["Understanding" in psychiatry -Part 2 : From incomprehensibility to an attitude of participative communication]. / "Verstehen" in der Psychiatrie ­ Teil 2 : Vom Unverständlichen zur Verständigungsdisposition.

BACKGROUND: Starting from a systematic research of "incomprehensibility" we propose a turn from an epistemological analysis of "to understand" to an anthropological perspective relying on participative communication in a shared space of resonance. METHOD: We propose a systematization of the modes of understanding and of incomprehensibility based on a two-dimensional model combining epistemological and ontological perspectives. Finally, we outline "understanding" as a medical stance related to the healing relationship, which implies a disposition to get involved in a participative communication. We put forward the hypothesis that acceptance of the otherness of the patient, without the intention of a complete appropriation of meaning, could be noted as crucial feature of the anthropological approach. RESULTS: In clinical medicine, especially in psychiatry, "not understood" is threefold: as "misunderstanding", as "not-understanding" (as a temporary lack of understanding), and as incomprehensibility (to understand, that there is nothing to be understood). Incomprehensibility may only allow for interpretative operations up to a certain limit. This unidirectional understanding as a diagnosing subsumption or as a psychological explanation in order to grasp meanings has to be completed by a bi-directional personal approach based on an engaging attitude (dialogical as well as quiescent) while acknowledging the incomprehensible. DISCUSSION: A second-person-perspective emphasizes the healing relationship as an existential encounter, especially in personal liminal situations for the patient. From an anthropological perspective "to understand" has not only to be grasped as a semantic agreement, but also as an attitude towards participative communication. That means a disposition to get involved in the encounter with the mentally ill without aiming for grasping rationally significances or even to attribute meanings. The stance therefore should be based on an awareness for the patient's idiosyncrasy as well as on the empathetic production of a shared space of resonance within the healing relationship.

["Understanding" in psychiatry-part 1 : Philosophical sources and concept analysis]. / "Verstehen" in der Psychiatrie ­ Teil 1 : Philosophische Quellen und Begriffsanalyse.

BACKGROUND: The dichotomy comprehension/understanding vs. explanation has been initially developed with a legitimating intention for the humanities vis à vis the natural sciences. This investigation examines the different usages of understanding/comprehension in psychiatry and psychotherapy as well as its relevance for medical practice. METHOD: Critical discussion of the historical roots of the comprehension-explanation dichotomy and its introduction into the psychiatry by Jaspers. A propaedeutic logical analysis of the concept of "understanding" will be proposed. This investigation aims to elucidate latent dimensions in the usage of "understanding" in psychiatry and psychotherapy. In more detail the operation of assignment and attribution will be discussed as well as the elucidation of individual meaning and supraindividual significance. RESULTS: The term analysis shows that "to understand" as a predicate is gradually and polysemic; its definition must take the different logically additive meanings into account. These meanings can be condensed into three dimensions: i. Rational diagnostic assignment; ii. Elucidation of meaning through individual empathetic re-experiencing as a psychological approach respectively the supraindividual elucidation of significance, and; iii. Dialogic attitude. Psychological understanding roots in Jaspers' epistemology on assignment to and alignment with supraindividual meaningful connections and not on empathetic re-experiencing. DISCUSSION: "To understand" as a logical operation of assignment and as meaning elucidation takes for granted a predicate in its transitive first-person perspective ("who" should be understood, as objectified) in conjunction to a third-person perspective ("what" should be understood). This analysis should be complemented by a first-person perspective ("who" should be understood, as a subject) in conjunction with a dialogic second-person perspective ("how" should be understood, following a mutual disposition). This last approach will be discussed in an additional article.

[Care differences in a consultation and liaison service]. / Versorgungsunterschiede im Konsiliar- und Liaisondienst.

