Development of a Task-Exposure Matrix (TEM) for Pesticide Use (TEMPEST).

INTRODUCTION: Pesticides have been associated with increased risks for a range of conditions including Parkinson's disease, but identifying the agents responsible has proven challenging. Improved pesticide exposure estimates would increase the power of epidemiological studies to detect such an association if one exists. METHODS: Categories of pesticide use were identified from the tasks reported in a previous community-based case-control study in Scotland. Typical pesticides used in each task in each decade were identified from published scientific and grey literature and from expert interviews, with the number of potential agents collapsed into 10 groups of pesticides. A pesticide usage database was then created, using the task list and the typical pesticide groups employed in those tasks across seven decades spanning the period 1945-2005. Information about the method of application and concentration of pesticides used in these tasks was then incorporated into the database. RESULTS: A list was generated of 81 tasks involving pesticide exposure in Scotland covering seven decades producing a total of 846 task per pesticide per decade combinations. A Task-Exposure Matrix for PESTicides (TEMPEST) was produced by two occupational hygienists who quantified the likely probability and intensity of inhalation and dermal exposures for each pesticide group for a given use during each decade. CONCLUSIONS: TEMPEST provides a basis for assessing exposures to specific pesticide groups in Scotland covering the period 1945-2005. The methods used to develop TEMPEST could be used in a retrospective assessment of occupational exposure to pesticides for Scottish epidemiological studies or adapted for use in other countries.

A review of the data quality and comparability of case-control studies of low-level exposure to benzene in the petroleum industry.

PURPOSE: Published case-control studies of risks of leukaemia following low exposures to benzene in the distribution of petroleum (gasoline) have not all identified the same level of risk, but the studies have had differences in cohort inclusion, case determination and availability of occupational and lifestyle data. We reviewed the quality and comparability of the data from three (of four) studies. METHODS: Through site visits, discussions with the investigators and reading study reports, we reviewed and audited the methods used for selecting cases and controls, for estimating individual exposures and for analysing and interpreting the data. Case-control comparisons of exposures were examined using customized graphs. RESULTS: We found that there were no issues of subject selection, methods or general data quality that were likely to have distorted their internal comparisons; we could not check in detail whether the metric for exposure assessments was the same across the studies; the exposure assessments for the Australian study required the least backward estimation, and the Canadian, which also had fewest cases, the most; evidence of an increased risk at higher exposures in Australia was convincing. CONCLUSIONS: The findings are consistent with some effect of benzene at higher lifetime exposures. A proposed pooled analysis should improve quantification of any exposure-response relationship.

A panel study of air pollution in subjects with heart failure: negative results in treated patients.

OBJECTIVES: To investigate preclinical adverse effects of ambient particulate air pollution and nitrogen oxides in patients with heart failure. METHODS: A cohort of 132 non-smoking patients living in Aberdeen, Scotland, with stable chronic heart failure were enrolled in a repeated-measures panel study. Patients with atrial fibrillation or pacemakers were excluded. Participants were studied for 3 days every 2 months for up to 1 year with monitoring of pollutant exposure and concurrent measurements of pathophysiological responses. Measurements included daily area concentration of particulate matter with a median aerodynamic diameter of <10 micrometres (PM(10)), particle number concentration (PNC) and nitrogen oxides; daily estimated personal concentration of particulate matter with a median aerodynamic diameter of <2.5 micrometres (PM(2.5)) and PNC exposures; and 3-day cumulative personal nitrogen dioxide (NO(2)). Concurrent meteorological data were recorded. Blood was taken at the end of each 3-day block for assays of markers of endothelial activation, inflammation and coagulation. Cardiac rhythm was monitored by ambulatory Holter monitor during the final 24 h of each block. RESULTS: The average 24 h background ambient PM(10) ranged from 7.4 to 68 microg.m(-3) and PNC from 454 to 11 283 particles.cm(-3). No associations were demonstrated between the incidence of arrhythmias, heart rate variability or haematological/biochemical measures and any variations in pollutant exposures at any lags. CONCLUSION: Assuming that low-level pollution affects the parameters measured, these findings may suggest a beneficial effect of modern cardioprotective therapy, which may modify responses to external risk factors. Widespread use of such drugs in susceptible populations may in future reduce the adverse effects of air pollution on the heart.

