Use of plant- and period-specific job-exposure matrices in studies on occupational cancer

Job-exposure matrices were constructed and applied in the estimation of past exposures in a case-referent study nested within a cohort of Finnish woodworkers. The objective was to avoid bias in the risk estimates because of a misclassification of exposures. The matrices were constructed separately for each plant under study and each calendar year of follow-up. The level of exposure was incorporated in the matrices, since rather comprehensive data on exposures were available. The individual work histories were converted to exposure histories by a computer program which calculated several exposure indicators (eg, level and dose, with and without allowance for a latency period). The comparison between several indicators was thought to provide additional information for the final evaluation of results. The use of the plant- and period-specific job exposure matrices may be considered in cohort and nested case-referent studies on occupational hazards as an alternative to other procedures used in the estimation of exposures. Specific matrices may find broader applicability along with the increasing availability of detailed hygienic data.     

A comparison of clinical and research DSM-III-R diagnoses of schizophrenia in a Finnish national birth cohort

As a prerequisite to the use of the Finnish National Hospital Discharge Register in psychiatric epidemiological research, we studied the diagnostic reliability of the register in terms of the psychiatric morbidity experienced by a national birth cohort. We investigated all entries to the register for a sample based upon the Northern Finland 1966 birth cohort at the age of 16 years (n=11017). Until the end of 1993 (age 27 years), a total of 563 subjects had a register diagnosis indicating a psychiatric illness, 37 of them being schizophrenia. When operational criteria (DSM-III-R) were applied to clinical information in the available original hospital records for cases of psychosis, personality disorder and substance abuse (n=249), 71 fulfilled criteria for schizophrenia, including all of the 37 cases in the register and an additional 34 (48% false-negatives), most frequently diagnosed in the register as schizophreniform or other psychosis. Despite the official use of DSM-III-R nomenclature, it appears that the clinical concept of schizophrenia in Finland, manifest within the register, remains very restrictive. The application of operational criteria is a necessary prerequisite for scientific research on schizophrenia.     

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.     

Image processing in digital chest radiography: effect on diagnostic efficacy.

The usefulness of digital image processing of chest radiographs was evaluated in a clinical study. In 54 patients, chest radiographs in the posteroanterior projection were obtained by both 14 inch digital image intensifier equipment and the conventional screen-film technique. The digital radiographs (512 x 512 image format) viewed on a 625 line monitor were processed in three different ways: (1) standard display; (2) digital edge enhancement for the standard display; and (3) inverse intensity display. The radiographs were interpreted independently by three radiologists. The diagnoses were confirmed by CT, follow-up radiographs and clinical records. Chest abnormalities of the films analyzed included 21 primary lung tumors, 44 pulmonary nodules, 16 cases with mediastinal disease and 17 cases with pneumonia/atelectasis. Interstitial lung disease, pleural plaques, and pulmonary emphysema were found in 30, 18 and 19 cases, respectively. The sensitivity of conventional radiography when averaged overall findings was better than that of the digital techniques (P less than 0.001). The differences in diagnostic accuracy measured by sensitivity and specificity between the three digital display modes were small. Standard image display showed better sensitivity for pulmonary nodules (0.74 vs 0.66; P less than 0.05) but poorer specificity for pulmonary emphysema (0.85 vs. 0.93; P less than 0.05) compared with inverse intensity display. We conclude that when using 512 x 512 image format, the routine use of digital edge enhancement and tone reversal at digital chest radiographs is not warranted.     

EEG reactivity correlates with neuropsychological test scores in Down's syndrome

Introduction – Down's syndrome patients express a neurodegenerative disorder and mental retardation. We studied the reactivity of EEG and its correlation with neuropsychological test score in Down's syndrome. Material and methods – We studied 32 patients with Down's syndrome and 31 controls for blocking of occipital EEG activity. The temporo-occipital EEG with eyes open (EO) was compared with resting EEG with eyes closed (EC), (EC/EO ratio). Results – Both Down patients and controls showed significant diminution of alpha, beta and theta activity and decrease of EEG frequency with EO. However, there was a significant impairment in Down patients in the EC/EO ratio in alpha band, compared to controls. The controls had no correlation of the alpha EC/EO ratio with age or gender. The Down patients showed a significant correlation of this variable with age which is in accordance with a gradually progressing disease. They had also significant correlations of the alpha EC/EO ratio and neuropsychological test scores which indicates that this ratio may be a more general measure of cerebral or hemispherical dysfunction than a mere impairment of visual activation. Down patients also showed significant differences in resting EEG variables, compared to the controls, even if the conventional EEG showed normal or mildly slowed dominant occipital rhythm in most of the patients. The correlation analysis between resting EEG and EC/EO ratio variables pointed out that they are relatively independent, representing different factors in the regulation of EEG. Conclusions – We believe that the alpha EC/EO ratio of EEG add a new domain in the assessment of cerebral dysfunction in Down's syndrome.     

Auditory event-related potentials and cognitive function of preterm children at five years of age.

