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Biomedical subjects

R L Ashley

Publications and source records attributed to R L Ashley.

At least 55 records · Page 3Linked to original sources
PubMed1993

History of circumcision, medical conditions, and sexual activity and risk of penile cancer.

BACKGROUND: Epidemiological evidence suggests lack of neonatal circumcision as the strongest risk factor for penile cancer, but the role of sexually transmitted diseases in the etiology of penile cancer has remained unclear. PURPOSE: To further clarify risk factors for penile cancer, we examined the role of circumcision, personal characteristics and habits (such as smoking), sexually transmitted diseases, past sexual activity, and medical conditions of the penis. METHODS: A population-based, case-control study was conducted in western Washington state and in the province of British Columbia. We interviewed 110 men with penile cancer diagnosed from January 1979 to July 1990 and 355 control subjects from the general population, frequency matched to case subjects on age and date of diagnosis. Tumor tissue from 67 case subjects was tested for human papillomavirus (HPV) DNA by polymerase chain reaction. Results of blood tests from 69 case subjects and 208 control subjects were available for study. STATISTICALLY SIGNIFICANT RESULTS: Relative to men circumcised at birth, the risk for penile cancer was 3.2 times greater among men who were never circumcised and 3.0 times greater among men who were circumcised after the neonatal period. For current smokers, the risk was 2.8 times that of men who never smoked. The risk among men reporting a history of genital warts was 5.9 times that of men reporting no such history. Of 67 tumors tested for HPV DNA, 49% were positive; the majority of these positive tumors (70%) were type 16, which has been associated with anogenital carcinoma. Relative risks (RRs) associated with a reported history of penile rash or penile tear were 9.4 and 3.9, respectively. Among men not circumcised at birth, RRs associated with presence of smegma and difficulty in retracting the foreskin were 2.1 and 3.5, respectively. Twenty-eight percent of case subjects, compared with only 10% of control subjects, reported 30 or more sexual partners, and men with HPV-positive tumors were more likely to report a greater number of sexual partners. CONCLUSIONS: These results suggest that the absence of neonatal circumcision and potential resulting complications are associated with penile cancer. Additionally, medical conditions of the penis, sexual activity, infection with HPV, and smoking may increase the risk for penile cancer. IMPLICATIONS: A larger study would allow examination of interrelationships of circumcision, infection with HPV, and smoking as risk factors.

Aged↗
PubMed1993

An enzyme immunoassay for the direct detection of adenovirus in clinical specimens.

A total of 414 clinical samples were tested by an enzyme immunoassay (EIA) for direct detection of adenovirus as well as cultured in Graham 293, A549, and human diploid foreskin fibroblast cells. Adenovirus was detected in 69 (16.7%) of 414 clinical specimens. The EIA detected adenovirus in 51 (12.3%) of 414 specimens; two were EIA positive only. Adenovirus was isolated from 67 (16.2%) of 414 specimens; 18 were culture positive only. Compared with viral isolation, EIA had a sensitivity of 73.4% and a specificity of 99.4%, with a positive predictive value of 96% and a negative predictive value of 95%.

Adenovirus Infections, Human↗
PubMed1992

Underdiagnosis of genital herpes by current clinical and viral-isolation procedures.

BACKGROUND: The current clinical strategy for diagnosing genital herpes simplex virus (HSV) infection in women relies on clinical findings plus the selective use of viral culture. The effectiveness of this approach for identifying women with genital herpes is unknown. METHODS: We performed physical examinations, colposcopy, Pap smears, viral cultures, and HSV type-specific serologic assays of 779 randomly selected women attending a sexually transmitted disease clinic. RESULTS: Evidence of HSV type 2 infection was detected in 363 women (47 percent), and 9 others (1 percent) had positive cultures indicative of urogenital or anal infection with HSV type 1. Of these 372 women, only 82 (22 percent) had symptoms. Fourteen women (4 percent) had viral shedding without symptoms, 60 (16 percent) had formerly had symptomatic episodes, and 216 (58 percent) had antibodies to HSV-2 with neither viral shedding nor a history of clinical episodes. Characteristic ulcerations of the external genitalia were present in only two thirds of the 66 women with positive HSV cultures; the others had atypical genital lesions or asymptomatic viral shedding. Isolation of HSV from a genitourinary tract specimen was the most sensitive (77 percent) test for confirming a first episode of infection. The detection of HSV-2-specific antibodies was the most sensitive (97 percent) way to confirm symptomatic reactivations of HSV-2 infection. HSV-2 serologic testing also identified the 290 women with asymptomatic HSV-2 infections (37 percent), including 14 (5 percent) who were shedding virus asymptomatically on the day of the examination. CONCLUSIONS: The current strategy for diagnosing genital HSV infection in women misses many cases. Newly developed type-specific serologic methods can identify women with recurrent genital HSV-2 infection, as well as those with unrecognized or subclinical infection.

