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Uwomj Volume 76, No. 1, Western University

University of Western Ontario Medical Journal

Schulich School of Medicine & Dentistry

Esophageal Cancer, Edward Yu

Oncology Publications

No abstract provided.

Cholecystectomy Deferral In Patients With Endoscopic Sphincterotomy, Vivian Mcalister, Eric Davenport, Elizabeth Renouf

Surgery Publications

BACKGROUND: Cholecystectomy is not required in up to 64% of patients who adopt a wait-and-see policy after endoscopic clearance of common bile duct stones. Although reports of retrospective cohort series have shown a higher mortality among patients who defer cholecystectomy, it is not known if this is due to the patients' premorbid health status or due to the deferral of cholecystectomy. Randomised clinical trials of prophylactic cholecystectomy versus wait-and-see have not had sufficient power to demonstrate differences in survival.

OBJECTIVES: To evaluate the beneficial and harmful effects of cholecystectomy deferral (wait-and-see) versus elective (prophylactic) cholecystectomy in patients who have had …

Altered Placental And Fetal Expression Of Igfs And Igf-Binding Proteins Associated With Intrauterine Growth Restriction In Fetal Sheep During Early And Mid-Pregnancy., Barbra De Vrijer, Meredith L Davidsen, Randall B Wilkening, Russell V Anthony, Timothy Regnault

Paediatrics Publications

The insulin-like growth factors (IGFs) are postulated to be altered in association with the development of intrauterine growth restriction (IUGR). The present studies examined placental and fetal hepatic mRNA concentration of components of the IGF system at two time points (55 and 90 d gestational age, dGA; Term 147 dGA) in a hyperthermia (HT)-induced sheep model of placental insufficiency-IUGR. Maternal plasma insulin and IGF-I were constant at 55 and 90 dGA and were unaffected by treatment. Umbilical vein insulin concentrations tended to be reduced at 90 dGA following HT exposure. Caruncle IGF-I mRNA was increased at 90 dGA in HT …

In Search Of The Anglophone Doctor In Jacques Ferron’S Story “Le Petit William”, Vivian C. Mcalister, Christiane I. Mcalister

Surgery Publications

The story of ‘Le Petit William’ (Contes anglais, 1964) is based on Ferron’s experiences as a general practitioner in the Gaspé in 1946. A medical event, use of the maternal left lateral position by a sage-femme to deliver a baby boy, becomes allegory. The sage-femme had learned the technique from a visiting Anglophone doctor. A simple joke, which superficially appears to be the story’s culmination, takes on a sombre political tone when considered in the light of the Latin epigraph. Trips to the Gaspé, a review of the history of obstetrics and speculation are used in this paper to understand …

Na+/K+ -Atpase Regulates Tight Junction Formation And Function During Mouse Preimplantation Development., Michelle I Violette, Pavneesh Madan, Andrew J Watson

Obstetrics & Gynaecology Publications

Research applied to the early embryo is required to effectively treat human infertility and to understand the primary mechanisms controlling development to the blastocyst stage. The present study investigated whether the Na(+)/K(+)-ATPase regulates tight junction formation and function during blastocyst formation. To investigate this hypothesis, three experimental series were conducted. The first experiments defined the optimal dose and treatment time intervals for ouabain (a potent and specific inhibitor of the Na(+)/K(+)-ATPase) treatment. The results demonstrated that mouse embryos maintained a normal development to the blastocyst stage following a 6-h ouabain treatment. The second experiments investigated the effects of ouabain treatment …

The Role Of Radiation Therapy On Medically Inoperable Clinically Localized Non-Small Cell Lung Patients: London Regional Cancer Program (Lrcp) Clinical Experience, Michael Lee, Edward Yu, Robert Ash, Patricia Tai, Larry Stitt, George Rodrigues, Rashid Dar, Mark Vincent, Richard Inculet, Richard Malthaner

Oncology Presentations

Lung cancer is the most frequent cause of cancer death in both men and women in North America. In 2006, an estimated 22,700 Canadians will be diagnosed with lung cancer and 19,300 will die of it (Canadian Cancer Statistics 2006).

Approximately 15-20% of NSCLC patients present with early or localized disease.

Surgical resection of T1-2N0 NSCLC remains the treatment of choice for this population, and results in a 5-year survival rate of 50-70%.

