Biomedical subjects

P M Vacek

Publications and source records attributed to P M Vacek.

At least 19 recordsLinked to original sources

PubMed1998

Estrogen-receptor-related protein p29 in primary nonsmall cell lung carcinoma: pathologic and prognostic correlations.

BACKGROUND: Estrogen-dependent intracellular processes are important in the growth regulation of normal tissue and may play a role in the regulation of malignancies. Utilization of estrogen receptor assays in breast carcinoma is well established, but the role of such evaluation in other cancers largely is unknown. In this study, immunohistochemical expression of estrogen receptor (ER) and the ER-related protein p29 was correlated with survival of patients with nonsmall cell carcinoma of the lung. METHODS: All patients with a tissue diagnosis of primary nonsmall cell bronchogenic carcinoma diagnosed over a 6-year period at the Medical Center Hospital of Vermont were reviewed. Assays for p29 and ER using a streptavidin-biotin immunoperoxidase method were performed on each tumor. Results were correlated with clinical data, including survival. RESULTS: Of 111 tumors examined, 109 (98%) were positive for p29 whereas none of the tumors reacted with ER (ER1D5). The relation between p29 expression and survival time was different for men and women. A statistically significant negative relation for women was observed; this relation was most pronounced in patients with Stage I and II tumors. A positive but not statistically significant relation was observed for men. CONCLUSIONS: The ER-related protein p29 commonly is expressed in nonsmall cell carcinomas of the lung. The relation between p29 and survival time is different for males and females, suggesting the presence of gender specific factors that may influence tumor growth and overall patient survival, especially in patients with early stage lung carcinoma.

Adenocarcinoma↗

PubMed1998

Gene mutations with characteristic deletions in cord blood T lymphocytes associated with passive maternal exposure to tobacco smoke.

We have investigated the molecular effects of passive maternal cigarette exposure in a newborn population and consider the possible implications of the observed genetic changes in the development of neoplastic diseases in children. We present a distribution analysis of somatic mutational events in a reporter gene, HPRT, in cord blood T lymphocytes from newborns after transplacental exposure to cigarette smoke. Analysis of 30 HPRT mutant isolates from 12 newborn infants born to mothers with no evidence of environmental exposure to cigarette smoke and 37 HPRT mutant isolates from 12 infants born to mothers exposed to passive cigarette smoke showed a significant difference in the HPRT mutational spectrum in those exposed in utero to cigarette smoke. The most notable change was an increase in 'illegitimate' genomic deletions mediated by V(D)J recombinase, a recombination event associated with hematopoietic malignancies in early childhood. Recent epidemiological studies of maternal and paternal cigarette smoke exposure and childhood cancers may need to be re-interpreted, given these results.

Base Sequence↗

PubMed1998

Effects of the intensity and timing of asbestos exposure on lung cancer risk at two mining areas in Quebec.

Mortality data from 9609 workers at two asbestos mining areas in Quebec were analyzed to assess the effects of the intensity and timing of exposure on lung cancer risk. Summary exposure measures based on differing assumption were computed for lung cancer cases and matched controls and were fitted to the data using conditional logistic regression. A non-linear relationship between intensity and risk fit both mining areas, but risk was greater at one area than the other. At the mine with lower risk, exposure occurring more than 30 years prior to death had little effect, while at the other mine risk did not vary with time since exposure and men starting employment before 1924 were at elevated risk. The results point to differences in dust composition at the two areas and illustrate the difficulties in estimating risk.

Adult↗

PubMed1998

Estimated gains in birth weight associated with reductions in smoking during pregnancy.

