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Biomedical subjects

L Corey

Publications and source records attributed to L Corey.

At least 343 records · Page 19Linked to original sources
PubMed1986

Spectrum of rectal biopsy abnormalities in homosexual men with intestinal symptoms.

Homosexually active men have frequent intestinal and rectal symptoms resulting from sexually acquired gastrointestinal infections. We evaluated the histologic findings in rectal biopsy specimens obtained from 89 homosexual men with intestinal symptoms and 11 homosexual men without intestinal symptoms. All had undergone comprehensive microbiologic evaluation for rectal and enteric pathogens. Rectal biopsy specimens were evaluated without knowledge of clinical or microbiologic data by a standardized method for the presence or absence of abnormal histologic features. Forty-six percent of specimens from symptomatic men and 27% of those from asymptomatic men were abnormal. Acute inflammation was the most frequent histologic abnormality and was more frequent in men who had pathogens (51%) than men without pathogens (24%, p less than 0.02). Acute but not chronic inflammation was seen also in specimens from homosexual men without intestinal symptoms. Intestinal spirochetosis was present in specimens from 23 (26%) of the symptomatic and 5 (45%) of the asymptomatic men. In 5 of the 89 symptomatic men, biopsy features of idiopathic inflammatory bowel disease (IIBD) were present; all 5 of these men were infected with either Treponema pallidum or Chlamydia trachomatis. Features of IIBD were present in 25% of those infected with C. trachomatis or T. pallidum. Chronic inflammation was more frequent in men infected with C. trachomatis, syphilis, or herpes simplex virus type II: 31% vs. 3%, p = 0.0002. Acute inflammation was present in specimens from men with proctitis or proctocolitis and enteritis as well as in those from asymptomatic men, whereas chronic inflammation was present only in specimens from men with proctitis or proctocolitis. Both acute and chronic inflammation were more frequent when biopsy specimens of the abnormal mucosa were examined. When specimens from men with single infections were analyzed, histology was rarely diagnostic. We conclude that acute inflammation is frequent in rectal biopsy specimens from symptomatic and asymptomatic homosexual men; chronic inflammation is infrequent, but when present is significantly associated with syphilis, herpes simplex virus type II, and C. trachomatis infection.

Adult↗
PubMed1986

Laboratory diagnosis of herpes simplex virus infections. Principles guiding the development of rapid diagnostic tests.

While the incidence of many bacterial sexually transmitted diseases appears to be decreasing, the complications and frequency of viral sexually transmitted diseases in developed countries has increased over 10-fold in the last decade. Since 1975 genital herpes simplex virus infections have increased at a rate of 12% in the United Kingdom. Significant advances in our understanding of the epidemiology, natural history, and therapy of symptomatic genital herpes has occurred in the last 5 yr. In order to properly utilize this information, however, more widespread availability of laboratory diagnostic testing for herpes simplex virus is needed. The availability of tissue culture isolation facilities for herpes simplex virus has expanded to many community hospitals. More importantly, rapid assays to detect herpes simplex virus using monoclonal and polyclonal antibodies in enzyme-linked immunosorbent assay and immunofluorescent assays and/or detection of herpes simplex virus deoxyribonucleic acid by hybridization methods have also been developed. Recent studies indicate that these assays approach the sensitivity of viral isolation when samples from mucocutaneous lesions are taken. These rapid assays have also allowed clinicians to more rapidly diagnose serious herpes simplex virus infection such as neonatal herpes and to institute antiviral therapy earlier in the course of disease. Although the specificity of these assays in high prevalence populations appears excellent, few studies have evaluated these assays in populations where the prevalence of herpes simplex virus is low. Rapid assays for herpes simplex virus also appear to have decreased sensitivity (less than 60%) in detecting asymptomatic excretion of herpes simplex virus from the lower genital tract.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Viral↗
PubMed1986

The offspring of twins as sampling units in pedigree analysis of congenital anomalies.

A statistical model was developed to determine the likelihood of a twin kinship, that is, the offspring of a pair of monozygotic or dizygotic twins under three types of inheritance: sporadic, single locus fetal genetic, and single locus maternal genetic. Samples of 8,000 kinships were simulated for a discrete trait under various hypotheses, and the likelihood determined for each type of etiology. The results indicated that the pedigree analysis procedures formulated here could efficiently detect sporadic or single locus effects with a power approaching 100%, although the parameter estimates obtained were slightly biased. Further analyses revealed that the type of pedigree analysis formulated in this study was found to have equivalent power for equal or unequal frequencies of kinships by the sex and zygosity of the twin parent. It was suggested that further studies be carried out that included the twins and spouses in the likelihood equations, as well as tests of more sophisticated models.

