Medical Specialties Commons^™

Susceptibility To Fatty Acid-Induced Β-Cell Dysfunction Is Enhanced In Prediabetic Diabetes-Prone Biobreeding Rats: A Potential Link Between Β-Cell Lipotoxicity And Islet Inflammation, Christine Tang, Anthony E. Naassan, Astrid Chamson-Reig, Khajag Koulajian, Tracy T. Goh, Frederick Yoon, Andrei I. Oprescu, Husam Ghanim, Gary F. Lewis, Paresh Dandona, Marc Y. Donath, Jan A. Ehses, Edith Arany, Adria Giacca

Paediatrics Publications

β-Cell lipotoxicity is thought to play an important role in the development of type 2 diabetes. However, no study has examined its role in type 1 diabetes, which could be clinically relevant for slow-onset type 1 diabetes. Reports of enhanced cytokine toxicity in fat-laden islets are consistent with the hypothesis that lipid and cytokine toxicity maybe synergistic. Thus, β-cell lipotoxicity could be enhanced in models of autoimmune diabetes. To determine this, we examined the effects of prolonged free fatty acids elevation on β-cell secretory function in the prediabetic diabetes-prone BioBreeding (dp-BB) rat, its diabetes-resistant BioBreeding (dr-BB) control, and normal Wistar-Furth …

Progastrin Stimulates Colonic Cell Proliferation Via Cck2r- And Β-Arrestin-Dependent Suppression Of Bmp2, Guangchun Jin, C. Benedikt Westphalen, Yoku Hayakawa, Daniel L. Worthley, Samuel Asfaha, Xiangdong Yang, Xiaowei Chen, Yiling Si, Hongshan Wang, Yagnesh Tailor, Richard A. Friedman, Timothy C. Wang

Paediatrics Publications

Background & Aims Progastrin stimulates colonic mucosal proliferation and carcinogenesis through the cholecystokinin 2 receptor (CCK2R) - partly by increasing the number of colonic progenitor cells. However, little is known about the mechanisms by which progastrin stimulates colonic cell proliferation. We investigated the role of bone morphogenetic proteins (BMPs) in progastrin induction of colonic cell proliferation via CCK2R. Methods We performed microarray analysis to compare changes in gene expression in the colonic mucosa of mice that express a human progastrin transgene, gastrin knockout mice, and C57BL/6 mice (controls); the effects of progastrin were also determined on in vitro colonic crypt …

Mice That Express Human Interleukin-8 Have Increased Mobilization Of Immature Myeloid Cells, Which Exacerbates Inflammation And Accelerates Colon Carcinogenesis, Samuel Asfaha, Alexander N. Dubeykovskiy, Hiroyuki Tomita, Xiangdong Yang, Sarah Stokes, Wataru Shibata, Richard A. Friedman, Hiroshi Ariyama, Zinaida A. Dubeykovskaya, Sureshkumar Muthupalani, Russell Ericksen, Harold Frucht, James G. Fox, Timothy C. Wang

Paediatrics Publications

Background & Aims: Interleukin (IL)-8 has an important role in initiating inflammation in humans, attracting immune cells such as neutrophils through their receptors CXCR1 and CXCR2. IL-8 has been proposed to contribute to chronic inflammation and cancer. However, mice do not have the IL-8 gene, so human cancer cell lines and xenograft studies have been used to study the role of IL-8 in colon and gastric carcinogenesis. We generated mice that carry a bacterial artificial chromosome that encompasses the entire human IL-8 gene, including its regulatory elements (IL-8Tg mice). Methods: We studied the effects of IL-8 expression in APCmin+/- mice …

P38 Mapk Regulates Cavitation And Tight Junction Function In The Mouse Blastocyst., Christine E Bell, Andrew J Watson

