On biases in a study of the effects of occupational and individual factors on the risk of neck trouble.
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Bias↗
Biomedical subjects
M Nurminen
Publications and source records attributed to M Nurminen.
Pocket-sized spirometer for monitoring bronchial challenge procedures.
Diagnosis of occupational asthma is verified by inhalation challenge testing when frequent monitoring of peak expiratory flow (PEF) or forced expiratory volume in 1 s (FEV1) is needed. FEV1 measurements also allow frequent monitoring of changes in small airways. For the follow-up of lung function of suspected occupational asthma, a reliable, personal and mobile device is needed. We studied the accuracy of a pocket-sized spirometer, Micro Plus Spirometer (MP), compared with our former combination of two devices, i.e. the values of forced expiratory volume in 1 s (FEV1) with those measured with the Vitalograph bellow spirometer (V); and the peak expiratory flow (PEF) values with the values obtained with a Wright PEF meter (W). In healthy control subjects, the values of FEV1 obtained with Micro Plus correspond well to those obtained using a bellow spirometer (R = 0.97) and the mean difference (MP-V) was -0.06 1 irrespective of the mean FEV1 value. W gives smaller PEF values than the MP; the mean difference in PEF (MP-W) was 44 1 min-1, but the values increased linearly with increasing flow. The poor relation between PEF values might be based on the low reliability of the Wright device. In patient follow-up, the FEV1 values measured with MP and V showed a good correlation (R = 0.99). The PEF values in patients increase linearly measured with W vs. MP with increasing flow values. In conclusion, we found the pocket-sized spirometer a handy and useful device for monitoring bronchial challenge procedures in patients with suspected occupational asthma. The number of exhalations during the challenge test follow-up is lessened when FEV1 and peak expiratory flow (PEF) can be measured simultaneously.
Adult↗
Asbestos bodies in bronchoalveolar lavage in relation to asbestos bodies and asbestos fibres in lung parenchyma.
In Finland, unlike other countries, anthophyllite asbestos has been widely used due to its domestic production in 1918-1975. In this particular context, the aim of the present study was to analyse the relationship between asbestos bodies (ABs) in bronchoalveolar lavage (BAL) fluid and the concentration of ABs and the different amphibole asbestos fibres in lung tissue. Sixty five BAL lung tissue sample pairs from patients with pulmonary disease were analysed. The concentration of ABs in BAL fluid and lung tissue was determined with optical microscopy, and the concentration, type and dimensions of asbestos fibres in lung tissue with scanning electron microscopy. There was a significant correlation between the concentrations of ABs in BAL fluid and in lung tissue (r = 0.72; p < 0.001), between the concentrations of ABs and amphibole asbestos fibres in lung tissue (r = 0.73; p < 0.001), and between the concentration of ABs in BAL fluid and the concentration of amphibole asbestos fibres in lung tissue (r = 0.64; p < 0.001). In patients who had been exposed mainly to commercial anthophyllite, significantly higher concentrations of ABs were observed per total pulmonary amphibole fibre burden, as compared to patients whose main exposure was to crocidolite/amosite. The anthophyllite fibres in lung tissue were longer than the crocidolite/amosite fibres. The relationship between asbestos body counts in lung tissue and in bronchoalveolar lavage fluid was similar to previous international observations. When using the asbestos body count to predict the underlying total pulmonary amphibole asbestos burden in Finnish patients, however, it should be borne in mind that the relationship between the two parameters seems to be different with anthophyllite as compared to crocidolite/amosite fibres.
Adult↗
Pulmonary asbestos bodies and asbestos fibers as indicators of exposure.
