Steven Burr

Occurrence and Risk of Cochleotoxicity in Cystic Fibrosis Patients Receiving Repeated High-Dose Aminoglycoside Therapy

ABSTRACT Cystic fibrosis (CF) patients receive repeated courses of aminoglycoside therapy. These patients would consequently be expected to be more susceptible to cochleotoxicity, a recognized side effect with single courses of aminoglycoside therapy. The primary aim of this retrospective study was to establish the incidence and severity of auditory deficit in CF patients. Standard (0.25- to 8-kHz) and high-frequency (10- to 16-kHz) pure-tone audiometry was carried out in 70 CF patients, and the results were compared with the results from 91 control subjects. These subjects were further divided into pediatric and adult groups. Of 70 CF patients, 12 (1 pediatric) displayed hearing loss considered to be caused by repeated exposure to aminoglycosides. There was a nonlinear relationship between the courses of therapy received and the incidence of hearing loss. The severity of the loss did not appear to be related to the number of courses received. Assuming the risk of loss to be independent for each course, preliminary estimates of per course risk of hearing loss were less than 2%. Upon comparison with previous clinical studies and experimental work, these findings suggest that the incidence of cochleotoxicity in CF patients is considerably lower than would be expected, suggesting that the CF condition may confer protection against aminoglycoside cochleotoxicity.

Cytotoxicity, cell cycle arrest, and apoptosis in breast cancer cell lines exposed to an extract of the seed kernel of Mangifera pajang (bambangan).

An extract of Mangifera pajang kernel has been previously found to contain a high content of antioxidant phytochemicals. The present research was conducted to investigate the anticancer potential of this kernel extract. The results showed that the kernel crude extract induced cytotoxicity in MCF-7 (hormone-dependent breast cancer) cells and MDA-MB-231 (non-hormone dependent breast cancer) cells with IC50 values of 23 and 30.5 microg/ml, respectively. The kernel extract induced cell cycle arrest in MCF-7 cells at the sub-G1 (apoptosis) phase of the cell cycle in a time-dependent manner. For MDA-MB-231 cells, the kernel extract induced strong G2-M arrest in cell cycle progression at 24h, resulting in substantial sub-G1 (apoptosis) arrest after 48 and 72 h of incubation. Staining with Annexin V-FITC and propidium iodide revealed that this apoptosis occurred early in both cell types, 36 h for MCF-7 cells and 24 h for MDA-MB-231 cells, with 14.0% and 16.5% of the cells respectively undergoing apoptosis at these times. This apoptosis appeared to be dependent on caspase-2 and -3 in MCF-7 cells, and on caspase-2, -3 and -9 in MDA-MB-231 cells. These findings suggest that M. pajang kernel extract has potential as a potent cytotoxic agent against breast cancer cell lines.

Cytotoxicity and polyphenol diversity in selected parts of Mangifera pajang and Artocarpus odoratissimus fruits

Purpose – Research on cancer chemopreventive properties of fruits has increased in recent years. Polyphenols have been suggested to exert such effects. The purpose of this paper is to determine the cytotoxic activity of Mangifera pajang (bambangan) and Artocarpus odoratissimus (tarap) crude extracts against selected cancer cell lines (i.e. ovarian, liver and colon cancer) and to compare the amount of selected polyphenols (phenolic acids, flavanones, flavonols and flavones) in the kernel, peel and flesh of M. pajang; and the seed and flesh of A. odoratissimus.Design/methodology/approach – Cytotoxicity activity of the extracts are investigated using MTT (3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide) assay while polyphenols are determined using high performance liquid chromatography.Findings – The results show that only the kernel and peel extracts from M. pajang display cytotoxic activity in liver and ovarian cancer cell lines with IC50 values ranging from 34.5 to 92.0  μg/ml. The proliferat...

