Alan J. Wilson

Aquaporin 1 is an independent prognostic factor in pleural malignant mesothelioma.

Malignant mesothelioma (MM) is an aggressive cancer of serosal membranes, mostly pleura. It is related to asbestos exposure and its incidence in most industrialized countries is projected to remain stable or to increase until 2020. Prognosis remains poor. Clinical prognostic scoring systems lack precision. No prognostic tissue markers are available. Aquaporin 1 (AQP1) is a cell membrane channel involved in water transport, cell motility, and proliferation. A blocker and an agonist are available.

Effects of nonionic contrast media on the blood-brain barrier. Osmolality versus chemotoxicity.

This study was performed to assess the relative contributions of contrast medium osmolality and chemotoxicity to contrast-induced blood-brain barrier (BBB) damage. Experimental carotid angiography was carried out in rabbits with mannitol at an osmolality of 714 mOsm/kg, with the nonionic, monomeric contrast media iohexol and ioversol at similar osmolalities, and with the nonionic, dimeric contrast media iodixanol and iotrolan at osmolalities less than half that of the mannitol. The amount of damage caused by the procedure was assessed by determining the amount of intracerebral extravasation of intravascularly injected technetium-99m-pertechnetate. Mannitol caused no detectable BBB damage, but all four contrast media caused BBB damage that was significantly more severe than that caused by mannitol. The BBB damage caused by carotid angiography with iohexol, ioversol, iodixanol, and iotrolan was not attributable to their osmolalities, but due to some other physical and/or chemical effects of these media on the BBB.

Aquaporin-1 in blood vessels of rat circumventricular organs

Although the water channel protein aquaporin-1 (AQP1) is widely observed outside the rat brain in continuous, but not fenestrated, vascular endothelia, it has not previously been observed in any endothelia within the normal rat brain and only to a limited extent in the human brain. In this immunohistochemical study of rat brain, AQP1 has also been found in microvessel endothelia, probably of the fenestrated type, in all circumventricular organs (except the subcommissural organ and the vascular organ of the lamina terminalis): in the median eminence, pineal, subfornical organ, area postrema and choroid plexus. The majority of microvessels in the median eminence, pineal and choroid plexus, known to be exclusively fenestrated, are shown to be AQP1-immunoreactive. In the subfornical organ and area postrema in which many, but not all, microvessels are fenestrated, not all microvessels are AQP1-immunoreactive. In the AQP1-immunoreactive microvessels, the AQP1 probably facilitates water movement between blood and interstitium as one component of the normal fluxes that occur in these specialised sensory and secretory areas. AQP1-immunoreactive endothelia have also been seen in a small population of blood vessels in the cerebral parenchyma outside the circumventricular organs, similar to other observations in human brain. The proposed development of AQP1 modulators to treat various brain pathologies in which AQP1 plays a deleterious role will necessitate further work to determine the effect of such modulators on the normal function of the circumventricular organs.

Safety of carbon dioxide as a contrast medium in cerebral angiography

An increasing number of studies report the safety and effectiveness of carbon dioxide (CO2) as a digital subtraction angiographic contrast agent for intraarterial use below the diaphragm. Concerns about the possible neurotoxic effects of CO 2 within the cerebral circulation may be hindering its more widespread use below the diaphragm, because of the potential for reflux into the brain due to its buoyancy. These same concerns have also suppressed any consideration of CO 2 as a potential contrast agent for cerebral angiography. These concerns have been supported by a study (1) in which rats received single intracarotid injections of CO 2 in a range of doses, causing irreversible blood-brain barrier (BBB) damage and severe neurological deficits, with death occurring within 24 hours at the higher doses. Multifocal ischemic infarction was observed histologically as early as 6 hours after injection (1). Conversely, in a more recent study, dogs received multiple aortic arch and intracarotid injections of CO 2 but showed no EEG changes, no neurological deficits up to 6 months later, and no macroscopic pathological brain changes (2). There is clearly conflicting evidence about the safety of CO 2 within the cerebral circulation, and this investigation was undertaken with the intention of resolving the issue. Short-term studies were undertaken to determine the effects of intracarotid CO 2 on the BBB, and medium-term

Perceptions of optimal conditions for teaching and learning: a case study from Flinders University

Effective teaching and learning in higher education is an important focal point of literature around the globe. Various models are presented as desirable and fostering optimal conditions for teaching and learning. However, each model must be examined within the context of its institutional culture, mission and strategic plan to ascertain if it meets the envisaged goals. The Reinventing Teaching Project survey conducted at Flinders University in 2009 provided a unique opportunity for academic staff and students across all faculties to respond to a survey that explored their perceptions of optimal learning conditions and assessed if the campus environment was conducive to effective teaching and learning practices. The exploratory study was designed to gather qualitative and quantitative data on the motivation of teachers and learners to engage with learning and learners (or not). The results of the survey present valuable insights into what teachers and learners consider to be important attributes of optimal teaching and learning and indicate a number of similarities and differences among teacher-student perceptions. This paper identifies and discusses some of the pertinent outcomes of the study to provide a framework for other similar studies.

