[Why Strive after Clinical Social Medicine? From Epidemiological Association to Personalized Social Medicine: a Case of Breast Cancer Care]. / Klinische Sozialmedizin - Warum? Von der epidemiologischen Assoziation zur personalisierten Sozialmedizin am Beispiel der Versorgung bei Mammakarzinom.

Advances in biomedicine, especially molecular biology and genetics, gave rise to the concept of personalized medicine targeting the patient's individual characteristics and needs to ensure the best possible therapy and healthcare. This concept, however, can be successfully implemented only if due consideration is given to (psycho-)social factors, as is shown for instance by considerably reduced post-therapy survival rates among cancer patients in regions with lower socioeconomic status, How breast cancer patients, for instance, find their way back to daily life and work after initial treatment at a breast center is substantially determined by multiple factors going beyond pure medical care. These factors critically affect health status and therapy outcomes, but are missing in current research agenda. A profound expertise in social medicine is required to respond in ways tailored to the individual's healthcare needs that go beyond just medical therapy. This expertise comprises, in particular, knowledge of inequality of access to healthcare due to varying health competence that in turn, results in inequality of health outcome and care. Competence in social medicine both in the clinic and outpatient care can help to individually target negative factors that originate from the social environment as well as from deficits in communication and coordination in the healthcare system and have an effect on the health status of patients..This, however, requires institutionalization of (clinical) social medicine and in particular, better opportunities for advanced training in social medicine in clinical departments and outpatient units.

[Plea for a strengthening of clinical social medicine]. / Plädoyer für eine Stärkung der klinischen Sozialmedizin.

Social medicine is concerned--in the midst of a constantly changing society--with the social and economic conditions that influence health, disease and medical care. A comprehensive medical care therefore requires medical doctors who, beyond the biomedical issues, realize diseases in the context of the social needs of the individual person and systematically include these in their prevention, treatment and rehabilitation concepts.The system of social security, particularly the health care system, depends on medical doctors' expertise in helping patients for the appropriate use of services from the system of social security. According to the German professional education regulations for doctors the additional specialization in "social medicine" also includes the competence for "assessment of the nature and extent of health disorders and their classification in the framework of social security systems". This judgment is one part of the tasks of the Medical Services belonging to the various branches of the social security system. It is also provided in practice by medical doctors with competence in social medicine working in acute care facilities.

[Country-specific differences in the utilisation profiles of cross-border health care point to differentiated degrees of interest and selective use. Results of a German-Swiss pilot project]. / Länderspezifische Unterschiede bei den Inanspruchnahmeprofilen grenzüberschreitender Gesundheitsversorgung weisen auf differenzierte Interessenlage und selektive Nutzung hin. Ergebnisse aus einem deutsch-schweizerischen Pilotprojekt.

AIM: The pilot project Lörrach-Basel was implemented in 2007 to reduce the border effect in respect to the health care services for the citizens of the region. The study deals with the questions as to which patient groups utilise cross-border health care, with special regard to the accompanying financial streams, and what implications these utilisation profiles will have for the development of a health region. METHODS: Applications for cost assumption and hospital routine data concerning cross-border care, data of legal health insurance schemes of both participating countries for the financing of border crossers' medical care, in addition, question-related contents from expert interviews with hospitals or rehabilitation facilities in both countries and a random sample from routine hospital data of treatments in Switzerland under complementary private insurance terms were analysed. RESULTS: Regarding the actual use of the pilot project by Swiss insured persons in the second project year, an exclusive utilisation appeared in the area of rehabilitation with a total of 125 cases. 73% of all treatments took place in two rehabilitation centres. Only 8 cases from the German side corresponded to the framework of the pilot project and concerned - according to contract - highly specialised in-patient care. The applications for cost assumption addressed to German legal health insurance schemes aimed at a wide spectrum which went beyond the offer within the pilot project's framework. Only one-half of the top 10 locations by number of applications are a partner in the pilot project. When looking at the whole transnational patient mobility in the border region of Basel-Lörrach, including the cases financed by complementary insurances and schemes for border crossers, but with the exception of private insured persons, a nearly well-balanced mutual use of the medical offers (scale: by 4 million Euros) is found concerning the costs. Persons insured in Basel consume more medical care within the scope of the compulsory health insurance in Lörrach than persons, insured in Lörrach, consumed in Basel; the reverse trend appears for treatment cases financed by complementary insurances. CONCLUSIONS: The differences concerning age groups, contents and kinds of treatment point in the direction of a search for complementary potentials with the aim of adapting the cross-border health care offers to the future needs of the region.