Bar workers' health and environmental tobacco smoke exposure (BHETSE): symptomatic improvement in bar staff following smoke-free legislation in Scotland.

OBJECTIVE: To examine changes in the health of bar workers after smoke-free legislation was introduced. DESIGN: Longitudinal study following bar workers from before legislation introduction, at 2 months after introduction and at 1 year to control for seasonal differences. SETTING: Bars across a range of socio-economic settings in Scotland. PARTICIPANTS: 371 bar workers recruited from 72 bars. INTERVENTION: Introduction of smoke-free legislation prohibiting smoking in enclosed public places, including bars. MAIN OUTCOMES MEASURES: Change in prevalence of self-reported respiratory and sensory symptoms. RESULTS: Of the 191 (51%) workers seen at 1-year follow-up, the percentage reporting any respiratory symptom fell from 69% to 57% (p = 0.02) and for sensory symptoms from 75% to 64% (p = 0.02) following reductions in exposure, effects being greater at 2 months, probably partly due to seasonal effects. Excluding respondents who reported having a cold at either baseline or 1 year, the reduction in respiratory symptoms was similar although greater for "any" sensory symptom (69% falling to 54%, p = 0.011). For non-smokers (n = 57) the reductions in reported symptoms were significant for phlegm production (32% to 14%, p = 0.011) and red/irritated eyes (44% to 18%, p = 0.001). Wheeze (48% to 31%, p = 0.006) and breathlessness (42% to 29%, p = 0.038) improved significantly in smokers. There was no relationship between change in salivary cotinine levels and change in symptoms. CONCLUSIONS: Bar workers in Scotland reported significantly fewer respiratory and sensory symptoms 1 year after their working environment became smoke free. As these improvements, controlled for seasonal variations, were seen in both non-smokers and smokers, smoke-free working environments may have potentially important benefits even for smokers.

A normative study of levels of uranium in the urine of British Forces personnel.

OBJECTIVES: The UK Ministry of Defence (MoD) controls a biological monitoring programme that includes testing for uranium in personnel who served in the conflict in Iraq in 2003. To help interpret the results, the MoD commissioned this study to quantify a normative reference distribution of urinary uranium concentrations in military personnel who had not served in that conflict. METHODS: The study selected and visited various military establishments to recruit a representative mix of ranks, genders and occupational groups (combat, support and auxiliary). A standardised protocol and recruitment questionnaire were used. The 125 ml spot urine samples collected were analysed for uranium and creatinine concentrations and (where possible) for uranium isotope (238)U/(235)U ratio. RESULTS: Samples from 732 eligible subjects were analysed. Adjusted uranium concentrations ranged up to 556 ng.g(-1) creatinine, somewhat higher than reference values quoted for the USA but much lower than recorded in granite areas such as Finland. Isotope ratio measurements were available for 125 samples (17%) with the highest concentrations; these all had a natural isotope signature and no evidence of depleted uranium (DU). On average, urinary uranium concentrations were somewhat lower in officers than in other ranks; they differed also across the services, the Navy being lowest and the Army highest. The levels give no concern regarding health risks in the personnel studied. CONCLUSION: Since even the highest values were from natural sources, we assume the differences represent differences in ingestion of natural uranium. Definition of a reference distribution or normal values will depend on the subpopulation of interest.

Dust related risks of clinically relevant lung functional deficits.