OBJECTIVE: To compare the estimated effect on birth weight of reductions in maternal cigarette consumption and urinary cotinine during pregnancy. STUDY DESIGN: An observational study of 641 women with complete data on cigarette consumption, urinary cotinine and infant birth weight. Correlation and regression analyses were used to examine relationships between birth weight, cigarette consumption and urinary cotinine at first and last prenatal visits. RESULTS: Correlations of cigarette consumption and urinary cotinine with infant birth weight were -.23 and -.30 (first visit) and -.26 and -.31 (last visit); all P values were < .001. The regression equation relating urinary cotinine concentrations at first and last visits to infant birth weight explained a significantly larger proportion of the variability in birth weight than the equation relating cigarette consumption at these visits to infant birth weight, 11% vs. 7%, P = .04. Among continuing smokers, both equations predicted gains in birth weight in association with reductions in cigarette consumption, but quitting smoking before the first visit was associated with the most weight gain. As compared to the average infant birth weight of a woman who smoked 20 cigarettes per day throughout pregnancy, the estimated gain in birth weight would be 105 g if she cut down by 10 cigarettes per day after the first visit, 210 g if she quit after this visit and 310 g if she quit before the first visit. CONCLUSION: For women still smoking at their first prenatal visit, infant birth weight is already compromised, but subsequent reductions in cigarette consumption are associated with gains in birth weight. For women who cannot quit smoking, these reductions need to be substantial if increases in birth weight of > 100 g are to be achieved.

Adult↗

PubMed1997

The effects of maternal cigarette smoke exposure on somatic mutant frequencies at the hprt locus in healthy newborns.

We utilized the hprt T-cell cloning assay to prospectively determined the somatic mutant frequency at the hprt locus of fetal T-lymphocytes exposed in utero to maternal active and passive cigarette smoke. In addition, a maternal questionnaire was administered to evaluate a number of social and medical parameters that may effect hprt mutant frequency. Newborn cord blood plasma cotinine levels were determined on all subjects to compare in utero tobacco metabolite levels with maternal smoking histories. A total of 63 newborns were enrolled and placed into four groups: Group I (n = 21), newborns whose mothers had no history of active or passive cigarette exposure during the pregnancy; Group II (n = 12), newborns whose mothers actively smoked cigarettes throughout the pregnancy; Group III (n = 8), newborns whose mothers actively smoked cigarettes during first trimester only; and Group IV (n = 22), newborns whose mothers were exposed only to passive cigarette smoke. Our analysis showed no statistically significant difference in hprt mutation frequency between any of the four groups. A significant increase in plasma cord blood cotinine was detected in Group II, newborns whose mothers were active cigarette smokers throughout the pregnancy. Our data indicate that exposure to active and passive maternal cigarette smoke in utero does not result in a significant increase in somatic mutant frequency as determined by the hprt T-cell cloning assay.

Clone Cells↗

PubMed1997

Assessing the effect of intensity when exposure varies over time.

In epidemiologic studies, analysis of the relationship between exposure intensity and risk is complicated by the fact that exposures often take place over extended periods, during which intensities can vary substantially. To relate exposure to outcome, it is necessary to combine information about duration, intensity and timing into a summary measure of exposure. If the aim of the exposure-response analysis is to estimate the risk associated with differing exposure intensities, the results depend on the manner in which one incorporates intensity into the summary exposure metric. Most metrics used to summarize exposure, such as the cumulative exposure index, are time-weighted summations of intensity. They are thus based on the assumption that for any fixed time point, the effect of a unit of exposure is proportional to its intensity. This paper describes an approach for constructing and fitting summary measures of exposure that one can use to incorporate alternative assumptions about the effect of exposure intensity, as well as effects relating to the timing of exposure. Data from a study of lung cancer mortality in asbestos miners and millers serve to illustrate the method. Exposure metrics based on various functions of intensity and time of exposure are constructed and fitted to the data using conditional logistic regression. The results demonstrate how the choice of a function for quantification of exposure can affect the exposure-response analysis and the risk estimates it yields.

Asbestos↗

PubMed1997

Smoking in pregnancy, exhaled carbon monoxide, and birth weight.

