Surveillance case definitions for work related upper limb pain syndromes.

OBJECTIVES: To establish consensus case definitions for several common work related upper limb pain syndromes for use in surveillance or studies of the aetiology of these conditions. METHODS: A group of healthcare professionals from the disciplines interested in the prevention and management of upper limb disorders were recruited for a Delphi exercise. A questionnaire was used to establish case definitions from the participants, followed by a consensus conference involving the core group of 29 people. The draft conclusions were recirculated for review. RESULTS: Consensus case definitions were agreed for carpal tunnel syndrome, tenosynovitis of the wrist, de Quervain's disease of the wrist, epicondylitis, shoulder capsulitis (frozen shoulder), and shoulder tendonitis. The consensus group also identified a condition defined as "non-specific diffuse forearm pain" although this is essentially a diagnosis made by exclusion. The group did not have enough experience of the thoracic outlet syndrome to make recommendations. CONCLUSIONS: There was enough consensus between several health professionals from different disciplines to establish case definitions suitable for use in the studies of several work related upper limb pain syndromes. The use of these criteria should allow comparability between studies and centres and facilitate research in this field. The criteria may also be useful in surveillance programmes and as aids to case management.

Non-specific symptoms in response to hazard exposure in the workplace.

Recent concerns in occupational health have shown a shift in emphasis from the study of diseases with well-established pathology toward the investigation of conditions characterized by a range of nonspecific symptoms. Exposure to potential hazards differing widely in terms of their physical nature or chemical composition, for example, electromagnetic fields, organophosphate-based pesticides, and organic solvents, frequently results in the reporting of a relatively consistent group of symptoms. Furthermore, these symptoms may arise among groups of workers where no specific physical or chemical cause can be implicated; for example, in many cases of sick building syndrome. The role of psychosocial factors in the expression of ill-health has been well-documented in the psychological literature. Important modifying factors include the attitudes and belief systems of the individuals concerned, certain personality and behavior patterns, and the presence of current stress or pre-existing psychological distress. In addition, social processes may be involved in the generation and reinforcement of health concerns at the group level. These include the workers' perceptions of the competence and credibility of managers and professionals, and the influence and involvement of the media, pressure groups, and the legal system. A proper understanding of the association between putative hazards and the reporting of nonspecific symptoms therefore requires consideration not only of the direct physical pathway between hazard and harm, but also an assessment of factors which may modify the relationship between exposure and symptom reporting. The results of such investigations have important implications for determining the focus of any management and control strategies which may subsequently be implemented in the workplace.

Quality control of biomarker measurement in epidemiology.

The throughput and complexity of a biomarker assay will determine the amount of effort that can be expended on quality control and assurance. Clinical chemistry quality control procedures can be readily applied to simpler chemical analysis such as blood lead and cholesterol, but even complex cell-based biomarker techniques such as HPRT mutation analysis and cytogenetics benefit from a formal quality control approach. Collaborative interlaboratory exercises are essential, especially when no certified reference material is available, and these can play a central role in the control of laboratory drift. Recommendations are made for the quality control of biomarker measurement based on clinical chemistry techniques. These include recommendations for coding samples so that the laboratory scientist is unaware of exposure status and for the use of formal laboratory protocols.

Modifiers of non-specific symptoms in occupational and environmental syndromes.

Many occupational and environmental health hazards present as an increased reporting of non-specific symptoms such as headache, backache, eye and respiratory irritation, tiredness, memory problems, and poor concentration. The pattern and number of such symptoms is surprisingly constant from hazard to hazard suggesting that common psychological and social factors, not directly related to the exposure may be involved. A recent workshop (see acknowledgements) was held to review the pattern of symptoms in varying hazardous situations and the psychological mechanisms behind the genesis and maintenance of symptoms. The involvement of both direct physicochemical and psychological mechanisms in symptom generation and reporting in any situation was discussed and is reported here. A model that identifies the issues that need to be considered in any epidemiological study based on the incidence or prevalence of non-specific symptoms is proposed.

The use of multiple parameters to characterize cadmium-induced renal dysfunction resulting from occupational exposure.

