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Biomedical subjects

L Corey

Publications and source records attributed to L Corey.

At least 361 records · Page 20Linked to original sources
PubMed1985

Humoral immune response to herpes simplex virus type 2 glycoproteins in patients receiving a glycoprotein subunit vaccine.

Serial serum specimens from 22 herpes simplex virus (HSV)-seronegative recipients of an HSV type 2 (HSV-2) glycoprotein subunit vaccine were analyzed by radioimmunoprecipitation and polyacrylamide gel electrophoresis for the development of antibodies to HSV-2 gB, gD, and g80, a complex of gC and gE. Volunteers received 50 (n = 12) or 100 micrograms (n = 10) of vaccine at days 0, 28, and 140; sera were drawn weekly for 8 weeks and again at days 140, 147, and 365. Among seronegative volunteers, antibody to gB was detected 2 weeks after the first dose, while antibodies to g80 and gD were detected after the second dose (day 35). Antibodies to nonglycosylated HSV-specific proteins were not detected. A dose-response effect between recipients of 50- and 100-micrograms doses was observed in the proportion of vaccine recipients seroconverting to g80 and in the proportion of recipients retaining antibodies to both gD and g80 over time. Diminishing complement-independent neutralizing antibody titers occurred after the second dose and were associated with loss or reduction of detectable antibody to gD. Volunteers who were seropositive for HSV-1-specific antibody (n = 11) were also enrolled in the trial and received 50-micrograms doses of vaccine. Vaccination resulted in conversion to HSV-2 complement-independent neutralizing antibody specificity or indeterminant specificity in 10 of 11 volunteers. These shifts were accompanied by changes in the radioimmunoprecipitation and polyacrylamide gel electrophoresis profile. These changes, which were apparent by 14 days after the first vaccine dose, included de novo appearance or increased levels of antibody to g80 and increased levels of antibody to gD and gB. These studies document the immunogenicity of solubilized glycoproteins gB, gD, gC, and, possibly, gE in humans.

Antibodies, Viral↗
PubMed1985

Diagnosis of genital herpes simplex virus infections.

Genital herpes simplex virus (HSV) infections have increased markedly in the last ten years. The clinical distinction between HSV and other infectious and noninfectious causes of genital ulcer can be difficult. As such, laboratory confirmation of HSV infection should be used for all women who present with ulcerative or clinically atypical genital lesions. Isolation of the virus in tissue culture remains the gold standard for the laboratory diagnosis of HSV infections. However, many new diagnostic methods of detecting HSV antigens in clinical specimens have been developed. Those procedures appear most useful in specimens taken from genital lesions, and at present they are unproven as reliable methods of obstetric management. Serologic methods can be useful in detecting past HSV infection; however, serodiagnosis is a less sensitive and timely procedure in patients with acute HSV infection.

Female↗
PubMed1985

Occupational exposure to hepatitis B in paramedics.

To determine their occupational risk for hepatitis B infection, 59 Seattle paramedics were tested for hepatitis B serum markers. Evidence of antibody to hepatitis B surface antigen (anti-HBs) or antibody to hepatitis B core antigen (anti-HBc) was found in 25%, a rate five times that of a similar Seattle population. Seropositivity did not correlate with age, race, clinical history, or length of service. Of the 15 paramedics with seropositivity to hepatitis B virus six initially had low titers of either anti-HBs or anti-HBc. Four of the six demonstrated persistent low-grade seropositivity on retesting. Paramedics are at increased risk of hepatitis B infection. The high frequency of low-titer anti-HBs suggests that frequent low-level exposure to hepatitis B virus occurs in this population; hepatitis B vaccine should be strongly considered for paramedics.

Allied Health Personnel↗
PubMed1984

A double-blind study of oral acyclovir for suppression of recurrences of genital herpes simplex virus infection.

Patients with frequently recurring genital herpes were enrolled in a double-blind placebo-controlled trial comparing 200-mg acyclovir capsules, given five or two times daily, with placebo. Of 47 placebo recipients, 44 (94 per cent) had recurrences during the 120-day treatment period, compared with 13 (29 per cent) of 45 patients treated with acyclovir five times daily and 18 of 51 (35 per cent) treated with acyclovir twice daily (P less than 0.001 for each regimen compared with placebo). The median time to the first clinical recurrence was 18 days in placebo recipients, compared with over 120 days in both acyclovir-treated groups (P less than 0.001 for both groups compared with placebo). The mean monthly recurrence rate during the medication period was 0.86 in placebo recipients, compared with 0.13 in patients treated with acyclovir five times daily and 0.14 in patients treated with acyclovir twice daily (P less than 0.001 for both groups compared with placebo). While receiving therapy, 86 of 96 acyclovir-treated patients had over a 50 per cent reduction in their pretreatment recurrence rate. Breakthrough recurrences in acyclovir recipients were of shorter duration and associated with a lower frequency of viral shedding than recurrences in placebo recipients. After medication was discontinued, the subsequent recurrence rate returned to pretreatment frequencies. Daily oral acyclovir was well tolerated. We conclude that oral acyclovir given for four months markedly reduces but does not completely prevent recurrences of genital herpes and does not influence the long-term natural history of the disease.

