Animal studies outcome measures

The overall evidence from studies in animals supports the observations of lead neurobehavioral effects in humans. As pointed out by Cory-Slechta (1995), studies in animals have provided a direct measurement of the behavioral process per se, and have done so in the absence of the covariates (e.g., socioeconomic status, parental IQ) known to affect IQ scores in human studies. It is also worth noting that animal studies, in which the experimental design is carefully controlled, have shown that the timing of exposure is crucial, that different neurobehavioral outcomes are affected differently (different thresholds), and that some behavioral alterations last longer than others. 

We are using the term inadequate sleep instead of sleep deprivation in our title for a number of reasons. First, few studies have aimed specifically to deprive children or adolescents of sleep. We describe some research on experimental sleep restriction in children but most of these studies fall far short of common deprivation paradigms in animals or even adult humans. Instead, most research in younger humans has assessed outcome measures such as school grades, self-reported sleepiness, and so forth as a function of variations in self-selected or usual sleep patterns with the expectation that children and adolescents who obtain lower than normal amounts of sleep will manifest deficits. Thus, inadequate sleep is defined by sleep characteristics of a sample. We also wanted to note some of the literature on sleep that is disturbed or disrupted due to disease processes such as apnea or periodic leg movements the duration of sleep in sleep disorders may or may not be shortened or restricted although it is likely fragmented and otherwise abnormal. We decided on the term inadequate sleep with the hope that it would encompass these different areas of concern. 

However, the most important driving force for performing in vitro toxicity studies is a scientific one if one wishes to study the toxicity mechanisms of action of a compound, it is no longer appropriate to rely on the apical endpoints for toxicity that are the commonly measured parameters in an animal study. A focus on these mechanisms, in relation to the events following the molecular initiating event, eventually leading to an adverse outcome gives... 

Azole compounds have been tested in the mouse model of Chagas disease in numerous laboratories. Direct comparisons between studies can be difficult because of the use of diffident protocols, diffierent strains of T. cruzi, and different outcome measurements. A pardculady problematic challenge with all of these studies is the test of cure of the animals. The tests include hemoculture, xenodiagnosis, serology, PCR, tissue analysis, and combinations of these. The reader is referred to the original papers for details. 

Untreated, oleander seed poisoning carries a mortality of 10% in Sri Lanka and treatment of yellow oleander poisoning is limited to the use of repeated doses of activated charcoal and atropine [17 antidigoxin antibodies are not available for routine use because of the high cost. Based on an animal study and on a small phase II study in patients with yellow oleander poisoning, a double-blind, randomized, placebo-controlled trial has been set up to assess the effectiveness of fructose-l,6-diphosphate (FDP) in acute yellow oleander poisoning [18 ]. Eligible patients will be randomized to either FDP or an equal amount of isotonic saline. The primary outcome measure will be sustained reversion to sinus rhythm at a rate of over 50/minute within 2 hours. Secondary outcomes will include death, reversal of hyperkalaemia at 6, 12, 18, and 24 hours, and maintenance of sinus rhythm. 

The second section concentrates on study results and current knowledge, and attempts to summarize what we know as a result of research in relation to lead and intelligence, educational attainment, behaviour, and other psychometric measures. The contribution of animal studies, and studies with electrophysiological outcome measures, to current knowledge is assessed. The problems in interpreting the existing data are discussed in relation to some of the methodological issues described in the first section. 

The last sessions of the workshop were specifically devoted to discussions with all the invited speakers and representatives participating. There were four separate sessions under different headings design and statistics, outcome measures, exposure assessment, and animal studies. These topics were chosen during the meeting as a result of the interest, and in some cases controversy, that had been apparent in these areas, and they also provided convenient headings under which to discuss future directions. The four sessions were summarized by Professor Yule who acted as rapporteur. 

In general, the evidence from animal studies suggests that more attention should be paid to the nature of the task the child is required to do in a test situation, and that as well as recording an outcome score in terms of correct responses, other measures of performance such as incorrect responses, false positives, speed of response, and trials to criterion should be recorded. For... 

Research with animals can make a valuable contribution to two of the areas discussed earlier outcome measures and exposure assessment. It can indicate which outcome measures are most sensitive to lead effects and which outcomes are insensitive, provide information on the types of processes involved, and inform the choice of outcome measures for studies of children it also provides an opportunity to study the kinetics of lead in relation to the measures of body lead burden most frequently obtained in studies of humans. The effect of chelation therapy on lead levels in the brain, and the relation of these to levels of lead in blood and bone, is another area where animal work can inform studies of children. The limitations of extrapolation from animal data to studies of humans are addressed in the review section of this book. While it is unlikely that the rat provides an adequate model of... 

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