OBJECTIVE: To examine the relation of cigarette consumption and exhaled carbon monoxide levels during pregnancy and to assess the effect of these smoking measures on birth weight. METHODS: Cigarette consumption and exhaled carbon monoxide levels were recorded at the first prenatal visit and the 36-week visit from women who smoked early in pregnancy. Analysis of variance was used to compare birth weights for differing levels of cigarette consumption and exhaled carbon monoxide. Correlation and regression analyses were used to estimate the effects of the smoking measures at both prenatal visits on birth weight. RESULTS: Cigarette consumption and exhaled carbon monoxide levels at both visits were associated significantly with birth weight. After the first prenatal visit, a reduction in cigarette consumption of at least nine cigarettes per day or in exhaled carbon monoxide of 8 parts per million (ppm) was associated with gains in birth weight of 100 g or more. The proportion of low birth weight (LBW) infants increased significantly with increasing levels of cigarette consumption and with increasing concentrations of exhaled carbon monoxide. CONCLUSION: Substantial reductions in cigarette consumption or in exhaled carbon monoxide levels after the first prenatal visit are needed to achieve gains in birth weight. Not smoking, or having an exhaled carbon monoxide level less than 5 ppm minimizes the likelihood of having an LBW infant.

Adult↗

PubMed1997

Effects of low dose methotrexate on the bone mineral density of patients with rheumatoid arthritis.

OBJECTIVE: To determine the effects of low dose methotrexate (MTX) on bone mineral density (BMD) of patients with rheumatoid arthritis (RA). METHODS: We examined the relationship between BMD and disease modifying antirheumatic drug (DMARD) use with data from a prospective, randomized, placebo controlled trial assessing the effects of calcium and vitamin D3 supplementation on BMD of patients with RA. Measurements of BMD of the lumbar spine and femoral neck were performed at baseline and at yearly followup visits over 3 years. RESULTS: Information about DMARD use and BMD was available for 133 patients at baseline, and for 95 patients at Year 3. Lumbar spine and femoral neck BMD of MTX and non-MTX treated patients were similar at the start of the study. At the end of 3 years of followup, there was no significant differences in the change in BMD of the femoral neck and lumbar spine in MTX and non-MTX treated patients, in general. However, patients treated with prednisone > or = 5 mg/day plus MTX had greater loss of BMD in the lumbar spine than patients treated with a similar dose of prednisone without MTX (difference -8.08% over 3 years; p = 0.004). CONCLUSION: At the end of 3 years, low dose MTX use was not associated with change in femoral neck or lumbar spine BMD in patients who were not treated with corticosteroids. However, among patients treated with prednisone > or = 5 mg/day, combined treatment with MTX and prednisone was associated with greater bone loss in the lumbar spine than treatment with prednisone without MTX.

Absorptiometry, Photon↗

PubMed1996

Calcium and vitamin D3 supplementation prevents bone loss in the spine secondary to low-dose corticosteroids in patients with rheumatoid arthritis. A randomized, double-blind, placebo-controlled trial.

BACKGROUND: Therapy with low-dose corticosteroids is commonly used to treat allergic and autoimmune diseases. Long-term use of corticosteroids can lead to loss of bone mineral density and higher risk for vertebral fractures. Calcium and vitamin D3 supplementation is rational therapy for minimizing bone loss, but little evidence for its effectiveness exists. OBJECTIVE: To assess 1) the effects of supplemental calcium and vitamin D3 on bone mineral density of patients with rheumatoid arthritis and 2) the relation between the effects of this supplementation and corticosteroid use. DESIGN: 2-year randomized, double-blind, placebo-controlled trial. SETTING: University outpatient-care facility. PATIENTS: 96 patients with rheumatoid arthritis, 65 of whom were receiving treatment with corticosteroids (mean dosage, 5.6 mg/d). INTERVENTION: Calcium carbonate (1000 mg/d) and vitamin D3 (500 IU/d) or placebo. MEASUREMENTS: Bone mineral densities of the lumbar spine and femur were determined annually. RESULTS: Patients receiving prednisone therapy who were given placebo lost bone mineral density in the lumbar spine and trochanter at a rate of 2.0% and 0.9% per year, respectively. Patients receiving prednisone therapy who were given calcium and vitamin D3 gained bone mineral density in the lumbar spine and trochanter at a rate of 0.72% (P = 0.005) and 0.85% (P = 0.024) per year, respectively. In patients receiving prednisone therapy, bone mineral densities of the femoral neck and the Ward triangle did not increase significantly with calcium and vitamin D3. Calcium and vitamin D3 did not improve bone mineral density at any site in patients who were not receiving corticosteroids. CONCLUSION: Calcium and vitamin D3 prevented loss of bone mineral density in the lumbar spine and trochanter in patients with rheumatoid arthritis who were treated with low-dose corticosteroids.