Congenital Abnormalities↗
PubMed1986

A placebo-controlled trial of topical 8% arildone cream early in recurrent genital herpes.

Arildone is an aryl diketone which is inhibitory in vitro against herpes simplex virus type 2 at a concentration of 2 micrograms/ml or less. One hundred forty-five patients with recurrent genital herpes were enrolled in a multicenter, randomized, placebo-controlled, double-blind trial to evaluate the efficacy and safety of an 8% arildone cream. Patients initiated therapy a mean of 9.9 h and a maximum of 24 h after the reported onset of lesions and applied medication 6 times daily for 7 days. The duration of viral shedding was shorter among women (P less than 0.05) and the duration of local itching was shorter among men (P less than 0.05) in patients that received arildone than in those that received placebo, but there were no significant differences between treatment groups in duration of pain, time to crusting or healing of lesions, or percentage of patients developing new lesions. Mild local irritation after application of ointment was common and occurred equally in both treatment groups. Despite early application, topical arildone cream was ineffective in the therapy of acute recurrences of genital herpes.

Administration, Topical↗
PubMed1986

Type specificity of complement-fixing antibody against herpes simplex virus type 2 AG-4 early antigen in patients with asymptomatic infection.

We evaluated the type specificity of complement-fixing (CF) antibody against the AG-4 early antigen of herpes simplex virus (HSV) type 2 (HSV-2) by comparing a commercial AG-4 CF kit (Simplex-2; Gene Link Australia, Inc., Princeton, N.J.) with quantal microneutralization (MN) and absorption-Western blotting in testing sera from patients with and without a history of genital herpes. Sera characterized as HSV type 1 (HSV-1) or HSV-2 positive or negative by MN were selected and tested by CF, and those with discordant results were further analyzed for specific antibodies by absorption with HSV-1 or HSV-2 antigen and Western blotting with heterologous HSV proteins. A total of 34 of 42 (81%) sera HSV-2 positive by MN, 19 of 43 (44%) sera HSV-1 positive by MN, and 0 of 19 sera negative by MN were positive by CF. Absorption-Western blotting showed that 12 of 18 (67%) sera HSV-1 positive by MN but positive by CF had no HSV-2-specific antibody and that all 7 sera HSV-2 positive by MN but negative by CF had HSV-2-specific antibody. When MN and absorption-Western blotting data were combined to analyze patients with no history of genital herpes, 7 of 19 (37%) with no HSV-2-specific antibody were positive by CF, and 7 of 27 (26%) with HSV-2-specific antibody were negative by CF. The positive and negative predictive values for the CF test were 78 and 75%, respectively, in this group. The presence of antibody to the HSV AG-4 antigen does not discriminate sufficiently between HSV-1- and HSV-2-infected patients to be of value in predicting HSV-2 infection in the absence of symptomatic disease.

Antibodies, Viral↗
PubMed1986

Recurrent genital herpes and suppressive oral acyclovir therapy. Relation between clinical outcome and in-vitro drug sensitivity.

To evaluate the association between in-vitro resistance of herpes simplex virus type 2 to acyclovir and breakthrough recurrences of herpes despite chronic suppressive therapy, we determined the in-vitro sensitivity of herpes simplex virus isolated before, during, and after therapy. One hundred eighty-three virus isolates from 107 patients were tested. Before therapy, the median amount of drug required to inhibit 50% of the virus in tissue culture (ID50) was 0.91 microgram/mL. The median ID50 after therapy was 0.99. Six isolates from patients with culture-positive breakthrough recurrences were evaluated. The median ID50 was 0.90 microgram/mL (range, 0.39 to 1.55). The development of breakthrough recurrences could not be correlated with infection with strains of herpes simplex virus type 2 that were resistant to acyclovir in vitro. Acyclovir-resistant strains are not commonly recovered from patients during acyclovir therapy, nor does there seem to be a high frequency of resistance after 4 months of chronic suppressive therapy.

Acyclovir↗
PubMed1985

Genital herpes in pregnancy: risk factors associated with recurrences and asymptomatic viral shedding.

