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Biomedical subjects

L Corey

Publications and source records attributed to L Corey.

At least 271 records · Page 15Linked to original sources
PubMed1991

Acquired immunodeficiency syndrome. Cerebrospinal fluid findings in patients before and during long-term oral zidovudine therapy.

Fifty-two patients with acquired immunodeficiency syndrome were enrolled in this study to evaluate the relationship between cerebrospinal fluid (CSF) zidovudine concentrations and neurologic and human immunodeficiency virus (HIV) culture findings. Paired HIV-CSF culture and neurologic measurements were available in 30 and 45 patients, respectively. Twenty-nine patients were assessable for zidovudine CSF concentrations. Patients underwent lumbar puncture and neurologic testing before and after 8 weeks or more of oral zidovudine therapy (600 to 1500 mg/d). After 8 weeks of therapy, the frequency of HIV isolation from CSF cultures was unchanged. Significant neurologic improvement by examination was noted in 61.5% (32/52) of the patients. The median CSF zidovudine concentration among 29 patients was 0.047 mg/L (range, 0.015 to 0.198 mg/L). No correlation between CSF zidovudine concentration, cumulative dose, or HIV isolation from CSF and persistence or resolution of neurologic symptoms or signs was observed. The mechanisms by which zidovudine improves neurologic function are unclear and appear unrelated to direct clearance of virus from CSF.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Pharmacokinetics of acyclovir in the term human pregnancy and neonate.

Concern about neonatal herpes often leads to cesarean delivery of infants in women with a history of genital herpes. The antiviral drug acyclovir has been used effectively to suppress genital herpes simplex virus recurrences in nonpregnant adults. Its administration to pregnant women with recurrent genital herpes may reduce herpes simplex virus recurrences and thus may decrease the cesarean section rate among this population. To study the pharmacokinetics, safety, and patient tolerance of suppressive oral acyclovir, either 200 mg (n = 7) or 400 mg (n = 8) was administered orally every 8 hours to pregnant women with a history of recurrent herpes simplex virus, from 38 weeks' gestation until delivery. The mean +/- SD plasma levels for the 200 and 400 mg groups, respectively, were: first dose peak, 1.7 +/- 0.6 and 2.3 +/- 1.0 mumol/L; steady-state trough, 0.7 +/- 0.3 and 0.8 +/- 0.6 mumol/L; steady-state peak, 1.9 +/- 1.0 and 3.3 +/- 1.0 mumol/L. In late gestation maternal acyclovir pharmacokinetics were similar to those of nonpregnant adults from other studies. Acyclovir was concentrated in the amniotic fluid; however, there was no accumulation in the fetus (mean maternal/infant plasma ratio at delivery was 1.3). Acyclovir was well tolerated, and no toxicity was seen in the mothers or infants. The administration of acyclovir, 400 mg every 8 hours, appears appropriate for use in an efficacy and safety study regarding suppression of herpes simplex virus recurrences during the last weeks of pregnancy.

Acyclovir↗
PubMed1991

Pharmacokinetic disposition of zidovudine during pregnancy.

Zidovudine pharmacokinetics was determined in three human immunodeficiency virus type 1-seropositive women receiving zidovudine (200 mg orally every 4 h) from 19 to 39 weeks of pregnancy and postpartum. Zidovudine concentrations were measured using high-pressure liquid chromatography, and pharmacokinetic analyses were done using model-independent methods. For the pregnant versus postpartum periods, peak zidovudine levels (mean +/- 1 SD) were 3.9 +/- 1.7 mumol/l versus 4.3 +/- 0.04 mumol/l (P = .56); elimination half-lives were 1.3 +/- 0.6 versus 1.0 +/- 0.3 h (P = .41); areas under the concentration curve were 4.5 +/- 1.0 mumol/l x h and 6.8 +/- 0.5 mumol/l x h (P = .02); apparent total body clearances were 2.5 +/- 0.6 l/h/kg and 1.7 +/- 0.4 l/h/kg (P = .05); and apparent steady state volumes of distribution were 3.9 +/- 1.0 l/kg and 2.6 +/- 0.8 l/kg (P = .07), respectively. Umbilical cord serum levels ranged from 113%-127% of maternal levels. No persistent adverse effects of zidovudine therapy were seen in the three women or their babies.