Adult↗

PubMed1995

Effects of low dose corticosteroids on the bone mineral density of patients with rheumatoid arthritis.

OBJECTIVE: To assess the effect of low doses of corticosteriods on the bone mineral density (BMD) of patients with rheumatoid arthritis (RA). METHODS: A cross sectional study of BMD as measured by dual photon x-ray of the femoral neck and lumbar spine (lateral view) in 139 patients with RA followed in a university setting. RESULTS: The mean daily dose of prednisone taken by the study group was 4.15 mg/day. Patients receiving daily doses of prednisone between 1 to 4 mg/day had similar BMD to patients who were not receiving corticosteroids, but patients taking 5-9 mg/day and those taking > 10 mg/day had significantly lower BMD of the lumbar spine (84.28 and 80.51% of controls, respectively) than patients who received 1-4 mg/day (99.16% of controls). The effect of corticosteroids remained significant when other risk factors such as disease severity, disease duration, functional class, and activity level were controlled for. No significant relationship between prednisone dose and BMD of the femoral neck was seen at the low doses studied. CONCLUSION: Low dose corticosteroid use has a significant effect on BMD of the lumbar spine.

Absorptiometry, Photon↗

PubMed1994

Determination of hprt mutant frequencies in T-lymphocytes from a healthy pediatric population: statistical comparison between newborn, children and adult mutant frequencies, cloning efficiency and age.

Somatic cell mutant frequencies at the hprt locus of the X-chromosome were measured with the T-lymphocyte cloning assay in a healthy pediatric population. Assays were performed on 49 subjects (29 males and 20 females) ranging in age from 0.08 to 15.2 years. A statistical analysis of the thioguanine-resistant (TGr) mutant frequency (MF), unselected cloning efficiency (CE) and age was performed using data obtained in this study and those previously obtained in our laboratory on 66 newborn umbilical cord blood samples and 230 adult blood samples. For statistical comparisons pediatric subjects were divided into 4 groups. Group I included cord blood samples (age 0 years); Group II were subjects between 0 and 5 years; Group III were between 6 and 11 years and Group IV were between 12 and 17 years. The ln MF of Groups I and II were significantly lower than Groups III and IV (p < 0.05). The mean ln MF for each of Groups I-IV was significantly lower than the adult value. The cloning efficiency for Group I was significantly lower than that for Groups II-IV and adults. The relationships among the ln MF, unselected CE and age were expressed by the equations: ln (MF) = 0.945 -2.453 CE (p < 0.001) and ln (MF) = 0.114 + 0.063 age (p 0.004). The slope coefficients for unselected CE and age were significantly different from adults (p < 0.05). Regression analysis of combined data from Groups I-IV and adults were performed using both age and unselected CE as well as terms to reflect differences in their relationships with ln MF in adults and children. The results showed that the intercept and the age coefficients differ significantly for children and adults after adjustment for CE and yielded the following equations: ln (MF) = 0.548 -1.676 CE + 0.075 age, (Groups I-IV) and ln (MF) = 2.263 -1.676 CE + 0.014 age (adults). An alternative statistical model using ln (age ), ln (MF) = 0.381 -1.767 CE + 0.673 ln (age + 1), (p < 0.001), describes the rapid increase in MF with age that levels off in late adolescence. These findings demonstrate the changing influence of age on mutant frequency in the pediatric population as compared to the adult populations. These studies also illustrate that the increase in background somatic mutant frequencies at the hprt locus in T-lymphocytes is not linear from birth to adolescence and is significantly different from that seen in the adult population.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

PubMed1994

Traditional and nontraditional histopathologic predictors of recurrence in uterine endometrioid adenocarcinoma.

