Compulsory admissions of patients with mental disorders: State of the art on ethical and legislative aspects in 40 European countries.

BACKGROUND: Compulsory admission procedures of patients with mental disorders vary between countries in Europe. The Ethics Committee of the European Psychiatric Association (EPA) launched a survey on involuntary admission procedures of patients with mental disorders in 40 countries to gather information from all National Psychiatric Associations that are members of the EPA to develop recommendations for improving involuntary admission processes and promote voluntary care. METHODS: The survey focused on legislation of involuntary admissions and key actors involved in the admission procedure as well as most common reasons for involuntary admissions. RESULTS: We analyzed the survey categorical data in themes, which highlight that both medical and legal actors are involved in involuntary admission procedures. CONCLUSIONS: We conclude that legal reasons for compulsory admission should be reworded in order to remove stigmatization of the patient, that raising awareness about involuntary admission procedures and patient rights with both patients and family advocacy groups is paramount, that communication about procedures should be widely available in lay-language for the general population, and that training sessions and guidance should be available for legal and medical practitioners. Finally, people working in the field need to be constantly aware about the ethical challenges surrounding compulsory admissions.

Analysis and behavior of colistin during anaerobic fermentation.

A new analytical method for the determination of colistin in fermenter samples was developed followed by a study on the behavior of this substance during anaerobic fermentation. Analysis of colistin A and B was carried out by liquid chromatography-tandem mass spectrometry. Separation of the analytes was performed on a Security Guard column (4×3mm). Fourteen fermentation tests in batch as well as in continuous reactors were carried out. After 44days of anaerobic digestion of cattle manure, initially spiked with 500mg/kg of colistin sulfate, a considerable decrease of the colistin concentration to less than 1mg/kg could be observed. Furthermore, the daily production of biogas and methane was measured. A correlation between gas production and colistin concentration could not be determined. However, an increase of 10% of the cumulative methane production was observed in those fermenters spiked with an initial bolus of 500mg/kg colistin.

Perfluorooctanoic acid and perfluorooctane sulfonate in liver and muscle tissue from wild boar in Hesse, Germany.

Approximately 15,000 tons of wild boar meats (Sus scrofa) are consumed per year in Germany. Boar meat therefore plays a definite role in regard to human diet. Because they are omnivores and because of their high body fat quotient, wild boar may accumulate large concentrations of persistent organic compounds, such as halogenated hydrocarbons, and could thus possibly serve as bioindicators for persistent xenobiotics. In addition, consumption of wild boar meat and liver could lead to increased contaminant levels in humans. Between 2007 and 2009, we tested a total of 529 livers and 506 muscle tissue samples from wild boar for the presence of perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS). PFOA concentrations ≤45 µg/kg and PFOS concentrations ≤1,780 µg/kg were detected in the liver samples. PFOA concentrations ≤7.4 µg/kg and PFOS concentrations ≤28.6 µg/kg were detected in muscle tissue. Our results show that PFOS may be detected in considerably greater concentrations than PFOA in organs and tissues, which is in agreement with results from other published studies. The comparisons between both organs for the same substance, as well as the comparisons between the substances within an organ, showed clear and statistically significant differences at P < 0.0001. Assuming a tolerable daily intake value of PFOA (1.5 µg/kg bw/d) and PFOS (0.15 µg/kg bw/d) as recommended by the European Food Safety Authority, the results of model calculations based on the maximum concentrations of PFOA and PFOS found in wild boar indicate that there should be no PFC-related health danger resulting from moderate consumption of wild boar meat or liver.

Carryover of perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) from soil to plants.

