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Biomedical subjects

L Corey

Publications and source records attributed to L Corey.

At least 379 records · Page 21Linked to original sources

Monoclonal antibodies to herpes simplex viruses: use in antigenic typing and rapid diagnosis.

Four monoclonal antibodies that react specifically with cells infected with herpes simplex viruses (HSV) are described. One of these antibodies (3-G11) reacts with a glyco-protein C complex (molecular weight, 80,000 and 120,000) that is specific for HSV type 1, while the other three antibodies (6-A6, 6-E12, and 6-H11) react with proteins that are specific for HSV type 2 and that have molecular weights of 140,000, 55,000, and 38,000, respectively. The monoclonal antibodies possessed sufficient specificity to allow rapid serotyping of HSV obtained either from infected cells in culture or directly from patients. In immunofluorescence tests the antibodies were used to serotype 263 culture isolates of HSV, while in preliminary tests performed with specimens obtained directly from patients, the antibodies demonstrated 88% of the sensitivity of tissue culture isolation.

Antibodies, Monoclonal↗

In vitro sensitivity to acyclovir in genital herpes simplex viruses from acyclovir-treated patients.

Genital isolates of herpes simplex virus (HSV) from patients given acyclovir or placebo were tested in vitro for sensitivity to acyclovir. Isolates obtained before therapy were sensitive to acyclovir concentrations of 0.01-19 micrograms/ml, with 86 of 97 isolates inhibited by less than 1 microgram/ml. Before therapy, six patients had isolates of HSV type 2 with ID50 values (concentrations of drug reducing viral cytopathic effect by 50%) of greater than 3 micrograms/ml. Plaque purification revealed mixed populations of virus; some clones were associated with high and some with low rates of acyclovir phosphorylation. Sensitivity to acyclovir decreased in isolates obtained after therapy from four of 25 patients given acyclovir and three of 30 patients given placebo. The occurrence of this change with similar frequency in the two groups suggests that factors other than the use of acyclovir influence the in vitro sensitivity of clinical HSV isolates to this agent. In one patient in whom an acyclovir-resistant, thymidine kinase-negative strain of HSV type 2 emerged during therapy, infection subsequently recurred. The isolate responsible for the recurrence was sensitive to acyclovir and had a high level of acyclovir-phosphorylating activity.

Acyclovir↗

Treatment of primary first-episode genital herpes simplex virus infections with acyclovir: results of topical, intravenous and oral therapy.

Three double-blind, placebo-controlled evaluations of acyclovir were performed in first-episode genital herpes infections. In one trial intravenous acyclovir or saline was administered in hospital over 5 days. In the other two trials, 10-day courses of oral, or 7-day courses of topical acyclovir and respective placebos were followed up in the outpatient department. Regular assessments included staging examinations, culture of lesions and blood and serum analyses. No patient discontinued medication because of an adverse reaction, although one quarter of topically treated patients complained of local irritation on application. The placebo-controlled evaluations indicate that, if given within the first 7 days after the onset of lesions, topical, intravenous and oral acyclovir are useful in shortening the course of first-episode primary genital herpes. The clinical and virological effects of intravenous and oral acyclovir were more marked than those of topical treatment in the reduction of viral shedding; the time to complete healing of lesions; and in the reduction of new lesion formation. Systemic preparations of acyclovir also decreased the symptoms of herpes simplex virus urethritis and intravenous acyclovir those of herpes simplex virus cervicitis. Neither systemic treatment, however, was effective in delaying or reducing the frequency of subsequent recurrences, which may be related to the development of early ganglionic infection. Despite this, acyclovir treatment is a significant advance in the management of primary genital herpes.

Acyclovir↗

Typing of clinical herpes simplex virus isolates with mouse monoclonal antibodies to herpes simplex virus types 1 and 2: comparison with type-specific rabbit antisera and restriction endonuclease analysis of viral DNA.

A total of 122 clinical isolates of herpes simplex virus (HSV) from 107 patients were typed by using an indirect immunoperoxidase technique with commercially available type-specific rabbit antisera, recently developed mouse monoclonal antibodies to HSV types 1 and 2, and restriction endonuclease analysis of viral DNA. With the commercially available type-specific rabbit antisera, 34% of clinical HSV isolates were of indeterminate type; 63% of them were typed as HSV type 1 and 37% as HSV type 2 by using monoclonal antibody and restriction enzyme typing systems. Typing by immunofluorescence assay with the monoclonal antibodies gave identical results to those obtained by restriction enzyme analysis. Simultaneous infection with both HSV types was demonstrated by monoclonal antibody typing in five isolates from three patients. These findings were subsequently confirmed by plaque purification and restriction endonuclease analysis of viral DNA. Monoclonal antibodies were as sensitive as restriction enzyme analysis for the typing of clinical HSV isolates. Because of their simplicity, they are more amenable to use in clinical laboratories than is restriction endonuclease analysis.

