Rohan L. Rasiah

Intraarterial Propofol Is Not Directly Toxic to Vascular Endothelium

To determine if accidental intraarterial injection of propofol results in vascular damage, the effect of bolus administration of propofol on vascular smooth muscle and the endothelium was investigated using the isolated rabbit ear artery. Ear artery segments, removed from urethane anesthetized rabbits, were perfused with Krebs solution (1 ml.min-1) and pressurized to 60 mmHg before being constricted with extraluminal norepinephrine (1.8-4.2 x 10(-6) M). The external diameter of the vessel was measured by an array of light-dependent diodes. Functional responsiveness was determined by the degree of constriction to norepinephrine and the subsequent dilatation of the artery to intraluminal acetylcholine (2 x 10(-6) M) and glyceryl trinitrate (2 x 10(-6) M), and by the myogenic reactivity to a pressure increase from 60 to 100 mmHg. These responses were measured before and after perfusion with 1% propofol for 120 s. Administration of propofol did not result in any vasoactivity nor did it increase the sensitivity to norepinephrine. Vessels maintained their capacity to dilate to both agents, while the myogenic activity was unaffected. Histologic examination of the propofol exposed vessels showed no changes to smooth muscle structure, and the endothelial layer remained intact.

Population pharmacokinetics of perhexiline from very sparse, routine monitoring data.

Using NONMEM, the population pharmacokinetics of perhexiline were studied in 88 patients (34 F, 54 M) who were being treated for refractory angina. Their mean ± SD (range) age was 75 ± 9.9 years (46–92), and the length of perhexiline treatment was 56 ± 77 weeks (0.3–416). The sampling time after a dose was 14.1 ± 21.4 hours (0.5–200), and the perhexiline plasma concentrations were 0.39 ± 0.32 mg/L (0.03–1.56). A one-compartment model with first-order absorption was fitted to the data using the first-order (FO) approximation. The best model contained 2 subpopulations (obtained via the

Propofol attenuates the myogenic response of vascular smooth muscle.

MIXTURE subroutine) of 77 subjects (subgroup A) and 11 subjects (subgroup B) that had typical values for clearance (CL/F) of 21.8 L/h and 2.06 L/h, respectively. The volumes of distribution (V/F) were 1470 L and 260 L, respectively, which suggested a reduction in presystemic metabolism in subgroup B. The interindividual variability (CV%) was modeled logarithmically and for CL/F ranged from 69.1% (subgroup A) to 86.3% (subgroup B). The interindividual variability in V/F was 111%. The residual variability unexplained by the population model was 28.2%. These results confirm and extend the existing pharmacokinetic data on perhexiline, especially the bimodal distribution of CL/F manifested via an inherited deficiency in hepatic and extrahepatic CYP2D6 activity.

Simplified Sizing of Low-Density Lipoprotein Using Polyacrylamide Gradient Gel Electrophoresis of Plasma

The myogenic response is the tendency of certain vessels, most notably small arteries and arterioles, to constrict in response to an increase in illtravascular pressure. The effects Of ProPofol On the myogenic response Of the isolated pressurized rabbit ear artery were studied in segments preconstricted either with norepinephrine or 5-hydroxytryptamine and subjected to pressure increases from 60 to 100 mm Hg applied either rapidly (jumps over 500 ms) or slowly (ramps Over 120 s). In the control experiments the preconstricted vessels initially dilated, then rapidly returned toward their initial diameter. In response to pressure ramps, vessels slowly dilated, but closely retained their resting diameter. Administration of propofol (1.6 × 10 −4 to 1.6 × 10−3 M) resulted in dilation of the constricted vessels. With pressure jumps vessels had a reduced capacity to recover their initial diameters, and with pressure ramps vessels dilated to greater diameters. When the concentration of vasoconstrictor was increased to antagonize the propofol-induced dilation the myogenicity was not restored. This attenuation of myogenicity, distinct from the drugs v∼sodilator effect may represent a further mechanism by which anesthetic agents can affect cardiovascular function.

Statistical moments for placental transfer of solutes in man.

