Differential effects of endogenous lithium on neurobehavioural functioning: a study on auditory evoked potentials.

Lithium occurs naturally in food and water. Low environmental concentrations in drinking water are associated with mental illnesses and behavioural offences, and at therapeutic dosages it is used to treat psychiatric (especially affective) disorders, partly by facilitating serotonergic (5-HT) neurotransmission. As little is known about the psychophysiological role of nutritional lithium in the general population, endogenous lithium concentrations were hypothesised to be associated with measurable effects on emotional liability and the loudness dependence (LD) that is proposed as one of the most valid indicators of 5-HT neurotransmission. Auditory evoked potentials of healthy volunteers [N=36] with high (>2.5 microg/l) or low (<1.5 microg/l) lithium serum concentrations were recorded. Emotional liability was assessed using the Brief Symptom Inventory (BSI). Low-lithium levels correlated with Somatisation while correlations between lithium and LD were not significant. Still, LD correlated positively with Paranoid Ideation, negatively with Anxiety and, in the high-lithium group, inversely with further aspects of emotional liability (Depression, Psychological Distress). In conclusion, the effects of low levels of endogenous lithium are associated with emotional liability, and high levels with some protective effects, although findings remain inconclusive regarding LD. Potential benefits of endogenous lithium on neurobehavioural functioning, especially in high-risk individuals, would have public health implications.

Substance-related environmental monitoring: Work group 'Environmental Monitoring'-Position paper.

BACKGROUND: Due to the requirements of the EU Water Framework Directive and other legal regulations (e.g., national laws like the German Federal Soil Protection Act), but also due to the implementation of the new EU chemicals management system REACH, environmental monitoring will gain increasing importance for the surveillance of environmental quality as well as for the assessment of chemicals. Against this background, the Work Group on 'Environmental Monitoring' of the Division of 'Environmental Chemistry and Ecotoxicology' within the German Chemical Society has compiled a position paper on substance-related environmental monitoring. SCOPE: Core elements of this position paper are the definitions of important terms like monitoring, exposure monitoring, effect monitoring, and integrated monitoring. Moreover, temporal and spatial aspects (monitoring of spatial distributions, trend monitoring, and retrospective monitoring) and their applications are discussed. The main focus of this position paper is the coverage of aspects which have to be observed for the preparation and implementation of a monitoring program. Essential is the clear specification of the targets of the monitoring which determine the development of the monitoring concept and its realization, e.g., if environmental media (compartments) or organisms are most appropriate as samples for the aim of the study. Of course, also the properties of the target substances are important (e.g., lipophilicity/bioaccumulation as pre-requisite for an exposure monitoring with organisms). Finally, the monitoring phases of sample planning, sampling, storage and transport of samples, selection of analytical methods, quality assurance measures as well as reporting are discussed. PERSPECTIVES: An important issue for the future is to link the quantification of chemicals in environmental compartments (exposure and pollution monitoring) more closely to the study of biological effects (effect monitoring) than has been the case up to now. Furthermore, by inclusion of a spatial differentiation, a comprehensive evaluation of the state of an ecosystem can be obtained and the relevance of the results improved. Practical examples of monitoring studies which illustrate various aspects covered in this position paper will be presented in a series of publications by members of the Work Group in the following issues of this journal.

C-reactive protein levels and clinical symptoms following gadolinium administration in hemodialysis patients.

