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Biomedical subjects

K L Noller

Publications and source records attributed to K L Noller.

At least 55 records · Page 3Linked to original sources

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↗

Cryptorchism and maternal estrogen exposure.

A case-control study of in utero estrogen exposure and cryptorchism was carried out using as cases males born in Rochester, Minnesota, during the years 1943-1973 who were diagnosed as having cryptorchism. Two different control groups were selected for comparison, control group I being more closely matched than control group II. The estimated relative risks (RR) for estrogen exposure were 1.3 (95% confidence interval (CI) = 0.5-3.1) and 1.1 (95% CI = 0.5-2.6) for control groups I and II, respectively. In the univariate analysis, the only significantly elevated relative risks found were those for bleeding and spotting in the third trimester for cases versus control group II (RR = 3.7; 95% CI = 1.1-15.7), birth weight less than 2,500 g for cases versus control group II (RR = 3.4; 95% CI = 1.3-9.9), and gestational age of 40 weeks or less for cases versus control group I (RR = 1.8; 95% CI = 1.2-2.9). No elevated relative risks were associated with other problems during the index pregnancy or with prior pregnancies, nor with progestin exposure, smoking, presentation at delivery, or mode of onset of labor. Multivariate analysis also provided no evidence to suggest that in utero estrogen exposure is associated with cryptorchism in male offspring.

Adult↗

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↗

Detection of chlamydial cervicitis by Papanicolaou stained smears and culture.

The ability of the cervical Papanicolaou (Pap) smear to detect cervicitis associated with Chlamydia trachomatis was investigated. Cultures and cervical cytology samples were obtained from 487 women seen at the Mayo Clinic Department of Obstetrics and Gynecology and at the Sexually Transmitted Disease clinic of the Olmsted County Health Department. Adequate pap smears contained endocervical or metaplastic cells. Thirty-seven patients had positive Chlamydia cultures; of these, 14 were cytologically suggestive of Chlamydia, 10 were negative but satisfactory, and 13 were unsatisfactory. Of the 450 patients with negative cultures, 21 had cytologic findings suggesting infection. Thus, of 35 cases suggestive cytologically, 14 (40%) were confirmed by culture. Of the 21 false-positive cytologies, eight were in postpartum women. Because of problems with specificity and inadequate smears, cervical cytology specimens should not replace culture as a means of detection, but can identify women who should be cultured for C. trachomatis.

Cells, Cultured↗

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↗

Fertility and outcome of pregnancy in women exposed in utero to diethylstilbestrol.

Fertility and outcome of pregnancy were examined in women participating in the National Cooperative Diethylstilbestrol Adenosis (DESAD) Project. We compared 618 subjects who had prenatal exposure to DES with 618 control subjects. Fertility, measured in terms of pregnancies achieved, did not differ between the women exposed to DES and the controls. An increased risk of unfavorable outcome of pregnancy was associated with DES exposure (the relative risk of any unfavorable outcome of pregnancy was 1.69; P less than 0.001). Speculation on biologic mechanisms that might produce this difference is premature, since additional data about these subjects must be collected. Among DES-exposed women who became pregnant, 81 per cent had at least one full-term live birth.

Abnormalities, Drug-Induced↗

Breast cancer in DES-exposed mothers: absence of association.

Reports in the popular press have suggested that exposure to diethylstilbestrol (DES) is followed by an abnormally high incidence of breast cancer. The reports were based on a reanalysis of data not considered ominous originally; and both data and analyses are summarized here. In addition, new data are presented on mothers of young women enrolled in the National DESAD Project at its Mayo Clinic Center. Among 408 women given DES, there were 8 confirmed instances of breast cancer, in comparison with an expected number of 8.1, based on breast cancer incidence rates among parous women in the local population. A previous case-control study of the possible association of antihypertensive therapy and breast cancer in the local population revealed DES exposure in 10% of the breast cancer group and 12% of the controls. These apparently negative results clearly indicate a need of further studies of the alleged effect of DES.

Adult↗

Lack of evidence for cancer due to use of metronidazole.

Experimental studies have shown that metronidazole is carcinogenic in rodents and mutagenic in bacteria. In 771 women given metronidazole for the treatment of vaginal trichomoniasis, more cancers developed than had been expected after exclusion of carcinoma of one uterine cervix (observed, 24 cases; expected on the basis of the Connecticut Tumor Registry, 21.7; expected on the basis of the Third National Cancer Survey, 18.4). However, the excess was not statistically significant (P greater than 0.05). The observed and expected numbers of breast-cancer cases were the same, but four lung-cancer cases were observed, whereas 0.6 would have been expected. This finding is confounded by the fact that all four lung cancers developed in women who were smokers. Overall, we observed no appreciable increase in cases of cancer.

