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Mark H. Kleinman Mark D. Smith Edit Kurali Sarah Kleinpeter Kaina Jiang Yongxia Zhang Sonya A. Kennedy-Gabb Anthony M. Lynch Chris D. Geddes 《Regulatory toxicology and pharmacology : RTP》2010
The existing regulatory guidance for photosafety testing of new drug products states that studies are warranted for those chemicals that both absorb light in the range of 290–700 nm, and that are either applied locally/topically, or “reach” (EMEA)/“significantly partition” (FDA) to the skin or eyes. The initial in vitro study recommended for the assessment of phototoxic potential is the 3T3 Neutral Red Uptake (NRU) Assay. The current study was undertaken to establish superior triggers for the initiation of biological photosafety testing. In this study, photophysical and photochemical parameters for 40 drug or drug-like molecules were studied. Principal Component Analysis (PCA), Partial Least Squares-Discriminant Analysis (PLS-DA), and a fivefold cross-validation PLS algorithm were used to evaluate the relationship between subsets of photophysical and photochemical parameters with the 3T3 NRU PIF/MPE (Photo Irritation Factor/Mean Photo Effect) results. The parameters most indicative of a 3T3 NRU positive PIF or MPE score were the extent of degradation in solution, the quantum yield of formation of singlet oxygen and the relative formation of superoxide anion. The results demonstrate that while absorption of light is critical to the induction of a light-induced process, it is the resultant events that may be used to predict the 3T3 NRU assay result. It is therefore proposed that the trigger for photosafety testing be revised to include a molecular basis for photoreactivity. From this limited investigation, estimated thresholds leading to 3T3 NRU positive results due to photodegradation, formation of singlet oxygen quantum yield or a relative superoxide anion formation value are proposed. 相似文献
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Reducing mortality, especially premature death, is a major goal of the fight against cancer. In this study, we have analyzed trends in malignant melanoma (MM) mortality in the European Community (EC) as a whole and for each country. The data (obtained from the World Health Organization data bank) have been analyzed for the period 1970-90, by age groups (20-44, 45-64, 65-74, 75+ years). Trends are presented as percentage change of mortality rate for each three-year period in comparison with the rate in the first one (1970-72). The mortality from MM in the EC as a whole increased for both genders (men, +89.2 percent; women, +72.6 percent), with statistically significant trends in all age classes. Northern countries experienced mortality changes about 30 to 50 percent less than the EC average increase. Greater changes were seen in southern European countries, in which recent standardized rates are near to those observed in northern European populations. Among Mediterranean people, the highest increase (more than fourfold) was observed in Spain. The significant increase found for the younger age class makes unlikely the risk of misclassification with other skin cancers. No future decrease in MM mortality in the EC is indicated from these data. 相似文献
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Hamady ZZ Malik HZ Finch R Adair R Al-Mukhtar A Prasad KR Toogood GJ Lodge JP 《Annals of surgical oncology》2006,13(11):1493-1499
Background Many colorectal liver metastasis patients are denied surgical resection on the basis of tumour size. The aim of this study was to explore the impact of metastasis size on modern liver resection.Methods Using a prospectively collected database, this was a retrospective analysis of 484 consecutive patients who underwent liver resection for colorectal liver metastases between 1993 and 2003. The cohort was divided into two groups: smaller metastases (<8 cm) and larger metastases (≥ 8 cm). Those with larger metastases were then further stratified into big metastases (8–12 cm) and giant metastases (>12 cm). Demographic, pathological, surgical technique and outcome data were compared between the groups.Results There were 88 (18%) patients with metastases measuring 8 cm or larger. There was an association between higher carcinoembryonic antigen (CEA) and cancer antigen (CA) 19-9 levels and larger metastases. The actuarial 5-year survival for patients with larger metastases was 38% compared with 42% for smaller metastases (not statistically significant). Patients with giant metastases had poorer overall and disease-free survival (both nonsignificant) compared with those with big metastases: 29% and 28% at 5 years, respectively.Conclusion Patients with colorectal liver metastasis greater than 8 cm and up to 12 cm in size should not be treated differently from those with smaller lesions. 相似文献
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Nutrition education messages were written about eight different foods or food products in eight different styles. Styles were suggestions, instructions using 'should', rhetorical questions using 'how about' or 'why not', statements of fact, positive commands, positive commands followed by negative commands or vice versa. Subjects (n 160) rated messages for persuasiveness and also stated how often they already complied with each message. Scores were adjusted to remove the contributions related to sex, age group, social class, reported compliance and food about which the message had been written. The main factor influencing score for persuasiveness was the extent to which subjects claimed to be already complying with the messages. There were no significant effects of the method of construction of messages on score using one-way analysis of variance. 相似文献
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Joanna M.L. Geddes Alan Tennant M. Anne Chamberlain 《Disability and rehabilitation》2013,35(12):529-538
Purpose : This paper describes the application of the handicap dimension of the International Classification of Impairments, Disabilities and Handicaps. Method : A method of assessing four of the six roles (or areas of expected competency) was developed and applied to an inpatient population, aged 16 to 65 years, receiving specialist rehabilitation following neurological damage. Handicap assessment was a collaborative process by a multidisciplinary team. Difficulties were experienced in measuring inter-rate reliability in the busy, clinical setting. Results : We conclude that handicap assessment in an in-patient rehabilitation unit which uses a multidisciplinary approach to treating patients with complex physical, sensory and cognitive problems is both feasible and useful. Conclusion : The developed scale, The Leeds Assessment Scale of Handicap, provides a valid and valuable summary of human disadvantage, complementing the common disability assessments. 相似文献