Biomedical subjects

B S Hulka

Publications and source records attributed to B S Hulka.

At least 19 recordsLinked to original sources

PubMed1992

Methodological issues in epidemiologic studies using biologic markers.

Biologic markers are becoming prominent features of many classical epidemiologic studies. Their existence has also modified the character of some epidemiologic research such that the term "transitional epidemiologic studies" may be warranted. In the latter type of study, collaboration between laboratory and epidemiologic investigators is integral to the research. In this paper, goals, characteristics, and examples of transitional epidemiologic research are presented. Pertinent features are highlighted, including sources of misclassification and confounding, and elements of study design useful in reducing these potential biases. Sample size issues, transformation of variables, and sources of variability acquire enhanced importance. The study examples presented are intended to illustrate the altered substrate for these methodological features in studies using biologic markers.

Analysis of Variance↗

PubMed1992

Biomarkers of pesticide exposure.

Incorporation of biomarkers in studies of occupational exposure hazards is now recognized as a highly useful adjunct to the surrogate measures employed in the past, for example, time worked, ambient air data, interview responses. Application to studies of workers potentially exposed to pesticides has barely begun and provides many challenges to chemist/epidemiologist teams. This review indicates several excellent studies employing multiple-exposure measures to document the validity of specific biomarkers for particular exposure situations. In general, exposure reflected by urinary assays of specific pesticides is a low percentage of that indicated by dermal or breathing zone measures. Markers for many of the pesticides in current usage have yet to be developed and validated, and information on population variability is generally lacking for existing markers. The challenge provided by the complexity of multiple, and often unknown, exposures to individuals in pesticide environments has begun to be addressed employing cytogenetic or urinary measures that attempt to integrate these complex exposures. The lack of data regarding sensitivity and specificity of biomarkers, especially in complex exposure situations, is a major problem that perhaps will best be addressed by studies combining nonspecific measures with specific ones, utilizing stored sample banks created for that purpose. Expanding the repertoire of available biomarkers of pesticide exposure and employing multiple ones in well-designed study protocols will provide critical tools in the evaluation of pesticide safety and design of appropriate measures to minimize adverse exposures. Ironically, one of the problems that biological markers of exposure can help overcome, reliance on poorly measured ambient exposure data, hampers the evaluation of the markers themselves. Therefore, the combination of in vitro, animal, and human data will give the best picture of a marker's performance. (Wilcosky 1990).

Biomarkers↗

PubMed1992

Barrier methods of contraception and cervical intraepithelial neoplasia.

This North Carolina-based case-control study examined risk factors for cervical intraepithelial neoplasia (CIN). Cases were 103 women with biopsy-confirmed CIN II or III who were recruited from a referral dysplasia clinic. Controls were 258 family practice patients with normal cervical cytology. All subjects were interviewed regarding their sexual and reproductive history, Pap smear screening, active and passive cigarette exposures, and contraceptive use patterns. When compared with controls, cases were half as likely to have ever used barrier methods of contraception; the adjusted odds ratio was 0.5 (95% CI 0.2-0.9). The risk of CIN II/III decreased further with increasing years of barrier method use. Recency, latency, and age at first barrier method use were all associated with a reduced risk of CIN. Men and women should carefully consider the range of benefits of barrier method use as a means to reduce their risk of unwanted pregnancies, sexually transmitted diseases, and cervical neoplasia.

Adult↗

PubMed1992

Oral contraceptive use and cervical intraepithelial neoplasia.

To explore the somewhat controversial relationship between oral contraceptives and pre-invasive cervical cancer, 103 cases of biopsy-confirmed cervical intraepithelial neoplasia (CIN) II or CIN III were compared with 258 controls who had normal cervical cytology. Cases were slightly less likely than controls to have ever used oral contraceptives; the odds ratio, controlling for age, socioeconomic status, barrier method use, smoking history, age at first sexual intercourse, number of sex partners, current marital status, and number of Pap smears, was 0.7 (95% CI 0.3-1.6). Recency, latency, duration, and age at first oral contraceptive use were evaluated and in no instance was oral contraceptive use positively associated with CIN. This study adds to the body of knowledge that oral contraceptives are not associated with pre-invasive cervical cancer. Further, if oral contraceptive users continue to be regularly screened, their risk of developing the more invasive lesions should be very low.

