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Biomedical subjects

B Hulka

Publications and source records attributed to B Hulka.

14 recordsLinked to original sources

Prior hrt use, ethnicity and mammographic density.

PURPOSE: Mammographic density has been strongly associated with breast cancer risk in several studies. To clarify possible pathogenic mechanisms underlying this relationship, we assessed factors affecting mammographic density in postmenopausal women.METHODS: Percent density (PD) was measured on pre-randomization mammograms from 425 participants in the Women's Health Initiative clinical trial; no women were currently using HRT. Trained observers used a previously validated computer-assisted thresholding technique to measure PD (ratio of dense areas to breast area) on craniocaudal films. Univariate relationships were assessed between PD and age, parity, education, history of HRT use, age at first birth, abortion history, alcohol use, serum cholesterol, physical activity, smoking, dietary fat intake, body-mass index (BMI), and waist-to-hip ratio (WHR). Multivariable regression was used to identify predictors of PD (log transformed), controlling for confounders.RESULTS: PD ranged from 0-60% with mean 8%. Age, gravidity, BMI, and WHR were negatively associated with PD. Mean PD in the highest tertiles of BMI and WHR was nearly half that in the lowest. Ethnicity (50% white, 28% black, and 19% Hispanic) and hysterectomy status (50% had intact uterus) were unassociated with PD. Controlling for age, BMI, WHR, smoking, hysterectomy status, prior HRT, and nulliparity, mean PD differed significantly by ethnicity, with black women having highest PD. However, the effect of prior HRT use differed by uterine status. In women with uteri intact, ethnicity, but not prior HRT use, was related to PD after controlling for age, BMI, and WHR. In hysterectomized women, ethnicity was unrelated to PD, while previous HRT was associated with lower PD.CONCLUSIONS: Gravidity, ethnicity and body shape and size are associated with mammographic density in postmenopausal women. Previous hormone use predicts lower PD, but only among hysterectomized women. This may be due to the higher frequency of oophorectomies in this group, which may lower PD and increase likelihood of HRT use. Planned analyses of entire sample of 1050 women will clarify the effect of these and other factors on density, and on density change in followup mammograms.

Journal Article↗

p53 mutations in benign breast tissue.

PURPOSE: Patients with benign breast biopsies that exhibit atypical epithelial proliferation or fibroadenoma may be at increased risk for invasive breast cancer. We hypothesized that molecular markers might also be useful to evaluate the malignant potential of nonneoplastic breast tissue. PATIENTS AND METHODS: Study subjects belonged to a cohort of 6,805 women who underwent biopsy for nonmalignant breast disease at the Mayo Clinic and Rochester-affiliated hospitals between 1967 and 1981. As part of a nested case-control study that compared subjects who developed invasive breast cancer with those who did not, we analyzed a sample of 60 benign breast biopsies for the following markers: HER-2/neu and p53 over-expression by immunohistochemistry, HER-2/neu and PRAD-1 amplification using differential polymerase chain reaction (PCR), and p53 mutation using single-strand conformation analysis (SSCA) and direct DNA sequencing by asymmetric PCR. RESULTS: None of 60 biopsies showed amplification of HER-2/neu or PRAD-1. Five samples exhibited low-level immunoreactivity to the HER-2/neu protein product. Fourteen samples exhibited focal or diffuse immunoreactivity to the p53 protein. Point mutations in the p53 gene were found in five samples: three of these samples exhibited mutations that altered the amino acid sequence. Only two of five samples with p53 mutation exhibited p53 overexpression. Histologic diagnoses on three samples with nonconservative p53 mutation were, respectively, nonproliferative fibrocystic change, papillomatous hyperplasia, and fibroadenoma. CONCLUSION: The clinical significance of p53 mutation, p53 overexpression, and low-level HER-2/neu expression in benign breast tissue remains to be determined. Further research will be necessary to evaluate whether these markers could serve as useful adjuncts to histology in evaluation of the malignant potential of benign breast tissue.

Base Sequence↗

Farming and prostate cancer mortality.

Although farmers appear to be at an increased risk of prostate cancer, the specific exposures which produce the excess risk remain unexplained. This study was based on a retrospectively assembled cohort of male Manitoba, Saskatchewan, and Alberta, Canada, farmers age 45 years or older identified in the 1971 Canadian censuses of population and agriculture. The cohort was linked to the Canadian National Mortality Database using an iterative computer record linkage system for the period June 1971 to the end of 1987. A total of 1,148 prostate cancer deaths and 2,213,478 person-years were observed. Using Poisson regression, the study examined the relation between the risk of dying from prostate cancer and various farm practices as identified on the 1971 Census of Agriculture, including exposure to chickens, cattle, pesticides, and fuels. A weak, but statistically significant, association was found between number of acres sprayed with herbicides in 1970 and risk of prostate cancer mortality. When the analysis was restricted to farmers believed to be subject to the least amount of misclassification, the risk associated with acres sprayed with herbicides increased (rate ratio (RR) = 2.23 for 250 or more acres sprayed; 95% confidence interval (CI) 1.30-3.84; test for trend, p < 0.01). No other farm exposure examined was associated with any detectable pattern of increased or decreased risk. These findings encourage further research to examine the effects of herbicides on prostate cancer.

