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Biomedical subjects

L Corey

Publications and source records attributed to L Corey.

At least 235 records · Page 13Linked to original sources
PubMed1993

Detection of hepatitis C virus RNA: comparison of one-stage polymerase chain reaction (PCR) with nested-set PCR.

We evaluated a new hepatitis C virus RNA assay based on one-stage PCR followed by liquid hybridization with an oligonucleotide probe and compared it with nested-set PCR. The one-stage and nested-set PCR assays had identical sensitivities in analytical experiments and showed 100% concordance when clinical specimens were used. One-stage PCR may be less prone to contamination than nested-set PCR.

DNA, Viral↗
PubMed1993

Human herpesvirus 6 DNA in peripheral blood cells and saliva from immunocompetent individuals.

Human herpesvirus 6 (HHV-6) genome equivalents were quantitated in peripheral blood mononuclear cells (PBMCs) and saliva from 20 healthy individuals by the polymerase chain reaction (PCR). Nineteen of 20 subjects (95%) harbored HHV-6 DNA: 18 (90%) had HHV-6 in their PBMCs and 18 had HHV-6 in their saliva. Quantitative PCR revealed HHV-6 DNA levels ranging from negative to 4,000 HHV-6 genome equivalents per 10(6) PBMCs and from negative to 200,000 HHV-6 genome equivalents per ml of saliva. Longitudinal saliva samples from 15 HHV-6-seropositive subjects revealed salivary HHV-6 DNA persistence in 13 subjects. HHV-6 antibodies were detected in 17 of 19 subjects, with titers ranging from 1:400 to 1:51,200 (geometric mean titer, 1:2,500). Antibody titers did not correlate with HHV-6 DNA levels in PBMCs or saliva (P = 0.27 and P = 0.44, respectively). One subject with persistent HHV-6 DNA lacked detectable HHV-6 antibodies. The high prevalence of HHV-6 DNA in PBMCs and saliva supports the concept that HHV-6 exists at these sites in normal individuals.

Adult↗
PubMed1993

Herpes simplex virus detection from genital lesions: a comparative study using antigen detection (HerpChek) and culture.

The sensitivity of a rapid enzyme immunoassay test (HerpChek Direct Herpes Simplex Virus Antigen Test [DuPont Medical Products, Wilmington, Del.]) for the detection of herpes simplex virus (HSV) antigens in patient specimens was compared with HSV culture. HerpChek positivity for HSV occurred with 179 (65%) of 275 lesion specimens, whereas culture for HSV was positive for 145 (53%) lesions (P = 0.002). HerpChek was twice as sensitive as culture for the detection of HSV in late-stage lesions and was equivalent to culture for the detection of HSV in early lesions. We conclude that HerpChek provides greater sensitivity than culture for HSV detection in late-stage genital lesions.

Adolescent↗
PubMed1993

Herpes simplex virus infection of human fibroblasts and keratinocytes inhibits recognition by cloned CD8+ cytotoxic T lymphocytes.

CD8+ cytotoxic T lymphocytes (CTL) clones with specificity for herpes simplex virus (HSV) were derived from two donors with genital HSV-2 infection. These CTL clones specifically lysed HSV-infected autologous B lymphoblastoid cells, but not HSV-infected fibroblasts. Exogenous peptide loading sensitized both cell types to lysis by an HSV-specific CTL clone of known specificity. HSV infection rendered fibroblasts refractory to peptide sensitization. HSV infection also rendered fibroblasts and keratinocytes insensitive to lysis by allospecific CD8+ CTL clones. Lysis of B lymphoblastoid cells in this system was only slightly reduced by HSV infection. Reduction of fibroblast allospecific lysis was dose and time dependent and was blocked by acyclovir, indicating the involvement of a late HSV gene product. HSV caused a reduction of fibroblast cell surface HLA class I antigen, at least in part due to reduction of synthesis of heavy chain-beta 2 microglobulin heterodimers. These results suggest that HSV-induced blockade of antigen presentation by cutaneous cells to CD8+ CTL may be a mechanism by which HSV limits or evades the immune response of the host.

