Predictive value and limitations of animal models for human transplantation: do we need more models for facial transplantation?

Animal models have traditionally provided the basis for preliminary investigation of new techniques prior to trials taking place in human subjects. The timing of when to proceed with human trials is difficult, as the accuracy of preclinical models can only be determined with hindsight. This review outlines the progression from transplantation in animal models to man. Now that many transplant procedures are well established, it is possible to assess the predictive value and limitations of animal models. These results are of great importance in the current debate about composite tissue allotransplantation (CTA) and in particular facial transplantation. This progression of CTA from animal models to man is outlined and compared with early renal, cardiac, and liver transplants. There is some evidence to suggest that animal models may have been misleading in CTA and that this has effectively delayed the transition to humans. The role for animal models in facial transplantation, which is currently making the step to clinical trials, is discussed.     

Hospital Episode Statistics and trends in ophthalmic surgery 1998 – 2004

Background  

Hospital episode statistics (HES) is a UK national database for the National Health Service (NHS), now available online. The purpose of this study was to observe trends in ophthalmic operations performed during the period from 1998 to 2004, using this data.     

The immunolocalisation of the neuroendocrine specific protein PGP9.5 during neurogenesis in the rat.

We have examined the immunolocalisation of the protein gene product (PGP) 9.5 during neurogenesis in the rat embryo. PGP9.5 was first present at 11.5 days gestation (E11.5): all morphologically recognisable nerve cell bodies and fibres were immunoreactive. In routinely processed, wax-embedded tissues, using a standard immunocytochemical technique, PGP9.5 polyclonal antibody specifically demonstrated the developing nervous system and primitive adrenal chromaffin cells.     

Air pollution and daily mortality: a hypothesis concerning the role of impaired homeostasis.

We propose a hypothesis to explain the association between daily fluctuations in ambient air pollution, especially airborne particles, and death rates that can be tested in an experimental model. The association between airborne particulates and mortality has been observed internationally across cities with differing sources of pollution, climates, and demographies and has involved chiefly individuals with advanced chronic illnesses and the elderly. As these individuals lose the capacity to maintain stable, optimal internal environments (i.e., as their homeostatic capacity declines), they become increasingly vulnerable to external stress. To model homeostatic capacity for predicting this vulnerability, a variety of regulated physiologic variables may be monitored prospectively. They include the maintenance of deep body temperature and heart rate, as well as the circadian oscillations around these set-points. Examples are provided of the disruptive changes shown by these variables in inbred mice as the animals approach death. We consider briefly the implications that the hypothesis may hold for several epidemiologic issues, including the degree of prematurity of the deaths, the unlikelihood of a threshold effect, and the role that coarse, noncombustive particles may play in the association.     

Intubating conditions after vecuronium and atracurium given in divided doses (the priming technique)

Intubating conditions have been assessed at 60 s following administration of vecuronium 0.1 mg kg-1 or atracurium 0.5 mg kg-1 given either as a single dose after induction of anaesthesia with thiopentone or in divided doses; vecuronium 0.015 mg kg-1 followed 4 or 6 min later by 0.085 mg kg-1, or atracurium 0.075 mg kg-1 followed 4 or 6 min later by 0.425 mg kg-1. In the divided dose groups the smaller initial (priming) dose was given prior to induction of anaesthesia. Onset and duration of clinical relaxation were assessed using a peripheral nerve stimulator. The intubating conditions at 60 s improved significantly, with the use of relaxants in divided doses being acceptable in 80 and 70% of patients, respectively, with vecuronium and atracurium, but the conditions are not as good as those commonly found using suxamethonium. Priming at 6 min has no advantage over priming at 4 min. The onset of complete block was accelerated with priming, but the difference was not significant. The duration of clinical relaxation of vecuronium was significantly prolonged by giving it in divided doses. Unpleasant awareness of muscle weakness was observed in 15 patients, requiring early induction of anaesthesia in five of them.