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Biomedical subjects

M S Tockman

Publications and source records attributed to M S Tockman.

At least 19 recordsLinked to original sources
PubMed1995

Rapid decline in FEV1. A new risk factor for coronary heart disease mortality.

Coronary heart disease (CHD) is the leading cause of mortality in the United States. The present cohort study was conducted to determine whether rate of FEV1 loss independently predicts CHD mortality in apparently healthy men. White male Baltimore Longitudinal Study of Aging (BLSA) participants without CHD underwent clinical evaluation at 2-yr intervals; 883 had satisfactory pulmonary and lipid studies and returned for a least one visit. Cases were BLSA subjects without CHD on entry who died a "coronary death" (death from acute myocardial infarction, sudden death, or congestive heart failure in the presence of coronary artery disease). Forced expiratory maneuvers followed American Thoracic Society guidelines. Serum cholesterol, blood pressure, cigarette smoking, and body mass index were obtained from the BLSA database. There were 79 CHD deaths and 804 survivors during an average follow-up of 17.4 yr. After adjustment for age, initial FEV1% predicted, smoking status, hypertension, and cholesterol, a time-dependent proportional hazards model showed that cardiac mortality, but not all causes of mortality, generally increased with increasing quintile of FEV1 decline for the entire cohort (relative risk [RR] 2.92-5.13) and separately for the subset of never-smokers. Thus, excess CHD mortality follows a large decline in FEV1, independent of the initial FEV1% predicted, cigarette smoking, and other common CHD risk factors.

Adolescent↗
PubMed1994

Microsatellite alterations as clonal markers for the detection of human cancer.

Microsatellite instability has been reported to be an important feature of tumors from hereditary nonpolyposis colorectal carcinoma (HNPCC) patients. The recent discovery of genetic instability in small cell lung carcinoma, a neoplasm not associated with HNPCC, led us to investigate the possible presence of microsatellite alterations in other tumor types. We examined 52 microsatellite repeat sequences in the DNA of normal and tumor pairs from 100 head and neck, bladder, and lung cancer patients by the polymerase chain reaction. Although alterations were rare in dinucleotide repeats, larger (tri- or tetranucleotide) repeats were found to be more prone to expansion or deletion. We screened 100 tumors with a panel of nine tri- and tetranucleotide repeat markers and identified 26 (26%) that displayed alterations in at least one locus. This observation prompted us to examine the possibility of using microsatellite alterations as markers to detect clonal tumor-derived cell populations in pathologic samples. The identical microsatellite alterations detected in the primary tumors were successfully identified in corresponding urine, sputum, and surgical margins from affected patients. This study demonstrates that appropriately selected microsatellite loci are commonly altered in many cancers and can serve as clonal markers for their detection.

Base Sequence↗
PubMed1994

Dietary n-3 polyunsaturated fatty acids and smoking-related chronic obstructive pulmonary disease. Atherosclerosis Risk in Communities Study Investigators.

BACKGROUND: Fish contain n-3 polyunsaturated fatty acids, principally eicosapentaenoic acid and docosahexaenoic acid, which are known to interfere with the body's inflammatory response and may be of benefit in chronic inflammatory conditions. METHODS: We studied the relation between the dietary intake of n-3 fatty acids and chronic obstructive pulmonary disease (COPD) in 8960 current or former smokers participating in a population-based study of atherosclerosis. Intake of fatty acids was estimated with a dietary questionnaire. The presence of COPD was assessed by a questionnaire on respiratory symptoms and by spirometry. Three case definitions of COPD were used: symptoms of chronic bronchitis (667 subjects), physician-diagnosed emphysema reported by the subject (185 subjects), and spirometrically detected COPD (197 subjects). RESULTS: After control for pack-years of smoking, age, sex, race, height, weight, energy intake, and educational level, the combined intake of eicosapentaenoic acid and docosahexaenoic acid was inversely related to the risk of COPD in a quantity-dependent fashion. The adjusted odds ratio for the highest quartile of intake as compared with the lowest quartile was 0.66 for chronic bronchitis (95 percent confidence interval, 0.52 to 0.85; P < 0.001 for linear trend across the range of intake values), 0.31 for physician-diagnosed emphysema (95 percent confidence interval, 0.18 to 0.52; P for linear trend, 0.003), and 0.50 for spirometrically detected COPD (95 percent confidence interval, 0.32 to 0.79; P for linear trend, 0.007). CONCLUSIONS: A high dietary intake of n-3 fatty acids may protect cigarette smokers against COPD.