Adult↗
PubMed1991

Recovery of human immunodeficiency virus type 1 from semen: minimal impact of stage of infection and current antiviral chemotherapy.

Because exposure to semen is important for the sexual transmission of human immunodeficiency virus type 1 (HIV), the relationship of stage of infection and antiviral chemotherapy to isolation of HIV from semen was investigated. Whereas HIV was isolated from peripheral blood mononuclear cells of all seropositive persons tested, it was isolated from semen in only 11 (32%) of 34 men, including 3 of 6 who were studied sequentially over time. HIV was isolated from 6 (32%) of 19 semen specimens from 14 asymptomatic persons (Centers for Disease Control [CDC] class II or III) and from 10 (28%) of 36 semen specimens from 20 symptomatic patients (CDC class IV). Isolation of HIV from semen did not correlate with CD4+ or CD8+ T lymphocytes counts or zidovudine therapy. Seropositive men may shed HIV in semen early in the course of infection, and zidovudine therapy seems to have no effect on the recovery of HIV and, thus, on the potential for sexual transmission of HIV.

HIV Infections↗
PubMed1991

Fertility parameters in men infected with human immunodeficiency virus.

The effect of human immunodeficiency virus type 1 (HIV) infection on semen parameters that assess fertility was investigated in 50 semen specimens from 21 asymptomatic or minimally symptomatic HIV-seropositive men and 3 specimens from 3 men with AIDS. HIV was isolated from 15 (30%) of 50 specimens from asymptomatic or minimally symptomatic persons and from 1 of 3 specimens from patients with AIDS. The men with AIDS all had pyosemia and grossly abnormal sperm. In contrast, semen specimens from other seropositive men did not differ significantly from semen specimens from healthy seronegative semen donors. No abnormality in sperm count, morphology, numbers or types of leukocytes in semen, or other seminal parameters was associated with HIV shedding in semen. Zidovudine therapy did not affect sperm morphology or seminal characteristics. Thus, although patients with AIDS had abnormal semen, the laboratory parameters that assess fertility were not affected by shedding of HIV in semen or concomitant therapy with zidovudine.

Acquired Immunodeficiency Syndrome↗
PubMed1991

A double-blind, placebo-controlled cytogenetic study of oral acyclovir in patients with recurrent genital herpes.

The antiherpes drug acyclovir breaks chromosomes in vitro at millimolar concentrations and at highly toxic doses in rodents but does not induce single-gene mutations. Recurrent genital herpes patients were examined to determine if such chromosomal damage occurs in peripheral lymphocytes during acute or chronic acyclovir therapy. Patients were randomly assigned to receive acyclovir suppressively and for recurrences, placebo suppressively and acyclovir for recurrences, or placebo suppressively and for recurrences (n greater than or equal to 20 for each group; all treatment double-blind). Normal volunteers and acyclovir-treated cultures served as additional controls. Cytogenetic analyses were done at enrollment (pretreatment), on day 5 of acute acyclovir or placebo treatment for the first postenrollment recurrence (postacute), and at the end of a year on study (postchronic). Cells in metaphase, 150 for each patient, were examined at each time point for structural and numerical chromosomal abnormalities. No cytogenetic effects of chronic or acute oral acyclovir treatment were found relative to lifestyle controls, pretreatment controls, or placebo treatment.

Acyclovir↗
PubMed1991

Extended duration of herpes simplex virus DNA in genital lesions detected by the polymerase chain reaction.

To evaluate the utility of the polymerase chain reaction (PCR) for documenting herpes simplex virus (HSV) in persons with reactivated genital lesions viral isolation was compared with a recently developed PCR method. Three women experiencing four episodes of recurrent genital herpes were followed for 10 days per episode with daily examination and duplicate swabs of the lesions, one for HSV culture and one for PCR. HSV type 2 was cultured from three of four episodes and the mean duration of viral isolation from recurrent genital lesions was 2.6 days. PCR detected HSV DNA from lesion swabs during all four episodes, and HSV DNA was positive for an average of 6.8 days. HSV DNA was demonstrated in ulcerative lesions on 15 of 17 days versus 3 of 17 days by viral isolation (P less than .01). HSV PCR became negative when the lesions reepithelialized. These data suggest that PCR is a more sensitive measure of HSV infection than routine viral culture and that PCR detects the presence of HSV at times when culture is negative.

