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L Corey

Publications and source records attributed to L Corey.

At least 253 records · Page 14Linked to original sources
PubMed1992

Evaluation of new anti-infective drugs for the treatment of uncomplicated gonorrhea in adults and adolescents. Infectious Diseases Society of America and the Food and Drug Administration.

Gonorrhea is among the most common sexually transmitted diseases. Treatment for uncomplicated gonorrhea should be efficacious in > or = 95% of cases. Because patients with gonococcal infections often have other sexually transmitted diseases concurrently, individuals enrolled in clinical trials of therapy for gonorrhea should also be evaluated for infection with Chlamydia trachomatis and for syphilis. Testing for other pathogens should be considered in light of the clinical presentation. The presence of gonococcal infection is defined by a positive culture of a specimen obtained from an appropriate mucosal site. Patients enrolled in clinical trials should be otherwise-healthy adults who agree to return for follow-up assessment. These patients should be stratified by gender and anatomic site of infection. The preferred study design is a prospective, randomized, double-blind, active-control comparison. In some circumstances, however, historical controls may suffice. The study drug must have an efficacy rate of > or = 95% in genital and rectal infections. Microbiological eradication, demonstrated by negative cultures of samples from all potentially infected mucosal sites at follow-up, is the sole determinant of efficacy.

Adolescent↗
PubMed1992

Evaluation of new anti-infective drugs for the treatment of sexually transmitted chlamydial infections and related clinical syndromes. Infectious Diseases Society of America and the Food and Drug Administration.

This guideline addresses clinical trials of new antimicrobial agents in the treatment of uncomplicated genital infections caused by Chlamydia trachomatis and of syndromes resembling chlamydial infections. The most common clinical manifestations of chlamydial infection are urethritis in men and mucopurulent cervicitis in women. However, many chlamydial infections are not associated with inflammatory symptoms or signs. Culture is the diagnostic standard for defining the presence of C. trachomatis, although nonculture tests may be used in screening patients for enrollment in clinical trials. Susceptibility testing for C. trachomatis is laborious and difficult to standardize; only a few clinical isolates need to be tested in vitro. Prospective, randomized, double-blind, active-control comparative studies are recommended. Eradication of C. trachomatis defines both microbiological success and overall cure for chlamydial infection, but clinical and nonmicrobiological laboratory criteria are paramount in assessing the therapeutic response in nonchlamydial urethritis or cervicitis.

Anti-Bacterial Agents↗
PubMed1992

Evaluation of new anti-infective drugs for the treatment of syphilis. Infectious Diseases Society of America and the Food and Drug Administration.

Syphilis is caused by Treponema pallidum, a spirochetal bacterium pathogenic only for humans. The clinical course of disease is divided into three stages interspersed by periods of latency. Penicillin remains the treatment of choice for all stages of infection; tetracycline or erythromycin may be used as therapeutic alternatives in defined circumstances. Patients enrolled in clinical trials should be evaluated clinically, microscopically, and serologically for the presence of the spirochete. All participants, after undergoing counseling and giving informed consent, should be tested for infection with human immunodeficiency virus. Specific criteria exist for diagnosis of syphilis and response to therapy. It may be desirable to perform a small, uncontrolled, open trial of a new anti-infective drug for the collection of preliminary evidence of efficacy. A larger-scale, randomized, active-control comparative clinical trial is necessary to prove efficacy.

Animals↗
PubMed1992

Special issues in clinical trials of new anti-infective drugs for the treatment of sexually transmitted diseases. Infectious Diseases Society of America and the Food and Drug Administration.

Several special issues arise in relation to clinical trials of therapy for sexually transmitted diseases. These issues include the desirability of including adolescents and both pregnant and nonpregnant women in the trial, the use of unapproved control regimens, problems with antimicrobial susceptibility testing due to inadequate methodology and the need for prompt treatment, the need to assess agents for treatment of syndromes of unknown microbial etiology, toxicity considerations related to the use of single-dose regimens, management of the sexual partners of the participants in the trial, analysis of data despite the high frequency of minor protocol violations, sexual reexposure to infection during the trial, and the potential for loss, alteration, or falsification of data because of the relative simplicity of the usual protocol design and the diagnostic reliance on specimens that are routinely discarded.