Patients deemed medically inoperable have been treated with non-surgical therapies, such as radiation therapy(RT), while some patients have simply been observed without any tumor therapy because of …

Cyclosporin Versus Tacrolimus For Liver Transplanted Patients, Elizabeth Haddad, Vivian Mcalister, Elizabeth Renouf, Richard Malthaner, Mette S. Kjaer, Lise Lotte Gluud

Surgery Publications

A systematic review of randomized clinical trials (RCT) was undertaken to evaluate the beneficial and harmful effects of immunosuppression with cyclosporin versus tacrolimus for liver transplanted patients. MEDLINE, EMBASE, Cochrane Central and Hepato-Biliary Group Controlled Trials Registers were searched. Using fixed and random effects model, relative risk (RR), values <1 favoring>tacrolimus, with 95% confidence intervals (CI) were calculated. Of 717 potentially relevant references, 16 RCTs were eligible for inclusion. Mortality and graft loss at 1 year were significantly reduced in tacrolimus-treated recipients (Death: RR 0.85, 95% CI 0.73-0.99; graft loss: RR 0.73, 95% CI 0.61-0.86). Tacrolimus reduced the number of recipients …

Body Contouring After Massive Weight Loss, Edited By A. Aly, Vivian Mcalister

Data and Test Instruments

Nowhere is the failure of the health care system, as currently managed, more evident than in the surgical care of obesity. A marked contrast has emerged between surgery in the United States and Canada for these patients. It is not clear whether the reluctance to supply surgical services in Canada is due to a bias in favour of “more deserving” patients or whether the considerably higher rate of obesity surgery in the US is due to the excesses of private enterprise. Governments have acknowledged that an element of the former proposition is true by referring obese patients to centres in …

Placental Expression Of Angiopoietin-1, Angiopoietin-2 And Tie-2 During Placental Development In An Ovine Model Of Placental Insufficiency-Fetal Growth Restriction., Amy S Erickson Hagen, Ryan J Orbus, Randall B Wilkening, Timothy Regnault, Russell V Anthony

Paediatrics Publications

Fetal growth restriction (FGR) is associated with increased perinatal morbidity and mortality, and often results from functional placental insufficiency. Placentation requires extensive vasculogenesis and subsequent angiogenesis, in both maternal and fetal tissues. Angiopoietin-1 (Ang-1) and Angiopoietin-2 (Ang-2) are angiogenic growth factors expressed in the placenta, and compete for binding to a common receptor, Tunica interna endothelial cell kinase-2 (Tie-2). Our objective was to examine Ang-1, Ang-2 and Tie-2 expression in ovine placental tissue obtained from normal and FGR pregnancies throughout gestation. Fetal cotyledon and maternal caruncle tissue concentrations of Ang-1, Ang-2 and Tie-2 mRNA were assessed by real-time reverse transcriptase-polymerase …

Roles Of Na,K-Atpase In Early Development And Trophectoderm Differentiation., Gerald M Kidder, Andrew J Watson

Obstetrics & Gynaecology Publications

Before implantation into the uterine wall, the mammalian embryo undergoes a period of cell division, cell shape change, and cell differentiation leading to the formation of an outer epithelium, the trophectoderm. The trophectoderm is the part of the embryo that initiates uterine contact and, after transformation to become the trophoblast, uterine invasion. Similar to the kidney nephron, the trophectoderm is a transporting epithelium with distinct apical and basolateral membrane domains; its function is to facilitate transepithelial Na+ and fluid transport for blastocoel formation. That transport is driven by Na,K-adenosine triphosphatase (ATPase) localized in basolateral membranes of the trophectoderm. Preimplantation embryos …

Clinical Kidney Transplantation: A 50th Anniversary Review Of The First Reported Series, Vivian Charles Mcalister

Surgery Publications

BACKGROUND: Histories of kidney transplantation rarely mention a series reported by Gordon Murray of Toronto and published by the American Journal of Surgery 50 years ago.

METHODS: The papers and biographies of Gordon Murray were reviewed in the context of knowledge at that time about renal failure management to determine their contribution to transplantation research and to current practice.

RESULTS: Murray proceeded from a unique leadership position in vascular surgery, anticoagulation therapy, and dialysis to undertake a rational series of animal experiments and human trials of kidney transplantation that led him to the practices of graft irrigation, cold storage, pelvic …

P38 Mitogen-Activated Protein Kinase (Mapk) First Regulates Filamentous Actin At The 8-16-Cell Stage During Preimplantation Development., Andrew J M Paliga, David R Natale, Andrew J Watson