Low-density lipoprotein (LDL) particles can be separated into subfractions according to size by non-denaturing polyacrylamide gradient gel electrophoresis. Established research methods require specialised equipment and are frequently unsuited to the clinical laboratory. In this study, we utilised a colour flat bed scanner in conjunction with shareware image analysis software to compare LDL particle diameters of isolated LDL with LDL in whole plasma. LDL was isolated by ultracentrifugation and electrophoresed on 3-13% gels (Gradipore; Sydney, Australia) for 2400 Volt-hours in parallel with plasma and molecular size standards. Coomassie Blue-stained gels were scanned in reflexive mode using a colour flat-bed scanner and Adobe Photoshop 3.0 software. Density traces of each lane were obtained using NIH Image software (public domain, USA). LDL particle diameters were determined from calibration curves of the log of molecular diameter of standards against migration distance. There was a good correlation between LDL particle diameters obtained using isolated LDL and whole plasma (r = 0.87, P < 0.001; n = 22). However, the group means (+/- S.D.) (24.7 +/- 0.6 and 24.8 +/- 0.5 nm respectively) were statistically different on the paired t-test (P < 0.05). It is unclear whether this numerically small difference is due to alterations in LDL during the longer preparative procedures for LDL, or to matrix effects during electrophoresis of plasma samples. In conclusion, plasma samples stained with Coomassie Blue and scanned with a colour flat bed scanner can conveniently be used for LDL particle sizing by non-denaturing polyacrylamide gradient gel electrophoresis.

Thinking in Pharmacy Practice: A Study of Community Pharmacists’ Clinical Reasoning in Medication Supply Using the Think-Aloud Method

The placental transfer of red blood cells and solutes in man has been investigated by statistical moment analysis, using the impulse‐response technique. Model compounds of different lipophilicity (sucrose, water, antipyrine, propranolol and labetalol) were injected with a vascular reference (labelled red blood cells) as boluses into either the foetal or maternal circulation of a single‐pass perfused placental lobule. Maternal and foetal venous outflow fractions were collected at intervals ranging from 1 to 600s. Perfusion was conducted at maternal flow rates of 4 and 6 mL min−1 and foetal flow rates of 2 and 3 mL min−1, respectively, to yield a constant materno‐foetal flow ratio of 2. The outflow concentration‐time profile curves were analysed by statistical moment analysis.

Gamification for Education: Designing a Pharmacy Education Game

Medication review and supply by pharmacists involves both cognitive and technical skills related to the safety and appropriateness of prescribed medicines. The cognitive ability of pharmacists to recall, synthesise and memorise information is a critical aspect of safe and optimal medicines use, yet few studies have investigated the clinical reasoning and decision-making processes pharmacists use when supplying prescribed medicines. The objective of this study was to examine the patterns and processes of pharmacists’ clinical reasoning and to identify the information sources used, when making decisions about the safety and appropriateness of prescribed medicines. Ten community pharmacists participated in a simulation in which they were required to review a prescription and make decisions about the safety and appropriateness of supplying the prescribed medicines to the patient, whilst at the same time thinking aloud about the tasks required. Following the simulation each pharmacist was asked a series of questions to prompt retrospective thinking aloud using video-stimulated recall. The simulated consultation and retrospective interview were recorded and transcribed for thematic analysis. All of the pharmacists made a safe and appropriate supply of two prescribed medicines to the simulated patient. Qualitative analysis identified seven core thinking processes used during the supply process: considering prescription in context, retrieving information, identifying medication-related issues, processing information, collaborative planning, decision making and reflection; and align closely with other health professionals. The insights from this study have implications for enhancing awareness of decision making processes in pharmacy practice and informing teaching and assessment approaches in medication supply.

Comparing Animation with Video For Teaching Communication Skills

A key motivator for the use of serious games has been the notion that “gamification” provides users with an additional level of engagement. This study examines a traditional model of usability in terms of engagement and efficacy, presenting the results obtained from a formative evaluation of a serious game prototype that has been developed to assist in pharmacy education.

Marketing of rural and remote pharmacy practice via the digital medium.

In this paper, we describe a case study that compares the use of animation and video for teaching communication skills to pharmacy students. We present an appropriate framework outlining the key communication criteria that were used to develop a three part, patient-pharmacist communication scenario. This scenario was scripted, filmed in a community pharmacy, and edited into a six minute sequence before being converted to an equivalent animation sequence by using digital filters. Both the video and animation were compared in a usability trial using 37 students studying pharmacy. These students were divided into two groups, each experiencing either the video or animation sequence before being asked to provide subjective feedback of the usefulness of the approach for teaching communication. Both the video and animation group provided equivalent positive feedback about the approach. The two groups then experienced the alternative representation, either video or animation and were asked to nominate a preference. Both groups indicated a significant preference for the video presentation. It is recognized that the design and style of the animation may impact on the general validity of these outcomes and as such the paper also provides a detailed discussion of relevant design issues.

Feasibility of establishing an early indicator for ototoxicity in children using otoacoustic emissions

Aim:  The shortage of community and hospital pharmacists is particularly acute in rural and remote areas of Australia. Pharmacy students, in particular, as those who may be able to alleviate this shortage, need to be made more aware of the challenges and rewards of rural pharmacy practice. A marketing tool was developed to promote rural and remote pharmacy practice as a career option. A DVD was produced from interviews with health professionals working in rural and remote areas of Australia. This DVD will complement current rural practical placements, which have been incorporated into the curriculum of Australian schools of pharmacy.