Increasing or decreasing nervous activity modulates the severity of the glio-vascular lesions of 1,3-dinitrobenzene in the rat : effects of the tremorgenic pyrethroid, bifenthrin, and of anaesthesia

Abstract To test the hypothesis that altered neuronal activity may influence the extent and severity of the glio-vascular lesions produced by 1,3-dinitrobenzene (DNB), rats were either given the tremorgenic pyrethroid, Bifenthrin, or anaesthetised during various dosing schedules of DNB. When compared with controls dosed only with DNB, Bifenthrin tremor made both the ataxia and other functional effects caused by DNB more pronounced. Lesions in the brain stem were made significantly more severe and widespread across three dose levels of DNB. Centres such as facial nuclei, motor nuclei of fifth nerve, subthalamic nuclei and mamillary bodies, not damaged by DNB alone, were also affected in some animals. In contrast, general anaesthesia by either isoflurane ur urethane decreased the severity of the lesions, this being more pronounced with urethane. The character of the tissue changes, however, was not altered by these additional procedures. These findings support the suggestion that neuronal activity is one important determinant of the selective vulnerability of sensitive brain stem nuclei to glio-vascular damage from DNB intoxication.

Group in-course assessment promotes cooperative learning and increases performance.

The authors describe and evaluate a method to motivate medical students to maximize the effectiveness of dissection opportunities by using In‐Course‐Assessments (ICAs) to encourage teamwork. A students final mark was derived by combining the group dissection mark, group mark for questions, and their individual question mark. An analysis of the impact of the ICA was performed by comparing end of module practical summative marks in student cohorts who had, or had not, participated in the ICAs. Summative marks were compared by two‐way ANOVA followed by Dunnets test, or by repeated measures ANOVA, as appropriate. A cohort of medical students was selected that had experienced both practical classes without (year one) and with the new ICA structure (year two). Comparison of summative year one and year two marks illustrated an increased improvement in year two performance in this cohort. A significant increase was also noted when comparing this cohort with five preceding year two cohorts who had not experienced the ICAs (P <0.0001). To ensure that variation in the practical summative examination was not impacting on the data, a comparison was made between three cohorts who had performed the same summative examination. Results show that students who had undertook weekly ICAs showed significantly improved summative marks, compared with those who did not (P <0.0001). This approach to ICA promotes engagement with learning resources in an active, team‐based, cooperative learning environment. Anat Sci Educ 7: 224–233.

Cellular assessment of the extract of bambangan (Mangifera pajang) as a potential cytoprotective agent for the human hepatocellular HepG2 cell line.

This study was conducted to investigate the potential of bambangan (Mangifera pajang) fruit extracts in the protection against oxidative damage caused by tert-butyl hydroperoxide in the human hepatocellular HepG2 cell line. Proteins which might be involved in the cytoprotective mechanism were investigated using western blotting technique. Quercetin was used as a positive control. The results showed that only the kernel extract of M. pajang and quercetin displayed cytoprotective activity in HepG2 cells, with EC(50) values of 1.2 and 5.3μg/ml, respectively. Expression of quinone reductase, glutathione reductase and methionine sulfoxide reductase A proteins were significantly up-regulated by quercetin, suggesting their involvement in the cytoprotective activity of quercetin. However, expressions of only glutathione reductase and methionine sulfoxide reductase A proteins were significantly up-regulated by the kernel extract, again suggesting their involvement in the cytoprotective activity of bambangan kernel extract. Future study is needed to investigate the involvement of other cytoprotective proteins in the cytoprotection mechanism.

Delivery and use of individualised feedback in large class medical teaching.