OBJECTIVES: The aim of the study was to analyze the correlation between pulmonary concentrations of asbestos bodies and asbestos fibers and to characterize asbestos body counts from lung tissue of Finnish patients occupationally exposed and unexposed to asbestos. METHODS: Ninety-nine surgically treated lung cancer patients were investigated. The number of asbestos bodies in iron-stained 5-micrometers histological lung tissue sections was determined by optical microscopy, and the pulmonary concentration of asbestos fibers was assessed by scanning electron microscopy. The correlation between asbestos body and asbestos fiber counts was calculated with linear regression. The asbestos body and asbestos fiber concentrations were also compared with exposure history according to a personal interview of the patients. RESULTS: The average number of asbestos bodies ranged from < 0.1 to 750 asbestos bodies per tissue section. All the cases with definite exposure showed an average of at least one asbestos body per tissue section. An average of at least one asbestos body per section was, however, detected in 34% of the patients with unlikely exposure. The regression equation log (AF) = -0.429 + 0.600.log (AB) was found to predict the concentration of asbestos fibers (AF, 10(6) fibers.g-1) corresponding to a given number of asbestos bodies (AB) in a section of lung tissue. CONCLUSIONS: The background level of asbestos bodies in the lungs of patients with no specific asbestos exposure seems to be higher in Finland than in other countries. In medicolegal cases, the methodological variation involved in asbestos fiber and asbestos body counting must be recognized and all available exposure data should be used to produce the best possible estimate of the exposure.
Adult↗
Heterologous production of the P1 porin of Neisseria meningitidis in bacillus subtilis: the effect of an N-terminal extension on the presentation of native-like epitopes.
The major outer membrane protein P1 (class 1) of Neisseria meningitidis has been produced as inclusion bodies in Bacillus subtilis with the aim to develop a vaccine based on it. The protein produced in high yield in B. subtilis contained an N-terminal extension of 11 amino acid residues which was found to be necessary for expression in the production system. In the present study we asked whether or not the removal of this extension would effect the conformation of this protein in liposomes as judged by its immunogenic properties. A methionine was engineered in front of the mature P1 protein to provide a chemical cleavage site for CNBr to remove the extension. The CNBr-cleaved protein, complexed with phospholipids, elicited high titers of antibodies binding to the meningococcal cells similarly to the noncleaved protein. This suggests that the BacP1 protein can serve as an effective vaccine component irrespective of the presence, or absence, of this N-terminal extension.
Animals↗
The Neisseria meningitidis outer membrane protein P1 produced in Bacillus subtilis and reconstituted into phospholipid vesicles elicits antibodies to native P1 epitopes.
Class 1 outer membrane protein (P1) of Neisseria meningitidis group B is considered a promising vaccine candidate because P1 subtype-specific antibodies have been shown to be protective in an animal model. We have previously described the production of P1 in the Gram-positive Bacillus subtilis as intracellular inclusion bodies, from which the protein (BacP1) is easily purified (Nurminen et al., Mol. Microbiol., 1992, 2499-2506). We show here that the purified BacP1 can be reconstituted into phospholipid vesicles with the formation of the native immunodominant surface epitopes. The detergent-solubilized, completely denatured BacP1 was fused with phospholipid-detergent micelles during detergent removal by dialysis or gel filtration to yield protein-lipid vesicles (liposomes). When mice were immunized with these liposomes, they produced high titers of antibodies reacting in a P1 subtype-specific manner with meningococcal cells indicating the presence of conformation-dependent P1-specific epitopes in the liposomes. The results suggest that a vaccine candidate for meningococcal disease could be developed from the BacP1-liposomes. They furthermore demonstrate the feasibility of refolding a denatured outer membrane protein, which has never been exposed to lipopolysaccharide, into a native-like conformation.
Amino Acid Sequence↗
To use or not to use the odds ratio in epidemiologic analyses?
This paper argues that the use of the odds ratio parameter in epidemiology needs to be considered with a view to the specific study design and the types of exposure and disease data at hand. Frequently, the odds ratio measure is being used instead of the risk ratio or the incidence-proportion ratio in cohort studies or as an estimate for the incidence-density ratio in case-referent studies. Therefore, the analyses of epidemiologic data have produced biased estimates and the presentation of results has been misleading. However, the odds ratio can be relinquished as an effect measure for these study designs; and, the application of the case-base sampling approach permits the incidence ratio and difference measures to be estimated without any untenable assumptions. For the Poisson regression, the odds ratio is not a parameter of interest; only the risk or rate ratio and difference are relevant. For the conditional logistic regression in matched case-referent studies, the odds ratio remains useful, but only when it is interpreted as an estimate of the incidence-density ratio. Thus the odds ratio should, in general, give way to the incidence ratio and difference as the measures of choice for exposure effect in epidemiology.
Data Interpretation, Statistical↗
Health status and exposure of workers at a pilot brown coal liquefaction plant in Australia, 1985-1991.
