Evidence of placental haemorrhage and preterm delivery.

OBJECTIVE: To evaluate evidence of placental haemorrhage (PH) obtained through maternal interviews, patient charts and placental pathology examinations as potential indicators of a 'bleeding pathway' to preterm delivery (PTD). DESIGN: Prospective cohort. SETTING: Fifty-two clinics in five communities in Michigan, USA (1998-2004). POPULATION: A subset (n = 996) of cohort participants with complete placental pathology data. METHODS: First-trimester bleeding and placental abruption were ascertained by mid-trimester interviews and chart review, respectively. Disc-impacting blood clot was defined as a gross placental examination finding of a blood clot impacting adjacent tissue. Microscopic haemorrhage was defined as 'high' (top quintile) scores on an aggregate measure of placental pathology findings suggestive of atypical maternal vessel haemorrhage. These four PH indicators were compared with one another and with risk of PTD assessed by logistic regression analyses. MAIN OUTCOME MEASURES: Preterm delivery and PTD subtypes (i.e. <35 weeks, 35-36 weeks; spontaneous, medically indicated) compared with term deliveries. RESULTS: Placental abruption cases had 2.3-fold to 5.5-fold increased odds of the other three PH indicators. Disc-impacting blood clots and microscopic haemorrhage were associated with one another (odds ratio [OR] = 4.6), but not with first-trimester bleeding. In a multivariable model that included all four PH indicators and confounders, risk of PTD < 35 weeks was elevated with first-trimester bleeding (OR = 1.9 [1.0, 3.4]), placental abruption (OR = 5.2 [1.7, 16.2]), disc-impacting blood clots (OR = 2.3 [1.0, 5.0]) and microscopic haemorrhage (OR = 2.4 [1.4, 4.2]). CONCLUSIONS: Multiple clinical and subclinical PH indicators are associated with PTD, particularly early PTD.

Breast carcinoma etiology: current knowledge and new insights into the effects of reproductive and hormonal risk factors in black and white populations.

BACKGROUND: A crossover in breast carcinoma incidence at ages 45-49 years has been observed between black and white women, with blacks experiencing higher incidence at younger ages and lower incidence after age 50 years. Can this phenomenon be partially explained by the differences in the distributions of reproductive risk factors? This article focuses on the effects and distributions of age at first full term pregnancy (FFTP), parity, and oral contraceptive (OC) use in younger versus older and black and white populations. Effects of hormone replacement therapy (HRT) are also summarized. METHODS: A literature review was conducted and information integrated on the effects and distributions of reproductive and hormonal risk factors in black and white populations, the crossover effect of parity, and the Pike model of "breast tissue age." RESULTS: Overall, early age at FFTP and higher parity decreased risk for both races. Distributions of age at FFTP and parity varied widely between the two races. Based on the effects and distributions of age at FFTP and parity, the authors formulated the hypothesis that a crossover in incidence curves between the two races would be expected, rather than be considered an anomaly. Regarding OC use, generally a stronger increase in risk was observed for younger women than for older women. Regarding HRT, a recent meta-analysis observed an increased risk of 1.35 for 5 years of use or more. CONCLUSIONS: To promote public health in diverse populations, and to provide further insight into breast carcinoma etiology, research needs to focus on multicultural differences and similarities in the relation of hormonal risk factors and breast carcinoma.

Hormone replacement therapy with estrogen or estrogen plus medroxyprogesterone acetate is associated with increased epithelial proliferation in the normal postmenopausal breast.

The relative effects of postmenopausal hormone replacement therapy (HRT) with estrogen alone vs. estrogen+progestin on breast cell proliferation and on breast cancer risk are controversial. A cross-sectional observational study was carried out to examine the proliferative effects of HRT with estrogen or estrogen plus the progestin, medroxyprogesterone acetate, in breast tissue of postmenopausal women. Benign breast biopsies from 86 postmenopausal women were analyzed with antiproliferating cell nuclear antigen (anti-PCNA) and Ki67 antibodies to measure relative levels of cell proliferation. Epithelial density and estrogen and progesterone receptor status were also determined. The women were categorized either as users of: 1) estrogen (E) alone; 2) estrogen+medroxyprogesterone acetate (E+P); or 3) no HRT. Compared with no HRT, the breast epithelium of women who had received either E+P or E alone had significantly higher PCNA proliferation indices, and treatment with E+P had a significantly higher index (PCNA and Ki67) than treatment with E alone. Breast epithelial density was significantly greater in postmenopausal women treated with E and E+P, compared with no HRT. Thus, the present study shows that postmenopausal HRT with E+P was associated with greater breast epithelial cell proliferation and breast epithelial cell density than E alone or no HRT. Furthermore, with E+P, breast proliferation was localized to the terminal duct-lobular unit of the breast, which is the site of development of most breast cancers. Further studies are needed to assess the possible association between the mitogenic activity of progestins and breast cancer risk.

