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Biomedical subjects

K K Holmes

Publications and source records attributed to K K Holmes.

At least 19 recordsLinked to original sources

A cohort study of the risk of cervical intraepithelial neoplasia grade 2 or 3 in relation to papillomavirus infection.

BACKGROUND: Human papillomavirus (HPV) has been associated with cervical intraepithelial neoplasia, but the temporal relation between the infection and the neoplasia remains unclear, as does the relative importance of the specific type of HPV, other sexually transmitted diseases, and other risk factors. METHODS: We studied prospectively a cohort of 241 women who presented for evaluation of sexually transmitted disease and had negative cervical cytologic tests. The women were followed every four months with cytologic and colposcopic examinations of the uterine cervix and tests for HPV DNA and other sexually transmitted diseases. RESULTS: Cervical intraepithelial neoplasia grade 2 or 3 was confirmed by biopsy in 28 women. On the basis of survival analysis, the cumulative incidence of cervical intraepithelial neoplasia at two years was 28 percent among women with a positive test for HPV and 3 percent among those without detectable HPV DNA: The risk was highest among those with HPV type 16 or 18 infection (adjusted relative risk as compared with that in women without HPV infection, 11; 95 percent confidence interval, 4.6 to 26; attributable risk, 52 percent). All 24 cases of cervical intraepithelial neoplasia grade 2 or 3 among HPV-positive women were detected within 24 months after the first positive test for HPV. After adjustment for the presence of HPV infection, the development of cervical intraepithelial neoplasia was also associated with younger age at first intercourse, the presence of serum antibodies to Chlamydia trachomatis, the presence of serum antibodies to cytomegalovirus, and cervical infection with Neisseria gonorrhoeae. CONCLUSIONS: Cervical intraepithelial neoplasia is a common and apparently early manifestation of cervical infection by HPV, particularly types 16 and 18.

Adolescent

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

Chronic Chlamydia trachomatis infections in infants.

OBJECTIVE: --To study the natural history of Chlamydia trachomatis infections in infants. DESIGN: --Bacteriologic and serologic study of an inception cohort. SETTING: --University of Washington Medical Center, Seattle. PARTICIPANTS: --Twenty-two infants with C trachomatis infections either not treated early in life or recurring after antimicrobial treatment. MAIN OUTCOME MEASURES: --Persistence of infection in various anatomic sites, antibody responses to specific serovars (serologic variants) of C trachomatis, and serovars of isolates from mothers and infants. RESULTS: --The cumulative proportion of infants still infected at the age of 1 year was 35%. Infection persisted in the conjunctiva, nasopharynx, and oropharynx in one child for as long as 866 days (28.5 months), when she was cured by treatment. In none of the infants did serologic tests suggest acquisition of infection other than at birth. Isolates of C trachomatis from mothers and their respective infants were always of the same serovar. CONCLUSIONS: --Many infants infected with C trachomatis at birth remain infected for months or years in the absence of specific antimicrobial therapy. Such infections may be confused with those acquired by sexual abuse.

Antibodies, Bacterial

Risk assessment and laboratory diagnosis of trichomoniasis in men.

Control of Trichomonas vaginalis is assuming higher priority because recent studies have suggested that trichomoniasis enhances susceptibility to human immunodeficiency virus infection and the risk for delivery of low-birth weight infants. In a cross-sectional study, 50 cases were identified among 447 men attending a sexually transmitted disease clinic. As previously reported, trichomoniasis was associated with nonchlamydial nongonococcal urethritis. Other risk factors included sexual contact with an infected woman or prior treatment for trichomoniasis or nongonococcal urethritis. Urethral and first-void urine cultures were positive in 80% and 68% of positive cases, respectively. When combined, these two cultures diagnosed 49 (98%) of 50 cases. These data suggest that criteria for selection of men for culture should include presence of nonchlamydial nongonococcal urethritis, recent exposure to trichomoniasis, or a history of trichomoniasis or nongonococcal urethritis. In addition, combining urethral and urine sediment cultures may prove accurate for evaluating T. vaginalis infection.

Adolescent

Prevalence and cytologic manifestations of human papilloma virus (HPV) types 6, 11, 16, 18, 31, 33, 35, 42, 43, 44, 45, 51, 52, and 56 among 500 consecutive women.

The prevalence and associated cytologic manifestations of cervical infection with human papillomavirus (HPV) types 6, 11, 16, 18, 31, 33, 35, 42, 43, 44, 45, 51, 52, and 56 were studied among 500 consecutive women attending the Harborview Medical Center Sexually Transmitted Diseases (STD) Clinic in Seattle, WA. Using radiolabeled-probes without prior amplification of DNA, HPV DNA was detected in cervical specimens from 120 (24%) of the women and was found to be more prevalent than Chlamydia trachomatis (13%), Neisseria gonorrhoeae (12%), or mucopurulent cervicitis (20%). High-risk HPV types 16 or 18 were present alone in 5% of the women; intermediate-risk types 31, 33, 35, 45, 51, 52, or 56 in 3%; and low-risk types 6, 11, 42, 43, and 44 in 5%. In an additional 8% HPV DNA was detected but could be characterized only as being type 6, 11, 16, 18, 31, 33, or 35. Each grouping of HPV types was equally associated with squamous intraepithelial lesions (SILs) of the cervix. In the absence of SIL and koilocytosis, the cytologic changes associated with HPV infection included frequent binucleation and variation in nuclear size and chromatin distribution. Parakeratosis and hyperkeratosis without nuclear atypia were not associated with HPV DNA. The natural history and clinical significance of these HPV-associated lesions remain to be defined.