Aged↗

Comparison of DNA adducts from exposure to complex mixtures in various human tissues and experimental systems.

DNA adducts derived from complex mixtures of polycyclic aromatic compounds emitted from tobacco smoke are compared to industrial pollution sources (e.g., coke ovens and aluminum smelters), smoky coal burning, and urban air pollution. Exposures to coke oven emissions and smoky coal, both potent rodent skin tumor initiators and lung carcinogens in humans, result in high levels of DNA adducts compared to tobacco smoke in the in vitro calf thymus DNA model system, in cultured lymphocytes, and in the mouse skin assay. Using tobacco smoke as a model in human studies, we have compared relative DNA adduct levels detected in blood lymphocytes, placental tissue, bronchoalveolar lung lavage cells, sperm, and autopsy tissues of smokers and nonsmokers. Adduct levels in DNA isolated from smokers were highest in human heart and lung tissue with smaller but detectable differences in placental tissue and lung lavage cells. Comparison of the DNA adduct levels resulting from human exposure to different complex mixtures shows that emissions from coke ovens, aluminum smelters, and smoky coal result in higher DNA adduct levels than tobacco smoke exposure. These studies suggest that humans exposed to complex combustion mixtures will have higher DNA adduct levels in target cells (e.g., lung) as compared to nontarget cells (e.g., lymphocytes) and that the adduct levels will be dependent on the genotoxic and DNA adduct-forming potency of the mixture.

Adult↗

Plasma selenium and skin neoplasms: a case-control study.

Although experimental studies in animals show that selenium may prevent cancer, case-control studies of internal human cancers have been difficult to interpret because neoplastic tissue sequesters selenium. We therefore conducted a case-control study to examine the association between plasma selenium level and skin cancer, a neoplasm with minimal tumor mass at the time of diagnosis. The mean selenium level among patients with either basal cell epithelioma (N = 142), squamous cell carcinoma (N = 48), or both (N = 50), was 0.141 micrograms/g. This was significantly lower than the mean plasma selenium level of the 103 control subjects, which was 0.155 micrograms/g. The noncancer control groups were drawn from current clinic patients and past clinic patients. The logistic estimate of the odds ratio for the lowest versus the highest decile of selenium for all cases combined versus the group of current patient controls was 4.39; for all cases combined versus the past patient controls, the logistic estimate of the odds ratio was 5.81.

Adult↗

Effectiveness of the neonatal transport team.

This study was performed to determine the effectiveness of a hospital-based transport team in lowering mortality in newborns. The medical records of 603 outborn infants weighing from 500 to 2500 g and having primary respiratory disorders were reviewed. The infants were admitted to 1 of 3 regional neonatal centers between January 1, 1977 and September 30, 1980. The 2 centers without transport teams admitted 304 outborn infants, of whom 62 (20%) expired by 120 h of age. The center with a transport team admitted 184 team-transported infants and 115 nonteam-transported infants, of whom 38 (13%) expired by 120 h of age. Outborn infants admitted to the hospitals without a neonatal transport team had a 60% (p less than 0.01) greater mortality compared to those admitted to the hospital with a transport team. At the onset of intensive care, the babies transported to the nonteam hospitals had a greater incidence of hypothermia and acidosis which may be related to their increased mortality. We conclude that hospitals without the services of a neonatal transport team may have significantly more deaths among low birth weight infants with respiratory disease than comparable hospitals with neonatal transport teams.

Humans↗

Factors influencing the occurrence of advanced cervical carcinoma.

The continued occurrence of advanced cervical carcinoma (stage II, III, IV) was studied. Patients were evaluated with regard to age, racial origin, socioeconomic status, geographic distribution, and presenting symptoms. Particular emphasis was placed on the role of screening in disease detection. The disturbing finding was that of the 170 patients reviewed, disease was diagnosed by screening examination in only 20 patients. Furthermore, 62 patients were not diagnosed even though they were exposed to the health care system. Factors which influence obtaining Pap smears are discussed, with suggestions as to how to enhance use of the Pap smear.

Adult↗