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Biomedical subjects

C G Prober

Publications and source records attributed to C G Prober.

At least 37 records · Page 2Linked to original sources

T cell recognition and cytokine production elicited by common and type-specific glycoproteins of herpes simplex virus type 1 and type 2.

T cell recognition of common and type-specific herpes simplex virus (HSV) glycoproteins was measured in 72 subjects. T cells were stimulated with whole HSV-2 antigen and glycoproteins gB2, gD2, and gG2. T cell proliferation in response to HSV-2 antigen and gG2 was significantly higher in subjects with HSV-2 infection than in those with HSV-1 infection only; responses to gB2 and gD2 were the same. T helper (Th) type 1 and Th2 cytokine production in response to whole HSV-2 antigen, gB2, and gD2 was evaluated in 33 subjects. Interleukin (IL)-2 and interferon-gamma responses to most antigens were significantly higher among HSV-2-seropositive subjects than among seronegative subjects. IL-4 synthesis was negligible; IL-10 was produced in seronegative and seropositive persons, but HSV-2 antigen responses were significantly higher in HSV-2-seropositive persons. Naturally acquired immunity to HSV involves T cell recognition of common and type-specific glycoproteins, prominent Th1 responses, and discordant Th2 responses with little IL-4 but substantial IL-10 production.

Antigens, Viral↗

Application of the polymerase chain reaction to the diagnosis and management of neonatal herpes simplex virus disease. National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group.

Cerebrospinal fluid (CSF) specimens from 77 neonates with herpes simplex virus (HSV) disease were evaluated retrospectively by polymerase chain reaction (PCR). Samples were collected from 202 infants enrolled in a National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group trial that compared vidarabine with acyclovir for the treatment of neonatal HSV infection. HSV DNA was detected in the CSF of 26 (76%) of 34 infants with CNS disease, in 13 (93%) of 14 infants with disseminated infection, and in 7 (24%) of 29 with skin, eye, or mouth (SEM) involvement. One of the 7 PCR-positive SEM patients subsequently developed severe neurologic impairment. Eighteen (95%) of 19 infants with positive CSF PCR results after the completion of 10 days of antiviral therapy experienced significant morbidity or mortality. Application of PCR to neonatal HSV disease may provide additional information on which clinical decisions may be based, although its diagnostic utility outside the research setting is unproven.

Brain↗

Pharmacokinetic optimisation of the treatment of septic arthritis.

Early diagnosis and treatment of septic arthritis improves the potential for a favourable outcome. Optimal treatment includes the prompt and judicious use of effective antimicrobial agents coupled with prompt drainage of the affected joint. Adequate drainage may be accomplished by means of repeated closed large-bore needle aspiration, arthroscopy, or an open surgical procedure. The purpose of this article is to describe optimal antimicrobial therapy based upon available pharmacokinetic data. The host-dependent vulnerability to specific pathogens, local antibacterial susceptibility patterns and knowledge of antibacterial activity at the site of infection must all be taken into account when planning appropriate treatment. This article does not address arthritis secondary to human and animal bites, diabetic foot infections, mycobacteria, fungi, Lyme spirochaete, or other nonbacterial causes of septic arthritis.

Adult↗

Cesarean delivery for women presenting with genital herpes lesions. Efficacy, risks, and costs.