Aged↗
PubMed1994

Does dietary vitamin A protect against airway obstruction? The Atherosclerosis Risk in Communities (ARIC) Study Investigators.

A recent report based on data from the first National Health and Nutrition Examination Survey suggested that low intake of vitamin A may be associated with a greater risk of airway obstruction. We attempted to replicate these findings in a population-based sample of middle-aged adults (n = 15,743) who participated in the baseline examination of the Atherosclerosis Risk in Communities (ARIC) Study. Vitamin A intake was estimated from a 66-item food frequency questionnaire, and the presence of airway obstruction was determined by spirometry. Although airway obstruction was associated in ARIC with well-established risk factors such as age, sex, and smoking, there was little evidence for a role of vitamin A. With only one exception, vitamin A intake was unrelated to airway obstruction in all smoking categories using either categorical or continuous measures of lung function (FEV1, FVC, FEV1/FVC). Only among current smokers in the upper tertile of lifetime cigarette smoking (> 41 pack-years) was the odds ratio of having airway obstruction for the lowest quartile of vitamin A intake compared with the highest quartile elevated (1.7 [95% confidence interval 1.1 to 2.7]). Despite some biological plausibility that vitamin A intake may prevent obstructive lung disease, the inability to demonstrate association in a larger population study, with better estimation of usual dietary intake, casts doubt on the existence of causal relationship.

Airway Obstruction↗
PubMed1994

The early detection of second primary lung cancers by sputum immunostaining. LCEWDG Investigators. Lung Cancer Early Detection Group.

STUDY OBJECTIVE: To determine whether monoclonal antibody (Mab) detection of tumor-associated antigen expressed on sputum epithelial cells precedes clinical presentation of second primary lung cancer. DESIGN SETTING/PARTICIPANTS: Eleven oncology centers collaborate in the accrual of 1,000 patients with stage I non-small cell lung cancer (NSCLC) who had undergone resection. The Mabs examined in this study (624H12, 703D4) detect two promising oncofetal/differentiation markers (ie, a difucosylated Lewis X and a 31-Kd glycoprotein antigen). INTERVENTIONS: Induced sputum specimens are evaluated for quality, then are Papanicolaou and immunostained by independent central laboratories at enrollment and annually thereafter. The predictive value of Mab markers is compared with routine morphologic study for detection of second primary lung cancer during an anticipated 3 years of accrual and 1 year of follow-up. MEASUREMENTS AND RESULTS: Five hundred eighty of an anticipated 1,000 patients have been accrued on schedule. Patients are primarily white (88.6%), former smokers (75.9%), men (55.6%), with a median age of 66.7, and joined the study at an average of 3.7 years following resection of a stage 1 NSCLC (34.4% squamous, 43.6% adenocarcinoma). Central laboratories found less dysplasia and more unsatisfactory specimens (27.3%) than do the accrual institution laboratories. Immunostaining identifies more suspicious cells than does morphologic study. However, only two second primary lung cancers (eight total deaths) have occurred to date. CONCLUSIONS: Halfway through the accrual, we describe the study design and preliminary observations. This study illustrates rational selection of carcinogenesis markers by linkage of marker expression on preneoplastic specimens with subsequent expression on tumor tissue.

