Deficits in visuospatial processing contribute to quantitative measures of freezing of gait in Parkinson's disease.

OBJECTIVES: The aim of this study was to investigate whether an objective measure of freezing of gait (FOG) using a validated alternating stepping in place (SIP) task, is related to executive and/or visuospatial cognitive impairment in Parkinson's disease (PD). METHODS: We studied prospectively 30 PD subjects with the Unified Parkinson's Disease Rating Scale (UPDRS) III, the FOGq, Trail Making Test Part B (TMTB), Wisconsin Card Sorting, Initiation/Perseveration, Matrix Reasoning (MR) and Block Design (BD). PD subjects performed three, 100s trials of alternative SIP while standing on two force platforms to assess the number and duration of freezing episodes (FE), SIP rhythmicity and symmetry. RESULTS: Freezers had larger cycle asymmetry and arrhythmicity than non-freezers (P<0.05). Performance on BD and MR tests differentiated freezers from non-freezers (P<0.04; P=0.001, respectively). BD performance negatively correlated with the FOGq total (P<0.05), the number and duration of FE (P<0.01), SIP arrhythmicity and asymmetry (P=0.01, P<0.05). MR performance negatively correlated with all FOGq #3 and total as well as SIP FE metrics (P≤0.01), except for SIP asymmetry. CONCLUSION: Deficits in visuospatial perception and reasoning not in executive function differentiated freezers from non-freezers. Deficits in visuospatial processing negatively correlated with all SIP freeze metrics, whereas deficits in executive function were only correlated with SIP arrhythmicity, the FOGq total and the duration of freezing episodes. These results suggest that deficits in visuospatial processing to perform a motor task contribute to FOG and that different cognitive deficits may contribute to different aspects of freezing in PD. This is the first study to our knowledge that has compared metrics of freezing to cognitive tasks in the visuospatial and visual reasoning domains.

Lung fiber burden in the Nottingham gas mask cohort.

A cohort of 1,154 employees, mainly women, who had worked 1940-1945 on the manufacture of military gas masks using filter pads containing 20% crocidolite, was traced through 2003, by which time 65 were known to have died from mesothelioma. The last known death with mesothelioma was in 1994, whereas a further 5 cases would have been expected in those with known duration of exposure. Lung tissue samples, from 50 deaths from mesothelioma and 20 other causes, had been analyzed for mineral fiber content. For ten of the mesothelioma cases data on fiber size were collected. Crocidolite fiber concentrations were analyzed in relation to exposure by time and duration. Fiber concentrations overall fell fairly steadily by decade of death, and increased with length of exposure up to 36 months and then fell sharply. The annual rate of elimination estimated by regression was 7.5% corresponding to a half life of 9.2 years. The proportion of fibers longer than 6 mum increased over time implying that the shorter fibers were eliminated more rapidly than the longer ones. The decline in concentrations with time confirms the hypothesis that crocidolite and, by inference, other amphibole fibers are slowly removed from the lung, but since the longer more carcinogenic fibers were cleared more slowly it is unclear to what extent this clearance explains the slowing down of the increase in mesothelioma mortality from about 40 years from the most recent exposure. The exact biostatistical models which most closely conform with the data remain open to question.

Lung cancer and exposure to arsenic in rural Bangladesh.

BACKGROUND: Arsenic is a known carcinogen but the risk of lung cancer from the widespread contamination of drinking water in rural Bangladesh has not been estimated. OBJECTIVES: To determine whether estimated exposure of villagers in Bangladesh to arsenic in drinking water differed between those with lung cancer and those with non-malignant lesions. METHODS: Data were obtained from 7286 subjects who underwent lung biopsy in 2003-2006 at a diagnostic centre taking referrals from throughout Bangladesh. Analysis was limited to 5372 people living in villages for the last 10 years who reported using tube well water. Of these, 3223 with a primary lung tumour were enrolled as cases and 1588 with non-malignant lesions as referents in an unmatched analysis. Arsenic exposure was estimated by average concentrations for each of 64 districts. Logistic regression was used to test the effects of age, arsenic and smoking on risk and to investigate relationship to cell type. RESULTS: Male cases were older than referents and more likely to smoke, to smoke >20 units/day and to smoke bidi-small, hand-rolled cigarettes. Odds ratios for lung cancer increased steadily with mean arsenic concentration, but the confidence interval excluded 1.0 only at concentrations >100 mug/l (OR 1.45, 95% CI 1.16 to 1.80). This trend was seen only in smokers where the increased risk at >100 mug/l was 1.65 (95% CI 1.25 to 2.18). A similar trend was seen in women smokers. Squamous cell lung cancer was more frequent in smokers and, having adjusted for smoking, in districts with arsenic concentrations >100 mug/l. CONCLUSIONS: Among Bangladeshis who smoke, those whose drinking water is contaminated with arsenic at concentrations >100 mug/l are at increased risk of lung cancer. With high levels of exposure misclassification and short latency of exposure, the study cannot estimate or exclude the likely long term risk in non-smokers and at lower arsenic concentrations.