BACKGROUND: The investigation of the real density of care by a consultation-liaison service (CLS) as a function of patient groups, settings and diagnoses makes sense with respect to a better allocation of resources. OBJECTIVE: Are there differences concerning the density of care by a CLS in a general hospital depending on patient groups and on the psychiatric diagnosis? METHOD: A retrospective (2012-2015) survey of all consultations (n = 7081 corresponding to 4080 patients) was carried out based on the CLS documentation for quality assurance. Bivariate tests (i.e. χ2-test and ANOVA) and multivariate linear and logistic models were used to investigate group differences and associations. RESULTS: The number of consultations achieved corresponded to 3.2 % of the total admissions to hospital, especially internal medicine (22.3 %), surgery (26.1 %) as well as gynecology and obstetrics (21.1 %). A suicide attempt was the reason for treatment in 3.3 %. Each patient received on average 1.7 consultations lasting 75 min but only 25 % received 2 or more consultations. Patients with psychiatric comorbidities, non-oncology patients as well as female and young patients received a more intensive care by CLS. Patients with depressive and somatoform disorders received a higher density of treatment. DISCUSSION: The psychotherapeutic interventions performed did not follow the expected diagnostic patterns in other settings. Systemic interventions with indirect treatment should be given priority in older patients and especially in patients with organic mental disorders.

[Man at the Frontier of his Being: Scope of the Concept of "Limit Situation" in Psychiatry and Psychotherapy Following Jaspers' Existential Ontology]. / Der Mensch an seinen Grenzen - Tragweite von "Grenzsituation" für die Psychiatrie nach Jaspers.

BACKGROUND: The existential concept of "limit situation" was proposed by Jaspers as the inevitable threshold of human beings at their ordinary mode of being, namely Dasein, which has to be crossed to reach Existence as the proper mode of being after having transcended an existential challenge. A failure at facing limit situations indicates that they are ineluctable and have to be assumed. METHOD: The starting point is the analysis of Jaspers' concept of limit situations, both within the antinomic structure of the human condition as well as the duality of being-in-the-world. An attempt is made here to interpret the ontological determination of the limit situation as an ontic one, which could be relevant to psychiatric and psychotherapeutic practice. RESULTS: The distinction between Dasein and Existence as modes of being is at the basis of Jaspers' existential philosophy. Limit situations cannot be veiled; therefore, they require a transcendence movement of the self in order to overcome enclosures and to reach the mode of being of Existence as authentic selfhood. Jaspers creates an ontological typology of limit situations in which suffering plays a key role. An ontic correspondence for psychiatry and psychotherapy refers to the importance of critical life events, of suicidality, of rigid thought styles and behavior patterns as enclosures; illness is both a limit situation in itself and also its consequence. In anthropological terms, the concepts of existential vulnerability and competence in dealing with limit situations have proved to be rewarding. DISCUSSION: The ontic correspondence to Jaspers' ontological concept of limit situations suggested by the author makes a fruitful contribution to psychiatry and psychotherapy, because it draws attention to the person-environment fit as a possible predetermined breaking point that could lead to psychopathologically relevant failure. Critical life events understood as relational, as well as existential vulnerability and defense mechanisms biographically illuminated could contribute to an improvement of competence in dealing with limit situations within the psychotherapeutic practice.

[Characteristics of Hospitalized Mentally ill Spanish Migrants in Germany - Results of a Statistical Reanalysis]. / Stationär behandelte psychisch kranke spanische Migranten der ersten Generation in Deutschland - Ergebnisse einer Reanalyse.

OBJECTIVE: To draft a clinical profile of mentally ill first-generation Spanish immigrants in Germany treated in a special setting in their native language and to identify possible correlations between time of onset of a mental disorder and migration and also between degree of utilization and clinical as well as care variables. METHOD: Statistical reanalysis of individual data (n = 100) of a previously published descriptive study with aggregated data corresponding to 15 variables. Correlations are calculated using chi-square as well as Fisher's exact test. Multivariate regression and logistic models were conducted. In addition to the explained variance of the models (R(2)), analyses of residuals as well as post-hoc power analyses (1-ß) were performed. RESULTS: A quarter of the sample (26 %) was mentally ill before migration; most of the patients received treatment very late (about 10 years after onset) and became chronically ill. Half of the sample shows a relevant somatic comorbidity and large average lengths of inpatient stays (54 days). In 16 % of treated cases, repatriation had to be organized. The degree of chronicity correlates with mental illness prior to migration. Severe mood disorders and psychoses occur late after having migrated, addictions and neurotic disorders are equally distributed over time. DISCUSSION: Migration can not be set in a causal relationship with the development of mental disorders, although there is a positive correlation between affective disorders and the duration of the migration status. Chronicity is related to an outbreak of the disease before migration. The sample is relatively homogeneous (one nationality, first generation), but loses epidemiological representativeness (not related to a catchment area).

