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Biomedical subjects

R H Kaufman

Publications and source records attributed to R H Kaufman.

At least 91 records · Page 5Linked to original sources

Increased incidence of cervical and vaginal dysplasia in 3,980 diethylstilbestrol-exposed young women. Experience of the National Collaborative Diethylstilbestrol Adenosis Project.

The incidence rates of dysplasia and carcinoma in situ (CIS) of the cervix and vagina were determined in 3,980 young women exposed prenatally to diethylstilbestrol. Strict criteria were developed to minimize selection bias among the subset of 744 pairs of matched exposed and unexposed (control) cohort participants, all of whom were identified through review of prenatal obstetrical records. A high degree of compliance was achieved throughout the seven-year study period since in each group about 90% of the women remained as active participants, kept 77% of the annual anniversary examinations, and had separate Papanicolaou smears of the cervix and vagina performed in 99% of the anniversary examinations. The incidence rate for dysplasia and CIS was significantly higher in the women exposed to diethylstilbestrol than in those not exposed in the matched cohort (15.7 v 7.9 cases per 1,000 person-years of follow-up). The rates were higher in the exposed women if squamous metaplasia extended to the outer half of the cervix or onto the vagina. In other respects, the matched cohorts were strikingly similar.

Adult↗

Transplantation of normal and ectopic human endometrial tissue into athymic nude mice.

Implants or tiny circumscribed nodules of endometrial tissue were found in all female mice given intraperitoneal injections of fragments of human normal (proliferative and secretory) or ectopic (endometrioma) endometrium. Half of these animals received estrogen supplementation and the other half received none. The endometriosis tissue present in these animals at 28 or 56 days after inoculation consisted of glands and stroma with an infiltration of hemosiderin-laden macrophages. Glands in tissue transplants of animals given supplemental estrogen tended to be larger, and the secretory endometrium tended to revert to a proliferative pattern. Palpable nodules at the site of subcutaneous inoculations of proliferative endometrium became undetectable grossly and microscopically within 24 to 32 days, whereas endometrioma tissue remained detectable for up to 70 days and resembled the intraperitoneal tissue microscopically. This study demonstrates that human endometrial tissue can be successfully transplanted into the nude mouse and will retain its basic morphology.

Animals↗

Upper genital tract abnormalities and pregnancy outcome in diethylstilbestrol-exposed progeny.

Previous studies have suggested that there is an association between genital tract abnormalities and pregnancy outcome in women exposed to diethylstilbestrol (DES) in utero. In a collaborative study, 676 DES-exposed women had hysterosalpingographic examinations, and the findings were related to the outcome of pregnancy in 327 of these women. The findings revealed that (1) there is a considerable variation of frequency of different types of upper genital tract anomalies in women from different sources and with different motivations for enrollment in the study, (2) the presence of structural cervical changes and vaginal epithelial changes are markers for the likelihood of abnormalities in the uterine fundus, (3) women with upper genital tract abnormalities have increased odds for poor pregnancy outcome as compared to women with normal hysterosalpingographic findings, and (4) although some abnormalities were most often or consistently associated with poor pregnancy outcome, no specific changes could be related to specific types of pregnancy outcomes.

Abortion, Spontaneous↗

Structural anomalies of the cervix and vagina in women enrolled in the Diethylstilbestrol Adenosis (DESAD) Project.

Among women exposed in utero to diethylstilbestrol (DES) and enrolled in the Diethylstilbestrol Adenosis (DESAD) Project, structural anomalies of the cervix or vagina were found in 25% of the 1,655 subjects identified by review of prenatal records, 43% of the 800 who themselves requested entry into the project, and 49% of the 1,089 referred by physicians but in only 2% of the 963 control subjects. Among the 367 cases found by record review to have complete information on the DES exposure, multivariate analysis indicated close association of the anomalies with the gestational week of first exposure and the total dose. Also, the prevalence rate of the anomalies was lower among subjects who had been pregnant and higher among those with later age at menarche.

Abnormalities, Drug-Induced↗

Gardnerella vaginalis vaginitis. The current opinion.

Gardnerella vaginalis, a gram-negative bacillus, was first described in 1954. The associated clinical entity, vaginitis, first described in 1955, is controversial. The disease has specific symptoms, signs and diagnostic criteria. It has a symbiotic relationship with anaerobic bacteria. Whether G. vaginalis is a pathogen or normal inhabitant of the vagina is a subject of debate. The term nonspecific vaginitis should not be used for G. vaginalis vaginitis. G. vaginalis is sexually transmitted.