BACKGROUND: Until recently, gadolinium (Gd)-enhanced magnetic resonance imaging (MRI) has increasingly replaced iodinated contrast agent examinations in dialysis patients, although only limited data existed about the clinical safety of Gd contrast agents in these patients. Specific clinical adverse events (AEs), including nephrogenic systemic fibrosis, were linked to Gd exposure in dialysis patients. An inflammatory reaction or transmetallation may be involved. STUDY DESIGN: Secondary analysis of a 5-day observational study in a parent cardiovascular study with repetitive cardiac MRI (32 patients) and patients undergoing Gd-enhanced MRI for clinical indications (6 patients). Clinical information and samples were obtained according to parent protocol. SETTING & PARTICIPANTS: Dialysis patients at a university-based dialysis unit. PREDICTOR: Gd-chelate complex. 37 of 38 patients underwent 64 MRI studies with Gd-diethylenetriamine penta-acetic acid (Gd-DTPA). 25 of these patients underwent additional MRI studies with gadobutrol (n = 10), 0.9% saline (n = 7), or both (n = 8), and 1 patient received gadobutrol only. OUTCOMES: Clinical adverse events; C-reactive protein (CRP) levels on days 1, 3, and 5 after MRI; Gd levels in blood and urine after MRI. RESULTS: CRP levels increased 10-fold on day 3 after MRI in 87% of MRI studies with Gd-DTPA (+59.3 +/- 57.9 mg/L [P < 0.001] versus -0.9 +/- 3.7 mg/L with gadobutrol versus -0.9 +/- 8.5 mg/L with 0.9% saline). 77 mild to moderate and 3 serious AEs were observed in 24 patients. CRP levels and adverse events did not correlate with Gd blood concentrations. CRP level increase or AEs were not observed after MRI with gadobutrol or 0.9% saline. LIMITATIONS: Observational study without randomization, risk of bias because of multiple MRI studies in a limited patient cohort. CONCLUSION: Gd-DTPA, but not gadobutrol, induces an acute-phase reaction and clinical AEs in dialysis patients. Additional investigations have to analyze the underlying pathomechanism.

Assessment of environmental worry in health-related settings: Re-evaluation and modification of an environmental worry scale.

The aim of this article was to re-evaluate and possibly modify the standardized Environmental Worry Scale (EWS) by Hodapp et al. [1996. Evaluation eines Fragebogens zur Erfassung von Umweltbesorgnis. Z. Gesundheitspsychologie IV(1), 22-36] with regard to its content and structure. In order to do this, 161 participants were chosen as a reference group to take part in a survey. The data were analyzed and a factor analysis yielded two instead of one component of worry, namely "personal" and "general" environmental worry, leading to a new evaluation method. This revised evaluation method was then applied to patients (n=227) with or without self-reported multiple chemical sensitivity (MCS) and thus used in the context of reported health complaints. The outlined results indicate that the assessment of worry as proposed by Hodapp et al. [1996. Evaluation eines Fragebogens zur Erfassung von Umweltbesorgnis. Z. Gesundheitspsychologie IV(1), 22-36] should be elaborated by the newly developed evaluation method with which a ratio determined by "personal" and "general" worry can be calculated. In addition to analyzing the absolute quantity of worry, the calculated ratio allows to draw conclusions on the structure of worry. It will be discussed to what extent the results present new insights into the role of worry among patients suffering from environmental diseases.

Internal phthalate exposure over the last two decades--a retrospective human biomonitoring study.