Adolescent↗
PubMed1992

Human papillomaviruses, herpes simplex viruses, and the risk of oral cancer in men.

A population-based case-control study was conducted in western Washington state to examine the relations between infection with human papilloma viruses (HPV), herpes simplex viruses (HSV), and risk of oral squamous cell cancer in men. Interviews were completed on 131 oral cancer cases diagnosed between January 1985 and December 1989 and 136 controls frequency matched to cases on age and date of diagnosis who were obtained by random digit dialing. The risk for oral cancer among men with 30 or more sexual partners was 2.4 times that of men with four or fewer partners (95% confidence interval (CI) 1.0-5.9). Men who ever practiced oral sex had lower risk for oral cancer relative to men who never practiced oral sex (relative risk (RR) = 0.4, 95% CI 0.2-0.8). Analyses of exfoliated oral cavity cells for the presence of HPV-6 DNA with polymerase chain reaction revealed that men with an oral HPV-6 infection had 2.9 times the risk for oral cancer of noninfected men (95% CI 1.1-7.3), whereas men with an oral HPV-16 infection had 6.2 times the risk for oral cancer of noninfected men (crude RR = 6.2, 95% CI 0.7-52.2). Relative risks associated with serologically detected HSV-1 and HSV-2 infections were 0.8 (95% CI 0.3-1.7) and 1.8 (95% CI 0.7-4.6), respectively. The authors conclude that HPV-6 is associated with oral cancer. Although men infected with HPV-16 and HSV-2 were at elevated risk, these associations may have been due to chance. The role of specific sexual practices in the transmission of viruses to the oral cavity remains unclear.

Antibodies, Viral↗
PubMed1992

Prevalence of herpesvirus, human T-lymphotropic virus type 1, and treponemal infections in Southeast Asian refugees.

Sera obtained for treponemal serology (VDRL) from 193 Southeast Asian refugees representing five ethnic groups seen in a primary care clinic were examined for antibodies to human T-lymphotropic virus type 1 (HTLV-1), human herpes-virus-6 (HHV-6), Epstein-Barr virus (EBV), and cytomegalovirus (CMV). The seroprevalence was highest for EBV (99%), followed in decreasing order by CMV (95%), HHV-6 (26%), and HTLV-1 (0.6%). The VDRL was positive in 15% of patients. The highest seroprevalence to HHV-6 was noted in the Chinese (33%) and the lowest in the Laotian hilltribes, the Mien and Hmong (14%). Antibody to HHV-6 was most prevalent among patients under 20 and those between 60 and 69 years of age. Differences were not found among ethnic groups in the seroprevalence of HTLV-1, EBV, or CMV.

Adult↗
PubMed1992

Herpes simplex virus-2 (HSV-2) type-specific antibody correlates of protection in infants exposed to HSV-2 at birth.

Western blot analysis was used to compare the herpes simplex virus (HSV)-2 antibody profiles of 40 infants less than 2 wk of age who had been exposed to maternal genital HSV-2 at birth. 4 mothers were HSV seronegative at delivery and seroconverted to HSV-2 ("primary infection"), 9 had HSV-1 antibodies and seroconverted to HSV-2 ("nonprimary first episode infection"), and 27 were HSV-2 seropositive ("recurrent infection"). Neonatal herpes infections developed in 1 of 4 infants of women with primary infection, in 3 of 9 infants of women with nonprimary first episode infection, and in none of the 27 infants of women with recurrent HSV-2. Antibodies to HSV-2 proteins gG-2, VP5, and ICP35 were detected in 83, 89, and 72% of the 36 uninfected infants, respectively. None of the four infected infants had detectable antibodies to gG-2 and only one (25%) had antibodies to VP5 or ICP35. The more limited profiles of the 13 infants born to mothers with first episodes of HSV-2 were then analyzed separately; these profiles were similar among infected and uninfected infants except for gG-2, which elicits antibodies that are type specific for HSV-2. None of the infected infants versus seven of nine (78%) uninfected infants were gG-2 seropositive. These comparisons suggest that maternal type-specific antibodies may play a role in preventing neonatal infection after exposure to HSV-2.

Antibodies, Viral↗
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

Serological responses to cytomegalovirus during renal transplant rejection.

