The epidemiologic study of birth defects and pesticides.
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Abnormalities, Drug-Induced↗
Biomedical subjects
T Nurminen
Publications and source records attributed to T Nurminen.
Expression of CYP1A1, CYP1B1 and CYP3A, and polycyclic aromatic hydrocarbon-DNA adduct formation in bronchoalveolar macrophages of smokers and non-smokers.
Variability in the expression of enzymes metabolizing carcinogens derived from cigarette smoke may contribute to individual susceptibility to pulmonary carcinogenesis. This study was designed to determine the effects of smoking and 3 major cytochrome P450 (CYP) enzymes, i.e., CYP1A1, CYP1B1 and CYP3A, which metabolize polycyclic aromatic hydrocarbons (PAH) on PAH-DNA adduct formation in the bronchoalveolar macrophages (BAM) of 31 smokers and 16 non-smokers. CYP protein levels were determined by immunoblotting and PAH-DNA adduct levels by the nuclease P1 enhanced (32)P-postlabeling method. The expression of specific CYP forms was confirmed by reverse transcriptase-polymerase chain reaction (RT-PCR) from 10 additional samples. CYP3A protein, CYP3A5 by RT-PCR, was detected in the majority of samples from smokers and non-smokers. The levels of CYP3A appeared to be lower in active smokers than in ex-smokers (p = 0.10) or never smokers (p = 0.02). CYP1A1 was not detectable by either immunoblotting or RT-PCR. The expression of CYP1B1 was low or undetectable in most samples. The PAH-DNA adduct levels were higher (mean 1.57/10(8) nucleotides) in samples from smokers compared with non-smokers (mean 0.42/10(8) nucleotides, p < 0.001) and the number of adducts correlated with the number of cigarettes smoked daily (regression analysis, p < 0. 001). Higher levels of adducts were detected in samples from smokers with a high level of CYP3A compared with those with a low level (regression analysis, p = 0.002). As CYP3A5 is abundant in both lung epithelial cells and BAM, its association with adduct formation suggests that this CYP form may be important in the activation of cigarette smoke procarcinogens.
Adult↗
Leukocyte adhesion--an integrated molecular process at the leukocyte plasma membrane.
Leukocyte adhesion is of pivotal functional importance, because most leukocyte functions depend on cell-cell contact. It must be strictly controlled, both at the level of specificity and strength of interaction, and therefore several molecular systems are involved. The most important leukocyte adhesion molecules are the selectins, the leukocyte-specific beta2-integrins and the intercellular adhesion molecules. The selectins induce an initial weak contact between cells, whereas firm adhesion is achieved through integrin intercellular adhesion molecular binding. Although studies during the past twenty years have revealed several important features of leukocyte adhesion much is still poorly understood, and further work dealing with several aspects of adhesion is urgently needed. In this short essay, we review some recent developments in the field.
Carbohydrate Metabolism↗
Spontaneous abortions among Finnish flight attendants.
We conducted a retrospective cohort study to investigate whether work as a cabin attendant is related to an increased risk for spontaneous abortion. Data on female cabin crew members were linked to medical records on pregnancies. There were 1751 eligible pregnancies for the final analysis. Flight attendants who worked during early pregnancy had a slightly elevated risk of spontaneous abortion, as compared with attendants who were pregnant outside a time span of active flying (odds ratio [OR] = 1.3; 95% confidence interval [CI], 0.9 to 1.8). During the earliest years of the study period (1973 through 1977), the risk seemed to be decreased (OR = 0.4; 95% CI, 0.2 to 1.1), whereas during the later years (1978 through 1994) the risk was increased (OR = 1.6; 95% CI, 1.1 to 2.4). The results are in agreement with earlier studies, showing suggestive evidence of a slightly increased risk of spontaneous abortion among female cabin crew members.
Abortion, Spontaneous↗
Methodologic issues in epidemiologic risk assessment.