Association between method of delivery and puerperal infectious complications in the perinatal database of Baden-Württemberg 1998-2001.

The strongest argument against caesarean delivery relates to maternal complications. Evidence supporting this for elective operations is controversial. The perinatal database 1998-2001 of the German state of Baden-Württemberg was studied to assess the maternal obstetrical risk associated with caesarean delivery with regard to puerperal infectious complications. For statistical analysis the chi2 test, Fisher's exact test, Mantel-Haenszel statistics and relative risks were used to describe the risk of exposure. Surgical delivery was associated with a significantly higher risk of infectious disorders (p < 0.0001). There was a significantly higher risk of septicaemia in the group undergoing caesarean compared to vaginal delivery (p < 0.0001), for pregnancies with and without risk factors of infection, and also for caesarean delivery prior to labour and rupture of membranes (ROM) and singleton gestations (RR 8.56; 95% CI 4.4-16.65, stratum without risks). The rate of wound disorders was found to be significantly increased in the case of surgical delivery (p < 0.0001). After exclusion of pregnancies with risk factors for infectious complications and multi-fetal gestation, a significantly higher risk was also found for caesarean delivery prior to labour and ROM versus vaginal delivery (RR 16.97; 95% CI 14.16-20.34). Caesarean delivery significantly increased the likelihood that a woman would experience fever in puerperium (p < 0.0001), for pregnancies with and without ante- or perinatal risk factors for infectious complications, and also when caesarean delivery prior to labour and ROM and singletons in the cephalic presentation were considered separately (RR 11.03; 95% CI 9.39-12.96; stratum without risks). Considering the obstetrical challenge of how more women can deliver with fewer complications, reducing unnecessary caesarean delivery still seems to be an appropriate approach.

[The structurizing effect of minimum quantitative requirements for inpatient care]. / Der strukturgebende Aspekt von Mindestmengenanforderungen im stationären Sektor.

PURPOSE: German social law ( section sign 137 SGB V) authorized the partners in health care to establish and develop a catalogue of procedures for which quality is associated with volume. There is lack of evidence regarding the volume limits. Other aspects need to be taken into account, first of all by consultation of performance data analysis. METHODS: Inpatient-data of hospitals in Baden-Wurttemberg were studied to make out possible effects of volume standard codes on health care provision. For each procedure studied an ICPM- tracer was defined and a volume limit fixed. RESULTS: If a limit affects many hospitals but a small portion of health care to be changed, it means, that only very low volume providers would be excluded. An adequate network of care can be achieved by joining volumes from neighbouring regions. The analysis showed that 39 % of the regions offering pancreatectomy come to a minimum volume of ten operations per year. A volume below 5 procedures per year is performed in 12 regions. If these small amounts are brought together, about two thirds of the regions involved in this segment of care could continue with a local offer corresponding to that defined standard. For certain high-risk conditions or procedures centralisation has already taken place (e. g. coronary bypass surgery). CONCLUSIONS: Based on appropriate analysis of the data of all partners in health care concepts can be tailored to the needs of the statutory health care system and accompanying activities involved from the very beginning. Risks have to be taken into consideration, including rarefaction of health care offers, disparities in care and on the other hand economically motivated decentralization, where risk adapted centralisation was necessary.