Validity and reproducibility of a food frequency questionnaire among Hispanic and non-Hispanic white women in New Mexico.

The purpose of this study was to assess the validity and reproducibility of an interviewer-administered, semi-quantitative food frequency questionnaire (FFQ) among 132 volunteer New Mexico Hispanic (H) and non-Hispanic white (NHW) women, aged 35-74 years, with (n = 47) and without (n = 85) a breast cancer history, and to add to the limited data presently available on the performance of FFQs among different ethnic groups. Validity was measured at one month and six months from baseline against four-day food records, and reproducibility was tested by comparing FFQs. Unadjusted validity correlation coefficients were highest at one month, ranging from 0.38 (polyunsaturated and monounsaturated fat) to 0.57 (calcium); energy-adjusted correlation coefficients were highest at six months, ranging from 0.15 (polyunsaturated fat) to 0.68 (calcium). Energy-adjusted correlation coefficients were statistically significant by ethnicity for vitamins A and C, protein, carotene and calcium, and by case status for saturated fat, folate, fiber, and vitamins A and E. Reproducibility correlation coefficients (unadjusted) ranged from 0.40 (polyunsaturated fat) to 0.71 (carbohydrate, retinol); energy-adjusted correlation coefficients ranged from 0.42 (vitamin E) to 0.78 (fiber), and differed significantly by ethnicity for saturated fat and retinol, and by case status for carbohydrate. Overall, our FFQ has comparable characteristics to other FFQs and is suitable for use with New Mexico's H and NHW women.

Rapid HbA1c testing in a community setting.

OBJECTIVE: To determine whether the DCA 2000 analyzer provides valid and reliable HbA1c results when used under field conditions and operated by nonmedical personnel. This study was part of a community diabetes education program, the Native American Diabetes Project, in which HbA1c was measured as an indicator of average glycemic control. RESEARCH DESIGN AND METHODS: Two study samples were taken, the first in the spring of 1994 and the second in the spring of 1995. Seven community members in 1994 and six new community members in 1995 were trained over 2 days, using standard protocol, to operate the DCA 2000 HbA1c analyzer and to collect two capillary blood samples from participants in the Native American Diabetes Project. Duplicate DCA 2000 HbA1c measurements performed by the community workers were compared with measurements from a high-performance liquid chromatography (HPLC) system. Validity and reliability measures were calculated. RESULTS: Of the participants, 43 were studied in 1994 and 14 in 1995. Comparison of the mean DCA 2000 results with those of HPLC showed high validity, with the absolute relative difference between the mean DCA 2000 and the external reference of HPLC (magnitude of mean DCA 2000-HPLC magnitude of /HPLC) as 4.0 and 2.0% for 1994 and 1995, respectively. The Pearson correlation coefficients (r) between these two measures were 0.968 and 0.996 for 1994 and 1995, respectively. While the 1994 data appeared to have less validity for values > 10%, they included only one value with a 60-min warm-up of the DCA analyzer. The 1995 data, all collected after a 60-min warm-up, had good correlation throughout the range of values. The within-run reliability was excellent, with an intraclass correlation coefficient of reliability of 0.959 and 0.975 for paired samples, for 1994 and 1995 respectively. The mean coefficient of variation for these paired measures was 3.0% in 1994 and 2.8% in 1995. Both validity and reliability were improved by changing the warm-up period of the DCA 2000 analyzer from 5 to 60 min. All correlation coefficients were statistically significant (P < 0.0001). CONCLUSIONS: The DCA 2000 gave valid and reliable HbA1c results when operated in a community setting by nonmedical personnel. Extending the warm-up period of the device to 60 min slightly improved the validity and reliability of the test.

Breast mammographic pattern: a concatenation of confounding and breast cancer risk factors.

