The generation mechanisms and repeatability of 2F1-F2 distortion product otoacoustic emissions: study on normally hearing subjects.

The 2F1-F2 distortion product otoacoustic emission (DPOAE) is considered to consist of two generation mechanisms, the so-called place-fixed and wave-fixed mechanisms, depending on the frequency ratio F2/F1. The general assumption is that for a small frequency ratio there is a predominantly place-fixed emission mechanism, while with a larger frequency ratio there is a predominantly wave-fixed mechanism. There is also a lack of published data on the repeatability of the two components when separated. One aim of this study was therefore to identify the wave-fixed and place-fixed components of the 2F1-F2 DPOAE using a time-window separation method. The second aim was to quantify the test-retest repeatability of the separated 2F1-F2 DPOAE components in a group of normally hearing subjects. Results confirmed the presence of wave-fixed and place-fixed components for 2F1-F2 and a predominance of place or wave-fixed DPOAE as a function of frequency ratio. This pattern varied somewhat among subjects. Moreover, regardless of which component was stronger for any F2/F1, both components were highly repeatable across time within individual ears.

Altered venous function and deep venous thrombosis following proximal femoral fracture.

The effect of surgery for femoral neck fracture on lower limb venous blood flow and its relationship to deep vein thrombosis was investigated in 179 patients. Blood flow was measured using strain gauge plethysmography before surgery, in the 1st week after surgery, and at 6 week review. There was a significant reduction in both venous outflow and venous capacitance, affecting both fractured and non-fractured legs but significantly greater in the fractured leg. Venous function remained significantly impaired in both lower limbs 6 weeks after surgery. There was a significant correlation between the reduction in venous function and the development of deep vein thrombosis.

Changes in coagulability as measured by thrombelastography following surgery for proximal femoral fracture.

The effect of surgery for femoral neck fracture on whole blood coagulation and the relationship of altered coagulation to deep venous thrombosis were investigated in 250 patients. Whole blood coagulation was measured using thrombelastography preoperatively, in the early postoperative period and at 6-week review. Significant hypercoagulability was demonstrated after surgery and persisted to 6-week review. A significant correlation between hypercoagulability and the development of deep venous thrombosis is demonstrated. Hypercoagulability is shown to be a major factor in thrombosis formation following proximal femoral neck fracture surgery.

Biological monitoring values for occupational exposure: a United Kingdom perspective.

Policy developments in the United Kingdom have been aimed at facilitating the appropriate use of biological monitoring. Recent initiatives have established clear criteria for the interpretation of biological monitoring results, and new guidance that deals with the ethical and practical issues involved in operating an effective biological monitoring programme has been promulgated. The United Kingdom now has a system of non-statutory biological monitoring guidance values. There are two types, the health guidance value and the benchmark guidance value. Over a number of years, biological monitoring programmes have shown that they help in reducing exposure by regular monitoring and demonstrating adequate control.

New technologies in the use of exhaled breath analysis for biological monitoring.

Breath analysis is an attractive non-invasive procedure for screening workers exposed to solvents. It has been used in numerous laboratory based studies and for field research. Despite the obvious advantages in routine biological monitoring it has failed to become widely accepted as a tool in occupational hygiene. Recent advances in breath sampling and analysis are such that it is likely to become more widely used in the future. In this paper, the past 5 years have been reviewed to try to assess what developments might now contribute to the increased use of breath analysis in biological monitoring; in particular, the development of a selected ion flow tube mass spectrometer for real time direct analysis of trace gases in breath and the more immediately available and less expensive indirect methods involving collection devices with adsorbent tubes is important. The introduction of guidance values for biological monitoring with clear advice on sampling times and the recognition of the importance of quality assurance programmes will help improve confidence in the technique.

A biological monitoring study of 1-methoxy-2-propanol: analytical method development and a human volunteer study.

1-Methoxy-2-propanol (M2P) is finding increasing industrial use as a less toxic alternative to the short-chained ethylene glycol ethers. Like most glycol ethers, M2P is readily absorbed through the skin and biological monitoring is therefore appropriate in assessing occupational exposure. An analytical method, suitable for routine monitoring, was developed for the determination of free M2P in urine. The method involves solvent extraction, gas chromatography-mass spectrometry and is sensitive (detection limit 1 mumol/l), specific and reproducible (intra- and inter-assay coefficients of variation 5% and 9%, respectively). A human volunteer study, involving six volunteers, was also conducted. Volunteers were exposed to 100 ppm M2P for 8 h (the occupational exposure standard in the UK) including a 30-min break. Post-exposure levels of free M2P in urine were found to reach up to 110 mumol/l). Levels of M2P were also monitored in blood (maximum 103 mumol/l) and exhaled air samples (up to 252 nmol/l). The volunteer study showed that M2P is rapidly excreted in urine with a half-life of less than 2.6 h.

