Disabling work-related persistent photosensitivity following photoallergic contact dermatitis from chlorpromazine and olaquindox in a pig breeder.

The use of veterinary medicines and medicated feed has a potential for the exposure of agricultural workers to pharmaceuticals with phototoxic and photoallergic side-effects. We present a 67-year-old self-employed farmer and pig breeder with a 22-year history of severe persistent photosensitivity following photoallergic contact dermatitis due to direct occupational dermal and airborne contact to chlorpromazine (sedative) and olaquindox (antibiotic and animal growth promoter, AGP). His first dermatitis symptoms appeared at the age of 45 when the pig breeding was intensified. He showed erythematous, scaly, and pruritic plaques localized symmetrically on the sun-exposed backs of his hands, fingers, and forearms, spreading to his face and other sun-exposed body sites. Without protective measures, he injected the animals with chlorpromazine. Besides, for several years he mixed by hand a powder containing olaquindox into the pigs' dry food. Epicutaneous and photo-patch tests showed positive reactions to promethazine, chlorpromazine, and olaquindox. In spite of the complete avoidance of the identified photoallergens for several years, his life is still extremely disabled due to the persistent photosensitivity. Our case report stresses the observation that olaquindox and chlorpromazine as phototoxic agents and photoallergens are capable of inducing a persistent and severe photosensitivity for many years, even after termination of exposure. Although the use of phenothiazine derivates and APGs for animals has meanwhile been banned in the European Union (EU), AGPs are still widely used in Asia. Physicians, especially occupational physicians, should be still aware of these phototoxic and photoallergic agents to reduce the burden of skin disease at work.

Mutagenicity of cytochrome P450 2E1 substrates in the Ames test with the metabolic competent S. typhimurium strain YG7108pin3ERb5.

UNLABELLED: Poor metabolic competence of in vitro systems was proposed to be one of their major shortcomings accounting for false negative results in genotoxicity testing. For several "low molecular weight cancer suspects" this was specifically attributed to the lack of cytochrome P450 2E1 (CYP2E1) in conventional in vitro metabolising systems. One promising attempt to overcome this problem is the transfection of "methyltransferase-deficient"S. typhimurium strains with the plasmid pin3ERb5. This plasmid contains DNA encoding for a complete electron transport chain, comprising P450 reductase, cytochrome b5 and cytochrome P450 2E1. In order to answer the question if CYP2E1 substrates that yield negative or inconclusive results in the Ames test can be activated by metabolic competent bacterial strains, we used YG7108pin3ERb5 to investigate the following compounds: acetamide, acrylamide, acrylonitrile, allyl chloride, ethyl acrylate, ethyl carbamate, methyl-methacrylate, vinyl acetate, N-nitrosopyrrolidine, trichloroethylene and tetrachloroethylene. N-Nitrosodiethylamine served as a positive control. In addition to these known or proposed CYP2E1 substrates, we investigated the polycyclic aromatic hydrocarbon benzo[alpha]pyrene and the heterocyclic aromatic amines 2-aminofluorene and 2-aminoanthracene. RESULTS: The extensive metabolic competence of the transformed strain is underlined by results showing strong mutagenicity between 10 and 500 micro g N-nitrosopyrrolidine per plate. Unexpectedly, 2-aminoanthracene was mutagenic at a concentration range between 25 and 250 micro g per plate using YG7108pin3ERb5. Moreover, we demonstrate for the first time a clear response of sufficiently characterised allyl chloride in the Ames test at a reasonably low concentration range between 300 and 1500 micro g per plate. We achieved similar results in the parent strain YG7108 with conventional metabolic activation. Without metabolic activation less pronounced mutagenicity occurred, suggesting a contribution of a direct alkylating effect. Propylene oxide is usually contained in allyl chloride as stabilizer at amounts up to 0.09%. Though YG7108 revealed to be very sensitive towards propylene oxide, allyl chloride dissolved in water was not mutagenic, showing that no water soluble compounds contribute to its mutagenicity. None of the remaining compounds showed mutagenic effects using YG7108pin3ERb5. CONCLUSION: YG7108pin3ERb5 and its parent strain YG7108 are sensitive for compounds which are negative in conventional tester strains including N-nitrosodiethylamine, N-nitrosopyrrolidine, propylene oxide and allyl chloride.

Can student tutors act as examiners in an objective structured clinical examination?

CONTEXT: The dissemination of objective structured clinical examinations (OSCEs) is hampered by requirements for high levels of staffing and a significantly higher workload compared with multiple-choice examinations. Senior medical students may be able to support faculty staff to assess their peers. The aim of this study is to assess the reliability of student tutors as OSCE examiners and their acceptance by their peers. METHODS: Using a checklist and a global rating, teaching doctors (TDs) and student tutors (STs) simultaneously assessed students in basic clinical skills at 4 OSCE stations. The inter-rater agreement between TDs and STs was calculated by kappa values and paired t-tests. Students then completed a questionnaire to assess their acceptance of student peer examiners. RESULTS: All 214 Year 3 students at the University of Göttingen Medical School were evaluated in spring 2005. Student tutors gave slightly better average grades than TDs (differences of 0.02-0.20 on a 5-point Likert scale). Inter-rater agreement at the stations ranged from 0.41 to 0.64 for checklist assessment and global ratings; overall inter-rater agreement on the final grade was 0.66. Most students felt that assessment by STs would result in the same grades as assessment by TDs (64%) and that it would be similarly objective (69%). Nearly all students (95%) felt confident that they could evaluate their peers themselves in an OSCE. CONCLUSIONS: On the basis of our results, STs can act as examiners in summative OSCEs to assess basic medical skills. The slightly better grades observed are of no practical concern. Students accepted assessment performed by STs.

Strong mutagenic effects of diesel engine emissions using vegetable oil as fuel.

Diesel engine emissions (DEE) are classified as probably carcinogenic to humans. In recent years every effort was made to reduce DEE and their content of carcinogenic and mutagenic polycyclic aromatic compounds. Since 1995 we observed an appreciable reduction of mutagenicity of DEE driven by reformulated or newly designed fuels in several studies. Recently, the use of rapeseed oil as fuel for diesel engines is rapidly growing among German transportation businesses and agriculture due to economic reasons. We compared the mutagenic effects of DEE from two different batches of rapeseed oil (RSO) with rapeseed methyl ester (RME, biodiesel), natural gas derived synthetic fuel (gas-to-liquid, GTL), and a reference diesel fuel (DF). The test engine was a heavy-duty truck diesel running the European Stationary Cycle. Particulate matter from the exhaust was sampled onto PTFE-coated glass fibre filters and extracted with dichloromethane in a soxhlet apparatus. The gas phase constituents were sampled as condensates. The mutagenicity of the particle extracts and the condensates was tested using the Salmonella typhimurium/mammalian microsome assay with tester strains TA98 and TA100. Compared to DF the two RSO qualities significantly increased the mutagenic effects of the particle extracts by factors of 9.7 up to 59 in tester strain TA98 and of 5.4 up to 22.3 in tester strain TA100, respectively. The condensates of the RSO fuels caused an up to factor 13.5 stronger mutagenicity than the reference fuel. RME extracts had a moderate but significant higher mutagenic response in assays of TA98 with metabolic activation and TA100 without metabolic activation. GTL samples did not differ significantly from DF. In conclusion, the strong increase of mutagenicity using RSO as diesel fuel compared to the reference DF and other fuels causes deep concern on future usage of this biologic resource as a replacement of established diesel fuels.