In a retrospective human biomonitoring study we analyzed 24h urine samples taken from the German Environmental Specimen Bank for Human Tissues (ESBHum), which were collected from 634 subjects (predominantly students, age range 20-29 years, 326 females, 308 males) in 9 years between 1988 and 2003 (each n >or= 60), for the concentrations of primary and/or secondary metabolites of di-n-butyl phthalate (DnBP), di-iso-butyl phthalate (DiBP), butylbenzyl phthalate (BBzP), di(2-ethylhexyl) phthalate (DEHP) and di-iso-nonyl phthalate (DiNP). Based on the urinary metabolite excretion we estimated daily intakes of the parent phthalates and investigated the chronological course of the phthalate exposure. In over 98% of the urine samples metabolites of all five phthalates were detectable indicating a ubiquitous exposure of the German population to all five phthalates throughout the last 20 years. The median daily intakes in the subsets between 1988 and 1993 were quite constant for DnBP (approx. 7 microg/kg bw/d) and DEHP (approx. 4 microg/kg bw/d). However, from 1996 the median levels of both phthalates decreased continuously until 2003 (DnBP 1.9 microg/kg bw/d; DEHP 2.4 microg/kg bw/d). By contrast, the daily intake values for DiBP were slightly increasing over the whole time frame investigated (median 1988: 1.1 microg/kg bw/d; median 2003: 1.4 microg/kg bw/d), approximating the levels for DnBP and DEHP. For BBzP we observed slightly decreasing values, even though the medians as of 1998 levelled off at around 0.2 microg/kg bw/d. Regarding daily DiNP exposure we found continuously increasing values, with the lowest median being 0.20 microg/kg bw/d for the subset of 1988 and the highest median for 2003 being twice as high. The trends observed in phthalate exposure may be associated with a change in production and usage pattern. Female subjects exhibited significantly higher daily intakes for the dibutyl phthalates (DnBP p=0.013; DiBP p=0.004). Compared to data from US National Health and Nutrition Examination Surveys (NHANES) exposure levels of the dibutyl phthalates were generally higher in our German study population, while levels of BBzP were somewhat lower. Overall, for a considerable 14% of the subjects we observed daily DnBP intakes above the tolerable daily intake (TDI) value deduced by the European Food Safety Authority (EFSA) (10 microg/kg bw/d). However, the frequency of exceedance decreased during the years and was beneath 2% in the 2003 subset. Even though transgressions of the exposure limit values of the EFSA and the US Environmental Protection Agency (US EPA) occurred only in a relatively small share of the subjects, one has to take into account the cumulative exposure to all phthalates investigated and possible dose-additive endocrine effects of these phthalates.

Applicability of a set of diagnostic tests in indoor air health research.

Following recommendations from literature, 22 diagnostic tests for the most frequent complaints of indoor air health problems were selected and assessed for their applicability in epidemiological studies. The tests were applied seven times during one year to 40 volunteers who to all appearances were not affected by indoor air health problems. Most psychophysical tests (e.g., Continuous Performance Test) turned out to be suitable, but physiological tests were either heavily disturbed by technical problems (e.g., portable electrogastrography), or biased by application techniques (e.g., acoustic rhinometry), or were simply too time-consuming (e.g., PC-based voice analysis). Hence, as standardized measurements and quantitative diagnostic tests in epidemiological indoor air health research may contribute to a better understanding of cause-effect relationships and yield new approaches for preventive and therapeutic strategies, more research is urgently needed to develop and evaluate suitable physiological tests and functional measurements.

Communication problems with environment-related health disorders as illustrated by a multiple chemical sensitivity (MCS) chatroom.

The problem of communication in treating multiple chemical sensitivity (MCS) was analysed and evaluated using the documentation of an MCS chatroom which was set up in April 2001 following the TV programme Gesundheitsmagazin Praxis (Health Magazine: Practice). Approaches were developed for solving communication problems in the chatroom. A total of 490 cases were evaluated, most of which (355) were directly or indirectly affected, 76 came from self-help groups and 10 were from 4 guest experts invited by ZDF (Zweites Deutsches Fernsehen, Second German TV channel). Of these 4 experts, 2 were environmental medicine specialists, 1 psychosomatics expert and 1 psychiatrist. Fourty-nine of the cases included a petition for chatroom participants to join a class-action law. Aside from exchanging basic information on MCS, frequent topics of discussion on the air were the assessment of physicians, clinics, self-help groups and experts. The participants also expressed their views on problems with society, politics, the economy, science and social security. Another common topic was communication in the chatroom itself, which for the most part consisted of sarcasm and insults, which were cause for conflicts in the chatroom. These communication problems led to the conclusion that a chatroom is not the best medium for discussing MCS. If a chatroom is to be used profitably to this end, it is imperative to have a well-defined organisational framework which allows the exchange of current, scientifically accurate information while keeping discussions from escalating and degenerating into arguments.

Environmental agents as cause of health disorders in children presented at an outpatient unit of environmental medicine.