A novel device for capturing breath samples for solvent analysis.

We have developed a novel breath sampling device suitable for capturing a portion of end-tidal air. This breath sample is then transferred onto a Perkin Elmer automated thermal desorption (ATD) sampling tube which is subsequently analysed by ATD-gas chromatography-mass spectrometry (GCMS). The breath sampler has been evaluated in the laboratory, in brief field trials and in human volunteer studies. The method is sensitive with a typical detection limit of 1 nmol/l and reproducible with an overall coefficient of variation between 5% and 15% for collection and analysis of breath samples from volunteers. The field trials used the sampler to assess exposure to solvents in several industries including the shoe manufacturing industry, the inks and coatings industry and at dry cleaning establishments. The sampler was found easy to use and reliable. Solvents detected include ethyl acetate (6.4-25.5 nmol/l), propan-2-ol (3.4-39.3 nmol/l), 2-butanone (0-6.6 nmol/l) and tetrachloroethene (0-557 nmol/l). The breath sampler was also used to monitor the elimination of solvents in breath from human volunteers after exposure chamber studies. More than 500 breath samples have been analysed from 24 volunteers in exposures to 10 different solvents (toluene, trimethyl benzene, tetrachloroethene, tetrahydrofuran, acetone, propan-2-ol, xylene, 2-butanone, 1-methoxy-2-propanol and n-hexane). The breath sampler allowed the rapid and non-invasive collection of data on elimination of solvents.

An investigation of occupational metal exposure in thermal spraying processes.

A cross-sectional study of 34 workers engaged in thermal spraying at six worksites was undertaken in order to determine levels of exposure to and uptake of metals during different metal spraying activities. Levels of exposure to cobalt, chromium and nickel were highest in plasma sprayers and, on occasions exceeded UK Occupational Exposure Limits. Exposure to metals during detonation gun and electric arc spraying was better controlled and levels remained below the relevant Occupational Exposure Limits throughout the study period. Urinary levels of cobalt and nickel mirrored the airborne concentrations and the highest urine concentrations were again found in plasma sprayers. Urinary chromium levels were highest in electric arc sprayers, which may also reflect an increased body burden in this group due to a longer history of exposure. The findings clearly indicate that exposure to and uptake of metals may exceed UK Occupational Limits or Standards when spraying is performed manually or semi-automatically and where control relies on local exhaust ventilation (LEV) and personal respiratory protective equipment (RPE).

Recent policy and technical developments in biological monitoring in the United Kingdom.

In 1996 the United Kingdom's Health and Safety Executive introduced biological monitoring guidance values for six substances, butoxyethanol, N,N-dimethylacetamide, lindane, methylene-bis(2-chloroaniline), mercury and methylenedianiline. These guidance values were set as either health-based values or hygiene-based values calculate according to the 90th percentile (benchmark concept). Recent technical developments from the Health and Safety Laboratory are described in this paper and include: (i) the use of breath analysis as a useful non-invasive routine monitoring technique; (ii) flow cytometry as a means for measuring different patterns of immune cell activation from workers exposed to respiratory sensitisers when compared with those exposed to chemical irritants; (iii) the use of molecular techniques to explore the possible role of individual susceptibility in the development and severity of glomerulonephritis; (iv) the development of expert systems for predicting the skin permeability of chemicals, and respiratory and skin sensitisation.

The determination of silver in whole blood and its application to biological monitoring of occupationally exposed groups.

A sensitive and rapid technique for directly measuring silver in blood, using electrothermal atomization atomic absorption spectrophotometry (ETAAS) is described. The method can be used to analyse precisely up to 40 blood samples a day in duplicate. Well-mixed, whole blood samples, collected in EDTA, were diluted 1 + 4 with a diluent containing 40 g l.-1 ammonium dihydrogen orthophosphate and 0.5 ml l.-1 Triton X-100. Aliquots of diluted blood were then analysed by ETAAS using wall atomization with a pyrolytically coated tube. The coefficient of variation for within-run precision was 4.55% at 10 micrograms 1.-1 and 5% at 25 micrograms 1.-1 Between-run variation, it was 4.1% at 25 micrograms l.-1 The analytical recovery for the method was 98% +/- 3% at both 8 and 30 micrograms 1. -1 The detection limit of the method was 0.1 microgram 1. -1, which was sufficiently sensitive to distinguish exposed from non-exposed individuals. Blood silver levels in unexposed subjects were found to be between < 0.1 and 0.2 micrograms 1. -1. Blood silver levels were determined in 98 occupationally exposed workers involved in bullion production, cutlery manufacture, chemical manufacture, jewelery production and silver reclamation. Blood silver levels ranged from 0.1 to 23 micrograms 1.-1, with some of the highest levels found in silver reclaimers.