Aged↗
PubMed1993

Cytometric validation of immunocytochemical observations in developing lung cancer.

Video-enhanced optical microscopy objectively confirms that immunocytochemical biomarker supplementation of routine cytology permits separation of (1) "pre"-cancer epithelial cells from JHLP screened individuals who subsequently developed lung cancer from (2) similarly atypical epithelial cells from JHLP participants who did not. The establishment of a bank of sputum cytology specimens along with a data respository of 5-yr follow-up and clinical outcome had permitted banked specimens to be immunostained and scored against a gold standard of subsequent histologic lung cancer. A highly skilled cytopathologist, interpreting immunostained screening sputum specimens and blinded to the clinical outcome, originally was able to correctly predict clinical outcome with 88.7% accuracy compared to this "gold standard" (Tockman et al., J Clin Oncol 1988;6:1685-1693). This study presents an independent confirmation of that earlier immunocytochemical classification through feature extraction of digitally recorded, transmission optical microscope video images of immunostained, moderately atypical sputum cells from the original slides.

Cytodiagnosis↗
PubMed1993

Biomarkers of carcinogen exposure and cancer risk in a coke plant.

To evaluate the association between an indicator of carcinogen exposure (peripheral blood leukocyte DNA adducts of polycyclic aromatic hydrocarbons) and an early indicator of neoplastic transformation (sputum epithelial cell membrane antigens binding by monoclonal antibodies against small cell lung cancer and against nonsmall cell lung cancer), a survey of 350 coke-oven workers and 100 unexposed workers was planned. This paper reports a pilot investigation on a subgroup of 23 coke-oven workers and 8 unexposed controls. A "gas regulator" worker with positive tumor antigen binding was identified. Results show that smokers, subjects with decreased pulmonary function (forced expiratory volume in 1 sec/forced vital capacity% < 80), and those with morphological dysplasia of sputum cells have higher levels of DNA adducts. The gas regulators showed the highest values for adducts; however, no significant difference of adduct levels was found between the coke-oven group and unexposed controls.

Adult↗
PubMed1992

Considerations in bringing a cancer biomarker to clinical application.

Specific challenges face our application of emerging biomarkers to early lung cancer detection. These challenges might be considered frontiers to be bridged between established biomedical disciplines, requiring expertise often beyond the range of individual investigators. Cross-disciplinary research already has led to new appreciation of the mechanisms which underlie the phenotypic expression of the transformed cell and places within our grasp the tools which might lead to successful early lung cancer detection. Prior to the successful application of newly described markers, further cross-disciplinary research must (a) refine the selection of biologically appropriate markers, (b) validate such markers against acknowledged disease end points, (c) establish quantitative criteria for marker presence/absence, and (d) confirm marker predictive value in prospective population trials.

Biomarkers, Tumor↗
PubMed1992

Rational targets for the early detection of lung cancer.

The fact that routinely effective treatments for disseminated lung cancer are not available has prompted the search for effective early detection systems. It is important to identify lung cancer while it is still confined to the bronchial epithelium and is potentially curable with local modalities. We have previously reported on an immunologically based assay to identify antigens expressed on shed bronchial epithelial cells. This assay resulted in a statistically significant correlation of immunostaining with the eventual development of lung cancer 2-4 years prior to routine clinical detection. Attempts to further improve this approach require an understanding of the basis for its success. Based on the work of Hakomori and coworkers, this difucosylated Lewis X structure would be a likely marker of carcinogenic transformation of the bronchial epithelium. In fact, an antibody to this structure was useful for sputum immunocytochemistry analysis for early lung cancer detection. Other carbohydrate structures would also be reasonable markers to evaluate for early detection application, based on the known pattern of expression of these structures in fetal, dysplastic, and neoplastic lung tissue. Another antibody used for sputum immunostaining recognizes a 31-kd protein structure; the antibody is not a known member of a likely class of early detection targets. The reported cases of lung cancer missed by the immunostaining approach included principally adenocarcinoma of the lung, suggesting that the addition of a marker(s) of that type of morphologic differentiation should be considered. Markers to dissect the various forms of lung adenocarcinoma are being characterized and are available for evaluation in early detection applications.(ABSTRACT TRUNCATED AT 250 WORDS)

Antigens, Neoplasm↗
PubMed1991

Pulmonary function and respiratory symptoms in wildland firefighters.