Adolescent↗
PubMed1992

Evaluation of new anti-infective drugs for the treatment of genital infections due to herpes simplex virus. Infectious Diseases Society of America and the Food and Drug Administration.

This guideline addresses clinical trials of new therapies for genital infections due to herpes simplex virus (HSV). Of the two types of virus, HSV-2 is the more common pathogen. Both HSV-1 and HSV-2 become latent in sacral nerve root ganglia and intermittently reactivate. Patients who have frequent recurrences (more than four per year) may be candidates for long-term suppressive therapy. In both first-episode and recurrent genital HSV infections, lesions should be cultured for HSV. Testing for human immunodeficiency virus is encouraged but not required. Serum antibodies to HSV-1 and HSV-2 should be quantitated at enrollment and 3-5 weeks thereafter. Randomized, double-blind, active-control comparative studies are generally recommended. Placebo-controlled trials may be appropriate for recurrent genital herpes or for suppression of recurrences. Final evaluation should generally take place 10-15 days after the completion of therapy.

Anti-Infective Agents↗
PubMed1992

Diminished interferon-gamma and lymphocyte proliferation in neonatal and postpartum primary herpes simplex virus infection.

Interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha production and lymphocyte proliferation in response to herpes simplex virus (HSV) antigen were assessed in 13 neonates and 3 parturient women with primary HSV infection. In comparison with 9 nonparturient adults, the neonates and parturient women showed significantly (P less than .01) diminished HSV antigen-stimulated lymphocyte proliferation and IFN-gamma production in the first 3-6 weeks after onset of infection. TNF alpha production did not differ significantly among HSV-infected groups. The impairment in neonatal cellular immunity was due, at least in part, to a specific deficit in response to HSV antigen. Lymphocyte proliferation and TNF alpha production in response to the mitogen concanavalin A (ConA) were comparable in adults and infants, but ConA-stimulated IFN-gamma production in infants was diminished throughout the study period. In contrast, HSV antigen-stimulated IFN-gamma production was comparable in infants and adults after 6 weeks. Not all patients with diminished cellular immune responses to HSV antigen manifested severe clinical disease. Nevertheless, patients with significant clinical morbidity had diminished cellular immune responses to HSV antigen. These results suggest that delayed acquisition of antigen-specific cellular immunity in primary HSV infection predisposes to more severe clinical disease.

Antibodies, Viral↗
PubMed1992

Vaccination of vaccinia-naive adults with human immunodeficiency virus type 1 gp160 recombinant vaccinia virus in a blinded, controlled, randomized clinical trial. The AIDS Vaccine Clinical Trials Network.

The safety and immunogenicity of a human immunodeficiency virus type 1 (HIV-1) gp160 recombinant vaccinia virus (HIVAC-1e) vaccine was evaluated in vaccinia-naive, healthy adults at low risk for acquiring HIV-1 infection. Volunteers (n = 36) were randomized to receive HIVAC-1e or control vaccinia virus at two dosages by bifurcated needle puncture at 0 and 2 months; 12 HIVAC-1e and 6 control vaccinia virus recipients received either 10(6) or 10(7) pfu/mL at each inoculation. There was no significant difference in lesion size, level of viral replication, or systemic symptoms after vaccination with HIVAC-1e or control vaccinia virus. Of 22 HIVAC-1e recipients with lesion formation, 16 developed low-titer gp160-specific antibody responses detectable by Western blot. The peak response occurred between days 70 and 120 and was still detectable at day 365 in 9 of 18 vaccinees. gp160-specific lymphoproliferative responses were detected in 5 of 10 vaccinees. Vaccination with HIVAC-1e was safe in vaccinia-naive, healthy adults and could induce both humoral and cell-mediated gp160-specific immune responses.

AIDS Vaccines↗
PubMed1992

Development of the Virginia Congenital Anomalies Reporting and Education System (VaCARES): two pilot projects.