Within the scope of a joint project to study soil-to-plant carryover of polyfluorinated compounds (PFCs), five cultivated plants (spring wheat, oats, potatoes, maize, and perennial ryegrass) were sown or planted in Mitscherlich pots. Six variants per species were used, each with a different concentration level of PFOA and PFOS (from 0.25 to 50 mg/kg as aqueous solution) to detect possible concentration dependence in the transfer of these two PFCs from soil to plant. PFOA and PFOS were detected by liquid chromatography-tandem mass spectrometry after appropriate sample preparation (partial drying, mincing, homogenizing, extraction). Since PFOA and PFOS presently represent the most widely studied PFCs, they are classified as "leading compounds." The results show that concentrations of PFOA/PFOS in the plants vary greatly, depending on the concentrations applied to the soil. PFOA values were higher than PFOS values in all plants except potatoes, in which these differences could be quite substantial. From the results presented here it can be seen that uptake and storage are much more intensive in the vegetative portion of the plant than relocation in the storage organs. This is particularly evident from the the comparison of concentrations found in the grain and ear and those in the straw or rest of the plant in spring wheat, oats, and maize. Transfer from "soil to crops" provides a possible explanation for the presence of PFCs in foodstuffs and in human body fluids such as blood, plasma, serum, or breast milk. The aim of the present study was to determine whether a statistically significant, concentration-dependent carryover of PFOA and PFOS in crop plants can take place, which would provide a potential entrance point for these substances into the food chain.

Estrogenic activity of musk fragrances detected by the E-screen assay using human mcf-7 cells.

The widespread use of synthetic musk fragrances and the resultant presence of these substances and their metabolites in the aquatic environment (as well as their accumulation in human adipose tissue) raises the question of whether musk fragrances display endocrine and in particular estrogenic activity. A variety of musk fragrances were tested using the E-screen assay. A statistically significant increase in proliferation rate of human MCF-7 breast cancer cells was detected for two nitro musks (musk xylene, musk ketone), a major metabolite of musk xylene ( p-amino-musk xylene), and the polycyclic musk fragrance AHTN. This indicates that these substances do, in fact, demonstrate estrogenic activity. Coincubation with the antiestrogen tamoxifen showed that the increase in proliferation rate by the musk fragrances is estrogen receptor-mediated. It must be noted, however, that the effective estrogenic strength and estrogenic potency were low compared to 17 b-estradiol. The naturally occurring fragrance muscone from the group of macrocyclic musk fragrances, a group of substances that have not yet been well characterized in respect to their toxicological properties, has also been shown to be weakly estrogenically active in vitro. E-screen analysis showed that the nitro musk metabolites o-amino musk xylene and 2-amino-MK, the macrocyclic musk fragrances ethylene brassylate, ethylene dodecandioate, and cyclopentadecanolide, are not estrogenically active.

Application of the E-screen assay to test for oestrogenically active substances in swine feed.

A pig breeder in central Hesse (Germany) noticed the occurrence of enlarged vulvae in female piglets. Intoxication with oestrogenically active substances by contamination of two feed mixes ingested by the mother sows appeared to be a possible cause. Using a combined technique of the DFG analytical method S19 and the E-screen assay, two feed samples were found to contain powerful oestrogenically active compounds. By co-incubation with the anti-oestrogen tamoxifen it could be clearly demonstrated that the oestrogenic activity was mediated by the oestrogen receptor. These results demonstrate that use of the E-screen assay in combination with the DFG analytical method S19 provides a simple and readily usable prescreening method for the routine detection of oestrogenically active compounds in animal feed. The results from the E-screen assay show that the sows ingested 10-80 microg oestradiol equivalents per day in their feed. Because of the bioavailability of these substances, the oestrogenic active compounds seem to be transferred into the milk and passed to the piglets via suckling. The milk of the dam appears to contain this substance in biologically active form and at such high concentrations that the female piglets had enlarged vulvae.

Acute hepatotoxicity of the polycyclic musk 7-acetyl-1,1,3,4,4,6-hexamethyl-1,2,3,4-tetrahydronaphtaline (AHTN).

Synthetic musks are present in fine fragrances, cosmetics, soaps and laundry detergents. One of the most important synthetic musks is 7-acetyl-1,1,3,4,4,6-hexamethyl-1,2,3,4-tetrahydro-naphthaline+ ++ (AHTN; annual production: about 1500 metric tons). An increasing number of studies show that AHTN accumulates in surface water and fish and can be detected in human adipose tissue, as well in human milk. In the present report it is shown that a single high dose of AHTN leads to acute hepatic damage in rats, characterized by single cell necrosis, inflammation, swelling of liver parenchymal cells, and the presence of cytoplasmic condensations in the hepatocytes, while at the ultrastructural level disorganization of the rough endoplasmic reticulum and mitochondria as well as focal cytolysis is evident. Furthermore, evidence is presented that AHTN is not genotoxic, does not induce peroxisome proliferation, and does not lead to the induction of drug-metabolizing enzymes as phenobarbital and 3-methylcholanthrene do.

