Creatinine adjustment of biological monitoring results.

BACKGROUND: Biological monitoring (BM) aids exposure assessment but where this is based on incomplete collections of single urine voiding measurement of creatinine is often used to adjust analyte concentrations for the effects of fluid balance. AIMS: To provide reference data on creatinine concentrations in urine samples from a population of UK workers. METHODS: Urine samples sent to the Health and Safety Laboratory were analysed for creatinine by an automated kinetic Jaffe technique using alkaline picric acid and the results stored in a database. Statistical analysis of the data used linear mixed effects models on the natural log-transformed data. RESULTS: Between 1996 and 2007, the laboratory analysed 49 506 urine samples from 20 433 UK adult workers. In the 42 817 samples where gender was known, 93% were from men and 7% were from women. The overall mean and median creatinine concentrations were both 12 mmol/l corresponding to 1.36 g/l. The mean (13 mmol/l) and median (12 mmol/l) creatinine concentrations for men were higher than those (9 and 10 mmol/l, respectively) for women. CONCLUSIONS: Gender differences in creatinine concentrations and the range of 0.3-3.0 g/l (2.653 and 26.53 mmol/l) traditionally used for confirming acceptability of urine samples mean that 2.5% of samples from male and 9% from female workers were flagged as 'low creatinine' and required a repeat sample. In addition, care should be taken interpreting any apparent gender differences in BM results to ensure that they are due to exposure and not an artefact of creatinine adjustment.

Urinary biomarkers and occupational musculoskeletal disorders in the lower limbs.

BACKGROUND: Causation of occupational musculoskeletal disorders of the lower limbs (LLMSDs) may be multifactorial, including abnormal biological processes. Clinically validated biomarkers that reflect degradation of bone, cartilage and synovial tissue may be useful in identifying such processes in those presenting with LLMSD. AIMS: To investigate two urinary biomarkers as objective measures of occupational LLMSDs. METHODS: This cross-sectional study involved both working (n = 146) and case cohorts (n = 62); the latter were derived from general practitioner referrals or those occupationally re-deployed due to LLMSDs. Urine measurements of the c-telopeptides of collagens I and II and two validated quantitative questionnaires [SF12v2 and the Rheumatoid and Arthritis Outcome Score (RAOS) questionnaires] were the outcome measures. RESULTS: Urinary collagen II biomarker had largely the same significant discriminant power in distinguishing working from case cohorts, as several item scores within the RAOS questionnaire. Increased perceived pain within the RAOS questionnaire was statistically correlated to higher levels of the collagen II biomarker in all subjects and the combined working cohorts. However, both the pain score and the collagen II biomarker were significant but independent variables in distinguishing cases from non-cases. High levels of current or past sports activity involving the lower limbs were not significant explanatory variables of the collagen II levels. Collagen I biomarker showed no discriminant power between cases and working cohorts, suggesting that increased bone turnover was not a significant feature in the LLMSD cases. CONCLUSIONS: Urinary c-telopeptide of collagen II showed promise as a non-invasive, objective marker of abnormal biological process in LLMSDs.

Uptake and quality of health surveillance for noise and hand-arm vibration.

BACKGROUND: Health surveillance (HS) is required for employees if noise or hand-arm vibration (HAV) exposures are likely to be above exposure action levels. The extent to which employers comply with Health and Safety Executive (HSE) regulations is unclear. AIMS: To establish the uptake and quality of HS for noise and HAV in high-risk industries. METHODS: A cross-sectional telephone-based questionnaire study involving employers in high-risk industries for noise or HAV. RESULTS: A total of 246 and 386 interviews were completed for noise and HAV, respectively. The uptake of HS in the cohorts was 17 and 10%, respectively. Selection of those companies thought to have 'higher risk' increased the uptake to 25 and 18%, respectively. The proportion of companies carrying out HS was strongly related to the size of the company, with smaller companies less likely to provide this for their employees. A large proportion of companies that reported having HS in place had formal procedures for managing exposed workers (90 and 83% for noise and HAV, respectively), received feedback on individual workers (81 and 80%) and some reported that they used this information to inform their risk management process (58 and 63%). The frequency of HS for HAV was in line with that suggested in HSE guidance in 70% of cases, however, for noise, it was often utilized more frequently. CONCLUSIONS: While many of the companies appear to be following HSE guidance, there is a significant number that are not. Further initiatives that engage with smaller companies may help increase HS provision.