BackgroundFormative feedback that encourages self-directed learning in large class medical teaching is difficult to deliver. This study describes a new method, blueprinted feedback, and explores learner’s responses to assess its appropriate use within medical science teaching.MethodsMapping summative assessment items to their relevant learning objectives creates a blueprint which can be used on completion of the assessment to automatically create a list of objectives ranked by the attainment of the individual student. Two surveys targeted medical students in years 1, 2 and 3. The behaviour-based survey was released online several times, with 215 and 22 responses from year 2, and 187, 180 and 21 responses from year 3. The attitude-based survey was interviewer-administered and released once, with 22 responses from year 2 and 3, and 20 responses from year 1.Results88-96% of learners viewed the blueprinted feedback report, whilst 39% used the learning objectives to guide further learning. Females were significantly more likely to revisit learning objectives than males (p = 0.012). The most common reason for not continuing learning was a ‘hurdle mentality’ of focusing learning elsewhere once a module had been assessed.ConclusionsBlueprinted feedback contains the key characteristics required for effective feedback so that with further education and support concerning its use, it could become a highly useful tool for the individual and teacher.

A double-blind atropine trial for active learning of autonomic function

Here, we describe a human physiology laboratory class measuring changes in autonomic function over time in response to atropine. Students use themselves as subjects, generating ownership and self-interest in the learning as well as directly experiencing the active link between physiology and pharmacology in people. The class is designed to concomitantly convey the importance of bias in experimentation by adopting a double-blind placebo-controlled approach. We have used this class effectively in various forms with ∼600 students receiving atropine over the last 16 yr. This class has received favorable feedback from staff and students of medicine, pharmacy, and neuroscience, and we recommend it for such undergraduates. The learning objectives that students are expected to achieve are to be able to 1) know the ethical, safety, and hygiene requirements for using human volunteers as subjects; 2) implement and explain a double-blind placebo-controlled trial; 3) design, agree, and execute a protocol for making (and accurately recording) precise reproducible measurements of pulse rate, pupil diameter, and salivary flow; 4) evaluate the importance of predose periods and measurement consistency to detect effects (including any reversibility) after an intervention; 5) experience direct cause-and-effect relationships integrating physiology with pharmacology in people; 6) calculate appropriate summary statistics to describe the data and determine the datas statistical significance; 7) recognize normal variability both within and between subjects in baseline physiological parameters and also recognize normal variability in response to pharmacological treatment; 8) infer the distribution and role of muscarinic receptors in the autonomic nervous system with respect to the heart, eye, and mouth; 9) identify and explain the clinical significance of differences in effect due to the route and formulation of atropine; 10) produce and deliver a concise oral presentation of experimental findings; and 11) produce a written report in the form of a short scientific research article. The results of a typical study are presented, which demonstrate that the administration of atropine by a subcutaneous injection elicited a significant increase in pulse rate and pupil diameter and a significant decrease in salivary flow, whereas administration of atropine in an oral liquid elicited significant effects on pulse rate and salivary flow, and an oral solid format elicited a significant alteration in salivary flow alone. More detailed analysis of the salivary flow data demonstrated clear differences between the routes of administration and formulation in the onset and magnitude of action of atropine.

Accounting for test reliability in student progression: the reliable change index

Developed by Jacobson and Truax, the reliable change index (RCI) provides a measure of whether the change in an individuals score over time is within or beyond that which might be accounted for by measurement variability. In combination with measures of whether an individuals final score is closer to those of one population or another, this provides useful individual‐level information that can be used to supplement traditional analyses.

Twelve tips for assessment psychometrics

Abstract It is incumbent on medical schools to show, both to regulatory bodies and to the public at large, that their graduating students are “fit for purpose” as tomorrow’s doctors. Since students graduate by virtue of passing assessments, it is vital that schools quality assure their assessment procedures, standards, and outcomes. An important part of this quality assurance process is the appropriate use of psychometric analyses. This begins with development of an empowering, evidence-based culture in which assessment validity can be demonstrated. Preparation prior to an assessment requires the establishment of appropriate rules, test blueprinting and standard setting. When an assessment has been completed, the reporting of test results should consider reliability, assessor, demographic, and long-term analyses across multiple levels, in an integrated way to ensure the information conveyed to all stakeholders is meaningful.