We studied cross-seasonal changes in pulmonary function and respiratory symptoms in 52 wildland firefighters in Northern California. The mean cross-seasonal change in forced expiratory volume in 1 second (FEV1) was -1.2% (95% confidence interval [CI] -0.5%, -2.0%) with a corresponding mean change in forced expiratory volume (FVC) of -0.3% (95% CI 0.4%, -1.0%). Decreases in FEV1 and FVC were most strongly associated with hours of recent fire-fighting activity (P = .002 and .01, respectively). When the study group was divided into three categories based on recent fire-fighting activity, firefighters in the high activity category (mean +/- SE, 73 +/- 7 hours of fire-fighting in previous week) had a -2.9% (130 mL) change in FEV1 and a -1.9% (102 mL) change in forced vital capacity (FVC). There was a significant cross-seasonal increase in most respiratory symptoms evaluated. Several symptoms (eye irritation, nose irritation, and wheezing) were associated with recent fire-fighting. These findings suggest that wildland firefighters experience a small cross-seasonal decline in pulmonary function and an increase in several respiratory symptoms. Research is under way to identify the fire conditions and specific components of exposure that produce pulmonary irritants, and to examine the potential reversibility of acute pulmonary change.

Adolescent↗
PubMed1990

Serum retinol and airway obstruction.

The relation of serum retinol and carotenoids to airway obstruction was investigated in a population-based study. Respiratory symptoms and the pulmonary function of 83 white males were assessed in 1979 5 years after their blood had been drawn. Airway obstruction in 1979, defined as a forced expiratory volume in 1 second which was equal to or less than 75% of the forced vital capacity, was associated with a decreased 1974 level of serum retinol.

Aged↗
PubMed1989

Biological monitoring of fire fighters: sister chromatid exchange and polycyclic aromatic hydrocarbon-DNA adducts in peripheral blood cells.

Fire fighters are exposed to potentially carcinogenic combustion and pyrolysis products during the course of their work. The present study was designed to test 43 fire fighters and matched controls for DNA damage which might be related to occupational carcinogen exposures. Using peripheral blood lymphocytes, we examined (a) baseline sister chromatid exchange (SCE) frequency and (b) SCE induction by in vitro mutagenic challenge with mitomycin C. Using nucleated peripheral blood cells, we examined (c) polycyclic aromatic hydrocarbon-DNA adduct levels by assessing benzo(a)pyrene diol epoxide (BPDE)-DNA antigenicity. Exposures were determined from histories of fire-fighting activity. The presence of confounding factors (e.g., tobacco smoking, charcoal-broiled food consumption, etc.) was determined by questionnaire. Plasma cotinine levels were measured to assess recent exposures to tobacco smoke. White fire fighters exhibited a significantly higher risk for the presence of detectable BPDE-DNA antigenicity than white controls (odds ratio, 3.4; 95% confidence interval, 1.08-10.5 after adjustment). Consumption of charcoal-broiled food less than 3 times a month was associated with a smaller proportion of individuals exhibiting measurable (positive) BPDE-DNA antigenicity, while consumption of broiled food greater than 3 times a month did not affect the proportion of positive individuals. Daily alcohol consumption was associated with a larger proportion of individuals exhibiting positive BPDE-DNA antigenicity, (P = 0.07). Tobacco smoking and charcoal-broiled food consumption, but not fire fighting, were associated with increased levels of baseline SCE. Sensitivity to SCE induced by mitomycin C in cultured peripheral lymphocytes was similar in fire fighter and control groups. However, sensitivity of individual fire fighters to mitomycin C-induced SCE was correlated with number of fires fought in the previous 24 h.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
PubMed1989

Respiratory risk factors and mortality: longitudinal studies in Washington County, Maryland.

