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1.  Remembering Dr. Frederick Griffith Pearson 
Canadian Journal of Surgery  2016;59(6):367-368.
Canada has lost a remarkable surgeon and leader. Dr. Frederick Griffith “Griff” Pearson, aged 90, died in Kitchener, Ont., on Aug. 10, 2016, surrounded by his wife, Hilppa Pearson, and his family.
PMCID: PMC5125916
2.  Validation of Airway Wall Measurements by Optical Coherence Tomography in Porcine Airways 
PLoS ONE  2014;9(6):e100145.
Examining and quantifying changes in airway morphology is critical for studying longitudinal pathogenesis and interventions in diseases such as chronic obstructive pulmonary disease and asthma. Here we present fiber-optic optical coherence tomography (OCT) as a nondestructive technique to precisely and accurately measure the 2-dimensional cross-sectional areas of airway wall substructure divided into the mucosa (WAmuc), submucosa (WAsub), cartilage (WAcart), and the airway total wall area (WAt). Porcine lung airway specimens were dissected from freshly resected lung lobes (N = 10). Three-dimensional OCT imaging using a fiber-optic rotary-pullback probe was performed immediately on airways greater than 0.9 mm in diameter on the fresh airway specimens and subsequently on the same specimens post-formalin-fixation. The fixed specimens were serially sectioned and stained with H&E. OCT images carefully matched to selected sections stained with Movat’s pentachrome demonstrated that OCT effectively identifies airway epithelium, lamina propria, and cartilage. Selected H&E sections were digitally scanned and airway total wall areas were measured. Traced measurements of WAmuc, WAsub, WAcart, and WAt from OCT images of fresh specimens by two independent observers found there were no significant differences (p>0.05) between the observer’s measurements. The same wall area measurements from OCT images of formalin-fixed specimens found no significant differences for WAsub, WAcart and WAt, and a small but significant difference for WAmuc. Bland-Altman analysis indicated there were negligible biases between the observers for OCT wall area measurements in both fresh and formalin-fixed specimens. Bland-Altman analysis also indicated there was negligible bias between histology and OCT wall area measurements for both fresh and formalin-fixed specimens. We believe this study sets the groundwork for quantitatively monitoring pathogenesis and interventions in the airways using OCT.
PMCID: PMC4064993  PMID: 24949633
3.  Expression of Matrix Metalloproteinase-1 in Alveolar Macrophages, Type II Pneumocytes, and Airways in Smokers: Relationship to Lung Function and Emphysema 
Lung  2014;192(4):467-472.
An imbalance between proteolytic enzymes and their inhibitors is thought to be involved in the pathogenesis of chronic obstructive pulmonary disease. Matrix metalloproteinase-1, also known as interstitial collagenase, has been implicated as a potentially important proteinase in the genesis of chronic obstructive pulmonary disease and, more specifically, emphysema.
We performed quantitative immunohistochemical assessment of matrix metalloproteinase-1 expression in the resected lung of 20 smokers/ex-smokers who had varying severity of airflow obstruction and emphysema and compared this with the lungs of 5 nonsmokers. Emphysema was measured using a morphometric measure of the lungs’ surface area/volume ratio and with qualitative and quantitative computed tomography (CT) measures of emphysema.
There were significantly more matrix metalloproteinase-1-expressing alveolar macrophages and type II pneumocytes as well as a greater percentage of small airways that stained positively for matrix metalloproteinase-1 in the lungs of smokers than in those of nonsmokers (p < 0.0001, p < 0.0001, and p = 0.0003, respectively). The extent of staining of type II pneumocytes and airways for matrix metalloproteinase-1 was significantly related to the extent of smoking (p = 0.012 and p = 0.013, respectively). In addition, the extent of matrix metalloproteinase-1 staining of alveolar macrophages was related to the lung surface area/volume ratio and to qualitative estimates of emphysema on CT.
These findings suggest that cigarette smoking increases expression of matrix metalloproteinase-1 in alveolar macrophages as well as in alveolar and small airway epithelial cells. Smokers who develop emphysema have increased alveolar macrophage expression of matrix metalloproteinase-1.
Electronic supplementary material
The online version of this article (doi:10.1007/s00408-014-9585-6) contains supplementary material, which is available to authorized users.
PMCID: PMC4104162  PMID: 24792232
Computed tomography; Emphysema; Expression; Immunohistochemistry; Metalloproteinase; Lung
4.  Probability of Cancer in Pulmonary Nodules Detected on First Screening CT 
The New England journal of medicine  2013;369(10):910-919.
Major issues in the implementation of screening for lung cancer by means of low-dose computed tomography (CT) are the definition of a positive result and the management of lung nodules detected on the scans. We conducted a population-based prospective study to determine factors predicting the probability that lung nodules detected on the first screening low-dose CT scans are malignant or will be found to be malignant on follow-up.