In 1986 legislation established the Virginia Congenital Anomalies Reporting and Education System (VaCARES). The system has three goals: to collect data that can be used to evaluate possible causes of congenital anomalies, to improve diagnosis and treatment, and to let parents and physicians know what resources are available to aid children born with anomalies. All children (from birth to age 2) with congenital anomalies admitted to Virginia hospitals after January 1, 1987, are being reported to VaCARES; VaCARES then contacts their families and physicians. Before the system was implemented statewide, its procedures were thoroughly tested through two pilot projects in selected hospitals. During the pilots, it was concluded that birth certificates alone are inadequate for case ascertainment. According to hospital reports, the incidence of all congenital anomalies during Pilot II was 562 out of 10,034 births (5.6%); birth certificates showed an incidence of only 83 out of 10,034 births (0.8%). During Pilot I, 3,466 (73.8%) of the diagnoses reported were perinatal conditions; the list of reportable conditions was accordingly altered, reducing perinatal conditions reported in Pilot II to 5 diagnoses (0.4%). It was estimated that there will be about 5000 to 7000 reports submitted to VaCARES each year. It was also shown that parents should be sent general rather than specific information about their child's birth defect and that quality control and close contact with reporting hospitals are essential to maintain the integrity of the registry data.

Congenital Abnormalities↗
PubMed1992

Use of aminotransferase, hepatitis C antibody, and hepatitis C polymerase chain reaction RNA assays to establish the diagnosis of hepatitis C virus infection in a diagnostic virology laboratory.

Clinical and therapeutic decisions for hepatitis C virus (HCV) infection depend on factors that include documentation of past infection as well as identification of those who might benefit from antiviral chemotherapy with systemic interferon. To evaluate the ability of a diagnostic laboratory to accurately identify such patients, we compared results obtained with serum transaminase assays, two HCV antibody assays (enzyme immunoassay [EIA] and immunoblot), and a polymerase chain reaction (PCR)-based assay for HCV RNA using a group of consecutively submitted samples within our university-based diagnostic virology laboratory and sera from a population of random blood donors. One hundred percent of specimens with R values of greater than 3.0 in the HCV EIA were positive in the confirmatory immunoblot. However, 25% of specimens with EIA R values of between 1.0 and 3.0 were not confirmed by either recombinant immunoblot assay (RIBA) or RNA PCR assay (false-positive specimens). A significant correlation (P less than 0.01) between increasing reactivity in the RIBA and positivity in the RNA PCR assay was found. The incidence of HCV viremia, as determined by the RNA PCR assay, was 73% for confirmed seropositive specimens, 33% for seropositive specimens with indeterminate RIBA results, 12% for seronegative specimens obtained from infected patients, and 2.0% for seronegative specimens obtained from uninfected blood donors. In contrast, serum transaminase testing did not correlate with the RNA PCR assay for HCV. Use of the EIA and immunoblot assay followed by RNA PCR testing will identify most patients who are viremic with HCV.

Alanine Transaminase↗
PubMed1992

Human CD8+ herpes simplex virus-specific cytotoxic T-lymphocyte clones recognize diverse virion protein antigens.

The role of the HLA class I-restricted, CD8+, herpes simplex virus (HSV)-specific cytotoxic T lymphocytes (CTL) in the control of human HSV infections is controversial because previous reports suggest that a substantial portion of the antigen-specific lytic response is mediated by CD4+ cells. To address this question directly, we isolated HSV-specific CD8+ CTL clones from a patient with recurrent genital herpes. These CTL were cloned by coculturing responder peripheral blood mononuclear cells (PBMC) with phytohemagglutinin-stimulated PBMC that had been infected with live HSV-2 and then irradiated prior to the addition of responder cells. After 1 week, CTL were cloned by limiting dilution using phytohemagglutinin stimulation and allogeneic feeder PBMC. Seven clones were isolated; all seven clones were CD8+ CD4- CD3+ DRbright, six lysed only HSV-2-infected targets, and one lysed both HSV-1- and HSV-2-infected targets. Antigen presentation was restricted by two to three different HLA class I loci. To determine the antigens recognized by these HSV-specific CTL, target cells were infected with HSV in the presence of acyclovir, 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole, or cycloheximide in a series of drug block/release protocols to limit the repertoire of viral gene expression to select transcriptional classes. Five of the clones exhibited a different pattern of cytotoxicity, suggesting that each recognized a distinct HSV antigen. One of the clones appears to be directed against an immediate-early antigen; six of the clones recognize virion proteins. Five of these clones recognized internal virion proteins that could be introduced into target cells by HSV infection in the absence of virus gene expression. Antigen specificity was further tested by using vaccinia virus vectors that express glycoproteins gD2 and gB2 or the tegument protein VP16. One clone lysed vaccinia virus/gD2-infected target cells; the remaining clones did not recognize any of these gene products. The diversity of the CD8+ response from a single individual indicated that several different antigens are recognized when presented in the context of a variety of class I HLA alleles, a pattern that markedly differs from that described for another human herpesvirus, cytomegalovirus.