OBJECTIVE: In our previous study, auditory event-related potentials (AERPs) in preterm 1-year-old children had a positive deflection at 150-350 ms that correlated positively with their 2-year neurodevelopmental outcome. In a study of the same subjects at age 5, our aim was to assess AERPs and their relationship to neuropsychological test results. METHODS: Preterm small (SGA, n=13), appropriate for gestational age (AGA, n=15), and control (n=13) children were assessed with an Easy paradigm presenting a large frequency change accompanied with occasional novel sounds, and a Challenging paradigm presenting small frequency and duration changes with a rapid rate. The preterm children underwent neurocognitive tests. RESULTS: Easy paradigm. The P1 response to frequency deviant was smaller and MMN larger in the preterm than in the control children. Challenging paradigm. The P1 response to standard, frequency, and duration deviants was smaller in the preterm than in the control children. The N2 response to frequency deviant was larger in the preterm than in the control children. AGA and SGA children had similar AERPs. The P1, N2, and MMN amplitudes correlated with verbal IQ and NEPSY language subtests. CONCLUSIONS: Small P1 response(s) appears to be typical for preterm children. SIGNIFICANCE: Small P1 response in preterm children may suggest altered primary auditory processing.     

Enhanced metabolic activation of chemical hepatocarcinogens in woodchucks infected with hepatitis B virus

The metabolism of chemical carcinogens was investigated in liverpreparations from 28 captive woodchucks (Marmotamonax). Of these,23 were naturally infected with the wood-chuck hepatitis virus(WHV), and eight also had primary hepatocellular carcinoma (PHC).Twenty-nine parameters were investigated in liver subcelhilarfractions, including cross-reactivity with HBsAg, and biochemicalparameters, such as -glutamyl transpeptidase, cytochrome P-450and mirosomal monooxygenases (aryl hydrocarbon hydroxylase,ethodycoumarin and ethoxyresorufin deethylases, amino-pyrineand dimethylnitrosamine demethylases, and testosterone 7-and16ß- and 6ß-hydroxylases), uridine 5'-diphos-phoglucuronosyltransferase, GSH and related enzymes (peroxidase, reductaseand S-transferase), as well as other cytosolic enzyme activities(glucose 6-phosphate and 6-phosphogluconate dehydrogenases,NADPH- and NADH-dependent diaphorases, and DT diaphorase). Inaddition, liver preparations were used in order to quantifythe metabolic activation into bacterial mutagens of five procarcinogens(aflatoxin B¹, the pyrolysis products Trp-P-2 and MelQ, 2-aminofluoreneand dimethylnitrosamine) and the decrease of potency of threedirect-acting mutagens (sodium di-chromate, ICR 191 and 4-nitroquinoline1-oxide). WHV infection produced a significant stimulation ofcarcinogen metabolism, as shown by the simultaneous change indetoxification parameters (GSH depletion) and activation indices(enhancement of microsomal monooxygenases and of pro-carcinogenactivation into mutagenic metabolites). There were no significantdifferences between WHV-positive samples from animals, withoutPHC and the noncancerous tissue of PHC-bearing animals, whereasa decrease of both activation and detoxification indices wasrecorded in the turmorous tissue. There was a considerable interindividualvariability among WHV carriers, which was tentatively ascribedto genetic factors. Pregnancy was the only known factor influencingthe results in WHV carriers. However, even by excluding pregnantanimals, the effects on carcinogen metabolism produced by WHVinfection were still statistically significant. These results,together with previous data obtained in humans, revealed thatmetabolic factors may play a role in the synergism between viralhepatitis and chemical hepato-carcinogens in the etiopathogenesisof PHC.     

Immunochemical characterization of cytochrome P-450 isozymes responsible for benzene oxidation in the rat liver

The contribution of cytochrome P-450 isozymes to benzene metabolismin liver microsomes from fed, fasted, pyrazole-, pbenobarbital(PB)- and ethanol-treated rats and in respective isocaloriccontrols was investigated using monoclonal antibodies (mAbs).Clone 1-7-1 mAb did not inhibit benzene metabolism, whereasclone 2-66-3 inhibited only in PB-induced microsomes at a highconcentration of benzene (6.26 mM), and clone 1-91-3 mAb inhibitedbenzene metabolism in all cases. The degree of inhibition wasas follows: fed isocaloric control PB < fasted < pyrazole ethanol. The pattern of inhibition was similar with clone 1-91-3for low (0.23 mM) and high concentrations of benzene, exceptin PB-induced mkrosomes. Western blot analysis showed that clone1-7-1 mAb did not bind any liver mkrosomal protein in the regionof cytochrome P-450s, whereas with clone 2-66-3 a clear-cutband was seen only in liver microsomes from PB-treated rats,with clone 1-98-1, a band was detected in mkrosomes from alltreated groups, in the following order: PB = isocaloric control< fed < fasted < pyrazole < ethanol. These resultsindicate that (i) cytochromes P-450b,e and P-450J contributeto benzene metabolism in rat liver; (ii) the former has a lowaffinity to benzene and is induced by PB; and (iii) P-450J hasa high affinity to benzene and is induced by 1-day fasting,pyrazole and ethanol, but decreased by PB treatment.