Contamination of human milk in Middle Hesse, Germany--a cross-sectional study on the changing levels of chlorinated pesticides, PCB congeners and recent levels of nitro musks.

Human milk samples from women in Middle Hesse, Germany were chemically analyzed for contamination levels of alpha-, beta- and gamma-HCH, HCB, p,p'-DDE and p,p'-DDT as well as the PCB-congeners no. 28, 31, 49, 52, 101, 118, 138, 153, 156, 170 and 180. Changes in concentrations of these compounds in human milk over an extended time period were studied by comparing samples from 1984/85, 1990/91 and 1995. In addition, concentrations of the nitro-aromatic compounds musk xylene and musk ketone were determined in the 1995 samples. The study showed statistically highly significant (p<0.001) reductions in levels of beta- and gamma-HCH, HCB, p,p'-DDE and p,p'-DDT, in human milk from 1995 compared to samples from 1984/85. A weakly significant reduction (p<0.05) of alpha-HCH was also observed. For low-chlorinated PCB congeners, on the other hand, a highly significant increase of PCB no. 28 was detected and concentrations of congeners no. 31, 49 and 52 remained unchanged. Concentrations of the high-chlorinated congeners no. 101, 138, 153 and 180 dropped (highly significant). A highly significant reduction of PCB no. 118 and 156 occurred between 1990/91 and 1995, but a highly significant increase was found for no. 170. Lower levels of hydrocarbon contamination of human milk samples from 1995 than were found in samples from 1984/85 and 1990/91 can be seen to result partially from voluntary reductions, but primarily reflect restrictive environmental legislation in the Federal Republic of Germany. Mean concentrations of musk xylene and musk ketone in samples from 1995 were 41 microg/kg and 10 microg/kg milk fat, respectively.

Species and organ dependence of PCB contamination in fish, foxes, roe deer, and humans.

According to previous experimental results, PCBs are deposited in muscle fat in animals and in humans, although they also reach the brain, the liver, and the lungs. The aim of the present study was to determine the concentrations of the so-called "indicator PCBs" (PCB nos. 28, 52, 101, 138, 153, 180), as described by the German ordinance for maximum concentrations of contaminants in foodstuffs, in muscle tissue, liver, and brain of four different species: fish, fox, roe deer, and humans, all exposed to PCBs directly in their environment. Potential target organs for the accumulation of these congeners were also to be identified. Furthermore, the organs or tissues were to be identified in which PCBs are accumulated, and unusual patterns of accumulation or breakdown of particular PCBs, for example the "dioxin-like PCBs" (coplanar PCBs) determined. For humans, the lungs were also included in these studies. Statistical comparison of PCB concentrations in samples from wild animals and humans showed that in spite of its relatively high fat concentration, brain tissue in all of the species examined (with the exception of fish) appeared to be better protected against accumulation of PCB than liver or muscle tissue. This protection may be the result of the blood-brain barrier, as witnessed by the relatively uniform concentration of PCBs throughout the various organs of fish, since the blood-brain barrier of fish is considerably less efficient than that of mammals. No peculiarities were found in regard to distribution of the coplanar PCBs over the other congeners in this study. This applies to the brain and other organs or tissues of the four species that were examined. Accumulations of PCBs and coplanar PCBs in the liver were only found in fox and roe deer. In contrast, humans were found to have accumulations of the high-chlorinated biphenyls studied here as well as PCB no. 118 in muscle tissue fat and not in the liver. Unexpectedly, low-chlorinated biphenyls were found to accumulate in the human lung. The results of this study show that the lung represents a target organ for the accumulation of potentially metabolically activated low-chlorinated biphenyls, indicating that the possible biological effects of PCBs on the lungs will need to receive more attention in the future.

Chlororganic pesticides and polychlorinated biphenyls in breast tissue of women with benign and malignant breast disease.

