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Biomedical subjects

R Ashley

Publications and source records attributed to R Ashley.

At least 37 records · Page 2Linked to original sources
PubMed1999

Human herpesvirus 6 infections after bone marrow transplantation: clinical and virologic manifestations.

Human herpesvirus 6 (HHV-6) DNA levels in peripheral blood mononuclear cells were prospectively evaluated in 20 cytomegalovirus-seronegative allogeneic marrow transplant patients and in 10 healthy control subjects. Blood and saliva specimens obtained weekly for 3 months after transplant were evaluated by quantitative HHV-6 polymerase chain reaction. One of 20 patients experienced primary HHV-6 infection after marrow transplant (seroconversion, HHV-6 viremia, skin rash); 18 of 20 had increased peripheral blood mononuclear cell HHV-6 DNA levels consistent with asymptomatic reactivations, and 1 patient experienced a reactivation-associated skin rash. Genotyping revealed HHV-6 variant B DNA in all cases. Therapy with acyclovir or intravenous immunoglobulin was not correlated with lower HHV-6 DNA levels. Thus, asymptomatic HHV-6 reactivations appear to be common following allogeneic marrow transplantation. Among HHV-6-seronegative and viral DNA-negative patients, primary HHV-6 infection can ensue in association with self-limited clinical symptoms, including diffuse maculopapular rash.

Adult↗
PubMed1999

Clinical course of patients with serologic evidence of recurrent genital herpes presenting with signs and symptoms of first episode disease.

BACKGROUND AND OBJECTIVES: The care of patients with first episode and recurrent genital herpes differs with respect to therapy and source partner evaluation. Of 498 persons who presented with what appeared by history and symptoms to be a first episode of genital herpes, we identified 41 who had serologic evidence of remotely acquired herpes simplex virus 2 (HSV-2) infection. GOALS: To define the natural history of these individuals with previously unrecognized HSV-2 and to evaluate if any clinical or historical features could differentiate these people from persons with true first episode infection. STUDY DESIGN: Observational cohort study. RESULTS: Clinical overlap existed in the frequency of local symptoms, fever, and size of genital lesions between those with remotely acquired versus recently acquired genital herpes. The frequency of new sexual partners and recent sexual history were also similar in the two groups. However, on follow-up, the lesions of persons with remotely acquired HSV-2 healed more rapidly and subsequently recurred less frequently than those of true primary HSV-2. CONCLUSIONS: Even in a referral clinic with experienced clinicians, almost 10% of persons who are judged to have first episode genital herpes have evidence of remotely acquired HSV-2, suggesting that clinical differentiation of first episode genital herpes from previously acquired infection is difficult. Type-specific serologic testing assists the clinician in correctly classifying the infection and determining the potential source partner.

Adolescent↗
PubMed1999

Limits in reliability of glycoprotein G-based type-specific serologic assays for herpes simplex virus types 1 and 2.

Type-specific serologic assays for herpes simplex virus (HSV) types 1 and 2 based on glycoprotein G-1 (gG-1) (HSV-1) and gG-2 (HSV-2) discriminate between antibodies against HSV-1 and HSV-2. We previously developed a Western blot assay using gG-1 and gG-2 expressed in baculovirus, performed extensive validation studies, and determined that it was both sensitive and specific for type-specific detection of HSV antibody. Here we report that, among a cohort of Thai military recruits, the serostatus of some individuals changed from positive to negative over time (6.6% among those ever positive for HSV-1, and 14.9% among those ever positive for HSV-2). We tested a subset of these specimens in three other gG-based assays: an enzyme-linked immunosorbent assay, an immunoblot strip assay, and a Western blot assay. Positive-to-negative shifts occurred in every assay; the frequency of the shifts ranged from 6. 1% to 21.2% of the specimen sets tested. There was only limited agreement among the assays concerning which individuals lost reactivity. This inaccuracy, exhibited by all of the assay protocols, was not predicted by validation studies employing specimens from cross-sectional studies and was most pronounced in HSV-2 testing. This argues for the inclusion of serial blood specimens in serologic assay validation procedures.

