Management of postoperative nausea and vomiting: focus on palonosetron

Postoperative nausea and vomiting (PONV) remains a significant problem in modern anesthetic practice, with an incidence in high-risk groups of up to 80%. In addition to being unpleasant and distressing for the patient, PONV has the potential to adversely affect patient and surgical outcomes. Advances in PONV prophylaxis over recent years include using non-pharmacological means to reduce baseline risk, a change to less emetogenic anesthetic techniques and the combination of multiple antiemetic drugs. The 5-hydroxytryptamine-3 (5-HT3) antagonists have proven a particularly valuable addition to the armamentarium against PONV. Palonosetron is a second-generation 5-HT3 antagonist that has recently been approved for prophylaxis against PONV. It has unique structural, pharmacological and clinical properties that distinguish it from other agents in its class. This review summarizes current evidence on PONV prophylaxis, reviews the 5-HT3 antagonists in particular and focuses on the established and future roles of palonosetron

Talking Change - A comparative narrative analysis of language use amongst external consultants and internal change agents in delivering organisational change.

This paper reports an investigation into the existence of material differences between the respective approaches to change management of consultants and corporate managers. The narrative accounts proffered by participants are examined in three primary dimensions, sensemaking, sensegiving and overcoming resistance to change. Relationships between these dimensions are explored and an effort at establishing best practice approaches is made

Spreading of trisiloxanes over thin aqueous layers

Surfactants are widely spread in nature and are increasingly used in industry as wetting, cleaning and disinfecting agents. Recently, there are newly discovered trisiloxane and other silicone based surfactants which show very unusual spreading behaviour. Although a number of experimental and theoretical investigations have been carried out, the underlying spreading mechanism remains unclear. Experiments using trisiloxanes and comparison with 3 different ethylene glycol monododecyl ethers (C12E4, C12E5, and C12E6) surfactants were performed to understand the influence of Marangoni force as the driving force for the spreading. We then compared our experimental results to available theoretical prediction in the literature. The obtained experimental data showed the opposite trend as compared with the theoretical predictions developed for a regular surfactants. The latter is assumed to be a special feature of “suprspreaders”

Structural and Functional Analyses of Liver Cysts from the BALB/c-cpk Mouse Model of Polycystic Kidney Disease

Liver cysts arising from hepatic bile ducts are a common extra-renal pathology associated with both autosomal dominant and recessive polycystic kidney disease in humans. To elucidate the functional and structural changes inherent in cyst formation and growth, hepatic bile duct epithelia were isolated from the BALB/ c-cpk mouse model of polycystic kidney disease. Light and transmission electron microscopy revealed substantial fibrosis in the basal lamina surrounding hepatic bile duct cysts isolated from heterozygous (BALB/c-cpk/+) and homozygous (BALB/c-cpk/cpk) animals. Scanning electron microscopy and length analysis of normal, precystic and cystic bile ducts provided the unique observation that primary cilia in cholangiocytes isolated from bile ducts and cysts of animals expressing the mutated cpk gene had lengths outside the minimal and maximal ranges of those in cells lining bile ducts of wild-type animals. Based on the hypothesis that PKD is one of several diseases characterized as ciliopathies, this abnormal variability in the length of the primary cilia may have functional implications. Electrophysiological analyses of freshly isolated cysts indicate that the amiloride-sensitive epithelial Na(+) channel (ENaC) is inactive/absent and cAMP-mediated anion secretion is the electrogenic transport process contributing to cyst fluid accumulation. Anion secretion can be stimulated by the luminal stimulation of adenylyl cyclase

5-hydroxytryptamine (5-HT) cellular sequestration during chronic exposure delays 5-HT₃ receptor resensitization due to Its subsequent release