AIM: To quantify the risks of clinically important deficits of FEV1 in coal miners in relation to cumulative and average concentrations of respirable dust. METHODS: Data were studied from over 7000 men who had been surveyed in the late 1970s. Linear regression equations for the association between FEV1 and self-reported breathlessness on mild exertion were used to define clinically important levels of FEV1 deficit, and the probabilities that individuals with different dust exposures would experience these deficits were calculated. RESULTS: Levels of FEV1 were lower among breathless men than among others, with a large overlap of the distributions. The relations between standardised FEV1 and breathlessness were constant over all age and smoking groups. A decrease of 100 ml in FEV1 was associated with an increase of 1.12 in the odds of reporting breathlessness. FEV1 deficits of -0.367, -0.627, and -0.993 l (designated as "small", "medium", and "large" deficits) were, on average, associated with proportional increases of risks of breathlessness by factors of 1.5, 2.0, and 3.0 respectively. Cumulative respirable dust exposure ranged up to 726 gh/m3, mean 136 gh/m3 (British Medical Research Council measurement convention). An increase of 50 gh/m3 was associated with an increase of about 2% in the proportion of men with small deficits in FEV1. For medium deficits the increases ranged from 1.5% to 2%, depending on age. A similar pattern was seen for large deficits, but with smaller increases. CONCLUSIONS: In the unlikely event of continuous exposure at the proposed new maximum respirable dust limit for British mines of 3 mg/m3 (ISO-CEN measurement convention) for a working lifetime, the risk of a medium deficit of FEV1 for a non-smoker at age 60 would be estimated to be 34%, compared with 25% for zero dust exposure; for smokers, about 54% compared with 44%.

Quetiapine in patients with schizophrenia. A high- and low-dose double-blind comparison with placebo. Seroquel Study Group.

BACKGROUND: Quetiapine fumarate (Seroquel [ICI 204,636]) is an atypical dibenzothiazepine antipsychotic with a greater affinity for 5-hydroxytryptamine2 (5-HT2) receptors than for D2 dopamine receptors; its efficacy in patients with schizophrenia was shown in early phase 2 trials (maximum dose, 750 mg/d). METHODS: In this multicenter, double-blind, placebo-controlled trial, 286 patients hospitalized with chronic or subchronic schizophrenia (DSM-III-R) were randomized to 6 weeks of treatment with high-dose quetiapine fumarate (< or = 750 mg/d), n = 96; low-dose quetiapine fumarate (< or = 250 mg/d), n = 94; or placebo, n = 96. The Brief Psychiatric Rating Scale (BPRS) and Clinical Global Impression Severity of Illness item scores were the primary efficacy variables. Secondary efficacy variables included the BPRS positive-symptom cluster score, the Modified Scale for the Assessment of Negative Symptoms summary score (United States only), and the total score from the negative scale of the Positive and Negative Syndrome Scale (Europe only). Scores were analyzed using an analysis of covariance for change from baseline at end point with last observations carried forward. The model included baseline score (covariate), center, and treatment. Extrapyramidal symptoms were assessed using the Simpson-Angus Scale and the Barnes Akathisia Scale; abnormal involuntary movements were assessed using the Abnormal Involuntary Movement Scale. Frequency distributions of grouped change-from-baseline scores were analyzed using chi 2 tests. RESULTS: Of 280 patients in whom the efficacy of quetiapine was evaluated, 159 (42% of those receiving high-dose treatment; 57%, low-dose treatment; and 59%, placebo) withdrew before trial completion, primarily because of treatment failure. Significant (P < .001, BPRS; P = .003, Clinical Global Impression Severity of Illness item; and P = .003, BPRS positive-symptom cluster) differences were identified between patients receiving high-dose quetiapine and placebo for both primary efficacy variables, with end point differences in the BPRS positive-symptom cluster score showing quetiapine's consistency in reducing positive symptoms. The reduction of negative symptoms was less consistent; high-dose quetiapine was superior on the Modified Scale for the Assessment of Negative Symptoms but not on the negative scale of the Positive and Negative Syndrome Scale. Quetiapine was well tolerated and did not induce extrapyramidal symptoms, sustained elevations of prolactin, or clinically significant changes in hematologic parameters. CONCLUSIONS: Quetiapine is an effective antipsychotic with a favorable safety profile. The optimum dose is probably greater than 250 mg/d.

Effects of insulation on the temperature within farrowing huts and the weaning weights of piglets reared on a commercial outdoor pig unit.

The air temperatures inside uninsulated and insulated huts were recorded on an outdoor pig unit in the south of England between September 1997 and September 1998, and the herd's production parameters were also recorded. During the summer the temperatures inside some of the uninsulated huts exceeded 45 degrees C, but the temperatures inside the insulated huts were lower and fluctuated less. Despite the high temperatures, the weaning weight of piglets reared in the uninsulated huts were often higher than those of the piglets reared in the insulated huts, possibly as a result of the higher mortality of small piglets in the uninsulated huts, especially during the winter. The weaning weights of the piglets were higher during the summer.