We analyzed data from two cohorts of participants undergoing low-dose CT screening. The development data set included participants in the Pan-Canadian Early Detection of Lung Cancer Study (PanCan). The validation data set included participants involved in chemoprevention trials at the British Columbia Cancer Agency (BCCA), sponsored by the U.S. National Cancer Institute. The final outcomes of all nodules of any size that were detected on baseline low-dose CT scans were tracked. Parsimonious and fuller multivariable logistic-regression models were prepared to estimate the probability of lung cancer.
In the PanCan data set, 1871 persons had 7008 nodules, of which 102 were malignant, and in the BCCA data set, 1090 persons had 5021 nodules, of which 42 were malignant. Among persons with nodules, the rates of cancer in the two data sets were 5.5% and 3.7%, respectively. Predictors of cancer in the model included older age, female sex, family history of lung cancer, emphysema, larger nodule size, location of the nodule in the upper lobe, part-solid nodule type, lower nodule count, and spiculation. Our final parsimonious and full models showed excellent discrimination and calibration, with areas under the receiver-operating-characteristic curve of more than 0.90, even for nodules that were 10 mm or smaller in the validation set.
Predictive tools based on patient and nodule characteristics can be used to accurately estimate the probability that lung nodules detected on baseline screening low-dose CT scans are malignant. (Funded by the Terry Fox Research Institute and others; number, NCT00751660.)
PMCID: PMC3951177  PMID: 24004118
5.  The use of thoracoscopy to enhance medical students’ interest and understanding of thoracic anatomy 
Annals of Thoracic Medicine  2012;7(3):145-148.
To develop a video-based educational tool designed for teaching thoracic anatomy and to examine whether this tool would increase students’ stimulation and motivation for learning anatomy.
Our video-based tool was developed by recording different thoracoscopic procedures focusing on intraoperative live thoracic anatomy. The tool was then integrated into a pre-existing program for first year medical students (n = 150), and included cadaver dissection of the thorax and review of clinical problem scenarios of the respiratory system. Students were guided through a viewing of the videotape that demonstrated live anatomy of the thorax (15 minutes) and then asked to complete a 5-point Likert-type questionnaire assessing the video's usefulness. Apart from this, a small group of entirely different set of students was divided into two groups, one group to view the 15-minute video presentation of thoracoscopy and chest anatomy and the other group to attend a 15-minute lecture of chest anatomy using radiological images. Both groups took a 10-item pretest and post-test multiple choice questions examination to assess short-term knowledge gained.
Of 150 medical students, 119 completed the questionnaires, 88.6% were satisfied with the thoracoscopic video as a teaching tool, 86.4% were satisfied with the quality of the images, 69.2% perceived it to be beneficial in learning anatomy, 96.2% increased their interest in learning anatomy, and 88.5% wanted this new teaching tool to be implemented to the curriculum. Majority (80.7%) of the students increased their interest in surgery as a future career. Post-test scores were significantly higher in the thoracoscopy group (P = 0.0175).
Incorporating live surgery using thoracoscopic video presentation in the gross anatomy teaching curriculum had high acceptance and satisfaction scores from first year medical students. The video increased students’ interest in learning, in clinically applying anatomic fact, and in surgery as a future career.
PMCID: PMC3425046  PMID: 22924072
Medical students; thoracic anatomy; thoracoscopy
6.  An Epidemic of Burkholderia cepacia Transmitted between Patients with and without Cystic Fibrosis 
The Journal of Infectious Diseases  1999;179(5):1197-1205.
Burkholderia cepacia is an important pathogen in cystic fibrosis (CF) and an infrequent cause of nosocomial infection in non-CF patients. This report describes a large hospital outbreak that appeared to involve both patient groups, a previously unrecognized phenomenon. Ribotype restriction fragment length polymorphism (RFLP) profiles and pulsed-field gel electrophoresis–resolved macrochromosomal RFLPs were analyzed, a ribotype-based phylogenic tree was constructed, and case-control and cohort studies were performed. A single dominant clone was found in both CF and non-CF groups. Phylogenic analysis suggests that it has evolved independently and that such highly transmissible strains can emerge rapidly and randomly. Acquisition risk in the CF patients was linked to hospitalization (odds ratio = 5.47, P = .0158, confidence interval = 1.28–26.86) and was associated with significantly increased mortality rates. Infection control policies must now consider this threat of transmission between non-CF and CF patients.
PMCID: PMC3325287  PMID: 10191223
7.  Donepezil Associated Bradyarrhythmia in a Patient with Dementia with Lewy Bodies (DLB) 
Dementia with Lewy bodies (DLB) is a neurodegenerative condition that results in loss of mesopontine cholinergic neurons and sympathetic deinnervation. While acetylcholinesterase inhibitors (ChE-Is) have been shown to improve cognitive and behavioral deficits in DLB, these patients may be more susceptible to bradyarrhythmetic side effects from this class of drugs due to the autonomic insufficiency associated with the disease. We present a patient who experienced a dose-dependent, symptomatic sinus bradyarrhythmia with donepezil doses at and greater than 5 mg. Due to underlying autonomic dysfunction, patients with DLB may be at increased risk of bradyarrhythmia resulting from treatment with ChE-Is.