Animals↗

Intravenous acyclovir for the treatment of primary genital herpes.

Thirty-one patients with first episodes of genital herpes were randomized in a double-blind fashion to intravenous treatment with saline placebo or acyclovir, 5 mg/kg body weight at 8-hour intervals, for 5 days. The median duration of viral shedding from genital lesions after the onset of therapy was significantly shorter for patients given acyclovir (2 days) than for those given placebo (13 days), p less than 0.001. Viral shedding from the pharynx, cervix, urethra, and urine were also shorter in acyclovir-treated patients. (p less than or equal to 0.01 for each comparison). Local and systemic symptoms were shortened by a mean of 5 days and healing of genital lesions by a mean of 12 days in acyclovir-treated patients. (p less than 0.01). Complications during treatment, such as extragenital lesions or urinary retention requiring catheterization, developed in four patients given placebo and in none given acyclovir. (p less than 0.05). Intravenous acyclovir substantially decreases the symptoms, duration of lesions, and complications of primary genital herpes.

Acyclovir↗

Genital herpes simplex virus infections: clinical manifestations, course, and complications.

The clinical course and complications of 268 patients with first episodes and 362 with recurrent episodes of genital herpes infection were reviewed. Symptoms of genital herpes were more severe in women than in men. Primary first-episode genital herpes was accompanied by systemic symptoms (67%), local pain and itching (98%), dysuria (63%), and tender adenopathy (80%). Patients presented with several bilaterally distributed postular ulcerative lesions that lasted a mean of 19.0 days. Herpes simplex virus was isolated from the urethra, cervix, and pharynx of 82%, 88%, and 13% of women with first-episode primary genital herpes, and the urethra and pharynx of 28% and 7% of men. Complications included aseptic meningitis (8%), sacral autonomic nervous system dysfunction (2%), development of extragenital lesions (20%), and secondary yeast infections (11%). Recurrent episodes were characterized by small vesicular or ulcerative unilaterally distributed lesions that lasted a mean of 10.1 days. Systemic symptoms were uncommon and 25% of recurrent episodes were asymptomatic. The major concerns of patients were the frequency of recurrences and fear of transmitting infection to partners or infants.

Adult↗

Genital herpes simplex virus infections: current concepts in diagnosis, therapy, and prevention.

Genital herpes simplex virus infection is the commonest cause of genital ulcerations in persons in industrialized nations. Overlap in the clinical manifestations of genital herpes with other infectious and noninfectious causes of genital ulcerations often requires clinicians to seek laboratory confirmation of the cause of a genital ulcer. The sensitivity of any laboratory procedure for detecting herpes simplex virus infection differs with the stage of the disease. Isolation of the herpes simplex virus in tissue culture is the most sensitive and specific laboratory test for the confirmation of genital herpes; cytologic and antigen detection techniques are approximately 50% and 70% as sensitive as viral isolation. The antiviral compound acyclovir is the first medication useful for the management of persons with genital herpes. Prevention of transmission of infection and recurrences of disease, however, has not been achieved. Description of the clinical manifestations of disease, its variable recurrence rate, and potential for future infectivity are issues that physicians should discuss with patients who have genital herpes.

Acyclovir↗

Ineffectiveness of topical idoxuridine in dimethyl sulfoxide for therapy for genital herpes.

The efficacy and toxicity of topical applications of 30% idoxuridine in dimethyl sulfoxide, dimethyl sulfoxide alone, or saline in 96 recurrent and 39 first episodes of genital herpes simplex virus (HSV) infection were compared. Drug was applied to lesions four times daily for seven days. In recurrent episodes, the duration of viral shedding after beginning idoxuridine in dimethyl sulfoxide use was significantly shorter (0.6 days) than with dimethyl sulfoxide (1.4 days) or saline (2.0 days) (P less than .05). In primary episodes, viral shedding lasted 2.6 days with idoxuridine in dimethyl sulfoxide and 8.4 days with dimethyl sulfoxide or saline. Idoxuridine in dimethyl sulfoxide had no effect in recurrent or primary HSV on duration of symptoms, new lesion formation, healing time, or risk of subsequent recurrence. Complications in patients given idoxuridine in dimethyl sulfoxide included local burning, generalized contact dermatitis, and vulvar carcinoma in situ. Thirty percent idoxuridine in dimethyl sulfoxide has no effect on clinical manifestations of genital HSV infection and may be hazardous.

