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Biomedical subjects

J A Stolwijk

Publications and source records attributed to J A Stolwijk.

At least 19 recordsLinked to original sources

Risk of congenital malformations associated with proximity to hazardous waste sites.

Concern about environmental pollutants has increased; however, it remains unclear whether chronic exposures to toxic chemicals in the environment occur at doses sufficient to produce adverse health effects in humans. To date, community studies have not adequately addressed this question. In this study, the authors linked two existing data bases of the New York State Department of Health to evaluate the relation between congenital malformations and residential proximity to hazardous waste sites in New York State. A total of 9,313 newborns with congenital malformations and 17,802 healthy controls living in proximity to 590 hazardous waste sites in 1983 and 1984 were evaluated. After the authors controlled for several possible confounding factors, results indicated that maternal proximity to hazardous waste sites may carry a small additional risk of bearing children with congenital malformations (odds ratio (OR) = 1.12, 95% confidence interval (Cl) 1.06-1.18). Higher malformation rates were associated with both a higher exposure risk (no exposure risk: OR = 1.00; low exposure risk: OR = 1.09, 95% Cl 1.04-1.15; high exposure risk: OR = 1.63, 95% Cl 1.34-1.99) and documentation of off-site chemical leaks (not exposed: OR = 1.00; exposed, but no leaks at site: OR = 1.08, 95% Cl 1.02-1.15; exposed, and leaks found at site: OR = 1.17, 95% Cl 1.08-1.27). The increased rates detected may be important in terms of their public health implications. Further research is necessary to strengthen causal inferences regarding the teratogenicity, of waste site exposure.

Adolescent

Isolation of two distinct epithelial cell lines from a single feline mammary carcinoma with different tumorigenic potential in nude mice and expressing different levels of epidermal growth factor receptors.

From a single spontaneous feline mammary carcinoma, two subpopulations of epithelial tumor cells have been isolated. The variant cells were established as cell lines designated K248C and K248P. DNA ploidy analysis showed that the two cell lines represented cell populations already present in the original tumor. Chromosome analysis confirmed the feline origin of K248C and K248P and demonstrated that in addition to unique marker chromosomes characteristic for each cell line, both cell lines had several marker chromosomes in common. These data suggest that the two cell populations arose from a hypothetical single ancestor which diverged during tumor progression. The K248C and K248P cell lines differed from one another with respect to their tumorigenicity in athymic mice and epidermal growth factor (EGF) receptor content. The K248C cells were highly tumorigenic as indicated by a short latency period and high take rate. The K248P cells were poorly tumorigenic. Southern blot analysis revealed that the K248C cells contained an amplified EGF receptor gene that was accompanied by elevated levels of EGF receptor RNA and protein. The K248C cells were growth inhibited in vitro at EGF concentrations that stimulated growth of K248P cells. The amplification of the EGF receptor gene could be detected only in DNA derived from K248C cells at high passage numbers and not in DNA derived from the original tumor and K248C cells at low passage numbers. These data suggest that amplification of the EGF receptor gene occurred during establishment of the K248C cell line.

Animals

Indoor 222Rn levels in New York State, North Carolina, and South Carolina.

Results are presented from approximately 9000 Rn measurements made in New York state, North Carolina, and South Carolina. The estimated statewide geometric mean concentrations were 28.1 Bq m-3 and 55.8 Bq m-3 for basements in New York state, 27.5 Bq m-3 for living rooms and 108.9 Bq m-3 for basements in North Carolina, and 25.0 Bq m-3 for living rooms in South Carolina.

Air Pollutants, Radioactive

Sick-building syndrome.

The sick-building syndrome (SBS) is defined as the occurrence of an excessive number of subjective complaints by the occupants of a building. These complaints include headache, irritation of the eyes, nose, and throat, lethargy, inability to concentrate, objectionable odors, and less frequently, nausea, dizziness, chest tightness, etc. These complaints will always be reported by a fraction of the occupants of any building if a questionnaire is administered that asks the respondent to recall any subjective symptoms they remember having had in the last 2 weeks or or over some period of time. It is often considered that SBS symptom reports have a minimum prevalence of about 15 to 20% for a 2-week recall period. SBS symptoms reported by 30% or more of occupants are indicative of conditions in the building environment that warrant attention. It is not often that a clear, single cause is responsible for the excess symptom reports. The following factors, often in combinations, are seen to contribute to SBS: outdoor air supply that is inadequate, ventilation distribution or effectiveness that is inadequate, the presence of temporary or long-term sources of contaminants such as tobacco smoke, adhesives, composite materials such as chipboard, and the growth of microorganisms in the HVAC equipment or in carpets or other furnishings. Depending on which causes contribute, the condition may be intermittent or even temporary. Psychosocial factors such as labor-management relations and satisfaction or dissatisfaction with other factors in the work environment can have a profound influence on the level of response of the occupants to their environment. Although hard data are difficult to collect, it is likely that productivity in the office environment is sensitive to conditions causing SBS.

Air Pollution, Indoor

Flow cytometric DNA ploidy analysis of feline mammary tumors.