Obstetrics & Gynaecology Publications

UNLABELLED: Blastocyst formation is essential for implantation and maintenance of pregnancy and is dependent on the expression and coordinated function of a series of proteins involved in establishing and maintaining the trans-trophectoderm ion gradient that enables blastocyst expansion. These consist of Na/K-ATPase, adherens junctions, tight junctions (TJ) and aquaporins (AQP). While their role in supporting blastocyst formation is established, the intracellular signaling pathways that coordinate their function is unclear. The p38 MAPK pathway plays a role in regulating these proteins in other cell types and is required for embryo development at the 8-16 cell stage, but its role has not …

Localization Of Pain-Related Brain Activation: A Meta-Analysis Of Neuroimaging Data, Emma G. Duerden, Marie Claire Albanese

Paediatrics Publications

A meta-analysis of 140 neuroimaging studies was performed using the activation-likelihood-estimate (ALE) method to explore the location and extent of activation in the brain in response to noxious stimuli in healthy volunteers. The first analysis involved the creation of a likelihood map illustrating brain activation common across studies using noxious stimuli. The left thalamus, right anterior cingulate cortex (ACC), bilateral anterior insulae, and left dorsal posterior insula had the highest likelihood of being activated. The second analysis contrasted noxious cold with noxious heat stimulation and revealed higher likelihood of activation to noxious cold in the subgenual ACC and the amygdala. …

Effects Of Age And Symptomatology On Cortical Thickness In Autism Spectrum Disorders, Krissy A.R. Doyle-Thomas, Emma G. Duerden, Margot J. Taylor, Jason P. Lerch, Latha V. Soorya, A. Ting Wang, Jin Fan, Eric Hollander, Evdokia Anagnostou

Paediatrics Publications

Several brain regions show structural and functional abnormalities in individuals with autism spectrum disorders (ASD), but the developmental trajectory of abnormalities in these structures and how they may relate to social and communicative impairments are still unclear. We assessed the effects of age on cortical thickness in individuals with ASD, between the ages of 7 and 39 years in comparison to typically developing controls. Additionally, we examined differences in cortical thickness in relation to symptomatology in the ASD group, and their association with age. Analyses were conducted using a general linear model, controlling for sex. Social and communication scores from …

Dietary Exposures And Allergy Prevention In High-Risk Infants, Edmond S. Chan, Carl Cummings, Mark Feldman, Ruth B. Grimes, Barbara Grueger, Larry B. Pancer, Anne Rowan Legg, Ellen P. Wood, Fabian P. Gorodzinsky, Nestor Cisneros, Janet Roberts, Adelle Atkinson, Zave Chad, Marie Josée Francoeur, Linda Kirste, Douglas Mack, Marie Noel Primeau, Timothy Vander Leek, Wade Watson

Paediatrics Publications

Allergic conditions in children are a prevalent health concern in Canada. The burden of disease and the societal costs of proper diagnosis and management are considerable, making the primary prevention of allergic conditions a desirable health care objective. This position statement reviews current evidence on dietary exposures and allergy prevention in infants at high risk for developing allergic conditions. It revisits previous dietary recommendations for pregnancy, breastfeeding and formula feeding, and provides an approach for introducing solid foods to high-risk infants. While there is no evidence that delaying the introduction of any specific food beyond six months of age helps …

B.03 Clinical Utility Of Critical Care Eeg Monitoring In A Canadian Paediatric Centre, Saptharishi Lalgudi Ganesan

Data and Test Instruments

No abstract provided.

Male Gender Promotes An Increased Inflammatory Response To Lipopolysaccharide In Umbilical Vein Blood., Shunaha Kim-Fine, Timothy Regnault, James S Lee, Sarah A Gimbel, Jill A Greenspoon, Jonathan Fairbairn, Kelly Summers, Barbra De Vrijer

Paediatrics Publications

OBJECTIVES: To establish gender-specific differences in maternal and fetal immune response in healthy human fetuses at term.

METHODS: Forty-five women with elective caesarean sections for uncomplicated singleton pregnancies were recruited for two studies. Using a multiplex biomarker immunoassay system, unstimulated maternal and fetal plasma concentrations of interleukin (IL)-1β, IL-1ra, IL-6, IL-8, macrophage inflammatory protein (MIP)-1α, and tumor necrosis factor (TNF)-α were measured from one study population. Lipopolysaccharide (LPS)-stimulated cytokine response was measured in a second study.

