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Biomedical subjects

L Corey

Publications and source records attributed to L Corey.

At least 307 records · Page 17Linked to original sources
PubMed1988

Therapy of herpes zoster with oral acyclovir.

Oral acyclovir therapy for herpes zoster has been studied in double-blind, placebo-controlled trials of two dosages, 400 mg and 800 mg five times per day for 10 days. Compared with placebo recipients, recipients of the high-dosage acyclovir experienced a significantly shortened period of viral shedding, significantly accelerated time to 50 percent scabbing, significantly accelerated time to 50 percent healing, and after two days of therapy, significantly less frequent formation of new lesions. The duration and severity of acute pain were less in acyclovir recipients, with differences in pain severity achieving statistical significance (p = 0.03) between Days 3 and 10 and correlating with the treatment differences in new lesion formation. In studies of the 400 mg five times per day dose schedule, differences between acyclovir and placebo recipients were not significant. In a six-month follow-up of recipients in the higher dosage study, the acyclovir recipients experienced less post-zoster pain than placebo recipients; differences in the prevalence of pain were most significant for the presence of a persistent pain in the first three months of follow-up. Oral acyclovir at these dosages appears to be free of adverse reactions. In summary, oral acyclovir at a dosage of 800 mg five times per day for 10 days for treatment of acute herpes zoster is superior to 400 mg five times per day and favorably alters the course of the disease.

Acyclovir↗
PubMed1988

Antibody to human immunodeficiency virus (HIV) and suboptimal response to hepatitis B vaccination.

STUDY OBJECTIVE: To analyze the relation between human immunodeficiency virus (HIV) infection and the antibody response to plasma-derived hepatitis B vaccine. DESIGN: Open-label longitudinal cohort study; blinded laboratory studies. SETTING: University-affiliated municipal hospital. PATIENTS: Homosexually active men with negative assays for hepatitis B surface antigen (HBsAg), hepatitis B core antigen, and antibody to HBsAg; recruited in a sexually transmitted disease clinic or referred from community practitioners. INTERVENTIONS: Immunization with 20 micrograms of plasma-derived hepatitis B virus vaccine intramuscularly, repeated after 1 and 6 months; standardized evaluation at entry and at 1, 2, 6, and 7 months. MEASUREMENTS AND MAIN RESULTS: Low antibody response or nonresponse to vaccination occurred in 7 of 16 HIV-seropositive patients, compared with 6 of 68 HIV-seronegative patients (P = 0.002). Median levels of antibody to HBsAg 7 months after the first vaccine dose were 205.3 sample ratio units for HIV-seronegative patients and 15.5 sample ratio units for HIV-seropositive patients. By multivariate analysis, vaccine response was associated with HIV antibody status and not with cytomegalovirus infection, lymphocyte subset results, or impaired cutaneous delayed hypersensitivity. CONCLUSIONS: Infection with HIV is associated with suboptimal antibody response to plasma-derived hepatitis B virus vaccine. Determination of antibody levels after vaccination in HIV-seropositive patients may be warranted.

Adult↗
PubMed1988

Oral acyclovir for treatment of first-episode herpes simplex virus proctitis.

Twenty-nine patients with first-episode rectal herpes simplex virus infection were enrolled in a double-blind trial of oral acyclovir, 400 mg five times daily, vs placebo treatment. Eighty percent of those receiving acyclovir compared with 25% of placebo recipients no longer had herpes simplex virus isolated from their rectal lesions three days after onset of therapy. The median duration of rectal lesions and viral excretion from rectal lesions (median, five and zero days, respectively) was significantly shorter in patients treated with acyclovir than in placebo-treated patients (14 and 11 days, respectively). Durations of local signs and symptoms of proctitis, such as rectal pain, discharge, and friability, were shorter in acyclovir recipients than in placebo recipients, but these differences were not statistically significant. Daily administration of 2 g of oral acyclovir for ten days alleviates some of the clinical signs of herpes simplex virus rectal infection.

Acyclovir↗
PubMed1988

Differential effect of systemic acyclovir treatment of genital HSV-2 infections on antibody responses to individual HSV-2 proteins.

