Biomedical subjects

Jesper Kristiansen

Publications and source records attributed to Jesper Kristiansen.

11 recordsLinked to original sources

PubMed2006

Differences in national legislation for the implementation of lead regulations included in the European directive for the protection of the health and safety of workers with occupational exposure to chemical agents (98/24/EC).

BACKGROUND: The European Council Directive 98/24 on the protection of the health and safety of workers exposed to chemical agents sets out provisions for environmental and biological monitoring, making specific reference to binding limit values and health surveillance measures for those with exposure to lead OBJECTIVES: To compare how the Directive has been implemented at a national level in EU countries and to determine whether workers receive equivalent protection. METHODS: Information on selected key issues was collected from 14 EU countries by means of a structured questionnaire. RESULTS: National occupational exposure limit values generally reflect that set by the Directive (0.15 mg/m(3)), but in five cases lower limits are set. National binding biological limit values range from 20 microg/100 ml blood in one country up to 80 microg/100 ml blood in others. The risk to the unborn child is generally recognised with specific measures for women of child-bearing potential or those that are pregnant or breast feeding. In only three countries are special arrangements included for young workers. Limits at which medical surveillance is put into effect are more consistent at 40 microg/100 ml in most countries. The Directive also refers to guidelines for health surveillance but none have been issued with respect to lead. Thus monitoring strategies and requirements for analytical performance vary considerably. CONCLUSIONS: The results of this survey suggest that protection of workers against the risk of exposure to lead at work is far from uniform across the European Union. Such disparity may also have implications on the requirements set at national level for laboratories measuring lead in blood and/or air. In the interest of harmonisation within the EU, further consideration should be given to the Annex II of the EC Directive 98/24, taking into account the suggestions for lower binding limit values for lead; this should include full guidelines for medical surveillance and requirements for laboratories should be issued.

Environmental Monitoring↗

PubMed2005

Increased levels of interstitial potassium but normal levels of muscle IL-6 and LDH in patients with trapezius myalgia.

The mechanisms behind the development of work-related trapezius pain are suggested to involve both peripheral and central components, but the specific contribution of alterations in muscle nociceptive and other substances is not clear. Female patients with chronic trapezius myalgia (N=19; TM) and female controls (N=20; CON) were studied at rest, during 20 min repetitive low-force exercise and recovery, and had their interstitial concentrations of potassium (K(+)), lactate dehydrogenase (LDH), interleukin-6 (IL-6) and collagen turnover determined in the trapezius muscle by the microdialysis technique. K(+) levels were at all time points higher in TM than in CON (P<0.0001). Baseline levels of LDH and IL-6 were similar in both groups. In response to exercise pain intensity, rated perceived exertion, and the concentrations of K(+), LDH and IL-6 increased significantly in both groups. [K(+)] immediately decreased to baseline levels in CON but remained elevated during the first 20 min of recovery in TM (P<0.01) whereafter it returned to baseline level. In all subjects taken together mean [K(+)] correlated negatively with pressure pain threshold of trapezius (P<0.001), positively with mean pain intensity VAS (P<0.001) and mean perceived exertion (P<0.001). Rises in muscle LDH and IL-6 as well as the anabolic ratio for collagen type I was not significantly different between groups. In conclusion, patients with chronic pain in the trapezius muscle had increased levels of interstitial potassium. This finding could be causally related to myalgia or secondary to pain due to deconditioned muscle or altered muscle activity pattern.

Adult↗

PubMed2005

Remediation of soil from lead-contaminated kindergartens reduces the amount of lead adhering to children's hands.