Ninety-three consecutive operative cases of myometrial invasive endometrioid adenocarcinoma of the uterus without evidence of extrauterine spread at surgery were reviewed to determine whether any histopathologic features other than those traditionally reported might predict recurrence. Recurrence was associated with traditionally analyzed features of deep myometrial invasion, high FIGO grade, vascular space invasion, and cervical stromal invasion as well as patient age. In addition, a diffuse pattern of myometrial invasion was associated with an increased risk for recurrence. Contrary to results from previous studies, no increased risk was seen with high nuclear grade or the presence of perivascular lymphocytic infiltrates. When adjusted for traditional parameters, perivascular lymphocytes and a tumor-host inflammatory response were associated with prolonged time to recurrence. A desmoplastic host response or residual adenomyosis were unrelated to recurrence.

Abdominal Neoplasms↗

PubMed1994

Development of a community breast screening promotion program using baseline data.

The process of developing a comprehensive community-based breast screening program for the Breast Screening Program Project is presented in this article. Behavior change theories were used to develop a program effects model which served as the conceptual foundation for a comprehensive breast screening program. This program would enlist professional and lay resources to promote breast screening through public and physician education and through improved access to mammography. Baseline survey data were used to focus program components on educational needs of women ages 40 and older for participating in regular mammography, clinical breast exam, and breast self-exam. The program effects model was also used as an evaluation framework to specify the intermediate changes that will be accomplished to reach a hypothesized 15% increase in screening participation between a study area receiving the program and two comparison areas. Results of this study will be of immediate value to other communities planning breast screening promotion programs.

Adult↗

PubMed1994

Comparability of telephone and household breast cancer screening surveys with differing response rates.

We compared telephone and household surveys as methods for obtaining information about breast cancer screening. The study population was comprised of women age 40 years or older who were permanent residents of two large areas of Florida. We contacted women using random digit dialing for the telephone survey. We used a stratified multistage design for the household survey. Response rates were 49% (telephone) and 77% (household). Distributions of most screening (mammography, clinical examination, and breast self-examination) and demographic variables were comparable for the two surveys; income was higher in the telephone survey. Both surveys underestimated the proportion of older women, based on 1990 Census data.

Adult↗

PubMed1993

Metallothionein in human lung carcinoma.

Eleven pairs of surgically resected lung cancers and corresponding non-neoplastic lung tissue were evaluated for metallothionein (MT) and metal content (cadmium and copper) by the heme/109Cd binding assay and atomic absorption spectroscopy, respectively. Tissue samples, obtained from patients ranging in age from 51 to 79, included six adenocarcinomas, two small cell carcinomas, one mixed cell carcinoma, one squamous cell carcinoma, and one carcinoma of non-primary origin (i.e., melanoma). Paired t-tests showed that metallothionein and copper concentrations in lung tumor tissue were significantly elevated when compared to non-malignant lung tissue. Cu was the major metal associated with the 10 kDa MT fraction in lung tumors whereas Cd was the primary metal bound to MT from non-neoplastic lung tissue. Since Cu-thionein is also known to be elevated in fetal lung tissue, the possibility exists that MT might represent an oncodevelopmental product which is useful as a biomarker for the early detection of lung carcinoma.

Adenocarcinoma↗

PubMed1993

Measurement of HPRT mutant frequencies in T-lymphocytes from healthy human populations.