Flow cytometric DNA analysis was performed on biopsies from 9 nonmalignant and 111 malignant (primary and metastatic) feline mammary lesions. In our series, 46.3% of the primary mammary carcinomas appeared to be aneuploid, whereas all but one benign breast lesion were diploid. The degree of aneuploidy in carcinomas was low, with a relatively high number of primary tumors (12 of 82) displaying hypodiploidy. Aneuploidy was not found to be correlated with any specific histological tumor type, vascular invasion, tumor size, or histological malignancy grade or with the separate components thereof. Comparison of the ploidy in primary and metastatic tumors from the same cases revealed a remarkable stability, both in time and location of appearance of the metastases. It is concluded that with respect to DNA ploidy feline mammary carcinoma has more in common with canine mammary carcinoma than with human mammary carcinoma. Further prospective studies are necessary to clarify the implications of aneuploidy in feline mammary carcinoma for tumor behavior and prognosis.

Aneuploidy

Simulation model of lung cancer incidence related to smoking and radon daughter exposure.

In recent years, the residential exposure to radon daughters has become a cause for concern as a contributing factor for lung cancer. In order to evaluate the population's risk consequences of different interpretations of the results of epidemiological studies in cohorts of uranium miners, a simulation model has been formulated. In the model, a defined population is generated as a set of individuals with a distribution of characteristics and exposures as they are known to exist in the defined population. The risk for each individual of being diagnosed with lung cancer in the next year can be determined, based on whatever interpretation is being evaluated. The risk can then be translated into an annual number of cases, and suitable controls can be identified as well. Both cases and controls have their individual risk factors of radon daughter exposure and history of cigarette smoking, and it is possible to subject these cases and controls to statistical analyses appropriate to case-control studies. This analysis can be used to see to what extent the original risk equation can be retrieved, and to what extent other risk formulations can be rejected. The simulation model can be used to evaluate conclusions drawn from prior epidemiological studies, as well as for evaluations of the effectiveness of designs for proposed studies.

Age Factors

Assessment of population exposure and carcinogenic risk posed by volatile organic compounds in indoor air.

A number of air pollutants are being found in low concentrations in indoor and outdoor air. Several studies have measured these concentrations for a large number of compounds in hundreds of residences. The concentrations range over several orders of magnitude over time and space. The log-normal distributions that are found make it possible to assess the impact on the health of populations, especially for genotoxic effects for which a threshold concentration is not expected to exist. Spreadsheets can be constructed which incorporate the unit risk of a substance for cancer, the distribution of concentrations of the substance in the population, and the size of the population into an assessment of the expected excess cases of cancer that can be attributed to the population exposure to such a toxicant. This approach allows for the evaluation of population risk for different substances as found in different environments, and for the evaluation of the relative efficacy of different strategies for population risk reduction.

Air Pollutants

Shelter and indoor air.

Improvements in outdoor air quality that were achieved through the implementation of the Clean Air Act accentuate the quality of the indoor air as an important, if not dominant, factor in the determination of the total population exposure to air contaminants. A number of developments are adding important new determinants of indoor air quality. Energy conservation strategies require reductions in infiltration of outdoor air into buildings. New materials introduced in the construction and in the maintenance of buildings are contributing new air contaminants into the building atmosphere. Larger buildings require more and more complex ventilation systems that are less and less under the individual control of the occupants. All of these factors contribute to the current reality that indoor air contains more pollutants, and often at higher concentrations, than outdoor air. Especially in the larger buildings, it will be necessary to assure that an adequate quantity of fresh air of acceptable quality is provided to each individual space, and that no new sources of pollutants are added to a space or a whole building without appropriate adjustments in the supply of fresh air.

Air Pollution

Representativity of human mammary tumor cell cultures: DNA-cytophotometry as a method for checking tumour cell characteristics.

Short term cultures (3-6 days) of 40 primary human mammary carcinomas were prepared and compared with the original tumours from which they were derived. As a criterion the nuclear DNA Frequency Distribution Pattern (FDP), cytophotometrically measured, was used. Comparisons were made between the FDPs of smears of freshly-cut tumour surfaces and their cultures. Twenty-nine (73%) cultures showed FDPs identical with the smears. Eleven cultures (27%) showed gross shifts in ratios between different peaks or showed a complete loss of one or more peaks in the FDP and were classified as not representative. Our results show that it is necessary to check primary mammary tumour cultures to determine whether or not they are representative of the original tumour. This is especially so if conclusions are to be drawn from the cultures about the original tumour. Analysis of FDPs in the cell islands of the cultures (migration of cells from attached clumps) resulted in a better understanding of the FDPs found in the smears. We showed that cultures of human mammary tumours either can be composed of cell islands with identical FDPs (diploid or aneuploid) or may show heterogeneity between different cell islands within one tumour.

Breast Neoplasms

Assessment of exposure to indoor air contaminants from combustion sources: methodology and application.