Administration, Topical↗

Double-blind controlled trial of topical acyclovir in genital herpes simplex virus infections.

Sixty-nine patients with first episodes and 111 with recurrent episodes of genital herpes simplex virus (HSV) infection were enrolled in a double-blind trial comparing a 5 percent topical acyclovir ointment versus placebo, polyethylene glycol (PEG). Among acyclovir recipients with first episodes of genital herpes, the mean duration of viral shedding from genital lesions, 2.0 days, mean duration of local pain or itching, 3.6 days, and mean time to healing of lesions, 11.2 days, were less than in placebo recipients 4.6, 6.7, and 15.8 days, respectively (p less than 0.05 for each comparison). Among patients with recurrent genital herpes, the mean duration of viral shedding from genital lesions was 0.8 days in acyclovir recipients compared with 1.7 days in placebo recipients (p less than 0.001). Among men with recurrent genital herpes, the mean time to crusting and healing of lesions was 3.5 and 7.5 days in acyclovir recipients compared with 5.0 and 9.7 days in placebo recipients, p = 0.03 and 0.07, respectively. No significant differences in the duration of symptoms or healing times were noted between acyclovir- and placebo-treated women with recurrent genital herpes. Acyclovir therapy was not associated with a decrease in frequency of clinical recurrences or an increase in the time of the next recurrence in patients with either first or recurrent genital herpes. Topical acyclovir appears effective in shortening some of the clinical manifestations of genital HSV infections.

Acyclovir↗

Patient-initiated therapy for recurrent genital herpetic infections.

Therapy for recurrent genital herpes is difficult to evaluate because of the short duration of lesions and viral shedding. Very early treatment, however, can be begun by patients who experience prodromes before onset of lesions. We have found prodromes to occur in 73 percent of male and 84 percent of female patients; 57 percent of the men and 68 percent of the women experienced prodromes in at least three out of every four recurrent episodes. Variables that might affect results of such a patient-initiated study evaluating topical acyclovir included: application of the ointment (drug or placebo) without prodrome (10 percent); the possibility of a false prodrome (less than or equal to 10 percent); long intervals between experiencing a prodrome and ointment application (15 percent greater than 24 hours); the inability to sense a prodrome during sleep; lack of ointment application to the involved areas with initial or later lesions (approximately 15 percent); noncompliance of enrollees in returning for study evaluations (greater than or equal to 10 percent). Such variables will need to be considered when the code is broken in this multicenter study, as well as for patient-initiated studies with other formulations of acyclovir or with other drugs. Earlier negative studies with other agents given within two to three days of appearance of lesions might also require reevaluation with similar patient-initiated studies.

Acyclovir↗

A trial of topical acyclovir in genital herpes simplex virus infections.

Seventy-seven patients with first episodes of genital herpes and 111 with recurrent episodes were enrolled in a double-blind trial comparing topical acyclovir with a placebo (polyethylene glycol ointment). Among acyclovir-treated patients with first-episode primary genital herpes, the mean duration of viral shedding (4.1 days) and the time to complete crusting of lesions present at the initiation of therapy (7.1 days) were shorter than among placebo recipients (7.0 and 10.5 days, respectively) (P less than 0.05). Acyclovir-treated patients with recurrent herpes had a shorter duration of viral shedding than placebo recipients (0.95 vs. 1.90 days) (P = 0.03). Among the patients with recurrent herpes, acyclovir reduced the time to crusting of lesions in men but had no effect on the symptoms or healing times in women. Topical acyclovir shortens the duration of viral shedding and accelerates healing of some genital herpes simplex virus infections.

Acyclovir↗

Recurrent genital herpes simplex virus infection in pregnancy: infant outcome and frequency of asymptomatic recurrences.

Eighty pregnant patients with a history of recurrent genital herpes simplex virus (HSV) infection were followed up with frequent genital examinations and cultures for HSV during their pregnancies. Recurrences of genital HSV during pregnancy were documented in 67 patients. Ninety-six percent of these had external genital lesions noted at some time during their pregnancy. One hundred eighty-six (93%) of the 199 recurrences of the disease were associated with external genital lesions. Of 13 episodes of asymptomatic viral shedding documented in this patient population, six were from the vulva alone, five were from the cervix alone, and two were from both the vulva and the cervix. Of 11 episodes of cervical HSV shedding, seven were asymptomatic and four were associated with external symptomatic lesions. Despite frequent recurrences of genital HSV infection during pregnancy, all study patients were delivered at term, and although they had a high rate of delivery by cesarean section (32.5%), the outcome of their infants was good.

Adolescent↗