The radiological properties of a novel lung tissue substitute.

Lung phantoms have been manufactured using commercially available, polyurethane foam products. Some of these materials are no longer available; therefore, a new lung tissue substitute was developed. The elemental composition and radiological properties of the new lung tissue substitute are described in this paper. Because the lung tissue substitute will be used to manufacture phantom lungs that will be used to evaluate chest counting systems, it is necessary to know the radiological properties of the material. These properties must be compared with reference materials and materials that have been used for lung phantoms in the past. The radiological properties of interest include the electron density, mean excitation energy, electron stopping power and photon mass attenuation coefficients. In all these properties, the calculated values for the new lung tissue substitute closely matched the calculated values of ICRU Publication 44 lung tissue. Good agreement was also found when the new lung tissue substitute was compared with the Griffith lung tissue substitute described by the ICRU. The new material was determined to be an excellent lung tissue substitute.

Sixty years on: the price of assembling military gas masks in 1940.

BACKGROUND: Between 1940 and 1944 military gas masks with filter pads containing 20% crocidolite were assembled in a Nottingham factory. METHODS: Records supplied by the late Professor Stephen Jones were of 1154 persons, mainly women, who had worked in the factory during this period; they included many deaths from mesothelioma. A systematic effort was therefore made to establish causes of death for the whole cohort. RESULTS: Of 640 employees with full name and sex recorded, 567 (89%) were traced. Of these, 491 had died, including 65 from mesothelioma, though only 54 were certified as such. After exclusion of these 54, standardised mortality ratios were significantly raised for respiratory cancer (SMR 2.5) and carcinomatosis (SMR 3.2). The pattern of mortality in the remaining 514 employees without full identification was similar, but a low tracing rate (40%) did not justify their further analysis. The first death from mesothelioma was in 1963 (22 years after first exposure) and the last in 1994, whereas a further 5.0 cases would have been expected between 1996 and 2003 (p = 0.0065). CONCLUSION: These findings in a cohort followed over 60 years after brief exposure to crocidolite confirm a high and specific risk of mesothelioma (28% peritoneal) and perhaps of lung cancer some 20-50 years later. The statistically significant absence of further mesothelioma cases during the past eight years suggests that crocidolite, though durable, is slowly removed.

Incidence by occupation and industry of work-related skin diseases in the United Kingdom, 1996-2001.

BACKGROUND: Work-related skin disease is common but few cases are documented in statutory reports or disability systems. Voluntary reporting by specialist physicians provides more complete information. AIMS: To summarize incidence rates of work-related skin diseases reported by consultant dermatologists and occupational physicians, with emphasis on contact and allergic dermatitis by occupation and industry. METHODS: Cases reported in 1996-2001 to the EPIDERM and OPRA national surveillance schemes were analysed by causal agent, occupation and industry, with incidence rates calculated against appropriate denominators. RESULTS: Average annual incidence rates based on data from dermatologists were 97 per million overall, 74 for contact dermatitis and 14 for neoplasia. The corresponding rates for occupational physicians were 623 overall, 510 and 2, respectively. For infective disease, the rates for occupational physicians were 28 compared to 2 for dermatologists. Contact dermatitis was most frequently attributed to rubber chemicals, soaps and cleaners, wet work, nickel and acrylics; most cases of contact urticaria were attributed to rubber chemicals or foods and flour. The pattern of incidence rates by occupation and industry was complex, but correlated with the probable type of exposure. Rates of contact dermatitis were highest among skilled workers in the petrochemical and rubber and plastic manufacturing industries, with machine operators and technical workers in metal and automotive industries also at increased risk. High proportions of cases attributed to rubber chemicals were in nurses and technicians in the health and social services. CONCLUSIONS: These findings identify jobs and types of work where contact with causal agents is common and potentially preventable.

Incidence by occupation and industry of acute work related respiratory diseases in the UK, 1992-2001.