A methodology for assessing indoor air pollutant exposures is presented, with specific application to unvented combustion by-products. This paper describes the method as applied to a study of acute respiratory illness associated with the use of unvented kerosene space heaters in 333 residences in the New Haven, Connecticut, area from September 1982 to April 1983. The protocol serves as a prototype for a nested design of exposure assessment which could be applied to large-scale field studies of indoor air contaminant levels. Questionnaires, secondary records, and several methods of air monitoring offer a reliable method of estimating environmental exposures for assessing associations with health effects at a reasonable cost. Indoor to outdoor ratios of NO2 concentrations were found to be 0.58 +/- 0.31 for residences without known sources of NO2. Levels of NO2 were found to be comparable for homes with a kerosene heater only and those with a gas cooking stove only. Homes with a kerosene heater and a gas stove had average two-week NO2 levels approximately double those with only one source. Presence of tobacco smokers had a small but significant impact on indoor NO2 levels. Two-week average levels of indoor NO2 were found to be excellent predictors of total personal NO2 exposure for a small sample of adults. Residences with kerosene space heaters had SO2 levels corresponding to the number of hours of heater use and the sulfur content of the fuel. Formaldehyde levels were found to be low and not related to unvented combustion sources. NO2, SO2, and CO2 levels measured in some of the residences were found to exceed those levels specified in current national health standards.

Air Pollutants

Comparative thermoregulatory responses of resting men and women.

Three men and three women were exposed to transients of air temperature (range, 16--48 degrees C). Whole-body sweating rate, local tissue heat flows, and O2 consumption in the cold were linearly related to a weighted sum of tympanic and mean skin temperatures, called "central drive," During changes in air temperature, changes in subjects' scaled estimates of thermal sensation and discomfort led changes in the physiological responses and central drive. Women's thermoregulatory responses were similar to the men's, but were shifted toward higher (warmer) values of central drive. This shift was about 0.3 degrees C for responses to heat and about 0.6 degrees C for responses to cold. With respect to the women, the mean thus showed delayed responses to the cold, and approached steady state in the cold more slowly.

Body Temperature

Skin blood flow and sweating changes following exercise training and heat acclimation.

Eight subjects underwent an exercise training program (10 days at 75% VO2max for 1 h/day at 25 degrees C db/13 degrees C wb) and a heat-acclimation program (10 days at 50% VO2max for 1 h/day at 35 degrees C db/32 degrees C wb). The relations of chest sweat rate and of forearm blood flow to internal temperature were determined for each subject at a 25 degrees C ambient temperature before training, between training and acclimation, and following acclimation. Training shifted the vasodilation and sweating thresholds toward lower internal temperatures, and acclimation further lowered these thresholds. All threshold shifts were statistically significant (P less than 0.05). Training and acclimation both appeared to increase the slope of the sweating relation, but these effects were not statistically significant. Changes in the slope of the blood flow relation were small and inconsistent. Since arm blood flow is higher at any given internal temperature after acclimation, the lower blood flow which is reported to accompany heat acclimation must result from the lower body temperatures.

Acclimatization

Responses to the thermal environment.

Human responses to the thermal environment and to internal heat production serve to maintain a narrow range of internal body temperatures of 36-38 C. There are two categories of responses: voluntary or behavioral responses, and involuntary or physiological autonomic responses. Voluntary or behavioral responses consist generally of avoidance or reduction of thermal stress by modification of the body's immediate environment by modification of clothing insulation or by comfort conditioning of his microenvironment. Physiological responses consist of peripheral vasoconstriction to reduce the body's thermal conductance and increased heat production by involuntary shivering in the cold, and peripheral vasodilation to increase thermal conductance and secretion of sweat for evaporative cooling in hot environments. Autonomic responses are proportional to changes in internal and mean skin temperatures. Repeated exposures to heat, humidity, and exercise will modify the physiological response mechanisms by acclimation to produce more effective responses. Physiological responses also depend on the point in a diurnal cycle, on physical fitness, and on the sex of the individual. Behavioral responses rely on thermal sensations and thermal discomfort. Thermal discomfort appears to be closely related to the level of autonomic responses so that warm discomfort is closely correlated with skin wettedness, and cold discomfort similarly relates to cold extremities and shivering activity.

Acclimatization

Nocturnal lowering of thresholds for sweating and vasodilation.

Six subjects exercised on a bicycle ergometer at 60-70% of maximal aerobic power in a 25 degrees C ambient. Experiments on each subject were conducted at night (4:00-5:30 A.M.) and in daytime (noon-4:30 P.M.). Chest sweating rate (msw) was measured with resistance hygrometry. Forearm blood flow (BF), with an arm skin temperature of 35.5 +/- 1.2 degrees C (SD), was measured with electrocapacitance plethysmography. Esophageal temperature (Tes) was measured with a thermocouple at the level of the left atrium, and mean skin temperature (Tsk) was calculated from a weighted average of temperatures at three sites. Tes was corrected to a skin temperature of 33 degrees C as follows: T'es = Tes + (Tsk - 33 degrees C)/8. This correction reflects the relative contributions of Tes and Tsk to control of msw:T'es and BF:T'es relations were not consistently changed. In any given subject, thresholds for sweating and vasodilation were shifted about equally. These shifts averaged 0.57 degrees C (range: 0.23-0.93 degrees C)for msw and 0.63 degrees C (range: 0.17-0.98 degrees C) for BF.

Adult