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Biomedical subjects

Jesper Bo Nielsen

Publications and source records attributed to Jesper Bo Nielsen.

15 recordsLinked to original sources
PubMed2006

Willingness-to-pay for a population program aimed at reducing dietary salt in Denmark.

BACKGROUND: High intake of salt increases blood pressure and the risk of cardiovascular disease. Population programs aimed at reducing dietary salt may be cost-effective, but little is known about people's valuation of such programs. METHODS: A random sample (n = 924) of Danish people aged 20-74 was interviewed in-person in year 2000. They were asked how much they would be willing to contribute in additional tax for a population program that would half the intake of salt. The respondents were randomized to presentation of effectiveness format (number-needed-to-treat (NNT), relative risk reduction (RRR), avoided cases of heart attack or increase in longevity). RESULTS: In total, 57% were unwilling to contribute to the program (63%, 51%, 51% and 63% in the NNT-, RRR-, case- and longevity-groups, respectively). The mean willingness-to-pay among the remaining 43% was $30 per person per month. While in Denmark, the annual net program cost would be $148 millions in the most unfavorable scenario, the aggregate willingness-to-pay was $468 millions. CONCLUSIONS: A public health program may be worthwhile even though only a minority of the population is willing to contribute towards it. People's valuation is moderately sensitive to format of the program information.

Adult↗
PubMed2006

[Multiple chemical sensitivity, a well-defined illness?].

Some people react to smells or chemicals at levels far below toxicological thresholds with nonspecific symptoms, fear and social isolation. They may be diagnosed with multiple chemical sensitivity. There is no empirical evidence indicating that this condition is explained by toxicological mechanisms, even though a number of theories have been proposed. The authors of this review conclude that this is a functional condition. These patients need information and treatment in accordance with this fact. Instead of being advised how to avoid exposure to chemicals, they should be properly trained in appropriate confrontation with the chemicals encountered in everyday life.

Humans↗
PubMed2006

Interactions of skin thickness and physicochemical properties of test compounds in percutaneous penetration studies.

OBJECTIVES: To determine the effect of skin thickness on the percutaneous penetration and distribution of test compounds with varying physicochemical properties using in vitro systems. Studies were carried out in accordance with OECD guidelines on skin absorption tests. METHODS: Percutaneous penetration of caffeine (log P -0.01), testosterone (log P 3.32), propoxur (log P 1.52) (finite dose in ethanol to water vehicle ratio) and butoxyethanol (log P 0.83) (undiluted finite dose or as an infinite dose 50% [v/v] aqueous solution) through skin of varying thicknesses under occluded conditions was measured using flow through cells for 8-24 h. Saline (adjusted to pH 7.4) was used as receptor fluid, with BSA added for studies with testosterone and propoxur. Following exposure, the remaining surface dose was removed by swabbing and the skin digested prior to scintillation counting. RESULTS: The maximum flux of caffeine was increased with decreasing skin thickness, although these differences were found to be non-significant. The presence of caffeine in the skin membrane was not altered by skin thickness. Maximum flux and cumulative dose absorbed of testosterone and butoxyethanol (in both finite and infinite doses) were markedly reduced with full thickness (about 1 mm thick) skin compared with split thickness skin (about 0.5 mm). Maximum flux of propoxur (dissolved in 60% ethanol) was clearly higher through skin of 0.71 mm than through skin of 1.36 mm, but no difference was found between 0.56 and 0.71 mm. The proportion of propoxur present in the membrane after 24 h increased significantly over the complete range of thicknesses tested (0.56-1.36 mm). CONCLUSIONS: A complex relationship exists between skin thickness, lipophilicity and percutaneous penetration and distribution. This has implications for risk assessment studies and for the validation of models with data from different sources.

2,4-Dichlorophenoxyacetic Acid↗
PubMed2005

Topical use of tea tree oil reduces the dermal absorption of benzoic acid and methiocarb.

