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Biomedical subjects

K Noller

Publications and source records attributed to K Noller.

10 recordsLinked to original sources
PubMed2006

Mortality in women given diethylstilbestrol during pregnancy.

We used Cox regression analyses to assess mortality outcomes in a combined cohort of 7675 women who received diethylstilbestrol (DES) through clinical trial participation or prenatal care. In the combined cohort, the RR for DES in relation to all-cause mortality was 1.06 (95% CI = 0.98-1.16), and 1.11 (95% CI = 1.02-1.21) after adjusting for covariates and omitting breast cancer deaths. The RR was 1.07 (95% CI = 0.94-1.23) for overall cancer mortality, and remained similar after adjusting for covariates and omitting breast cancer deaths. The RR was 1.27 (95% CI = 0.96-1.69) for DES and breast cancer, and 1.38 (95% CI=1.03-1.85) after covariate adjustment. The RR was 1.82 in trial participants and 1.12 in the prenatal care cohort, but the DES-cohort interaction was not significant (P = 0.15). Diethylstilbestrol did not increase mortality from gynaecologic cancers. In summary, diethylstilbestrol was associated with a slight but significant increase in all-cause mortality, but was not significantly associated with overall cancer or gynaecological cancer mortality. The association with breast cancer mortality was more evident in trial participants, who received high DES doses.

Adult↗
PubMed2001

Long-term cancer risk in women given diethylstilbestrol (DES) during pregnancy.

From 1940 through the 1960s, diethylstilbestrol (DES), a synthetic oestrogen, was given to pregnant women to prevent pregnancy complications and losses. Subsequent studies showed increased risks of reproductive tract abnormalities, particularly vaginal adenocarcinoma, in exposed daughters. An increased risk of breast cancer in the DES-exposed mothers was also found in some studies. In this report, we present further follow-up and a combined analysis of two cohorts of women who were exposed to DES during pregnancy. The purpose of our study was to evaluate maternal DES exposure in relation to risk of cancer, particularly tumours with a hormonal aetiology. DES exposure status was determined by a review of medical records of the Mothers Study cohort or clinical trial records of the Dieckmann Study. Poisson regression analyses were used to estimate relative risks (RR) and 95% confidence intervals (CI) for the relationship between DES and cancer occurrence. The study results demonstrated a modest association between DES exposure and breast cancer risk, RR = 1.27 (95% CI = 1.07-1.52). The increased risk was not exacerbated by a family history of breast cancer, or by use of oral contraceptives or hormone replacement therapy. We found no evidence that DES was associated with risk of ovarian, endometrial or other cancer.

Breast Neoplasms↗
PubMed2000

Incidence of squamous neoplasia of the cervix and vagina in des-exposed daughters.

PURPOSE: Women exposed to diethylstibestrol (DES) in utero are known to have an excess risk of clear cell adenocarcinoma of the vagina and cervix, in addition to vaginal epithelial changes, but the effect on the incidence of squamous neoplasia is uncertain. This study evaluated the long-term risk of developing high-grade squamous neoplasia of the genital tract among women exposed prenatally to diethylstilbestrol.METHODS: A cohort comprising 3899 DES-exposed and 1374 unexposed daughters was followed for thirteen years (1982-1995) for pathology-confirmed diagnoses of high-grade squamous neoplasia. A pathologist blinded to exposure status reviewed seventy-seven percent of cases. Poisson regression analysis was used to compute relative risks (RR) and 95% confidence intervals (CI) controlling for age, calendar year, screening history and other covariates.RESULTS: The RR (95% CI) among DES-exposed versus unexposed, based on 111 cases of high-grade disease, was 2.12 (1.19-3.77). Adjustment for screening history had little effect, but when the analysis was restricted to a group highly screened before 1982, the risk was reduced. Risk estimates were higher among women exposed earlier in gestation; the RR (95% CI) for exposure within 7 weeks of the last menstrual period was 2.82 (1.43-5.53).CONCLUSIONS: The findings support an association between in utero DES exposure and high-grade squamous neoplasia, although a role for more intensive screening among DES-exposed women in the production of this excess could not be completely ruled out.

