Heather Sampson

Variation in enzymes of arylamine procarcinogen biotransformation among bladder cancer patients and control subjects.

Arylamines such as 2-naphthylamine and 4-aminobiphenyl are suspected human bladder procarcinogens that require bioactivation to DNA-reactive species to exert their carcinogenic potential. The goals of the present study were (i) to assay for the presence of the arylamine acetyltransferases NAT1 and NAT2, and of the cytochrome P450 isoform CYP1A2, in human bladder epithelium; and (ii) to determine whether the activities of these arylamine biotransforming enzymes differ between bladder cancer patients and control subjects. We measured in-vitro enzyme activities in biopsies of normal, undiseased bladder epithelium obtained from 103 bladder cancer patients. NAT1 activity was detectable in all samples, with mean levels higher than those found in human liver. Kinetic evidence also suggested low levels of NAT2 expression in this tissue, but there was no detectable CYP1A2 by either enzymatic or immunochemical measurements. We also compared several probe drug indices of in-vivo NAT1, NAT2 and CYP1A2 activity between 53 bladder cancer patients and 96 cancer-free control subjects who were carefully matched for age, gender and smoking status. NAT1 and NAT2 genotypes were also determined. No significant differences were found between bladder cancer patients and control subjects for a number of individual phenotypic or genotypic predictors of enzyme function. Our results suggest that although expression of particular arylamine biotransforming enzymes within the bladder tissue could play a significant role in locally bioactivating arylamine procarcinogens in theory, interindividual variations in CYP1A2, NAT1 and NAT2 activities do not significantly differ between bladder cancer patients and control subjects when potential arylamine exposures are controlled for

Electromotive Drug Administration of Lidocaine as an Alternative Anesthesia for Transurethral Surgery

PURPOSE A multicenter study was undertaken to evaluate the safety, efficacy and cost of electromotive drug administration of intravesical lidocaine to produce bladder local anesthesia as an alternative to traditional methods of spinal or general anesthesia. MATERIALS AND METHODS A total of 94 patients were enrolled in the study who had either a history of bladder tumor that required cold cup bladder biopsy with fulguration for possible recurrence as a comparison trial, a bladder tumor treated with transurethral resection/fulguration or benign prostatic hyperplasia/carcinoma treated with transurethral resection. Pain scores using a Verbal Rating Scale were recorded for each individual biopsy, fulguration and resection event. Data for direct and indirect costs were collected using a standardized form for each patient to capture the details of the procedure, including times, drugs and disposables for each patient. RESULTS There was a significant reduction in pain for patients who received electromotive intravesical lidocaine compared to no anesthesia for biopsy (p<0.03). Similarly, electromotive intravesical lidocaine for bladder biopsy and transurethral bladder tumor resection/fulguration was associated with higher patient satisfaction compared to previous treatments (p<0.00002). In contrast, electromotive intravesical lidocaine was insufficient for 3 of 6 transurethral prostatic resections. The cost per patient was about

What makes public health studies ethical? Dissolving the boundary between research and practice

146 Cdn less with electromotive intravesical lidocaine than with conventional general/spinal anesthesia. CONCLUSIONS Electromotive intravesical lidocaine may be a safe, effective and affordable form of anesthesia for the ambulatory care of patients requiring transurethral bladder biopsy, resection or fulguration with a potential for cost savings.

Resource development in otolaryngology-head and neck surgery: an analysis on patient education resource development.

BackgroundThe generation of evidence is integral to the work of public health and health service providers. Traditionally, ethics has been addressed differently in research projects, compared with other forms of evidence generation, such as quality improvement, program evaluation, and surveillance, with review of non-research activities falling outside the purview of the research ethics board. However, the boundaries between research and these other evaluative activities are not distinct. Efforts to delineate a boundary – whether on grounds of primary purpose, temporality, underlying legal authority, departure from usual practice, or direct benefits to participants – have been unsatisfactory.Public Health Ontario has eschewed this distinction between research and other evaluative activities, choosing to adopt a common framework and process to guide ethical reflection on all public health evaluative projects throughout their lifecycle – from initial planning through to knowledge exchange.DiscussionThe Public Health Ontario framework was developed by a working group of public health and ethics professionals and scholars, in consultation with individuals representing a wide range of public health roles. The first part of the framework interprets the existing Canadian research ethics policy statement (commonly known as the TCPS 2) through a public health lens. The second part consists of ten questions that guide the investigator in the application of the core ethical principles to public health initiatives.The framework is intended for use by those designing and executing public health evaluations, as well as those charged with ethics review of projects. The goal is to move toward a culture of ethical integrity among investigators, reviewers and decision-makers, rather than mere compliance with rules. The framework is consonant with the perspective of the learning organization and is generalizable to other public health organizations, to health services organizations, and beyond.SummaryPublic Health Ontario has developed an ethics framework that is applicable to any evidence-generating activity, regardless of whether it is labelled research. While developed in a public health context, it is readily adaptable to other health services organizations and beyond.

Research ethics by design: A collaborative research design proposal

BackgroundThere is a need for educational tools in the consenting process of otolaryngology-head and neck procedures. A development strategy for the creation of educational tools in otolaryngology-head and neck surgery, particularly pamphlets on the peri-operative period in an adenotonsillectomy, is described.MethodsA participatory design approach, which engages key stakeholders in the development of an educational tool, is used. Pamphlets were created through a review of traditional and grey literature and then reviewed by a community expert in the field. The pamphlets were then reviewed by an interdisciplinary team including educational experts, and finally by less vulnerable members of the target population. Questionnaires evaluating the pamphlets’ content, layout, style, and general qualitative features were included.ResultsThe pamphlets yielded high ratings across all domains regardless of patient population. General feedback was provided by a non-vulnerable patient population and final pamphlets were drafted.ConclusionsBy using a participatory design model, the pamphlets are written at an appropriate educational level to incorporate a broad audience. Furthermore, this methodology can be used in future resource development of educational tools.

Allelic Deletion Fingerprinting of Urine Cell Sediments in Bladder Cancer

Privacy by Design, a globally accepted framework for personal data management and privacy protection, advances the view that privacy cannot be assured solely by compliance with regulatory frameworks but must become an organisation’s default mode of operation. We are proposing a similar template for the research ethics review process. The Research Ethics by Design framework involves research ethics committees engaging researchers during the design phase of the proposal so that ethical considerations may be directly embedded in the science as opposed to being viewed as addendums after the fact. This collaborative research design proposal results in the establishment of a culture of ethical research rather than research with ethical oversight. Both researchers and research ethics committees come to view the review process as one in which individual protection and collective benefit co-exist in a doubly-enabling positive-sum manner.