How to assess long-term effects of occupational exposure.
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Adult↗
Biomedical subjects
P Paoletti
Publications and source records attributed to P Paoletti.
The assessment of respiratory function in a patient with dyspnoea and severe hypoxaemia.
In the investigation of dyspnoea and severe hypoxaemia the clinical relevance of multiple diagnostic techniques was studied. The patient was sequentially studied utilizing several techniques. The degree of lung impairment by spirometry, diffusing capacity for carbon monoxide, haemodynamics, pulmonary gas exchange, ventilation-perfusion relationships assessed by the multiple inert gases elimination techniques, ventilation and perfusion lung scans, gallium 67 scintigraphy, bronchoalveolar lavage and high resolution computerized tomography, twice over a period of 12 months during recovery under treatment. A marked impairment of pulmonary gas exchange was first explained by diffusion impairment and ventilation-perfusion mismatch. The multiple inert gas elimination technique allowed determination of the cause of hypoxaemia by ventilation-perfusion inequality. A pathological correlate of the ventilation-perfusion inequality was the appearance of honeycomb lungs detected by high resolution computed tomograph and active alveolitis by bronchoalveolar lavage. All results were consistent with a diagnosis of fibrosing alveolitis. The patient was evaluated again during treatment. Some functional improvement occurred despite persistence of the same pathological findings. In conclusion, this study demonstrates the value of information derived from different tests. Physiological correlations complemented by pathological observations expand understanding of the pathogenesis of disease. These procedures contribute to understanding mechanisms responsible for functional impairment.
Bronchoalveolar Lavage Fluid↗
CEASE (Collaborative European Anti-Smoking Evaluation): a challenging multicentre trail organized by the European Respiratory Society.
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Administration, Cutaneous↗
Simvastatin, an inhibitor of cholesterol biosynthesis, shows a synergistic effect with N,N'-bis(2-chloroethyl)-N-nitrosourea and beta-interferon on human glioma cells.
The effect of simvastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, on human glioma cell growth was investigated. When incubated with simvastatin, cell proliferation decreased in a concentration-dependent fashion, as measured by cell number and [3H]-thymidine incorporation into DNA (concentration producing 50% inhibition, 60 nM). The effect was detectable 12 h after cells were exposed to the drug and persisted for 2 days. Addition of mevalonate to cells exposed effect of simvastatin in combination with beta-interferon and N,N'-bis(2-chloroethyl)-N-nitrosourea, both antitumoral drugs, was also evaluated by cell growth inhibition assay. The concentration producing 50% inhibition for each of these drugs was 650 units/ml and 50 nM, respectively. Subliminal concentrations of beta-interferon or N,N'-bis(2-chloroethyl)-N-nitrosourea were incubated together with 1 nM simvastatin. The data were analyzed with the aid of an isobologram using the concept of an envelope of additivity. Simultaneous cell exposure to simvastatin with either N,N'-bis(2-chloroethyl)-N-nitrosourea or beta-interferon produced a strong synergistic inhibitory effect on cell proliferation. These data provide in vitro support for the possibility that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, utilized as plasma cholesterol-lowering agents, could potentiate the effect of antiblastic drugs on tumor growth.
Anticholesteremic Agents↗
Air pollution and health.
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Air Pollution↗
Residual volume in a general population. Effects of body size, age, cigarette smoking, and respiratory symptoms.
Residual volume (RV) was obtained by subtracting vital capacity from total lung capacity determined by the single breath helium dilution (TLCsb) to measure CO diffusing capacity in 2,680 subjects (8 to 64 years old) of a general population sample. There were 712 normal subjects (243 male and 469 female subjects) selected to evaluate the pattern of RV by age and to derive reference values for internal comparisons. From 8 to 20 years old, RV showed an increase because of the cross-sectional body size effect; after 20 to 30 years, RV was still increasing, however, at a lower level. Age and height coefficients were significantly related to RV in younger and older ages, both in male and female subjects. The RV percent predicted and RV/TLC percent were higher in smokers when compared to nonsmokers and exsmokers (the difference was significant in male subjects). A dose-response effect was observed between RV percent predicted, RV/TLC percent, and pack-years. The RV percent predicted and RV/TLC percent were significantly higher in smokers and nonsmokers with FEV1 percent predicted below the normal limit (the difference was significant in male subjects). Moreover, higher values of RV percent predicted and RV/TLC percent were observed in subjects with wheezy symptoms in male smokers and nonsmokers. A negative significant correlation was observed between RV/TLC percent and the diffusing capacity adjusted for lung volume (DL/VA) in smokers, exsmokers and nonsmokers of both sexes, confirming the hypothesis that the decrease in DL/VA may be ascribed to the enlargement of terminal air spaces. In conclusion, determination of RV by the single breath helium dilution method is suitable in epidemiology, and it allows additional important information for understanding the physiopathologic mechanisms related to the pathogenesis of chronic obstructive lung disease.