Journal Article↗
PubMed2000

Continued follow-up of pregnancy outcomes in diethylstilbestrol-exposed offspring.

OBJECTIVE: To evaluate long-term pregnancy experiences of women exposed to diethylstilbestrol (DES) in utero compared with unexposed women. METHODS: This study was based on diethylstilbestrol-exposed daughters, the National Collaborative Diethylstylbistrol Adenosis cohort and the Chicago cohort, and their respective nonexposed comparison groups. Subjects who could be traced were sent a detailed questionnaire in 1994 that contained questions on health history, including information on pregnancies and their outcomes. We reviewed 3373 questionnaires from exposed daughters and 1036 questionnaires from unexposed women. RESULTS: The response rate was 88% among exposed and unexposed women. Diethylstilbestrol-exposed women were less likely than unexposed women to have had full-term live births and more likely to have had premature births, spontaneous pregnancy losses, or ectopic pregnancies. Full-term infants were delivered in the first pregnancies of 84.5% of unexposed women compared with 64. 1% of exposed women identified by record review (relative risk [RR] 0.76, confidence interval [CI] 0.72, 0.80). Preterm delivery of first births occurred in 4.1% of unexposed compared with 11.5% of exposed women, and ectopic pregnancies in 0.77% of unexposed compared with 4.2% of exposed women. Spontaneous abortion was reported in 19.2% of DES-exposed women compared with 10.3% in control women (RR 2.00, CI 1.54, 2.60). According to complete pregnancy histories (many women had more than one pregnancy), preterm births were more common in DES-exposed women (19.4% exposed versus 7.5% unexposed (RR 2.93 CI 2.23, 3.86). Second-trimester spontaneous pregnancy losses were more common in DES-exposed women (6.3% versus 1.6%; RR 4.25, CI 2.36, 7.66). More first-trimester spontaneous abortions occurred in DES-exposed women than in controls (RR 1.31, CI 1.13, 1.53), and DES-exposed women had at least one ectopic pregnancy more often than unexposed women (RR 3.84, CI 2.26, 6.54). CONCLUSION: Pregnancy outcomes in DES-exposed women were worse than those in unexposed women.

Abortion, Spontaneous↗
PubMed1997

Neoplasia associated with atypical glandular cells of undetermined significance on cervical cytology.

The clinical importance of atypical glandular cells of undetermined significance (AGUS) on cervicovaginal smear has not been well defined. Between January 1990 and April 1996, 127 smears were reported as showing AGUS changes by the cytopathology division at the University of Massachusetts Medical Center. The medical records of these women were reviewed: 17 women were excluded because of previous hysterectomy or gynecologic cancer, 85 were biopsied, 16 were followed by repeat smears, and 9 were lost to follow-up. Forty-four women had negative biopsies or cervicitis. There were 15 endometrial lesions: 10 hyperplasias (2 with atypia) and 5 adenocarcinomas. Twenty-five women had cervix lesions including 3 endocervical atypias, 12 low-grade cervical intraepithelial neoplasia (CIN), 6 high-grade CIN, one adenocarcinoma in situ, and 3 invasive adenocarcinomas. One patient had ovarian cancer. Two of the 16 women followed by repeat pap smear eventually had a cancer diagnosis: one with cervix cancer and one with colon cancer. We were unable to identify a subgroup of women with AGUS who were at increased risk for serious pathology when we compared multiple demographic variables, symptoms, or the presence of coexistent squamous abnormalities on cervical cytology. The mean age of the 15 women with endometrial lesions was 59.9 years, which was significantly older than those patients with cervix lesions who had a mean age of 38.9 years. The presence of AGUS on cervical cytology is a marker for significant gynecologic neoplasia and should be investigated with colposcopically directed biopsies, endocervical curettage, and, in older women, endometrial biopsy.