Risk related to contaminated soil is based on the oral intake of soil and dust among children. This exposure is a consequence of mouthing behaviour, which exposes children to whatever adheres to their hands or toys. This project compared hand exposure of children to lead following outdoor playground activities before and after an intervention. The intervention consisted of replacement of contaminated top soil from the most intensively used playground areas and coverage of bare soil with wood chips or grass. We included children from three kindergartens: one with very low levels of lead in soil and two kindergartens with an average lead concentrations in soil of 100-200 mg/kg. Measurements of lead in soil 5-7 weeks after interventions in two kindergartens verified that the interventions had effectively reduced the potential exposure to lead from the most intensively used areas of the playgrounds. The average lead concentration in soil after intervention was below 10 mg/kg. We found a good agreement between the average concentration of lead in soil and the amount of lead on the hands of the children. Thus, the exposure marker worked and had the advantage compared to a blood sample, that we could evaluate the effect of the interventions shortly after they were accomplished using a noninvasive method. The amount of lead on the hands measured in one of the two kindergartens after the remediation (0.73 microg) was not significantly different from the control kindergarten (0.58 microg). Children from the second kindergarten still had higher median exposures to lead (1.29 microg), but a large overlap existed with several children having lower amounts of lead on their hands than some children from the control kindergarten. Large variations in the amount of lead on hands were observed. Variations may reflect true differences in concentrations of lead in soil, but may also reflect different behavior and playing patterns. Our study demonstrated, that it was possible in a cost-effective way to reduce exposure significantly and to verify the effect with a sensitive, noninvasive method shortly after the interventions had been implemented..

Child↗

PubMed2004

Increase in interstitial interleukin-6 of human skeletal muscle with repetitive low-force exercise.

Interleukin (IL)-6, which is released from muscle tissue during intense exercise, possesses important metabolic and probably anti-inflammatory properties. To evaluate the IL-6 response to low-intensity exercise, we conducted two studies: 1) a control study with insertion of microdialysis catheters in muscle and determination of interstitial muscle IL-6 response over 2 h of rest and 2) an exercise study to investigate the IL-6 response to 20 min of repetitive low-force exercise. In both studies, a microdialysis catheter (cutoff: 3,000 kDa) was inserted into the upper trapezius muscle of six male subjects, and the catheters were perfused with Ringer-acetate at 5 microl/min. Venous plasma samples were taken in the exercise study. The insertion of microdialysis catheters into muscle resulted in an increase in IL-6 from 8 +/- 0 to 359 +/- 171 and 484 +/- 202 pg/ml after 65 and 110 min, respectively (P < 0.001). Similarly, in the exercise study, IL-6 increased to 289 +/- 128 pg/ml after a 55-min rest (P < 0.001). During the subsequent repetitive low-force exercise, muscle IL-6 further increased to 1,246 +/- 461 pg/ml and reached 2,132 +/- 477 pg/ml after a 30-min recovery (all P < 0.001). In contrast to this, plasma IL-6 did not significantly change in response to exercise. We conclude that upper extremity, low-intensity exercise results in a substantial increase in IL-6 in the interstitium of the stabilizing trapezius muscle, whereas no change is seen for plasma IL-6.

Adult↗

PubMed2004

Increase in muscle nociceptive substances and anaerobic metabolism in patients with trapezius myalgia: microdialysis in rest and during exercise.

Local metabolic changes are suggested to be involved in muscle pain development in humans. Nineteen women with chronic work-related trapezius myalgia (TM) and 20 healthy female controls (CON) were studied during baseline rest, 20 min repetitive low-force exercise, and 120 min recovery. Interstitial serotonin (5-HT), glutamate, lactate, pyruvate, and blood flow were determined by microdialysis in the trapezius muscle. Baseline pressure pain threshold (PPT) was lower (143+/-18 (TM) vs. 269+/-17 (CON)kPa) (mean+/-SEM), pain intensity (visual analogue scale, VAS) higher (33+/-5 vs. 2+/-1mm), muscle 5-HT higher (22.9+/-6.7 vs. 3.8+/-1.3 nmol/l), and glutamate higher (47+/-3 vs. 36+/-4 micromol/l) in TM than in CON (all P<0.05), whereas muscle blood flow was similar in groups. Furthermore, muscle pyruvate was higher (180+/-15 vs. 135+/-12 micromol/l) and lactate higher (4.4+/-0.3 vs. 3.1+/-0.3 mmol/l) in TM than in CON (P<0.001). In response to exercise, VAS and glutamate increased in both TM and CON (all P<0.05). In TM only, lactate and pyruvate increased significantly (P<0.02), whereas blood flow increased to similar levels in both groups. During the initial 20 min recovery period, blood flow remained increased in TM (P<0.005) whereas it decreased to baseline levels in CON. In conclusion, patients with chronic work-related TM have increased levels of muscle 5-HT and glutamate that were correlated to pain intensity (r=0.55, P<0.001) and PPT (r=-0.47, P<0.001), respectively. In addition, TM was associated with increased anaerobic metabolism, whereas a normal rise in blood flow was seen with exercise. These findings indicate that peripheral nociceptive processes are active in work-related TM.