Exposure assessment in health assessments for hand-arm vibration syndrome.

BACKGROUND: Assessing past cumulative vibration exposure is part of assessing the risk of hand-arm vibration syndrome (HAVS) in workers exposed to hand-arm vibration and invariably forms part of a medical assessment of such workers. AIMS: To investigate the strength of relationships between the presence and severity of HAVS and different cumulative exposure metrics obtained from a self-reporting questionnaire. METHODS: Cumulative exposure metrics were constructed from a tool-based questionnaire applied in a group of HAVS referrals and workplace field studies. These metrics included simple years of vibration exposure, cumulative total hours of all tool use and differing combinations of acceleration magnitudes for specific tools and their daily use, including the current frequency-weighting method contained in ISO 5349-1:2001. RESULTS: Use of simple years of exposure is a weak predictor of HAVS or its increasing severity. The calculation of cumulative hours across all vibrating tools used is a more powerful predictor. More complex calculations based on involving likely acceleration data for specific classes of tools, either frequency weighted or not, did not offer a clear further advantage in this dataset. This may be due to the uncertainty associated with workers' recall of their past tool usage or the variability between tools in the magnitude of their vibration emission. CONCLUSIONS: Assessing years of exposure or 'latency' in a worker should be replaced by cumulative hours of tool use. This can be readily obtained using a tool-pictogram-based self-reporting questionnaire and a simple spreadsheet calculation.

Biomonitoring at the UK Health and Safety Laboratory.

The UK Health and Safety Laboratory (HSL) provides research and analytical support to the Health and Safety Executive, other Government Departments and employers. In the area of biomonitoring HSL conducts research studies and provides an analytical service for regular surveillance of worker exposure to hazardous substances. This paper gives brief examples of how data from such studies can be used to develop biological monitoring guidance values for isocyanates, polycyclic aromatic hydrocarbons and hexavalent chromium. In addition, a study of occupational exposure to copper chrome arsenic wood preservatives is briefly described to show how biological monitoring can be used for post-approval surveillance of a biocide.

Exposure to antineoplastic drugs in two UK hospital pharmacy units.

STUDY OBJECTIVES: To carry out an environmental and biological monitoring study in two UK hospital pharmacy units involved in the preparation of antineoplastic drugs. PARTICIPANTS AND METHODS: The two units studied used isolators for drug preparation. One used isolators operating at positive pressure relative to external atmospheric pressure, whereas the other used negative pressure isolators. Monitoring utilized the measurements of methotrexate, ifosfamide, cyclophosphamide and platinum reflecting the platino-coordinated drugs, such as cisplatin and carboplatin. Personal and static atmospheric and floor wipe samples were collected together with preshift and post-shift urine samples over a 4-day consecutive monitoring period. During the study period both units operated to their normal procedures. RESULTS: Measurable amounts of cytotoxic drugs were detected on the floors of both units and on the disposable gloves worn by staff preparing the drugs. There was also evidence in both units of some very low-level drug absorption from urine measurements, using the most sensitive analytical technique of platinum analysis. The absorption of platinum containing drugs in the unit using negative-pressure isolators was significantly higher, even though less platinum containing drug was prepared per day. Urine measurements in both units were below the detection limit for the other measured drugs. Although the unit using positive-pressure isolators handled daily approximately five times the drug quantities handled with the negative pressure unit, the general levels of external contamination and urine measurements did not reflect this difference. Comparison of the relative levels of glove and floor contamination between the two units was not clear-cut and appeared to depend on the specific cytotoxic drug being monitored. CONCLUSIONS: The levels of external contamination on the floor and gloves, and absorbed dose from urine measurements found in this study showed considerable improvement over many earlier, non-UK studies using comparable exposure measurements. These earlier studies were in facilities using laminar flow/microbiological safety cabinets and where staff were likely to be involved in both drug preparation and administration. Our data did not suggest that the differential pressure of the isolator to the pharmacy atmosphere was an overarching factor in the risk of operator exposure under normal operation. There remains a need to investigate the sources of the low-level drug contamination found in the pharmacies even when using isolators to prepare cytotoxic drugs. This study, and related studies of hospital oncology ward staff, appear to be the only recent UK studies of occupational cytotoxic drug exposure using environmental and biological monitoring techniques.