PMCID: PMC2879079  PMID: 20505440
8.  Genetic Diversity of Trichomonas vaginalis Clinical Isolates Determined by EcoRI Restriction Fragment Length Polymorphism of Heat-Shock Protein 70 Genes 
Restriction fragment length polymorphism (RFLP) analysis using a multilocus heat-inducible cytoplasmic heat-shock protein 70 (Hsp70) hybridization probe with EcoRI-digested genomic DNA was used in molecular typing of 129 Trichomonas vaginalis isolates. Results indicate that Trichomonas organisms exhibit considerable polymorphism in their Hsp70 RFLP patterns. Analysis of seven American Type Culture Collection reference strains and 122 clinical isolates, including 84 isolates from Jackson, Mississippi, 18 isolates from Atlanta, Georgia, and 20 isolates from throughout the United States, showed 105 distinct Hsp70 RFLP pattern subtypes for Trichomonas. Phylogenetic analysis of the Hsp70 RFLP data showed that the T. vaginalis isolates were organized into two clonal lineages. These results illustrate the substantial genomic diversity present in T. vaginalis and indicate that a large number of genetically distinct Trichomonas isolates may be responsible for human trichomoniasis in the United States.
PMCID: PMC2786270  PMID: 19190222
9.  Strategic faculty recruitment increases research productivity within an academic university division 
Canadian Journal of Surgery  2009;52(5):401-406.
Research is an important mandate for academic surgical divisions. However, there is widespread concern that the current health care climate is leading to a decline in research activity. A University of British Columbia (UBC) academic surgical division attempted to address this concern by strategically recruiting PhD research scientists to prioritize research and develop collaborative research programs. The objective of our study was to determine whether this strategy resulted in increased research productivity.
We reviewed the UBC Department of Surgery database to assess research funding obtained by the Division of General Surgery for the years 1994–2004. We searched MEDLINE for peer-reviewed publications by faculty members during this period.
Research funding increased from a mean of Can$417 292 per year in the 5 years (1994/95–1998/99) before the recruitment of dedicated PhD scientists to a mean of Can$1.3 million per year in the 5 years following the recruitment strategy (1999/2000–2003/04; p = 0.012). Funding for the initial 5 years was Can$2.1 million, including 1 Canadian Institutes of Health Research (CIHR) grant. Funding increased to Can$6.8 million, including 22 CIHR grants over the subsequent 5 years (p < 0.001). Collaborative research led to the awarding of multidisciplinary grants exceeding Can$4 million with divisional members as principle or coprinciple investigators. From 1994/05 to 1998/99, the total number of peer-reviewed publications was 116 (mean 23.2, standard deviation [SD] 7 per year), increasing to 144 from 1999/2000 to 2003/04 (mean 28.8, SD 13 per year). The trend was for publications in journals with higher impact factors in the latter 5-year period.
Strategic recruitment resulted in increased and sustained research productivity. Interactions between research scientists and clinicians resulted in successful program grant funding support. These results have implications for sustaining the research mission within academic departments of surgery.
PMCID: PMC2769093  PMID: 19865575
10.  Resource Utilization and Costs during the Initial Years of Lung Cancer Screening with Computed Tomography in Canada 
Journal of Thoracic Oncology  2014;9(10):1449-1458.
It is estimated that millions of North Americans would qualify for lung cancer screening and that billions of dollars of national health expenditures would be required to support population-based computed tomography lung cancer screening programs. The decision to implement such programs should be informed by data on resource utilization and costs.
Resource utilization data were collected prospectively from 2059 participants in the Pan-Canadian Early Detection of Lung Cancer Study using low-dose computed tomography (LDCT). Participants who had 2% or greater lung cancer risk over 3 years using a risk prediction tool were recruited from seven major cities across Canada. A cost analysis was conducted from the Canadian public payer’s perspective for resources that were used for the screening and treatment of lung cancer in the initial years of the study.
The average per-person cost for screening individuals with LDCT was $453 (95% confidence interval [CI], $400–$505) for the initial 18-months of screening following a baseline scan. The screening costs were highly dependent on the detected lung nodule size, presence of cancer, screening intervention, and the screening center. The mean per-person cost of treating lung cancer with curative surgery was $33,344 (95% CI, $31,553–$34,935) over 2 years. This was lower than the cost of treating advanced-stage lung cancer with chemotherapy, radiotherapy, or supportive care alone, ($47,792; 95% CI, $43,254–$52,200; p = 0.061).
In the Pan-Canadian study, the average cost to screen individuals with a high risk for developing lung cancer using LDCT and the average initial cost of curative intent treatment were lower than the average per-person cost of treating advanced stage lung cancer which infrequently results in a cure.
PMCID: PMC4165479  PMID: 25105438
Lung cancer screening; Cost analysis; Cost-effectiveness

Results 1-10 (10)