[Maternal postpartum anaemia--tendencies and variability, considering different hospital categories--research on the basis of Perinatology in Baden-Württemberg]. / Mütterliche Anämie post partum -- Entwicklungstendenzen und Variabilität unter Berücksichtigung unterschiedlicher Klinikkategorien -- Untersuchung auf der Basis der Perinatalerhebung in Baden-Württemberg.

BACKGROUND: Postpartum anaemia continues to be the most common puerperal complication in Germany. Interest, however, increases in maternal quality of life after delivery and with regard to scarce resources in the costs associated with anaemia. MATERIAL AND METHODS: With this background, perinatal survey data of Baden-Wurttemberg 1998 - 2003 (566,920 pregnancies) were studied regarding development and variability of anaemia in pregnancy and puerperium. RESULTS: The anaemia rate post-partum increased from 1998 to 2003 (1998 12.2 %, 2003 15.6 %). This is a significant trend. The category of small hospital departments, however, had lower rates in 2003 than in 1998. Significant differences exist between the rates of the hospital categories. High-volume departments show the highest rate (e. g., 2003: hospital departments > 1000 deliveries per year 23.2 %, consultant departments < 500 deliveries per year 9.4 %). The differences existed throughout the observed period and remained significant when all pregnancies with risk factors associated with higher blood loss were not taken into account and methods of delivery were considered separately. In 2003, anaemia during pregnancy, up to then documented for less then 2 % of the pregnancies, showed a much higher rate (e. g., high-volume departments: 6-fold higher than in 2002). DISCUSSION: Many factors may contribute to these differences, including aspects of obstetrical management, volume-outcome associations, and documentation. CONCLUSIONS: Reducing interhospital variability includes the option of reducing anaemia rates post-partum. Analysis and reflection of these results within the departments may suggest strategic changes concerning prevention, therapy, obstetric management, and workload as well as documentation habits.

[Is there a voucher for the impact of quality assurance/-improvement methods in foreign countries?]. / Gibt es Belege für den Impact qualitätssichernder/-fördernder Verfahren in anderen Ländern?

AIMS: Internationally, the implementation of diagnosis-related group systems has underlined the importance of quality assurance and improvement in health care systems. Support is expected by various concepts based on different theories and traditions. Published experience and knowledge of other countries with long-standing DRG systems and data in literature are studied to see whether there is an evidence-based impact of quality assurance and quality improvement on health care systems. METHODS: Relevant data was searched for in the Cochrane-database, the INAHTA-databases DARE, NHSEED and HTA, in DIMDI and the Medline-database of the NIH as well as generally in the internet, addressing the different countries. RESULTS: Several tools of quality assurance and quality improvement like accreditation, evidence-based medicine and guidelines exist in most of the 18 countries studied. Some of them, such as registries and audits, have marked national characteristics. Similar problems in provision of health care are reported internationally. There is broad consensus as to the aspects to be addressed in quality improvement concepts. Though international consensus on effective organization and methods of external assessment is growing there is only limited evidence for efficiency and general applicability of the different tools. Their cost impact, too, has not undergone systematic evaluation. Procedures like feedback strategies and reflection have been identified as having the potenzial to change the practice of health care professionals on a local level, but evidence for system-related impact is missing. Above all, for all concepts of quality improvement there is no real evidence of clinical benefit in the sense of better patient outcomes. CONCLUSIONS: None of the various tools for quality improvement in health care proves superior so far. It remains unclear which tool suits best for which intended improvement and in which context. Although quality improvement as a strategy meets with wide approval and appears to be a correct health policy, it remains doubtful whether it really improves clinical outcome and patient-centred health care. Public health research should address these questions. New concepts (e. g. integrating different tools of quality assurance and improvement or DMP systems) need evaluation prior to their broad implementation. Social medicine is called upon to mediate between the consented health care aims of society and medicine.

[Registries as a method to promote quality improvement--an investigation based on the example of assisted reproduction]. / Register als Methode der Qualitätsförderung--Eine Untersuchung am Beispiel der Reproduktionsmedizin.