In 1985, Brown Coal Liquefaction (Victoria) Pty Ltd (BCLV) commenced operation of a pilot plant that investigated the feasibility of producing oil from brown coal. The plant operated for five years. This study aimed to use exposure and health information routinely collected by the company to characterize various health parameters of the workforce and to investigate whether any adverse health measures were exposure-related. About 1680 persons were employed at some time or other by BCLV, and the primary study population consisted of 408 workers who had a medical examination at the end of employment and who consented to being in an epidemiological study. Reported photosensitivity was associated with higher cumulative skin exposure (RR = 1.85; 95% CI = 1.22-2.78), with an exposure-response relationship of increasing risk with increasing skin exposure being suggested. There was no consistent evidence that chemical exposure at BCLV had any negative effect on the haematological, biochemical, endocrine or lung function of workers at the plant. However, the maximum follow-up period of less than eight years limits the ability of the study to detect any emerging chronic effects.
Adult↗
Linkage failures in ecological studies.
Ecological studies require a methodological theory distinct from that used in individual-level epidemiological studies. This article discusses the special problems that need to be considered when planning ecological studies or using the results of such studies. Ecological studies are much more sensitive to bias from model mis-specification than are results from individual-level studies. For example, deviations from linearity in the underlying individual-level regressions can lead to inability to control for confounding in ecological studies, even if no misclassification is present. Conditions for confounding differ in individual-level and ecological analyses. For ecological analyses of means, for example, a covariate will not be a confounder if its mean value in a study region is not associated with either (i) the mean exposure level across regions, or (ii) the mean outcome (disease rate) across regions. On the other hand, effect modification across areas can induce ecological bias even when the number of areas is very large and there is no confounding. In contrast to individual-level studies, independent and nondifferential misclassification of a dichotomous exposure usually leads to bias away from the null hypothesis in aggregate data studies. Failure to standardize disease, exposure and covariate data for other confounders (not included in the regression model) can lead to bias. It should be borne in mind that there is no method available to identify or measure ecological bias. While this conclusion may sound like a general criticism of ecological studies, it is not. It does, however, serve as a reminder of the problems that need to be considered when one designs, analyses, or critically evaluates ecological studies.
Bias↗
Determination of 24 variously sulfated galactosaminoglycan- and hyaluronan-derived disaccharides by high-performance liquid chromatography.
In this report we describe a very sensitive high-performance liquid chromatographic method for the determination of 24 nonsulfated and variously sulfated disaccharides present in chondroitin sulfates, dermatan sulfates, and hyaluronic acid. The method is superior to others in that monosulfated disaccharides at either C-2 or C-3 of the uronic acid moieties and mono-, di-, and trisulfated disaccharides containing N-sulfated galactosamine as well as non-, mono-, and oversulfated disaccharides derived from iduronic acid can be determined. Following chondroitinase digestions of tissue extracts or purified hyaluronic acid, chondroitin sulfate, and dermatan sulfate, the non-, di-, and trisulfate delta-disaccharides, are separated by direct injections into HPLC, whereas the monosulfated delta-disaccharides are chromatographed after a simple reduction of the galactosamine carbonyl group with sodium borohydride. The various sulfated delta-disaccharides are separated on an amino column (Econosphere NH2) and recorded at 231 nm. The column is eluted isocratically with 5 mM sodium dihydrogen orthophosphate, pH 2.55, for nonsulfated delta-disaccharides; 50 mM sodium dihydrogen orthophosphate, pH 2.50, for reduced monosulfated; and 50 mM sodium sulfate-10 mM sodium acetate, pH 5.0, for the separation of di- and trisulfated delta-disaccharides. A linear detector response was obtained for injections up to 50 micrograms of delta-disaccharides. As little as 5-8 ng of nonsulfated, 8-11 ng of monosulfated, 12-15 ng of disulfated, and 25-30 ng of trisulfated delta-disaccharides can be reliably detected. Application of this HPLC method to the analysis of various glycosaminoglycans in conjunction with chondroitinase AC, ABC, or B digestions and sulfatase hydrolysis adds to the knowledge of the structural spectrum of the galactosaminoglycans. It was thus possible to identify 24 different disaccharides in chondroitinase-susceptible glycosaminoglycans, including all C-5 epimeric disaccharides and those sulfated at C-2 or C-3 of the uronic acids and at the amino group of the galactosamine.