A mammographic pattern of > 25% radiodensity is associated with increased risk for breast cancer. Mammographic pattern is influenced by age, body weight, reproductive factors, and race/ethnicity. The interaction among these factors in predicting breast radiographic pattern, and their association with the presence of histologic markers of increased risk of breast cancer, is poorly defined. To elucidate the relations among epidemiologic, radiographic, and histologic markers of breast cancer risk, the authors studied these factors in an unselected forensic autopsy series, accumulated between 1978 and 1983, of 486 women aged 15-98 years at death. Older age and/or postmenopausal status was the strongest predictor of radiolucent breast pattern. Obesity, defined as a Quetelet index (weight(kg)/height(m)2) of > 25, and large breast size were also highly significant predictors of breast radiolucency. Factors related to parity were not significant predictors of breast parenchymal pattern. Native American race was an independent predictor of breast radiolucency in this population. A dense parenchymal pattern was associated with increased prevalence of marked cystic change and the presence of duct epithelial hyperplasia in women under age 35. The results support the association of breast radiodensity with ethnic/racial, reproductive, and histologic factors predictive of cancer risk. However, this association is overshadowed by the effects of obesity and aging or menopause.

Silicosis and lung cancer risk in underground uranium miners.

The presence of radiographic silicosis as a risk factor for lung cancer was assessed in a case-control study conducted within a study cohort of New Mexico underground uranium miners. Chest radiographs were interpreted for the presence of silicosis for 65 lung cancer cases and 216 controls. The presence of silicosis on the chest radiograph taken closest to the start of employment or on the latest radiograph available was not associated with lung cancer risk after adjustment for cumulative exposure to radon progeny. The odds ratio associated with the presence of any type of opacity indicative of pneumoconiosis on the chest x ray closest to the start of employment was 1.33 (95% confidence interval, 0.31-5.72). For the most recent available chest x ray, the corresponding odds ratio was 1.16 (95% confidence interval, 0.35-3.84). Although the findings are limited by the relatively small number of subjects, the lack of association of silicosis with lung cancer suggests that silica exposure should not be regarded as a major uncertainty in extrapolating radon risk estimates from miners to the general population.

Prediction of iron absorption based on iron status of female blood donors.

Iron stores were assessed in 27 postmenopausal healthy women who donated five units of blood (approximately 485 mL/unit) over approximately 1 y. The mean (+/- SD) age was 67.7 +/- 4.0 y and the average time between successive blood donations was approximately 10 wk (range 8-30 wk). Steady-state iron stores at entrance were 10.59 +/- 3.88 mg/kg body wt (mean +/- SD) and declined to 1.03 +/- 3.20 mg/kg by the fifth donation. Determination of iron stores was based on biochemical measures of iron status at each donation. Iron intakes were 23.3 +/- 10.1 mg/d. From these data we developed equations that can be used to predict the frequency at which healthy postmenopausal women can donate blood without becoming iron deficient. The ability of elderly women to become successful blood donors depends primarily on initial iron stores, iron intake, and frequency of donation. Women with low steady-state iron stores may be able to donate only two times per year without becoming iron deficient.

Seroprevalence of HIV-1 and hepatitis B and C in prostitutes in Albuquerque, New Mexico.

A survey of persons soliciting sex in an area known to be frequented by prostitutes in Albuquerque, NM, included 43 females and 66 males. Seroprevalence rates found in this population-based study were as follows: human immunodeficiency virus type 1 (HIV-1), 3%; hepatitis B, 39%; hepatitis C, 45%. Increased age, intravenous drug use, and condom use were independent risk factors for hepatitis B. Female gender and intravenous drug use were independent risk factors for hepatitis C. Neither sharing injection equipment nor engaging in receptive anal intercourse was independently associated with hepatitis B or C.

Combined effects of body size, parity, and menstrual events on breast cancer incidence in seven countries.

A biologically motivated breast cancer incidence rate function was fit to data from a published case-control study conducted in countries whose incidence is high (Wales and the United States), moderate (Brazil, Greece, and Yugoslavia), and low (Japan and Taiwan). The data include personal characteristics of 3,925 breast cancer cases and 11,327 controls interviewed in selected hospitals in 1964-1968. Parameters in the function specify the dependence of age-specific breast cancer incidence rates on age at menarche, age at menopause, occurrence and timing of full-term pregnancies, and body mass. Parameters were estimated separately for high-, moderate-, and low-risk countries. Examination of residuals provided little evidence of inadequacy of the fitted function in describing combined effects of the characteristics studied. The following patterns were seen in all three risk groups: 1) Incidence rates jump to a higher level after first childbirth, but then increase with age more slowly thereafter. 2) Rates increase with age more slowly after menopause than before. 3) Rates change quadratically with body mass index among all women, although the main trend varies: Rates decrease with body mass among premenopausal women in high-risk countries, but increase with body mass in all other groups of women. Similarities of parameter estimates across countries suggest that reproductive events and body fat exert similar effects on all women, regardless of breast cancer rates in their country of residence.