Renal function has been examined in a group of 77 subjects occupationally exposed to cadmium fume and dust, together with a referent group of 103 age- and socioeconomically matched subjects. Fourteen biochemical parameters were measured on each subject. Three different ways of combining the information from all 14 tests were used to identify those subjects with renal dysfunction. These were first to count the number of parameters in which a subject recorded an abnormal test result. Second, the z value was computed for each parameter for each person by comparison with the mean and standard deviation of a derived normal population; these z scores were then summed. Lastly a multivariate distance measure, Mahalanobis D2, was determined for each subject from the distribution of normal subjects. The three approaches showed a considerable degree of agreement in identifying subjects with renal dysfunction, but they also displayed complementary strengths and weaknesses. The consensus of the three techniques was then taken to define truly dysfunctional subjects and each of the 14 parameters, and some combinations of pairs of parameters were tested as to their sensitivity and specificity. For this group of subjects, it was not possible to improve greatly on the use of retinol binding protein on its own. Were a second parameter to be chosen, it would be desirable to choose one reflecting the glomerular filtration rate, but the absence of a suitable sensitive biological monitoring parameter precludes a firm recommendation.

Evidence that a beta-N-glucuronide of 4,4'-methylenebis (2-chloroaniline) (MbOCA) is a major urinary metabolite in man: implications for biological monitoring.

Urine samples from workers exposed to 4,4'-methylenebis (2-chloroaniline) (MbOCA) contain a labile metabolite(s) that, on hydrolysis, yields the parent compound at concentrations two to three times those of free MbOCA. Evidence has now been obtained that the major labile metabolite is an N-glucuronide of MbOCA. The N-glucuronide of MbOCA was synthesised chemically, characterised by thermospray mass spectrometry, and found to have a pseudomolecular (M + 1) ion at m/z 443/445. MbOCA and [14C] uridine diphosphoglucuronic acid [( 14C]UDPGA) were incubated with liver microsomes from rats induced with polychlorinated biphenyls. The stoichiometry of the reaction product was about 1:1 (MbOCA:UDPGA). This product, the chemically synthesised glucuronide, and the labile urinary metabolite had identical chromatographic and hydrolytic (heat and beta-glucuronidase) properties. These studies show that the major labile conjugate of MbOCA in the urine of workers exposed to this compound is probably the mono N-glucuronide. In view of the lability of this compound and the fact that its concentration in urine is two to three times that of free MbOCA, it is essential that any strategy for the biological monitoring of exposed workers takes into account the N-glucuronide.

Interactions of m-xylene and aspirin metabolism in man.

In a series of experiments to investigate interactions between industrial solvents and common medications the interaction between m-xylene and aspirin was studied. As both these substances are metabolised and excreted as glycine conjugates there would possibly be competition for this conjugation pathway. Five male volunteers were exposed on separate occasions to m-xylene by inhalation (100 ppm), aspirin (1500 mg) by mouth, and m-xylene and aspirin together under controlled conditions in an exposure chamber. Urine and blood samples were collected and analysed for m-xylene, aspirin, and their metabolites. The amounts of the major glycine conjugates produced from m-xylene (m-methylhippuric acid) and aspirin (salicyluric acid) were significantly reduced by about 50% when m-xylene and aspirin were coadministered. There appears to be a mutual inhibition on the formation of the respective glycine conjugates. It is suggested that the inhibition is due to competition for either the enzymes, acyl-CoA synthetase, or glycine N-acylase. These findings have implications in the biological monitoring of workers exposed to m-xylene.

Clinical and immunological investigations of respiratory disease in workers using reactive dyes.