Adult↗
PubMed1991

Genital warts, other sexually transmitted diseases, and vulvar cancer.

To determine whether specific sexually transmitted diseases were associated with an increased risk of vulvar cancer, we conducted a case-control study among residents of three countries in western Washington. We identified, interviewed, and obtained blood samples from women with in situ (n = 180) and invasive (n = 53) vulvar cancer, 18-79 years of age, who were first diagnosed with these diseases during 1980-1988. We compared their responses with those of 466 women from the general population who were identified by means of random digit dialing. On average, women with vulvar cancer reported a greater number of prior sexual partners than did controls. The risk of vulvar cancer was elevated among women who reported a prior history of condyloma (for in situ cancer, RR = 15.8; for invasive disease, RR = 17.3) or gonorrhea (for in situ cancer, RR = 2.2; for invasive disease, RR = 5.0). Women who were seropositive to herpes simplex virus type 2 (HSV-2) were at higher risk for carcinoma in situ than were controls (RR = 2.0). A history of nonspecific vaginitis, trichomoniasis, syphilis, or seropositivity to cytomegalovirus was not related to case-control status. These results indicate that only a subset of sexually transmitted diseases, particularly human papillomavirus, may play a role in the development of vulvar cancers.

Adolescent↗
PubMed1991

Subclinical manifestations of vulvar human papillomavirus infection.

We studied the presence of human papillomavirus (HPV) DNA by in situ hybridization in 74 colposcopically defined subclinical vulvar lesions obtained from 51 patients (mean age 25 years, range 18-42 years) referred for atypical Papanicolaou smears to the Colposcopy Clinic. Serial sections of formalin-fixed, paraffin-embedded biopsy tissue were stained by routine hematoxylin and eosin stain or were separately hybridized with biotin-labeled probes of HPV types 6, 11, 16, and 18 at high stringency and with mixed HPV probes at low stringency. Histologic evidence of HPV infection (koilocytosis or dysplasia) was found in eight lesions. Overall, 10 lesions were positive by in situ hybridization with HPV DNA. Although certain colposcopic features were more strongly associated with HPV DNA than others were, we were unable to demonstrate any consistent correlation between HPV DNA positivity or specific HPV DNA types and colposcopic categories. There was little correlation between HPV DNA positivity and the histopathologic incidence of HPV infection and dysplasia. Three of the 10 hybridization-positive lesions were severely dysplastic as compared with 0 of 64 nonhybridizing lesions. In spite of this association between HPV DNA and dysplasia, HPV DNA hybridization added no additional clinically relevant information to the histopathologic findings. We emphasize the significance of careful colposcopic examination of the vulva with directed biopsies.

Adult↗
PubMed1991

Pharmacokinetic evaluations of low- and high-dose zidovudine plus high-dose acyclovir in patients with symptomatic human immunodeficiency virus infection.

The pharmacokinetics of zidovudine were evaluated in 41 patients with Centers for Disease Control HIV class IVA infection. The patients were assigned escalating doses of zidovudine (300, 600, or 1,500 mg daily) and were randomized to receive either zidovudine alone or zidovudine with a high dose of acyclovir (4,800 mg per day). Single and multiple intravenous- and oral-dose pharmacokinetic studies were performed on days 1 and 7 and weeks 6 and 12 of therapy. Zidovudine concentrations were analyzed by high-pressure liquid chromatography. Pharmacokinetic parameters were estimated by noncompartmental methods. Zidovudine concentrations in serum declined in a biphasic manner, with half-lives ranging from 1 to 2 h, and were independent of acyclovir administration or length of zidovudine therapy. The median time of peak concentrations in serum following oral doses was 0.75 h (range, 0.25 to 3 h). Accumulation of zidovudine in serum was not observed, but the maximum concentration of drug in serum (Cmax) and the area under the concentration-time curve increased proportionally with increased zidovudine doses. Mean day 7 oral Cmax values were 0.20 +/- 0.12, 0.55 +/- 0.33, and 1.0 +/- 0.5 micrograms/ml for 17 patients receiving total daily doses of, respectively, 300, 600, and 1,500 mg of zidovudine alone, whereas Cmax values were, respectively, 0.27 +/- 0.18, 0.43 +/- 0.33, and 1.2 +/- 0.80 micrograms/ml for 15 comparably treated recipients of zidovudine plus acyclovir (P was not significant). The median bioavailability of oral zidovudine was 67% (42 to 120%) and did not vary with dosage. Absolute and apparent total body clearances were similar among the patients given the various zidovudine doses regardless of whether there was concomitant acyclovir therapy. Drug-related toxicities were observed more frequently in the subjects who received high doses of zidovudine than they were in those who received median and low doses of zidovudine (P=0.03). Overall, acyclovir did not influence the disposition of zidovudine over a wide range of zidovudine doses. No unusual toxicities could be attributed to the zidovudine and high-dose acyclovir combination during the 12-week observation period.