Lung cancer mortality and exposure to radon progeny in a cohort of New Mexico underground uranium miners.

A cohort of 3469 males with at least 1 y of underground uranium mining experience in New Mexico was assembled and mortality followed up through 31 December 1985. The mean and median cumulative exposures for the cohort were 0.39 J h m-3 and 0.12 J h m-3 (111.4 and 35.0 Working Level Months [WLM]), respectively. Overall, mortality in the cohort was significantly increased (standardized mortality ratio [SMR] = 1.1, 95% confidence interval [CI] = 1.02-1.2) relative to the general population of the state. By cause, significant increases were observed for lung cancer (SMR = 4.0, 95% CI 3.1-5.1) and for external causes of death (SMR = 1.5, 95% CI 1.3-1.7). The risk of lung cancer increased for exposure categories above 100 WLM; the excess relative risk increased by 0.5% per mJ h m-3, 95% CI 0.2-1.5 (1.8% per WLM, 95% CI 0.7-5.4). Data were consistent with a multiplicative interaction between smoking and exposure to Rn progeny in an exponential relative risk model. The risk of lung cancer varied substantially with age at observation; the odds ratios rose more steeply with exposure to Rn progeny for those less than age 55 y at observation.

Parity factors and prevalence of fibrocystic breast change in a forensic autopsy series.

The relationship of reproductive factors, such as nulliparous vs ever-parous status, age at first birth, and total parity, with morphologic prevalence of fibrocystic changes were examined using autopsy material from three ethnic/racial groups at varying risks for breast cancer. Although there was a trend toward a protective effect of ever-parous status, there was no statistically significant difference in the prevalence of fibrocystic disease in any group defined by parity status. The ethnic differences in the prevalence of fibrocystic changes were not explained by the differences in parity status distribution for the three ethnic/racial groups.

Radiographic microcalcification and parenchymal patterns as indicators of histologic "high-risk" benign breast disease.

Breast tissue from a forensic autopsy series of 486 women (15 to 98 years of age) was studied radiographically and by histologic sampling. Prevalence of Wolfe P2/Dy parenchymal patterns decreased with age. Radiographic nonvascular microcalcification and histologic presence of marked ductal epithelial hyperplasia and lobular microcalcification increased with age. Both of these histologic parameters of increased risk for breast cancer correlated with the presence of radiographic microcalcification and Wolfe P2/Dy parenchymal pattern. The predictive value of the radiographic parameters for presence of "high-risk" proliferative fibrocystic change increased with age.

The area of cancer in transurethral resection specimens as a prognostic indicator in carcinoma of the prostate: a computer-assisted morphometric study.

We used a computerized interactive morphometric method to determine total area of tissue and total area of cancer in routinely stained sections from each of 79 cases of prostatic adenocarcinoma, diagnosed by transurethral resection (TURP). The ability of two morphometrically determined parameters (area of cancer and percent area of cancer) to predict survival was compared with results obtained from two estimates of tumor area commonly used in clinical practice (number of chips and percent of chips involved by cancer). Total Gleason score was also determined. All patients were diagnosed prior to 1981, allowing follow-up of at least 5 years, or until death. Using the Cox proportional hazards regression analysis, our two morphometrically determined parameters, as well as the percentage of chips involved by cancer and total Gleason score, were significant predictors of survival. In contrast, the total number of chips involved by cancer did not reach statistical significance as a predictive factor for survival. By using our morphometrically determined area measurements as a bench mark for clinical utility of area estimates of cancer in TURP specimens, we concluded that calculating the percentage of involved chips yields prognostic information that closely approaches the "ideal" of these more time-consuming computer-assisted techniques.

Age and race related changes in mammographic parenchymal patterns.

The relationship between breast parenchymal patterns and age was examined in a nonselected, nonreferred group. The three major racial-ethnic subgroups represented have markedly different incidences of breast cancer, with Anglos (nonHispanic caucasians), Hispanics, and American Indians having higher to lower incidence rates of breast cancer, respectively. Mammograms were performed in 519 victims of nonhospital, nonnatural or unexplained deaths in New Mexico. The percentage of dense breast patterns (DY + P2) decreased with age for all groups. American Indian women showed a much earlier shift to a lower density parenchymal pattern than Anglo or Hispanic women. At older ages Indian women continued to have a slightly lower percentage of dense breast patterns than the other groups. The changes in breast parenchymal pattern with age and ethnic groups may reflect factors related to risk of breast cancer.