Acyclovir↗
PubMed1992

Herpes simplex virus-2 (HSV-2) type-specific antibody correlates of protection in infants exposed to HSV-2 at birth.

Western blot analysis was used to compare the herpes simplex virus (HSV)-2 antibody profiles of 40 infants less than 2 wk of age who had been exposed to maternal genital HSV-2 at birth. 4 mothers were HSV seronegative at delivery and seroconverted to HSV-2 ("primary infection"), 9 had HSV-1 antibodies and seroconverted to HSV-2 ("nonprimary first episode infection"), and 27 were HSV-2 seropositive ("recurrent infection"). Neonatal herpes infections developed in 1 of 4 infants of women with primary infection, in 3 of 9 infants of women with nonprimary first episode infection, and in none of the 27 infants of women with recurrent HSV-2. Antibodies to HSV-2 proteins gG-2, VP5, and ICP35 were detected in 83, 89, and 72% of the 36 uninfected infants, respectively. None of the four infected infants had detectable antibodies to gG-2 and only one (25%) had antibodies to VP5 or ICP35. The more limited profiles of the 13 infants born to mothers with first episodes of HSV-2 were then analyzed separately; these profiles were similar among infected and uninfected infants except for gG-2, which elicits antibodies that are type specific for HSV-2. None of the infected infants versus seven of nine (78%) uninfected infants were gG-2 seropositive. These comparisons suggest that maternal type-specific antibodies may play a role in preventing neonatal infection after exposure to HSV-2.

Antibodies, Viral↗
PubMed1991

Inability of enzyme immunoassays to discriminate between infections with herpes simplex virus types 1 and 2.

OBJECTIVE: To determine the accuracy of three commercial enzyme immunoassays in detecting and subtyping antibodies to herpes simplex virus type 1 or 2. DESIGN: Cross-sectional. SETTING: Referral medical center. PATIENTS: Ninety patients with culture-positive lesions caused by infection with herpes simplex virus type 1 or 2. The results of Western blot and glycoprotein G immunodot enzyme assays showed that an additional 53 patients had subclinical herpes simplex virus 2 infection, that another 20 patients had subclinical herpes simplex virus type 1 infection, and that 23 patients were seronegative. MEASUREMENTS: Three commercial enzyme immunoassays were used to determine herpes simplex virus antibody subtypes. MAIN RESULTS: All three commercial assays performed poorly in all patient groups (except in patients who were seronegative for herpes simplex virus). Among the 40 patients with a first episode of genital herpes, seroconversion to the appropriate viral type was shown by the three assays in only 33%, 55%, and 75% of cases. Among patients with recurrent genital herpes, the three commercial assays identified more than 90% of patients with only herpes simplex virus type 2 antibodies but failed to identify herpes simplex virus type 2 infections in 58% to 76% of patients with antibodies to both virus subtypes. The three assays correctly identified only 55%, 75%, and 85% of the 53 "silent carriers" of herpes simplex virus type 2. Overall, the three enzyme immunoassays detected herpes simplex virus type 2 antibodies in 60%, 62%, and 93% of patients with subtype 2 infections and falsely detected type 2 antibodies in 8%, 27%, and 49% of patients with type 1 infections. CONCLUSION: Currently licensed enzyme immunoassays give inaccurate or misleading results about the correct herpes simplex virus infecting subtype.

Antibodies, Viral↗
PubMed1991

Neonatal herpes simplex virus infection in relation to asymptomatic maternal infection at the time of labor.