RESULTS: There were no significant gender differences in either maternal or fetal unstimulated plasma cytokine concentrations, but concentrations of the proinflammatory cytokines IL-1β and …

Overexpression Of Pyruvate Dehydrogenase Kinase 1 And Lactate Dehydrogenase A In Nerve Cells Confers Resistance To Amyloid Β And Other Toxins By Decreasing Mitochondrial Respiration And Reactive Oxygen Species Production, Jordan T. Newington, Tim Rappon, Shawn Albers, Daisy Y. Wong, R. Jane Rylett, Robert C. Cumming

Paediatrics Publications

Background: Aerobic glycolysis promotes resistance against Aβ toxicity. Results: Increased LDHA and PDK1 expression attenuates mitochondrial activity and confers resistance to Aβ. These proteins are down-regulated in a transgenic Alzheimer disease (AD) mouse model, and PDK1 is decreased in AD brain. Conclusion: PDK and LDHA are central mediators of Aβ resistance. Significance: Drugs that augment aerobic glycolysis may enhance brain cell survival in AD patients. © 2012 by The American Society for Biochemistry and Molecular Biology, Inc.

Genetic And Environmental Vulnerabilities In Children With Neurodevelopmental Disorders, Annette Karmiloff-Smith, Dean D'Souza, Tessa M. Dekker, Jo Van Herwegen, Fei Xu, Maja Rodic, Daniel Ansari

Paediatrics Publications

One might expect that children with varying genetic mutations or children raised in low socioeconomic status environments would display different deficits. Although this expectation may hold for phenotypic outcomes in older children and adults, cross-syndrome comparisons in infancy reveal many common neural and sociocognitive deficits. The challenge is to track dynamic trajectories over developmental time rather than focus on end states like in adult neuropsychological studies. We contrast the developmental and adult approaches with examples from the cognitive and social domains, and we conclude that static models of adult brain lesions cannot be used to account for the dynamics of …

Civilian Trauma Care - Learning From The Military Experience, Vivian Mcalister

Data and Test Instruments

In the 21st century, military and civilian trauma surgeons bring similar solutions to similar problems, learning one from another. The objective of this presentation is to review military trauma care in Afghanistan for aspects that may influence civilian practice at home. • Comprehensive trauma care system: guidelines, registry, review • Protocols for care: damage control; massive blood transfusion policy; mass casualty care • Techniques: resuscitative thoracotomy; decompressive craniectomy; pelvic-gluteal hemorrhage control • Rehabilitation: Mild traumatic brain injury • Delegated medical acts: medics / PAs

Cystatin C For The Assessment Of Gfr In Neonates With Congenital Renal Anomalies, Guido Filler, Joanne Grimmer, Shih Han Susan Huang, Erika Bariciak

Paediatrics Publications

No abstract provided.

Analysis Of The Mmp-Dependent And Independent Functions Of Tissue Inhibitor Of Metalloproteinase-2 On The Invasiveness Of Breast Cancer Cells, Logan A. Walsh, Mario A. Cepeda, Sashko Damjanovski

Paediatrics Publications

Matrix metalloproteinases (MMPs) are secreted endopeptidases that play an essential role in remodeling the extracellular matrix (ECM). MMPs are primarily active during development, when the majority of ECM remodeling events occurs. In adults, elevated MMP activity has been observed in many pathological conditions such as cancer and osteoarthritis. The proteolytic activity of MMPs is controlled by their natural inhibitors - the tissue inhibitor of metalloproteinases (TIMPs). In addition to blocking MMP-mediated proteolysis, TIMPs have a number of MMP-independent functions including binding to cell surface proteins thereby stimulating signaling cascades. TIMP-2, the most studied member of the family, can both inhibit …

Male Breast Cancer, Edward Yu

Data and Test Instruments

No abstract provided.