This paper reviews methodologic issues pertinent to the application of epidemiology in risk assessment and discusses concerns in the presentation of results from such an activity. Assessment of the health risks associated with occupational and environmental exposures involves four phases: hazard identification, i.e., the detection of the potential for agents to cause adverse health effects in exposed populations; exposure assessment, i.e., the quantification of exposures and the estimation of the characteristics and sizes of the exposed populations; dose-response assessment, i.e., the modeling for risk realization; and risk characterization, i.e., the evaluation of the impact of a change in exposure levels on public health effects. The risk-assessment process involves limitations of exposure data, many assumptions, and subjective choices that need to be considered when using this approach to provide guidance for health policy or action. In view of these uncertainties, we suggest that the provision of estimates of individual risk and disease burden in a population must be accompanied by the corresponding estimates of precision; risks should be presented in a sufficiently disaggregated form so that population heterogeneities are not lost in the data aggregation; and different scenarios and risk models should be applied. The methods are illustrated by an assessment on the health impacts of exposure to silica.
Decision Support Techniques↗
Shift work and reproductive health.
Nonstandard workhours may disturb normal body functions, but their relation to reproductive outcome is poorly understood. Two newly published studies suggest an association between rotating shift work and prolonged waiting time to pregnancy. Seven of nine studies on spontaneous abortion suggest that some forms of shift work may be associated with increased risk. Four studies indicate that shift work including night schedules may be related to preterm birth. Moreover, some results have related rotating schedules to intrauterine growth retardation. In the published studies, the type of work schedule examined has varied, and the applied definition of shift work has not necessarily been clear. The main interest areas, however, have been work involving evening and night shifts, rotating or changing schedules, and the irregularity of work patterns. Although the evidence is not ample and remains ambiguous, it is prudent to consider shift work as a potential risk to reproduction.
Abortion, Spontaneous↗
Pulmonary expression of glutathione S-transferase M3 in lung cancer patients: association with GSTM1 polymorphism, smoking, and asbestos exposure.
To characterize the relative roles of glutathione S-transferases (GST) M1 and M3 in the susceptibility to lung cancer, the pulmonary expression of GSTM3 was quantified immunochemically and related to the GSTM1 genotype in 100 lung cancer patients. Among active smokers and recent ex-smokers (for 6 years or less), parenchymal GSTM3 expression was lower in patients with a homozygous GSTM1 null genotype than in those who were GSTM1 positive and had similar smoking habits (P < 0.001 and P = 0.004, respectively). However, in long-term ex-smokers (for 15 years or longer) GSTM3 was not affected by the GSTM1 genotype. Among active smokers and recent ex-smokers who were homozygous GSTM1 null, those with a definite or probable exposure to asbestos expressed GSTM3 at significantly higher levels than those for whom it was unlikely (P = 0.04). A similar effect of the homozygous GSTM1 null genotype on GSTM3 expression was not detected in the bronchial epithelium when GSTM3 was visualized immunohistochemically. Different mechanisms may result in an increased risk of either squamous cell or adenocarcinomas in patients with the homozygous GSTM1 null genotype. Low expression of GSTM3 due to smoking in the parenchymal lung of GSTM1 null individuals can theoretically favor the development of adenocarcinoma. Our data indicated a predominance of this tumor type in patients with low expression of GSTM3.
Adult↗
Agricultural work during pregnancy and selected structural malformations in Finland.
We studied the relation between birth defects and maternal agricultural work in a nationwide time- and area-matched case-referent series of 1,306 pairs of infants (581 orofacial clefts, 365 central nervous system defects, 360 skeletal defects) obtained through the Finnish Register of Congenital Malformations. We supplemented the Register data, including the mothers' latest and previous pregnancies, diseases, consumption of drugs and alcohol, smoking habits, and the like, with detailed interviews on the mothers' work conditions. When all of the birth defects were pooled and agricultural work was compared with nonagricultural work in the first trimester of pregnancy, the adjusted odds ratio was 1.4 [95% confidence interval (CI) = 0.9-2.0]. For orofacial clefts, the corresponding odds ratio was 1.9 (95% CI = 1.1-3.5). An industrial hygienist's blinded assessment indicated that seven mothers of infants with orofacial clefts and three reference mothers had been exposed to pesticides in agricultural work; the adjusted odds ratio for work with pesticide exposure, when compared with unexposed agricultural work, was 1.9 (95% CI = 0.4-8.3). Exposure to solvents did not explain the observed association.