Upper limb disability in HAVS cases--how does it relate to the neurosensory or vascular elements of HAVS?

AIMS: Hand-arm vibration syndrome (HAVS) consists of vascular, neurosensory and musculoskeletal components, characterized by symptoms that include Raynaud's phenomenon, tingling and numbness in the hands. However, there has been little published data on the effects of HAVS on the capability to carry out normal daily tasks. We have investigated the application of the widely-used disability, arm, shoulder and hand (DASH) disability questionnaire that reflects functionality problems in the upper extremities, as well as symptoms, in a HAVS cohort. METHODS: The cohort consisted of 118 males who, as a part of their health surveillance, had been referred for further assessment and Stockholm workshop staging. This process involved medical interview, physical examination and quantitative tests covering neurosensory function, manual dexterity and handgrip strength. RESULTS: The relationship between DASH outcome metric and a combination of quantitative tests reflecting a range of abnormalities found in HAVS, supports the validity of this questionnaire in HAVS studies. The data suggest that HAVS cases have a greater level of upper extremity disability compared with a general population. The study confirms that disability in HAVS is very largely related to sensorineural Stockholm workshop staging, rather than vascular staging. Any influence of vibration-induced Raynaud's phenomenon on upper extremity disability is related to the frequency of blanching attacks rather than their extent across the digits. CONCLUSION: This study strengthens the importance of identifying and preventing the exacerbation of the neurosenory component of HAVS, that unlike the blanching attacks of the vascular component does not have such an obvious pathognomic signal.

The diagnostic value of finger systolic blood pressure and cold-provocation testing for the vascular component of hand-arm vibration syndrome in health surveillance.

BACKGROUND: Hand-arm vibration syndrome (HAVS) is a complex condition with vascular, sensorineural and musculoskeletal components. A number of quantitative tests have been used for assisting in the diagnosis of HAVS and grading disease severity. AIMS: To investigate and compare the diagnostic value of finger systolic blood pressure (FSBP) and rewarming of finger skin temperature (FST) following cold-provocation testing, in the assessment of vascular HAVS. METHODS: Twenty-four individuals with vascular HAVS (Stockholm Workshop stage 2 or 3V) and 22 control subjects underwent FSBP measurements at 30, 15 and 10 degrees C and monitoring of FST following immersion of the hands in water at 15 degrees C for 5 min. RESULTS: There was a significant reduction in median FSBP% in the vascular HAVS group in the change in FSBP from 30 to 15 degrees C adjusted for brachial blood pressure (FSBPC%). There was no difference in the median time for FST to rewarm by 4 degrees C between HAVS cases and controls. The sensitivity and specificity of FSBP to discriminate between the groups varied between 44 and 61% and 91 and 95%, respectively. The sensitivity and specificity for the time for FST to rewarm by 4 degrees C were 71 and 77%. CONCLUSIONS: There is little evidence that the described form of finger rewarming after cold-provocation testing is a useful diagnostic test for vascular HAVS, although it may have some moderate influence in ruling out vascular problems. Based on our data, the FSBP may also have limited use in confirming a positive diagnosis of vibration-induced vascular problems. The higher specificity of the FSBP test suggests it may have some value in ruling out the vascular component of HAVS. The data from this study do not confirm the diagnostic power of FSBP for the vascular component of HAVS reported by a few other investigators.

Carbon monoxide poisoning in two workers using an LPG forklift truck within a coldstore.

BACKGROUND: This report describes carbon monoxide (CO) poisoning in two workers using a hired forklift truck within a coldstore. The diagnosis was not considered until day 6 of the incident, and so measurements of blood or breath CO at the time of acute illness were unavailable. AIMS: To determine whether CO poisoning may be diagnosed retrospectively, where blood or breath CO measurements are unavailable, in the context of this particular incident. METHODS: Detailed clinical histories were obtained. Estimation of possible levels of CO exposure were made based on computer biokinetic modelling based on the Coburn-Foster-Kane equation. RESULTS: The combined method used supports the diagnosis of CO poisoning in these two cases. CONCLUSIONS: Clinical assessment, in combination with mathematical exposure modelling, may lead to successful retrospective diagnosis of CO poisoning and identify putative work activities. CO poisoning should be suspected whenever internal combustion engines are used within buildings and workers complain of relevant symptoms. Hospital departments should maintain a high level of vigilance towards such incidents as this, and should routinely undertake a direct measure of the saturation of haemoglobin by CO, i.e. blood carboxyhaemoglobin or breath CO.