Animals↗
PubMed1992

Infection of Macaca nemestrina by human immunodeficiency virus type-1.

After observations that Macaca nemestrina were exceptionally susceptible to simian immunodeficiency virus and human immunodeficiency virus type-2 (HIV-2), studies of HIV-1 replication were initiated. Several strains of HIV-1, including a recent patient isolate, replicated in vitro in peripheral blood mononuclear cells (PBMCs) and in CD4-positive M. nemestrina lymphocytes in a CD4-dependent fashion. Eight animals were subsequently inoculated with either cell-associated or cell-free suspensions of HIV-1. All animals had HIV-1 isolated by cocultivation, had HIV-1 DNA in their PBMCs as shown by polymerase chain reaction, and experienced sustained seroconversion to a broad spectrum of HIV-1 proteins. Macaca nemestrina is an animal model of HIV-1 infections that provides opportunities for evaluating the pathogenesis of acute HIV-1 replication and candidate vaccines and therapies.

Animals↗
PubMed1992

Underdiagnosis of genital herpes by current clinical and viral-isolation procedures.

BACKGROUND: The current clinical strategy for diagnosing genital herpes simplex virus (HSV) infection in women relies on clinical findings plus the selective use of viral culture. The effectiveness of this approach for identifying women with genital herpes is unknown. METHODS: We performed physical examinations, colposcopy, Pap smears, viral cultures, and HSV type-specific serologic assays of 779 randomly selected women attending a sexually transmitted disease clinic. RESULTS: Evidence of HSV type 2 infection was detected in 363 women (47 percent), and 9 others (1 percent) had positive cultures indicative of urogenital or anal infection with HSV type 1. Of these 372 women, only 82 (22 percent) had symptoms. Fourteen women (4 percent) had viral shedding without symptoms, 60 (16 percent) had formerly had symptomatic episodes, and 216 (58 percent) had antibodies to HSV-2 with neither viral shedding nor a history of clinical episodes. Characteristic ulcerations of the external genitalia were present in only two thirds of the 66 women with positive HSV cultures; the others had atypical genital lesions or asymptomatic viral shedding. Isolation of HSV from a genitourinary tract specimen was the most sensitive (77 percent) test for confirming a first episode of infection. The detection of HSV-2-specific antibodies was the most sensitive (97 percent) way to confirm symptomatic reactivations of HSV-2 infection. HSV-2 serologic testing also identified the 290 women with asymptomatic HSV-2 infections (37 percent), including 14 (5 percent) who were shedding virus asymptomatically on the day of the examination. CONCLUSIONS: The current strategy for diagnosing genital HSV infection in women misses many cases. Newly developed type-specific serologic methods can identify women with recurrent genital HSV-2 infection, as well as those with unrecognized or subclinical infection.

Adolescent↗
PubMed1992

Human papillomaviruses, herpes simplex viruses, and the risk of oral cancer in men.

A population-based case-control study was conducted in western Washington state to examine the relations between infection with human papilloma viruses (HPV), herpes simplex viruses (HSV), and risk of oral squamous cell cancer in men. Interviews were completed on 131 oral cancer cases diagnosed between January 1985 and December 1989 and 136 controls frequency matched to cases on age and date of diagnosis who were obtained by random digit dialing. The risk for oral cancer among men with 30 or more sexual partners was 2.4 times that of men with four or fewer partners (95% confidence interval (CI) 1.0-5.9). Men who ever practiced oral sex had lower risk for oral cancer relative to men who never practiced oral sex (relative risk (RR) = 0.4, 95% CI 0.2-0.8). Analyses of exfoliated oral cavity cells for the presence of HPV-6 DNA with polymerase chain reaction revealed that men with an oral HPV-6 infection had 2.9 times the risk for oral cancer of noninfected men (95% CI 1.1-7.3), whereas men with an oral HPV-16 infection had 6.2 times the risk for oral cancer of noninfected men (crude RR = 6.2, 95% CI 0.7-52.2). Relative risks associated with serologically detected HSV-1 and HSV-2 infections were 0.8 (95% CI 0.3-1.7) and 1.8 (95% CI 0.7-4.6), respectively. The authors conclude that HPV-6 is associated with oral cancer. Although men infected with HPV-16 and HSV-2 were at elevated risk, these associations may have been due to chance. The role of specific sexual practices in the transmission of viruses to the oral cavity remains unclear.