BACKGROUND AND METHODS: To define the risk factors associated with neonatal acquisition of herpes simplex virus (HSV) infection, we prospectively obtained HSV cultures from the cervix and external genitalia of 15,923 pregnant women in early labor who were without symptoms or signs of genital HSV infection. Follow-up of the women with positive cultures for HSV and their HSV-exposed infants included serologic tests and serial cultures for HSV. RESULTS: HSV was isolated from 56 of the women (0.35 percent), 18 of whom (35 percent) had serologic evidence of a recently acquired, subclinical first episode of genital HSV infection, and 34 of whom (65 percent) had reactivation of HSV. Neonatal HSV developed in 6 of 18 infants (33 percent) born to the women with a first episode of genital HSV, and in 1 of 34 infants (3 percent) born to the women with reactivation of HSV (P less than 0.01); neonatal HSV also occurred in three of the infants born to the 15,867 women with negative cultures. Neonatal HSV-2 occurred in 1 of 4 infants born to mothers seronegative at delivery for both HSV-1 and HSV-2, in 4 of 12 infants exposed to HSV-2 whose mothers had only HSV-1 antibodies at delivery, and in none of the infants born to 31 women who were HSV-2-seropositive. An increased risk of neonatal HSV was associated with exposure to viral shedding from the cervix and the use of fetal-scalp electrodes. CONCLUSIONS: Of the asymptomatic women who shed HSV in early labor, about a third have recently acquired genital HSV, and their infants are 10 times more likely to have neonatal HSV than those of women with asymptomatic reactivation of HSV. The presence of maternal antibodies specific to HSV-2 but not HSV-1 appears to reduce the neonatal transmission of HSV-2. Further studies are necessary to determine whether screening and prophylactic treatment are warranted for infants of HSV-2-seronegative mothers who shed HSV-1 or HSV-2 in early labor.

Antibodies, Viral↗
PubMed1991

Safety of and immunological response to a recombinant vaccinia virus vaccine expressing HIV envelope glycoprotein.

In a randomised phase I trial of a recombinant vaccina virus vaccine expressing the gp160 envelope gene of the human immunodeficiency virus (HIVAC-1e) 35 healthy, HIV-seronegative males, 31 of whom had a history of smallpox immunisation and 4 of whom were vaccinia naive, were vaccinated and then boosted 8 weeks later with HIVAC-1e or standard NY strain vaccinia virus. The frequency, duration, and titre of virus isolation from the vaccination site and occurrence of local side-effects were similar between the two groups of vaccinees. Vaccinia-naive (vac-n) subjects shed virus from the vaccination site for longer and at a higher titre than did vaccinia-primed (vac-p) individuals (19 vs 7 days and 10(7) vs 10(5) pfu/ml, respectively). In-vitro T-cell proliferative responses to one or more HIV antigen preparations developed in 13 of 16 vaccinia-primed subjects inoculated with HIVAC-1e. T-cell responses were, however, transient and in no subject did antibodies to HIV become detectable. The 2 vaccinia-naive subjects vaccinated with HIVAC-1e showed strong T-cell responses to homologous and heterologous strains of whole virus and to recombinant gp160 protein that remained detectable for over a year; antibodies to HIV envelope also developed in both. Recombinant vaccinia virus vaccines induce T-cell priming to the foreign gene products in most individuals. If used as the sole immunising agent they will be most efficacious in vaccinia-naive individuals.

Adult↗
PubMed1991

A controlled trial comparing vidarabine with acyclovir in neonatal herpes simplex virus infection. Infectious Diseases Collaborative Antiviral Study Group.