[Decentralized outpatient teams in community-based psychiatric care: comparison of two Bavarian rural catchment areas]. / Dezentrale ambulante Teams in der gemeindenahen psychiatrischen Versorgung : Zwei bayerische ländliche Regionen im Vergleich.

BACKGROUND: Psychiatric outpatient clinics (PIAs) are an indispensable care service for crisis intervention and multidisciplinary treatment of people suffering from severe and persistent mental disorders. The decentralization of outpatient clinics can be understood as a further step in the deinstitutionalization process. METHODS: This cross-sectional study (n=1,663) compared the central outpatient clinic with the decentralized teams for the year 2010 by means of analyses of variance, χ(2)-tests and robust multivariate regression models. The longitudinal assessment (descriptively and by means of Prais-Winsten regression models for time series) was based on all hospitalizations for the two decentralized teams (n = 6,693) according to partial catchment areas for the time period 2002-2010 in order to examine trends after their installation in the year 2007. RESULTS: Decentralized teams were found to be similar with respect to the care profile but cared for relatively more patients suffering from dementia, addictive and mood disorders but not for those suffering from schizophrenia and personality disorders. Decentralized teams showed less outpatient care costs as well as psychopharmacological expenses but a lower contact frequency than the central outpatient clinic. Total expenses for psychiatric care were not significantly different and assessed hospitalization variables (e.g. total number of annual admissions, cumulative length of inpatient-stay and annual hospitalizations per patient) changed slightly 3 years after installation of the decentralized teams. The number of admissions of people suffering from schizophrenia decreased whereas those for mood and stress disorders increased. DISCUSSION: Decentralized outpatient teams seemed to reach patients in rural regions who previously were not reached by the central outpatient clinic. Economic figures indicate advantages for the installation of such teams because care expenses are not higher than for patients treated in centralized outpatient clinics and because hospitalization figures for the whole catchment area did not increase.

[Consequences of the German federal Guardianship Law after reunification (1992-2009)]. / Auswirkungen des Betreuungsgesetzes im wiedervereinigten Deutschland (1992-2009).

BACKGROUND: The Guardianship Law became effective in the year 1992 with the intention of replacing the paternalistic-restrictive model by a model based on the principles of participation and empowerment. METHODS: Data from the Federal Ministry of Justice were used to examine the development of 12 legal guardianship parameters over a period of 17 years (1992-2009) at the level of federal states. Due to the completely different practise in both parts of Germany before reunification, the development will be analysed separately for the old and the new federal states. RESULTS: All examined parameters indicate an increase of legal guardianship. The highest increases were found for enlargement of the task scope (+606%) and for approval of contention measures (+868%). With the exception of involuntary commitment rates, in the new federal states the mean values of all variables score higher than in the old federal states. Legal guardianship installation only increased for the old federal states significantly (T(9)=6.64; p=0.007); however, the guardianship expenses were higher, but not significantly, for the new federal states. DISCUSSION: In spite of the legal changes in the direction of a dynamic instrument in mental health care, the practise of the Legal Guardianship Law indicates a continuous increase of guardianship orders since 1992. It is necessary to recognise that a slowdown of the upward trend is not in sight. Therefore it is pertinent to call those persons in charge of regulating legal guardianship to consider their daily practise carefully. On the other hand it is a task of mental health services research to analyse the driving factors of the presented developments.

[German practice of involuntary commitment at both federal and state level after introduction of the Guardianship law (1992-2009)]. / Deutsche unterbringungsrechtliche Praxis auf Bundes- und Länderebene nach Einführung des Betreuungsgesetzes (1992-2009).