Western blot and reflectance densitometry were used to evaluate the antibody response from patients treated with systemic acyclovir during their primary episodes of genital HSV-2 infection. Of 39 patients studied, 10 received oral acyclovir, 10 received intravenous acyclovir, and 19 received placebo. Total antibody levels as well as levels of antibodies to individual HSV-2 proteins (gB, gG, gC/gE, VP16, gD, and p45) were determined in convalescent phase sera. The median number of HSV-2 proteins recognized and the total amount of HSV-2 antibody were significantly lower in acyclovir than placebo treated patients (P less than or equal to 0.01). Levels of antibodies to individual proteins were also lower in sera from acyclovir versus placebo treated patients: gB (P = 0.013), gC/gE (P = 0.017), VP16 (P = 0.001), gD (P = 0.009), and p45 (P = 0.015). Antibody response to gG-92 and to a newly described gG species, gG-70, was not significantly different among treatment groups. A low number of proteins recognized by convalescent serum antibodies were associated with a higher number of lesions at first recurrence (P = 0.02) and with a longer duration of the first recurrent episode (P = 0.02). Low levels of total antibody were associated with shorter times to first recurrence (P = 0.05). Low levels of antibody to VP16 (P = 0.05) and gD (P = 0.01) were associated with longer duration of the first recurrence.

Acyclovir↗
PubMed1988

Analysis of a major target of the human immune response to cytomegalovirus using monoclonal antibodies.

Two murine monoclonal antibodies (C6D1 and D2B1) were found to react with a set of cytomegalovirus (CMV)-infected cell polypeptides, which comprise a major target of the human immune response to CMV. C6D1 reacted with proteins of 50 kilodaltons (KD) and 40KD molecular weight; D2B1 reacted with these two proteins plus a third of 35KD. Western blot analysis demonstrated that these protein targets also react with serum antibody from patients with acute or latent CMV infection. Immunofluorescence staining of CMV-infected diploid fibroblast cells by C6D1 and D2B1 showed that the protein targets are found in the nucleus throughout the course of viral infection. The proteins were shown to be late proteins dependent on viral DNA synthesis for their expression. Not all wild-type CMV strains tested expressed proteins that react with C6D1 and D2B1. Using an immunofluorescence stain of diploid fibroblasts infected with CMV strains from infected patients, we found that 70 of 76 (92%) wild-type strains reacted with C6D1 and 23 of 24 (96%) with D2B1. One strain was not reactive with either C6D1 or D2B1. Western blot analysis of 11 wild-type strains revealed that two isolates either lack the C6D1 and D2B1 protein targets or have forms of these proteins that migrate at different molecular weights.

Animals↗
PubMed1988

Tolerance and efficacy of recombinant human interferon gamma in the treatment of refractory genital warts.

PURPOSE: The intralesional administration of recombinant interferon alpha has led to resolution of genital warts in 50 to 70 percent of cases. However, continuous warts do not respond to such treatment, and human papillomavirus (HPV) infection of other anatomic sites remains untreated, so infection may continue to be transmitted. Since interferons have shown promise as effective therapies for genital warts, we decided to investigate the tolerance and efficacy of recombinant human interferon gamma in the treatment of refractory genital warts. PATIENTS AND METHODS: Nineteen women and nine men with refractory genital warts were treated in an open-label, dose-response trial of intramuscular recombinant human interferon gamma. RESULTS: Complete responses were seen in two (7 percent) and partial responses were seen in 13 (46 percent). Of 12 women with concomitant cervical HPV infection, eight demonstrated resolution with therapy. Response rates were higher in those patients who had warts less than nine months (73 percent) prior to therapy and in women (63 percent). Responses were not associated with HPV type. Flu-like symptoms during treatment were frequent but well tolerated. Transient abnormal laboratory results were more frequent with daily administration than with three times weekly therapy. Eleven of 16 subjects treated with cryotherapy after treatment with interferon experienced long-term remissions. CONCLUSIONS: In ambulatory patients with refractory genital warts, recombinant human interferon gamma appears to be biologically active and to have few adverse effects. The high efficacy rate achieved in subjects treated with cryotherapy after treatment with interferon suggests that further studies of combination therapy with these modalities are warranted.