Adolescent↗
Bronchial hyperresponsiveness, genetic predisposition and environmental factors: the importance of epidemiological research.
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Air Pollution↗
[The soluble IL-2 receptor in malignant hemopathies].
The increase in the serum levels of the IL-2 receptors is due to its release both in vivo and in vitro from activated cells or neoplastic cells expressing it constitutively. The diagnostic, prognostic and physiopathologic significance of the sIL-2R was investigated by testing the serum of 271 haemopathic patients in various stages of the disease. In HCL the elevated sIL-2R level has a diagnostic value. In HD the sIL-2R level appears to be directly correlated with the extent of the disease and is equally important in the follow up of patients with HCL, NHL, HD, AL and MDS, where the serum level of the soluble receptor is usually associated with the biological and clinical activity of the disease. Unlike other B lymphoproliferations, patients with Multiple Myeloma on average show only slightly elevated levels of soluble receptor with no significant differences related to the stage or evolution. As for the chronic myeloproliferative disorders, we found only slightly elevated values in ET and PV, with frankly pathological values in CML during a blastic crisis or in the accelerated phase and in MFI during the clinically active phase of the disease.
Adult↗
Radioimmunoassay of glioma associated antigen in CSF and its usefulness for the diagnosis and monitoring of human glioma.
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Antigens, Neoplasm↗
A study on the biological behavior of human brain tumors. Part I. Arachidonic acid metabolism and DNA content.
The study of proliferative characteristics and biochemical aspects seem to be of great importance in order to define brain neoplastic behavior. The purpose of this study is to verify the existence of any possible correlation between Arachidonic Acid (AA) metabolism and proliferative characteristics in 30 meningiomas and 30 neuroepithelial tumors. The most represented metabolite in neuroepithelial tumors is TxB2, while 6-Keto-PGF1 alpha is the lowest represented product. Unimodal DNA distribution was observed in 66% of neuroepithelial tumors and in 87% of meningiomas. Aneuploidy was more frequent in glioblastomas and anaplastic meningiomas as previously reported; AA overall synthesis capacity and profile were similar between unimodal and bimodal cases of neuroepithelial tumors. Total AA metabolite, as well as TxB2 and PGD2, synthesis capacity are significantly higher in cases with S-phase cell percentage greater than or equal to 3% than in cases with S-phase % less than 3%. Total production of AA metabolites via the cyclooxygenase pathway is significantly higher in meningiomas with bimodal DNA distribution than in cases with unimodal DNA content; when considering S-phase cell percentage, similarly to what observed in neuroepithelial tumors, meningiomas with S% greater than 3% shows a significantly higher overall synthesis capacity for AA. AA metabolism capacity well correlates with proliferative patterns in neuroepithelial tumors: the relationship depends preferentially on TxB2 and PGD2 synthesis capacity. In cases of meningiomas, the amount of AA metabolites seem to be related to DNA content and proliferative activity when anaplastic features are histologically demonstrated.
Aneuploidy↗
A study on the biological behavior of human brain tumors. Part II: Steroid receptors and arachidonic acid metabolism.
The significance of steroid receptors (SR) in human brain tumors is presently a field of intense investigation in order to clarify some aspects of the biological behavior of these neoplasms. We studied the relationship between the presence of steroid receptors and the production of metabolites of the arachidonic acid cascade which have been reported to have a role in the biological behavior of some human tumors. We found that some metabolites of arachidonic acid are produced in different amounts in brain tumors which either did or did not express some steroid receptors. In particular the PGE2 were higher in estrogen receptors (ER) positive meningiomas than in ER negative ones and 6-keto-PGF1 alpha, the stable metabolite of prostacyclin, is significantly higher in androgen receptors (AR) negative meningiomas than in AR positive ones. In neuroepithelial tumors the glucocorticoid receptors (GR) positive cases synthesized more TxB2 and less PGE2 than the GR negative ones. Our data seem to suggest that some correlations exist between the presence of some steroid receptors and arachidonic acid metabolite production.
Arachidonic Acid↗
"Ex vivo" release of eicosanoid from human brain tissue: its relevance in the development of brain edema.
