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According to OECD guideline 405 revised in 1987 Draize eye tests need not be performed for severely irritating and corrosive chemicals if results from 'well-validated alternative studies' are presented. In 1988 a validation study on alternatives to the Draize eye test was started in Germany to establish 'well-validated alternative methods' for this purpose. During database development, the last stage of the validation programme, 136 chemicals from the German chemical industry were classified in a blind trial with the 3T3 cell neutral red/kenacid blue cytotoxicity assay and the hen's egg chorioallantoic membrane (HET-CAM) test using fertile chicken eggs. The major goal of this stage of validation was to demonstrate the feasibility and limitations of the two alternative methods. Chemicals were, therefore, selected as representatives of chemical structural groups as well as of physicochemical and toxicological properties. In addition, some of the chemicals were chosen because they were of interest to the cosmetic and detergent industries. Draize eye testing data in vivo were provided by industry. In contrast to data from a previous interlaboratory assessment trial, it was impossible to correlate cytotoxicity data to the EEC classification for in vivo eye irritation. However, seven of 10 severely irritating chemicals (EEC labelling R-41) could be identified correctly in the HET-CAM assay, whereas test conditions of the study described here did not allow identification of irritating chemicals (EEC labelling R-36). The HET-CAM test is, therefore, fulfilling the criteria of a 'well-validated alternative method' according to OECD guideline 405 and should be incorporated into eye irritation testing at the earliest possible stage to reduce effectively the suffering of rabbits in the Draize eye test. Although an 80% correct prediction of 'non-labelled' chemicals in the HET-CAM test is encouraging, for safety assessment of non-irritant chemicals, for use as cosmetic formulations, for example, both government and industry will accept an in vitro assay only if its prediction of the absence of irritant properties is 100% correct.

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A progressive, hereditary disease has been observed in Basset Hounds, which appears clinically and neuromorphologically as myoclonus epilepsy (ME) and is similar to Lafora-Glueck disease in humans. The characteristic intracellular accumulations are typical myoclonus inclusion bodies. Four forms of inclusion bodies (IB) can be distinguished: a) very small, homogeneous, PAS-positive IBs, b) IBs consisting of an accumulation of PAS-positive particles, c) IBs with a concentric internal structure and a smooth or radial outer zone, and d) IBs with a homogeneous center, concentric layering, light intermediate zone, and a smooth outer zone. The occurrence of IBs is restricted largely to nerve cells. Here they are located mainly in pericarya, to a lesser extent in dendrites, and rarely in the neurites of the peripheral nervous system. IBs are also found in samples of skeletal muscle where they lie between myofibrils or beneath the sarcolemma. They are slightly basophilic in HE-staining and markedly PAS-positive. In transmission electron micrographs IBs prove to consist of chain-like filamentous material of varying density with focal concentrations. They are similar to IBs of the brain. Both muscular and neuronal IBs lack surrounding membranes. Diagnosis of Lafora disease in dogs by examination of muscle biopsies is discussed.

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A national interlaboratory study to validate two alternative methods to the Draize rabbit's eye test, co-ordinated by ZEBET at the German Federal Health Office (BGA), is described. The aim of the study is to classify chemicals according to their irritation potential using the neutral red/kenacid blue (NR/KB) cytotoxicity assay and the hen's egg chorioallantoic membrane (HET-CAM) test. During the last two years 12 toxicology laboratories from industry, universities and other research institutions have tested 32 substances from a variety of chemical classes, characterized by a broad spectrum of locally irritating properties, using the NR/KB cytotoxicity test and the HET-CAM assay. Intra- and interlaboratory reproducibility of the two methods was investigated under standardized conditions. The so-far limited evaluation of the interlaboratory assessment phase of validation indicates that the results of the Draize rabbit's eye test correlate better with the results of the HET-CAM test than with those of the cytotoxicity test as far as false negative results are concerned. However, the intra- and interlaboratory reproducibility of the cytoxicity test is better than that of the HET-CAM test. The validation project has recently entered the stage of database development during which 150 chemicals will be tested in seven laboratories to provide information on whether and to what extent the NR/KB test and the HET-CAM test can replace the Draize rabbit's eye test for the classification and labelling of chemicals with regard to their eye irritation potential.

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Data is presented of the post-mortem macroscopic and microscopic examination of two Toy Poodles with multiple enchondromatosis (Ollier syndrome). In both animals opening and maturation disorders of the growth plates were found in several skeletal locations. Due to the dogs' age difference at necropsy (14 and 4 months), some variation was also present in occurrence and appearance of primary and secondary alterations, which gave rise to some conclusions regarding development and progression of the disease. Chondrodysplasia, a characteristic of several breeds, is considered to be the essential factor in the pathogenesis of multiple enchondromatosis in the described cases.

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The clinical and radiological findings of three related Miniature Poodles with multiple enchondromatosis (Ollier's disease) are presented. Persisting, in part ossified growth plate cartilage foci were found bilaterally in the humerus, radius, ulna, femur, tibia and fibula of each dog and in one dog in some metacarpal and metatarsal bones. The ribs and many vertebral bodies were also affected. There was evidently no bone formation in the sternebrae. All three dogs first attracted attention at the ages of four to six months, with spontaneous bilateral femoral neck fractures. The mode of inheritance of the condition is not yet clear, but based on the known pedigree data a dominant effect appears unlikely.

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Parents, other family members, and health care professionals play an important role in the life of a child who has diabetes. The parents especially are constantly called upon to help make judgments regarding a child's diabetes management. As a child gets older, parents do not make as many of these judgments directly but are available to help the child make his own judgments. Even when a child starts to gain more independence and take over more aspects of his diabetes management, the need for ever-present support is still there. It may not be apparent at times but parents, other family members, and health care professionals must remember that the support is always needed.

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