Adult↗
PubMed1998

Association between cytomegalovirus seroconversion and upper genital tract infection among women attending a sexually transmitted disease clinic: a prospective study.

To study relationships between acquisition of cytomegalovirus (CMV), sexual activity, and sexually transmitted diseases, 245 CMV-seronegative women were followed (median, 23 months) in a sexually transmitted disease clinic between 1980 and 1988. Thirty-six (15%) seroconverted (10%-12%/year). At entry, seroconverters were younger (P = .03), were younger at sexual debut (P = .004), and had more sex partners (P = .004) than non-seroconverters. During follow-up, seroconverters had more sex partners, had more new sex partners (P = .05 for each), and were more likely to have gonorrhea, chlamydia, or pelvic inflammatory disease. At seroconversion, Chlamydia trachomatis was isolated from cervix in 14%, versus 3% of non-seroconverters (odds ratio [OR], 4.5; 95% confidence interval [CI], 1.3-14.9). Signs of upper genital tract infection were present in 8% of seroconverters versus 2% of non-seroconverters (OR, 4.7; 95% CI, 1.0-21.8). Acquisition of CMV in these women was associated with sexual activity, sexually transmitted diseases, and signs of upper genital tract infection.

Adolescent↗
PubMed1998

Sexually transmitted infections in female sex workers: reduced by condom use but not by a limited periodic examination program.

BACKGROUND AND OBJECTIVES: The sexually transmitted diseases (STD) control program for female sex workers (FSW) in Lima, Peru, provided periodic serological tests for syphilis and cervical smears for gonococci, but not medication for STD or condoms. GOAL OF THIS STUDY: To assess program effectiveness. STUDY DESIGN: We assessed prevalence of current STD and serum antibody to STD pathogens in FSW in relation to program participation and to condom use. RESULTS: Program participation was not associated with significantly reduced rates of current gonococcal or chlamydial infections or Venereal Disease Research Laboratory (VDRL) titers > or =4 with reactive fluorescent treponemal antibody absorption (FTA-ABS). However, regardless of control program participation, consistent condom use was associated with reduced prevalence of gonorrhea, and with significantly reduced seroreactivity for FTA-ABS, C. trachomatis, anti-hepatitis B core (HBc), and anti-human T-lymphotropic virus type I. Anti-HBc was associated with years of receiving penicillin injections for syphilis prophylaxis. CONCLUSION: The scope, quality, and efficacy of STD control programs must be technically appropriate, well managed, and adequately financed. The safety of marginal programs warrants scrutiny.

Adult↗
PubMed1998

Safety and efficacy of sub-antimicrobial-dose doxycycline therapy in patients with adult periodontitis.

The objectives of the studies presented here were to assess the safety and efficacy of the adjunctive administration of sub-antimicrobial-dose doxycycline (SDD) for the treatment of adult periodontitis and to confirm the optimal dosing regimen. The studies summarized included four double-blind, placebo-controlled, randomized clinical trials, conducted over a period of 9 to 12 months. Analysis of efficacy data demonstrated that adjunctive SDD treatment resulted in: (1) increases in clinical attachment levels; (2) decreases in probing pocket depths; and (3) reductions in bleeding on probing in patients with adult periodontitis. There were no significant adverse events or unwanted long-term antimicrobial effects associated with orally administered SDD. The results of these clinical trials indicate that the adjunctive use of SDD 20 mg BID is an effective and well-tolerated regimen which can significantly improve several indices of periodontal health.

Adult↗
PubMed1996

Asymptomatic maternal shedding of herpes simplex virus at the onset of labor: relationship to preterm labor.