We studied the role played by CMV in kidney transplant rejection by recording serological responses to CMV replication in cadaver graft recipients and recording clinical graft rejection by monitoring acute changes in renal function and the appearance of antidonor lymphocyte antibody (anti-Dab). If CMV plays a significant role in rejection, clinical rejection should correlate with CMV activity; if CMV does not play a role, clinical rejection would be likely to correlate with anti-Dab but not necessarily with CMV activity. We selected retrospectively 18 rejectors and 18 nonrejectors by clinical criteria and assayed for anti-Dab (by fluorescence-activated flow cytometry) and CMV antibody (by complement fixation and Western blot for IgG and IgM) over a 3-6-month period after transplantation. Primary CMV infection occurred in 8 of 12 (67%) CMV seronegative graft recipients and reactivation or reinfection occurred in 16 of 24 (67%); 12 of 14 (86%) rejectors developed anti-Dab compared with 2 of 18 (11%) nonrejectors (P less than 0.00001). Active CMV infection occurred in 11 of 18 (61.1%) rejectors and 13 of 18 (72.2%) nonrejectors (P = 0.36), and in 8 of 15 (53.3%) of those who developed anti-Dab and 12 of 17 (70.6%) of those who did not (P = 0.26). The results show no evidence to link CMV activity with kidney graft rejection.

Adolescent↗
PubMed1990

A chronic "postinfectious" fatigue syndrome associated with benign lymphoproliferation, B-cell proliferation, and active replication of human herpesvirus-6.

A 17-year-old, previously healthy woman developed an acute "mononucleosis-like" illness with an associated "atypical" pneumonitis, followed by years of debilitating chronic fatigue, fevers, a 10-kg weight loss, night sweats, and neurocognitive symptoms. Thereafter, her sister developed a similar but less severe illness. The patient developed marked, chronic lymphadenopathy and splenomegaly, with associated persistent relative lymphocytosis and atypical lymphocytosis and with thrombocytopenia. After 3 years of illness, a splenectomy was performed, which resulted in some symptomatic improvement, prompt weight gain, and resolution of all hematologic abnormalities. Serial immunologic studies revealed a strikingly elevated number of activated B lymphocytes and a T lymphopenia, which improved but did not return to normal postsplenectomy. No causal association was found with any of several infectious agents that could produce such a lymphoproliferative illness. However, both the patient and her sister had evidence of active infection with the recently discovered human herpesvirus-6. Seven years after the onset of the illness, the patient and her sister remain chronically ill.

Adolescent↗
PubMed1990

Secondary T-cell lymphoproliferation after marrow transplantation.

Secondary lymphoproliferative syndromes in immunosuppressed patients have been characterized as polyclonal or monoclonal B-lineage disorders nearly always associated with Epstein-Barr virus (EBV) infection. The authors now report three patients with a distinctly different lymphoproliferative syndrome. Two patients with common acute lymphoblastic leukemia antigen (CALLA) (CD10)-positive acute lymphoblastic leukemia and one patient with acute myelogenous leukemia, respectively, received high-dose chemoradiotherapy followed by marrow transplantation from either an HLA-identical sibling or HLA-mismatched parent. All three patients developed severe graft-versus-host disease (GVHD), requiring immunosuppressive treatment with corticosteroids. A secondary malignant T-cell lymphoproliferation occurred 2, 21, and 43 months, respectively, after marrow transplantation. In all three cases the lymphoid cells expressed T-cell surface antigens and were morphologically and immunophenotypically distinct from the malignant cells present before transplantation. One tumor was of host cell origin, one was probably of donor origin, and the tumor origin in the third case could not be determined. The authors were unable to find any evidence for EBV, human T-cell lymphotropic virus type I or II, human immunodeficiency virus, or human herpesvirus 6.

Adolescent↗
PubMed1990

Detection of asymptomatic initial herpes simplex virus (HSV) infections in animals immunized with subunit HSV glycoprotein vaccines.

The evaluation of herpes simplex virus (HSV) vaccine efficacy will require methods to detect asymptomatic acquisition of HSV infection and to assess the risk of recurrences in these patients. HSV-infected vaccinees should develop antibodies to HSV polypeptides not included in subunit vaccines. Sera from 57 HSV glycoprotein-vaccinated guinea pigs that had asymptomatic initial infections after genital HSV type 2 challenge were collected after vaccination but before HSV challenge and again 30 days after HSV challenge to determine the antibody response to HSV polypeptides. Antibodies to nonvaccine HSV polypeptides were detected in sera collected after viral challenge from 32 (56%) of these 57 animals. Twenty-six (81%) of the 32 animals with detectable antibody developed recurrent disease; however, recurrences also developed in 11 (44%) of the remaining 25 that did not show detectable antibody to nonvaccine HSV polypeptides. The magnitude of vaginal viral shedding during the initial disease period following challenge was significantly lower in animals that did not develop antibody to nonvaccine polypeptides compared with those that did develop antibody (area under the viral shedding curve, 5.2 +/- 3.2 versus 18.1 +/- 5.8; P less than 0.0001) . These data suggest that detection of antibody to nonvaccine HSV polypeptides will identify the majority (70%) of initially asymptomatic vaccinees that develop recurrent disease but that latency can be established even with markedly reduced levels of viral replication that did not induce a detectable antibody response.