Antibodies, Viral↗
PubMed1992

Asymptomatic reactivation of herpes simplex virus in women after the first episode of genital herpes.

OBJECTIVE: To determine frequency, anatomic site, and host factors associated with asymptomatic shedding of herpes simplex virus after initial episodes of genital herpes. DESIGN: Cohort study with follow-up for a median of 63 weeks. SETTING: Referral clinic. PATIENTS: Women (306) with first episode of herpes; 43 had primary herpes simplex virus type 1, and 227 and 36 had primary and nonprimary herpes simplex virus type 2, respectively. MEASUREMENTS: Cultures were obtained for herpes simplex virus every 4 to 6 weeks at times in which genital lesions and symptoms were not present. MAIN RESULTS: Asymptomatic shedding was detected among 11.9%, 18.3%, and 22.9% of women with primary herpes simplex virus type 1, primary HSV type 2, and nonprimary HSV type 2, respectively. Among patients with type 2 infection, previous type 1 antibody was associated with a lower rate of asymptomatic vulvar shedding. Asymptomatic cervical shedding was 3 times more frequent during the first three months after resolution of primary type 2 disease than during later time periods. In contrast, the rate of symptomatic recurrent herpes did not change over time. CONCLUSIONS: Asymptomatic genital herpes simplex type 2 is more common than type 1. Asymptomatic genital shedding occurs more often during the first 3 months after acquisition of primary type 2 disease than during later periods. Patients with HSV type 2 should be advised of this high early rate of asymptomatic shedding and of potential transmission to sexual partners.

Adult↗
PubMed1992

Risk factors for the sexual transmission of genital herpes.

OBJECTIVE: To determine the risk of sexual transmission of genital herpes simplex virus (HSV) in heterosexual couples. DESIGN: Prospective study of couples who were participants in a clinical trial. Each source partner had symptomatic, recurrent genital HSV, and each susceptible partner was without serologic or clinical evidence of genital herpes. Couples were followed for a median of 334 days. SETTING: Two university-based research clinics. PATIENTS: One hundred forty-four heterosexual couples were studied out of an initial enrollment of 214 couples. MAIN OUTCOME MEASURES: Development of culture-proven HSV infection or type-specific antibodies in the susceptible partner. MAIN RESULTS: Transmission occurred in 14 (9.7%) couples, including 11 (16.9%) of 65 couples with male and 3 (3.8%) of 79 with female source partners (P = 0.05). The annual rate of acquisition was higher (31.8%) in susceptible female partners who lacked antibodies to either HSV type 1 or 2 at entry compared with females with HSV type 1 antibodies at entry (9.1%). Couples avoiding transmission of HSV reported fewer days with genital lesions in source partners. Detailed histories were available at the time of transmission in 13 couples. In nine couples, transmission occurred when the source partner was reported to be asymptomatic and in four, it resulted from sexual contact at the time of prodrome (1 case) or within hours before lesions were first noticed by the source partner (3 cases). CONCLUSIONS: Despite clear recognition of genital herpes in source partners, there was substantial risk for transmission; in 70% of patients, transmission appeared to result from sexual contact during periods of asymptomatic viral shedding. The risk for acquisition of HSV was higher in women than men, and previous HSV type 1 infection appeared to reduce the risk for acquisition of HSV type 2 infection among women.

Adult↗
PubMed1992

A randomized, double-blind, phase I/II trial of tumor necrosis factor and interferon-gamma for treatment of AIDS-related complex (Protocol 025 from the AIDS Clinical Trials Group).