Acyclovir↗
PubMed1984

Treatment of recurrent genital herpes simplex infections with oral acyclovir. A controlled trial.

Two hundred fifty patients were entered into a multicenter trial to evaluate the efficacy and toxicity of orally administered acyclovir for treatment of recurrent genital herpes. The study consisted of part A, in which patients entered the study within 48 hours of the onset of lesions, and part B, in which patients self-initiated therapy as soon as possible after the onset of a recurrent episode. In both parts, patients received either acyclovir (200 mg) or placebo, five times daily for five days. In both parts, the duration of virus shedding and the time to crusting and healing of lesions were shorter among acyclovir recipients than among placebo recipients. In part B, fewer acyclovir recipients formed new lesions during the study medication period than did placebo recipients. When parts A and B were compared directly, the duration of virus shedding and the times required for crusting and healing of lesions were significantly shorter among acyclovir recipients in part B than among acyclovir recipients in part A. No significant differences in the duration of itching and pain or in the times of subsequent recurrence were noted between acyclovir and placebo groups in either part A or part B. No significant toxic or adverse reactions were seen in acyclovir recipients. Oral acyclovir shortens the duration of virus shedding and the duration of lesions in patients with recurrent genital herpes. These effects are more pronounced when therapy is self-initiated by patients early in the course of a recurrent episode.

Acyclovir↗
PubMed1984

Herpes simplex viral pneumonitis in childhood.

We report two cases of herpes simplex pneumonia in children. One patient had Down syndrome, and the other was immunosuppressed by cancer therapy. Both had interstitial pneumonitis with nonspecific physical, radiographic, and laboratory findings, and both died. The diagnosis of herpes simplex pneumonia was made by isolation of herpes simplex virus from autopsy lung cultures as well as by demonstration of antigen in the tissue with an immunoperoxidase procedure. Inasmuch as herpes simplex pneumonia is a potentially treatable infection, early virologic studies are recommended in immunocompromised children with progressive pneumonitis of undetermined cause.

Antigens, Viral↗
PubMed1984

Secretory IgA antibody in cervicovaginal secretions from women with genital infection due to herpes simplex virus.

Sequential samples of cervicovaginal secretions from women with untreated first and recurrent episodes of genital infection due to herpes simplex virus type 2 (HSV-2) were assayed for IgA antibodies to HSV-2 by using fluorescent antibodies to human secretory piece (sIgA) and human IgA. Among women with first-episode genital herpes, sIgA antibody to HSV-2 was detected in 20 of 31 women from whom HSV was isolated from the cervix, compared with four of 13 women from whom it was not (P less than .05). Among women with first-episode genital herpes, the mean titer of sIgA antibody to HSV-2 peaked between days 9 and 16 of disease, whereas among women with recurrent genital HSV, the peak occurred at days 3-8 of disease. HSV-2 was not isolated from the cervix from any of 130 samples taken when titers of sIgA antibody to HSV-2 were greater than or equal to 1:2, compared with 98 of 259 samples taken when titers were less than or equal to 1:2 (P less than or equal to .01).

Adult↗
PubMed1984

Herpes simplex virus type-2 glycoprotein-subunit vaccine: tolerance and humoral and cellular responses in humans.

Twenty-three subjects were administered three doses of inactivated herpes simplex virus (HSV) type 2 (HSV-2) glycoprotein-subunit vaccine, with doses 2 and 3 being given four and 22 weeks after dose 1. Both HSV-neutralizing antibody and antibody effective in antibody-dependent cell-mediated cytotoxicity were detected in serum samples of 12 of the 13 initially seronegative subjects by week 8. The geometric mean titers of both antibody types decreased between weeks 8 and 22 but increased one week after dose 3. HSV-neutralizing antibody remained detectable in serum samples of seven of the 10 initially seronegative subjects assayed seven months after dose 3. Cell-mediated immunity was detected by lymphocyte transformation responses to HSV-2 after vaccine administration in 12 of the 13 initially seronegative subjects. Unlike humoral antibody, which waned over time, in vitro cell-mediated immune responses remained stable over the seven-month follow-up period after dose 3. This HSV-2-subunit vaccine is well tolerated and elicits both humoral and cell-mediated immune responses to HSV.

