralization, was not predictive of disease classification or outcome. Second, the frequency and intensity of antibody responses to immunologically recognized HSV polypeptides in newborns with central nervous system and disseminated infections were greater than those in newborns with infections localized to the skin, eye, and mouth. Third, the long-term outcome in HSV-infected newborns could be predicted by the quantity of antibodies to the immediate-early infected cell polypeptide ICP 4. These data provide insight into host response to individual polypeptides and their potential value in predicting long-term prognosis.

Antibodies, Viral↗
PubMed1988

Protection against herpetic ocular disease by immunotherapy with monoclonal antibodies to herpes simplex virus glycoproteins.

In this paper we describe the ability of monoclonal antibodies to prevent herpetic stromal or interstitial keratitis following corneal infection in an outbred mouse model. Monoclonal antibodies recognizing antigenic determinants on glycoproteins B, C, D, and E of herpes simplex virus type 1 were injected intraperitoneally into CF-1 outbred mice 24 or 48 h following inoculation of the cornea with the RE strain of herpes simplex virus type 1. Passive, postexposure immunization with monoclonal antibodies had little effect on the severity of the initial corneal infection or the frequency of latent viral infections in the trigeminal ganglia, except for virus-neutralizing antibodies specific for glycoproteins B and D. A significant correlation was found between the severity of epithelial keratitis and the frequency of latent ganglionic infections. However, immunization with monoclonal antibodies protected the mice against encephalitis and prevented the development of necrotizing stromal keratitis that leads to permanent corneal scarring and blindness. This form of herpetic ocular disease does not respond to antiviral chemotherapy. Since nonneutralizing monoclonal antibodies were just as effective in prevention of encephalitis and stromal keratitis as ones that neutralized the virus in vitro, and antibodies were not administered until 24 or 48 h after corneal inoculation, we suggest that inactivation of infectious virus is not the only protective mechanism in this model.

Animals↗