To determine safety and efficacy of tumor necrosis factor (TNF) and interferon-gamma (IFN gamma) in the treatment of patients with acquired immunodeficiency syndrome (AIDS)-related complex, a randomized, double-blind study was conducted. Twenty-five patients with AIDS-related complex and CD4 lymphocytes less than or equal to 500 x 10(6)/L attended an AIDS Clinical Trials Unit of a tertiary referral center. Patients were administered tumor necrosis factor (TNF) (10 micrograms/m2) or IFN gamma (10 micrograms/m2), or both intramuscularly three times weekly for 16 weeks. Side effects from all three preparations included fever, constitutional symptoms, and local reactions. No significant hematologic, hepatic, renal, or coagulation abnormalities were observed. CD4 lymphocyte counts, beta 2-microglobulin, p24 antigen levels, and anti-p24 antibody did not change significantly during therapy. Similarly, no significant change was noted in rates of HIV isolation from peripheral blood mononuclear cells or plasma. TNF and IFN gamma were tolerable after premedication with acetaminophen; however, no significant change in markers of human immunodeficiency virus infection was demonstrated. These cytokines alone do not appear to be of benefit, nor do they appear to hasten the progression of HIV infection.

AIDS-Related Complex↗
PubMed1992

Interference of recombinant soluble CD4 immunoglobulin G in flow cytometric measurement of CD4+ lymphocytes.

Recombinant soluble CD4 covalently linked to an immunoglobulin G heavy chain (rCD4-IgG) was evaluated clinically for the treatment of human immunodeficiency virus infection. The interference of rCD4-IgG with the measurement of peripheral blood CD4 lymphocytes by whole-blood lysis flow cytometric analysis was investigated using three commercial monoclonal antibody reagents. Addition of rCD4-IgG resulted in an artifactual decrease in measured CD4 number at rCD4-IgG levels of greater than or equal to 1 micrograms/mL; the threshold for this decrease was dependent on the concentration of monoclonal antibody in the commercial preparation used for the measurement of CD4. This artifactual decrease in CD4 cell count was observed in two patients who received rCD4-IgG intravenously. The apparent decrease in CD4 count was eliminated with the use of a single phosphate-buffered saline wash step before the addition of monoclonal antibody. rCD4-IgG can bind to anti-CD4 antibody and lower the measured CD4 cell count in vitro; this interference can be eliminated by a single or a double wash step and is necessary when using the whole-blood lysis flow cytometric technique of enumerating CD4 lymphocytes in patients receiving rCD4-immunoglobulin G.

Antigens, CD↗
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

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

Chancroid is a mucocutaneous infection caused by Haemophilus ducreyi that produces ulcerative lesions and enhances the efficiency of transmission of human immunodeficiency virus (HIV). Confirmation of infection by culture of H. ducreyi is essential in therapeutic trials. Minimal inhibitory concentrations of antibiotics for the isolate should be determined by agar dilution. Patients should be evaluated by appropriate laboratory tests for syphilis, infection with herpes simplex virus, gonorrhea, and (in North America) infection with Chlamydia trachomatis. The clinical history of the disease should be recorded and ulcers, buboes, and lymphadenitis mass described. Whenever possible, study participants also should be tested for HIV infection. Randomized, prospective, double-blind, active-control comparative clinical trials are preferred for evaluation of the safety and efficacy of new anti-infective drugs. Otherwise-healthy men and women should be enrolled in these studies. Patients with active syphilis or genital herpes should be excluded. Microbiological and clinical outcomes are paramount.

Anti-Infective Agents↗
PubMed1992

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

The three major vaginal infections are yeast vulvovaginitis, Trichomonas vaginalis vaginitis, and bacterial vaginosis. In terms of signs and symptoms, these disorders overlap substantially with one another and with other infections. Therefore, the diagnosis of candidiasis and trichomoniasis requires isolation of the responsible pathogen. For the diagnosis of bacterial vaginosis, all other potential causes of vaginal infection must be excluded and specified laboratory criteria must be met. Clinical trials must be carefully designed to control for coexisting pathogens, for potential efficacy of treatment against more than one microbe, and for variable end points used to define clinical response. Prospective, randomized, double-blind, active-control comparative studies are preferred. Follow-up evaluations 5-7 days and 4-6 weeks after the completion of therapy are required for the assessment of outcome. Laboratory studies of vaginal fluid (culture and/or microscopic examination) are paramount in the final appraisal of outcome.

Anti-Infective Agents↗