Evaluation of the rat tail model for estimating dermal absorption of lindane

Dermal absorption of the insecticide lindane was determined following topical application of ring 14C-labeled lindane to the tail of Sprague-Dawley rats. The tail was tested as a practical alternative to the rat mid-dorsal (back) region, and the data obtained were compared to those with rat back and with those of rhesus monkeys in our previous reports. There was no significant difference between total percentage urinary 14C recovery for rats dosed on the tail with occlusive tail covers (52 +/- 6.2%; t1/2 = 2.7 d) compared to those with nonocclusive covers (55 +/- 4.4%; t1/2 = 2.9 d). Neither the total percentage urinary recovery nor the t1/2 values obtained for the rat tail and rat back models differed significantly. Carbon-14 activity was still detectable in urine samples taken after 72 d post-treatment. However, an extensive tissue analysis failed to demonstrate 14C activity persisting at 72 d, with the exception of trace levels detected in blood serum and tail tissue. Advantages of the rat tail model are highlighted.     

Aseptic bone necroses as a late complication following successful treatment of leukemias and severe aplastic anemia

Aseptic bone necrosis is a well known complication after corticosteroid treatment in adults and several hundred cases have been reported. Alterations in fat metabolism with vascular occlusion due to fat embolization, as well as microtraumata and osteoporosis are discussed as etiologic factors. In contrast, aseptic bone necrosis in relation to corticosteroid treatment is rare in children and adolescents. We therefore report 3 patients, aged from 10 to 18 years, suffering from severe aplastic anemia, meningeal relapse after acute lymphocytic leukemia and acute myelocytic leukemia respectively, who developed aseptic bone necrosis 6, 11, and 20 months following the onset of corticoid therapy. The patients survive from 28+ to 50+ months after diagnosis of their initial hematologic disease, as it can be expected today for increasing numbers of patients. We therefore believe, that aseptic bone necrosis may represent a serious therapy related complication and suggest that, diagnostic examination in patients with suspicious complaints of the hip, shoulder or knee should also exclude the possibility of a bone necrosis after leucemic relapse has been ruled out. Since radiological changes only develop several weeks to months after the onset of the clinical symptoms and because of the disabling consequences for patients, misdiagnosed at the beginning, a 99 technetium bone scan should be done as early as possible. Corticosteroids, despite their serious side effects are still being considered as a important part of hematologic therapy and are not being omitted in the near future, so that the earliest possible diagnosis of bone necrosis will remain of great importance.(ABSTRACT TRUNCATED AT 250 WORDS)     

The demise of the randomised controlled trial: bibliometric study of the German-language health care literature, 1948 to 2004

Background  

In order to reduce systematic errors (such as language bias) and increase the precision of the summary treatment effect estimate, a comprehensive identification of randomised controlled trials (RCT), irrespective of publication language, is crucial in systematic reviews and meta-analyses. We identified trials in the German general health care literature.     

Involvement of ADAM10 in axonal outgrowth and myelination of the peripheral nerve

The disintegrin and metalloproteinase 10 (ADAM10) is a membrane‐anchored metalloproteinase with both proteolytic and disintegrin characteristics. Here, we investigate the expression, regulation, and functional role of ADAM10 in axonal outgrowth and myelination of the peripheral nerve. Expression pattern analysis of 11 ADAM family members in co‐cultures of rat dorsal root ganglia (DRG) neurons and Schwann cells (SCs) demonstrated the most pronounced mRNA expression for ADAM10. In further studies, ADAM10 was found to be consistently upregulated in DRG‐SC co‐cultures before the induction of myelination. Neurons as well as SCs widely expressed ADAM10 at the protein level. In neurons, the expression of ADAM10 was exclusively limited to the axons before the induction of myelination. Inhibition of ADAM10 activity by the hydroxamate‐based inhibitors GI254023X and GW280264X resulted in a significant decrease in the mean axonal length. These data suggest that ADAM10 represents a prerequisite for myelination, although its activity is not required during the process of myelination itself as demonstrated by expression analysis of myelin protein zero (P0) and Sudan black staining. Hence, during the process of myelin formation, ADAM10 is highly upregulated and appears to be critically involved in axonal outgrowth that is a requirement for myelination in the peripheral nerve. © 2009 Wiley‐Liss, Inc.     

Early Intestinal Changes Following Abdominal Radiotherapy

PURPOSE: To compare tests for intestinal function with clinical scores after abdominal irradiation. PATIENTS AND METHODS: At the Department of Radiotherapy, Erfurt, Germany, intestinal changes were studied in 91 patients receiving abdominal radiotherapy between 1992 and 1996. Conventional fractionation (1.8-2 Gy per fraction, total doses 30.6-62.5 Gy) was applied. Before and at weekly intervals during radiotherapy, the clinical response was scored according to RTOG/EORTC for the upper and lower gastrointestinal (GI) tract. Resorption tests for vitamin B(12) and D-xylose were performed before the onset and immediately after treatment. RESULTS: The clinical response displayed a well-defined dose-effect relationship with grade 1 effects in 5% and 50% of the patients at about 10 Gy and 50 Gy, respectively. For grade 2 reactions, 5%- and 50%-effective doses were 20-30 Gy and 60-80 Gy. Effects in the upper and lower GI tract were highly correlated. Changes in body weight did not show a correlation with other clinical symptoms. Changes in resorption also displayed a significant dose effect. However, no correlation was found with the clinical symptoms in the individual patient. CONCLUSION: In the present study, the clinical manifestation of intestinal side effects according to RTOG/EORTC criteria was reflected by neither the vitamin B(12) nor by the D-xylose resorption test. Hence, these tests cannot be regarded as useful for objective quantitation of intestinal radiation injury.