AIMS: Intracytoplasmic sperm injection is a method of assisted reproduction (AR) covered by Statutory Health Care in Germany, since the guidelines of the concerned health authority (Bundesausschuss der Arzte und Krankenkassen--national board of medical doctors and health care insurance) have been changed in 2002, although open questions concerning its risk profile still exist. It is desirable to consider how collection and handling of data about these treatments can be utilised, so that the risks associated with assisted reproduction can be minimised and procedures be regulated in an adequate manner. Therefore this paper investigates the requirements of a national register in order to achieve a fact-based comparison of results. METHOD: Factors influencing the problems around malformation rate and multiple pregnancy in assisted reproduction were searched for in international literature and traced in documentation already available in the German context. Pathways for collection and handling of the problem-associated data are suggested. RESULTS: Up to now relevant data are kept separately. Data links are a precondition, if the existing documentation collected for different purposes should be used to evaluate and survey AR activities. This applies to the following long-standing German data collections: perinatologic and neonatologic survey, obstetric and paediatric patient documentation and the IVF registry. Further more data links to death cause registry and public health data (e. g. health check for school entering children) have to be considered. Comparing different types of international registration best surveys were found by compulsory registries under official control. CONCLUSIONS: Results are suitable for comparison if treatment is carried out under equivalent circumstances and complete standardized data are collected. Foreign examples show that appropriately designed registries contribute to effective assessment in reproductive health technology. Institution-based data aggregation enables benchmarking as means of quality improvement.

Intimal plaque development and oxidative stress in cholesterol-induced atherosclerosis in New Zealand rabbits.

Although oxidative stress is well known in atherogenesis, the origin, nature and kinetics of free radicals involved have not been well described till now. Here, we correlated parameters of oxidative stress with cellular components during induction and stabilization of aortic intimal lesions which were induced in rabbits by feeding a cholesterol-enriched diet for 6 weeks and a normal diet for further 68 weeks. Plasma lipids, aortic plaque size and composition (macrophages, smooth muscle cells, oxidized LDL by morphometry), as well as aortic radical production (by luminol-enhanced chemiluminescence and TEMPO-9AC fluorescence) were measured after various time points. The parameters of oxidative stress were correlated with the different cellular components of the aortic plaques. The plaques increased until week 21, no significant regression was found until week 74, plasma cholesterol was maximal at week 6. Macrophages, oxidized LDL and generation of different species of free radicals were increased during plaque development, yet with different time kinetics. Whereas chemiluminescence correlated only weakly with the amount of intimal macrophages, strong correlations were found between TEMPO fluorescence and smooth muscle cells (r = 0.4778, P < 0.001) and between macrophages and oxidized LDL (r = 0.5896, P < 0.0001). Different indicators of oxidative stress were increased during plaque progression and stabilization. However, the various correlations show, that distinct types of reactive species secreted probably from macrophages and smooth muscle cells contribute to oxidative stress in the different phases of plaque development.

Disabling disturbance of olfaction in a dental technician following exposure to methyl methacrylate.

It is often difficult to diagnose dysosmia due to occupational olfactotoxic substances. The authors present a case of disabling disturbance of olfaction in a dental technician. This is very likely to have been caused by exposure to methyl methacrylate. From 1988-1992, the dental technician had very extensive and sustained contact with a self-polymerizing acrylic resin based on methyl methacrylate. Her perception of smell was still normal in 1988, but it deteriorated up to 1992. The olfactory disorders have persisted and impede social life and occupational rehabilitation.

[Quality of Statutory Inpatient Database Before Introducing DRGs]. / Formale Qualität von Leistungsdaten auf rahmengesetzlicher Grundlage im Vorfeld der DRG - Einführung.

According to the legislation of the Federal Republic of Germany (Gesundheitsstrukturgesetz 1993) defined performance figures must be listed for each case of inpatient care. As hospital morbidity data are essential for further development of the health care system and for introducing the DRGs, the corresponding statistical data of a German federal territory of the year 2000 were studied in respect of several aspects of their quality: conformity with the requirements of law, plausibility and ability to transport essential medical information. Notable variations were found between the departments and different medical disciplines without interdependence to variant hospital status. Only about 40 % of departments of surgical disciplines transferred data according to legal requirements. Some disciplines showed higher percentages of unspecific coding (e.g. traumatology). The described deficits impair data reliability. The study offers a feedback to hospital departments with regard to their formal data quality. Periodic investigation may thus help to improve data quality in future.

