An overview of animal models for investigating the pathogenesis and therapeutic strategies in acute hepatic failure

Acute hepatic failure （AHF） is a severe liver injury accompanied by hepatic encephalopathy which causes multiorgan failure with an extremely high mortality rate, even if intensive care is provided. Management of severe AHF continues to be one of the most challenging problems in clinical medicine. Liver transplantation has been shown to be the most effective therapy, but the procedure is limited by shortage of donor organs. Although a number of clinical trials testing different liver assist devices are under way, these systems alone have no significant effect on patient survival and are only regarded as a useful approach to bridge patients with AHF to liver transplantation. As a result, reproducible experimental animal models resembling the clinical conditions are still needed. The three main approaches used to create an animal model for AHF are： surgical procedures, toxic liver injury and infective procedures. Most common models are based on surgical techniques （total/partial hepatectomy, complete/transient devascularization） or the use of hepatotoxic drugs （acetaminophen, galactosamine, thioacetamide, and others）, and very few satisfactory viral models are available. We have recently developed a viral model of AHF by means of the inoculation of rabbits with the virus of rabbit hemorrhagic disease. This model displays biochemical and histological characteristics, and clinical features that resemble those in human AHF. In the present article an overview is given of the most widely used animal models of AHF, and their main advantages and disadvantages are reviewed.     

Risk Prediction Scores for Postoperative Mortality After Esophagectomy: Validation of Different Models

Background  Different prediction models for operative mortality after esophagectomy have been developed. The aim of this study is to independently validate prediction models from Philadelphia, Rotterdam, Munich, and the ASA. Methods  The scores were validated using logistic regression models in two cohorts of patients undergoing esophagectomy for cancer from Switzerland (n = 170) and Australia (n = 176). Results  All scores except ASA were significantly higher in the Australian cohort. There was no significant difference in 30-day mortality or in-hospital death between groups. The Philadelphia and Rotterdam scores had a significant predictive value for 30-day mortality (p = 0.001) and in-hospital death (p = 0.003) in the pooled cohort, but only the Philadelphia score had a significant prediction value for 30-day mortality in both cohorts. Neither score showed any predictive value for in-hospital death in Australians but were highly significant in the Swiss cohort. ASA showed only a significant predictive value for 30-day mortality in the Swiss. For in-hospital death, ASA was a significant predictor in the pooled and Swiss cohorts. The Munich score did not have any significant predictive value whatsoever. Conclusion  None of the scores can be applied generally. A better overall predictive score or specific prediction scores for each country should be developed. No score generally applicable     

Longitudinal Assessment of Cost in Health Care Interventions

We develop a method to estimate the cumulative cost of health interventions over a specified duration while controlling for a mix of patient-specific variables using data of total cost and associated length of treatment. A two-equation model for total cost and duration of treatment is estimated with the endogeneity of the latter accounted for in the model for cost. As an illustrative example, we apply our method to hospital costs and length of stay of patients undergoing cardiac procedures. Our method is relevant to economic evaluations of interventions since it accounts for the differential impact of treatment duration on total cost, in addition to patient characteristics. Our method allows greater use of total costs data, typically found in hospital records and claim files, that has not been previously attempted.     

Immunological concepts and the eye: A review of the classical and ocular Arthus reactions

Inflammatory processes can involve any tissue in the eye. Despite advances in therapy, the sequelae of inflammation continue to be a major cause of visual impairment. Knowledge of disease pathogenesis in clinical ocular inflammations remains imprecise, and defined models are crucial in developing this understanding and evolving rational approaches to treatment. This review analyzes the contributions that studies of the classical and Arthus ocular Arthus-type reactions have made as to how the eye functions as an immunological entity. The anticipated development of therapeutic agents that may modulate immune processes with remarkable specificity, gives a new impetus to such experimental studies.     

Critical values for linearity tests in time‐varying smooth transition autoregressive models when data are highly persistent

Summary In this paper, we derive asymptotic distributions for linearity tests in time‐varying smooth transition autoregressive models in the presence of a unit root. The limiting distributions are non‐standard because of the unit root assumption, and it is shown that the linearity hypothesis is rejected far too often (up to 30.9% of the times at a 5% significance level) when using critical values from a chi‐square distribution.     

Genetic differences in a tail suspension test for evaluating antidepressant activity

Tail suspension-induced immobility in rodents is specifically antagonized by antidepressants, and has been proposed as an animal model of depression. Marked differences in tail suspension-induced immobility were observed among nine inbred mouse strains, ranging from 1±0.3 to 96±8-s in a 300-s test period. Moreover, these nine strains could be ranked in four distinct groups based on their immobilities, in which Balb/cJ and DBA/2J mice displayed the highest and the lowest immobility times, respectively. While significant differences in open field activity were also observed among strains, these differences were unrelated to their immobility times in the tail suspension test. These findings strongly suggest that performance in this proposed animal model of depression is under specific genetic control, and may provide a useful tool to study neurochemical and neuroendocrine correlates of depression and antidepressant action.     

Neural basis of behavior: Animal models of human conditions

A variety of neurological disorders including Alzheimer's, Parkinson's, and Huntington's diseases are characterized by abnormalities within specific neuroanatomical and/or neurochemical systems. Approaches to the treatment of these and other neurological disorders are limited. The development and refinement of animal models which closely mimic human disease states would help elucidate the underlying neurobiological mechanisms of the disease as well as suggest novel therapeutic strategies for their prevention or alleviation. This symposium presents a variety of animal models that have helped us in understanding the human condition. The present introduction presents some clinically relevant findings obtained from basic experimental studies with animal models of Huntington's disease (HD) and Tourette Syndrome (TS). These studies demonstrate that animal models can provide a greater understanding of the symptomatology of disease states as well as suggest innovative new treatments.