Bacteriological Techniques↗

Maturation of vaginal and cervical epithelium in women exposed in utero to diethylstilbestrol (DESAD Project).

A total of 452 women with documented exposure in utero to diethylstilbestrol (DES) with epithelial findings present at the time of their initial examination have been evaluated prospectively to determine whether these findings changed over a period of 3 years. The examinations were all performed according to a strict protocol. Findings present at the time of the third annual examination were verified at a fourth examination. A verified decrease in the extent of epithelial findings occurred in 29.2% of these women and a verified increase in 6.6%; 53.1% had no change in the extent of epithelial findings, and 11.1% had a change that could not be verified at the time of the fourth visit. Analysis of many variables failed to identify a strong association between any variable and a decrease in the extent of the findings. It appears that the most important factor in the occurrence of changes in DES-associated findings is the passage of time.

Adolescent↗

Evidence of a possible direct action of Danazol on the human ovary.

Strong evidence is presented that Danazol might exert a direct action on the human ovary by binding to receptor-like receptors for progesterone and testosterone, in concentrations well within the pharmacological range of the treated patient. The possible significance of this finding in understanding Danazol's mode of action is discussed.

Adult↗

Occurrence of endometrial adenocarcinoma during lactation.

Endometrial adenocarcinoma is commonly seen in the perimenopausal and postmenopausal age groups. Certain medical conditions (such as diabetes, hypertension, and obesity) are often associated with development of this disease. Consequently, when irregular bleeding develops, a decision to sample the endometrium is often predicated on the patient's age and the presence of these associated conditions. Often, healthy young women receive empirical hormonal therapy for irregular bleeding without prior endometrial sampling. An unusual case of endometrial adenocarcinoma arising during lactation in a young healthy woman is presented.

Adenocarcinoma↗

Selected family planning and general health profiles in a teen health clinic.

To assess client utilization trends, selected characteristics including some aspects of family planning behavior of adolescent families were examined during the first two years of a Teen Health Clinic's operation. The majority of the girls attending the clinic were 16 years and under, nulliparous, and still living with one or more of their parents. While birth control services were the primary motivation for attendance, 25% of the girls came for a general health examination, information or counseling. Potentially significant problems, including venereal diseases, were found in 20% of the patients. Reproductive health trends and their implication for improving health care delivery and family planning for teenagers are discussed.

Adolescent↗

Kinetics of human antibody responses to primary genital herpes simplex virus infection.

5 patients with primary genital herpes simplex virus (HSV) infection were studied prospectively for the production of serum antibody reactivity as measured by the virus micro-neutralization test (NT), micro-solid phase radioimmunometric assay (micro-SPRIA), and antibody-dependent cellular-cytotoxic (ADCC) test. ADCC antibody was detected before reactivity measured by either NT or micro-SPRIA in 2 of the patients. A 3rd patient failed to produce neutralizing antibody, whereas specific activity was detected by the other two methods. In 2 other patients a good correlation was observed for development of antibody by all three methods. There were several discordant results in the kinetics of production of antibody detected by these assays, suggesting that not all individuals produce similar types of antiviral antibody.

Adult↗

Development of clear cell adenocarcinoma in DES-exposed offspring under observation.

Two cases of clear cell adenocarcinoma of the vagina detected at follow-up in young women exposed in utero to diethylstilbestrol are reported. One patient, aged 23, had been followed for 2 years before carcinoma was diagnosed; the second patient, aged 22, had been seen on a regular basis for 5 years, 8 months. In both instances, suspicion of the presence of carcinoma was aroused by the palpation of a small nodule in the vaginal fornix. Hysterosalpingography was performed on both patients and, in 1 instance, an abnormal x-ray film was reflected by the gross appearance of the uterine cavity found in the surgical specimen.

Adenocarcinoma↗

Carcinoma in situ of the vulva. The search for viral particles.

Biopsy specimens taken from eight women with squamous-cell carcinoma in situ of the vulva were studied with transmission electron microscopy for the presence of viral particles. In one of the specimens a 150-nm-diameter viruslike particle was found. The exact nature of this particle was not clear, but it could have represented an immature herpesvirus particle. In seven specimens no evidence of viral particles was detected. These findings provide further evidence that the positivity of vulvar carcinoma in situ for herpesvirus antigen is not due to the presence of whole virus particles.