Femoroacetabular impingement osteoplasty: is any resected amount safe? A laboratory based experiment with sawbones.

There is an increased risk of fracture following osteoplasty of the femoral neck for cam-type femoroacetabular impingement (FAI). Resection of up to 30% of the anterolateral head-neck junction has previously been considered to be safe, however, iatrogenic fractures have been reported with resections within these limits. We re-evaluated the amount of safe resection at the anterolateral femoral head-neck junction using a biomechanically consistent model. In total, 28 composite bones were studied in four groups: control, 10% resection, 20% resection and 30% resection. An axial load was applied to the adducted and flexed femur. Peak load, deflection at time of fracture and energy to fracture were assessed using comparison groups. There was a marked difference in the mean peak load to fracture between the control group and the 10% resection group (p < 0.001). The control group also tolerated significantly more deflection before failure (p < 0.04). The mean peak load (p = 0.172), deflection (p = 0.547), and energy to fracture (p = 0.306) did not differ significantly between the 10%, 20%, and 30% resection groups. Any resection of the anterolateral quadrant of the femoral head-neck junction for FAI significantly reduces the load-bearing capacity of the proximal femur. After initial resection of cortical bone, there is no further relevant loss of stability regardless of the amount of trabecular bone resected. Based on our findings we recommend any patients who undergo anterolateral femoral head-neck junction osteoplasty should be advised to modify their post-operative routine until cortical remodelling occurs to minimise the subsequent fracture risk.

Cell and wall morphology of intestinal arterioles from 4- to 6- and 17- to 19-week-old Wistar-Kyoto and spontaneously hypertensive rats.

To determine whether vascular smooth muscle cells around intestinal arterioles of various sizes undergo comparable changes in spontaneously hypertensive rats, 4- to 6-week-old (n = 10) and 17- to 19-week-old (n = 10) rats from the Wistar-Kyoto and the spontaneously hypertensive strains were used to study the external morphology of vascular smooth muscle cells by scanning electron microscopy and the vessel wall cross-sectional characteristics by light microscopy. At the time of fixation all vascular tone had been abolished. Scanning electron microscopy analysis revealed that all Wistar-Kyoto and spontaneously hypertensive rats at a given age have spindle-shaped vascular smooth muscle cells of comparable length and longitudinal width for a given branching order of arterioles. However, normal maturation is associated with elongation and widening of the vascular smooth muscle cells. Light and scanning electron microscopy indicated that a monolayer of vascular smooth muscle cells, wrapped at almost 0 degree to the vessel's radial axis, is maintained in adult spontaneously hypertensive rats. The radial thickness of this vascular smooth muscle cell monolayer was significantly (p less than 0.025) increased for only the largest arterioles of young and adult spontaneously hypertensive rats. This radial thickening of individual vascular smooth muscle cells increased the muscular component of the wall area for the largest arterioles by about 50% in adult spontaneously hypertensive rats. Other smaller submucosal arterioles of young and adult spontaneously hypertensive rats had normal vessel wall and vascular smooth muscle cell characteristics. These data indicate that hypertrophy in the smooth muscle cell's radial dimension is the primary morphological change in intestinal arterioles of spontaneously hypertensive rats. However, the vascular smooth muscle cell hypertrophy is confined to the largest arterioles such that the remaining smaller arteriolar vessels in the spontaneously hypertensive rat retain a normal smooth muscle cell and overall wall morphology.

Multiple fixed doses of "Seroquel" (quetiapine) in patients with acute exacerbation of schizophrenia: a comparison with haloperidol and placebo. The Seroquel Trial 13 Study Group.