Comparison of hair, nails and urine for biological monitoring of low level inorganic mercury exposure in dental workers.

Creatinine-corrected urine mercury measurements in spot urine samples are routinely used in monitoring workers exposed to inorganic mercury. However, mercury measurement in other non-invasive biological material has been used in some epidemiological studies. Dentists and dental nurses remain a group of workers with potential exposure to inorganic mercury through their handling of mercury-containing amalgam, although changes in work practices have reduced the current, likely exposure to mercury. Therefore, dental workers remain an occupational cohort in whom the value of using different biological media to identify exposure to low level inorganic mercury can be investigated. Samples of head hair, pubic hair, fingernails, toenails and urine were analysed for mercury content from a cohort of UK dentists (n=167) and a socioeconomically similar reference population (n=68) in whom any mercury exposure was primarily through diet. The mercury content in all biological material was significantly higher in the dental workers than in the control population (p<0.0001). The geometric mean and 90th percentile mercury concentrations in the urine samples from dentists were 1.7 and 7.3 micromol mol(-1) creatinine, respectively, with only one sample having a value at around the UK's Health and Safety Executive biological monitoring health guidance level of 20 micromol mol(-1) creatinine. Receiver operator characteristic analyses suggested that the ability of the biological material to discriminate between dentists and referents were fingernails>urine approximately equal to toenails>pubic hair approximately equal to head hair. Further investigation is warranted as to why fingernails appear to be such a good discriminator, possibly reflecting some contribution of direct finger contact with amalgam or contaminated surfaces rather than systemic incorporation of mercury into growing nails. Good correlation between head hair and pubic hair mercury levels in all subjects was obtained (r=0.832), which was significantly improved when hair samples weighing <10 mg were excluded (r=0.868). Therefore, under these exposure conditions and using the described pre-analytical washing steps, there is little influence from atmospheric contamination on the level of mercury content of head hair. The choice of non-invasive biological materials for mercury analysis depends on a number of considerations. These include the toxicokinetics of urinary mercury excretion, the growth rates of hair and nail, the nature and time-frame of exposure, and the fact that urine mercury may not reflect the body burden level from dietary methyl mercury. However, the data from this study suggests that urine mercury remains the most practical and sensitive means of monitoring low level occupational exposure to inorganic mercury.

Cytotoxic drug contamination on the outside of vials delivered to a hospital pharmacy.

We recently carried out a study of two UK hospital pharmacy units preparing cytotoxic drugs using isolators that showed low level contamination on floor surfaces and disposable gloves worn by staff. It has been suggested that this level of contamination may be related to some level of contamination on the drug vials as delivered from manufacturers rather than leakage from the isolators. We have investigated the level of cytotoxic drug contamination on the external surfaces of the drug vials as delivered to a hospital pharmacy stores. We monitored 30, randomly chosen vials for the drugs cisplatin, carboplatin, cyclophosphamide, ifosfamide and methotrexate using well-established methods. A 0.5 m2 floor area directly in front of the shelves used for storing the cytotoxic drugs was also wipe sampled and the disposable gloves worn while wiping the vials for each drug were also analysed. A significant number of vials had a quantifiable level of external contamination. Levels of contamination up to 344 ng/vial were found. Levels of glove and floor contamination for some drugs were found to be comparable with values found in our study of the clean rooms where the isolators were situated and the pharmacy staff prepared the cytotoxic drugs.

A critique of a UK standardized test of finger rewarming after cold provocation in the diagnosis and staging of hand-arm vibration syndrome.