New methods for determination of 2-butoxyethanol, butoxyacetaldehyde and butoxyacetic acid in aqueous systems, with special reference to cell culture conditions.

Ethylene glycol ethers, especially 2-ethoxyethanol and 2-butoxyethanol (BE) are frequently used in industry and household as solvents and detergents because of their excellent hydrophilic and lipophilic properties. BE and its oxidation products, butoxyacetaldehyde (BAL) and butoxyacetic acid (BAA), are mainly associated with haemolytic toxicity. No method to determine BAL in aqueous systems (e.g. urine or blood) has been published up to now. BAL was synthesized by dehydration of BE and identified by gas chromatography-mass spectrometry. For determination of BAL and BE with head space-capillary gas chromatography, water and HCl or sodium dihydrogen phosphate were added to the sample. No further extraction or derivatization were necessary. For BAA determination after adding HCl and sodium dihydrogen phosphate the samples were extracted with ethyl acetate and derivatized with 2,2,2-trichloroethanol/HCl. The analytical methods presented here are reliable, sensitive and rapid. The new methods were developed for mammalian cell culture systems, because such in vitro systems are especially useful for metabolic studies and have the advantage of choosing species and organ specificity. In the cell culture experiments presented here it was demonstrated that Opossum kidney cells are able to metabolize BAL to BAA within 24 h. After this interval, in the cells neither BAL nor BAA were accumulated, whereas BAA was found in the cell culture media.

Sodium monochloroacetate causes cytotoxic effects, an increased lactate and pyruvate level and induces ultra structural and cytoskeletal alterations in cultured kidney and liver epithelial cells.

1. Monochloroacetic acid (MCAA) and its sodium salt, sodium monochloroacetate (SMCA) are widely used in chemical industries as intermediates in the synthesis of carboxymethylcellulose, phenoxyacetic acid, thioglycolic acid, glycine, indigoid dyes and others. Moreover, MCAA has been found as a by-product of the chlorination disinfection of drinking water and as an environmental contaminant of the atmosphere from the photodechlorination reactions of chlorinated hydrocarbons. Little is known about the mode of action of both compounds on the cellular level. From cases of accidental poisoning of man it is known that MCAA accumulates in liver and kidney. 2. In this study, the cytotoxicity of SMCA on cultured liver (Chang liver cells) and kidney epithelial cells of the proximal tubule (Opossum kidney cells) was investigated and its effect on metabolism, ultrastructure and organization of cytoskeleton was examined. 3. Independent from the growth state of the cells (proliferating or quiescent), the results clearly show that SMCA causes a dose-dependent decrease in cell viability after an exposure period of 24 h. In all experiments, proliferating cells were more sensitive than quiescent and confluent cells. Liver cells were less sensitive against SMCA treatment than kidney epithelial cells. In contrast to liver cells, kidney cells exhibited a dose-dependent decrease in cell volume. The decrease in cell viability was accompanied by an increase of lactate and pyruvate concentrations released into the culture medium. In the case of Opossum kidney cells, lactate and pyruvate levels increased 5 - 6-fold, whereas in the case of Chang liver cells the increase was approximately twofold. While the ultrastructure of liver cells remained unaltered after drug treatment, kidney cells exhibited cytoplasmic vacuolization, membraneous disruption and especially mitochondrial alterations. In accordance with the changes in the ultrastructure of Opossum cells, was the reorganization of cytoskeletal elements with an increased stress fiber network at the basolateral surface as well as a partial depolymerization of microtubules and vimentin filaments. A cytoskeletal reorganization was not observed for Chang liver cells after SMCA treatment. 4. The results demonstrate that SMCA causes a dose-dependent cytotoxicity which is accompanied by metabolic, mitochondrial and cytoskeletal alterations in the cells.