Adult↗
PubMed1984

Alteration of lymphocyte transformation response to herpes simplex virus infection by acyclovir therapy.

To evaluate the effect of acyclovir (ACV) therapy on the cellular immune response, we sequentially followed 43 patients with culture-proven first episodes of genital herpes simplex virus (HSV) infection. Twenty-three patients who were treated with ACV and 20 who received placebo had blood obtained weekly during the first 6 weeks after onset of lesions and had their in vitro lymphocyte transformation (LT) response to inactivated HSV antigens measured. The mean stimulation index to HSV antigens at week 3 among patients treated with systemic ACV was 3.5 +/- 0.64 compared to 18.4 +/- 6.89 in their placebo-treated counterparts (P less than 0.05). The mean time to the development of the peak LT response to HSV antigens was 4.3 weeks in systemic-treated versus 3.4 in placebo-treated patients (P less than 0.05). The time to the development of the peak in vitro LT response to HSV antigens and the height of that response were, however, similar between topical ACV- and topical placebo-treated patients. The geometric mean HSV-2-neutralizing titer in convalescent sera was 5.4 in recipients of systemic ACV compared to 10.0 in patients treated with systemic placebo (P less than 0.05). The LT response to HSV antigen was also measured at the first recurrence in 11 patients. No differences were found in the time to first recurrence, lesion duration, number of lesions, or mean stimulation index response to inactivated HSV antigens between the six patients treated with systemic ACV during their primary episode and the five given placebo during their primary episode. Systemic ACV therapy appears to diminish the peak in vitro LT response to inactivated HSV antigens as well as to delay the time to development of that peak response. However, the cell-mediated immune response to subsequent episodes appears similar.

Acyclovir↗
PubMed1984

Effect of acyclovir treatment of primary genital herpes on the antibody response to herpes simplex virus.

Sera from patients with first episode primary genital herpes infections who were treated with the antiviral drug acyclovir were studied to determine the effect of therapy on the immune response to herpes simplex virus (HSV) glycoproteins and polypeptides. 63 patients were evaluated, 35 patients received acyclovir: 11 intravenously, 12 orally, and 12 topically, while 28 received placebo. Topical application of acyclovir had no effect on the immune response to HSV infection. However, both oral and intravenous acyclovir were associated with later development of antibodies to two glycoproteins (of 80,000 and 60,000 mol wt [IIg80 and gD, respectively]) and one nonglycosylated polypeptide of 66,000 mol wt (vp66). Antibody to IIg80 was present in convalescent phase serum in 13/23 systemic acyclovir recipients vs. 18/19 placebo recipients (P = 0.01) and antibody to gD was detected in 8/23 oral or intravenous acyclovir recipients vs. 11/19 placebo recipients (P = 0.06). The mean time to seroconversion to IIg80 (39.0 d) and gD (55.5 d) was significantly longer for systemic acyclovir recipients than for the placebo controls, 23.4 and 18.5 d, respectively (P less than 0.05 for each comparison). 7 (30%) of 23 systemic acyclovir recipients compared with 100% of the placebo recipients had antibody to vp66 by 30 d after onset of the primary episode (P less than 0.001). Subsequent untreated recurrences of genital herpes were associated with seroconversion to gD, IIg80, and vp66. Patients who lacked antibody to both gD and vp66 in sera taken before their first clinical recurrence of disease experienced a longer duration of the recurrent episode (10.8 d) than those who possessed antibody to both vp66 and gD (6.3 d) (P less than 0.05). In addition, the mean duration of lesions, number of lesions, and mean lesion area were greater in patients who lacked antibody to vp66 but had anti gD, as compared with those who had anti-p66 but lacked anti-gD; suggesting that antibody to vp66 correlated more closely with subsequent disease severity than did antibody to gD. Acyclovir therapy appears to influence the frequency and time of development of antibody to a number of different HSV-specific polypeptides. Further studies of the effects of antiviral therapies on the immune response to these proteins may help clarify the role of these polypeptides in the pathogenesis of disease.

Acyclovir↗
PubMed1984

Genital herpes simplex virus infections in adults.