Five fixed doses of the atypical antipsychotic "Seroquel" (quetiapine) were evaluated to delineate a dose-response relationship, as measured by changes from baseline in Brief Psychiatric Rating Scale (BPRS), Clinical Global Impression (CGI), and Modified Scale for the Assessment of Negative Symptoms (SANS) summary scores, and to compare efficacy and tolerability opposite placebo and haloperidol. Three hundred sixty-one patients from 26 North American centers entered this double-blind, placebo-controlled trial with acute exacerbation of chronic schizophrenia (DSM-III-R). Patients who completed a single-blind, placebo washout phase were randomized to double-blind treatment with quetiapine (75, 150, 300, 600, or 750 mg daily), haloperidol (12 mg daily), or placebo and evaluated weekly for 6 weeks. At end point, significant differences (p < 0.05, analysis of covariance) in adjusted mean changes from baseline were identified between the four highest doses of quetiapine and placebo for BPRS total, BPRS positive-symptom cluster, and CGI Severity of Illness item scores and between quetiapine 300 mg and placebo for SANS summary score. Differences between quetiapine and haloperidol were not significant. Dose-response modeling showed significant linear and quadratic functions of quetiapine dose for all primary efficacy variables. Notably, no significant safety concerns were identified as dose increased. Quetiapine was no different from placebo across the dose range studied regarding incidence of extrapyramidal symptoms or change in prolactin concentrations. Quetiapine is well tolerated and clinically effective in the treatment of schizophrenia. It is both superior to placebo and comparable to haloperidol in reducing positive symptoms at doses ranging from 150 to 750 mg/day and in reducing negative symptoms at a dose of 300 mg/day.

The role of mucins in host-parasite interactions: Part II - helminth parasites.

Some parasites express mucin-like molecules. These have possible roles in attachment and invasion of host cells and in the avoidance of host immune processes. Enzymes of parasite origin might also facilitate infection, either by degrading host mucus barriers or by generating binding sites on host cells. Host mucins have roles in preventing parasite establishment or in parasite expulsion. They, in turn, might be exploited by parasites, either as sources of fuel or binding sites, or as host-finding targets. Here, we describe the biochemical properties of mucins and mucin-like molecules in relation to interactions (established and putative) between helminth parasites and their hosts.

RNA and protein metabolism in the oviduct and endometrium of the ewe at pro-oestrus: Regulation by oestradiol and progesterone.

The effects on RNA and protein metabolism in the oviduct and endometrium at pro-oestrus of oestradiol and progesterone secreted during the oestrous cycle were examined, using the ovariectomized, hormone-treated ewe as a model system. Thirty ewes received hormone injections during a period of 13 days, according to schedules designed to simulate endogenous ovarian secretion of oestradiol and progesterone during the oestrous cycle. Hormone effects on RNA:DNA ratios and on rates of synthesis of protein and methylated RNA in vitro, as well as effects on oviducal and uterine weight, were examined. The results obtained suggest that endogenous ovarian hormones have the following effects in the intact ewe. The secretion of oestradiol at pro-oestrus rapidly increases rates of synthesis of protein and methylated RNA, and mean cell content of RNA in both the endometrium and oviduct. Oestradiol secreted during the previous luteal phase of the oestrous cycle markedly increases mean cell content of RNA and amounts of protein and methylated RNA synthesis occurring in both tissues at pro-oestrus. In the endometrium, progesterone secreted during the luteal phase increases the RNA:DNA ratio, and probably also the amounts of protein and methylated RNA synthesized at pro-oestrus, but there are no significant interactions between the effects of oestradiol and progesterone. Progesterone had no effect on either the amounts or rates of synthesis of protein or methylated RNA in the oviduct. The results are discussed in relation to the hormonal regulation of physiological functions of the oviduct and endometrium during the first few days after the onset of oestrus.

Hormone receptor levels and hormone, RNA and protein metabolism in the genital tract during the oestrous cycle of the ewe.