Adolescent↗

PubMed1990

Atypical metaplasia and incidence of bronchogenic carcinoma.

The prognostic implication of atypical squamous metaplasia of the respiratory tract has been uncertain, especially for mild atypia. The relation between degree of severity of atypical metaplasia as detected by sputum cytology and incidence of bronchogenic carcinoma was assessed among 14,414 men aged 45 years or older who smoked one or more packs of cigarettes per day. Trial participants underwent sputum cytologic evaluations every 4 months for an average of 7.4 years as part of the Cooperative Early Lung Cancer Detection Program of the National Cancer Institute and were followed for the development of lung cancer between 1971 and 1983 at three institutions: The Johns Hopkins University, the Memorial Sloan-Kettering Cancer Center, and the Mayo Clinic. Analysis with logistic regression controlling for age, race, occupational exposures to lung carcinogens, average number of cytology records per year, and smoking habits revealed that the estimate of the relative rate (RR) of developing bronchogenic carcinoma was greater among men who had mild atypia as compared with men who had negative cytology readings, but there were marked differences among institutions (RR = 1.1, 95% confidence interval (Cl) 0.8-1.5 at The Johns Hopkins University; RR = 1.6, 95% Cl 1.1-2.5 at the Memorial Sloan-Kettering Cancer Center; and RR = 2.5, 95% Cl 1.6-4.0 at the Mayo Clinic). Results suggest that mild atypia as detected by cytologic evaluation of sputum is an indicator of a modest elevation in risk of bronchogenic carcinoma.

Carcinoma, Bronchogenic↗

PubMed1990

Principles of bladder cancer screening in an intervention trial.

Screening for preclinical disease in asymptomatic people is an accepted activity in occupational health programs, public health programs, and physicians' offices. Yet, only diseases with high morbidity and mortality, a detectable, prolonged preclinical phase, and treatment that can improve survival if applied before the onset of clinical manifestations are suitable for screening. Furthermore, the screening test must be simple to perform, acceptable to providers and recipients, safe, reasonably pain-free, low-cost, and a valid estimator of the true disease state. Even so, screening will succeed only if the condition has a high prevalence in the population being screened, in order that enough persons with disease are identified and treated to justify the cost and the stress experienced by screen-positive, disease-negative subjects. The ultimate goal of screening is to reduce disease-specific mortality. The one recognized study design that can demonstrate a reduction in mortality from cancer of the urinary bladder is a randomized, controlled clinical trial of a screening modality, eg, urinary cytology, in a population previously exposed to occupational carcinogens.

Bias↗

PubMed1990

Oral contraceptives and breast cancer: a case-control study with hospital and community controls.

Several recent reports have noted an increase risk of breast cancer associated with the use of oral contraceptives (OCs) among various subgroups of young women. These reports spurred us to analyze data from a case-control study in North Carolina of 158 breast cancer patients, 326 hospital controls, and 1140 community controls less than 60 years of age. A logistic regression model was used to calculate odds ratios and 95% confidence intervals and to control for potential confounders. No association between ever-use of OCs and the risk of breast cancer was found for cases compared with either control group. No increased risk was observed for OC use before age 25 or before first full-term pregnancy, or in relation to duration of use, recency of use, or time since first use. Analysis of the subgroup of women less than 45 years of age also showed no relationship between OC use and breast cancer risk. However, an elevated risk of breast cancer was observed among nulliparous women with 5 or more years of OC use in comparisons with hospital controls (odds ratio 7.8) and community controls (odds ratio 2.3). This analysis was based on small numbers of subjects and the 95% confidence intervals touched or overlapped with 1. An unexpected association between duration of OC use and breast cancer risk was found among older premenopausal women in comparisons of cases with both control groups. For these women, a trend was evident in the odds ratio by duration of OC use, and the comparison between cases and community controls was statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1989

Dietary fat and breast cancer: case-control and cohort studies.