The toxic effects of angiographic carbon dioxide in the cerebral vasculature

Carbon dioxide (CO2) gas has been used clinically as an arterial contrast medium for more than 25 years. It has a number of advantages over iodinated contrast media, including its low cost, low viscosity, rapid elimination, buoyancy, and lack of nephrotoxic and allergic effects (1). Its disadvantages include the need to avoid air contamination and to use a dedicated injector system. When properly delivered and imaged, it produces images comparable to iodinated contrast media, and it is currently in use in all areas where iodinated contrast media are used, with the exception of the cerebral arterial vasculature (1). This exception is the result of concerns about the neurotoxicity of carbon dioxide in the cerebral vasculature. These concerns are based on animal studies showing severe neurotoxicity of carbon dioxide injected into the cerebral vasculature (2,3). Other animal studies, on the other hand, have been unable to demonstrate any neurotoxicity of carbon dioxide (1,4,5). Interpretation of these conflicting studies is complicated by the fact that most of them have not employed a systematic experimental approach, using different volumes, pressures, injection numbers, and injection sites within the same experiment. There are also concerns that, in some cases, the observation of neurotoxicity may have been influenced by air contamination and by high-pressure, explosive delivery of large volumes of carbon dioxide (1). It has been shown in this laboratory that multiple, nonexplosive internal carotid injections of carbon dioxide at clinically relevant doses in rabbits cause blood–brain barrier (BBB) breakdown that is still present 30 minutes later (6). This study was undertaken to investigate the reversibility of this BBB breakdown, and to examine brains for evidence of histologic damage 6 hours after multiple internal carotid injections of carbon dioxide delivered as reproducibly and benignly as possible. It is necessary to resolve the question of the neurotoxicity of carbon dioxide to determine both whether it is a safe neuroangiographic contrast medium and whether there is cause for concern about possible incidental reflux into the cerebral vasculature during carbon dioxide angiography below the diaphragm.

Carbon Dioxide Gas as an Angiographic Contrast Agent in the Cerebral Circulation

Carbon dioxide gas (CO2) has been in limited use in radiology as an intra-arterial, digital subtraction angiographic contrast medium for more than 20 years. It has a number of advantages over conventional iodinated contrast media, including its low cost, low viscosity, rapid pulmonary elimination, buoyancy, and lack of nephrotoxic and allergenic effects. Its disadvantages include the need to avoid air contamination and to use a dedicated injector system (Kerns et al.,1995). It has the potential to be used in all areas where iodine-containing contrast media are used, with the exception of the cerebral vasculature (Hawkins and Caridi, 1998). This exception is due to continuing concerns about the neurotoxicity of CO2 within the cerebral vessels. These concerns are due to a number of conflicting animal studies on the neurotoxicity of CO2 in the cerebral vasculature. Some studies have reported severe neurotoxicity (Coffey et al.,1984; Linstedt et al.,1997), while others have reported no neurotoxicity at all (Shifrin et al.,1990; Dimakakos et al,1998; Hawkins and Caridi, 1998). Interpretation of these inconsistent results is complicated by the fact that most have not used a systematic experimental approach, with different volumes, pressures, injection numbers and injection sites used within the same experiment. There have also been suspicions that air contamination, large volumes and explosive delivery of the CO2 may have contributed to the adverse findings (Hawkins and Caridi, 1998).

Effect of Additional Cations on the Twitching Reaction to Intracarotid, Nonionic Contrast Media in Rabbits

Previous investigations in this laboratory have confirmed the observation of facial muscle twitching during intracarotid injections of nonionic contrast media (CM) in rabbits. The reaction appears to be a locally mediated effect. To further investigate this reaction, cortical electroencephalogram (EEG) and facial electromyogram (EMG) recordings were made from rabbits receiving selective internal carotid artery (ICA) and external carotid artery (ECA) injections of CM. The effects of iopromide and iohexol were compared with and without the addition of sodium (Na) and calcium (Ca) ions at different concentrations. External carotid injections of iopromide also were performed in some animals paralyzed with D-tubocurarine to exclude the possibility that the reaction is due to an effect on peripheral nerves. The addition of between 5 and 20 mM Ca ions to both CM prevented the reaction but while the addition of Na ions (up to 150 mM) to iopromide had some preventative effect, it did not totally abolish the reaction. In those animals paralyzed with D-tubocurarine, the reaction to iopromide, as observed and recorded by EMG, was the same as that occurring in nonparalyzed animals. This finding is consistent with this reaction being independent of the peripheral nervous system.