Methylene bis (2-chloroaniline) (MbOCA): towards a biological monitoring guidance value.

Abstract We report the development and validation of a high performance liquid chromatography method for the determination of methylene bis (2-chloroaniline) (MbOCA) and its labile conjugates in urine. The method has been in regular use for the biological monitoring of workers exposed to MbOCA for the past 11 years. Following the development of a biological monitoring strategy, and the introduction of a biological action level by the Health and Safety Commission in 1984, there has been a steady fall in the proportion of workers whose urinary results are above the action level. We conclude that, in the absence of reliable health-based data, a guidance value based on the use of the 90th percentile derived from monitoring a cross-section of the industry, can be used to interpret biological monitoring results. The measurement of urinary MbOCA is a practical non-invasive way of monitoring workers which can be useful in helping to control exposure.

Exophthalmos and iatrogenic Cushing's syndrome.

A 38-year-old physician presented with a 9-month history of progressive self-administration of oral prednisone < or = 160 mg per day for Addison's disease. Examination demonstrated typical Cushingoid features and bilateral proptosis with elevated intraocular pressure. Computed tomography disclosed increased intraorbital adipose tissue. We hypothesize that the increased intraorbital adipose deposition was due to the differential binding of glucocorticoids to adipose tissue receptors and an enhancement of lipoprotein lipase activity. We conclude that the findings in this case may be related to glucocorticoid-induced changes in the ocular and periorbital structures. Cushing's syndrome should be considered in the differential diagnosis of acquired exophthalmos and elevated intraocular pressure and findings of increased orbital fat on orbital imaging.

A biological monitoring assessment of exposure to methylene dianiline in manufacturers and users.

This paper describes a cross sectional study in which biological monitoring was used to assess exposure to methylene dianiline (MDA) in a selection of United Kingdom industries that manufacture or use MDA. Samples of urine were collected from 411 workers, representing 45 factories engaged in various activities. All urine samples were analysed for MDA and its acetyl metabolites and results are reported as total MDA. In this study, 91% of postshift urine samples and 88% of preshift samples had less than 50 nmol MDA/mmol creatinine. Some evidence was obtained which showed that when exposure to MDA was through inhalation (as solid material or contaminated dust), postshift urine samples had higher MDA concentrations than samples taken preshift the next day. When exposure was most likely to be through the dermal route, urine samples taken preshift next day tended to have higher MDA concentrations than urine samples collected immediately postshift on the day of exposure. Therefore a biological monitoring sampling strategy for MDA must take account of the route of entry into the body. If exposure is likely to be via inhalation, postshift samples should be collected and if exposure is likely via the skin, preshift samples next day are more appropriate. The results show that in most factories, regardless of the route of exposure, it is possible to keep urinary MDA concentrations below 50 nmol/mmol creatinine. In the absence of a health based or hygiene based standard, the use of a "yardstick" as a target to aim for, which has been derived from good working practice across the industry, may be a useful way of helping to control exposure.

Aging and spontaneous reactivation of human plasma cholinesterase activity after inhibition by organophosphorus pesticides.

The in vitro rates of aging and spontaneous reactivation of human plasma cholinesterase (ChE) after inhibition by several organophosphorus pesticides (OPs) have been studied. After inhibition by OP the enzyme can undergo two simultaneous reactions; spontaneous reactivation to the active enzyme and 'aging' to an irreversibly inhibited form of the enzyme. The rates of these two reactions depend on the nature of the phosphoryl group of the OP bound to the active site of ChE. Most OPs registered for use in the UK have dimethoxy or diethoxy groups attached to the phosphorus atom. Reaction rate constants for aging and spontaneous reaction are reported. Dimethoxy OPs cause half-lives of aging in human plasma ChE of approximately 6 hours and 23 hours at 37 degrees C and 22 degrees C respectively; for diethoxy OPs the values are 12 hours and 39 hours. Reappearance of enzyme activity, after removal of OP, reduced any inhibition by a maximum of 25% for dimethoxy OPs; this reappearance of enzyme activity occurs with a 'half-life' of 5 hours and 15 hours at 37 degrees C and 22 degrees C. These effects, both in vivo and ex vivo, may have relevance in developing a monitoring strategy for dimethoxy OPs using plasma ChE measurements. Inhibition by diethoxy OPs spontaneously reactivates very slowly, even at 37 degrees C, and would not practically influence the measured inhibition. No spontaneous reactivation was detected in human plasma ChE inhibited by the methoxy-ethylamino substituted OP (propetamphos) or the methoxy-methylamino substituted OP (crufomate) during 45 hours incubation at 37 degrees C.

The effect of seafood consumption on the assessment of occupational exposure to arsenic by urinary arsenic speciation measurements.