OBJECTIVE: To assess the effect of cesarean delivery on neonatal and maternal morbidity and mortality and their associated costs for two populations of women presenting with genital herpes lesions at delivery: those with and those without a history of genital herpes. DATA SOURCES: MEDLINE (search for herpes simplex virus and neonatal, cesarean, and mortality) and recognized experts. DATA EXTRACTION: The quality of the overall data used for baseline values was graded using a predetermined scale. RESULTS: The practice of cesarean delivery for women with a history of genital herpes lesions that recur at delivery results in more than 1580 excess cesarean deliveries performed for every poor neonatal outcome prevented, a cost per neonatal herpes case averted of $2.5 million and a cost per quality-adjusted life-year gained of $203,000. For these women, lowering the efficacy of cesarean delivery or the herpes simplex virus vertical transmission rate could result in maternal deaths outnumbering neonatal deaths prevented. In contrast, cesarean delivery for women with no history of genital herpes simplex virus who have lesions at delivery has low maternal costs per neonatal benefit and saves money. CONCLUSIONS: Women who present with their first clinical episode of genital herpes at delivery should have a cesarean section performed. However, the current practice of cesarean delivery for women with a history of genital herpes lesions that recur at delivery results in high maternal morbidity and mortality at substantial financial expense, underscoring the urgency of examining alternative management strategies.

Cesarean Section↗

Detection of antibodies to herpes simplex virus type 2 with a mammalian cell line expressing glycoprotein gG-2.

The gene (US4) coding for herpes simplex virus type 2 (HSV-2) glycoprotein G (gG-2) was cloned and constitutively expressed in Chinese hamster ovary (CHO) cells. The expression vector containing the dihydrofolate reductase (dhfr) gene, and the HSV-2 US4 gene under the control of the Simian virus 40 early promoter (SV40 EP), was transfected into dhfr-deficient CHO cells. The transfected cells were selected and amplified using methotrexate (MTX). To demonstrate that the gG-2 produced in these transformed cells had antigenic determinants in common with the native glycoprotein, CHO cells expressing gG-2 were used in an immunofluorescent assay (IFA) for the detection of HSV-2 type-specific antibodies in human serum samples. Seven of eight serum samples from adults with prior episodes of culture proven HSV-2 infections were found to be positive by the IFA method whereas none of seven serum samples from young children with culture documented HSV-1 infections were positive by IFA. Thus the recombinant CHO : gG-2 cells have diagnostic utility in an HSV-2 specific serologic assay.

Journal Article↗

Herpetic vaginitis in 1993.

Substantial advances have been made in our understanding of HSV and genital herpes. The molecular biology of viral structure and function and the pathogenesis of infection have been elucidated to a large degree, and epidemiologic investigations, based on reliable type-specific assays, have been done. Diagnostic techniques have been refined, and the value of therapy has been defined. Currently, management strategies for pregnant women and their neonates are based on data rather than hypothesis, and rational counseling is feasible. The next major advance in the field would be the availability of a safe and effective vaccine, the development and investigation of which is being pursued vigorously.

Acyclovir↗

Neonatal herpes: vexing dilemmas and reasons for hope.

Neonatal herpes, one of the most feared infections during infancy, continues to command the attention of many investigators. In the past year, important new findings were reported pertaining to epidemiology, diagnosis, prevention, and treatment of this disease. Unfortunately, practical solutions for many clinical problems remain elusive. This review describes recent advances in our understanding of neonatal herpes with particular emphasis on the dilemmas and controversies associated with management and prevention. Although elimination of neonatal herpes remains a distant goal, the review discusses reasons for hope, including improved prevention strategies based on recent epidemiologic data, development of new rapid diagnostic methods, and progress in the quest for an effective vaccine.

Herpes Simplex↗

Identification of women at unsuspected risk of primary infection with herpes simplex virus type 2 during pregnancy.