Tea tree oil (TTO) is a complex mixture of terpene hydrocarbons. Intensive topical use of TTO in different cosmetics and investigations into its potential as an antimicrobial or anti-inflammatory agent has accentuated the need for studies on the toxicity of TTO. We have applied an experimental in vitro model using static diffusion cells with human skin to study penetration characteristics of terpinen-4-ol and the way TTO affects the barrier integrity of the skin and the percutaneous penetration of two chemicals covering a range of solubilities from 0.03 g/l (methiocarb) to 3.0 g/l (benzoic acid). Through GC-MS analysis we identified the major constituents of TTO. In our experimental set-up with full-thickness skin, only the least lipophilic ingredients of TTO penetrated the skin. Barrier integrity was evaluated through measurement of percutaneous penetration of tritiated water. Data indicate that 1% TTO does not affect barrier conditions. The Kp value for tritiated water was increased significantly at 5% TTO, which demonstrate that the barrier integrity is affected at this relatively low concentration of TTO. The barrier integrity is, however, not seriously damaged, but our data indicate an initiated and concentration-dependent effect on the barrier integrity. TTO changed the penetration characteristics for benzoic acid as well as for methiocarb. The general effect was that TTO reduced the maximal flux. For methiocarb, the lag-time was also prolonged by increasing the TTO concentration in the donor phase to 5%. Thus, TTO reduced the overall amount of benzoic acid as well as methiocarb entering the receptor chamber.

Administration, Topical↗
PubMed2004

In vitro percutaneous penetration of five pesticides--effects of molecular weight and solubility characteristics.

This study examined the in vitro percutaneous penetration of five pesticides covering a wide range of solubilities and different molecular weights, which allowed discussion of penetration of single pesticides as well as a comparison between penetration characteristics of different pesticides. The five pesticides were the fungicides methiocarb, pirimicarb and prochloraz; the growth retardant paclobutrazol; and the insecticide dimethoate. An experimental model with static diffusion cells mounted with human breast skin was used, and pesticide concentrations were quantified by high-performance liquid chromatography. Molecular weight as well as solubility affected dermal penetration and skin deposition. Thus, we conclude that for the passage of our test substances from the donor phase, through the skin, into the receptor, a too high as well as a too low lipophilicity may limit the rate and degree of skin penetration. Furthermore, the importance of the skin as a potential reservoir for systemic exposure after exposure has ended was demonstrated. Especially in relation to short-term occupational exposures, an exposure assessment based on penetrated pesticide at the end of a work shift may underestimate the exposure.

Breast↗
PubMed2003

Assessment of xenoestrogenic exposure by a biomarker approach: application of the E-Screen bioassay to determine estrogenic response of serum extracts.

BACKGROUND: Epidemiological documentation of endocrine disruption is complicated by imprecise exposure assessment, especially when exposures are mixed. Even if the estrogenic activity of all compounds were known, the combined effect of possible additive and/or inhibiting interaction of xenoestrogens in a biological sample may be difficult to predict from chemical analysis of single compounds alone. Thus, analysis of mixtures allows evaluation of combined effects of chemicals each present at low concentrations. METHODS: We have developed an optimized in vitro E-Screen test to assess the combined functional estrogenic response of human serum. The xenoestrogens in serum were separated from endogenous steroids and pharmaceuticals by solid-phase extraction followed by fractionation by high-performance liquid chromatography. After dissolution of the isolated fraction in ethanol-DMSO, the reconstituted extract was added with estrogen-depleted fetal calf serum to MCF-7 cells, the growth of which is stimulated by estrogen. After a 6-day incubation on a microwell plate, cell proliferation was assessed and compared with the effect of a 17-beta-estradiol standard. RESULTS AND CONCLUSIONS: To determine the applicability of this approach, we assessed the estrogenicity of serum samples from 30 pregnant and 60 non-pregnant Danish women thought to be exposed only to low levels of endocrine disruptors. We also studied 211 serum samples from pregnant Faroese women, whose marine diet included whale blubber that contain a high concentration of persistent halogenated pollutants. The estrogenicity of the serum from Danish controls exceeded the background in 22.7 % of the cases, while the same was true for 68.1 % of the Faroese samples. The increased estrogenicity response did not correlate with the lipid-based concentrations of individual suspected endocrine disruptors in the Faroese samples. When added along with the estradiol standard, an indication of an enhanced estrogenic response was found in most cases. Thus, the in vitro estrogenicity response offers a promising and feasible approach for an aggregated exposure assessment for xenoestrogens in serum.

Biological Assay↗
PubMed2003

How do individuals apply risk information when choosing among health care interventions?