Abnormalities, Drug-Induced↗
On adjusting for the outcome of previous pregnancies in epidemiologic reproductive studies.
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Abortion, Spontaneous↗
Maternal pesticide exposure and pregnancy outcome.
Exposure to pesticides is inherent in many agricultural jobs. Most of the interest in connection with pesticides and pregnancy outcome has been directed to birth defects. Some indications of an elevated risk of limb anomalies have been associated with ecologic exposure, maternal environmental exposure to pesticides determined by the mother's place of residence, and parental occupation involving potential pesticide exposure. Orofacial clefts have been related to maternal environmental exposure to pesticides and exposure in agricultural work. Moreover, there is evidence that maternal agricultural occupation and pesticide exposure may be associated with elevated risk of spontaneous abortion and stillbirth. However, some studies have found no indication of reproductive hazards but, altogether, the epidemiologic evidence is inconclusive as regards the risk of adverse pregnancy outcome.
Abortion, Spontaneous↗
Female noise exposure, shift work, and reproduction.
In addition to having possible direct effects on the fetus, noise induces a stress reaction in the mother, possibly causing reproductive disturbances. In shift work, many physiological functions and systems that are circadian in nature can be disturbed. Study results indicate that occupational noise at the level of approximately 85 dB LAeq(8 h) or higher and shift work, especially rotating schedules, may have independent negative effects on birth weight and length of gestation. Some forms of shift work have also been associated with early fetal loss. Moreover, some results have related noise exposure and shift work to menstrual disturbance and infertility. Although the evidence is not ample, it is prudent to consider exposure to high-level noise and shift work as risks to reproduction.
Birth Weight↗
Combined effect of CYP1A1 inducibility and GSTM1 polymorphism on histological type of lung cancer.
The combinations of the CYP1A1 inducibility and GSTM1 polymorphism have been investigated in relation to the histological type and peripheral or bronchial location of lung cancer in 54 surgically treated, current smoker lung cancer patients. The induced CYP1A1 was detected in 46 patients (85%) and the homozygous GSTM1 null genotype in 32 patients (59%). The role of CYP1A1 inducibility was found to be more important than that of GSTM1 polymorphism, because the non-inducible CYP1A1 was associated solely with bronchial tumours (P = 0.001), mainly squamous cell carcinomas. In patients with inducible CYP1A1, the expressing GSTM1 gene appeared to have a protective effect against contracting bronchial lung cancer, since 88% (14/16) of the lung tumours in this patient group were peripheral, whereas almost equal numbers of peripheral and bronchial tumours were observed in those patients lacking the gene (P = 0.037).
Aryl Hydrocarbon Hydroxylases↗
On classifying reproductive studies according to study design and using odds ratios in the presentation of results.
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Epidemiologic Methods↗
Physical work load, fetal development and course of pregnancy.
The effects of physical work load during pregnancy were analyzed in connection with a nationwide case-referent study that screened for associations between selected structural malformations and occupational exposures. The strain of the occupational activities of 1475 mothers of malformed infants and an equal number of mothers of noncase babies was assessed from a description of the work tasks by an expert using a standardized method reflecting energy expenditure. The noncase mothers' experience revealed a relation between physical load and growth retardation that has also been suggested by other epidemiologic studies. No relation was found between an increase in mean physical load and the occurrence of threatened abortion; yet work involving much standing had an increased risk. Mothers whose work included occasional high physical loads had more pregnancy-induced hypertension. The data showed unexpected associations between physical load and structural malformations.