Persistent chlorinated hydrocarbons assimilated through the diet may, as a result of their carcinogenic, immunotoxic, and, at least in regard to certain of these substances, estrogenic properties, play a role in the etiology of human breast cancer. As a consequence, increased concentrations of these ubiquitous environmental contaminants may be found in breast tissue of women suffering from malignant breast disease. To examine this possibility, surgically removed breast tissue samples from 65 women in Hesse, Germany were examined by capillary gas chromatography for p, p'-dichloro(diphenyl)trichloroethane (p,p'-DDT), p, p'-dichloro(diphenyl)-dichloroethane (p,p'-DDD), p, p'-dichloro(diphenyl)dichloroethene (p,p'-DDE), hexachlorobenzine (HCB), alpha-, beta-, and gamma-hexachlorocyclohexane (HCH) as well as the polychlorinated biphenyls (PCB) no. 28, 31, 49, 52, 101, 105, 118, 138, 153, 156, 170, and 180. Of the 65 patients, 45 were diagnosed with breast cancer. The control group of 20 women suffered from benign breast disease such as mastopathy. After statistical adjustment for age differences, higher concentrations of p,p'-DDT, p, p'-DDE, HCB as well as PCB-congeners no. 118, 138, 153, and 180 were detected in tissue from women with breast cancer than in tissue from control persons. These differences were weakly significant for p, p'-DDE (p = 0.017), for PCB 118 (p = 0.042) and for PCB no. 153 barely not significant (p = 0.083). On an average, a 62% higher concentration of p,p'-DDE was found in cancer tissue (cancer patients: 805 microg/kg fat; controls: 496 microg/kg fat) and 25% higher concentration of PCB no. 118 (81 microg/kg fat; 65 microg/kg fat). The concentrations of beta-HCH, PCB no. 156 and 170 were lower (not significant) in cancer tissue than in tissue from women with benign disease. PCB-congeners no. 105 and 149 as well as gamma-HCH could only be detected in individual tissue samples; congeners no. 28, 31, 49, 52, and 101 as well as alpha-HCH and p,p'-DDD were not detected in any of the samples. To rule out the possibility that the concentrations of chlorinated hydrocarbons measured were influenced by the surgical procedure, 20 samples of tissue that were at a distance (minimum 1 cm and maximum 3 cm) from the tumor, tissue that was in direct proximity to the tumor (no more than 5 mm from the tumor), and tumor tissue itself (center of tumor) were separately prepared and analyzed. The average concentrations of chlorinated hydrocarbons varied to differing degrees and only minimally in tumor and surrounding breast tissue, indicating that the surgical procedure did not influence the results.

Polychlorinated biphenyl congeners in foxes in Germany from 1983 to 1991.

Red foxes served as a biological indicator for the temporal development of environmental contamination with polychlorinated biphenyls (PCB). The concentration of PCB congeners nos. 28, 49, 52, 101, 138, 153, and 180 were analyzed in the body fat of 80 foxes (Canis vulpes) from Germany. The samples were from animals that had been submitted for examination in 1983, 1987, and 1991. Throughout this time period, a reduction was seen in the concentration of the highly chlorinated biphenyls 138, 153, and 180, whereas the concentration of the low-chlorinated congeners PCB nos. 28, 49, and 52 increased. No change in contamination with congener 101 was observed. These results show a trend toward reduction of environmental contamination with highly-chlorinated biphenyls since 1983, while contamination with low-chlorinated congeners is apparently increasing. An interesting observation is the disproportionately higher amount of 2,2',3,4,4',5,5'-hepatachlorobiphenyl (PCB 180) over that of 2,2',4,4',5,5'-hexachlorobiphenyl (PCB 153) in body-fat samples from all foxes analyzed. This phenomenon was also observed in 10 dogs examined as controls. Based on evidence from other authors of experimental toxicological studies on beagles, it appears that the fox possesses a similar cytochrome P-450 isoenzyme that can degrade 2,4,5-trichloro-substituted aromatic compounds. As a consequence, in canines, PCB 180 which is additionally meta-chloro substituted is accumulated to a greater degree than is PCB 153.

[Polychlorinated biphenyls (PCB) in fish from hatcheries and clarifying ponds]. / Polychlorierte Biphenyl (PCB) in Fischen aus Teichwirtschaften und Nachklärteichen.