OBJECTIVE: To determine if fetal growth restriction and prematurity are observed with subclinical shedding of herpes simplex virus (HSV) at the onset of labor. METHODS: Within 48 hours of delivery, cultures were taken from the cervix and external genitalia of 15,923 asymptomatic pregnant women without symptoms or signs of genital HSV infection; results were positive for HSV in 57. Each of these 57 women were compared with a control group composed of the three culture-negative women delivering immediately before and the three delivering immediately after each woman shedding HSV. RESULTS: The median birth weight for infants born to the 57 women with asymptomatic shedding was 3050 g, compared with 3360 g among the 342 women without asymptomatic shedding, a statistically significant difference (P < .002). These differences were due to very low birth weight (LBW) among the five infants of women with subclinical viral shedding secondary to recently acquired primary genital herpes; these five infants had a median gestational age of 33 weeks, compared with 37 weeks for the 14 infants of mothers with nonprimary, first-episode disease and 39 weeks for the 33 infants of women with reactivation disease, also a significant difference (P = .018). CONCLUSIONS: Asymptomatic genital shedding of HSV at the onset of labor because of subclinical primary genital HSV infection is associated with preterm delivery. Women who acquire genital HSV-2 before pregnancy and are shedding subclinically at the onset of labor experience no increase in adverse outcome. Thus, prevention of the prematurity and LBW associated with genital herpes means that acquisition of the infection in late pregnancy must be prevented.

Birth Weight↗
PubMed1996

Postinfectious chronic fatigue: a distinct syndrome?

Chronic fatigue syndrome (CFS) is often preceded by a viral illness and has recurrent "flu-like" symptoms. We compared demographic, clinical, and laboratory features (markers of inflammation and viral infection) among 717 patients with chronic fatigue (CF) with and without a self-reported postinfectious onset to identify associated clinical and biologic findings and to examine the subset of patients with CFS. Only subjective fever, chills, sore throat, lymphadenopathy, poorer functional status, and attribution of illness to a physical condition were significantly associated with a postinfectious onset. The features of patients with CFS were virtually identical to those of the broader category of patients with CF. We conclude that a postinfectious onset was not associated with a pattern of abnormalities across multiple psychosocial and biologic parameters.

Fatigue Syndrome, Chronic↗
PubMed1996

Relationship between antibodies to herpes simplex virus (HSV) and symptoms of HSV infection.

To determine the relationship between antibodies to herpes simplex virus (HSV) types 1 and 2 and diagnosis of orolabial and genital herpes, a cross-sectional survey was done among 869 sexually transmitted disease clinic attendees and 1594 blood donors in London. Among clinic attenders, the prevalence of HSV-1 infection was 59.5% and that of HSV-2 infection was 22.7%, and among blood donors the prevalence was 44.6% and 7.6%, respectively. The sensitivity and specificity of a diagnosis of oral herpes for the presence of HSV-1 antibody was almost identical in the 2 groups (clinic attendees: sensitivity, 33.1%, and specificity, 91.4%; blood donors: sensitivity, 32.3%, and specificity, 94.3%). A diagnosis of genital herpes was less sensitive for antibody for HSV-2 among donors than among clinic attenders (P < .001); however, the specificity was similar in the 2 populations (clinic attendees: sensitivity, 32.1%, and specificity, 96.6%; blood donors: sensitivity, 17.5%, and specificity, 99.5%). False-positive clinical histories were also relatively common (clinic attenders, 12%; donors, 6%). The sensitivity of the diagnosis of genital herpes would be improved if accurate serologic assays for detection of HSV type-specific antibodies were more widely available.

Antibodies, Viral↗
PubMed1996

The relationship of human papillomavirus-related cervical tumors to cigarette smoking, oral contraceptive use, and prior herpes simplex virus type 2 infection.