Obstetrics & Gynaecology Publications

BACKGROUND INFORMATION: The MAPK (mitogen-activated protein kinase) superfamily of proteins consists of four separate signalling cascades: the c-Jun N-terminal kinase or stress-activated protein kinases (JNK/SAPK); the ERKs (extracellular-signal-regulated kinases); the ERK5 or big MAPK1; and the p38 MAPK group of protein kinases, all of which are highly conserved. To date, our studies have focused on defining the role of the p38 MAPK pathway during preimplantation development. p38 MAPK regulates actin filament formation through the downstream kinases MAPKAPK2/3 (MAPK-activated protein kinase 2/3) or MAPKAPK5 [PRAK (p38 regulated/activated kinase)] and subsequently through HSP25/27 (heat-shock protein 25/27). We recently reported that 2-cell-stage murine …

Mitogen-Activated Protein Kinase (Mapk) Blockade Of Bovine Preimplantation Embryogenesis Requires Inhibition Of Both P38 And Extracellular Signal-Regulated Kinase (Erk) Pathways., Pavneesh Madan, Michele D Calder, Andrew J Watson

Obstetrics & Gynaecology Publications

Blastocyst formation, as a critical period during development, is an effective indicator of embryonic health and reproductive efficiency. Out of a number of mechanisms underlying blastocyst formation, highly conserved mitogen-activated protein kinase (MAPK) signaling has emerged as a major mechanism involved in regulating murine preimplantation embryo development. The objective of our study was to ascertain the role of MAPK signaling in regulating bovine development to the blastocyst stage. Using reverse transcriptase PCR and immunohistochemical staining procedures we have demonstrated that mRNA transcripts and polypeptides encoding p38 MAPK pathway constituents are detectable in preimplantation bovine embryos from the one-cell to the …

Investigating The Causes Of Low Birth Weight In Contrasting Ovine Paradigms., J M Wallace, Timothy Regnault, S W Limesand, W W Hay, R V Anthony

Paediatrics Publications

Intrauterine growth restriction (IUGR) still accounts for a large incidence of infant mortality and morbidity worldwide. Many of the circulatory and transport properties of the sheep placenta are similar to those of the human placenta and as such, the pregnant sheep offers an excellent model in which to study the development of IUGR. Two natural models of ovine IUGR are those of hyperthermic exposure during pregnancy, and adolescent overfeeding, also during pregnancy. Both models yield significantly reduced placental weights and an asymmetrically growth-restricted fetus, and display altered maternal hormone concentrations, indicative of an impaired trophoblast capacity. Additionally, impaired placental angiogenesis …

Effect Of Serum And Cumulus Cell Expansion On Marker Gene Transcripts In Bovine Cumulus-Oocyte Complexes During Maturation In Vitro., Michele D Calder, Anita N Caveney, Marc-Andre Sirard, Andrew J Watson

Obstetrics & Gynaecology Publications

OBJECTIVE: To determine the distribution of transcripts encoding the FSH receptor (FSHr), LH receptor (LHr), connexin 43 (Cx43), cyclooxygenase-2 (COX-2), and prostaglandin E(2) receptors 2 and 3 (EP2 and EP3) within bovine cumulus-oocyte complexes (COCs) and denuded oocytes and investigate the influence of gonadotropins, serum, and cumulus cell expansion on the abundance of transcripts encoding these genes.

DESIGN: Prospective controlled animal study.

SETTING: University research laboratory.

PATIENT(S): Animal models for human studies.

INTERVENTION(S): Cumulus-oocyte complexes were treated in culture with serum and gonadotropin-supplemented media to examine the effects to mRNA transcript levels.

MAIN OUTCOME MEASURE(S): Variation in mRNA transcript levels. …

Extended Vs. Small Field Irradiation In High Risk Post Esophagectomy Patients Receiving Combined Chemoradiation Therapy: A Decade Experience In Treatment Of Esophageal Cancer, Edward Yu, Patricia Tai, George Rodrigues, Robert Ash, Larry Stitt, Rashid A. Dar, Pauline Truong, Gregory M. Videtic, Richard Malthaner, Richard Inculet, Anna Tomiak, Jawaid Younus, Brian Dingle, Walter Kocha, Mark Vincent

Oncology Presentations

OBJECTIVE: To assess the impact of extended field irradiation with anastomotic coverage on local recurrence in high risk resected esophageal cancerpatients.

METHODS: From 1989-1999, high risk resected esophageal cancer cases receiving post-resection chemoradiation were reviewed. Adjuvant chemotherapy consisted of four cycles of fluorouracil-based regimens. Loco-regional irradiation with or without coverage of anastomotic site had radiation a dose range from 45-60 Gyat 1.8-2.0 Gy/fraction given with initial anterior-posterior/posterior-anterior arrangement with either extended (with anastomotic coverage), or small (without anastomotic coverage) field followed by oblique fields for boost.