A questionnaire survey of over 400 workers handling reactive dyes showed that over 15% had work related respiratory or nasal symptoms. Forty nine employees with symptoms were referred to chest clinics for detailed assessment. It was considered that in 19 the symptoms could be attributed to an irritant response to a variety of chemicals, including hydrochloric acid vapour, sulphur dioxide, and reactive dyes. Symptoms in 24 were attributed to an allergic reaction to a specific agent; in most (21) to one or more reactive dyes. Two patterns of allergic lower respiratory symptoms were identified; an immediate response of short duration and a longer lasting response, usually of several hours, sometimes accompanied by nocturnal asthma. A radioallergosorbent test (RAST) screen containing the most commonly used reactive dyes was used to detect specific IgE. Allergic symptoms to reactive dyes were strongly associated with specific IgE (17/21 employees) and atopy (18/21). Irritant symptoms were also associated with atopy (13/19) but only weakly associated with specific IgE (7/19).

Behavioral changes during exposure to 1,1,1-trichloroethane: time-course and relationship to blood solvent levels.

We report the results of an exposure chamber study in which volunteers were exposed to 0, 950 mg.m-3 (175 ppm) and 1,990 mg.m-3 (350 ppm) of 1,1,1-trichloroethane for 3.5 hours. The time-course of the behavioral changes and the relationship to blood concentrations of 1,1,1-trichloroethane were investigated. A pattern of performance deficits consistent with earlier work was found for some of the tests of psychomotor performance. The time-course of these appeared to be rapid, occurring in some cases within 20 minutes of exposure. For those tasks shown to be sensitive to 1,1,1-trichloroethane exposure, the development of performance changes followed the time-course of blood solvent levels. Two behavioral tests not previously used in this type of work were also employed. One was concerned with the distractability of attention and concentration (the Stroop test), and the other was concerned with analysing grammatical statements (the syntactic reasoning test). Different effects were found. In the Stroop test, enhanced performance was observed following exposure; however, the syntactic reasoning test was found to be resistant to solvent effects. Measures of short-term subjective well-being were not affected by exposure. It is suggested that the observations of time-course effects in performance and their relationship to change in blood solvent levels have implications for psychological test selection and for study designs for examining field exposure.

Urinary mutagenicity assays: a problem arising from the presence of histidine associated growth factors in XAD-2 prepared urine concentrates, with particular relevance to assays carried out using the bacterial fluctuation test.

The appearance of mutagenic activity in urine samples from a group of nurses and from unexposed individuals has been investigated using the bacterial fluctuation test. Apparent mutagenic activity was seen in samples from all subjects and did not appear to be related to any specific occupational or environmental exposure. This activity seems to be related to the presence of histidine or histidine-related auxotrophic growth factors in the urine concentrates, not completely removed by the recommended XAD-2 column procedure. It is suggested that the reliance on XAD-2 columns for the removal of histidine may produce spurious results when using this assay to screen populations for exposure to mutagenic chemicals.

Renal dysfunction in cadmium smelters: relation to in-vivo liver and kidney cadmium concentrations.

Biochemical indicators of renal dysfunction have been compared with liver and kidney cadmium levels measured by neutron activation analysis in a group of 37 cadmium smelters. Higher than normal concentrations of cadmium in the liver reflect past exposure; they were associated with evidence of renal dysfunction in workers exposed to cadmium for more than 10 years. A small group of 6 workers exposed to cadmium for only a short time (mean = 4.6 years) had high hepatic cadmium concentrations but normal renal function. Longitudinal studies are required to establish the natural history of renal dysfunction following cadmium accumulation in industrial workers.

Effect of alcohol on the kinetics of mandelic acid excretion in volunteers exposed to styrene vapour.

The effect of a dose of alcohol on the kinetics of mandelic acid excretion in four volunteers exposed to 220 mg/m3 styrene has been investigated under controlled exposure chamber conditions. Ethanol inhibited the excretion of mandelic acid, so that the peak excretion was delayed from the end of the exposure period until three hours afterwards. One hour after administration of ethanol blood mandelic acid concentrations were 56% of the levels found during the alcohol-free control exposure, and this was paralleled by a 15-fold rise in phenylethane 1,2 diol, the metabolic precursor of mandelic acid. It is suggested that the inhibition of the oxidation of this diol is related to the change in NAD +/NADH ratio produced by ethanol metabolism. The implications of this ethanol effect on the interpretation of urinary mandelic acid excretion when monitoring workers exposed to styrene are discussed.