Intensive care nurses' perceptions of brain death

Research during the last 2 decades has revealed significant confusion or lack of acceptance and inconsistent application of the brain death concept within the medical and nursing professions. The aim of this naturalistic and descriptive study was to investigate the extent to which a sample of 40 Australian intensive care nurses regarded brain death as a meaningful conception of death. In contrast with the majority of the literature pertaining to health care professionals' perceptions of brain death which has focused upon clinical knowledge, the study elicited the expression of personal beliefs. The study utilised a structured interview method with nurses from seven metropolitan intensive care units (ICUs). Transcript analysis revealed five categories of perception constituting a spectrum ranging from complete acceptance to complete rejection, with almost half (48%, n=19) the sample regarding the brain dead patient as less than completely meaningfully dead.

Rather than supporting the literature's suggestion that non-acceptance of the medico-legally recognised brain death notion is, necessarily, evidence of professional ignorance, the findings suggest the participants holding these perceptions were generally well-informed about brain stem function and brain death diagnosis. The study affirms the importance of supportive workplace environments which facilitate the expression of dissonant perceptions and proposes that educators and managers must acknowledge these dissonances.

"I could see, and yet, mon, I could na` see" : William Macewen, the agnosias, and brain surgery

Two little noticed cases in which William Macewen used symptoms of visual agnosia to plan brain surgery on the angular gyrus are reviewed and evaluated. Following a head injury, Macewen’s first patient had an immediate and severe visual object agnosia that lasted for about 2 weeks. After that he gradually became homicidal and depressed and it was for those symptoms that Macewen first saw him, some 11 months after the accident. From his examination, Macewen concluded that the agnosia clearly indicated a lesion in “the posterior portion of the operculum or in the angular gyrus.” When he removed parts of the internal table that had penetrated those structures the homicidal impulses disappeared. Macewen’s second patient was seen for a chronic middle ear infection and, although neither aphasic nor deaf, was ‘word deaf.’ Slightly later he became ‘psychically blind’ as well. Macewen suspected a cerebral abscess pressing on both the angular gyrus and the first temporal convolution. A large subdural abscess was found there and the symptoms disappeared after it was treated. The patients are discussed and Macewen’s positive results analysed in the historical context of the dispute over the proposed role of the angular gyrus as the visual centre.

Localisation and William Macewen`s early brain surgery part I: the controversy

Neurosurgery for the removal of brain tumours based on localising signs is usually dated from the 1884 operation by Bennett and Godlee. However, within weeks of that operation claims were made on behalf of William Macewen, the Glasgow surgeon, to have been the real pioneer of such surgery. According to Macewen's protagonists, he had conducted seven similar operations earlier than Bennett and Godlee and, in a notable 1888 address, Macewen described these seven pre-1884 cases and a number of others operated on after 1884. This paper, which is in two parts, contains an evaluation of the claims made for the priority of Macewen's pre-1884 operations. Part I deals mainly with Macewen's work in fields other than brain surgery that are relevant to it and sets out the facts of the controversy. It begins with a brief biography of Macewen, describes his pioneering work in antiseptic and aseptic surgery, his work on osteotomy and bone regeneration, and his use in brain surgery of the knowledge so gained. Part I concludes with an examination of the battle waged in the newspapers between Macewen's and Bennett's and Godlee's supporters, and of previously unpublished correspondence between Macewen himself, David Ferrier and Hughes Bennett. The primary records of the patients on whom Macewen operated, together with other materials relevant to the controversy, are examined in Part II.

Role of P-glycoprotein in limiting the brain penetration of glabridin, an active isoflavan from the root of Glycyrrhiza glabra.