An increased risk of breast cancer in relation to a high-fat diet has been reported in several case-control studies and one cohort study conducted in different parts of the world. Most of these studies provide data on the consumption of food groups high in animal fats, e.g., meats and dairy products. Studies reporting on the amount of fat constituents consumed, adjusted or unadjusted for total caloric intake, more frequently have shown no positive association. The latter studies are not all limited to countries such as the United States with an overall high dietary fat intake; one was reported from Japan where the traditional low-fat diet is giving way to more Western-style foods, resulting in greater dietary heterogeneity for the population. The hypothesis that dietary fat causes breast cancer has been seriously weakened by the recent negative reports from two U.S. cohort studies, employing well-recognized dietary assessment strategies and multivariable analytic methods. Still, the possibility exists that specific fat constituents either naturally present or produced during the food preparation process, or fats in the presence (or absence) of other foodstuffs could alter breast cancer risk. Different kinds of studies providing information on the biochemistry and biology of fats consumed by humans would help to give focus to future epidemiological studies.

Breast Neoplasms↗

PubMed1988

Cancer screening. Degrees of proof and practical application.

The purpose of this paper is to clarify the short-term and long-term objectives of screening for various cancers, and to indicate the kinds of data that are needed to determine whether or not the objectives are met. Cancers at various sites differ with respect to their innate suitability for screening. Criteria that enhance screening suitability include the potential for serious complications and a high rate of mortality (applicable to most cancers), a prolonged preclinical phase, and an existing therapy that is simpler and more effective in reducing the mortality rate when applied to preclinical disease than to clinically evident cancer. Tests and procedures suitable for screening are simple to perform, inexpensive, acceptable to patients and physicians, safe, relatively painless, and accurate, as measured by the test's sensitivity and specificity. The actual yield of previously undiagnosed cancer arising from a screening program will depend heavily on prevalence of disease in the screened population, specificity of the screening test, and successful follow-up of screen-positive patients with diagnosis and treatment. These issues are discussed in the context of four cancers and their respective screening modalities: cervical cancer and cytologic studies, breast cancer and mammography, colon cancer and fecal occult blood tests, and lung cancer and sputum cytologic studies. The quality of data on which screening decisions have been made for each of these cancers and tests varies. The cancers vary in terms of their relevant biologic characteristics and treatment effectiveness. Similarly, each screening procedure has its own particular advantages and disadvantages. Current American Cancer Society Guidelines for early detection of three of the cancers are presented.

Humans↗

PubMed1988

Benefits and risks of menopausal estrogen and/or progestin hormone use.

Current evidence is reviewed here on risks and benefits of estrogen and progestin use by peri- and postmenopausal women in relation to the following conditions: endometrial cancer, breast cancer, osteoporosis, and coronary artery disease (CAD). On balance, estrogen therapy appears to be beneficial for menopausal women, as it probably reduces the risks of CAD and osteoporosis, two of the major causes of mortality and morbidity. Although unopposed estrogen therapy increases the risk of endometrial cancer, that cancer is relatively rare and is not fatal in the vast majority of cases associated with estrogen use. Definitive conclusions about the relation of menopausal estrogens to breast cancer cannot be drawn due to inconsistent evidence to date. Although evidence from randomized controlled trials is lacking, biochemical and clinical evidence suggest that progestin supplementation is associated with a reduction in endometrial cancer risk in women taking menopausal estrogens. Progestin supplementation also may augment the beneficial effects of estrogens in providing protection against osteoporosis, although this effect is not yet well established. There is little direct evidence bearing on the relation of menopausal progestins to breast cancer. Although studies of CAD per se are lacking at present, progestins probably unfavorably alter lipoprotein profiles, thereby increasing a user's risk of CAD. Given the relatively high incidence and mortality of CAD in postmenopausal women, any negative effects on CAD risk could potentially counterbalance beneficial effects on other causes. We conclude that estrogen replacement therapy is of potential benefit to postmenopausal women, but that the question of progestin supplementation requires further study, particularly for CAD risk.

Breast Neoplasms↗

PubMed1987

Replacement estrogens and risk of gynecologic cancers and breast cancer.