The concentrations of soluble oestradiol and progesterone receptor proteins and several metabolic activities were measured in the genital tracts of ewes killed on Days 0 (oestrus), 2, 5, 10 or 14 of the oestrous cycle. In caruncular endometrium and in whole uterus the concentrations of oestradiol receptor (pmol steroid bound/mg tissue DNA) were highest at oestrus and declined steadily thereafter to minimal values at Day 14. The concentrations of progesterone receptor were highest on Days 0-5, then declined to low levels on Day 10-14. There was little metabolism of either [3H]oestradiol or [3H]progesterone in minces of whole uterus and with either steroid the pattern of metabolism did not change at any stage of the cycle. The in-vivo rates of synthesis of protein in caruncular endometrium and in isthmic oviduct were highest at or shortly after oestrus (Days 0-2), then declined to low levels on Days 10-14. RNA:DNA ratios in these two tissues were also greatest at oestrus and subsequently fell to minimal values by Day 14. The results are discussed in relation to ovarian secretion of oestradiol and progesterone during the oestrous cycle of the ewe.

Growth of the endometrium and cotyledons during pregnancy in the ewe: rates of protein secretion and synthesis and nuclear and cytosol steroid hormone receptor levels.

The time-course of cell hypertrophy and changes in in-vitro rates of secretion and synthesis of protein in intercaruncular and caruncular endometrium and maternal and fetal cotyledonary placenta have been examined during days 0-112 of pregnancy in the ewe. The concentrations of high-affinity receptors for oestradiol and progesterone in nuclear and cytosol fractions from these tissues were also determined. Protein secretion by intercaruncular endometrium increased 25-fold between days 0 and 84. On day 84 10(-5) M-colchicine blocked 75% of total secretion. Protein secretion did not increase in the other tissues. Protein synthesis and RNA:DNA ratio in intercaruncular endometrium increased steadily between days 0 and 112, whereas they did not change in caruncular endometrium between days 0 and 28 and declined in cotyledon between days 56 and 112. The levels of cytosol receptor for oestradiol and progesterone and of nuclear receptor for oestradiol in all tissues during days 56-112 were very low in relation to the corresponding levels in caruncular endometrium on day 0. The level of nuclear progesterone receptor in caruncular endometrium increased threefold between oestrus and day 28. The level of this receptor in cotyledon remained low on days 56-112, but in intercaruncular endometrium it increased to high values on days 84-112. The results demonstrated a major surge in secretory activity by the intercaruncular endometrium at around mid-gestation, which was associated with a marked increase in nuclear progesterone receptor levels but only a low level of nuclear oestradiol receptor. The observations do not suggest any important role for oestradiol or progesterone in the growth of fetal and maternal cotyledon.

Use of the short-term inflammatory response in the mouse peritoneal cavity to assess the biological activity of leached vitreous fibers.

We used a special-purpose glass microfiber sample, Johns-Manville Code 100/475, to study the effects of various acid and alkali treatments on biological activity as assessed by inflammation in the mouse peritoneal cavity, the leaching of Si, and the phase contrast optical microscopy (PCOM) fiber number. We used mild and medium treatments with oxalic acid and Tris buffer and harsh treatment with concentrated HCl and NaOH. Mild oxalic acid and Tris treatment for 2 weeks had no effect on any of the end-points, but prolonging the mild oxalic acid treatment time to 2 months reduced the biological activity and the fiber number. Medium oxalic acid treatment reduced the biological activity and the fiber number and caused a loss of Si. Medium Tris alkali treatment reduced the PCOM-countable fibers and the biological activity but did not cause a substantial loss of Si. Harsh treatment with strong HCl did not affect the fiber number or cause leaching but the biological activity was reduced; strong NaOH reduced the fiber number and biological activity, and caused marked leaching of Si. The medium oxalic acid conditions (pH 1.4) were more acid than those found in lung cells but produced the same effects (reduction in fiber number and biological activity) as the more physiological mild treatment (pH 4.0), when prolonged. This study suggests that medium oxalic acid treatment can be used as a short-term assay to compare loss of Si, reduction in fiber number, and change in biological activity of vitreous fibers.(ABSTRACT TRUNCATED AT 250 WORDS)

Short-term inhalation and in vitro tests as predictors of fiber pathogenicity.