It has now been established that infection with human papillomavirus (HPV) is necessary for the development of most cervical cancers. HPV is not sufficient for the development of cancer. Other exposures or host factors are necessary for cancer to occur. As part of an ongoing, population-based case-control study of invasive cervical cancer, we investigated the role of cigarette smoking, oral contraceptive (OC) use, and herpes simplex virus type 2 (HSV-2) as potential cofactors with HPV in the development of cervical cancer. Residents of three counties in western Washington State who were diagnosed with invasive squamous cell cervical cancer (n = 314) from January 1986 through December 1992 were interviewed about their sexual, reproductive, contraceptive, and cigarette smoking histories. Similar information was obtained from control women identified through random digit dialing (n = 672). The sera from 206 cases and 522 controls were tested for both HPV 16 capsid antibodies and HSV-2 antibodies. PCR was used to test paraffin-embedded tumor tissues for the presence of HPV DNA types 6, 16, 18, 31, 33, 35, and 39. Women with cervical cancer were more likely to be current smokers at diagnosis than population controls [relative risk (RR), 2.5; 95% confidence interval (CI), 1.8-3.4]. The risk associated with smoking was present to a similar extent among women positive and negative for HPV as measured by HPV 16 capsid antibodies and HPV DNA in the tumor tissue (cases). OC use was only important if first use was at an early age, particularly ages < or = 17 years (RR, 2.3; 95% CI, 1.4-3.8). There was only a slight risk for cervical cancer associated with antibodies to HSV-2 (RR, 1.2; 95% CI, 0.9-1.7). However, when we stratified by markers of HPV exposure, we found a significant increase in risk associated with HSV-2 among women negative for HPV 16 antibodies (RR, 2.0; 95% CI, 1.3-3.0), which was strengthened when we confined our analysis to cases whose tumors were HPV DNA negative (RR, 3.6; 95% CI, 1.6-8.0). There was no indication that cigarette smoking, OC use, or HSV-2 infection influence the ability of HPV infection to cause invasive cervical cancer. OC use may only be important in the etiology of invasive squamous cell cervical tumors if the use occurs at a critical time in the development of a woman's reproductive tract, at ages < or = 17 years. The majority of risk associated with HSV-2 was confined to HPV-negative tumors, indicating a possible separate pathway to disease that may account for 5-10% of invasive cervical cancers.

Adolescent↗
PubMed1995

Seroprevalence of herpes simplex virus infections in a family medicine clinic.

OBJECTIVES: To determine the prevalence of herpes simplex virus (HSV) antibody in a general medical practice setting and to assess the frequency of subclinical infection. DESIGN: Prevalence study. SETTING: A family practice clinic at the University of Washington Medical Center, Seattle. PARTICIPANTS: Five hundred randomly selected patients between the ages of 18 and 45 years. MAIN OUTCOME MEASURES: Serum samples were tested by Western blot assay to detect the presence of antibody to HSV type 1 (HSV-1) and HSV-2. Demographic information and clinical history of oral and genital herpes were obtained. RESULTS: One hundred fourteen patients (23%) were seropositive for HSV-2 antibody, 277 patients (56%) were seropositive for HSV-1 antibody, 59 patients (12%) were seropositive for both HSV-2 and HSV-1 antibodies, and 163 patients (33%) were seronegative for both. Women were almost twice as likely as men to be seropositive for HSV-2 antibody (28% vs 15%, P < .001). Blacks had the highest rates of HSV-2 antibody seropositivity (60%) compared with whites (20%) and Asians (6%) (P < .001). Other demographic correlates of seropositivity included being older, having fewer years of education, and having public insurance. The specificity of a clinical history of genital herpes or sores for HSV-2 infection was high (99%), but the sensitivity was low (27%). CONCLUSIONS: Herpes simplex virus infection is common among patients seeking primary care. Women, blacks, and patients of lower socioeconomic status are most likely to be seropositive for HSV-2 antibody. The high frequency of unrecognized HSV infection has implications for primary care physicians in counseling patients regarding HSV infection and transmission.

Adult↗
PubMed1995

Cervical but not urinary excretion of cytomegalovirus is related to sexual activity and contraceptive practices in sexually active women.

The relationship between sexual activity and genitourinary excretion of cytomegalovirus (CMV) was evaluated in 1481 women at a sexually transmitted disease (STD) clinic. Among 951 who were CMV-seropositive, 16.6% had CMV isolated, from cervix alone in 9.4%, urine alone in 3.8%, and both sites in 4.2%. Isolation rates were highest in young women (P < .001). Compared with those with only cervical infection, women shedding from both cervix and urine were younger, began sexual activity when younger, had more recent partners, and a higher frequency of CMV-specific IgM, suggesting recent CMV infection. By logistic regression, cervical CMV excretion was associated with concomitant gonococcal infection (P = .008) and was less frequent in those using barrier contraception (P = .036). Isolated urinary excretion of CMV was not associated with sexual activity, concomitant cervical infections, or use of contraception. Cervical CMV infection is related to sexual activity, acquisition of other STDs, or exogenous reinfection, and urinary CMV is not.