The two cancers specific to women for which substantial research on their relationship to exogenous estrogens has been reported are endometrial cancer and breast cancer. With the former, the link to estrogen use is well established. The estrogen use patterns associated with increased risk of endometrial cancer are characteristic of a promotional agent. The example serves as a prototype model for the study of an adverse health effect subsequent to a prescribed medication. However, modification in estrogen prescribing patterns have lowered significantly the endometrial cancer risk for patients. A relationship between estrogen replacement therapy and breast cancer is difficult to assess. Despite biologic plausibility, large epidemiologic studies have shown no association between estrogen use and breast cancer occurrence. Those studies suggesting a relationship find it concentrated in the high dose estrogen products and possibly among women who have had a prior bilateral oophorectomy. A convincing resolution to the current uncertainty is likely to require new approaches in laboratory, clinical, and epidemiologic research. Larger studies investigating more refined hypotheses within the same conceptual confines are unlikely to be productive.

Breast Neoplasms↗

PubMed1987

A case-control study of skin cancer in the tire and rubber manufacturing industry.

A case-control study was conducted in the tire and rubber manufacturing industry to examine the association of squamous cell carcinoma of the skin with rubber manufacturing materials presumed to be contaminated by polycyclic aromatic hydrocarbons. Sixty-five cases were compared to 254 matched controls for exposure to carbon black, extender oils, lubricating oils, rubber solvents, and rubber stock. Both magnitude and duration of exposure were compared using data from company personnel records. Rubber stock and lubricating oils were associated with skin cancer. The relative risk (RR) associated with the highest levels of rubber stock exposure was 2.2, and with the highest level of lubricating oil exposure it was 6.5. In analysis of subgroups of study members, the associations were strongest among workers who were born after 1900 (rubber stock, RR = 11.6; lubricating oil, RR = 4.5) and among workers whose skin cancer was diagnosed before the age of seventy (rubber stock, RR = 23.2; lubricating oil, RR = 28.3).

Adult↗

PubMed1987

Medical, life-style, and occupational risk factors for prostate cancer.

Information on suspected risk factors for prostate cancer was obtained from in-person interviews as part of a case-control study of tissue sex hormone receptors and serum hormone levels. The risk factors examined were medical history (including venereal disease), sexual history, smoking, alcohol consumption, and occupational exposures. Study subjects were 40 prostate cancer patients and 64 benign prostatic hyperplasia controls who were newly diagnosed during 1984-1985 at North Carolina Memorial Hospital in Chapel Hill. Subjects were white and black men aged 50 years and older. Comparisons of cases' and controls' past medical histories did not support a venereal disease hypothesis of prostate cancer etiology. The most prominent finding is an association with farming employment: 75% of cases compared to 38% of controls reported farmwork occupations. Exposures to pesticides and herbicides, while more common among the patients, did not account for the association detected for farming. No relationship was observed with cadmium exposure, the most frequently cited occupational risk factor for prostate cancer.

Adenocarcinoma↗

PubMed1987

Androgen receptors detected by autoradiography in prostatic carcinoma and benign prostatic hyperplastic tissue.

Androgen receptor (AR) content in prostatic tissues from patients with either cancer or benign prostatic hyperplasia (BPH) is of interest from at least two standpoints: receptors may be a feature of the pathogenesis of these conditions, and they may be important to the management and prognosis of prostatic cancer patients. For these reasons, a quantitative autoradiographic assay for AR content in prostatic tissues has been developed. Application of autoradiography to rodent tissues yielded results that were highly correlated with those from biochemical assays. Thus, the autoradiographic analyses with human tissues reported in this paper were undertaken. Average AR content in 22 prostatic carcinomas was lower than that in tissues from 14 patients with BPH; the median values of the affinity index, the quantitative estimate of receptor content, were 7.0 and 12.0, respectively. For the cancer tissues, a trend of declining receptor content with advancing stage of disease appeared but was not statistically significant. No association between receptor content and degree of tumor aggressiveness as measured by Gleason score and MD Anderson score was evident. Patient age and race were not related to receptor content in either type of tissue.

Aged↗

PubMed1987

Serum hormone levels among patients with prostatic carcinoma or benign prostatic hyperplasia and clinic controls.