A wide range of fiber types was tested in two in vitro assays: toxicity to A549 epithelial cells, as detachment from substrate, and the production of the proinflammatory cytokine tumor necrosis factor (TNF) by rat alveolar macrophages. Three of the fibers were also studied in vivo, using short-term inhalation followed by a) bronchoalveolar lavage to assess the inflammatory response and b) measurement of cell proliferation in terminal bronchioles and alveolar ducts, using incorporation of bromodeoxyuridine (BrdU). The amount of TNF produced by macrophages in vitro depended on the fiber type, with the man-made vitreous fibers, and refractory ceramic fibers being least stimulatory and silicon carbide (SiC) whiskers providing the greatest stimulation. In the epithelial detachment assay there were dose-dependent differences in the toxicity of the various fibers, with long amosite being the most toxic. However, there was no clear relationship to known chronic pathogenicity. Fibers studied by short-term inhalation produced some inflammation, but there was no clear discrimination between the responses to code 100/475 glass fibers and the more pathogenic amosite and SiC. However, measurements of BrdU uptake into lung cells showed that amosite and SiC produced a greater reaction than code 100/475, which itself caused no more proliferation than that seen in untreated lungs. These results mirror the pathogenicity ranking of the fibers in long-term experiments. In conclusion, the only test to show potential as a predictive measure of pathogenicity was that of cell proliferation in lungs after brief inhalation exposure (BrdU assay). We believe that this assay should be validated with a wider range of fibers, doses, and time points.

Weak associations in occupational epidemiology: adjustment for exposure estimation error.

Epidemiological studies often estimate the health effects of occupational exposures by multiple regression techniques. The standard theory of regression analysis is based on the assumption that the explanatory variables are known without error, and it has long been realised that departures from this assumption will lead to underestimation of the true regression coefficients. In reality, there may be considerable imprecision in the measurement of individuals' exposures to hazards in the workplace, but this is seldom taken into account in analyses. We therefore studied the effect of allowing for imprecision in the exposure estimate with more sophisticated statistical methods, using lung function data from a sample of 348 British miners exposed to mixed coal dust, over an eight-year period. Change in lung function over an eight-year period was regressed on cumulative dust exposure, weight, age and smoking habits. The error in the exposure estimation was assumed to be up to 30% of the total varience of the distribution of the exposure. Adjustment of the regression coefficients of lung function change on dust exposure for the estimation error using linear structural relationships increased the regression coefficient more than threefold compared with those calculated by standard regression analysis. The adjustment led to a change of the coefficients of age as well. The results indicate that a serious underestimation of the relation between lung function change and occupational exposure may occur, which might lead to false interpretations about the relative importance of the occupational exposure as a determinant of disease.

Variations in the carcinogenicity of tremolite dust samples of differing morphology.

Six samples of tremolite of different morphological type were prepared as dusts of respirable size and used in intraperitoneal injection studies in rats. Three "asbestiform" tremolites produced mesotheliomas in almost all animals, although with significantly different tumor-induction periods. A brittle type of fibrous tremolite which, when manipulated to prepare "respirable dust," produced a sample with relatively few asbestiform fibers remaining nonetheless produced tumors in 70% of rats. Two samples of nonfibrous tremolite produced respirable dust samples containing numerous elongated fragments with aspect ratios greater than 3:1, which therefore fitted the definition of respirable fibers. Both these samples produced relatively few tumors, although one had more long "fibers" than did the brittle tremolite that produced 70% of tumors. This study has therefore demonstrated that different morphologic forms of tremolite produce dusts with very different carcinogenic potential. Carcinogenicity does not depend simply on the number of elongated particles injected, and we need to develop methods of distinguishing carcinogenic tremolite fibers from relatively innocuous tremolite dusts, with similar numbers of elongated particles of similar aspect ratios.

Life table methods for quantitative impact assessments in chronic mortality.

Quantitative health impact assessments of chronic mortality, where the impacts are expected to be observed over a number of years, are complicated by the link between death rates and surviving populations. A general calculation framework for quantitative impact assessment is presented, based on standard life table calculation methods, which permits consistent future projections of impacts on mortality from changes in death rates. Implemented as a series of linked spreadsheets, the framework offers complete flexibility in the sex specific, age specific, and year specific patterns of baseline mortality death rates; in the predicted impacts upon these; in the weights or values placed on gains in life; and in the summary measures of impact. Impacts can be differential by cause of death. Some examples are given of predictions of the impacts of reductions in chronic mortality in the populations of England and Wales and of Scotland.