Adolescent

Association of human immunodeficiency virus and anal human papillomavirus infection among homosexual men.

BACKGROUND: A previous study of men with proctitis, proctocolitis, or enteritis showed an association of anal human papillomavirus (HPV) infection with human immunodeficiency virus (HIV) infection. Because anorectal abnormalities may confound an observed association between anal HPV DNA and HIV seropositivity, the present study was undertaken among consecutive homosexual men seeking HIV serologic testing who were unselected for anorectal symptoms. METHODS: Consecutive homosexual men underwent a standardized interview, physical examination, and collection of specimens for HIV serologic testing and detection of anal HPV DNA. RESULTS: Anal HPV DNA was detected in eight (31%) of 26 HIV-seropositive men and in 10 (8%) of 119 HIV-seronegative men (odds ratio, 5.8; 95% confidence interval, 1.1 to 30.1, adjusted for history of sexually transmitted disease, current anorectal symptoms, and age). When men with anorectal symptoms were excluded from the analysis, anal HPV DNA was detected in 27% of seropositive men compared with 8% of seronegative men (odds ratio, 4.4; 95% confidence interval, 1.4 to 13.4). There was no difference between HIV-seropositive and HIV-seronegative men with respect to distribution of type of HPV DNA. Men with group II or III and group IV HIV disease were 4.1 and 10.9 times, respectively, more likely than HIV-seronegative men to have anal HPV DNA detected. CONCLUSIONS: Because HIV-seropositive men appear to be at increased risk for the detection of anal HPV DNA, the natural course of anal HPV infection should be compared among HIV-seropositive and HIV-seronegative homosexual men.

Anus Diseases

A trial of minocycline given after exposure to prevent gonorrhea.

In a prospective evaluation of antibiotic prophylaxis against gonorrhea, 1080 men were given 200 mg of oral minocycline or placebo after sexual intercourse with prostitutes in a Far Eastern port. Later, at sea, gonococcal infection was detected in 57 of 565 men given placebo and 24 of 515 men given minocycline (P less than 0.001). Minocycline prophylaxis completely prevented infection by gonococci susceptible to 0.75 microgram or less of tetracycline per milliliter, reduced the risk of infection or prolonged the incubation period in men exposed to gonococci susceptible to 1.0 to 2.0 micrograms per milliliter, but did not prevent infection or prolong incubation in men exposed to gonococci resistant to 2.0 micrograms. Minocycline did not increase the proportion of asymptomatic infections. Minocycline prophylaxis would probably have limited effectiveness as a public-health measure because of the tendency to select resistant gonococci.

Administration, Oral

Clinical course and diagnosis of genital herpes simplex virus infection and evaluation of topical surfactant therapy.

A prospective study of 37 men and 32 women with culture-proved genital herpes simplex virus (HSV) infection was undertaken to characterize the clinical manifestations of the disease and effects of topical therapy with Nonoxynol 9, a nonionic surfactant active in vitro against HSV. The duration of pain, lesions, and virus shedding was significantly longer in initial than in recurrent genital HSV infection. Cervical HSV shedding occurred in 11 of 13 initial infections versus two of 19 recurrences (p less than 0.001). Type 1 HSV caused seven of 29 initial and none of 40 recurrent infections (p less than 0.01). Clinical recurrences within six weeks were detected more often in men than in women and were unrelated to the menstrual cycle. The influence of coitus on recurrence is unclear. Papanicolaou smears were transiently abnormal (Class II) in four (12.5 per cent) of 32 female patients. Evidence of herpesvirus was detected cytologic smears from only 28 (41 per cent) of 69 culture-proved external lesions and three (23 per cent) of 13 culture-positive cervices. Serology was also of limited diagnostic value except in testing paired sera from initial infections. The topical therapy had no beneficial effect.

Adult

Etiology, manifestations and therapy of acute epididymitis: prospective study of 50 cases.

There were 50 patients with acute epididymitis who were evaluated prospectively by history, examination and microbiologic studies, including cultures for aerobes, anaerobes, Neisseria gonorrhoeae, Chlamydia trachomatis and Ureaplasma urealyticum. Escherichia coli was the predominant pathogen isolated from the urine of men more than 35 years old, while Chlamydia trachomatis and Neisseria gonorrhoeae were the predominant pathogens isolated from the urethra of men less than 35 years old. The etiologic role of Escherichia coli and Chlamydia trachomatis was confirmed by isolation from epididymal aspirates from a high proportion of men with positive urine or urethral cultures for these agents. Chlamydia trachomatis epididymitis accounted for two-thirds of idiopathic epididymitis in young men and often was associated with oligospermia. Of 9 female sexual partners of men with Chlamydia trachomatis infection 6 had antibody to Chlamydia trachomatis, of whom 2 had positive cervical cultures for this organism and 2 others had non-gonococcal pelvic inflammatory disease. Antibiotic therapy with tetracycline was effective for the treatment of men with Chlamydia trachomatis epididymitis and should be offered to the female sex partners.