Acyclovir↗
PubMed1991

Chronic fatigue in adolescents.

Nine female and 6 male adolescents (mean age 14.5 +/- 1.7 [SD] years) were evaluated for chronic fatigue associated with at least three additional symptoms present for 18.4 +/- 8.4 months. Eleven subjects experienced the onset of symptoms with an acute illness (seven Monospot-positive). Medical history, physical examination, and laboratory testing yielded little helpful information. Serologic testing for Coxsackie B viruses 1 through 6, cytomegalovirus, Epstein-Barr virus, human herpesvirus 6, and Toxoplasma gondii in subjects and healthy controls provided little evidence for an infectious cause of persistent fatigue. Children's Depression Inventory scores and psychiatric interviews with the Schedule for Affective Disorders and Schizophrenia-Children's Version (K-SADS) identified five subjects with major depression. On the K-SADS, the 10 fatigued subjects without major depression endorsed many secondary symptoms of depression but were less likely than depressed psychiatric clinic patients to endorse primary symptoms such as depressed mood, guilt, and suicidality. At telephone follow-up 13 to 32 months after intake, 4 subjects were completely well, 4 markedly improved, and 7 unimproved or worse. Further research is necessary to determine whether chronic fatigue in adolescents is prodromal depression, a discrete psychosomatic condition, or an infectious or immunologic disorder that mimics depression.

Adolescent↗
PubMed1990

AIDS and HIV infection.

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Acquired Immunodeficiency Syndrome↗
PubMed1990

Chronic fatigue. A prospective clinical and virologic study.

To evaluate the clinical and virologic course of patients with chronic fatigue who had elevated Epstein-Barr virus (EBV) titers, we prospectively followed up 26 patients with serial cultures for EBV in blood and saliva and serial EBV serologic and clinical and psychiatric evaluations, and we compared these results with those for healthy controls. The frequency of isolating EBV in blood or demonstrating EBV infection by in situ hybridization in blood lymphocytes or in saliva was similar in patients and controls. The prevalence and titers of antibody to human herpesvirus type 6 were also similar in the two populations. Patients with chronic fatigue did demonstrate higher in vitro natural killer activity and lower in vitro interleukin 2 production than controls, and patients had a high frequency of DSM-III depressive illness. Over 50% of patients with chronic fatigue improved over the course of follow-up. Improvement was not associated with any discernible change in titers of EBV proteins. No evidence of ongoing EBV infection with either transforming or nontransforming strains was demonstrated in this population of patients with chronic fatigue. Clinically, most patients gradually improve over time.

Adult↗
PubMed1990

Sexually transmitted diseases in victims of rape.

The risk of acquiring a sexually transmitted disease as a result of rape is not known, in part because it is difficult to ascertain whether infections were present before the assault or acquired during it. To investigate this question, we examined female victims of rape within 72 hours of the assault and again at least one week after the assault. Of the 204 girls and women initially examined within 72 hours of the rape, 88 (43 percent) were found to have at least one sexually transmitted disease. These diseases included infections caused by Neisseria gonorrhoeae (6 percent of those tested), cytomegalovirus (8 percent), Chlamydia trachomatis (10 percent), Trichomonas vaginalis (15 percent), herpes simplex virus (2 percent), Treponema pallidum (1 percent), and the human immunodeficiency virus type 1 (HIV-1; 1 percent) and bacterial vaginosis (34 percent). Among the 109 patients (53 percent) who returned for at least one follow-up visit (excluding those who were found to be infected at the first visit or who were treated prophylactically), the incidence of new disease was as follows: gonorrhea, 4 percent (3 of 71); chlamydial infection, 2 percent (1 of 65); trichomoniasis, 12 percent (10 of 81); and bacterial vaginosis, 19 percent (15 of 77). There were no new infections with herpes simplex virus, cytomegalovirus, Trep. pallidum, or HIV-1, but follow-up serologic testing was performed in only 26 percent of the patients. On the basis of our assumptions that most venereal infections present within 72 hours of a rape were preexisting and that new infections identified 1 to 20 weeks later were acquired during the assault, we conclude that the prevalence of preexisting sexually transmitted diseases is high in victims of rape and that they have a lower but substantial additional risk of acquiring such diseases as a result of the assault.