One hundred forty-seven women with recurrent symptomatic genital herpes simplex virus acquired prior to the start of pregnancy (group 1) and 15 women whose first symptomatic episode of genital herpes was acquired during pregnancy (group 2) were followed weekly during the course of gestation. Among women with recurrent genital herpes antedating pregnancy, the mean number of recurrences per trimester increased from 0.97 to 1.26 to 1.63 in the first through third trimester, respectively (p less than 0.05 for comparison between each trimester). The median number of symptomatic recurrences of genital herpes during gestation was four in women in group 1 compared to one in women in group 2 (p less than 0.01). Asymptomatic viral excretion from the genital tract was, however, more common in women in group 2 (33%) than in women in group 1 (12.9%) (p less than 0.05). Herpes simplex virus was isolated at 5.5% of routine visits in group 2 women compared to 1% of routine visits among group 1 women. Logistic regression analysis indicated young age also was associated with more frequent asymptomatic viral shedding. Asymptomatic herpes simplex virus excretion was more common from the vulvar area than the cervix, and women in group 2 were more likely to shed virus from both sites simultaneously than women in group 1. Age and recent acquisition of genital herpes are risk factors for asymptomatic excretion of herpes simplex virus during pregnancy.

Adult↗
PubMed1985

Adenovirus infections in patients undergoing bone-marrow transplantation.

Viral infection is commonly observed after bone-marrow transplantation. We isolated adenovirus from 51 of 1051 patients undergoing marrow transplantation between 1976 and 1982. Of the 46 isolates available for typing, 13 (27.7 per cent) were of the closely related species 11, 34, or 35 (subgenus B). All 13 of the patients with these species had positive urine cultures. The species have previously been associated with the acquired immunodeficiency syndrome or with renal transplantation but are not commonly found in community surveys. Invasive infection was confirmed by biopsy or autopsy in 10 of 51 patients. Seven of the 10 had virus isolated from lung, and 4 died from pneumonia attributed to adenovirus. Two of the five patients with renal isolates had evidence of virally induced renal impairment, and both patients with liver isolates had adenovirus hepatitis. There was no common source that accounted for these adenovirus infections, and the most likely source of infection appeared to be endogenous viral reactivation. The only identifiable risk factor for the development of infection and for severe disease was the presence of moderate to severe graft versus host disease.

Adenoviridae Infections↗
PubMed1985

Humoral immune response to HSV-1 and HSV-2 viral proteins in patients with primary genital herpes.

The humoral immune response to HSV-1 and HSV-2 proteins was examined in patients with primary first-episode genital herpes. Ten patients had culture-proven HSV-1 infections, 37 had HSV-2 infections, and all were seronegative to HSV proteins before developing their infections. Development of serum antibodies to individual HSV proteins and glycoproteins was determined by immunoprecipitation of radiolabeled HSV-1- and HSV-2-infected cell proteins and subsequent gel electrophoresis. In HSV-1 patients, a sequential development of antibodies to HSV-1 proteins was observed with early appearance of antibodies to the nucleocapsid protein p148 and to glycoproteins gB and gC. Seroconversion to gD and to a polypeptide of 88,000 molecular weight (p88) occurred next, and, finally, seroconversion to gE and to a nonglycosylated 66,000 dalton protein p66. In HSV-2 patients, antibodies to HSV-2 proteins p148, gB, and p88 appeared within 1 week of onset of symptoms. Seroconversion to p66, gD, and to a complex of glycoproteins gC and gE ("g80") occurred later, at a mean time of approximately 3 weeks. Seroconversion to HSV-1 gB, p88, and p66 occurred significantly later than seroconversion to the homologous counterparts. Seroconversion within 21 days of onset to HSV-2 gD, g80, and p66 was associated with a longer time to the first recurrence in HSV-2 patients, suggesting a possible role of these antibodies, alone or in combination, in the maintenance of HSV-2 latency in humans.

Antibody Formation↗
PubMed1985

Cell-mediated immunity in human herpesvirus infection: analysis by monoclonal antibodies.

Peripheral blood lymphocytes (PBL) were obtained from heterosexual patients during the first or recurrent episodes of genital herpes simplex type 2 (HSV-2) infections. These cells were incubated with a panel of lymphocyte-specific monoclonal antibodies and examined by indirect immunofluorescence and flow cytometry. Lymphocyte proliferative responses to inactivated HSV-2 (UV-HSV-2) were also determined on repeat occasions using PBL obtained from patients with first episodes of infection. Flow cytometry analysis indicated that PBL obtained within 1 week after the onset of symptoms of first episode genital herpes exhibited significantly lower OKT 4 helper/OKT 8 suppressor T-cell ratios (1.26 +/- 0.12) than cells from either normal controls (2.44 +/- 0.3, P less than 0.01) or patients with recurrent genital HSV-2 infection (2.58 +/- 0.40, P less than 0.01). This lowered ratio was due to a decrease in OKT 4-positive helper T cells present early during initial infection (30.2 +/- 2.9, P less than 0.01 compared to recurrent disease patients or controls) and was not caused by a concomitant increase in OKT 8-positive T cells. No variation was observed during the course of infection in the proportion of total T cells as determined by EAET rosette formation or reactivity with the T-cell specific monoclonal antibody 9.6. PBL obtained from patients within 1 week after symptom onset exhibited a poor proliferative response to UV-HSV-2. Maximal proliferative responses occurred 6-9 weeks after disease onset and required the presence of OKT 4-positive T lymphocytes. The results of these experiments indicate that at different stages of disease, HSV infection is accompanied by fluctuations in the ratio of helper to suppressor T cells and alterations in antigen-specific lymphocyte proliferation. These findings suggest that variations in lymphocyte proliferative responses during the course of first episode genital herpes infection may reflect disease related variations in either the number or activity of circulating OKT 4-positive T lymphocytes.