Creatine↗

PubMed2004

Comparison of uncertainties related to standardization of urine samples with volume and creatinine concentration.

When measuring biomarkers in urine, volume (and time) or concentration of creatinine are both accepted methods of standardization for diuresis. Both types of standardization contribute uncertainty to the final result. The aim of the present paper was to compare the uncertainty introduced when using the two types of standardization on 24 h samples from healthy individuals. Estimates of uncertainties were based on results from the literature supplemented with data from our own studies. Only the difference in uncertainty related to the two standardization methods was evaluated. It was found that the uncertainty associated with creatinine standardization (19-35%) was higher than the uncertainty related to volume standardization (up to 10%, when not correcting for deviations from 24 h) for 24 h urine samples. However, volume standardization introduced an average bias of 4% due to missed volumes in population studies. When studying a single 24 h sample from one individual, there was a 15-20% risk that the sample was incomplete. In this case a bias of approximately 25% was introduced when using volume standardization, whereas the uncertainty related to creatinine standardization was independent of the completeness of the sample. The uncertainty of creatinine standardization is increased when studying single voids rather than 24 h urine samples. This is partially counteracted by the increased statistical power due to the increased number of samples for each individual. Furthermore, there is a considerable increase in convenience for the participants, when collecting small volumes rather than complete 24 h samples.

Adult↗

PubMed2004

An uncertainty budget for the measurement of ethanol in blood by headspace gas chromatography.

An uncertainty budget was constructed for the measurement of ethanol in blood by headspace gas chromatography. The uncertainty budget, covering the analytical range of ethanol concentrations up to 3.00 g/kg, included analytical uncertainty components, traceability uncertainty components, and effects caused by interindividual variation in blood water content. The analytical combined standard uncertainty was estimated from duplicate measurements of real samples and included contributions from headspace recovery, variation between columns, injection, repeatability of analytical signals, and statistical uncertainty of the calibration function. The traceability uncertainty was estimated in a sub-budget based on information about the calibrator and about the preparation of the aqueous standards. Two uncertainty components depended on the interindividual variation in blood water content. First, it caused uncertainty on the density of the blood, and second, it had an effect on the gas phase concentration of ethanol when doing the headspace sampling. These effects as well as their covariance were included in the uncertainty budget. For fresh blood samples, the analytical uncertainty was the dominating uncertainty component, accounting for approximately 90% of the variance. For blood samples collected 100 h postmortem, the interindividual variation in blood water content was the largest uncertainty component. It was demonstrated that subtracting a "safety margin" of 0.1 g/kg from the results was sufficient to keep the risk of committing a type 1 error below 0.1% in ethanol concentrations ranging up to 2 g/kg for fresh blood samples. This risk was higher for postmortem blood samples because of the higher uncertainty of measurement, but still less than approximately 1.4%.

Algorithms↗

PubMed2003

Experimental systemic contact dermatitis from nickel: a dose-response study.