Animals↗
PubMed1989

Transmission of genital herpes by donor insemination.

This report describes a donor in a therapeutic donor insemination program who asymptomatically acquired a primary herpes simplex virus type 2 (HSV-2) infection from his long-standing sexual partner. His fresh semen was used to inseminate two HSV-seronegative recipients; in one a primary HSV-2 infection developed, and in one it did not. Direct evidence of transmission from donor to recipient was documented by restriction enzyme analysis of the HSV-2 isolates obtained from the donor's semen and from the recipient's cervix. Because of the possibility of asymptomatic acquisition and transmission of HSV-2, semen donors and their sexual partners should undergo serologic screening for genital herpes using new, type-specific HSV serologic techniques.

Adult↗
PubMed1989

Genital herpes infections.

Genital herpes infections can be diagnosed by clinical criteria, but in most cases laboratory methods are superior. This article reviews the current methods available for detection of herpes simplex virus and for documenting infection by serology. The applicability and limitations of these methods are discussed.

Antibodies, Viral↗
PubMed1988

The association between genital ulcer disease and acquisition of HIV infection in homosexual men.

We analyzed the association of herpes simplex virus (HSV) infection and syphilis, the two most common causes of genital ulceration in homosexual men, with human immunodeficiency virus (HIV) infection in 200 men enrolled between 1983 and 1986 into a study evaluating the microbial causes of acute proctitis. Infection with HIV was independently associated with a history of syphilis, serologic evidence of syphilis, a history of HSV infection, and antibody to HSV-2. Antibody to HIV was not associated with a history of other genital infections or with antibody to Chlamydia trachomatis or HSV-1. Similar associations were observed in 111 asymptomatic homosexuals seen for HIV screening. Men who presented with primary HSV proctitis had a lower prevalence of HIV antibody than those with preexisting HSV-2 antibody (44% vs 68%); this suggests that HSV-2 infection antedated HIV infection. These data suggest that genital ulcerative diseases are an important risk factor for the acquisition of HIV infection in homosexual men; measures directed at control of these diseases may reduce the transmission of HIV in this population.

Adult↗
PubMed1988

Genital ulceration as a risk factor for human immunodeficiency virus infection.

Among 115 heterosexual men who presented with genital ulcers to a sexually transmitted disease clinic in Nairobi, Kenya, the prevalence of serum antibody to HIV was 16.5%. A past history of genital ulcers was reported by 12 (63%) of 19 men with antibody to HIV versus 30 (31%) of 96 without antibody (P = 0.008). HIV infection was also positively associated with lack of circumcision, but was not associated with the etiology of the current genital ulcer. Logistic regression analysis (adjusted for age, number of recent sex partners, recent prostitute contact, circumcision, tribal ethnic identity, past history of urethritis, and current diagnoses) confirmed only the association between prior history of genital ulcer disease and HIV infection; (P = 0.04, odds ratio 2.35, 95% confidence limits, 1.01-5.47). The incidence of genital ulcers, particularly chancroid, is much higher in parts of Africa than in Europe or North America. This may contribute to the increased risk of heterosexual transmission of HIV in Africa. Aggressive control of chancroid and syphilis may offer one very feasible approach to reducing transmission of HIV in this region.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Comparison of Western blot (immunoblot) and glycoprotein G-specific immunodot enzyme assay for detecting antibodies to herpes simplex virus types 1 and 2 in human sera.

Sera from patients with culture-proven genital herpes infections were tested for herpes simplex virus type 1 (HSV-1)- and HSV-2-specific antibodies by both a Western blot (immunoblot) technique (WBA) and immunodot enzyme assays (IEAs) specific for HSV-1 or HSV-2 glycoprotein G (gG). Of 137 serum samples tested, none was mistyped by either WBA or IEA. Both tests were most sensitive with sera obtained at least 21 days after onset of primary HSV-2 infections or sera drawn during recurrent HSV-2 genital episodes: 75 of 76 (99%) such serum samples were positive for HSV-2 antibody by WBA and 73 of 76 (96%) were positive by IEA. Of sera drawn earlier than 21 days from onset of primary genital HSV-2, antibodies to HSV-2 were detected in 25% by WBA and 8% by IEA. In patients with culture-proven primary genital HSV-1 infection, WBA detected antibodies to HSV-1 proteins in 16 of 17 (94%) serum samples drawn at least 21 days after onset of primary genital HSV-1 infection, compared with 9 of 17 (53%) serum samples tested for gG-1 by IEA. Both WBA and IEA are accurate and sensitive tests for HSV-2 antibody in patients convalescing from a first episode or having symptomatic or asymptomatic recurrent genital herpes. WBA was more sensitive than IEA in detecting seroconversion following primary HSV-1 genital herpes, although both assays may miss persons undergoing early seroconversion to HSV-2.

Antibodies, Viral↗