BACKGROUND: Given the steady rise of psychiatric coercive measures in Germany, the question arises whether this development is significantly influenced by the corresponding legal basis or through epidemiological, socio-economic or socio-structural factors. METHODS: Based on full surveys of the Federal Ministry of Justice we examined the development and associations of 10 indicators of coercive psychiatric measures over a period of 18 years. Time trends of all indicators have been descriptively analysed. Statistical associations between time trends and between involuntary and admissions economic indicators were analysed by regression models. RESULTS: All annual involuntary commitment rates have increased, judicial ordered physical restraint measures particularly strongly (848%). The rate of judicial rejections of applied involuntary measures showed the lowest increase. On the other hand, quotas of involuntary admissions remained stable. In former East Germany, the involuntary admission rates are only a third of those in the former West Germany. Results of regression analyses indicate an excess increase of physical coercive measures in psychiatric hospitals in relation to the increase of psychiatric admissions. In former East Germany the rate of involuntary admissions at the federal state level is negatively correlated with the average gross income. DISCUSSION: The continuous increase of coercive psychiatric measures in consequence to the change in the Guardianship law suggests that this change has influenced the practice. The differences at federal and state levels, and the sharper rise in the former East Germany by lower rates in comparison to the former West Germany need an explanation, as well as the fact that the rate of involuntary admissions is associated at least in the former East Germany with economic conditions.

Toxicity of Herbicide Mixtures to Tropical Freshwater Microalgae Using a Multispecies Test.

Agriculture within the Great Barrier Reef catchment area has contributed to pesticide contamination of adjacent freshwater ecosystems that flow into the Great Barrier Reef World Heritage Area. A novel multispecies toxicity test was used to assess the toxicity of diuron and hexazinone, 2 herbicides commonly detected within the Great Barrier Reef catchment area, to a community of 3 tropical freshwater microalgae: Monoraphidium arcuatum, Nannochloropsis-like sp., and Pediastrum duplex. Diuron was the most toxic herbicide, with 10% inhibition concentration (IC10) values of 4.3, 7.1, and 29 µg/L for P. duplex, M. arcuatum, and Nannochloropsis-like sp., respectively, followed by hexazinone, with IC10 values of 15, 18, and 450 µg/L, respectively Toxicity testing on 2 commercial formulations (Barrage, 13.2% hexazinone and 48.6% diuron; Diurex, 90% diuron) showed that additives in the commercial formulations did not significantly increase the toxicity of diuron. Direct toxicity assessments were carried out on water samples from the herbicide-contaminated Sandy Creek, which discharges to the Great Barrier Reef lagoon, and a clean reference site, Tully Gorge in the Tully River. Toxicity was observed in several Sandy Creek samples. Artificial herbicide mixtures were assessed in synthetic soft water and natural freshwaters, with toxic responses being observed at environmentally relevant concentrations. The present study successfully applied a novel multispecies tropical microalgal toxicity test, indicating that it is an effective tool for the assessment of herbicide toxicity in both natural and synthetic freshwaters. Environ Toxicol Chem 2021;40:473-486. © 2020 SETAC.

Amygdala reduction in patients with ADHD compared with major depression and healthy volunteers.

OBJECTIVE: Results in adult attention deficit hyperactivity disorder (ADHD) on structural brain changes and the clinical relevance are contradictory. The aim of this study was to investigate whether in adult patients with ADHD hippocampal or amygdala volumes differs from that in healthy controls and patients with major depression (MD). METHOD: Twenty patients with ADHD, 20 matched patients with MD and 20 healthy controls were studied with high resolution magnetic resonance imaging. RESULTS: Amygdala volumes in patients with ADHD were bilaterally smaller than in patients with MD and healthy controls. In ADHD, more hyperactivity and less inattention were associated with smaller right amygdala volumes, and more symptoms of depression with larger amygdala volumes. CONCLUSION: This study supports findings that the amygdala plays an important role in the systemic brain pathophysiology of ADHD. Whether patients with ADHD and larger amygdala volumes are more vulnerable to affective disorders needs further investigation.

Polymerase chain reaction and immunoassay--matrix assisted laser desorption mass spectrometry using tag-mass technology: new tools to break down quantification limits and multiplexes.

We present a new development of the Tag-Mass concept based on a photocleavable linker with tagged molecules for polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA) quantification coupled to mass spectrometry. PCR-MS and immunosorbent assay-MS with tagged oligonucleotides, bases, and antibodies will allow the acquisition of multiplexed information from genomic, transcriptomic, and proteomic experiments. This is a novel application of Tag-Mass from tissue imaging to fluid quantification and will open doors to several clinical applications ranging from biomarker-driven gene modulation to use at the patient's bedside following treatment.

Development of a toxicity identification evaluation protocol using chlorophyll-a fluorescence in a marine microalga.