Systemic contact dermatitis is usually seen as flare-up of previous dermatitis or de novo dermatitis similar to allergic contact dermatitis. Although systemic contact dermatitis from medicaments is a well-established entity, the existence of clinically relevant systemic reactions to oral nickel exposure, in particular systemic reactions to nickel in the daily diet, remains controversial. Several studies have shown that oral exposure to nickel can induce systemic contact dermatitis in nickel-sensitive individuals. In most of these studies, however, the exposure dose of nickel used has been considerably higher than the nickel content in the normal daily diet. The aim of the current investigation was to study dose-response dependency of oral exposure to nickel. In a double-blind, placebo-controlled oral exposure trial, 40 nickel-sensitive persons and 20 healthy (non-nickel-sensitive) controls were given nickel sulfate hexahydrate in doses similar to and greater than the amount of nickel ingested in the normal Danish daily diet. The nickel content in urine and serum before and after oral exposure was measured to determine nickel uptake and excretion. The influence of the amount of nickel ingested on the clinical reactions to oral exposure and on nickel concentrations in serum and urine was evaluated. Among nickel-sensitive individuals, a definite dose-response dependency was seen, following oral exposure to nickel. 7 of 10 nickel-sensitive individuals had cutaneous reactions to oral exposure to 4.0 mg nickel, an amount approximately 10 times greater than the estimated normal daily dietary intake of nickel. 4 of 10 nickel-sensitive individuals had cutaneous reactions to 1.0 mg nickel, a dose which is close to the estimated maximum amount of nickel contained in the daily diet. 4 of 10 nickel-sensitive individuals reacted to 0.3 mg nickel or to the amount equivalent to that contained in a normal daily diet, and 1 of 10 reacted to a placebo. None of the 20 healthy controls had cutaneous reactions to 4.0 mg nickel or to a placebo. Prior to oral exposure, there was no measurable difference in the amount of nickel in the urine or serum of nickel-sensitive persons and healthy controls. Following the oral challenge, the nickel content in the urine and serum of both nickel-sensitive and healthy control individuals was directly related to the dose of nickel ingested.

Administration, Oral↗

PubMed2003

The Guide to expression of uncertainty in measurement approach for estimating uncertainty: an appraisal.

BACKGROUND: The aim of the Guide to Expression of Uncertainty in Measurement (GUM) is to harmonize the different practices for estimating and reporting uncertainty of measurement. Although there are clear advantages in having a common approach for evaluating uncertainty, application of the GUM approach to chemistry measurements is not straightforward. In the above commentary, Krouwer suggests that the GUM approach should not be applied to diagnostic assays, because (a) the quality of diagnostic assays is to low, and (b) the GUM uncertainty intervals are too narrow to predict the outliers that occasionally trouble these methods. METHODS: Some of the examples presented by Krouwer are reviewed. Sodium measurements are modeled mathematically to illustrate the GUM approach to uncertainty. A standardized uncertainty evaluation process is presented. RESULTS: Modeling of sodium measurements demonstrates how the GUM uncertainty interval reflects the treatment of a bias: The width of the uncertainty interval varied depending on whether a correction for a calibrator lot bias was applied, but in both cases it was consistent with the distribution of measurement results. Expanding the uncertainty interval to include outliers runs counter to the definition of uncertainty. Used appropriately, the GUM uncertainty can be helpful in detecting outliers. In standardizing the uncertainty evaluation, the importance of the analytical imprecision and traceability was emphasized. It is problematic that manufacturers of commercial assays rarely inform about the uncertainty of the values assigned to the calibrators. As demonstrated by an example, external quality-assurance data may be used to estimate this uncertainty. CONCLUSIONS: The GUM uncertainty should be applied to measurements in laboratory medicine because it may actually support the forces that drive the work on improving the quality of measurement procedures. However, it is important that the GUM approach is made more manageable by standardizing the uncertainty evaluation procedure as much as possible. It is essential to focus on the traceability and uncertainty of calibrators and reagents supplied by manufacturers of assays. Information about uncertainty is necessary in the evaluation of the uncertainty associated with manufacturers' measurement procedures, and in general it may force manufacturers to increase their efforts in improving the metrologic and analytical quality of their products.