BACKGROUND: Primary infections with herpes simplex virus type 2 (HSV-2) acquired by women during pregnancy account for about half of the morbidity and mortality from HSV-2 among neonates. The other half results from reactivation of old infections. Better methods are needed to identify which women are at risk for primary HSV-2 infection. METHODS: We prospectively studied HSV-2 infections among pregnant women who were patients in private obstetrical practices. Using an enzyme-linked immunosorbent assay that detects type-specific antibodies to HSV-2 glycoprotein G, we determined the prevalence at base line of HSV-2 infections among pregnant women and their husbands, the frequency of discordance for infection between partners, and the risk of seroconversion during pregnancy among the seronegative women whose husbands were seropositive. RESULTS: The seroprevalence of HSV-2 was 32 percent among the 277 women followed throughout their pregnancies and 25 percent among the 190 husbands studied. Two thirds of the HSV-2-seropositive women had no history of genital herpes. Of the 190 couples, 139 (73 percent) were serologically concordant for HSV-2 antibodies (57 percent being seronegative and 16 percent being seropositive), whereas 51 couples (27 percent) were discordant, despite having been sexually intimate for a mean of 6.1 years. Eighteen women who were seronegative for HSV-2 (9.5 percent) had seropositive partners, of whom 10 (56 percent) had no history of genital herpes. Thus, approximately 5 percent of these pregnant women had an unsuspected risk of contracting a primary HSV-2 infection. One of the 18 seronegative women with a seropositive husband seroconverted to HSV-2 during pregnancy; none of the other women seroconverted. CONCLUSIONS: In this study about 10 percent of pregnant women were at risk of contracting a primary HSV-2 infection from their HSV-2-seropositive husbands. In addition, about a third of these women were seropositive for HSV-2 and thus at risk for asymptomatic, reactivated infections. Serologic testing of couples can identify women who are at risk for primary or reactivated HSV-2 infections during pregnancy.

Antibodies, Viral↗

Acyclovir treatment of varicella in otherwise healthy adolescents. The Collaborative Acyclovir Varicella Study Group.

STUDY OBJECTIVE: To determine whether orally administered acyclovir is of therapeutic benefit for varicella in otherwise healthy adolescents, and to compare the severity of the disease in adolescents with that in younger children. DESIGN: Multicenter, randomized, placebo-controlled, double-blind trial. SETTING: Patients' homes and university hospital clinics. PATIENTS: Sixty-eight adolescents between 13 and 18 years of age with varicella entered the study. Of the 62 adolescents with laboratory-confirmed varicella who were included in the final analysis, 31 received acyclovir and 31 received placebo. INTERVENTIONS: Placebo or an 800 mg acyclovir tablet was given orally four times daily for 5 days, beginning within 24 hours of onset of rash. MEASUREMENTS AND MAIN RESULTS: Acyclovir recipients had significant reductions in times to cessation of new lesion formation (p less than 0.001), maximum number of lesions (p = 0.019), and defervescence (p = 0.045). Mean constitutional illness score was significantly reduced on day 4 (0.5 vs 1.5, p = 0.05), as was the mean number of residual hypopigmented lesions present on 28-day follow-up examination (22.7 vs 92.7, p = 0.018). Two complications, both bacterial superinfections, occurred in placebo recipients. Adverse experiences and varicella-zoster virus antibody titers measured 28 days after enrollment were similar in both treatment groups. Comparison of placebo recipients with children 2 to 12 years of age participating in a companion study indicated that varicella is more severe in adolescents: mean maximum total lesions (421 vs 347, p = 0.003), mean maximum constitutional illness score (3.1 vs 2.2, p = 0.032), and mean number of residual lesions (92.7 vs 33.2, p = 0.01) were all greater in the adolescent population. CONCLUSIONS: Oral acyclovir therapy is safe and effective for treatment of varicella in otherwise healthy adolescents; this may be an appropriate subgroup for treatment with antiviral drugs because the disease is more severe in them than in younger children.

Acyclovir↗

The management of pregnancies complicated by genital infections with herpes simplex virus.

In this review we summarize current knowledge related to the identification of pregnancies that may be complicated by genital herpes and describe the consequences of maternal infections with genital herpes. We address the implications of this information for the management of genital herpes during pregnancy and at delivery and for the care of neonates exposed to herpes simplex virus at delivery. On the basis of the current data, we cannot make specific recommendations concerning many of the clinical problems that are caused by herpes simplex virus infections in pregnant women. We identify and discuss unresolved questions about optimal management.

Female↗