The serotonergic synapse is dynamically regulated by serotonin (5-hydroxytryptamine (5-HT)) with elevated levels leading to the down-regulation of the serotonin transporter and a variety of 5-HT receptors, including the 5-HT type-3 (5-HT(3)) receptors. We report that recombinantly expressed 5-HT(3) receptor binding sites are reduced by chronic exposure to 5-HT (IC(50) of 154.0 ± 45.7 μm, t(½) = 28.6 min). This is confirmed for 5-HT(3) receptor-induced contractions in the guinea pig ileum, which are down-regulated after chronic, but not acute, exposure to 5-HT. The loss of receptor function does not involve endocytosis, and surface receptor levels are unaltered. The rate and extent of down-regulation is potentiated by serotonin transporter function (IC(50) of 2.3 ± 1.0 μm, t(½) = 3.4 min). Interestingly, the level of 5-HT uptake correlates with the extent of down-regulation. Using TX-114 extraction, we find that accumulated 5-HT remains soluble and not membrane-bound. This cytoplasmically sequestered 5-HT is readily releasable from both COS-7 cells and the guinea pig ileum. Moreover, the 5-HT level released is sufficient to prevent recovery from receptor desensitization in the guinea pig ileum. Together, these findings suggest the existence of a novel mechanism of down-regulation where the chronic release of sequestered 5-HT prolongs receptor desensitization

A History of Drug Discovery for Treatment of Nausea and Vomiting and the Implications for Future Research.

The origins of the major classes of current anti-emetics are examined. Serendipity is a recurrent theme in discovery of their anti-emetic properties and repurposing from one indication to another is a continuing trend. Notably, the discoveries have occurred against a background of company mergers and changing anti-emetic requirements. Major drug classes include: (i) Muscarinic receptor antagonists-originated from historical accounts of plant extracts containing atropine and hyoscine with development stimulated by the need to prevent sea-sickness among soldiers during beach landings; (ii) Histamine receptor antagonists-searching for replacements for the anti-malaria drug quinine, in short supply because of wartime shipping blockade, facilitated the discovery of histamine (H1) antagonists (e.g., dimenhydrinate), followed by serendipitous discovery of anti-emetic activity against motion sickness in a patient undergoing treatment for urticaria; (iii) Phenothiazines and dopamine receptor antagonists-investigations of their pharmacology as "sedatives" (e.g., chlorpromazine) implicated dopamine receptors in emesis, leading to development of selective dopamine (D2) receptor antagonists (e.g., domperidone with poor ability to penetrate the blood-brain barrier) as anti-emetics in chemotherapy and surgery; (iv) Metoclopramide and selective 5-hydroxytryptamine3(5-HT3) receptor antagonists-metoclopramide was initially assumed to act only via D2 receptor antagonism but subsequently its gastric motility stimulant effect (proposed to contribute to the anti-emetic action) was shown to be due to 5-hydroxytryptamine4 receptor agonism. Pre-clinical studies showed that anti-emetic efficacy against the newly-introduced, highly emetic, chemotherapeutic agent cisplatin was due to antagonism at 5-HT3 receptors. The latter led to identification of selective 5-HT3 receptor antagonists (e.g., granisetron), a major breakthrough in treatment of chemotherapy-induced emesis; (v) Neurokinin1receptor antagonists-antagonists of the actions of substance P were developed as analgesics but pre-clinical studies identified broad-spectrum anti-emetic effects; clinical studies showed particular efficacy in the delayed phase of chemotherapy-induced emesis. Finally, the repurposing of different drugs for treatment of nausea and vomiting is examined, particularly during palliative care, and also the challenges in identifying novel anti-emetic drugs, particularly for treatment of nausea as compared to vomiting. We consider the lessons from the past for the future and ask why there has not been a major breakthrough in the last 20 years

Talking Change - A comparative narrative analysis of language use amongst external consultants and internal change agents in delivering organisational change.

This paper reports an investigation into the existence of material differences between the respective approaches to change management of consultants and corporate managers. The narrative accounts proffered by participants are examined in three primary dimensions, sensemaking, sensegiving and overcoming resistance to change. Relationships between these dimensions are explored and an effort at establishing best practice approaches is made

Students’ expectations of teaching: the business, accounting and economics experience

This paper reports on a study aimed at exploring student perceptions of teaching and learning in the disciplines of business, accounting and economics. Twenty-three students from two Sydney-based faculties were interviewed and their responses analysed qualitatively. Their educational expectations are articulated in five major pedagogical themes including delivering and presenting a lesson, encouraging class participation, providing academic feedback, the dilemma between structured and discussion-based tutorials, and the dynamics of learning through group work. Students’ responses reveal that they have strong and clear expectations about quality teaching, although some dissonances from the educational theory were identified with respect to exam-driven learning and over-emphasis of work-readiness oriented instruction. Implications for enacting quality teaching, curriculum delivery and design are discussed