Calibration↗

PubMed2002

Evaluation of accuracy and uncertainty of ELISA assays for the determination of interleukin-4, interleukin-5, interferon-gamma and tumor necrosis factor-alpha.

The comparison of analytical results calls for validation of the assays used, i.e. for the documentation of accuracy (trueness and precision), linearity and specificity. In addition, there is a growing demand for evaluation and documentation of traceability and uncertainty of analytical results. However, models for establishing the traceability and uncertainty of immunoassay results are lacking. Sandwich enzyme-linked immunosorbent assays (ELISAs) were developed for determination of the human cytokines interleukin-4 (IL-4), interleukin-5 (IL-5), interferon-y (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha). The accuracy of each of the assays was evaluated in the ranges of 1-15 microg/l (IL-4), 0.001-1 microg/l (IL-5), 0.5-2.5 microg/l (IFN-T) and 0.14-2.2 microg/l (TNF-alpha). Other evaluated performance characteristics were the limit of detection (LOD), immunological specificity, and robustness. Traceability was ensured by the use of World Health Organization International Standards (WHO IS). An uncertainty budget, which combined the contribution from all known uncertainty components, was established for each cytokine ELISA. The between-run relative analytical standard deviation (RSDA) of the assessed ELISAs was found to be in the range of 11-18%, except for IL-5 where RSDA increased at decreasing concentrations. The LOD was 0.12 microg/l, 0.0077 microg/l, 0.0069 microg/l and 0.0063 microg/l for IL-4, IL-5, IFN-gamma and TNF-alpha, respectively. Traceability to the WHO IS was established for each of the cytokines. The combined relative standard uncertainty (U(result)/C(result)) was 28%, 22-62%, 28% and 24% for the IL-4, IL-5, IFN-gamma and TNF-alpha results, respectively. The major contributions to uncertainty came from the relative analytical standard deviation and from the uncertainty of the mass concentration of the WHO IS. The uncertainty of the WHO IS was not stated in the accompanying certificate and was evaluated by other means. The largest sources of uncertainty were located outside our laboratory. This means that the possibilities to improve the reliability of the results produced by the ELISAs are very limited. The task of evaluating measurement uncertainty would be much easier if producers of international reference standards reported the uncertainty of the value of standards. The model for evaluating uncertainty presented in this paper is applicable to other types of assays and to most analytical methods.

Bias↗

PubMed2002

Comparison of procedures for evaluating laboratory performance in external quality assessment schemes for lead in blood and aluminum in serum demonstrates the need for common quality specifications.

BACKGROUND: The different scoring methods used by eight European External Quality Assessment Schemes (EQASs) for occupational and environmental laboratory medicine were compared to develop suitable quality specifications as a step toward harmonization. METHODS: Real results for blood lead and serum aluminum assays, reported by participants in Italian and United Kingdom EQASs, were evaluated according to individual scheme scoring criteria. The same results were then used to produce z scores using scheme-based between-laboratory SDs as the estimate of variability to determine whether simple performance-derived quality specifications produced better agreement among schemes. RESULTS: The schemes gave conflicting assessments of participants' performance, and participants judged to be successful by one scheme could be defined as performing inadequately by another. An approach proposed by Kenny et al. (Scand J Clin Lab Invest 1999;59:585), which uses clinical inputs to set targets for analytical imprecision, bias, and total error allowable, was then used to elaborate quality specifications. CONCLUSIONS: We suggest that the CLIA '88 recommendations for blood lead (+/- 40 micro g/L or +/- 10% of the target concentration, whichever is the greater) could be used as a quality specification, although a revision to +/- 30 micro g/L or +/- 10% is recommended. For serum aluminum, a suitable quality specification of +/- 5 micro g/L or +/- 20% of the target concentration, whichever is the greater, is suggested. These specifications may be used to compare laboratory performance across schemes.

Aluminum↗