The concentrations of six selected single polychlorinated biphenyl (PCB) congeners, for which legal tolerance levels became valid in 1988, and the congener no. 49 (2,2',4,5'-tetrachlorobiphenyl) were determined in the muscle tissue of 58 fishes from fish hatcheries and in 17 fishes from settle ponds. The fish were taken from flowing waters in the years 1986 and 1987. High and low chlorinated biphenyls were present in each sample, but the concentration of the low chlorinated biphenyls was distinctly lower than that of the higher chlorinated ones. Nevertheless these results demonstrate the intake of components of low chlorinated technical PCB mixtures in the environment and food chains. Compared with the investigations carried out in 1980/81 in fishes from fish hatcheries, a decrease of PCB contamination in the muscle tissues with regard to the technical mixture Clophen A 60 was observed. This is in accordance with the results our team obtained a short time previously in muscle tissue from foxes and in food-stuffs. The concentration of all PCB congeners determined in the muscle tissue from fish of settle ponds was significantly higher than in the tissue from fish taken from hatcheries. Thus, the PCB content depends on the PCB load in different environments. Therefore, fishes can be useful as bioindicators for the intake of low and high chlorinated PCB congeners in aquatic ecosystems.

[Polychlorinated biphenyls (PCB) in human adipose tissue]. / Polychlorierte Biphenyl (PCB) im menschlichen Fettgewebe.

This study describes the contamination of human adipose tissue with six selected polychlorinated biphenyls (PCB) known as "indicator congeners", with PCB no. 49 and the mixed inducer PCB nos. 156, 170, and 189. The low chlorinated biphenyls nos. 28, 49, and 52 could not be found in the tissue samples, while the average concentration of PCB no. 101 was 9.0 micrograms/kg. The content of PCB nos. 138, 153, and 180 was slightly below the values published by the "Deutsche Forschungsgemeinschaft" (DFG). The mixed inducer nos. 138, 156, 170, and 180 amounted to approximately 40% of all the PCBs measured. The PCB contamination was positively correlated with age: for the age group 61-70 years, with the exception of PCB no. 101, a distinct increase in the concentrations could be observed.

Histology and histochemistry of the liver of chickens after DENA induced hepatocarcinogenesis and ingestion of low chlorinated biphenyls.

Studies are presented which demonstrate the pathological effects of diethylnitrosamine (DENA) and polychlorinated biphenyls (PCB) in the liver of chickens. DENA, which has been shown to cause tumors in rats and chickens, was tested on 80 laying hens to determine whether changes in the liver during hepatocarcinogenesis were similar to those observed in rats. In addition, the hepatocarcinogenic and cocarcinogenic properties of Clophen C (CC), a technical mixture of low chlorinated biphenyls was tested on chickens. The livers of test animals were examined histologically for preneoplastic and neoplastic lesions. Histochemical methods were used to determine lipid and glycogen contents as well as changes in activity of alkaline phosphatase and gamma-glutamyl-transpeptidase. Putative preneoplastic lesions in the liver were first observed according to the substance and dosage applied as follows: DENA 1 X weekly (group II), beginning on day 258; DENA 2 X weekly (group III), beginning on day 183; and CC + DENA 2 X weekly (group V), beginning on day 231. Application of CC alone did not induce lesions. The concept that CC has cocarcinogenic capability was substantiated by the fact that animals from group V (CC + DENA 2 X weekly) developed twice as many tumors as did animals from group III (DENA 2 X weekly). Additionally, tumors developed earlier in the former group than in the latter.

False-positive results in the radioimmunoassay detection of stilbene derivatives after administration of fluorinated corticosteroids to animals.

During routine inspections, indications were found that the therapeutic use of fluocortolone or dexamethasone can cause false-positive results in the detection of stilbene derivatives by radioimmunoassay (RIA) in samples of animal origin. After experimental application of the fluorinated corticosteroids to rabbits or calves, the assumed false-positive RIA results were confirmed. The kinetics after application of dexamethasone were concomitant with the elimination of radioactive [3H]dexamethasone. Furthermore, it could be demonstrated that [3H]dexamethasone was transformed in the faeces of rabbits and calves. The metabolites formed were not completely separated by the extraction procedure used for the RIA and seemed to be responsible for the false-positive results.