Radon progeny exposure and lung cancer risk in New Mexico U miners: a case-control study.

A case-control study was conducted to describe lung cancer risk in a cohort of New Mexico underground U miners. The subjects included 65 cases and 230 age-matched controls, most with exposures below 3.50 J h m-3 (1000 WLM). The risk for lung cancer was increased for all cumulative exposures to Rn progeny of 0.35 J h m-3 (100 WLM) or greater. The odds ratios were unchanged with control for cigarette smoking. With exclusion of subjects with exposures above 3.50 J h m-3 (1000 WLM), the estimated excess relative risk was 0.3% per mJ h m-3 (1.1% per WLM). The risk was greater for younger subjects and the data were consistent with a multiplicative interaction between cigarette smoking and exposure to Rn progeny.

Cigarette smoking and lung cancer in New Mexico.

We have used population-based data for the state of New Mexico to calculate cigarette-smoking-specific incidence rates for lung cancer, cumulative incidence rates for lung cancer, and estimates of the proportion of lung cancer cases attributable to smoking. For white New Mexicans, the incidence of lung cancer increased with age and was markedly higher in smokers than in nonsmokers. From 25 through 84 yr of age, the cumulative incidence of lung cancer was 0.9% in nonsmoking males and 0.5% in nonsmoking females. The cumulative incidence rates were much higher for smokers; for males who smoked 20 or more cigarettes daily from age 25, the cumulative risk of lung cancer through age 84 was 31.7%. For females with the same cigarette smoking history, the estimate of cumulative incidence through age 84 years was 15.3%. The population-attributable risks for lung cancer associated with cigarette smoking were 89.5% for males and 85.5% for females.

Prevalence of benign, atypical, and malignant breast lesions in populations at different risk for breast cancer. A forensic autopsy study.

A forensic autopsy series of 519 women more than 14 years old was studied for prevalence of benign, atypical, and occult malignant breast lesions. The women included Anglos (non-Hispanic whites), Hispanics, and American Indians from New Mexico and Eastern Arizona. These three ethnic/racial groups are at markedly different risk for the development of breast cancer (Anglo 89 of 100,000 women per year, Hispanic 45.5, and American Indian 24.9. There were striking ethnic/racial and age-related differences in both the prevalence and magnitude of all forms of nonproliferative and proliferative fibrocystic disease. The various subsets of fibrocystic disease were highly associated with each other. Such lesions as apocrine metaplasia, sclerosing adenosis, and lobular microcalcification showed as much difference according to ethnic/racial background and age as the more common cystic change and duct epithelial hyperplasia. Atypical lobular and ductal hyperplasia, carcinoma in situ, and occult invasive carcinoma were uncommon and also occurred in ethnic/racial groups in a pattern that parallels the cancer risk in those groups.

History of residence and lung cancer risk in New Mexico.

Participants in a population-based case-control study of lung cancer in New Mexico between 1980 and 1982 were asked to identify all locations where they had resided for six months or more. These residential data were coded at the county and state levels and combined with county-level socioeconomic data from the 1910, 1930, 1950, and 1970 decennial censuses to generate indices of time lived in counties or metropolitan areas of different sizes, degrees of urbanization, or extents of employment in manufacturing industries. Urban residence was not associated with employment of male controls in jobs or industries considered to increase lung cancer risk. However, in the non-Hispanic white female controls, urban residence before age 30 years in a county of 500,000 or more residents was associated with a fourfold higher odds ratio for starting to smoke cigarettes. Male and female non-Hispanic controls who had ever lived in more populous counties smoked more cigarettes per day than did those who had not lived in such counties. Residential history patterns were the same in cases and controls; multiple logistic regression showed no consistent associations of the residence history variables with lung cancer risk.

Marriage to a smoker and lung cancer risk.

As part of a population-based case-control study of lung cancer in New Mexico, we have collected data on spouses' tobacco smoking habits and on-the-job exposure to asbestos. The present analyses include 609 cases and 781 controls with known passive and personal smoking status, of whom 28 were lifelong nonsmokers with lung cancer. While no effect of spouse cigarette smoking was found among current or former smokers, never smokers married to smokers had about a two-fold increased risk of lung cancer. Lung cancer risk in never smokers also increased with duration of exposure to a smoking spouse, but not with increasing number of cigarettes smoked per day by the spouse. Our findings are consistent with previous reports of elevated risk for lung cancer among never smokers living with a spouse who smokes cigarettes.