Somatic cell mutant frequencies at the hprt locus of the X-chromosome were measured with the T-lymphocyte cloning technique in healthy human populations. A statistical analysis was performed of assays from 232 individuals (77 males and 155 females) ranging in age from 19 to 80 years. Data from 4 donor groups were compiled: (a) 132 participants in a study of identical and fraternal twins; (b) 17 health care workers studied as part of an assessment of the risks of handling chemotherapeutic drugs; (c) 62 women with benign breast masses; and (d) 21 normal laboratory and office personnel. The relationship between age and mutant frequency (MF) was expressed by the equation: ln MF = 1.46 + 0.018 age (P < 0.001). Thus, MF increased by about 2% per year. Increases in cloning efficiency (CE) reduced the MF, as shown in the equation: ln MF = 2.91 - 1.32 CE (P < 0.001). CE was significantly related to age (CE = 0.47 - 0.002 age, P = 0.038), and the interdependent relationship between MF, age and CE expressed by the equation: ln MF = 1.99 - 1.13 CE + 0.016 age was significant at the P < 0.001 level. There was no statistically significant effect of donor gender or smoking history on MF in our population, but CE was significantly lower in males (P < 0.001). These findings confirm the importance of age and CE as factors which influence the thioguanine-resistant MF in circulating T-lymphocytes from normal adults.

Adult↗

PubMed1992

Expression of antioxidant enzymes in rat lungs after inhalation of asbestos or silica.

Several studies indicate that active oxygen species play an important role in the development of pulmonary disease (asbestosis and silicosis) after exposure to mineral dust. The present study was conducted to determine if inhaled fibrogenic minerals induced changes in gene expression and activities of antioxidant enzymes (AOE) in rat lung. Two different fibrogenic minerals were compared, crocidolite, an amphibole asbestos fiber, and cristobalite, a crystalline silicon dioxide particle. Steady-state mRNA levels, immunoreactive protein, and activities of selected AOE were measured in lungs 1-10 days after initiation of exposure and at 14 days after cessation of a 10-day exposure period. Exposure to asbestos resulted in significant increases in steady-state mRNA levels of manganese-containing superoxide dismutase (MnSOD) at 3 and 9 days and of glutathione peroxidase at 6 and 9 days. An increase in steady-state mRNA levels of copper, zinc-containing superoxide dismutase (CuZnSOD), was observed at 6 days. Exposure to asbestos also resulted in overall increased enzyme activities of catalase, glutathione peroxidase and total superoxide dismutase in lung. In contrast, silica caused a dramatic increase in steady-state levels of MnSOD mRNA at all time periods and an increase in glutathione peroxidase mRNA levels at 9 days. Activities of AOE remained unchanged in silica-exposed lungs. In both models, increases in gene expression of MnSOD correlated with increased amounts of MnSOD immunoreactive protein in lung and the pattern and extent of inflammation. These data indicate that the profiles of AOE are dissimilar during the development of experimental asbestosis or silicosis and suggest different mechanisms of lung defense in response to these minerals.

Animals↗

PubMed1991

The translocation of inhaled silicon dioxide: an empirically derived compartmental model.

The movement of inhaled silicon dioxide particles was studied by measuring the amounts in alveolar fluid and cells, lung tissue, and lymphoid tissue during the 6 months following short-term aerosol exposure of Fischer 344 rats. A variety of first-order compartmental models were fit to data from nine exposure experiments to identify the most feasible biologic pathways for the transfer of material among these sites and out of the body. A multivariate least-squares approach was used to simultaneously fit the data from several compartments. The results indicate that transfer between alveolar cells and lung tissue occurs in both directions, suggesting that silica can reenter the alveolar space from the lung tissue. This feature has not been included in previously published models. The results also indicate that transfer from lung tissue to the mediastinal lymph nodes and thymus is indirect; there are one or more unidentified extrapulmonary compartments that receive silica from the lung. Rates of transfer among compartments were dependent on mineral type (quartz or cristobalite), heat treatment, and exposure dose. There was no evidence for direct clearance from the alveolar space via the tracheobronchial tract.

Animals↗