BACKGROUND: Accurate diagnosis and staging of hand-arm vibration syndrome (HAVS) is important in health surveillance of vibration-exposed workers and the substantial number of related medico-legal cases. The measurement of the rewarming rate of fingers after cold provocation to the hands (CPT) has been suggested as a useful test in diagnosing HAVS. AIM: To investigate the diagnostic value of a standardized version of the CPT test using a 15 degrees C cold challenge for 5 min applied in the recent compensation assessment of UK miners. METHODS: Analysis of a subset of UK miners assessed at our unit, together with data from a small repeatability study of the standardized CPT in normal subjects. RESULTS: Rewarming time in the CPT was significantly lower in those subjects classified as vascular Stockholm stage 0 compared with Stockholm stages 1-3 combined, but did not discriminate between the stages of abnormality. Using the suggested cut-off in the CPT test, the sensitivity and specificity were calculated as 43 and 78%, respectively. Receiver operator characteristic analysis suggested that the rewarming time of highest accuracy gave a sensitivity of 66% and specificity of 59%. In 10 miners who reported unilateral hand blanching, there was no significant difference in CPT measurements between blanching and non-blanching hands. Repeat CPT measurements in normal subjects suggested mean differences of 52 and 107 s for each hand, and the Bland-Altman coefficient of repeatability was approximately 600 s for all fingers. CONCLUSION: Single application of this standardized CPT test may have limited value in diagnosing the vascular component of HAVS in an individual.

Biological monitoring of exposure to organophosphate pesticides.

Organophosphates (OPs) are readily absorbed through the skin and biological monitoring is an essential component of any comprehensive assessment of exposure. This paper presents a summary of our experience in a wide range of occupational studies. Additionally, we have conducted studies of non-occupational exposure and human volunteer studies looking at the kinetics of chlorpyrifos, propetamphos, diazinon and malathion. In non-occupationally exposed people, 95% of urinary alkyl phosphates do not exceed 72 micromol/mol creatinine. In occupationally exposed people, the corresponding 95th percentile of total urinary alkyl phosphates is 122 micromol/mol creatinine. In volunteer studies with 1 mg oral doses of chlorpyifos, diazinon and propetamphos the mean peak values were 160, 750 and 404 micromol/mol creatinine, respectively, and were not associated with any reduction in blood cholinesterase activity. The levels of OP metabolites seen in urine from workers potentially exposed to OPs are generally low and unlikely to cause significant reduction in blood cholinesterase activity.

Exposure to the organophosphate diazinon: data from a human volunteer study with oral and dermal doses.

Biological monitoring of occupational exposure to diazinon is possible by the determination of blood cholinesterase activity and by the measurement of metabolites in urine. However, there is little data to aid in the interpretation of results. This study gave oral (11 microg kg(-1) (36 nmol kg(-1)) body weight) and occluded dermal (100 mg (329 micromol)) doses of diazinon to five volunteers and analysed blood and urine samples for plasma and erythrocyte cholinesterase and urinary dialkyl phosphate (DAP) metabolites of diazinon: diethyl phosphate (DEP) and diethyl thiophosphate (DETP). Following oral and dermal exposure, peak urinary DAP levels occurred at 2 and 12 h, respectively. The apparent urinary elimination half-lives of DAP metabolites following oral and dermal exposure were approximately 2 and 9 h, respectively. Approximately 60% of the oral dose and 1% of the dermal dose was excreted as urinary DAP metabolites, with 90% of the dermal dose being recovered from the skin surface. On a group basis, there was no statistically significant mean depression in plasma or erythrocyte cholinesterase when compared with pre-exposure levels for either dosing experiment. The observed elimination kinetics of diazinon metabolites suggest a biological monitoring strategy for occupational exposure to diazinon based on urine samples collected at the end of shift.

Oral and dermal exposure to propetamphos: a human volunteer study.

Propetamphos ((E)-O-2-isopropylcarbonyl-1-methylvinyl-O-methylethyl phosphoramidothioate) is an organophosphate pesticide (OP) and has been used as an active ingredient in sheep dip where there is the potential for significant dermal exposure during dipping. Biological monitoring of exposure to propetamphos has until recently relied on the measurement of cholinesterase activity in plasma. Following the development of a novel method for the determination of propetamphos metabolites in urine, it is now possible to biologically monitor exposure using urine samples. This paper describes a human volunteer study involving oral and dermal exposure to propetamphos.

Development of a urinary biomarker for exposure to the organophosphate propetamphos: data from an oral and dermal human volunteer study.