Abortion, Threatened↗
Shift work, fetal development and course of pregnancy.
Information on 1475 mothers of infants with selected structural malformations and an equal number of mothers of "normal" babies was analyzed for a possible relationship between shift work and adverse pregnancy outcome or a complicated course of pregnancy. The primary data were obtained from the Finnish Register of Congenital Malformations supplemented by special interviews on the mothers' work conditions. No signs of a teratogenic risk were observed. The relationship between course of pregnancy and outcomes other than malformations was determined from the noncase mothers' experience. Threatened abortion and pregnancy-induced hypertension were not associated with rotating shift work alone, but in a noisy work environment moderate risks could not be ruled out. Rotating shift work was associated with a slight excess of babies small for their gestational age independently of noise exposure. The results suggest that further studies on the effects of different work schedules on pregnancy are worth consideration.
Adult↗
Occupational noise exposure and course of pregnancy.
The study examined the possible relation of occupational noise exposure to adverse pregnancy outcomes. The experience of 1,190 reference mothers from a case-referent study based on the Finnish Register of Congenital Malformations was scrutinized. Exposure to noise was blindly assessed from a description of the mother's workday by two industrial hygienists. Women with an estimated level of noise of around 80 dB LAeq(8 h) or higher were considered exposed. Threatened abortion was not associated with noise exposure alone, but, when it was combined with shift work, the adjusted risk was over twofold. The adjusted risk of pregnancy-induced hypertension was twice as high among the mothers exposed to noise in shift work, and the duration of their pregnancy was shorter. The analyses produced indications of a relation between noise and growth retardation which was not connected with shift work. There were significantly ascending trends in the proportions of these outcomes according to increasing exposure intensity.
Abortion, Threatened↗
Noise exposure during pregnancy and selected structural malformations in infants.
The study tested the hypothesis of exposure to noise during pregnancy being teratogenic. It included 1,475 Finnish mothers who had given birth to a malformed child (orofacial cleft or structural defect of the central nervous system, skeleton, or heart and great vessels) and 1,475 reference mothers. A special interview soon after delivery yielded the primary information on exposure. Of the 783 mothers who reported noise exposure in the first trimester, 370 were case mothers and 413 were referents. Hygienic assessment indicated that 102 case mothers and 103 referents had been exposed in the first trimester to a sound level of around 80 dB LAeq(8 h) or higher, the overall odds ratio being 1.0 (95% confidence interval 0.7-1.3). Adjustment for potential confounders by logistic regression methods gave similar results. There was no obvious trend suggesting a hazard when different exposure categories were considered.
Congenital Abnormalities↗
Office employment, work with video display terminals, and course of pregnancy. Reference mothers' experience from a Finnish case-referent study of birth defects.
In an examination of the possible harmful effects of work in an office environment and the use of a video display terminal (VDT) on the course of pregnancy, the experience of 1,475 reference mothers from a Finnish case-referent study of birth defects was analyzed. The study was based on the national Register of Congenital Malformations, whose data were supplemented with special interviews on mothers' work conditions. The group which worked in an office environment consisted of 239 women, of whom 60 had worked with video display terminals; 805 mothers had not worked in an office. Only mothers who had worked during most of their pregnancy and who had a singleton birth were included; hence 431 women were excluded from the analysis. The information on threatened abortion, length of gestation, birthweight, placental weight, and maternal blood pressure was analyzed. Office work involved no elevated risk of threatened abortion when compared with nonoffice work, and among the VDT users the proportion with symptoms related to an impending early termination of pregnancy was similar to that of other office workers. No unfavorable effects on the length of gestation were observed between the compared groups, and there were no differences in the birthweight of the babies when adjustment was made for gestational age or the other aspects under consideration. Thus the results did not suggest that office employment or work with video display terminals would be harmful for pregnancy.
Abortion, Threatened↗