BACKGROUND: Despite the use of vidarabine, herpes simplex virus (HSV) infection in neonates continues to be a disease of high morbidity and mortality. We undertook a controlled trial comparing vidarabine with acyclovir for the treatment of neonatal HSV infection. METHODS: Babies less than one month of age with virologically confirmed HSV infection were randomly and blindly assigned to receive either intravenous vidarabine (30 mg per kilogram of body weight per day; n = 95) or acyclovir (30 mg per kilogram per day; n = 107) for 10 days. Actuarial rates of mortality and morbidity among the survivors after one year were compared overall and according to the extent of the disease at entry into the study (infection confined to the skin, eyes, or mouth; encephalitis; or disseminated disease). RESULTS: After adjustment for differences between groups in the extent of disease, there was no difference between vidarabine and acyclovir in either morbidity (P = 0.83) or mortality (P = 0.27). None of the 85 babies with disease confined to the skin, eyes, or mouth died. Of the 31 babies in this group who were treated with vidarabine and followed for a year, 88 percent (22 of 25) were judged to be developing normally after one year, as compared with 98 percent (45 of 46) of the 54 treated with acyclovir (95 percent confidence interval for the difference, -4 to 24). For the 71 babies with encephalitis, mortality was 14 percent with vidarabine (5 of 36) and with acyclovir (5 of 35); of the survivors, 43 percent (13 of 30) and 29 percent (8 of 28), respectively, were developing normally after one year (95 percent confidence interval for the difference, -11 to 39). For the 46 babies with disseminated disease, mortality was 50 percent (14 of 28) with vidarabine and 61 percent (11 of 18) with acyclovir (95 percent confidence interval for the difference, -20 to 40); of the survivors, 58 percent (7 of 12) and 60 percent (3 of 5), respectively, were judged to be developing normally after one year (95 percent confidence interval for the difference, -40 to 50). Both medications were without serious toxic effects. CONCLUSIONS: In this multicenter, randomized, blinded study there were no differences in outcome between vidarabine and acyclovir in the treatment of neonatal HSV infection. The study lacked statistical power to determine whether there were sizable differences within the subgroups of those with localized HSV, encephalitis, or disseminated disease.

Acyclovir↗
PubMed1991

Predictors of morbidity and mortality in neonates with herpes simplex virus infections. The National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group.

BACKGROUND: In a controlled trial comparing acyclovir with vidarabine in the treatment of neonatal herpes simplex virus (HSV) infection, we found no significant difference between the treatments in adjusted mortality and morbidity. Hence, we sought to define for the entire cohort (n = 202) the clinical characteristics that best predicted the eventual outcome in these neonates. METHODS: Data were gathered prospectively at 27 centers between 1981 and 1988 in infants less than one month of age who had virologically confirmed HSV infection. We examined the outcomes by multivariate analyses of 24 variables. Disease was classified in one of three categories based on the extent of the involvement at entry into the trial: infection confined to skin, eyes, or mouth; encephalitis; or disseminated infection. RESULTS AND CONCLUSIONS: There were no deaths among the 85 infants with localized HSV infection. The mortality rate was significantly higher in the 46 neonates with disseminated infection (57 percent) than in the 71 with encephalitis (15 percent). In addition, the risk of death was increased in neonates who were in or near coma at entry (relative risk, 5.2), had disseminated intravascular coagulopathy (relative risk, 3.8), or were premature (relative risk, 3.7). In babies with disseminated disease, HSV pneumonitis was also associated with greater mortality (relative risk, 3.6). In the survivors, morbidity was most frequent in infants with encephalitis (relative risk, 4.4), disseminated infection (relative risk, 2.1), seizures (relative risk, 3.0), or infection with HSV type 2 (relative risk, 4.9). With HSV infection limited to the skin, eyes, or mouth, the presence of three or more recurrences of vesicles was associated with an increased risk of neurologic impairment as compared with two or fewer recurrences.

Consciousness↗
PubMed1991

Allogeneic marrow transplantation in patients positive for hepatitis B surface antigen.

Twenty patients who were positive for hepatitis B surface antigen (HBsAg) underwent allogeneic marrow transplant for malignancy or other underlying hematologic disease between 1975 and 1986. After transplant, one patient had serologic evidence of hepatitis B virus (HBV) reactivation whereas three patients had evidence of an immune response to HBV. Among four patients with serologic follow-up of 1 year or more, three remained positive for HBsAg and one became HBsAg negative. Six patients (30%) developed clinical evidence of venocclusive disease and seven patients (35%) developed acute graft-versus-host disease involving the liver, but the incidence of these complications was similar to that expected among patients who are not carriers of HBsAg. Three patients died with hepatorenal failure, but all three had venocclusive disease and the contribution of HBV infection to liver failure was unclear. Available liver specimens obtained at autopsy (six patients) or biopsy (two patients) all showed either HBsAg (one specimen) or hepatitis B core antigen (four specimens) or both (three specimens) by immunoperoxidase staining. Although HBV reactivation leading to hepatic failure has been reported among allogeneic marrow transplant recipients as well as other immunocompromised patients, we did not observe an increase in the incidence of severe liver disease after transplant among these 20 patients positive for HBsAg at the time of transplant, and do not consider positivity for HBsAg to be a contraindication to allogeneic marrow transplantation.

Adolescent↗