There are no publications on the frequency of environmental agents causing diseases in children presented at centers of environmental medicine. The aim of this study was to perform a statistical analysis of the data of children who visited the outpatient Unit of Environmental Medicine (UEM) at the University Hospital of Aachen, Germany. Data of all UEM patient files from January 1988 to September 1996 were evaluated. From a total of 682 patients, 75 were children (40 girls, 35 boys, age range 1-12 years). Forty-six children were presented with unspecific health disorders, 12 to examine a possible relationship between environmental agents and a current condition, mostly atopy (n = 10). Complaints were mucosal irritations (n = 38), unspecific (n = 19), dermatological (n = 16), gastrointestinal (n = 4), heart/circulation-related (n = 2), musculoskeletal (n = 1) and neurological (n = 1) symptoms. Wood preservatives were mentioned as suspected environmental causative agents in 22 cases, followed by unspecific indoor factors (n = 15), factories/disposal sites near homes (n = 9), formaldehyde (n = 5) and unspecific exposures (n = 5). Biomonitoring was done in 44 cases, local inspections and ambient monitoring in 10 cases. No evidence for a cause-and-effect relationship was found in 55 children, but was deemed possible in nine cases. In nine other children, a relatively high degree of exposure was determined by chemical analysis, but clinical relevance remained unclear. One child suffered from subclinical mercury poisoning caused by inadequate homeopathic medication. In most children referred to an environmental medicine center, it is difficult or impossible to verify an environmental cause using the diagnostic instruments currently available.

Predictive value of human biomonitoring in environmental medicine: experiences at the outpatient unit of environmental medicine (UEM) of the University Hospital Aachen, Germany.

There is little data on the distribution of biomonitoring parameters in patients at outpatient Units of Environmental Medicine (UEM). We evaluated the biomonitoring parameters of 646 UEM outpatients from our University Hospital 1988-1998. Few patients were exposed to specific substances. Data of patients who were not obviously exposed was analysed statistically (geometric mean, standard deviation, median, 95th percentile). Results were compared with reference values in literature. Normal distribution of biomonitoring parameters was rare. 95th percentiles for arsenic, chromium, selenium, zinc, phenol and toluene were below standard, 95th percentiles for copper and mercury above, and 95th percentiles for lead, cadmium, pentachlorophenol, lindane, and beta-hexachlorocyclohexane were within the published range of reference values. Thallium as well as most volatile organic compounds analyzed were below detection levels. Aluminum and fluorine exposure was rarely analysed. In view of these results, it is concluded that the indication for biomonitoring needs to be stringent as levels of biomonitoring parameters are generally not risen in patients of the UEM.

Working memory deficiencies in adults associated with low-level lead exposure: implications of neuropsychological test results.

BACKGROUND: Although lead exposure has steadily decreased in the last few years, some lead is still used in the metal processing industry, mostly for wall paints and plumbing. Recent studies on children showed neurobehavioral effects of low-level exposure, but little is known about the neurocognitive effects of lead concentrations in the upper reference range on adults. METHODS: The neuropsychological effects of lead exposure were examined in 39 adult outpatients at the Unit of Environmental Medicine (UEM), University Hospital, Aachen, Germany. All patients underwent a comprehensive medical examination, including psychiatric. Venous blood and urine samples were collected and tested for heavy metals and selenium. Since the neuropsychological examination was not expected to reveal any severe abnormalities, only specific attentiveness functions were analyzed (alertness, working memory, flexibility, intermodal comparison) since these areas were the likeliest to show objectifiable effects. The tests were conducted using a standardized computerized battery. RESULTS: Lead blood levels ranged from 1 to 65.6 microg/l (mean 27.4 +/- 16.2 microg/l). Although the neuropsychological test results of all patients were within the normal range, there were significant correlations between blood lead levels and the speed of information processing for working memory. CONCLUSIONS: The results indicate working memory dysfunctions in adults, the severity of which correlates directly with blood lead levels, supporting the hypothesis that increased blood lead levels can also be associated with measurable neurocognitive abnormalities.

Environmental factors as delusional contents in patients with schizophrenia.

