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Biomedical subjects

C G Prober

Publications and source records attributed to C G Prober.

At least 19 recordsLinked to original sources
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

Respiratory syncytial virus and ribavirin: quo vadis?

Respiratory syncytial virus is the major respiratory pathogen in infants and young children. Every year, this unique and ubiquitous virus accounts for substantial morbidity and occasional mortality in this age group. Until recently, therapy for respiratory syncytial virus infections was limited to supportive measures such as hydration, supplemental oxygen, and assisted ventilation. Therefore, the licensure of ribavirin in 1986 for treatment of respiratory syncytial virus infections raised hopes for specific and effective therapy. However, the use of ribavirin has been the subject of continuing controversy and debate. Despite at least eight controlled clinical trials involving collectively over 170 patients treated with ribavirin since 1983, no clear consensus has developed regarding which patients should be treated with ribavirin. Major issues are weaknesses in the design and methodology of studies that claim treatment efficacy, the clinical significance of the demonstrated treatment effects, potential teratogenicity to health care workers exposed to aerosolized ribavirin, and cost-effectiveness of the intervention. This review will explore each of these areas of controversy and consider the unanswered questions to which future research must be directed.

Animals↗
PubMed1992

Potential of population pharmacokinetics to reduce the frequency of blood sampling required for estimating kinetic parameters in neonates.

Data obtained from neonates receiving zidovudine as part of a phase I study were used to estimate the population pharmacokinetic parameters of this drug and to determine the minimum number of data points necessary to provide accurate estimates of the kinetic parameters and their variability. Analysis was performed with 541 concentrations of zidovudine, obtained from 32 infants and with a variety of reduced data sets using NONMEM (nonlinear mixed effect model). The reduced data sets were derived by randomly reducing the number of sampling time points per dosing interval and/or by randomly reducing the number of available subjects. We determined that accurate estimates of pharmacokinetic parameters and their variability were obtained with the inclusion of all 32 patients using only two concentration-time points per dose interval, provided that one of the points was obtained during the first 2 h after administration of the drug. The parameters themselves were adequately estimated with only 24 subjects and two concentration-time points per dose interval. We suggest that NONMEM should be used in addition to the traditional pharmacokinetic analysis to obtain more precise information directly in the population of interest with a minimum of blood sampling from each patient. This is especially critical in infants whose blood volumes are limited.

Biological Availability↗
PubMed1991

A controlled trial of aerosolized ribavirin in infants receiving mechanical ventilation for severe respiratory syncytial virus infection.

BACKGROUND: Although the antiviral agent ribavirin improves the course of lower respiratory tract disease in spontaneously breathing infants with respiratory syncytial virus infection, it is not known whether ribavirin can benefit infants with severe respiratory syncytial virus disease who require mechanical ventilation. METHODS: We conducted a randomized, double-blind, placebo-controlled evaluation of ribavirin (20 mg per milliliter) administered continuously in aerosolized form to infants receiving mechanical ventilation for respiratory failure that was caused by documented respiratory syncytial virus infection. RESULTS: Of the 28 infants (mean [+/- SD] age, 1.4 +/- 1.7 months) enrolled, 7 had underlying diseases predisposing them to severe infection (mean age, 3.0 +/- 2.6 months), and 21 were previously normal (mean age, 0.8 +/- 0.9 month). Among the 14 infants who received ribavirin, the mean duration of mechanical ventilation was 4.9 days (as compared with 9.9 days among the 14 who received placebo; P = 0.01), and the mean length of supplemental oxygen use was 8.7 days (as compared with 13.5 days; P = 0.01). The mean length of the hospital stay was 13.3 days after treatment with ribavirin and 15.0 with placebo (P = 0.04). When only the 21 previously normal infants were considered, the mean length of the hospital stay was 9.0 days for the ribavirin recipients and 15.3 days for those who received placebo (P = 0.005). CONCLUSIONS: In infants who require mechanical ventilation because of severe respiratory syncytial virus infection, treatment with aerosolized ribavirin decreases the duration of mechanical ventilation, oxygen treatment, and the hospital stay.

Aerosols↗
PubMed1991

Pharmacokinetics of acyclovir in the term human pregnancy and neonate.