Adolescent↗

Vaginal epithelial changes in young women enrolled in the National Cooperative Diethylstilbestrol Adenosis (DESAD) project.

Initial clinical findings are reported for the 3339 young women enrolled in the Diethylstilbestrol Adenosis (DESAD) project. Changes in the vaginal mucosa (VEC--vaginal epithelial changes), which were detected by colposcopy or iodine staining, occurred in 34% of 1275 participants identified by review of prenatal records 59% of participants who themselves requested entry into the project, and 65% of participants referred by a physician. Analysis of data on the 298 women who were identified by record review and whose prenatal records contained complete information about drug exposure indicated that VEC is most closely associated with the timing of the onset of intrauterine exposure to diethylstilbestrol (DES), total dose, and length of exposure. Frequency of VEC was also found to decrease with age. No instances of severe dysplasia, carcinoma in situ, invasive squamous cell adenocarcinoma, or clear cell carcinoma were observed among the women identified by record review.

Adenocarcinoma↗

Effect of elective induction on birth weight.

The 1,250 Mayo Clinic obstetric deliveries for 1976 were reviewed and 73 elective inductions were identified. Sixty-three of these mothers were successfully matched by gravidity, parity, and age within 5 years with healthy women in whom delivery was spontaneous at term. The mean birth weight for the electively delivered infants was greater than that for the controls, but the difference was not statistically significant. Mean gestation and 1-minute Apgar scores were similar for both groups. The neonatal problems observed, with the exception of elevated bilirubin levels, did not seem to point to any special hazard of induction. Even though pregnancy is interrupted, elective induction, as practiced at the Mayo Clinic, was not shown to produce a systematic reduction in birth weight.

Adult↗

Routine chest roentgenography in pregnancy.

In an effort to determine if routine prenatal chest roentgenograms were of practical value, the records of 12,109 consecutive deliveries at the Mayo Clinic were reviewed retrospectively. The roentgenograms were obtained during the first or second prenatal visit and additionally when warranted by notable symptoms or physical findings in subsequent prenatal visits. Forty-eight patients had appreciable roentgenographic abnormalities. The findings of the general medical examination (which was routinely done at the first prenatal visit) were reviewed to determine if the chest abnormalities would have been suspected from the results of physical examination alone. In every case, a positive history or abnormal physical finding would have suggested the presence of the major abnormality or of the need for roentgenography to be performed.

Adolescent↗

Pregnancy and its complications following cardiac valve prostheses.

Approximately 100 cases of pregnancy in women with cardiac valve prostheses have been reported in the world's medical literature. In most instances, the need for continuous anticoagulation therapy constituted a major concern in the obstetric management of these high-risk pregnancies, particularly since coumarin has been implicated as causing an increased frequency of fetal wastage or birth defects (or both). Of all women who received cardiac valve prostheses at the Mayo Clinic between 1965 and 1975, 23 conceived 40 times after the procedure. Fetal wastage was more than doubled in women receiving coumarin therapy at conception and during the first trimester, as compared with that in women not receiving coumarin therapy. Fetal wastage exceeded 80% in women with multiple-valve prostheses who received coumarin therapy throughout early pregnancy. There were no serious maternal sequelae in any of the women. One infant of a mother receiving anticoagulation therapy had mild nasal hypoplasia, but there were no other congenital anomalies in which coumarin had been previously implicated.

Abnormalities, Drug-Induced↗

Design and preliminary observations of National Cooperative Diethylstilbestrol Adenosis (DESAD) Project.

The National Cooperative Diethylstilbestrol Adenosis (DESAD) Project has completed the major portion of its enrollment phase with the examination of more than 3000 daughters of women taking synthetic nonsteroidal estrogens (denoted DES) during pregnancies occurring from the early 1940s to the mid-1960s. The aims of the Project are to fill urgent needs for information on the prevalence and incidence of structural and epithelial abnormalities or neoplastic changes and their complications in these young women. Participants are grouped by mode of entry as identified by prenatal record review (40.1%), documented as DES-exposed but walking in (25.1%), or referred (22.8%) to the DESAD Project for examination, and not documented as exposed but having gynecologic abnormalities typical of those associated with DES exposure (12.0%). This study cohort, in part having paired controls, will be examined annually for at least 5 years. Details of the design and selected preliminary findings are reported.

Adolescent↗