[Insufficient ventilation as the etiology of illness perception in an elementary school]. / Mangelhafte Lüftung als Auslöser von Befindlichkeitsstörungen in einer Grundschule.

PURPOSE: Two years after renovation of the classrooms in a primary school (installation of insulated windows and closing of the ventilation shaft) pupils and teachers complained about offensive odours, irritation of the eyes and of the nose, complaints of the respiratory tract, headaches and disturbed mental concentration. The presented study determines the causes, suggests measures for help and checks their effectiveness by means of measurements. METHODS: Before starting our measurements, the air quality had already been assessed by an expert. There was no evidence of elevated concentrations of air contaminants. Because of the content of phthalate plasticizers and flame retardants in the linoleum sealants there was an offensive odour. To determine the cause, the air in the subjective mostly affected classroom was analysed for phthalate plasticizers, their metabolites and alkyl phosphates. We also made aerosol measurements with a cascade impactor, determined bacterial counts in the air, and measured the indoor climate and the internal air flow. RESULTS: The concentrations of phthalate plasticizers and their metabolites in the air were not elevated significantly. The screening for alkyl phosphates was negative. The amount of inhalable particles was 0.046 mg/m3. The bacterial count in the air was negligible. On the other hand the indoor climate during the heating period in winter was remarkably changed. The average room temperature was 26 degrees C (reaching a maximum of 36 degrees C with direct sunlight in the classroom), the average humidity was 21% (minimum 7%) and the change of air was approximately 0.5 per hour. Reopening the ventilation shaft and tilting of only one window resulted in a much greater rate of air change. After installation of temperature regulators and regular use of the venetian blinds in the classroom, the room temperature and the relative humidity during the morning lessons were, as a rule, normalised. Among both pupils and teachers the reports of offensive odours and health disorders were subsequently clearly reduced. CONCLUSIONS: To determine the cause of health disorders indoors, it is apparently to be of great importance to carry out measurements of the climate as well as to assess the level of air contaminants. By use of modern energy-saving construction possible effects on the indoor climate should be be taken into account during the planning stage of changes to avoid health disorders resulting from changed interior climate conditions.

Aortic plaque size and endometrial response in cholesterol-fed rabbits treated with estrogen plus continuous or sequential progestin.

ERT is associated with a reduced incidence of coronary risk and cardiac events in postmenopausal women, but increases the risk of endometrial hyperplasia and carcinoma. Combined estrogen and progestin therapy protects the endometrium; however, its effects on heart disease risk factors are not completely known. In our study, 56 ovariectomized New Zealand White rabbits in 7 groups received a 0.5% cholesterol diet for 12 weeks. Controls were not treated with hormones. All other animals received (per kilogram body weight per week) intramuscular injections of either 0.3 mg estrogen (estradiol valerate) alone, 8.3 mg progestin (hydroxyprogesterone caproate) alone, estrogen and progestin continuously in 3 different dosages (0.3 and 8.3 mg; 1 and 8.3 mg; or 1 and 2.8 mg; estrogen and progestin, respectively), or 1 mg estrogen with 25 mg progestin sequentially in 2-week cycles. Eight non-ovariectomized animals served as further controls for endometrial analysis. Morphometric analysis of plaque size in the aortic arch showed that estrogen monotherapy, and the 3 combined therapies with 1 mg estrogen, significantly reduced intimal thickening (P<0.05). The application of progestin alone had no effect on plaque size. The endometrium was enlarged by 3-fold after estrogen treatment, and was decreased by half after progestin treatment, compared with control uteri (P<0.05). In all groups with combined hormone regimens, endometrial size was not significantly different from control uteri. However, these uteri showed more inflammatory reactions, especially when higher doses of hormones were given. In this animal model, doses of progestin that are able to successfully reduce the proliferative effect of estrogen on endometrium do not diminish the desirable antiatherosclerotic properties of estrogen.