AIMS: To summarise incidence rates and epidemiological characteristics of new cases of work related respiratory disease reported by specialist physicians in thoracic and occupational medicine, with particular reference to occupation, industry, and causal agents for asthma, inhalation accidents, and allergic alveolitis. METHODS: Cases reported 1992-2001 to the SWORD and OPRA national surveillance schemes, in which almost all UK chest and occupational physicians participate, were analysed by age, sex, cause, occupation, and industry, with incidence rates calculated against appropriate denominators. RESULTS: Excluding diseases of long latency, infrequently seen by occupational physicians, the distribution of diagnoses in the two specialties was similar, but with rates generally much higher in occupational than chest physicians. Occupational asthma was responsible for about 25% of cases overall, affecting mainly craft related occupations and machinists, and most often attributed to isocyanates, metals, grains, wood dusts, solders, and welding fume. These same occupations were those at highest risk from inhalation injuries, most frequently caused by irritant gases, vapours, and fume. Among medical technicians and nurses, however, glutaraldehyde and latex were the main causes of occupational asthma. Allergic alveolitis was seldom reported, with almost all cases in agriculture, forestry, and fishing. CONCLUSION: During the 10 year period studied, there were few changes in level of reported incidence, apart from some decline in occupational asthma and inhalation injuries. These results and their implications should be distinguished from much higher estimates of asthma made worse by work derived from population surveys, based on prevalence rather than incidence, and self-reported symptoms rather than diagnoses made by specialist physicians. Even so, the reported incidence of new cases of acute respiratory illness caused by work remains substantial.

Asbestos, asbestosis, and lung cancer: a critical assessment of the epidemiological evidence.

The question of whether lung cancer can be attributed to asbestos exposure in the absence of asbestosis remains controversial. Nine key epidemiological papers are reviewed in a point/counterpoint format, giving the main strengths and limitations of the evidence presented. Of the nine papers, two concluded that asbestosis was necessary and seven that it was not. However, the study design, nature and circumstances of exposure and method of analysis of the studies differed considerably, and none was considered definitive. It is concluded that, because of the relative insensitivity of chest radiography and the uncertain specificity of findings from histological examinations or computed tomography, it is unlikely that epidemiology alone can put either the strict scientific or practical medicolegal questions beyond doubt. It is probable that the issue may depend critically on asbestos fibre type, an aspect not so far addressed.

Dose limits for man do not adequately protect the ecosystem.

As has been noted by both of our participants, it is interesting to see that their views approached agreement during the course of the debate. This is not altogether unexpected since the topic is on that has many facets. It is fair to say that protecting man is an appropriate starting point for the protection of other more, or less, radiosensitive life forms sharing the planet with us. That there may be special situations requiring attention has been recognized by both of our participants. That the ICRP recognizes the need for further work on this topic is encouraging for ourselves as well as the 'bugs and bunnies'.

Mortality in a cohort of vermiculite miners exposed to fibrous amphibole in Libby, Montana.

BACKGROUND: Fibrous tremolite is a widespread amphibole asbestiform mineral, airborne fibres of which constitute an environmental hazard in Libby, Montana, northern California, and elsewhere. AIMS: To determine excess risk from lung cancer, mesothelioma, and all-cause mortality in a cohort of men exposed to tremolite, but no other form of asbestos. METHODS: Mortality by certified cause and various measures of exposure to tremolite and related amphibole fibres was assessed in a cohort of 406 vermiculite mineworkers in Libby, Montana, employed before 1963 and followed until 1999. RESULTS: Total deaths were: lung cancer 44 (SMR 2.40), non-malignant respiratory disease (NMRD) 51 (SMR 3.09), all causes 285 (SMR 1.27); included among the total were 12 deaths ascribed to mesothelioma (4.21% of all deaths). Adjusted linear increments in relative risks (per 100 f/ml.y), estimated by Poisson regression, were: lung cancer (0.36, 95% CI 0.03 to 1.20), NMRD (0.38, 95% CI 0.12 to 0.96), and all deaths (0.14, 95% CI 0.05 to 0.26). CONCLUSIONS: The all-cause linear model would imply a 14% increase in mortality for mine workers exposed occupationally to 100 f/ml.y or about 3.2% for a general population exposed for 50 years to an ambient concentration of 0.1 f/ml. Amphibole fibres, tremolite in particular, are likely to be disproportionately responsible for cancer mortality in persons exposed to commercial chrysotile, but to what extent cannot be readily assessed.

On the interpretation and use of neutron calibration coefficients.

Calibration laboratories provide measurement services that include determining the calibration coefficients for neutron survey meters and personal dosemeters. While there are numerous documents dealing with the procedures for calibration of neutron measuring devices, the purpose of this paper is to clarify the use of the particular dose equivalent conversion coefficients used at the National Institute of Standards and Technology and the Pacific Northwest National Laboratory for these calibrations.