Growth inhibition bioassays with the microalga Nitzschia closterium have recently been applied in marine Toxicity Identification Evaluation (TIE) testing. However, the 48-h test duration can result in substantial loss of toxicants over time, which might lead to an underestimation of the sample toxicity. Although shorter-term microalgal bioassays can minimize such losses, there are few bioassays available and none are adapted for marine TIE testing. The acute (5-min) chlorophyll-a fluorescence bioassay is one alternative; however, this bioassay was developed for detecting herbicides in freshwater aquatic systems and its suitability for marine TIE testing was not known. In this study, a chlorophyll-a fluorescence bioassay using the marine microalga Isochrysis galbana was able to detect contaminants other than herbicides at environmentally relevant concentrations and tolerated the physical and chemical manipulations needed for a Phase I TIE. Phase I TIE procedures were successfully developed using this chlorophyll-a fluorescence bioassay and used to identify all classes of contaminants present in a synthetic mixture of known chemical composition. In addition, TIEs with both the acute fluorescence bioassay and the standard growth inhibition bioassay identified the same classes of toxicants in a sample of an unknown complex effluent. Even though the acute chlorophyll-a fluorescence end point was less sensitive than the chronic cell division end point, TIEs with the chlorophyll-a fluorescence bioassay provided a rapid and attractive alternative to longer-duration bioassays.

[Treatment of chronic psychiatric disorders. Ethical and anthropological aspects]. / Behandlung chronisch psychisch kranker Menschen. Ethische und anthropologische Aspekte.

This paper outlines an approach to assessing chronicity in psychiatric disorders, which represents a challenge for clinical practice. We began by accepting conclusions from well accepted anthropological and clinical studies of patients with chronic psychiatric disorders. Based on such key conclusions, we formulated several assumptions centred round anthropological concepts as a comprehension tool. Such an anthropological framework might improve orientation in the clinical evaluation of chronic psychiatric disorders. Ethical implications resulting from the above approach are discussed, specifically those revolving around the concept of "problematic people". Based on these considerations, ten practical concepts concerning the recovery from chronic psychiatric illness are discussed.

Development and application of a multispecies toxicity test with tropical freshwater microalgae.

Microalgae are commonly used in ecotoxicity testing due to their ease of culturing and rapid cell division rates. These tests generally utilise a single species of algae; however, microalgae occur in the environment as complex communities of multiple species. To date, routine multispecies toxicity tests using tropical microalgae have not been available. This study investigated four tropical freshwater microalgal species for use in a chronic multispecies toxicity test based on the population growth (cell division) rate: Pediastrum duplex, Monoraphidium arcuatum, Nannochloropsis-like sp. and Chlorella sp. 12. Flow cytometric analysis identified the different fluorescence and light scattering properties of each algal species and quantified each species within multispecies mixtures. Following optimisation of test media nutrients and pH, a toxicity testing protocol was developed with P. duplex, M. arcuatum and Nannochloropsis-like sp. There were no significant differences in growth rates of each alga when tested over 72 h as single species or in multispecies mixtures. Atrazine and imazapic, two herbicides with different modes of action, were used to assess the sensitivity of the multispecies toxicity test. Atrazine was toxic to all species with 72-h IC10 values of 7.2, 63 and 280 µg/L for P. duplex, M. arcuatum and Nannochloropsis-like sp. respectively, while imazapic was not toxic to any species at concentrations up to 1100 µg/L. The toxicity of atrazine and imazapic to each microalgal species in the multispecies toxicity test was the same as that determined from single-species toxicity tests indicating that the presence of these microalgae in a mixture did not affect the toxicity of these two herbicides. This study is the first to develop a multispecies tropical microalgal toxicity test for application in freshwaters. This time- and cost-effective tool can be utilised to generate data to assist environmental decision making and to undertake risk assessments of contaminants in tropical freshwater environments.

Rapid flow cytometric method for the assessment of toxic dinoflagellate cyst viability.

The inadvertent transfer and dispersal of non-indigenous marine species via shipping ballast water is of increasing environmental concern. Despite a major global effort to develop new ballast water treatment technologies, their acceptance has been hampered by the lack of suitable indicator species for assessing treatment effectiveness. Resistant dinoflagellate cysts are one proposed test organism, however their use has been limited due to difficulties in assessing their viability after treatment. The paper describes the development of a rapid method to determine the viability of cysts of the dinoflagellate Alexandrium catenella using staining with SYTOX Green and flow-cytometric analysis. The viability of A. catenella cysts was inversely proportional to their ability to take up the stain. There was excellent agreement between cysts measured as viable/non-viable using flow cytometry and cyst viability determined in standard long-term germination tests. Advantages of the flow-cytometric method include high test precision and rapid testing times of < 2 days, compared to > 4 weeks using existing germination methods.