Adolescent↗
PubMed1988

First-episode, recurrent, and asymptomatic herpes simplex infections.

Genital herpes simplex virus infections should be classified into first-episode and recurrent infections. First-episode infections include true primary infections in patients with seronegative results who have never been infected with any type of herpes and nonprimary first-episode infections in patients who have been infected before and have serum antibody and humoral immunity, an example being genital infection with type 2 in adolescence after orolabial infection with type 1 in childhood. First-episode infections show more extensive disease, more systemic symptoms, and greater viral shedding than do recurrent infections. Ten percent to 15% of patients with first-episode primary genital herpes have oropharyngeal infections with the same virus strain. Herpesvirus can be isolated from the urethra in about 30% of male patients with first-episode infections. In recurrent vulvar herpes, virus can be isolated from the cervix in 10% to 15% of patients. Many genital lesions that clinically suggest something else turn out to be herpes; herpes may be diagnosed 5% of the time clinically but cultures are positive 14% of the time. Primary genital herpes type 2 infections recur about 95% of the time whereas type 1 infections recur about 50% of the time. Recurrences are highly unpredictable from patient to patient and time to time. The role of asymptomatic shedding in the spread of herpes is a major area for future study. Antiviral treatment is probably going to change the epidemiology of herpetic infections very little.

Adolescent↗
PubMed1988

Immunoblot analysis of the humoral immune response in primary cytomegalovirus infection.

Cytomegalovirus is a common infection in immunologically normal adults. It may cause an asymptomatic infection or may manifest symptomatically as heterophilic-negative mononucleosis. Studies of CMV infection in immunocompromised patients indicate that humoral immune response plays a role in modulating disease severity; however, the effect of antibodies to CMV in modifying disease expression and transmission in immunologically normal individuals has not been well characterized. Using immunoblot technology, we have demonstrated that immune serum from normal adults contains antibodies to at least 15 CMV-associated proteins and that there is strain-to-strain variation in the expression of these immunogens. The kinetics of the immune response were evaluated by using serial sera collected from normal adults after primary CMV infection; analysis of immunoblots of these sera identified one group of antibodies to CMV proteins that arise early and are stable over time, a second group that appear late after infection, and a third group that are variable among patients and over time.

Adult↗
PubMed1988

Transmission of genital herpes in couples with one symptomatic and one asymptomatic partner: a prospective study.

To determine the risk of transmission of genital herpes simplex virus (HSV) infection, we prospectively studied, for a median of six months, 38 couples who had been together for a median of 10 mo. In each couple, one partner had a history of symptomatic genital herpes and one did not. At entry, of the 38 asymptomatic, exposed partners, 21 were seronegative, and results of western blot analysis showed that seven had antibody to HSV type 1 (HSV-1), four to HSV type 2 (HSV-2), and six to both HSV-1 and HSV-2. One of the 28 exposed partners without antibody to HSV-2 at enrollment asymptomatically acquired HSV-2 infection, but four of 10 with antibody to HSV-2 at enrollment developed culture-proven HSV-2 infection during follow-up. Restriction endonuclease analysis of DNA from paired isolates revealed identical strains in three couples and different strains in one. In this group of asymptomatic sex partners of persons with genital herpes, asymptomatic and unrecognized acquisition of HSV-2 infection was common, but more than half of the exposed partners remained free of HSV-2 infection after a median of 16 mo of sexual contact.

Adult↗
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

Chronic-dose acyclovir to suppress frequently recurring genital herpes simplex virus infection: effect on antibody response to herpes simplex virus type 2 proteins.

