Mutant mouse pathology: an exercise in integration.
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Laboratory methods for measuring plasma ammonia concentration were reviewed. The ion-exchange method of analysis was evaluated using canine plasma from 15 clinically normal dogs and five dogs with portosystemic shunts. Mean and standard deviation was 40.3 +/- 8.1 microgram NH(3)/dl in normal dogs, and values ranged from 125 to 200 microgram NH(3)/dl in dogs with portosystemic shunts. Handling of blood samples properly for accurate results was found to require pre-chilled collection tubes, chilling the samples in an ice bath, immediate separation of plasma from red blood cells and immediate analysis for ammonia concentration. The ion exchange method was determined to be sufficiently accurate for clinical use and is suggested for any veterinary clinical pathology laboratory.
Studies comparing a new method with an established method, to assess whether the new measurements are comparable with existing ones, are frequently conducted in clinical pathology laboratories. Assessment usually involves statistical analysis of paired results from the 2 methods to objectively investigate sources of analytical error (total, random, and systematic). In this review article, the types of errors that can be assessed in performing this task are described, and a general protocol for comparison of quantitative methods is recommended. The typical protocol has 9 steps: 1) state the purpose of the experiment, 2) establish a theoretical basis for the method comparison experiment, 3) become familiar with the new method, 4) obtain estimates of random error for both methods, 5) estimate the number of samples to be included in the method comparison experiment, 6) define acceptable difference between the 2 methods, 7) measure the patient samples, 8) analyze the data, and 9) judge acceptability. The protocol includes the essential investigations and decisions needed to objectively assess the overall analytical performance of a new method compared to a reference or established method. The choice of statistical methods and recommendations of decision criteria within the stages are discussed. Use of the protocol for decision-making is exemplified by the comparison of 2 methods for measuring alanine aminotransferase activity in serum from dogs. Finally, a protocol for comparing simpler semiquantitative methods with established methods that measure on a continuous scale is suggested.
Many scientists are conducting research on human diseases which cannot be transmitted readily to laboratory animals or duplicated in the laboratory. Information offered by animal disease models should be compiled and made available to these scientists through the publication of extensive lists of animal disease models and annotated bibliographies for specific conditions.
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