Concern about neonatal herpes often leads to cesarean delivery of infants in women with a history of genital herpes. The antiviral drug acyclovir has been used effectively to suppress genital herpes simplex virus recurrences in nonpregnant adults. Its administration to pregnant women with recurrent genital herpes may reduce herpes simplex virus recurrences and thus may decrease the cesarean section rate among this population. To study the pharmacokinetics, safety, and patient tolerance of suppressive oral acyclovir, either 200 mg (n = 7) or 400 mg (n = 8) was administered orally every 8 hours to pregnant women with a history of recurrent herpes simplex virus, from 38 weeks' gestation until delivery. The mean +/- SD plasma levels for the 200 and 400 mg groups, respectively, were: first dose peak, 1.7 +/- 0.6 and 2.3 +/- 1.0 mumol/L; steady-state trough, 0.7 +/- 0.3 and 0.8 +/- 0.6 mumol/L; steady-state peak, 1.9 +/- 1.0 and 3.3 +/- 1.0 mumol/L. In late gestation maternal acyclovir pharmacokinetics were similar to those of nonpregnant adults from other studies. Acyclovir was concentrated in the amniotic fluid; however, there was no accumulation in the fetus (mean maternal/infant plasma ratio at delivery was 1.3). Acyclovir was well tolerated, and no toxicity was seen in the mothers or infants. The administration of acyclovir, 400 mg every 8 hours, appears appropriate for use in an efficacy and safety study regarding suppression of herpes simplex virus recurrences during the last weeks of pregnancy.

Acyclovir↗
PubMed1991

Investigation of varicella-zoster virus infection by polymerase chain reaction in the immunocompetent host with acute varicella.

A polymerase chain reaction (PCR) method developed to detect varicella zoster virus (VZV) in clinical samples is based on amplifying sequences of viral gene 31, the coding region for glycoprotein II. Its sensitivity was evaluated by amplification from plasmid VZV DNA containing VZV gene 31; 45 copies were detected in 1 microgram of human DNA. In testing within 24 h after the onset of varicella exanthem, 21 (75%) of 28 lesion samples were positive by VZV PCR, whereas VZV was isolated from only 21% by a standard tissue culture method. Only 1 (3.3%) of 30 samples of oropharyngeal secretions but peripheral blood mononuclear cells from 8 (67%) of 12 patients were positive. The sensitivity and specificity of the VZV PCR method indicates its usefulness for investigating the pathogenesis of VZV infection. Direct contact with cutaneous lesions rather than respiratory secretions may be the most important route of VZV transmission from healthy individuals with acute varicella.

Acute Disease↗
PubMed1990

Use of polymerase chain reaction for successful identification of asymptomatic genital infection with herpes simplex virus in pregnant women at delivery.

The polymerase chain reaction was adapted to the amplification of a herpes simplex virus (HSV) DNA sequence, common to HSV types 1 and 2 (HSV-1, HSV-2). The amplified product was detectable by ethidium-bromide staining or Southern hybridization of gels and by dot hybridization. The HSV polymerase chain reaction detected HSV DNA in samples obtained from eight patients with genital lesions from which HSV-2 was isolated in tissue culture and from four patients with labial lesions from which HSV-1 was isolated. The HSV polymerase chain reaction identified HSV in clinical specimens obtained from 11 women who had asymptomatic genital HSV infections at delivery. None of 11 samples obtained at delivery from women who had antibodies to HSV-2, but whose delivery cultures were negative, were positive by polymerase chain reaction and no false-positive reactions were obtained when the reaction mixture contained human cell DNA or varicella-zoster virus, cytomegalovirus, Epstein-Barr virus, or human papillomavirus DNA.

Blotting, Southern↗
PubMed1990

A prospective evaluation of primary genital herpes simplex virus type 2 infections acquired during pregnancy.

In order to study the epidemiology of herpes simplex type 2 (HSV-2) infections during pregnancy, we used an enzyme immunoassay to detect type-specific antibodies to HSV-2 glycoprotein G in serial blood samples obtained from a cohort of 1891 pregnant women. Blood samples obtained at about 17 and 32 weeks of gestation and at the time of delivery were assessed for antibody to HSV-2 glycoprotein G in order to evaluate the prevalence of past infections with HSV-2 and the rate of acquisition of HSV-2 infection during pregnancy. Three hundred eleven pregnant women (16.5%) were found to have had past infections with HSV-2. Four of the 1580 women who were initially seronegative developed antibodies to HSV-2 during pregnancy. The annualized rate of acquisition of HSV-2 infection in pregnant women was 0.58%. Three of four women had asymptomatic primary infections; all of the women had preexisting HSV-1 immunity. None of the women or their infants experienced any adverse consequences of gestational herpes. Based upon our very limited number of observations to date, asymptomatic primary episodes occurring in women with previous HSV-1 immunity may be of less consequence to the fetus and neonate than symptomatic true primary HSV-2 infections.

Adolescent↗