Cytotoxic effects of 2-butoxyethanol in vitro are related to butoxyacetaldehyde, an intermediate oxidation product.

Ethylene glycol ethers belong to a group of solvents with a wide spectrum of applications, particularly because of their compatibility to both hydrophilic and lipophilic systems. Especially ethylene glycol monobutyl ether (2-butoxyethanol, BE) is widely used as a key ingredient in many industrial and consumer cleaning products. Therefore, the risk of human exposure and toxicity by BE as well as its potential for environmental contamination have to be carefully evaluated. By using an established kidney epithelial cell line from the proximal tubule (opossum kidney cells), we investigated the effects of BE on viability, proliferative activity, volume and the organization of the intracellular cytoskeleton of the cells. The experiments were performed with freshly used BE and BE that had been stored at room temperature in the original packing for 3 months after use. After this period of storage the latter BE contained-besides butyraldehyde and n-butanol-0.5 vol% butoxyacetaldehyde (BAL) as measured by capillary gas chromatography and mass spectrometry. Freshly used BE did not cause a toxic effect in the in vitro assays at all concentrations tested (up to 1 mg/ml). In contrast, stored BE which contained BAL reduced cell viability and mitotic activity in a dose-dependent manner. The effective concentration of stored BE causing a 50% loss in cell viability (EC(50/24h)) was calculated to be 1 mg/ml. The toxic effect of stored BE also resulted in alterations of cell morphology and a depolymerization of actin-containing stress fibers. Moreover, administration of stored BE also caused a dose-dependent cell volume increase by the uptake of water, pointing to a necrotic process. In addition, synthesized BAL with a purity of 73.5% (gas chromatography) was also tested and caused an EC(50/24h) of 15 µg/ml, which is a 70-fold lower concentration when compared with stored BE. The present study provides evidence that BE possesses only a low cytotoxic potential in vitro, whereas the corresponding BAL, an intermediate in the oxidation process of BE to butoxyacetic acid, has marked toxic effects. The occurrence of the aldehyde might explain the predominant hematological effects of BE observed in vivo.

Investigations on the nephrotoxicity and hepatotoxicity of trivalent and hexavalent chromium compounds.

In contrast to trivalent chromium (Cr(III)) compounds, hexavalent chromium ((Cr(VI)) compounds are oxidizing agents capable of directly inducing tissue damage and possessing carcinogenic, mutagenic and teratogenic potency. After oral or dermal absorption of Cr(VI), the kidney is the main target organ for chromium accumulation, which might result in acute tubular necrosis in humans. In contrast, an acute toxic effect of Cr(VI) on the liver has not yet been described. Therefore, we used two established epithelial cell lines from the kidney (Opossum kidney cells) and the liver (Hep G2 cells) to design an in vitro-assay which is able to examine acute toxic effects of chromium compounds. Cells of both cell lines were treated with various concentrations of Cr(III) and Cr(VI) ranging from 0.01 micromol/l to 1 mmol/l for 24 h. Thereafter, cell morphology, organization of the intracellular cytoskeleton, number of viable cells and mean cell volume were examined. The results show that Cr(VI), but not Cr(III), has an acute cytotoxic effect and causes a dose-dependent loss in cell viability. The effective dose that caused 50% of cell death was 5 micromol/l for kidney epithelial cells and 50 micromol/l for liver epithelial cells. This means that kidney epithelial cells are 10 times more sensitive towards Cr(VI) treatment than liver epithelial cells and this might explain the known nephrotoxicity in vivo. The loss in cell viability was accompanied by a rounding and detachment of the cells and a marked reduction of intracellular F-actin-containing stress fibers. Microtubules and intermediate-sized filaments were observed to be unaffected. Only in the case of kidney epithelial cells, a dose-dependent cell volume increase was observed after Cr(VI) treatment at concentrations up to 50 micromol/l. At higher concentrations, the cell volume decreased due to the high number of cells undergoing lysis and the appearance of cellular fragments. Various chloride channel blockers with different specificities, molecular structures and inhibitory potentials were tested for their ability to prevent Cr(VI)-induced cell damage. None of the channel blockers was able to inhibit cell damage, suggesting that the uptake of Cr(VI) through the general anion transport system of the cell membrane might be only one facet of cellular uptake and toxification. The data presented here not only confirm the different organ-specific effects of Cr(III) and Cr(VI), but also provide a basis for future experiments on the understanding of acute toxicity of Cr(VI) compounds. Moreover, the results demonstrate that the designed in vitro-assay might be a useful tool to prove whether non-toxic Cr(III) can be oxidized to Cr(VI) under specific industrial conditions (for example, in the leather or chrome industry).