Propetamphos is a member of the vinyl phosphate group of insecticides and is mainly used for sheep dipping. There have been no published metabolic studies on the effect of propetamphos in man to date, although the present authors have published the identification of a metabolite. The present paper presents data from a human volunteer study investigating the toxicokinetics of the organophosphorus pesticide propetamphos following oral and dermal exposure. Five volunteers ingested a propetamphos dose of 10 micrograms kg-1 (35 nmol kg-1) body weight. Following a washout of 4 weeks, a 100 mg (356 mumol) dermal dose of propetamphos was applied, occluded to 80 cm2 of the inner forearm, for 8 h to the same five volunteers. In a pilot study (several weeks before the main study), one volunteer also received an occluded dermal dose of 50 mg (178 mumol) propetamphos. Unabsorbed propetamphos on the skin was washed off after 8 h and collected. Blood and urine samples were collected over 30 and 54 h for the oral and dermal exposures respectively. Blood samples were analysed for plasma and erythrocyte cholinesterase. Urine samples were analysed for a urinary metabolite of propetamphos: methylethylphosphoramidothioate (MEPT). Following oral and dermal exposure, peak urinary MEPT levels occurred at 1 and 10-12 h respectively. The apparent urinary elimination half-lives of MEPT had means of 1.7 h (oral exposure) and 3.8 h (dermal exposure). Approximately 40% of the oral dose and 1% of the dermal dose were recovered as urinary MEPT or metabolites, which could be hydrolysed to MEPT. Approximately 90% of the dermal dose was recovered from the skin washings. Data from a volunteer showed that a doubling of the dermal dose resulted in approximately double the concentration of total MEPT. Alkaline hydrolysis of urine samples increased the level of MEPT detected after both oral and dermal doses. The increase was greater and statistically significant (p < 0.001, paired t-test) for the dermal dose. This increase in MEPT suggests the presence of other MEPT-containing metabolites or conjugates. The difference in the increase between oral and dermal doses raises the question of a difference in metabolism between the two routes. No individual showed a significant depression compared with their pre-exposure levels of erythrocyte acetyl cholinesterase or plasma cholinesterase activity for either dosing route. However, on a group basis, there was a statistically significant mean depression in plasma cholinesterase activity at 8 and 24 h for oral exposure, with a maximum mean depression of 7% from pre-exposure levels at 8 h. Hydrolysis of urine samples had the effect of reducing the interindividual coefficient of variation (CV) for total excretion of MEPT following both oral (CV reduced from 36 to 8%) and dermal (CV reduced from 40 to 17%) exposure. The ability to detect and follow the elimination of low doses of propetamphos by measurement of 'total' (after hydrolysis) urinary MEPT suggests it is a suitable biomarker of propetamphos exposure. The comparatively short elimination half-lives suggest a strategy for biological monitoring of occupational exposure based on samples collected at the end of the shift.

Relationship between psychological state and level of activity of extrinsic gut innervation in patients with a functional gut disorder.

BACKGROUND: Anxiety and depression are known to be associated with alterations in central autonomic activity, and this may manifest as a functional gut disturbance. However, the final expression of motility disturbance is non-specific and non-quantifiable. This study examines the relationship between psychological state and psychosocial functioning with a new direct measure of the level of activity of extrinsic autonomic gut innervation, rectal mucosal Doppler blood flow. MATERIALS AND METHODS: Thirty four female patients (mean age 36 years, range 19--45) with constipation for greater than five years and 19 healthy women (mean age 38 years, range 21--60) were studied. They completed the general health questionnaire-28 point scale (GHQ-28; psychosocial functioning) and the Bem sex role inventory (BSRI; an index of women's psychological feelings about their own femininity). On the same day they underwent measurement of rectal mucosal Doppler blood flow, a new validated measure of the activity of gut extrinsic nerve innervation. Measurements were made during the follicular phase and in the fasted state. RESULTS: Women with constipation scored higher on the total GHQ-28 score and the somatisation (p=0.05) and anxiety (p=0.05) subscales of the GHQ-28. There was a negative correlation between mucosal blood flow and GHQ somatisation subscale (r=-0.45, p<0.005), anxiety (r=-0.38, p<0.05), and depression (r=-0.40, p<0.01) scores in women with constipation. Although constipated women scored no higher than controls on the BSRI, there was a significant negative correlation between blood flow and BSRI score (r=-0.49, p<0.005) for constipated women. CONCLUSIONS: General psychosocial function, somatisation, anxiety, depression, and feelings about female role are impaired in women with constipation and associated with altered rectal mucosal blood flow, a measure of extrinsic gut innervation. These findings suggest that psychological factors are likely to influence gut function via autonomic efferent neural pathways.