Hardness corrections for copper are inappropriate for protecting sensitive freshwater biota.

Toxicity testing using a freshwater alga (Chlorella sp.), a bacterium (Erwinnia sp.) and a cladoceran (Ceriodaphnia cf. dubia) exposed to copper in synthetic and natural freshwaters of varying hardness (44-375 mg CaCO3/l), with constant alkalinity, pH and dissolved organic carbon concentration, demonstrated negligible hardness effects in the pH range 6.1-7.8. Therefore, the use of a generic hardness-correction algorithm, developed as part of national water quality guidelines for protecting freshwater biota, is not recommended for assessing the toxicity of copper to these, and other, sensitive freshwater species. Use of the algorithm for these sensitive species will be underprotective because the calculated concentrations of copper in water that cause a toxic effect will be higher.

Copper bioavailability in a coastal environment of Northern Chile: comparison of bioassay and analytical speciation approaches.

An integrated approach including chemical speciation analyses and microalgal bioassays was used to assess the impact of copper from copper mining on a coastal area in Northern Chile. Dissolved copper ranged from <1 microg l(-1) at reference sites to 48 microgl(-1) at sites close to the mine discharge. Dissolved copper at sites closest to the discharge always exceeded seawater complexing capacities determined by anodic stripping voltammetry (ASV), and consequently labile copper was always detected (1-37 microg l(-1)). Agreement between ASV-labile copper and copper retained by cation exchange (ALSA) columns was excellent. Measured labile copper also accurately predicted bioavailable copper determined by growth inhibition of Nitzschia closterium and enzyme inhibition in Dunaliella tertiolecta. Seawater from Caleta La Lancha had the highest dissolved and labile copper and was the most toxic to micro-algal growth and enzyme activity. Previous studies at this site confirmed it had the lowest level of biodiversity, suggesting that copper may have both direct and indirect effects on these communities.

A comparative study of copper, lead, cadmium and zinc in human sweat and blood.

Zinc, cadmium, lead and copper in sweat from 24 male and 39 female volunteers were determined by anodic stripping voltammetry. Sweating was induced on the forearms by pilocarpine iontophoresis. Average values found for zinc, cadmium, lead and copper in sweat from males were 181 (range 25-863), 1.4 (less than 0.5-10), 41 (6-87) and 103 (less than 5-673) micrograms l-1, respectively. Zinc in sweat from females was significantly higher than in sweat from males (331 micrograms l-1, range 87-836 micrograms l-1), while sweat copper and sweat lead in females were lower (29 micrograms Cu l-1, range less than 5-146 micrograms Cu l-1 and 24 micrograms Pb l-1, range less than 5-66 micrograms Pb l-1). Those taking oral contraceptives showed increased sweat copper concentrations (94 micrograms Cu l-1, range less than 5-480 micrograms Cu l-1) and sweat lead concentrations (36 micrograms Pb l-1, range less than 5-70 micrograms Pb l-1). There was no sex-based difference for copper in sauna-induced sweat. Metal concentrations in sweat were compared with ceruloplasmin, alkaline phosphatase, and total and mobile copper and zinc concentrations in serum in males and females.

The determination of trace metals in sweat by anodic stripping voltammetry.

Sweating was induced on the forearm of subjects by pilocarpine iontophoresis, and the sweat collected on a small membrane filter. Zinc, cadmium, lead and copper were then determined in the filter by anodic stripping voltammetry (ASV) using one of two alternative techniques: leaching the filter with a supporting electrolyte (0.1 M NaNO3/0.002 M HNO3), followed by ASV of the leachate; or, direct ASV analysis of the trace metals in the membrane filter using a novel thin-layer cell. Average values found for zinc, cadmium, lead and copper in sweat from males were (micrograms 1-1): 720, less than 3, 15 and 80, respectively. Copper in sweat from females was lower (23 micrograms l-1) than for males, although use of oral contraceptives appeared to increase copper concentration.