Adult↗

Herpesvirus-induced antigens in squamous-cell carcinoma in situ of the vulva.

Antigens induced by herpes simplex virus Type 2 (HSV2) were found to be associated with squamous-cell carcinoma in situ of the vulva in nine of 10 patients. The HSV2-induced antigens are DNA-binding proteins that are normally present in the nuclei of infected cells, but in the cells of the carcinomas in situ they were found in the cytoplasm. Whole-virion structural antigens were not present, although there was serologic evidence of previous HSV2 infection in patients tested for the presence of antibodies. The observations reported here and the recent parallel rise in the prevalence of both HSV2 infections and vulvar carcinoma in situ, particularly in women under 40 years of age, suggest an association of HSV2 infection with this type of neoplasia, the nature of which remains to be determined.

Adult↗

Dysplasia and cytologic findings in 4,589 young women enrolled in diethylstilbestrol-adenosis (DESAD) project.

This report presents the cytologic findings and the rates of dysplasia for 4,589 young women enrolled in the National Cooperative Diethylstilbestrol-Adenosis (DESAD) Project. Mucinous columnar cells and/or metaplastic squamous cells with or without mucinous droplets were encountered in 22% of vaginal scrape smears from all diethylstilbestrol (DES)-exposed participants identified by review of prenatal records and in 43% of women in whom vaginal epithelial changes (VEC) were observed by colposcopy or by iodine staining. The frequency of cellular findings in the vaginal scrape smears was closely related to the timing of the administration of the DES to the mother. With increasing age of the daughters, the overall frequencies of both the mucinous and metaplastic cells decreased; relative to each other, an increasing proportion was metaplastic squamous cells. These data suggest that, as the women grow older, vaginal adenosis regresses by the process of squamous metaplasia. Endometrial type cells were found in 2% of vaginal scrape smears. Their cyclical occurrence during the menstrual cycle and lack of correlation with the presence of VEC indicated an origin from the uterine corpus rather than the tuboendometrial type of adenosis. Squamous cell dysplasia of the vagina and cervix was detected by biopsy or scrape smear specimens in 1.8% of DES-exposed women in the record review group. The rate of unexposed women was twice as high. In general, the rates of dysplasia were higher in the cervix than vagina, and the more severe degrees of dysplasia were encountered only in those women who were referred to the DESAD Project or who themselves requested entry. Four patients who were referred or who themselves requested entry were found to have clear cell adenocarcinoma of the vagina. The vaginal smear provided the first clue to the presence of an abnormality in three of them.

Adenocarcinoma↗

Intraepithelial carcinoma of the vulva with extension to the anal canal.

Ten patients with intraepithelial carcinoma of the vulva that extended to the anus were studied. The patients were seen and treated over a 3-year period, from January 1976 through December 1978. During the 10-year period before 1976 the authors had encountered no patients with this problem. Treatment consisted predominantly of a skinning vulvectomy with split-thickness skin graft and excision of the anal disease. Failure to recognize the extension to the anus will result in persistent disease following surgical therapy.

Adult↗

Nuclear DNA study of vulvar intraepithelial and invasive squamous neoplasms.

In this study, 59 vulvar intraepithelial squamous neoplasms (8 atypia and 51 carcinoma in situ) and 33 invasive squamous carcinomas were analyzed for their nuclear DNA content using Feulgen microspectrophotometry. Four cases of atypia had a polyploid DNA distribution. The remaining 4 cases of atypia and all cases of carcinoma in situ had an aneuploid pattern, and nearly two thirds of these had high ploidy stem cells (greater than 3N). This is in contrast to the low ploidy stem cells (less than 3N) seen in 70% of the invasive carcinomas and in 82% of the intraepithelial neoplasms in the vicinity of invasive carcinomas. This observation suggests that not all vulvar intraepithelial neoplasms have the same propensity to become invasive. Invasive carcinomas of comparable size and depth of invasion with low ploidy stem cells had a higher frequency of lymph node metastasis than those having high ploidy stem cells. The significance of nuclear DNA findings related to gynecologic neoplasms is discussed.

Aneuploidy↗