In a series of 50 consecutive cases in the outpatients' unit of Environmental Medicine (UEM) at the University Hospital of Aachen, Germany, five patients with the diagnosis of schizophrenia presented delusions of being poisoned by environmental factors. This case report illustrates the clinical features of the paranoid type of schizophrenic psychoses. Schizophrenia represents an important differential diagnosis in the interdisciplinary diagnosis and management of health problems attributed to environmental factors.

Nasal function in self-reported chemically intolerant individuals.

Nasal function has not yet been investigated under controlled exposures in individuals with self-reported Multiple Chemical Sensitivity (sMCS). Therefore, anterior rhinomanometry and acoustic rhinometry were applied in 12 individuals with sMCS, and 12 age-matched controls. The sMCS individuals and controls were selected on the basis of a standardized questionnaire. Controlled 4-hr exposures to ethylbenzene and 2-butanone were performed during 4 sessions. Exposures were close to the current German threshold limit values, and they approximated odor thresholds. Subjects with sMCS had a significant decrease in the flow value in anterior rhinomanometry, independent of substance and doses, compared with controls. This result suggests somatic reactions to the exposure. The result must be confirmed in additional studies, and pathophysiological examinations must be performed. For these investigations, anterior rhinomanometry was usable, but acoustic rhinometry can be recommended only after sufficient standardization has occurred. Furthermore, biochemical parameters of nasal mucosa must be considered.

Trends of the internal phthalate exposure of young adults in Germany--follow-up of a retrospective human biomonitoring study.

The exposure of the general population to phthalates is of increasing public health concern. Variations in the internal exposure of the population are likely, because the amounts, distribution and application characters of the phthalate use change over time. Estimating the chronological sequences of the phthalate exposure, we performed a retrospective human biomonitoring study by investigating the metabolites of the five most prominent phthalates in urine. Therefore, 24h-urine samples from the German Environmental Specimen Bank (ESB) collected from 240 subjects (predominantly students, age range 19-29 years, 120 females, 120 males) in the years 2002, 2004, 2006 and 2008 (60 individuals each), were analysed for the concentrations of mono-n-butyl phthalate (MnBP) as metabolite of di-n-butyl phthalate (DnBP), mono-iso-butyl phthalate (MiBP) as metabolite of di-iso-butyl phthalate (DiBP), mono-benzyl phthalate (MBzP) as metabolite of butylbenzyl phthalate (BBzP), mono-(2-ethylhexyl) phthalate (MEHP), mono-(2-ethyl-5-hydroxyhexyl) phthalate (5OH-MEHP), mono-(2-ethyl-5-oxohexyl) phthalate (5oxo-MEHP), mono-(2-ethyl-5-carboxypentyl) phthalate (5cx-MEPP) and mono-(2-carboxymethyl hexyl) phthalate (2cx-MMHxP) as metabolites of di(2-ethylhexyl) phthalate (DEHP), monohydroxylated (OH-MiNP), monooxidated (oxo-MiNP) and monocarboxylated (cx-MiNP) mono-iso-nonylphthalates as metabolites of di-iso-nonyl phthalates (DiNP). Based on the urinary metabolite excretion, together with results of a previous study, which covered the years 1988-2003, we investigated the chronological sequences of the phthalate exposure over two decades. In more than 98% of the urine samples metabolites of all five phthalates were detectable indicating a ubiquitous exposure of people living in Germany to all five phthalates throughout the period investigated. The medians in samples from the different years investigated are 65.4 (2002), 38.5 (2004), 29.3 (2006) and 19.6 µg/l (2008) for MnBP, 31.4 (2002), 25.4 (2004), 31.8 (2006) and 25.5 µg/l (2008) for MiBP, 7.8 (2002), 6.3 (2004), 3.6 (2006) and 3.8 µg/l (2008) for MBzP, 7.0 (2002), 5.6 (2004), 4.1 (2006) and 3.3 µg/l (2008) for MEHP, 19.6 (2002), 16.2 (2004), 13.2 (2006) and 9.6 µg/l (2008) for 5OH-MEHP, 13.9 (2002), 11.8 (2004), 8.3 (2006) and 6.4 µg/l (2008) for 5oxo-MEHP, 18.7 (2002), 16.5 (2004), 13.8 (2006) and 10.2 µg/l (2008) for 5cx-MEPP, 7.2 (2002), 6.5 (2004), 5.1 (2006) and 4.6 µg/l (2008) for 2cx-MMHxP, 3.3 (2002), 2.8 (2004), 3.5 (2006) and 3.6 µg/l (2008) for OH-MiNP, 2.1 (2002), 2.1 (2004), 2.2 (2006) and 2.3 µg/l (2008) for oxo-MiNP and 4.1 (2002), 3.2 (2004), 4.1 (2006) and 3.6 µg/l (2008) for cx-MiNP. The investigation of the time series 1988-2008 indicates a decrease of the internal exposure to DnBP by the factor of 7-8 and to DEHP and BzBP by the factor of 2-3. In contrast, an increase of the internal exposure by the factor of 4 was observed for DiNP over the study period. The exposure to DiBP was found to be stable. In summary, we found decreases of the internal human exposure for legally restricted phthalates whereas the exposure to their substitutes increased. Future investigations should verify these trends. This is of increasing importance since the European Commission decided to require ban or authorization from 1.1.2015 for DEHP, DnBP, DiBP and BzBP according to REACh Annex XIV.