A sample of 3,201 Danes was subjected to personal interviews in which they were asked to state their preferences for risk-reducing health care interventions based on information on absolute risk reduction (ARR) and relative risk reduction (RRR). The aim of the study was to measure the relative weighting of different types of risk information under various circumstances. The effect of presenting questions, and of explicitly formulating RRR, was analyzed. A preference for increases in RRR was demonstrated. There was a stronger inclination to choose the intervention that offered the highest RRR if RRR was explicitly stated. Individuals with more than 10 years of schooling also demonstrated a preference for increased ARR, but only when facing individually framed choices. In a social choice context, preferences for RRR remained intact, but the magnitude of ARR had no impact on choices. Results imply that social framing may induce a propensity to prefer interventions that target high-risk populations. Those respondents who had received < or = 10 years of schooling demonstrated preferences for RRR but not ARR, and no impact of social framing was observed.

Adult↗
PubMed2002

[General practitioners' perception of disease risks and benefit of prevention].

INTRODUCTION: Uncertainty and risk are central issues in relation to health and health care services. Healthy individuals do not necessarily fall ill, despite the presence of risk factors. Doctors, health service administrators, and patients are more inclined to choose interventions against risk factors, when information about the effects is presented in terms of relative risk reductions rather than absolute risk reductions. The aim of the study was to gain better insight into how general practitioners (GPs) perceive risk of disease, and whether this perception depends on the risk reduction being presented in absolute or relative terms. MATERIAL AND METHODS: Questionnaires with clinical episodes were sent to 1500 Danish GPs. The GPs were randomised into four groups of 375, all of whom received the same case history with information about risk reduction achieved through medical treatment phrased in terms of either relative risk reduction, absolute risk reduction, number needed to treat, or all of the aforementioned terms of risk reduction. The GPs were asked whether they would recommend medical treatment as primary prevention, knowing the case history and expected risk reduction. RESULTS: The GPs' attitude towards recommending medical treatment depended on the phrasing of risk reductions. Of the doctors who received all information on risk reductions, 72% would definitely or probably recommend medication, whereas 91% would recommend medication if only information about relative risk reduction was given, and 63% would recommend medication if information was given in terms of absolute risk reduction or number needed to treat. DISCUSSION: To advise patients rationally, knowledge of the patients' preferences, as well as consideration of all available measures of risk reductions, is needed.

Attitude of Health Personnel↗
PubMed2002

Number needed to treat: easily understood and intuitively meaningful? Theoretical considerations and a randomized trial.

Graphic representation was used to explore to what extent the number needed to treat (NNT) conveys the appropriate notion of benefit for the individual patient in interventions aimed at delaying adverse events. A sample of the Danish population (n = 675) was interviewed face to face, and asked whether they would consent to a hypothetical drug that reduces the risk of heart attack. The benefit of the drug was expressed in terms of NNT and was randomly set at 10, 25, 50, 100, 200, and 400. NNT does not convey information on the proportion of patients being helped by an intervention or the size of the delay of the adverse event intended to be prevented. The proportion of people consenting to the hypothetical drug was about 80%, irrespective of NNT, and some of those who rejected the drug misinterpreted the meaning of NNT. Lay people may have difficulties in understanding the meaning of NNT, and clinicians may do well to use the NNT with caution until more is known about how patients comprehend it.

Adult↗
PubMed2002

Danish GPs' perception of disease risk and benefit of prevention.

BACKGROUND: Uncertainty and risk are central issues in relation to health and health care services. Healthy individuals do not necessarily fall ill, despite the presence of risk factors. It has been documented that doctors, health service administrators and patients are more inclined to choose interventions against risk factors when information about the effects is presented in terms of relative risk reductions rather than absolute risk reductions. OBJECTIVES: The objective of the study was to gain better insight into how GPs perceive risk of disease, and how this perception is influenced by the way the risk is presented, e.g. whether changes in risk are presented in absolute or relative terms. METHODS: Questionnaires with clinical episodes were sent to 1500 Danish GPs. The GPs were randomized into four groups of 375, who all received the same case story with information about risk reduction achieved through medical treatment phrased in terms of either relative risk reduction, absolute risk reduction, number needed to treat or all of the aforementioned terms of risk reduction. The GPs were asked whether they would recommend medical treatment as primary prevention, knowing the case story and expected risk reduction. RESULTS: The GPs' attitude towards recommending medical treatment was dependent on the phrasing of risk reductions. Seventy-two per cent of doctors who received all information on risk reductions would definitely or probably recommend medication, while 91% would recommend medication if information only about relative risk reduction was given, and 63% would recommend medication if information was given in terms of absolute risk reduction or number needed to treat. CONCLUSION: In order to advise patients in a rational way, in addition to knowledge of the patients' preferences, doctors need to take into account all available measures of risk reductions.