To determine the effect of prolonged suppressive acyclovir therapy on the antibody response to herpes simplex virus type 2 (HSV-2) proteins, we studied sequential sera from 33 patients with frequently recurring (six or more recurrences per year) genital herpes. Twenty-two patients received 400 mg of oral acyclovir and 11 received placebo, twice daily for one year. Sera collected at enrollment, after six months and 12 months of therapy, and during the first recurrence after cessation of therapy were evaluated by western blot for levels of antibodies to HSV-2, gB, gG, gC/gE, VP16, and gD. Mean levels declined by 27%-39% after one year of acyclovir. The magnitude of the decrease in antibody levels was not correlated with disease severity either during or after therapy. Patients with high relative antibody levels to gB after therapy had more-severe first recurrences after therapy than did patients with antibody levels to gB less than or equal to the median. Antibody levels were not restored after the first untreated recurrence.

Acyclovir↗
PubMed1988

Genital ulceration as a risk factor for human immunodeficiency virus infection.

Among 115 heterosexual men who presented with genital ulcers to a sexually transmitted disease clinic in Nairobi, Kenya, the prevalence of serum antibody to HIV was 16.5%. A past history of genital ulcers was reported by 12 (63%) of 19 men with antibody to HIV versus 30 (31%) of 96 without antibody (P = 0.008). HIV infection was also positively associated with lack of circumcision, but was not associated with the etiology of the current genital ulcer. Logistic regression analysis (adjusted for age, number of recent sex partners, recent prostitute contact, circumcision, tribal ethnic identity, past history of urethritis, and current diagnoses) confirmed only the association between prior history of genital ulcer disease and HIV infection; (P = 0.04, odds ratio 2.35, 95% confidence limits, 1.01-5.47). The incidence of genital ulcers, particularly chancroid, is much higher in parts of Africa than in Europe or North America. This may contribute to the increased risk of heterosexual transmission of HIV in Africa. Aggressive control of chancroid and syphilis may offer one very feasible approach to reducing transmission of HIV in this region.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Colposcopic manifestations of cervical and vaginal infections.

We analyzed the associations of colposcopic features with cervical and vaginal pathogens and with clinical diagnoses in randomly selected women attending a clinic for sexually transmitted diseases. Logistic regression models were used to adjust for coinfections. Significant associations (P less than 0.01) were found for endocervical mucopus with C. trachomatis, N. gonorrhoeae, and herpes simplex virus (HSV); ulcers/necrotic areas with HSV; "strawberry cervix" with T. vaginalis; increased surface vascularity with HSV; hypertropic cervicitis with C. trachomatis; and immature metaplasia with C. trachomatis and cytomegalovirus. Koilocytosis on cervical cytology was significantly associated with an atypical transformation zone on colposcopy, as well as with satellite lesions. The presence of leukoplakia and ectocervical asperities were also associated with koilocytosis. Awareness of these associations is important for colposcopists to identify patients who need specific microbiologic studies. Although colposcopy is generally used to evaluate patients selected because of abnormal cytology, our study suggests that colposcopic examination could be a useful adjunct to cytology in screening for a variety of cervical and vaginal infections.

Adolescent↗
PubMed1988

Nosocomial transmission of rotavirus infection.

Children admitted to the infant ward between November 30, 1983, and May 5, 1984, were sampled for rotavirus antigen at admission and at 4-day intervals during subsequent hospitalization. Rotavirus was detected in 51 of 315 infants, 24 at the initial sampling and 27 after 72 hours of hospitalization (nosocomial cases). Forty-one of the cases were symptomatic and 10 were asymptomatic. Nosocomial rotavirus was detected in 5, 13 and 24% of children in the hospital for 4 to 8, 9 to 13 and greater than 13 days, respectively. Attending physicians clinically entertained the diagnosis of rotavirus infection in 58% of community-acquired cases but in only 22% of nosocomial cases. Subgrouping of 24 of the rotavirus isolates with monoclonal antibodies indicated that two-thirds of the isolates were Subgroup II, and the remainder were a mixed subgroup, with similar prevalences in the nosocomial and community-acquired cases. Only 11 of 27 instances of nosocomial rotavirus acquisition were epidemiologically associated with a rotazyme-positive roommate and in 4 of these instances different subgroups were present in the 2 roommates. These data suggest that infected roommates appear not to be a major source for direct transmission of nosocomial rotavirus infection.