Fetal exposure to phthalates--a pilot study.

The fetus is considered to be the most sensitive stage of life to the potential developmental and reproductive toxicity of the phthalates. But, data on human fetal exposure to phthalates is still scarce. In this pilot study we collected 11 pairs of amniotic fluid (AF) and corresponding maternal urine (MU) samples during Caesarean section and analysed them for several phthalate metabolites by LC-MS/MS. In all AF samples, metabolites of di-n-butyl phthalate (DnBP), diisobutyl phthalate (DiBP), butylbenzyl phthalate (BBzP), di(2-ethylhexyl) phthalate (DEHP) were detectable. For the first time, we were able to detect also oxidative phthalate metabolites in AF, with two carboxy metabolites of DEHP showing the highest abundance. In the MU samples, the concentrations of the phthalate metabolites were generally much higher than in the AF samples. There was a statistically significant linear correlation for the DiBP monoester (MiBP) (r=0.93; p<0.001) in the AF and MU samples. We also found a significant correlation for the DEHP monoester (MEHP) (r=0.91; p<0.001), although there was a most likely external contamination with MEHP in the MU samples. Our results suggest that several phthalates or their metabolites, respectively, reach the human fetus, which might be able to affect fetal health. Further research is needed to elucidate fetal metabolism of phthalates and to evaluate the in utero phthalate exposure and the potential effects on fetal reproductive development. Due to the continuous turn over of AF, urinary levels may be most appropriate for assessing both maternal and fetal phthalate exposure.

Clinical environmental medicine.

INTRODUCTION: Clinical environmental medicine deals with environmental effects on human health in individual patients. Patients seek medical advice for problems of many different kinds that may be due to environmental exposures; such exposures must be considered carefully along with other potential causes. An environmental medical assessment should include thorough medical history-taking and physical examination, the formulation of a differential diagnosis, and (whenever indicated) human biomonitoring, site inspections, and ambient monitoring. METHODS: This review of clinically relevant environment-related health disturbances is based on a selective evaluation of the pertinent literature and of own experiences. RESULTS: Overall, relevant environmental exposures can be identified in up to 15% of patients who attribute their health complaints to environmental factors. (Clinical disorders are more common and more severe in these patients.) 40% to 75% are found to suffer from other physical and/or emotional conditions without any specific environmental aspect, i.e., without any apparent or verifiable exposure. DISCUSSION: Despite the relative rarity of verifiable environmentally related health disturbances, these must be clearly identified and delimited to avoid further harmful exposures. Environmental medical counseling should include risk assessment and behavior recommendations for all patients who attribute their medical problems to their environment. Physicians performing specific environmental-medical diagnostic procedures must be aware of their limitations in order to avoid performing tests whose results have no therapeutic consequences and are thus of no help to either the physician or the patient.