Adolescent↗
PubMed1995

Recurrent brainstem encephalitis associated with herpes simplex virus type 1 DNA in cerebrospinal fluid.

A 47-year-old man had recurrent signs and symptoms of brainstem encephalitis over a 4-year period. Although CSF viral cultures were repeatedly negative, herpes simplex virus type 1 (HSV-1) DNA was detected in CSF by polymerase chain reaction (PCR). HSV-1-specific antibodies were absent at the time of the first positive PCR test, but CSF seroconversion to high HSV-1-specific antibody titer subsequently occurred. CSF antibody to cytomegalovirus (CMV) and varicella-zoster virus (VZV) was not detectable, nor could CMV, VZV, or Epstein-Barr virus nucleic acid be detected by CSF by PCR. This is the first report of the use of CSF PCR for the rapid antemortem diagnosis of herpetic brainstem encephalitis.

Brain Stem↗
PubMed1994

Recurrence rates in genital herpes after symptomatic first-episode infection.

OBJECTIVE: To evaluate the frequency of reactivation of genital herpes infection and to identify predictors for recurrence. DESIGN: Prospective, observational cohort study. SETTING: Research clinic. PATIENTS: 457 consecutive patients who did not have acute-phase serum antibodies to herpes simplex virus type 2 (HSV-2) but who did have herpes simplex virus (HSV) isolated from genital lesions. RESULTS: Eighty-nine percent of patients with HSV-2 had at least one recurrence during follow-up (median, 391 days); the median monthly recurrence rate was 0.34. Thirty-eight percent had at least 6 recurrences during the first year and 20% had more than 10 recurrences. The median monthly recurrence rate was 0.43 for men and 0.33 for women (difference, 0.10 [95% CI, 0.03 to 0.19]; P < 0.01). Twenty-six percent of women and 8% of men had no or 1 recurrence in year 1 of follow-up, whereas 14% of women and 26% of men had more than 10 recurrences. Patients who had severe primary HSV-2 infection (duration, > or = 35 days) had recurrences nearly twice as often (0.66 compared with 0.36 recurrences per month [95% CI, 0.18 to 0.57]) and had a shorter time to first recurrence when compared with those who had shorter first episodes. CONCLUSIONS: Almost all persons with initially symptomatic HSV-2 infection have symptomatic recurrences. More than 35% of such patients have frequent recurrences. Recurrence rates are especially high in persons with an extended first episode of infection, regardless of whether they receive antiviral chemotherapy with acyclovir. Men with genital HSV-2 infection have about 20% more recurrences than do women, a factor that may contribute to the higher rate of HSV-2 transmission from men to women than from women to men and to the continuing epidemic of genital herpes in the United States.

Acyclovir↗
PubMed1994

Antibody to herpes simplex virus type 2 as serological marker of sexual lifestyle in populations.

OBJECTIVES: To examine the epidemiology of antibody to herpes simplex virus type 2 and to assess its suitability as a serological marker of sexual behaviour in populations with high and low prevalences. DESIGN: Cross sectional survey. SETTING: Department of genitourinary medicine and blood donation centre in central London. SUBJECTS: Representative sample of 869 patients attending department between November 1990 and December 1991, and 1494 consecutive blood donors attending for donation between February and April 1992. METHOD: Participants had a blood sample taken for antibody testing with a novel type specific assay and completed a questionnaire. RESULTS: Prevalence of antibody differed significantly between the two groups (188/833 (22.7%) clinic attenders; 102/1347 (7.6%) blood donors). In both populations antibody was strongly associated with sex, sexual orientation, years of sexual activity, number of lifetime sexual partners, and past infection with sexually transmitted diseases after other factors were controlled for. Only 130 (45%) of all those with antibody had symptoms suggestive of genital herpes, and 79 (27.4%) had had genital herpes diagnosed. Of those without antibody to herpes simplex viruses type 1 and 2, 8.0% reported genital blisters or sores and 1.1% had had genital herpes diagnosed by a doctor. CONCLUSIONS: The strong relation between herpes simplex virus type 2 and sexual lifestyle suggests that the presence of antibody to the virus may be suitable for use as an objective, serological marker of patterns of sexual behaviour in different populations. These data show that only a minority of those infected with herpes simplex virus type 2 have a diagnosis of genital herpes or express clinical symptoms, making serological determinants of infection essential for epidemiological studies.