Psoas Abscess - A Teaching File, Adina Feinberg, Vivian Mcalister

Data and Test Instruments

Case Report: A 43-year-old woman presented to the emergency room at University Hospital, London Health Sciences Centre with an eight-day history of lower back pain. She had presented one-week prior with similar symptoms and was treated conservatively for sciatica. Since then, her pain had progressively increased

The Systemic Inflammatory Response After Spinal Cord Injury In The Rat Is Decreased By Α4Β1 Integrin Blockade, Feng Bao, Vanessa Omana, Arthur Brown, Lynne C. Weaver

Paediatrics Publications

The systemic inflammatory response syndrome (SIRS) follows spinal cord injury (SCI) and causes damage to the lungs, kidney, and liver due to an influx of inflammatory cells from the circulation. After SCI in rats, the SIRS develops within 12 h and is sustained for at least 3 days. We have previously shown that blockade of CD11d/CD18 integrin reduces inflammation-driven secondary damage to the spinal cord. This treatment reduces the SIRS after SCI. In another study we found that blockade of α4β1 integrin limited secondary cord damage more effectively than blockade of CD11d/CD18. Therefore we considered it important to assess the …

Association Of Cartilage-Specific Deletion Of Peroxisome Proliferator-Activated Receptor Γ With Abnormal Endochondral Ossification And Impaired Cartilage Growth And Development In A Murine Model, Roxana Monemdjou, Faezeh Vasheghani, Hassan Fahmi, Gemma Perez, Meryem Blati, Noboru Taniguchi, Martin Lotz, René St-Arnaud, Jean Pierre Pelletier, Johanne Martel-Pelletier, Frank Beier, Mohit Kapoor

Paediatrics Publications

Objective Long bones develop through the strictly regulated process of endochondral ossification within the growth plate, resulting in the replacement of cartilage by bone. Defects in this process can result in skeletal abnormalities and a predisposition to degenerative joint diseases such as osteoarthritis (OA). Studies suggest that activation of the transcription factor peroxisome proliferator-activated receptor γ (PPARγ) is an important therapeutic target in OA. To devise PPARγ-related therapies in OA, it is critical to identify the role of this transcription factor in cartilage biology. Therefore, this study sought to determine the in vivo role of PPARγ in endochondral ossification and …

The Dark Side Of Neuroplasticity, Arthur Brown, Lynne C. Weaver

Paediatrics Publications

Whether dramatic or modest, recovery of neurological function after spinal cord injury (SCI) is greatly due to neuroplasticity - the process by which the nervous system responds to injury by establishing new synaptic connections or by altering the strength of existing synapses. However, the same neuroplasticity that allows locomotor function to recover also produces negative consequences such as pain and dysfunction of organs controlled by the autonomic nervous system. In this review we focus specifically on structural neuroplasticity (the growth of new synaptic connections) after SCI and on the consequent development of pain and autonomic dysreflexia, a condition of episodic …

Embryo Collection Induces Transient Activation Of Xbp1 Arm Of The Er Stress Response While Embryo Vitrification Does Not., Tamara Abraham, Christopher L Pin, Andrew J Watson

Obstetrics & Gynaecology Publications

Embryo cryopreservation has become a standard procedure in the practice of assisted reproduction. While routinely performed in IVF labs, the effects of embryo vitrification on the molecular mechanisms governing preimplantation development remain largely unknown. The endoplasmic reticulum stress (ER stress) response is an evolutionary conserved mechanism that cells employ to manage ER stress. ER stress can be defined as an imbalance between protein synthesis and secretion within the ER. The primary focus of this study was to investigate whether standard embryo manipulations, including embryo collection, culture and vitrification, result in activation of the ER stress pathway in vitro and to …

Paediatricians, Social Media And Blogs: Ethical Considerations, Thérèse St-Laurent-Gagnon, Kevin W. Coughlin

Paediatrics Publications

The use of blogs, Facebook and similar social networking sites is rapidly expanding and, when compared with e-mail, may be having a significantly different impact on the traditional doctor-patient relationship. Characteristics specific to these online platforms have major implications for professional relationships, including the ‘Facebook effect’ (the relative permanence of postings) and the ‘online disinhibition effect’. The present practice point illustrates relevant ethical considerations and provides guidance to paediatricians and others concerning the prudent professional and personal use of social networking media.