Nephrotoxic effects of di-(2-ethylhexyl)-phthalate (DEHP) hydrolysis products on cultured kidney epithelial cells.

1. Di-(2-ethylhexyl)-phthalate (DEHP) possesses a great industrial value as a plasticizing agent and has become an ubiquitous environmental contaminant. In most species it is rapidly metabolized to mono-(2-ethylhexyl)-phthalate (MEHP) and 2-ethylhexanoic acid (2-EHA). Evaluation of toxicity of DEHP and its primary metabolites has been focussed on reproductive toxicity and hepatocarcinogenic properties. The aim of this study was to determine the nephrotoxic potential of both DEHP metabolites by use of cultured kidney epithelial cells (Opossum kidney cells; OK cells). 2. For this purpose, OK cells were exposed for 3 days to MEHP and 2-EHA at concentrations ranging from 0.1 -500 micromol/L and the toxicity as well as the effects on migratory activity and intracellular cytoskeleton were studied by cell biological, morphological and morphometric methods. 3. When compared with corresponding controls, treatment of OK cells with MEHP and 2-EHA, respectively, showed marked differences in cell viability between both DEHP metabolites. MEHP caused a dose-dependent decrease in cell viability (ED50 = 25 micromol/L) accompanied by a moderate swelling of the cells at concentrations up to 25 micromol/L. MEHP concentrations higher than 25 micromol/L caused a dose-dependent shrinkage of the cells and the occurrence of a high amount of cell debris as a result of cell lysis. 2-EHA did not cause a reduced viability or an altered cell volume. The migratory activity of OK cells was not significantly influenced by both metabolites. Moreover, MEHP toxicity resulted in a largely reduced and altered organization of F-actin (stress fibers), but not of myosin, microtubules and vimentin. 4. The study indicates that cultured epithelial cells can be used as a prescreening system to assess the nephrotoxicity of hazardous substances such as DEHP. As demonstrated in this study, only MEHP, but not 2-EHA, has a marked nephrotoxic effect in vitro.

[Plaque morphology after arterial interventions in the New Zealand white rabbit--which model of restenosis is most suitable?]. / Plaquemorphologie nach arteriellen Interventionen am Weissen Neuseelandkaninchen--Wann ist welches Restenosemodell geeignet?

PURPOSE: For evaluation of therapy for possible reduction of restenosis after PTA a suitable animal model is needed. The influence of different interventions on arterial plaque composition was analysed in New Zealand White Rabbits. MATERIAL AND METHODS: The following interventions were performed in the infrarenal aorta of New Zealand White Rabbits (n = 42): a) Balloon denudation (BD) with and b) without 0.5% cholesterol diet (CD), c) application of a Wiktor stent, d) CF without BD, and e) control group, 6 weeks after intervention morphometry and histology were performed. RESULTS: After BD the stenosis rate measured 26 +/- 18%, additional CD after prior BD increased the stenoses rate by 2.5 times up to 61.1%. After stent implantation there was only a thin neointimal layer (89 +/- 68 microns) around the stent wires. CONCLUSIONS: Neither implantation of stents nor single CD are suitable as restenosis models. BD with and without CD was followed by a distinct neointima formation with different cellular composition. The New Zealand White Rabbit constitutes an acceptable model for contemporary research in arteriosclerosis.