Adult↗
PubMed1985

Cytomegalovirus infection in sex partners: evidence for sexual transmission.

To examine the hypothesis that cytomegalovirus (CMV) is sexually transmitted, we determined the prevalences of antibody to CMV and viral shedding in 63 male sex partners of women with or without CMV infection, and CMV isolates from infected couples were compared by DNA restriction enzyme analysis. The prevalence of seropositivity by enzyme-linked immunosorbent assay was 31 (74%) of 42 men whose female partners were seropositive compared with five (31%) of 16 men whose partners were seronegative (P = .008). CMV was isolated from the semen or urine of four (22%) of 18 men whose female partners shed CMV from the cervix or urine compared with none of 42 whose partners were culture negative (P = .013). DNA restriction enzyme typing of CMV isolates from three pairs of sex partners showed that two of the couples were infected with common strains; epidemiologically unrelated isolates gave distinct patterns. Heterosexual contact is a major mode of transmission of CMV among some young adults.

Adult↗
PubMed1985

Ineffectiveness and toxicity of BCG vaccine for the prevention of recurrent genital herpes.

One hundred fifty-five patients with genital herpes were enrolled in a double-blind, placebo-controlled trial comparing 0.1 ml of intradermal BCG vaccine with placebo for the prevention of recurrent episodes of genital herpes. The mean rate or recurrence over 9 months of prospective follow-up was 0.528 recurrences per month in BCG recipients compared with 0.392 recurrences per month in placebo recipients (not significant). The BCG vaccine also failed to influence the duration of lesions in the first recurrent episode of genital herpes after vaccination. Six patients were given a second inoculation of BCG vaccine, and persistent cutaneous granulomas were noted in three of these six patients. Intradermal inoculation with BCG does not appear to affect the natural history of genital herpes, and repeated inoculations can be toxic.

Adult↗
PubMed1985

Isolation and characterization of six new genome types of human adenovirus types 1 and 2.

Several of the 41 types of human adenovirus have been divided into genome types based on aberrant restriction endonuclease digestion patterns of viral DNA. In the process of screening a large number of clinical adenovirus isolates by restriction endonuclease digestion of viral DNA, we have identified nine isolates from eight patients which were identified by neutralization as adenovirus type 1 or 2 but had aberrant cleavage patterns. Cleavage sites for the enzymes SmaI, EcoRI, HindIII, KpnI, and HpaI were mapped. The variants could be placed in six distinct groups based on cleavage patterns. The designation genome types 1a, 1b, 1c, 2b, 2c, and 2d are proposed for these isolates.

Adenoviridae Infections↗
PubMed1985

Comparison of neutralization and DNA restriction enzyme methods for typing clinical isolates of human adenovirus.

Sixty-five adenovirus isolates collected over a 3.5-year period were typed by both standard microneutralization techniques and restriction endonuclease digestion of viral DNA. Of the 65 isolates, 47 (72.3%) representing six adenovirus types could be typed by microneutralization. Eighteen isolates demonstrated partial neutralization with standard antisera to two or more adenovirus serotypes and thus could not be definitively typed. DNA analysis permitted typing of 64 of the 65 isolates (98.5%) (including four isolates which contained mixtures of two adenovirus types), and 12 different types were identified. Neutralization and DNA typing disagreed for five isolates, and in each case, digestion with multiple restriction endonucleases and DNA hybridization studies were consistent with the type assigned by DNA analysis. In addition, the DNA analysis method allowed the identification of genomic variants (genome types) of five adenovirus types. We conclude that typing clinical isolates of adenovirus by restriction endonuclease digestion of viral DNA can be done rapidly, provides additional epidemiological and typing information, and provides fewer ambiguous results than does typing by neutralization.

Adenoviruses, Human↗