This study sought to identify differences in serum hormone levels between prostatic cancer (CaP) patients, benign prostatic hyperplasia (BPH) patients, and clinic controls (CC). Serum testosterone, estradiol, and prolactin values were obtained from 35 CaP, 42 BPH, and 161 CC patients attending a single medical center between January 1984 and April 1985. Relative risk estimates adjusted for age and race were calculated to compare hormone values between each case group and the CC. The distributions of hormone values and the testosterone to estradiol (T/E) ratios were grouped into thirds with the lowest third forming the reference category. The relative risk estimates for BPH in the middle and high thirds of testosterone were greater than unity (1.26 and 2.10, respectively), whereas the relative risk estimates in the middle and high thirds of estradiol were less than unity (0.63 and 0.35, respectively). For the middle and high thirds of the T/E ratio, the relative risk estimates for BPH showed statistically significant three- to fourfold increases. Modest depression of serum testosterone and estradiol was noted for CaP patients compared to CC, although the differences were not statistically significant. This depression was interpreted to be a likely result of the malignant process rather than a cause of it, whereas the development of clinically evident BPH was felt to be a biologically plausible response to an elevated T/E ratio.

Age Factors↗

PubMed1987

The influence of exogenous estrogen use on survival after diagnosis of endometrial cancer.

For examination of the effect of prior exogenous estrogen use on survival after diagnosis of endometrial cancer, 244 endometrial cancer cases newly diagnosed at North Carolina Memorial Hospital, Chapel Hill, North Carolina, between 1970 and 1976 were followed until 1982. Estrogen users (n = 46) were younger, had less advanced disease, and were more likely to be nonobese and white than were nonusers (n = 198). The estimated probability of surviving (Kaplan-Meier) five years after diagnosis was 0.89 for users and 0.53 for nonusers. When adjusted for age, grade, stage, obesity, race, and treatment (using the Cox proportional hazards regression model), the survival probabilities throughout the period of observation for estrogen users continued to be higher. The adjusted hazard rate for a nonuser was 2.05 (95% confidence interval (Cl) 0.96-4.39) times that for an estrogen user. The adjusted hazard rate from endometrial cancer only was 4.01 (95% Cl 1.22-13.21) times greater among estrogen nonusers. The more frequent occurrence of endometrial cancer in an earlier stage and grade among estrogen users may not be the sole cause of their lower hazard rate from this disease.

Adult↗

PubMed1987

Cigarette smoking, alcohol consumption, and breast cancer risk.

The effects of cigarette smoking and alcohol consumption on breast cancer risk were investigated in 276 primary, histologically confirmed breast cancer patients and 1,519 community-based comparison subjects identified in 1977 and 1978 in North Carolina. Data on both behaviors and other pertinent personal and medical characteristics were obtained by interview. Analytic methods included stratification and logistic regression. Among current cigarette smokers of 1-20 cigarettes per day and over 20 per day, the odds ratios (ORs) adjusted for age, race, alcohol consumption, estrogen use, and oral contraceptive use for breast cancer were 0.75 [95% confidence interval (CI) 0.52-1.09] and 0.57 (95% CI 0.30-1.08), respectively. A decrease in risk was not seen in former smokers. With respect to alcohol consumption, the adjusted OR for those having one drink or more per week compared to those having less than one was 1.45 (95% CI 0.99-2.12). If the comparison was ever versus never drinkers, the adjusted OR was 1.47 (95% CI 1.10-1.97); for current drinkers versus nondrinkers, the adjusted OR was 1.89 (95% CI 1.40-2.56). The ORs were adjusted for age, race, cigarette smoking, estrogen use, an oral contraceptive use. These data supports those reports showing an inverse association of cigarette smoking and a positive association of alcohol consumption with breast cancer risk.

Adult↗

PubMed1986

Screening for cancer: lessons learned.

The purpose of this paper is to clarify the objectives of screening programs, particularly for cancer, characteristics of diseases suitable for screening, features of suitable screening tests, levels of program evaluation, and evidence on the advantages and disadvantages of screening. Diseases suitable for screening are those leading to serious morbidity and high mortality, those with a prolonged preclinical phase in their natural course, and those for which effective therapy is available following early diagnosis. Useful screening procedures have documented validity, acceptability, and safety and are performed with relative ease and modest cost. These generic issues in cancer screening are examined in the context of screening for cervical, breast, and lung cancer. Each of these cancers illustrates how to weigh different kinds of evidence when advocating or rejecting screening.

Adult↗