Attitude of Health Personnel↗
PubMed2002

Mercury-induced autoimmunity in mice.

We have studied the effect of gender, genetics, and toxicokinetics on immune parameters in mercury-induced autoimmunity in mice. Data strongly suggest that the mechanism for mercury-induced autoimmunity involves modification of the autoantigen fibrillarin by mercury followed by a T-cell-dependent immune response driven by the modified fibrillarin. Mice with different H-2 haplotypes were treated with (203)HgCl(2) in a dose of 0.5-16 mg Hg/L drinking water for 10 weeks. Whole-body accumulation and renal accumulation of mercury were assessed. Serum antinuclear antibodies were used to evaluate the autoimmune response, and serum immunoglobulin E (IgE) to study effects on T-helper cells of type 2. Strains with a susceptible H-2 haplotype developed autoantibodies to the nucleolar protein fibrillarin (AFA) in a dose-dependent pattern within 2 weeks. The substantially lower whole-body and organ mercury level needed to induce AFA in the susceptible A.SW strain compared with the H-2 congenic B10.S strain demonstrates that genetic factors outside the H-2 region modify the autoimmune response. Mouse strains without the susceptible haplotype did not develop any autoimmune reaction irrespective of dose and organ deposition of mercury. In susceptible mouse strains, males and females had different thresholds for induction of autoimmune reactions. In susceptible strains, serum IgE increased dose dependently and reached a maximum after 1-2.5 weeks. A susceptible H-2 haplotype is therefore a prerequisite for the autoimmune response. Mercury exposure will modulate the response, qualitatively through the existence of dose-related thresholds for autoimmune response and quantitatively as increasing doses cause increasing autoimmune response. Further, gender and non-H-2 genes modulate both the induction and subsequent development of AFA. Induction of IgE seems not to be mechanistically linked to the AFA response.

Animals↗
PubMedDate not supplied

Critical parameters in the MCF-7 cell proliferation bioassay (E-Screen).

The MCF-7 cell proliferation bioassay has grown in popularity as a rapid test for detecting potentially oestrogenic compounds. Several MCF-7 cell sublines with different sensitivities to oestrogens are currently used, with maximal proliferation responses ranging from two- to 10-fold above those of hormone-free controls. In the highly responsive MCF-7 BUS cell line, we evaluated critical assay parameters for test performance, including growth conditions, initial seeding densities and differences in growth stimulation in medium containing human serum or fetal calf serum as well as appropriate solvents for oestrogen-mimicking compounds. Modifications significantly reduced the labour-intensive steps and overall assay costs without affecting the sensitivity of the assay. Using this optimized test regimen, the responsiveness of treated MCF-7 BUS cells was consistently increased up to 11-fold over hormone-free controls. The specificity was characterized by examining the effects of oestradiol-17beta, the anti-oestrogen ICI 182,780, and dieldrin, a recognized xeno-oestrogen. The improved proliferation bioassay will be a useful tool in identifying potential xeno-oestrogens.

Biological Assay↗
PubMedDate not supplied

Effects of baseline risk information on social and individual choices.

This article analyzes preferences for risk reductions in the context of individual and societal decision making. The effect of information on baseline risk is analyzed in both contexts. The results indicate that if individuals are to imagine that they suffer from 1 low-risk and 1 high-risk ailment, and are offered a specified identical absolute risk reduction, a majority will ceteris paribus opt for treatment of the low-risk ailment. A different preference structure is elicited when priority questions are framed as social choices. Here, a majority will prefer to treat the high-risk group of patients. The preference reversal demonstrates the extent to which baseline risk information can influence preferences in different choice settings. It is argued that presentation of baseline risk information may induce framing effects that lead to nonoptimal resource allocations. A solution to this problem may be to not present group-specific baseline risk information when eliciting preferences.

Adult↗