The specific mechanism underlying the genesis of vasogenic brain edema is still debated: the role of arachidonic acid is considered extremely important, as it is a possible activator of self-maintaining reactions enhancing the release of vasoactive and cytotoxic compounds. The relationship between arachidonic acid metabolism and brain edema has been studied primarily in brain tissue samples or in the extracellular fluid, whereas the residual capacity of perilesional tissue to synthesize and release eicosanoids has not been investigated. In the present study, perilesional samples of brain tissue were available from 4 patients operated on for brain metastasis, from 8 patients who had malignant neuroepithelial tumors, from 4 with meningiomas, and from 5 with subarachnoid hemorrhage. A brain edema index was calculated from the preoperative computed tomographic scan. The "ex vivo" method allowed determination of the residual capacity of endogenous arachidonic acid metabolism. The edema index is significantly higher in patients with brain metastasis (6.5 +/- 0.8) and neuroepithelial tumors (3.6 +/- 0.2) than in those with meningiomas (1.5 +/- 0.06), subarachnoid hemorrhage (1.7 +/- 0.18), and in controls. In patients with metastatic and neuroepithelial tumors there is a significant correlation between peritumoral brain edema and the capacity to synthesize leukotriene C4 (P less than 0.05); the capacity to synthesize leukotriene C4 is also significantly elevated after subarachnoid hemorrhage (13.91 +/- 2.6 ng/ml of incubation medium) when compared with control cases (5.56 +/- 0.91). The capacity to synthesize prostacyclin is significantly higher in patients with brain metastasis than in those with neuroepithelial tumors and meningiomas (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
6-Ketoprostaglandin F1 alpha↗
Effects of daily cigarette consumption on respiratory symptoms and lung function in a general population sample of north-Italian men.
We assessed the respiratory effects of the number of cigarettes smoked daily (CIGD) in 748 male smokers of a general population sample living in the unpolluted area of the Po Delta (Italy). A standardized questionnaire, flow-volume curves (V/V), the diffusing capacity of carbon monoxide (DLCO) and the slope of the alveolar plateau of nitrogen (DN2%/l) were used. Subjects were divided according to the median value of the observed distribution of CIGD (1-19, 20+) and according to the tertile values of the observed distribution of pack-years (an index representing lifetime cigarette consumption; 1-7, 8-21, 22+). In those with a higher CIGD, the prevalence rate of chronic phlegm was always significantly increased, while the prevalence rate of wheeze was significantly higher if they had smoked 8+ pack-years. Using analysis of variance, adjusted for pack-years, DLCO indexes, FEF75-85 and Vmax75 were significantly reduced in those with higher CIGD. When multiple logistic models, accounting for the independent effects of age and pack-years, were used, significantly increased odds ratios (ORs) for symptoms (e.g. OR = 2.0 for phlegm, OR = 1.8 for cough, OR = 1.6 for wheeze) and abnormal DLCO (OR = 1.9) or DN2%/l (OR = 1.6) were associated with a daily consumption of 10 cigarettes. In conclusion, the amount of cigarettes currently smoked may add a negative effect to that caused by lifetime cigarette consumption on respiratory symptoms and lung function. Moreover, the use of diffusing capacity in general population surveys is advisable.
Adolescent↗
Relationship of respiratory symptoms and pulmonary function to tar, nicotine, and carbon monoxide yield of cigarettes.
The data from consecutive surveys of the Tucson Epidemiologic Study (1981-1988) were used to evaluate the relationship in cigarette smokers of respiratory symptoms and pulmonary function to tar, nicotine, and carbon monoxide (CO) yields of the cigarette. There were 690 subjects who reported smoking regularly in at least one survey, over age 15. After adjustment for intensity and duration of smoking and for depth of inhalation, the risk of chronic phlegm, cough, and dyspnea were not related to the tar and nicotine yields. In 414 subjects with pulmonary function tested in at least one of the three surveys the spirometric indices used were significantly related to the daily dose of tar, nicotine, and CO (product of the cigarette yield and daily number of cigarettes smoked). The effects were more pronounced for past than for current doses. However, the differentiation of pulmonary function due to various yields of cigarettes was small in comparison to the difference in pulmonary function between smokers and nonsmokers.
Age Factors↗
Respiratory effects of occupational exposure in a general population sample in north Italy.
We assessed the effects of occupational exposure in a general population sample living in an unpolluted rural area of North Italy. In the age range of 18 to 64 yr, there were 417 participants who reported any exposure to dusts, chemicals, or gases and 1,218 who reported no exposure. Each subject completed a standardized interviewer-administered questionnaire (CNR-questionnaire). A variable proportion of participants succeeded in performing flow-volume curves, diffusing capacity of carbon monoxide, and slope of alveolar plateau of nitrogen. There was no significant difference for symptom prevalence rates between exposed and nonexposed in men and women who smoke. In nonsmoking women, those exposed showed significantly higher prevalence rates for exertional dyspnea and asthma. Regarding lung function, in exposed male smokers there was a significantly higher slope of the alveolar plateau. In exposed female nonsmokers, FEV1 and forced expiratory flows were significantly lower. Multiple logistic models in the overall group, accounting for age, smoking, and pack-years, showed that work exposure was associated significantly with higher risks for all symptoms in men (e.g., odds ratio: 2.76 for dyspnea, 2.31 for asthma, 1.69 for cough, and 1.64 for phlegm); in females, the association was significant for dyspnea (OR = 3.74) and asthma (OR = 3.29). Exposed men also had a significantly higher risk for %FEV1 or FEV1/FVC% below 70 (OR = 1.45). Our findings confirm those of the other few epidemiologic surveys in general population samples and contribute to the suggestion of a causal association between occupational exposure and chronic obstructive pulmonary disease.