The determination of arsenite, arsenate, dimethylarsenic acid (DMA) and monomethylarsonic acid (MMA) in urine has been used for assessing occupational exposure to inorganic arsenic because these species were thought to be unaffected by dietary arsenic. However, this investigation reports how the consumption of certain types of seafood can lead to an increase in the amount of DMA excreted and hence an elevation in the urinary arsenic speciation total. Urine samples collected from volunteers between 4-20 hours after the ingestion of moderate-sized portions of mackerel, herring, crab or tuna, showed mean increases in the arsenic speciation totals of between 1.8 and 6.9 times compared with the levels in samples collected before the seafood was consumed. These findings have important implications in devising a biological monitoring strategy for workers exposed to inorganic arsenic.

The measurement of salivary cadmium by electrothermal atomic absorption spectrophotometry and its use as a biological indicator of occupational exposure.

We have examined the potential use of salivary cadmium measurements for the biological monitoring of occupational cadmium exposure, paying particular attention to the contamination risks associated with such measurements. We have developed a method for the direct determination of cadmium in saliva by graphite furnace atomic absorption spectrophotometry, which minimizes the risk of contamination during sample preparation and analysis. The limit of detection is 0.6 nmoll-1, which is sufficiently sensitive to discriminate between unexposed and occupationally exposed individuals. The method has been employed to measure cadmium levels in saliva samples collected by two different methods from an unexposed population, a group of ex-workers previously exposed to cadmium (Group 1), and two groups of currently exposed workers (Groups 2 and 3). Salivary cadmium levels were significantly raised in both of the groups of currently exposed individuals (group 2 median (Md) = 17 nmoll-1, group 3 Md = 70 nmoll-1, p greater than 0.0001), and in past workers with previous long-term exposure (Group 1 Md = 2.5 nmoll-1, p greater than 0.001) when compared with an unexposed population. The results suggest that the measurement of salivary cadmium may reflect recent exposure to the metal. However, considerable care must be taken in collecting samples because a risk of contamination during sampling is apparent with procedures commonly used for saliva collection, and for this reason the applicability of such measurements for biological monitoring is limited.

The response of evidential breath alcohol testing instruments with subjects exposed to organic solvents and gases. I. Toluene, 1,1,1-trichloroethane and butane.

Experimental work has been undertaken to investigate the potential interference of toluene, 1,1,1-trichloroethane and butane with the evidential breath alcohol testing instruments used in Great Britain (Lion Intoximeter 3000 and Camic Breath Analyser). Volunteers inhaled the volatile substances in an exposure chamber for up to 4 hours, at concentrations of 100, 350 and 600ppm respectively. Subsequently breath was tested on leaving the chamber. No interference was observed with the breath alcohol instruments when the subjects were exposed to toluene and 1,1,1-trichloroethane. A short-term response immediately after exposure was observed for subjects exposed to butane. Further analytical work involving blood and breath samples demonstrated that all three volatile substances were absorbed during exposure and were detectable in blood for at least 3 hours post-exposure. Their elimination post-exposure followed an exponential decay.

The response of evidential breath alcohol testing instruments with subjects exposed to organic solvents and gases. II. White spirit and nonane.

Following exposure to white spirit vapour, the effect of the expired solvent on evidential breath alcohol equipment was investigated under controlled exposure chamber conditions and in a simulated painting exercise. Five volunteers inhaled the solvent in an exposure chamber at a concentration of 100ppm for periods up to 4h 17min. Two other volunteers were exposed to white spirit while painting with domestic gloss paint in an unventilated room under which conditions exposure concentrations reached 185ppm for 20min. Following all white spirit exposures, volunteers underwent breath tests with the Lion Intoximeter 3000. In all instances the apparent alcohol responses were very small and never exceeded a reading of 1 microgram/100ml for breath samples more than 10min post-exposure. Simultaneous analytical work was conducted to demonstrate that white spirit was absorbed during exposure and was present in the breath and blood after the volunteers had left the exposure atmospheres. A further study involved the exposure of a volunteer to nonane vapour at 100ppm, demonstrating that this compound, being one of the principal components of white spirit, appears to be a good model for studying the uptake and elimination of white spirit.

Chest pain in the accident and emergency department: is chest radiography worthwhile?

Four per cent of patients attend the Accident and Emergency Department (A&E) present with chest pain. In this prospective study of 297 patients the value of chest radiography is assessed. Overall, 23% of chest X-rays (CXRs) had an abnormality which influenced management of the patient, rising to 40% in those patients admitted to Coronary Care. Twenty-nine per cent of CXRs were misinterpreted by Casualty Officers but resulted in the mismanagement of only six patients (3.3%). Potentially serious errors were averted by early CXR audit by a Radiologist.