Adolescent↗
PubMed1994

Frequent detection of genital herpes simplex virus DNA by polymerase chain reaction among pregnant women.

OBJECTIVE: To investigate the prevalence and level of genital herpes simplex virus (HSV) among women at delivery. DESIGN, PATIENTS, AND SETTING: A prospective analysis of HSV by culture and by polymerase chain reaction (PCR) of genital specimens and by HSV serologic studies in 100 asymptomatic women in labor; prospective analysis of HSV by PCR among 50 seronegative nonpregnant women at a student health center; and retrospective analysis of genital specimens for HSV by PCR from 17 HSV culture-positive women with uninfected neonates and from two HSV culture-negative women with HSV-infected neonates. All pregnant women were at a university hospital. MAIN OUTCOME MEASURES: Presence of HSV by culture and levels of HSV by quantitative, type-specific PCR in cervical and vulvar specimens; HSV serologic testing by Western blot. RESULTS: All of the 100 asymptomatic women in labor who were studied prospectively were HSV culture negative. In nine HSV was recovered by PCR. Herpes simplex virus was recovered by PCR in one of the 50 seronegative nonpregnant women; she soon became seropositive. All 17 culture-positive women had HSV recovered by PCR. High levels of HSV DNA were obtained by PCR from the two culture-negative women with infected neonates. Among those from whom HSV was recovered by PCR, HSV DNA levels were 250 times higher from culture-positive samples than from culture-negative samples (11,571 genome equivalents vs 46 genome equivalents; P < .001). CONCLUSIONS: The frequency of infant exposure to HSV DNA-containing secretions from HSV-seropositive mothers is about eight times higher than previously reported using HSV culture methods. High maternal levels of HSV DNA may be associated with an increased frequency of transmission of HSV to the infant.

Base Sequence↗
PubMed1994

Herpes simplex virus infection as a cause of benign recurrent lymphocytic meningitis.

OBJECTIVE: To identify the role of herpes simplex virus (HSV) in causing benign recurrent lymphocytic meningitis. DESIGN: Prospective cohort study. SETTING: Tertiary referral center. PATIENTS: 20 consecutive patients with a provisional diagnosis of benign recurrent lymphocytic meningitis had cerebrospinal fluid specimens submitted between 1990 and 1993 to the diagnostic virology laboratory. Thirteen patients met our criteria for benign recurrent lymphocytic meningitis. MEASUREMENTS: Herpes simplex virus DNA was detected in cerebrospinal fluid specimens using the polymerase chain reaction, followed by hybridization with a HSV-specific DNA probe. Herpes simplex virus type 1 and type 2 DNA products were distinguished by digestion with restriction enzymes and analysis by gel electrophoresis. Anti-HSV antibodies in cerebrospinal fluid were detected by immunoblot. RESULTS: The patients had 3 to 9 attacks (mean, 4.6 attacks) of benign recurrent lymphocytic meningitis during periods ranging from 2 to 21 years (mean, 8.4 years). Three of 13 patients had known recurrent genital herpes. Cerebrospinal fluid analysis showed 48 to 1600 cells/microL, glucose levels of more than 2.22 mmol/L (40 mg/dL), and protein levels of 41 to 240 mg/dL (0.41 to 2.4 g/L). Herpes simplex virus DNA and anti-HSV antibodies were detected in cerebrospinal fluid samples in 11 of 13 patients (84.6%; 95% CI, 55% to 98%). Ten of these 11 patients had HSV type 2 DNA and HSV type 2 antibodies. One patient had HSV type 1 DNA and HSV type 1 antibodies in the cerebrospinal fluid. The remaining two patients had only anti-HSV type 2 antibodies. CONCLUSIONS: Herpes simplex virus, predominantly HSV type 2, was the major agent causing benign recurrent lymphocytic meningitis that met our specified diagnostic criteria.

Adult↗