Adult↗
Prevalence rates of respiratory symptoms in Italian general population samples exposed to different levels of air pollution.
We surveyed two general population samples aged 8 to 64 living in the unpolluted, rural area of the Po Delta (northern Italy) (n = 3289) and in the urban area of Pisa (central Italy) (n = 2917). Each subject filled out a standardized interviewer-administered questionnaire. The Pisa sample was divided into three groups according to their residence in the urban-suburban areas and to outdoor air pollution exposure (automobile exhaust only or industrial fumes as well). Significantly higher prevalence rates of all the respiratory symptoms and diseases were found in Pisa compared with the Po Delta. In particular, rhinitis and wheezing symptoms were higher in all the three urban zones; chronic cough and phlegm were higher in the zone with the automobile exhaust and the additional industrial exposure. Current smoking was more frequent in the rural area, but the urban smokers had a higher lifetime cigarette consumption. Childhood respiratory trouble and recurrent respiratory illnesses were evenly distributed. Exposure to parental smoking in childhood and lower educational level were more frequent in Po Delta, whereas familial history of respiratory/allergic disorders and work and indoor exposures were more often reported in the city. Multiple logistic regression models estimating independently the role of the various risk factors showed significant odds ratios associated with residence in Pisa for all the symptoms but chronic phlegm. For example, those living in the urban-industrial zone had an odds ratio of 4.0 (4.3-3.7) for rhinitis and 2.8 (3.0-2.6) for wheeze with respect to those living in the Po Delta.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
Effects of home environment on respiratory symptoms and lung function in a general population sample in north Italy.
Effects of indoor pollution exposure were evaluated in a general population sample (n = 3,289) living in the Po River Delta area. Prevalence rates of chronic cough in men and dyspnoea in women were significantly higher in association with the use of bottled gas (propane) for cooking instead of natural gas (methane). Chronic cough and phlegm in men and dyspnoea in women were significantly associated with the use of a stove for heating. When combining type of heating and fuel used, in men a trend toward higher prevalence rates of chronic cough and phlegm was shown in those with stove or fan heating (regardless of the fuel); in women the trend reached statistical significance for dyspnoea. The relationship between stove (regardless of fuel) and decrease in forced expirograms was statistically significant only in women. In multiple logistic models, accounting for independent effects of age, smoking, pack-years, parents' smoking, socio-economic status, body mass index, significantly increased odds ratios were found in males for the associations of: bottled gas for cooking with cough (1.66) and dyspnoea (1.81); stove for heating with cough (1.44) and phlegm (1.39); stove fuelled by natural gas and fan or stove fuelled other than by natural gas with cough (1.54 and 1.66). In females, significantly increased odds ratios were found only for dyspnoea when associated with bottled gas for cooking (1.45), stove for heating (1.46), stove fuelled by natural gas (1.58), stove or fan fuelled other than by natural gas (1.73).(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
The Po River Delta epidemiological study of obstructive lung disease: sampling methods, environmental and population characteristics.
A longitudinal study on chronic obstructive lung disease (AOD) has been started in the Po River Delta in northern Italy. The first cross-sectional study was conducted in this previously unpolluted rural area before the start of operation of a large thermoelectric power plant (2,649 megawatt). A significant output of air pollutants is expected. This will permit us to carry out a "natural experiment" to study the effects of air pollutants (SO2 and suspended particulates). A multistage stratified cluster design was chosen. Stratification was based on age and socio-economic characteristics (SES) of households, and was performed in two steps, using the different indices computed from the census data. Geographic zones represented four areas of different predicted pollution exposure, once the plant started operating. There were 3,289 subjects in the selected age group (8-64) who agreed to participate (78%); only 11% refused to participate. The participants were representative of the clusters and SES. Participants had slightly fewer employed males, who did not participate due to work. The stratification and staging method allowed us to keep an acceptable level of precision and efficiency in the sample. In fact age-related differences were not found among the SES strata and geographic zones; various socio-economic characteristics, verified from the questionnaire information, were consistent with the SES stratification. Differences between geographic zones were related to the number of households of different SES within clusters; however this reflects the characteristics of the general population in the area.
Air Pollutants↗