Risk factors for temporal changes in chronic respiratory disease mortality were evaluated from two studies conducted in Washington County, Maryland. The first examined the mortality of a private census population (greater than 35,000 whites) enumerated in 1963 over two subsequent time periods by age, sex, and initial smoking status. The second examined the 10-yr mortality of a subset of the 1963 census (884 men who had undergone spirometry). We observed a fall in age-adjusted mortality from all causes and from arteriosclerotic heart disease (ASHD), but an increase in COPD mortality. However, the increase in these chronic pulmonary deaths is essentially confined to persons who were smoking cigarettes at the beginning of the study period. Furthermore, while smokers showed an increased mortality risk for all causes, the excess mortality risk did not fall uniformly across cigarette smokers. It is a major observation of this study that all-cause and cardiovascular (as well as pulmonary) mortality are significantly more often found among subjects with ventilatory impairment (independent of smoking status). Reasons for the association of ASHD mortality with impaired forced expiration are discussed. Thus, men at increased risk for three (ASHD, lung cancer, COPD) of the five leading causes of death (three of eight for women) may be identified by spirometry. Perhaps it is time that this test was more generally applied.

Adult↗
PubMed1988

Analysis of spirometric data from a national sample of healthy 6- to 24-year-olds (NHANES II).

The second National Health and Nutrition Examination Survey (NHANES II) incorporated spirometric examinations for a nationwide sample of individuals 6 to 24 yr of age. We analyzed spirometric data on 1,963 healthy, nonsmoking black and white subjects to derive prediction equations for FVC, FEV1, FEV3, PEF, Vmax50, Vmax75, and MMEF. The population was divided into three groups: children (6 to 11 yr of age); teens (males 12 to 20, females 12 to 17 yr of age); and young adults (males 21 to 24, females 18 to 24 yr of age). Using regression analysis, standing height appeared to be the most important predictor of pulmonary function across the entire age group, with the importance of the age variable decreasing in older ages. Controlling for other variables, blacks exhibited consistently lower respiratory function for most measures. This difference increased with age. Male FVC exceeded female FVC after 8 to 9 yr of age; however, female MMEF and Vmax50 performance equaled or exceeded males until approximately 13 yr of age. Males tended to outperform females with the same anthropometric characteristics in all age groups, except in the height range of 130 to 160 cm, where female flows and volumes were superior. Percentile growth curves were also developed to track lung development in clinical practice.

Adolescent↗
PubMed1988

Sex and race differences in the development of lung function.

The second National Health and Nutrition Examination Survey (1976 to 1980) provided spirometric examinations for a nationwide sample of individuals 6 to 24 yr of age. We analyzed spirometric data on 1,963 healthy, nonsmoking blacks and whites to examine sex and race differences in FVC, FEV1, FEV3, PEF, Vmax50, Vmax75, and mid-maximal expiratory flow (MMEF). The population was divided into three age groups: children (6 to 11), teens (males 12 to 20, females 12 to 17), and young adults (males 21 to 24, females 18 to 24). Controlling for sex, age, standing height, and body mass index, blacks had consistently lower levels of lung function for most measures. The inclusion of sitting height explained part of this reduction. Controlling for lung size using FVC as a surrogate, the performance of blacks on other spirometry measures was equal to whites in all age groups. Males tended to outperform females with the same anthropometric characteristics before the inclusion of FVC as a predictor variable. However, after controlling for lung size (FVC), female performance exceeded that of males. The higher female performance is particularly noticeable in the later flow measures. Both anatomic and physiologic factors may account for these findings.

Adolescent↗