Antigens, Viral↗
PubMed1988

Comparison of Western blot (immunoblot) and glycoprotein G-specific immunodot enzyme assay for detecting antibodies to herpes simplex virus types 1 and 2 in human sera.

Sera from patients with culture-proven genital herpes infections were tested for herpes simplex virus type 1 (HSV-1)- and HSV-2-specific antibodies by both a Western blot (immunoblot) technique (WBA) and immunodot enzyme assays (IEAs) specific for HSV-1 or HSV-2 glycoprotein G (gG). Of 137 serum samples tested, none was mistyped by either WBA or IEA. Both tests were most sensitive with sera obtained at least 21 days after onset of primary HSV-2 infections or sera drawn during recurrent HSV-2 genital episodes: 75 of 76 (99%) such serum samples were positive for HSV-2 antibody by WBA and 73 of 76 (96%) were positive by IEA. Of sera drawn earlier than 21 days from onset of primary genital HSV-2, antibodies to HSV-2 were detected in 25% by WBA and 8% by IEA. In patients with culture-proven primary genital HSV-1 infection, WBA detected antibodies to HSV-1 proteins in 16 of 17 (94%) serum samples drawn at least 21 days after onset of primary genital HSV-1 infection, compared with 9 of 17 (53%) serum samples tested for gG-1 by IEA. Both WBA and IEA are accurate and sensitive tests for HSV-2 antibody in patients convalescing from a first episode or having symptomatic or asymptomatic recurrent genital herpes. WBA was more sensitive than IEA in detecting seroconversion following primary HSV-1 genital herpes, although both assays may miss persons undergoing early seroconversion to HSV-2.

Antibodies, Viral↗
PubMed1988

Detection of herpes simplex virus DNA from genital lesions by in situ hybridization.

Lesion specimens from 118 episodes of recurrent genital herpes were used to compare herpes simplex virus (HSV) isolation with a direct specimen test for in situ DNA hybridization utilizing a biotinylated probe. The frequency of detection of HSV was similar with both tests; HSV was isolated from 81% of vesicular lesions, 76% of pustules, and 67% of ulcers, while HSV DNA was detected in 77, 76, and 55% of lesions in these stages, respectively. Utilizing both methods, HSV was identified in 91, 94, and 79%, respectively. The sensitivity and specificity of the DNA probe in comparison to standard viral isolation in tissue culture were 92 and 63%, respectively. Seven DNA-positive, viral isolation-negative specimens were obtained from patients who had positive culture confirmation at some time subsequent or prior to enrollment, suggesting that these were true positive results. The sensitivity of the DNA probe was dependent on cellular content of the specimen, and 36 (28%) of the 127 submitted specimens had fewer than 20 nonsuperficial cells. The DNA probe was rapid and convenient; its major disadvantage was the lack of type-specific information. The performance of the probe in lower-prevalence populations and in asymptomatic shedding of HSV remains to be evaluated.

Cells, Cultured↗
PubMed1988

Comparison of diploid fibroblast and rabbit kidney tissue cultures and a diploid fibroblast microtiter plate system for the isolation of herpes simplex virus.

We evaluated the relative sensitivities of two cell systems (rabbit kidney [RK] and human diploid fibroblast [DF; human embryonic tonsil]) in standard tube cultures versus DF cells in a 48-well microtiter plate system for the detection of both symptomatic and asymptomatic herpes simplex virus (HSV) infection. At least one system isolated HSV in 111 of 809 specimens (13.7%). HSV was isolated in RK tube cultures from 110 specimens (99%), in DF tube cultures from 91 specimens (82%), and in DF microtiter plates from 95 specimens (86%). The frequency of HSV isolation varied with the anatomic site and the presence or absence of a herpetic lesion. The sensitivities of the three culture systems remained similar whether the specimens were obtained from lesions or whether the specimens were taken to determine if asymptomatic excretion of HSV was present. While RK tube cultures were more sensitive than DF tube cultures, the DF microtiter plate system was as sensitive as DF tube cultures and its use is supported as a cheaper and less labor-intensive method for the detection of HSV.

Animals↗