Adolescent

Studies on gonococcus infection. XVII. IgA1-cleaving protease in vaginal washings from women with gonorrhea.

Vaginal washings from women attending a veneral disease clinic were examined for the presence of protease that cleaved IgA subclass 1 (IgA1). In a crude assay, vaginal washings cleaved [125I]IgA1 in 19 of 25 specimens from individuals from whom Neisseria gonorrhoeae were cultivated. Forty-six specimens from 104 women whose cultures were negative for N. gonorrhoeae also cleaved [125I]IgA1. Vaginal washings from six of six women with culture-proven gonorrhea cleaved [125I]IgA1 into low-molecular-weight components identical to those produced by partially purified IgA1-specific protease from gonococci. The hydrolysis of [125I]IgA1 by vaginal washings from women whose cultures were negative for N. gonorrhoeae yielded cleavage products that resembled those of trypsin or alpha-chymotrypsin. These findings indicate that gonococci residing in the female genital tract produce IgA1-specific protease that can be detected in the vaginal washings of infected women.

Electrophoresis, Polyacrylamide Gel

Ineffectiveness of erythromycin for treatment of Haemophilus vaginalis-associated vaginitis: possible relationship to acidity of vaginal secretions.

To assess the efficacy of oral erythromycin in the treatment of nonspecific vaginitis (NSV), conducted a nonrandom, unblinded pilot study among 17 women with symptoms and signs of NSV. At the completion of treatment, 10 of 13 patients had persistent symptoms, 9 of 13 had persistent abnormal discharge, and 11 of 13 had persistently positive cultures for Haemophilus vaginalis. Ten patients with persistent or relapsing NSV and four who did not complete erythromycin treatment were retreated with oral metronidazole, and 14 of 14 showed clinical improvement and eradication of H. vaginalis. The susceptibility of 27 clinical isolates of H. vaginalis to erythromycin was determined at pH 5.5, 6.0, 6.5, and 7.0. The minimal inhibitory concentration of erythromycin for H. vaginalis was approximately 10-fold higher at pH 5.5 than at pH 7.0. Erythromycin is not effective for the treatment of H. vaginalis-associated NSV; this may be partly attributable to the reduced activity of this drug in acidic vaginal secretions.

Erythromycin

Amine content of vaginal fluid from untreated and treated patients with nonspecific vaginitis.

We examined the vaginal washings from patients with nonspecific vaginitis (NSV) to seek biochemical markers and possible explanations for the signs and symptoms of this syndrome. Seven amines were identified including methylamine, isobutylamine, putrescine, cadaverine, histamine, tyramine, and phenethylamine. These amines may contribute to the symptoms of NSV and may contribute to the elevated pH of the vaginal discharge. They may also be partly responsible for the "fishy" odor that is characteristic of vaginal discharges from these patients. Among the seven amines, putrescine and cadaverine were the most abundant and were present in all vaginal discharges from each of ten patients before treatment. These amines are produced in vitro during growth of mixed vaginal bacteria in chemically defined medium, presumably by decarboxylation of the corresponding amino acids. We hypothesize the anaerobic vaginal organisms, previously shown to be quantitatively increased in NSV, are responsible for the amine production, because metronidazole inhibited the production of amines by vaginal bacteria in vitro, and Haemophilus vaginalis did not produce amines. H. vaginalis did release high concentrations of pyruvic acid and of amino acids during growth in peptone-starch-dextrose medium, whereas, other vaginal flora consumed both pyruvic acid and amino acids in the same medium during growth. These findings suggest that a symbiotic relationship may exist between H. vaginalis and other vaginal flora in patients with NSV.

Amines

Acute epididymitis: etiology and therapy.

Fifty patients with acute epididymitis were evaluated prospectively by history, examination, and microbiologic studies, including cultures for aerobes, anaerobes, N. gonorrhoeae, Chlamydia trachomatis, and Ureaplasma urealyticum. E. Coli was the predominant pathogen isolated from the urine of men over 35 years old and C. trachomatis and N. gonnorrheae were the predominant pathogens isolated from the urethra of men under 35. The etiologic role of E. Coli and C. trachomatis was confirmed by isolation from epididymal aspirates from a high proportion of men with positive urine of urethral cultures for these agents. C. trachomatis epididymitis accounted for two thirds of "idiopathic epididymitis" in men, and was often associated with oligozoospermia. Of nine female sexual partners of men with C. trachomatis infection, six had antibody to C. trachomatis, of whom two had positive cervical cultures for this organism, and the others had nongonococcal pelvic inflammatory disease. Antibiotic therapy with tetracycline was effective for the treatment of men with C. trachomatis epididymitis, and should be offered to their female sex partner.

Adolescent