RESULTS: One hundred eighty-eight charts were reviewed. Seventy-two patients were eligible for post-resection chemoradiation. …

Robot Assisted Ultrasound Imaged Guided Interstitial Lung Brachytherapy In A Porcine Model, Richard A. Malthaner, Edward Yu, Jerry J. Battista, Chris Blake, Donal Downey, Aaron Fenster

Oncology Presentations

We set out to see if permanent interstitial brachytherapy seeds could be safely and reproducibly inserted thoracoscopicaly with the ZEUS Robotic system and intraoperative ultrasound into in-vivo porcine lungs.

Rgs14 Is A Mitotic Spindle Protein Essential From The First Division Of The Mammalian Zygote., Luke Martin-Mccaffrey, Francis S Willard, Antonio J Oliveira-Dos-Santos, David R C Natale, Bryan E Snow, Randall J Kimple, Agnieszka Pajak, Andrew J Watson, Lina Dagnino, Josef M Penninger, David P Siderovski, Sudhir J A D'Souza

Obstetrics & Gynaecology Publications

Heterotrimeric G protein alpha subunits, RGS proteins, and GoLoco motif proteins have been recently implicated in the control of mitotic spindle dynamics in C. elegans and D. melanogaster. Here we show that "regulator of G protein signaling-14" (RGS14) is expressed by the mouse embryonic genome immediately prior to the first mitosis, where it colocalizes with the anastral mitotic apparatus of the mouse zygote. Loss of Rgs14 expression in the mouse zygote results in cytofragmentation and failure to progress to the 2-cell stage. RGS14 is found in all tissues and segregates to the nucleus in interphase and to the mitotic spindle …

Living Donor Liver Transplantation: Surgical Techniques And Innovations, Vivian Mcalister

Data and Test Instruments

A colleague and I attended a talk about a set of liver transplant experiments in mice, which the speaker had designed to undermine a commonly held immunological belief. My companion (who should have known better) afterward asked me rhetorically, "What's next? Heart transplantation in a tadpole?"When does the awe-inspiring give way to the commonplace? Technically wonderful surgery is considered ordinary not because it is commonly done but because the holder of this opinion has no image of the technique.Not long ago, resectional hepatic surgery was followed by the development of orthotopic liver transplantation. Although both techniques have matured into conventional …

Deletion Of The Na/K-Atpase Alpha1-Subunit Gene (Atp1a1) Does Not Prevent Cavitation Of The Preimplantation Mouse Embryo., L C Barcroft, A E Moseley, J B Lingrel, A J Watson

Obstetrics & Gynaecology Publications

Increases in Na/K-ATPase activity occur concurrently with the onset of cavitation and are associated with increases in Na(+)-pump subunit mRNA and protein expression. We have hypothesized that the alpha1-isozyme of the Na/K-ATPase is required to mediate blastocyst formation. We have tested this hypothesis by characterizing preimplantation development in mice with a targeted disruption of the Na/K-ATPase alpha1-subunit (Atp1a1) using embryos acquired from matings between Atp1a1 heterozygous mice. Mouse embryos homozygous for a null mutation in the Na/K-ATPase alpha1-subunit gene are able to undergo compaction and cavitation. These findings demonstrate that trophectoderm transport mechanisms are maintained in the absence of the …

P38 Mapk Signaling During Murine Preimplantation Development., David R Natale, Andrew J M Paliga, Frank Beier, S J A D'Souza, Andrew J Watson

Obstetrics & Gynaecology Publications

Mitogen-activated protein kinase (MAPK) pathways mediate some important cellular processes and are likely to also regulate preimplantation development. The role of p38 MAP kinase signaling during murine preimplantation development was investigated in the present study. p38 MAPK, p38-regulated or -activated kinase (PRAK; MK5), map kinase-activated protein kinase 2 (MK2), and heat shock protein 25 (hsp25) mRNAs and proteins were detected throughout preimplantation development. Two-cell stage embryos cultured in the presence of SB220025 and SB203580 (specific inhibitors of p38 MAPK alpha/beta), progressed to the eight-cell stage with the same frequency as controls; however, treated embryos halted their development at the 8- …

Uwomj Volume 73, No. 1, 2004, Western University

University of Western Ontario Medical Journal

Schulich School of Medicine & Dentistry

Living Donor Liver Transplantation: Surgical Techniques And Innovations By Koichi Tanaka, Yukihiro Inomaka, And Satoshi Kaihara, Vivian Mcalister

Data and Test Instruments

Living-donor liver transplantation combines the techniques of hepatic resection and transplantation. The principal difference between living donation of liver and resection is the absolute requirement in the former to maintain the integrity of the liver on each side of the dividing line. To do this, the surgeon must retain the vascular supply and drainage of both sides throughout the dissection, up to the moment of graft removal. In this book, Tanaka and colleagues take us through the surgery in a manner that is at once detailed and exciting, through the generous use of magnificent electronic photography.