Purpose. Glabridin is a major active constituent of Glycyrrhiza glabra which is commonly used in the treatment of cardiovascular and central nervous system (CNS) diseases. Recently, we have found that glabridin is a substrate of P-glycoprotein (PgP/MDR1). This study aimed to investigate the role of PgP in glabridin penetration across the blood–brain barrier (BBB) using several in vitro and in vivo models.
Materials and Methods. Cultured primary rat brain microvascular endothelial cells (RBMVECs) were used in the uptake, efflux and transcellular transport studies. A rat bilateral in situ brain perfusion model was used to investigate the brain distribution of glabridin. The brain and tissue distribution of glabridin in rats with or without coadministered verapamil or quinidine were examined with correction for the tissue residual blood. In addition, the brain distribution of glabridin in mdr1a(-/-) mice was compared with the wild-type mice. Glabridin in various biological matrices was determined by a validated liquid chromatography mass spectrometric method.
Results. The uptake and efflux of glabridin in cultured RBMVECs were ATP-dependent and significantly altered in the presence of a PgP or multi-drug resistance protein (Mrp1/2) inhibitor (e.g. verapamil or MK-571). A polarized transport of glabridin was found in RBMVEC monolayers with
facilitated efflux from the abluminal (BL) to luminal (AP) side. Addition of a PgP or Mrp1/2 inhibitor in both luminal and abluminal sides attenuated the polarized transport across RBMVECs. In a bilateral in situ brain perfusion model, the uptake of glabridin into the cerebrum increased from 0.42 T 0.09% at 1 min to 9.27 T 1.69% (ml/100 g tissue) at 30 min and was significantly greater than that for sucrose. Coperfusion of a PgP or Mrp1/2 inhibitor significantly increased the brain distribution of glabridin by 33.6j142.9%. The rat brain levels of glabridin were only about 27% of plasma levels when corrected by tissue residual blood and it was increased to up to 44% when verapamil or quinidine was coadministered. The area under the brain concentration-time curve (AUC) of glabridin in mdr1a(-/-) mice was 6.0-fold higher than the wild-type mice.
Conclusions. These findings indicate that PgP limits the brain penetration of glabridin through the BBB and PgP may cause drug resistance to glabridin (licorice) therapy for CNS diseases and potential drugglabridin interactions. However, further studies are needed to explore the role of other drug transporters (e.g. Mrp1-4) in restricting the brain penetration of glabridin.

Transport of cryptotanshinone, a major active triterpenoid in Salvia miltiorrhiza Bunge widely used in the treatment of stroke and Alzheimers disease, across the blood-brain

Cryptotanshinone (CTS), a major constituent from the roots of Salvia miltiorrhiza (Danshen), is widely used in the treatment of coronary heart disease, stroke and less commonly Alzheimer's disease. Our recent study indicates that CTS is a substrate for Pglycoprotein (PgP/MDR1/ABCB1). This study has investigated the nature of the brain distribution of CTS across the brain-blood barrier (BBB) using several in vitro and in vivo rodent models. A polarized transport of CTS was found in rat primary microvascular endothelial cell (RBMVEC) monolayers, with facilitated efflux from the abluminal side to luminal side. Addition of a PgP (e.g. verapamil and quinidine) or multi-drug resistance protein 1/2 (MRP1/2) inhibitor (e.g. probenecid and MK-571) in both luminal and abluminal sides attenuated the polarized transport. In a bilateral in situ brain perfusion model, the uptake of CTS into the cerebrum increased from 0.52 ± 0.1% at 1 min to 11.13 ± 2.36 ml/100 g tissue at 30 min and was significantly greater than that of sucrose. Co-perfusion of a PgP/MDR1 (e.g. verapamil) or MRP1/2 inhibitor (e.g. probenecid) significantly increased the brain distribution of CTS by 35.1-163.6%. The brain levels of CTS were only about 21% of those in plasma, and were significantly increased when coadministered with verapamil or probenecid in rats. The brain levels of CTS in rats subjected to middle cerebral artery occlusion and rats treated with quinolinic acid (a neurotoxin) were about 2- to 2.5-fold higher than the control rats. Moreover, the brain levels in mdr1a(-/-) and mrp1(-/-) mice were 10.9- and 1.5-fold higher than those in the wild-type mice, respectively. Taken collectively, these findings indicate that PgP and Mrp1 limit the brain penetration of CTS in rodents, suggesting a possible role of PgP and MRP1 in limiting the brain penetration of CTS in patients and causing drug resistance to Danshen therapy and interactions with conventional drugs that are substrates of PgP and MRP1. Further studies are needed to explore the role of other drug transporters in restricting the brain penetration of CTS and the clinical relevance.

Omega 3 fatty acids and the brain : review of studies in depression

The brain is a lipid-rich organ containing mostly complex polar  phospholipids, sphingolipids, gangliosides and cholesterol. These lipids are involved in the structure and function of cell membranes in the brain. The glycerophospholipids in the brain contain a high proportion of  polyunsaturated fatty acids (PUFA) derived from the essential fatty acids, linoleic acid and alpha-linolenic acid. The main PUFA in the brain are docosahexaenoic acid (DHA, all cis 4,7,10,13,16,19-22:6) derived from the omega 3 fatty acid, alpha-linolenic acid, and arachidonic acid (AA, all cis 5,8,11,14-20:4) and docosatetraenoic acid (all cis 7,10,13,16-22:4), both derived from the omega 6 fatty acid, linoleic acid. Experimental studies in animals have shown that diets lacking omega 3 PUFA lead to substantial disturbances in neural function, which in most circumstances can be restored by the inclusion of omega 3 PUFA in the diet. In the past 10 years there has been an emerging interest in treating neuropsychological  disorders (depression and schizophrenia) with omega 3 PUFA. This paper discusses the clinical studies conducted in the area of depression and omega 3 PUFA and the possible mechanisms of action of these PUFA. It is clear from the literature that DHA is involved in a variety of processes in neural cells and that its role is far more complex than simply influencing cell membrane properties.