Biological monitoring and exposure to mercury.

Occupational health professionals' interest in controlling mercury (Hg) exposure, and the use of biological monitoring in this context, has been ongoing for a number of years. Evidence from urinary Hg results in a number of UK firms who have undertaken some form of biological monitoring or occupational health surveillance suggest that exposure has decreased over the last 10-15 years. This decrease precedes the establishment in the UK of an advisory biological monitoring guidance value (HGV) for urinary Hg and the production of updated medical guidance from the Health & Safety Executive on Hg exposure (MS12 1996). This latter document recommends a urinary sampling interval for urinary Hg of between 1 and 3 months, which is consistent with the reported toxicokinetics of Hg excretion, but we highlight that urinary Hg represents integrated exposure over many previous months. Mercury is a recognized nephrotoxin and MS12 1996 mentions the use of regular dipstick protein estimations. We review our experience of investigating proteinuria and enzymuria in a large-scale cross-sectional occupational study. The incidence of Hg-induced renal disease is probably very rare at current exposure levels. Therefore acceptance of a high false-positive rate of proteinuria not related to Hg exposure needs to be considered in any urinary protein testing regime of Hg workers. The establishment of an HGV for urinary Hg has raised questions about the uncertainty associated with a urinary Hg result, including factors such as diurnal variation, whether urine correction by creatinine or specific gravity is preferable and the possibility of non-occupational sources of Hg contributing significantly towards breaching the HGV. Correction of urinary Hg results by creatinine or specific gravity and the use of a fixed sampling time, such as the beginning or end of the day, substantially reduce the uncertainty in a urinary Hg measurement. But even with good laboratory precision, an individual with a true urinary Hg excretion of 20 nmol/mmol creatinine could supply urine samples of between 14 and 26 nmol/mmol creatinine. The influence of dietary sources in the UK contributing to urinary Hg values approaching or exceeding the HGV is unlikely. The use of tribal or ethnic cosmetics and remedies needs to be considered if a urinary Hg result looks inappropriately high, as some such preparations have been found to contain Hg and can be absorbed through the skin. The ability of excessive chewers or teeth grinders who have a large number of dental amalgam fillings to breach the urinary HGV in the absence of substantial occupational Hg exposure has been reported in a few Scandanavian studies. We report here a likely case of this phenomenon. Since the establishment of the HGV, our biological monitoring Hg data from a number of industry sectors using inorganic or metallic Hg have suggested that a minority of samples (13%) are still greater than the HGV.

Psychological morbidity in women with idiopathic constipation.

OBJECTIVE: The aim of this study was to examine psychological morbidity in women with idiopathic constipation. METHODS: Three age-matched groups of 47 women with idiopathic constipation (excess straining or decreased bowel frequency), 28 healthy women, and 26 women with Crohn's disease completed a newly devised Perception of Female Self questionnaire, the Intimacy subscale of the Inventory of Interpersonal Problems, the Feminine Traits from the Bem Sex Role Inventory, and the General Health Questionnaire. Thirteen patients had a low bowel frequency (<2/wk), 30 had a normal bowel frequency, and four had increased bowel frequency (>3/day). Of 29 patients with a measured whole gut transit time, 19 had slow and 10 had normal transit. RESULTS: Patients with constipation had significantly increased psychological and social morbidity (anxiety, depression, and social dysfunction) (p = 0.022), increased somatization (p = 0.019), and less satisfaction in their sexual life (p = 0.001) than healthy women. Constipated women with slow transit or decreased bowel frequency did not differ significantly from those with normal transit and bowel frequency. Women with Crohn's disease did not differ significantly on any test from healthy controls. CONCLUSIONS: Women with idiopathic constipation have increased psychological morbidity, altered perception about female self, and impaired intimate relationships. These factors are not present in women with "organic" GI illness also associated with abdominal pain.