Animal carcinogenicity studies: 3. Alternatives to the bioassay

Conventional animal carcinogenicity tests take around three years to design, conduct and interpret. Consequently, only a tiny fraction of the thousands of industrial chemicals currently in use have been tested for carcinogenicity. Despite the costs of hundreds of millions of dollars and millions of skilled personnel hours, as well as millions of animal lives, several investigations have revealed that animal carcinogenicity data lack human specificity (i.e. the ability to identify human non-carcinogens), which severely limits the human predictivity of the bioassay. This is due to the scientific inadequacies of many carcinogenicity bioassays, and numerous serious biological obstacles, which render profoundly difficult any attempts to accurately extrapolate animal data in order to predict carcinogenic hazards to humans. Proposed modifications to the conventional bioassays have included the elimination of mice as a second species, and the use of genetically-altered or neonatal mice, decreased study durations, initiation-promotion models, the greater incorporation of toxicokinetic and toxicodynamic assessments, structure-activity relationship (computerised) systems, in vitro assays, cDNA microarrays for detecting changes in gene expression, limited human clinical trials, and epidemiological research. The potential advantages of non-animal assays when compared to bioassays include the superior human specificity of the results, substantially reduced time-frames, and greatly reduced demands on financial, personnel and animal resources. Inexplicably, however, the regulatory agencies have been frustratingly slow to adopt alternative protocols. In order to decrease the enormous cost of cancer to society, a substantial redirection of resources away from excessively slow and resource-intensive rodent bioassays, into the further development and implementation of non-animal assays, is both strongly justified and urgently required.     

生物医学动物实验中的实验设计和统计分析

实验设计和统计分析在动物实验研究的启动、实施和结果评价中起着关键的作用。我们对实验设计的因素、原则及实验设计类型进行了综述,阐明了统计分析在整个研究所有环节中的重要意义,并提出在生物医学动物实验中容易忽视的统计学分析的问题。     

The Design and Analysis of Twin Animal Experiments

The experimental design used in twin studies on veal calves at the University of Guelph during the years 1965–1968 combined split trials with uniformity trials on each treatment. Each replicate consisted of four twin pairs. Both members of one pair selected at random were put on treatment 1, both members of another pair were put on treatment 2, and the remaining two pairs were “split” with one twin from each pair randomly assigned to each treatment. There were a number of replicates of this basic design over the course of the experiment. The objective of this paper is: (i) to determine the feasibility of an overall analysis of the given design, (ii) to determine an accurate method for assessing treatment effects, and (iii) to find an efficient method for detecting the presence of treatment Xpair interaction.     

Alternatives to thumb replantation

LEARNING OBJECTIVES: After studying this article, the participant should: 1. Have a variety of options for thumb reconstruction. 2. Know the advantages and disadvantages of the nonmicrosurgical and microsurgical techniques for thumb reconstruction. 3. Understand the decision making from the variety of thumb reconstruction techniques based on patient needs. 4. Have a basic understanding of the various thumb reconstruction techniques discussed. The traumatic amputation of the thumb is an absolute indication for attempted replantation. The profound disability of the hand resulting from absence of the thumb, with loss of pinch and grasp, obliges the surgeon to make every attempt to replant the amputated thumb and preserve hand function. However, not all attempts at replantation result in survival of the amputated portion, and unreconstructable damage to or complete loss of the amputated part may preclude attempted replantation. In such situations, the surgeon must have alternative methods of dealing with the sequelae of thumb loss. This article will discuss nonmicrosurgical and microsurgical techniques for thumb reconstruction.