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Purpose: To evaluate proteinuria occurring early after ifosfamide therapy and to assess the use of changes in proteinuria in the prediction of severe chronic nephrotoxicity. Methods: One-dimensional sodium dodecyl sulphate polyacrylamide gel electrophoresis was used to characterize urine protein excretion in 12 children with solid tumours before and after the first course of ifosfamide treatment, and in 24 healthy children. Chronic nephrotoxicity was evaluated at 6 months after ifosfamide treatment and graded as none, mild, moderate or severe. Results: Urine from healthy children and from 10 of 12 patients before ifosfamide therapy showed a protein band with a molecular weight (95.4 kDa) corresponding to that of Tamm-Horsfall protein but no lower molecular weight proteins. After the first course of ifosfamide this 95.4-kDa protein was lost in six of ten patients with a concomitant appearance of a low molecular weight proteinuria (<70 kDa) in eight. Tamm-Horsfall protein was lost in two of five patients who subsequently developed no or mild nephrotoxicity and in four of five patients who subsequently developed moderate or severe nephrotoxicity. Conclusions: Early subclinical changes in urine protein excretion after ifosfamide, manifested by a loss of Tamm-Horsfall protein excretion, may be predictive of subsequent chronic nephrotoxicity. Received: 27 August 1996 / Accepted: 25 July 1997  相似文献   
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Di-(2-propylheptyl) phthalate (DPHP) is a high molecular weight polyvinyl chloride plasticizer. Since increasing production volume and broad utility may result in human exposure, an oral reference dose (RfD) was derived from laboratory animal data due to the lack of human data. In addition to liver and kidney, target organs were the thyroid, pituitary and adrenal glands in rats, recognizing that reproductive performance was not altered in two successive generations of DPHP-exposed rats. DPHP caused a reduction in pup and maternal body weights but not developmental or testicular effects typical of “phthalate syndrome.” DPHP was not genotoxic. Due to the lack of carcinogenicity data, there is inadequate information to assess carcinogenic potential. The RfD of 0.1 mg/kg-day was derived from the human equivalent BMDL10 of 10 mg/kg-day for thyroid hypertrophy/hyperplasia in male F1 adults from the two-generation study. While in utero exposure did not alter sensitivity to thyroid lesions compared to subchronic exposures beginning at 6 weeks of age, F1 adult males were the longest-term exposed population. The total uncertainty factor of 100x was comprised of intraspecies (10x), study duration (3x), and database (3x) factors but not an interspecies factor since rodents are more sensitive than humans to thyroid gland effects.  相似文献   
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Background  

The development of evidence-based clinical practice guidelines has gained wide acceptance in high-income countries and reputable international organizations. Whereas this approach may be a desirable standard, challenges remain in low-income settings with limited capacity and resources for evidence synthesis and guideline development. We present our experience using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach for the recent revision of the Kenyan pediatric clinical guidelines focusing on antibiotic treatment of pneumonia.  相似文献   
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