Adolescent↗
PubMed1990

Frequency of asymptomatic shedding of herpes simplex virus in women with genital herpes.

Twenty-seven women with recurrent genital herpes simplex virus infection underwent daily home culturing to detect asymptomatic genital herpes simplex virus shedding. Asymptomatic herpes simplex virus shedding was documented on 1% of the days on which cultures were obtained. Asymptomatic shedding from the vulva was as frequent as asymptomatic cervicovaginal shedding, and 45% of asymptomatic episodes were identified only by positive results from vulvar cultures. All women who obtained samples on more than 100 days and 80% of women who obtained samples on more than 50 days had documented asymptomatic viral shedding, compared with only 6% of those who obtained samples for fewer than 25 days. Asymptomatic shedding was not related to contraceptive use or menstrual cycle. These data suggest that all women with recurrent genital herpes simplex virus infection should be instructed about the possible risk, albeit infrequent, of asymptomatically shedding virus from the genital tract.

Adult↗
PubMed1990

Double-blind randomized clinical trial of self-administered podofilox solution versus vehicle in the treatment of genital warts.

PURPOSE: Genital warts are a highly prevalent and chronic sexually transmitted disease for which there is no completely satisfactory therapy. Conventional ablative therapy requires repeated treatment, often for months or years. This study was undertaken to evaluate the safety and efficacy of 0.5% podofilox in patient-administered treatment of penile warts. PATIENTS AND METHODS: Thirty-eight men with penile warts were randomly assigned to double-blind, self-administration of 0.5% podofilox solution or placebo, twice daily for 3 days per week for 4 weeks. Eleven podofilox and 15 placebo recipients with residual warts then received an additional 4 weeks of open-label treatment. RESULTS: By the end of treatment, podofilox recipients had their mean wart number and area reduced to 15.9% and 5.1% of baseline values, compared to 97.4% and 92.9% in the placebo group (p = 0.0001). Local adverse reactions were more common in the podofilox group, but were transient. Complete disappearance of warts was observed in 25 (53.3%) of 45 treatment courses, including open-label treatment. Recurrences of warts after therapy were frequent. Only 21% of patients remained free of warts 2 weeks after completing treatment, and subsequent recurrences were noted in all patients available for long-term follow-up, which is a common limitation of ablative therapy for genital warts. CONCLUSION: Podofilox 0.5% solution is effective in treating penile warts and is well tolerated in a self-administered regimen. Podofilox 0.5% offers potential advantages in safety and cost over podophyllin resin therapy of genital warts.

Adult↗
PubMed1990

A selective defect in tissue factor mRNA expression in monocytes from AIDS patients.

Expression of tumor necrosis factor (TNF alpha), tissue factor (TF), and interleukin 1-beta (IL-1 beta) mRNA was evaluated in monocytes isolated from patients infected with human immunodeficiency virus (HIV). There was a significant depression (66%) of the induced level of TF mRNA expression in response to lipopolysaccharide. Conversely, the response of TNF alpha and IL-1 beta, following LPS induction, was "normal." TF mRNA reduction was also observed to a lesser degree in AIDS-related complex patients (20%) but not in asymptomatic seropositives. TF is necessary for initiation of the coagulation protease cascade, leading to thrombin production and fibrin deposition, which play a role in inflammatory responses. Its selective reduction may be a factor in the diminished resistance to secondary infections observed in AIDS. Further, since the TF defect increases as patients progress toward AIDS, it may serve as a marker for disease progression.

Acquired Immunodeficiency Syndrome↗