Adult↗
PubMed1993

Breast cancer in mothers prescribed diethylstilbestrol in pregnancy. Further follow-up.

OBJECTIVE: Further assessment of the long-term risk of breast cancer associated with diethylstilbestrol (DES) during pregnancy. DESIGN: Follow-up continuation through June 1, 1989, of a historical cohort of DES-exposed and unexposed mothers ascertained by review of obstetric records. PARTICIPANTS: Totals of 3029 each of DES-exposed and unexposed mothers who had delivered live babies at four centers in the United States during 1940 through 1960. Questionnaires were returned for 92.6% of the DES-exposed and 88.8% of the unexposed women. MAIN OUTCOME MEASURES: Breast cancer incidence and mortality assessed from returned questionnaires and review of medical records and death certificates. MAIN RESULTS: The relative rate of breast cancer associated with DES exposure, after adjustment for demographic and reproductive variables, was 1.35 (95% confidence interval, 1.05 to 1.74). For 30 years or more following exposure, the relative rate was not appreciably higher (relative rate, 1.33; 95% confidence interval, 0.95 to 1.87) than that in earlier periods. Surveillance and increased detection seemed unlikely explanations for the increased risk, since DES-exposed women had excesses of both large and small breast cancers and the two cohorts reported similar breast cancer detection practices. A history of miscarriage before first term delivery was not associated with breast cancer occurrence. CONCLUSION: Exposure to DES during pregnancy is associated with a modest but statistically significant increased risk of breast cancer. Contrary to prior indications, the risk does not appear to increase greatly over time. The findings are sufficient to exclude the possibility of a doubling of risk for the period of 30 or more years following exposure.

Abortion, Spontaneous↗
PubMed1986

Upper genital tract changes and infertility in diethylstilbestrol-exposed women.

A possible relationship of upper genital tract abnormalities in the diethylstilbestrol-exposed woman and infertility was studied. Six hundred thirty-two women had roentgenography performed. Three hundred sixty-seven of these women were not using contraception and were actively trying to become pregnant. One hundred thirty-four (36%) of these women reported difficulties conceiving for a period of 1 or more years. Seventy-three percent of these women had abnormal hysterosalpingograms. The frequency of abnormal x-ray films in the women who did conceive within 1 year was essentially the same (74%). Furthermore, a similar number of women with normal x-ray films (37%) had difficulty conceiving as did women with abnormal x-ray films (36%). When specific hysterosalpingographic abnormalities were related to the presence or absence of infertility, it was observed that the presence of a constriction of the upper uterine cavity resulted in a 2.26-times greater likelihood that a woman would not be able to conceive. If a T-shaped uterus was found in association with constriction of the upper uterine cavity, the odds ratio for inability to conceive was found to be 2.63.

Abnormalities, Drug-Induced↗
PubMed1984

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↗
PubMed1984

Cross-sectional study of gross and fine motor development. Birth to 6 years of age.

A total of 187 healthy children between birth and six years of age were administered a comprehensive gross and fine motor development assessment. The assessment device was a hybrid instrument consisting of 192 items derived from 15 commonly used instruments. The purpose of the study was to 1) define motor behavior relative to a performance distribution expressed in age ranges, 2) identify patterns of performance across a range from birth to 6 years of age, and 3) assess the stability of performance by comparing select tasks with norms available in the literature. Emergence and achievement levels of successful performance were defined for 37 items relative to 68 percent and 95 percent of the children across the range from birth to 6 years of age. These results were compared with eight assessment devices. Emergence comparisons were found to be fairly similar to published norms; achievement comparisons showed a higher frequency of discrepancies with published norms. Performance patterns were displayed graphically to illustrate symmetry and asymmetry in normal development milestones.

Age Factors↗