Animals↗
Risk factors predicting chronic rejection of renal allografts.
Chronic rejection is clinically defined as a gradual but progressive impairment of renal allograft function in the absence of other specific causes. The risk factors predisposing to chronic rejection are incompletely known. In this prospective single-center project, logistic regression analysis was used to study the long-term outcome of 94 consecutive first renal allografts in relation to 10 potential risk factors. Whether serum lipid levels, histopathological changes or the mode of immunosuppressive therapy had a predictive value for chronic rejection was of special interest. The risk factors for renal allograft outcome were determined 2 years after the transplantation, when graft function was still normal, and the results were evaluated 2 years later. Occurrence of acute rejections, cold ischemia time, the high-density lipoprotein cholesterol level, and the high-density lipoprotein and total cholesterol ratio were not significant predictors of graft outcome. In a univariate analysis, triglyceride, total cholesterol, and low-density lipoprotein cholesterol level, and donor age were significantly related to graft outcome. In a logistic regression analysis, triple immunosuppressive therapy was better than any double-drug regimen in preventing the deterioration of renal allografts. Incipient histological changes in graft biopsy, quantitated as the "chronic allograft damage index," was the most important single predictor of chronic rejection. The effect of both the histological changes and low-density lipoprotein cholesterol on adverse graft outcome was level dependent.
Adult↗
Asbestos-related pleural plaques and lung cancer.
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Asbestos↗
Is there an association between pleural plaques and lung cancer without asbestosis?
OBJECTIVES: A recent review or meta-analysis of epidemiologic studies concluded that persons with asbestos-related pleural plaques do not have an increased risk of lung cancer in the absence of parenchymal asbestosis. The reviewer inferred that this conclusion provided indirect supportive evidence for the proposition that asbestosis is a necessary precursor of asbestos-related lung cancer. The objective of the present communication is to contest these claims. METHODS: Finnish epidemiologic data and population statistics were used to estimate the apparent risk ratio of lung cancer associated with radiographic signs of pleural plaques. Power calculations were applied to compute the needed population sizes to demonstrate that the association is statistically significant. RESULTS: Unrealistically large population studies would be needed to observe the statistical relation between pleural plaques and lung cancer, quantitated as a risk ratio of 1.1, resulting from relatively low levels of environmental asbestos exposure. In realistic and valid epidemiologic studies on heavily exposed subpopulations, a two- or threefold risk can be identified. CONCLUSIONS: Uninformative studies should not be interpreted as providing suppressive evidence that pleural plaques are a noncausal risk indicator of lung cancer. Even for the null hypothesis, the inference that asbestosis is a necessary causal link between asbestos and lung cancer is illogical.
Adult↗
Clinical utility of liquid-chromatographic analysis of effusions for hyaluronate content.
A previously described HPLC method for determining hyaluronate in effusions was used to analyze a consecutive series of effusions from 1039 patients with pleural fluids and from 571 patients with peritoneal fluids. A mesothelioma was verified histologically in 50 of the cases. The results were used to estimate the clinical utility of the analysis. With a cutoff of 75 mg/L for hyaluronate-derived uronic acid, assay specificity for a malignant mesothelioma was 100% and the sensitivity 56%. Only 20% of the effusions from the mesothelioma patients showed no evidence of increased production of hyaluronate. Cytological smears from the associated cell pellets were evaluated as malignant or suspicious for malignancy in only 28% or in a further 46% of the mesothelioma cases, respectively, leaving 30% of the pellets as cytologically false-negative. We also analyzed effusions from selected cases submitted from other hospitals, 154 of which had been diagnosed histologically as mesotheliomas. Concentrations of hyaluronate were increased in these cases too, but a considerable proportion of the samples showed evidence of losses of hyaluronate; consequently, the sensitivity of the assay in these samples was lower.
Ascitic Fluid↗
The role of alcohol in work-related fatal accidents in Australia 1982-1984.