Perinatal ω-3 polyunsaturated fatty acid supply modifies brain zinc homeostasis during adulthood

Dietary ω-3 polyunsaturated fatty acid (PUFA) influences the expression of a number of genes in the brain. Zinc transporter (ZnT) 3 has been identified as a putative transporter of zinc into synaptic vesicles of neurons and is found in brain areas such as hippocampus and cortex. Neuronal zinc is involved in the formation of amyloid plaques, a major characteristic of Alzheimer's disease. The present study evaluated the influence of dietary ω-3 PUFA on the expression of the ZnT3 gene in the brains of adult male Sprague-Dawley rats. The rats were raised and/or maintained on a control (CON) diet that contained ω-3 PUFA or a diet deficient (DEF) in ω-3 PUFA. ZnT3 gene expression was analyzed by using real-time PCR, free zinc in brain tissue was determined by zinquin staining, and total zinc concentrations in plasma and cerebrospinal fluid were determined by atomic absorption spectrophotometry. Compared with CON-raised animals, DEF-raised animals had increased expression of ZnT3 in the brain that was associated with an increased level of free zinc in the hippocampus. In addition, compared with CON-raised animals, DEF-raised animals had decreased plasma zinc level. No difference in cerebrospinal fluid zinc level was observed. The results suggest that overexpression of ZnT3 due to a perinatal ω-3 PUFA deficiency caused abnormal zinc metabolism in the brain. Conceivably, the influence of dietary ω-3 PUFA on brain zinc metabolism could explain the observation made in population studies that the consumption of fish is associated with a reduced risk of dementia and Alzheimer's disease.

Effects of dietary omega-3 polyunsaturated fatty acids on brain gene expression

Polyunsaturated fatty acids (PUFA) are essential structural components of the central nervous system. Their role in controlling learning and memory has been well documented. A nutrigenomic approach with high-density microarrays was used to reveal brain gene-expression changes in response to different PUFA-enriched diets in rats. In aged rats fed throughout life with PUFA-enriched diets, genes with altered expressions included transthyretin, α-synuclein, and calmodulins, which play important roles in synaptic  plasticity and learning. The effect of perinatal omega-3 PUFA supply on gene expression later in life also was studied. Several genes showed similar changes in expression in rats fed omega-3-deficient diets in the perinatal period, regardless of whether they or their mothers were fed omega-3 PUFA-sufficient diets after giving birth. In this experiment, among the down-regulated genes were a kainate glutamate receptor and a DEAD-box polypeptide. Among the up-regulated genes were a chemokine-like factor, a tumor necrosis factor receptor, and cytochrome c. The possible involvement of the genes with altered expression attributable to different diets in different brain regions in young and aged rats and the possible mode of regulatory action of PUFA also are discussed. We conclude that PUFA-enriched diets lead to significant changes in expression of several genes in the central nervous tissue, and these effects appear to be mainly independent of their effects on membrane composition. The direct effects of PUFA on transcriptional modulators, the downstream developmentally and tissue-specifically activated elements might be one of the clues to understanding the beneficial effects of the omega-3 PUFA on the nervous system.

Using accelerated, whole-of-brain learning techniques in higher education: principles and practice

Accelerated learning is an integrative method of learning, combining both sides of the brain to strengthen a student's relationship with self, teacher, subject matter and other students, and so assists students to achieve deep, rather than surface, learning. While the approach has been used to teach school pupils and trainees in the corporate world, its use in marketing education in universities is limited, and there are no reports of studies focusing on its use in postgraduate coursework degrees. Thus this paper examines how accelerated learning could be used in teaching marketing at universities at the MBA level. Some techniques are synthesised from the literature that are particularly appropriate for the students and constraints of an MBA program in a university. We conclude that accelerated learning techniques can be used and are effective in a MBA program. Essentially, accelerated learning incorporate many, already known ideas but it is a useful comprehensive framework.