Review Of Surgical Limits: The Life Of Gordon Murray By Shelly Mckellar, Vivian Mcalister

Data and Test Instruments

Gordon Murray ranks as Canada’s greatest surgical pioneer, to whom history has been most unkind. Shelley McKellar has written a surgical biography that goes a long way toward explaining how this came about, and gives us a good opportunity to reassess Murray’s extraordinary career.

A Null Mutation For Tissue Inhibitor Of Metalloproteinases-3 (Timp-3) Impairs Murine Bronchiole Branching Morphogenesis., Sean E Gill, M Cynthia Pape, Rama Khokha, Andrew J Watson, Kevin J Leco

Obstetrics & Gynaecology Publications

Tissue inhibitors of metalloproteinases (TIMPs) regulate extracellular matrix (ECM) degradation by matrix metalloproteinases (MMPs). We have examined the role of TIMP-3 on ECM homeostasis and bronchiole branching morphogenesis during murine embryogenesis. Employing an in vitro organ culture system, we found decreased bronchiolar branching in null lungs when compared with wild type (WT) counterparts after 2 days in culture. When a synthetic inhibitor of MMPs at low dose was added to the culture system, branching was augmented regardless of genotype. Gelatin and in situ zymography revealed that null lungs exhibited enhanced activation of MMPs throughout lung development. We analysed the impact …

Seek And Ye Shall Find, Vivian Mcalister

Data and Test Instruments

The United States has relaxed its ban on the importation of Canadian meat cuts from cattle less than 30 months of age. Mexico, too, is reopening its borders to Canadian beef.The principal argument Canada has used to reassure its trading partners is that only one older cow, and none of the 2,700 animals with which that cow came into contact, tested positive for mad-cow disease. Meanwhile, the Canadian Food Inspection Agency has detailed measures it is taking to prevent mad-cow disease, or bovine spongiform encephalopathy, "from entering Canada." Surveillance and testing of animals has been increased.But it's folly to try …

Aquaporin Proteins In Murine Trophectoderm Mediate Transepithelial Water Movements During Cavitation., Lisa C Barcroft, Hanne Offenberg, Preben Thomsen, Andrew J Watson

Obstetrics & Gynaecology Publications

Mammalian blastocyst formation is dependent on establishment of trophectoderm (TE) ion and fluid transport mechanisms. We have examined the expression and function of aquaporin (AQP) water channels during murine preimplantation development. AQP 3, 8, and 9 proteins demonstrated cell margin-associated staining starting at the 8-cell (AQP 9) or compacted morula (AQP 3 and 8) stages. In blastocysts, AQP 3 and 8 were detected in the basolateral membrane domains of the trophectoderm, while AQP3 was also observed in cell margins of all inner cell mass (ICM) cells. In contrast, AQP 9 was predominantly observed within the apical membrane domains of the …

Responsiveness Of Bovine Cumulus-Oocyte-Complexes (Coc) To Porcine And Recombinant Human Fsh, And The Effect Of Coc Quality On Gonadotropin Receptor And Cx43 Marker Gene Mrnas During Maturation In Vitro., Michele D Calder, Anita N Caveney, Lawrence C Smith, Andrew J Watson

Obstetrics & Gynaecology Publications

Substantially less development to the blastocyst stage occurs in vitro than in vivo and this may be due to deficiencies in oocyte competence. Although a large proportion of bovine oocytes undergo spontaneous nuclear maturation, less is known about requirements for proper cytoplasmic maturation. Commonly, supraphysiological concentrations of FSH and LH are added to maturation media to improve cumulus expansion, fertilization and embryonic development. Therefore, various concentrations of porcine FSH (pFSH) and recombinant human FSH (rhFSH) were investigated for their effect on bovine cumulus expansion in vitro. Expression of FSHr, LHr and Cx43 mRNAs was determined in cumulus-oocyte complexes to determine …

Evaluation Of Intra-And Inter-Fraction Motion In Breast Radiotherapy Using Electronic Portal Imaging Cine Loops, Chrison Lee, Edward Yu, Tomas Kron

Oncology Presentations

Parallel tangent breast irradiation is commonly used postbreast conservation surgery for early breast cancer patient without lymph node involvement to improve local disease control. Intra-fractional and inter-fractional variabilities are often presented in daily treatment setup. The present pilot study used Electronic Portal Imaging (EPI) to evaluate intra-and inter-fraction motion in patients undergoing simple breast tangent radiotherapy.