With the decline in prevalence of childhood-acquired oral-labial herpes simplex type 1 infections in some populations and the increasing incidence of genital herpes infections in adults, clinicians are more likely to see patients with severe primary, first-episode genital herpes infections. Complications of these primary infections may include aseptic meningitis and urine retention secondary to sacral radiculopathy or autonomic dysfunction. Presented are the clinical course of first-episode and recurrent infections, complications, diagnostic laboratory methods, and results of controlled clinical trials evaluating the efficacy of topical, intravenous, and oral preparations of acyclovir.

Acyclovir↗
PubMed1983

Neonatal herpes simplex virus infection in King County, Washington. Increasing incidence and epidemiologic correlates.

The incidence of neonatal herpes simplex virus (HSV) infection in King County, Washington, has increased progressively from a rate of 2.6 per 100,000 live births to King County residents during the years 1966 through 1969 to 4.8, 7.4, and 11.9 cases per 100,000 live births for the years 1970 through 1973, 1974 through 1977, and 1978 through 1981, respectively. Detailed interviews of the parents of newborns with neonatal HSV-2 infection revealed clinically symptomatic genital herpes in the mother or father in 65% of the parents and serological and/or cultural evidence of HSV-2 infection in the mother in the other 35% of cases. Clinically symptomatic first episodes of genital herpes during pregnancy occurred in four of the mothers who were delivered of newborns with neonatal HSV-2 infection; two of the mothers were symptomatic at the time of birth. The other 16 interviewed mothers who delivered newborns with neonatal HSV-2 infection all had serological and/or cultural evidence of past HSV-2 infection but were asymptomatic at term. All six newborns with neonatal HSV-1 infection acquired the disease from nongenital sources, and two newborns seemed to have acquired the disease from nonmaternal sources. These data indicate that detailed interviews of the parents are often useful in increasing the clinician's index of suspicion for neonatal HSV infection. The increased prevalence of genital HSV infection in the United States seems to be associated with a concomitant increase in neonatal HSV infection.

Adolescent↗
PubMed1983

The polymicrobial origin of intestinal infections in homosexual men.

To determine the microbial cause and the clinical and pathologic correlates of anorectal and intestinal symptoms in homosexually active men, we performed comprehensive microbiologic studies, anoscopy, sigmoid-oscopy, and rectal biopsy in men examined in a clinic for sexually transmitted diseases. Enteric pathogens were found in 95 of 119 consecutive homosexual men with anorectal or intestinal symptoms and in 29 of 75 randomly selected homosexual men without such symptoms (P less than 0.001). The syndromes of proctitis, proctocolitis, and enteritis were differentiated on the basis of predominant symptoms and findings on anoscopy and sigmoidoscopy. Neisseria gonorrhoeae, herpes simplex virus, Chlamydia trachomatis (non-lymphogranuloma venereum serotypes), and Treponema pallidum were associated with 80 per cent of cases with symptomatic proctitis. Known causes of colitis, including Campylobacter jejuni, Campylobacter fetus fetus, Shigella flexneri, Chl. trachomatis (lymphogranuloma venereum serotypes), Entamoeba histolytica, and Clostridium difficile, were identified in 60 per cent of the cases of proctocolitis. Giardia lamblia was the only agent significantly correlated with enteritis. These data demonstrate that intestinal symptoms in homosexual men are attributable to a complex spectrum of microorganisms, but that careful clinical classification can serve as a guide to the selection of microbiologic studies and to a rational initial choice of therapy.

Adult↗
PubMed1983

Herpes simplex virus proctitis in homosexual men. Clinical, sigmoidoscopic, and histopathological features.

Acute herpes simplex virus (HSV) infection was detected in 23 of 102 consecutively examined, sexually active male homosexuals who presented with anorectal pain, discharge, tenesmus, or hematochezia, as compared with 3 of 75 homosexual men without gastrointestinal symptoms (P less than 0.01). Findings that were significantly more frequent in men with HSV proctitis than in men with proctitis due to other infectious causes included fever (48 per cent), difficulty in urinating (48 per cent), sacral paresthesias (26 per cent), inguinal lymphadenopathy (57 per cent), severe anorectal pain (100 per cent), tenesmus (100 per cent), constipation (78 per cent), perianal ulcerations (70 per cent), and the presence of diffuse ulcerative or discrete vesicular or pustular lesions in the distal 5 cm of the rectum (50 per cent). Serologic evidence indicated that 85 per cent of the men with symptomatic HSV proctitis were having their first episode of HSV-2 infection. The diagnosis of HSV proctitis is suggested by the presence of severe anorectal pain, difficulty in urinating, sacral paresthesias or pain, and diffuse ulceration of the distal rectal mucosa.

Acute Disease↗