This paper describes the role of detectable blood alcohol in fatal work injuries. An attempt was made to identify all work-related fatalities that occurred throughout Australia in the period 1982-1984. A research team examined coroners' records and classified 1737 fatal injury cases as being work-related according to study definitions. The following were also extracted from data in coroners' records: (i) whether or not the description of the fatal event indicated that inebriation was likely to have been a factor; (ii) whether or not there was documentation of blood alcohol concentration (BAC), and if so, what it was. The likelihood of inebriation was assessed without knowledge of the victim's BAC. In 1030 (59 per cent) of the 1737 fatal work injury cases, a BAC determination was documented. Zero levels were detected in 867 fatalities (84 per cent), and 163 cases (16 per cent) had non-zero BAC. In the latter group the median BAC was 104 mg%. Sixty-five per cent of measurable BAC cases had BAC greater than 50 mg%. Fatality risk in the non-zero BAC group relative to that of the zero BAC group was elevated for the following factors: marital status--single (risk ratio (RR) = 1.7, 95 per cent confidence interval (CI) 1.1-2.8) or separated/divorced (RR = 2.4, CI 1.5-3.8); occupation as manager, executive or administrator (RR = 2.5, CI 1.5-5.8); and commuting (RR = 1.6, CI 1.2-2.0).(ABSTRACT TRUNCATED AT 250 WORDS)
Accidents, Occupational↗
Localized pleural plaques and lung cancer.
In a mass chest radiography survey conducted in 1971 for 7,986 residents of three Finnish communities, 604 subjects (7.6%) with pleural plaques but not other asbestos-related radiographic signs were identified. The same number of referents, each individually matched to each plaque carrier on sex, birth year, and community, was selected from among persons in the same source population with no pleural plaques. The two groups were followed for investigation of incidence of lung cancer during 1972-1989. Twenty-eight of those with plaques and 25 referents contracted lung cancer (crude conditional RR = 1.1; CL95 = 0.7, 1.9). The application of the proportional hazards model, with adjustment for sex, age, and residence, resulted in a hazard ratio of 1.1 (CL = 0.6, 1.8). The risk ratio estimate may be biased; hence, the result is inconclusive in regard to the predictive assessment of lung cancer risk among carriers of pleural plaques.
Adult↗
Assessment of excess risks in case-base studies.
Miettinen and Caro (J Clin Epidemiol 1989; 42: 325-331) [6] put forth principles of non-experimental assessment of excess risks in case-base studies; in such a design, risk difference is assessed by estimating the denominators of the proportions of cases among exposed and comparable unexposed subjects by means of a representative sample from the base population of the study. They provided appropriate formulations for the point estimation of risk differences for various exposure patterns with allowance for covariables by means of stratified analysis. However, in small samples point estimates can be uncertain. In this paper, first, likelihood-based statistics are derived which can be used for interval estimation (and also point estimation and significance testing) of risk differences. The unified approach generalizes to stratified analysis. Second, the procedure is parameterized for inferences about risk ratios using a chi-square function in analogy with the profile likelihood method for full cohort analysis. Third, the approach is extended from the study of a binary exposure variable to a risk function analysis under the Poisson regression model. The suggested estimation procedure is conceptually clear and computationally simple in that the modelling, unlike the models considered by Prentice (Biometrika 1986; 73: 1-11) [3] for the analysis of case-base data, focuses directly on the comparison of risks between exposure categories in the study base and thus involves no covariance between the cases and the base sample.
Case-Control Studies↗
The class 1 outer membrane protein of Neisseria meningitidis produced in Bacillus subtilis can give rise to protective immunity.
The class 1 outer membrane protein of Neisseria meningitidis B:15:P1.7,16 was expressed in Bacillus subtilis in high yield as intracellular aggregates. These were easy to isolate and the protein (called BacP1) could be solubilized under denaturing conditions. Sera of mice immunized with thus-solubilized BacP1 contained high titres of antibodies that reacted with the class 1 protein of the meningococcal envelope in immunoblots but did not react with native meningococcal envelope in enzyme immunoassays (EIA) or with intact meningococci in bactericidal assays. However, when the BacP1 protein was complexed with heterologous (Salmonella) lipopolysaccharide, the ensuing sera reacted with meningococcal envelope preparations in both EIA and immunoblots, showed subtype-specific bactericidal activity, and were protective in an infant rat meningitis model.
Amino Acid Sequence↗