L’utilisation des blogues, de Facebook et de sites de réseautage social similaires prend une expansion rapide. Par rapport …

Outer Space And Oocyte Developmental Competence., Andrew J Watson

Obstetrics & Gynaecology Publications

No abstract provided.

Mitogen-Activated Protein Kinase Phosphatase-1 Inhibits Myocardial Tnf-Α Expression And Improves Cardiac Function During Endotoxemia, Ting Zhang, Xiangru Lu, Paul Arnold, Yin Liu, Reshma Baliga, Hong Huang, John Anthony Bauer, Yusen Liu, Qingping Feng

Paediatrics Publications

Aims: Myocardial tumour necrosis factor-α (TNF-α) expression induces cardiac dysfunction in endotoxemia. The aim of this study was to investigate the role of mitogen-activated protein kinase phosphatase-1 (MKP1) pathway in myocardial TNF-α expression and cardiac function during endotoxemia. Methods and results: Lipopolysaccharide (LPS) increased MKP1 expression in the myocardium in vivo and in cultured neonatal cardiomyocytes in vitro. LPS-induced extracellular signal-regulated kinase (ERK) 1/2 and p38 phosphorylation in the myocardium was prolonged in MKP1 -/- mice. Myocardial TNF-α mRNA and protein levels were enhanced in MKP1 -/- compared with wild-type (WT) mice in endotoxemia, leading to a further decrease in …

Cd11d Antibody Treatment Improves Recovery In Spinal Cord-Injured Mice, Nicole M. Geremia, Feng Bao, Trina E. Rosenzweig, Todd Hryciw, Lynne Weaver, Gregory A. Dekaban, Arthur Brown

Paediatrics Publications

Acute administration of a monoclonal antibody (mAb) raised against the CD11d subunit of the leukocyte CD11d/CD18 integrin after spinal cord injury (SCI) in the rat greatly improves neurological outcomes. This has been chiefly attributed to the reduced infiltration of neutrophils into the injured spinal cord in treated rats. More recently, treating spinal cord-injured mice with a Ly-6G neutrophil-depleting antibody was demonstrated to impair neurological recovery. These disparate results could be due to different mechanisms of action utilized by the two antibodies, or due to differences in the inflammatory responses between mouse and rat that are triggered by SCI. To address …

Residual Renal Function Calculated From Serum Cystatin C Measurements And Knowledge Of The Weekly Standard Kt/V Urea, Shih Han Huang, Guido Filler, Robert M. Lindsay

Paediatrics Publications

No abstract provided.

Cardiac Failure Following Inadvertent Administration Of High-Dose Epinephrine Subcutaneously, Kim A. Tran, Douglas D. Fraser, Krista Hawrylyshyn, Kambiz Norozi

Paediatrics Publications

Our aim is to report the consequences of epinephrine toxicity leading to cardiac failure in a child and the successful management with dopamine and milrinone. A previously healthy 13-year-old girl undergoing a left tympanomastoidectomy was inadvertently administered 10 mL of 1:1000 epinephrine subcutaneously (0.175 mg/kg) on the left post auricular region in lieu of lidocaine. She developed sudden supraventricular tachycardia, hypertension and flash pulmonary edema. She was initially treated with propofol, nitrogycerin and increased peak end-expiratory pressure. Within 4 h, she remained tachycardic, but was hypotensive with an increased central venous pressure. Electrocardiogram and echocardiogram investigations showed ST changes indicative …

The Long And Short Of It: The Role Of Telomeres In Fetal Origins Of Adult Disease., Stephanie E Hallows, Timothy Regnault, Dean H Betts

Paediatrics Publications

Placental insufficiency, maternal malnutrition, and other causes of intrauterine growth restriction (IUGR) can significantly affect short-term growth and long-term health. Following IUGR, there is an increased risk for cardiovascular disease and Type 2 Diabetes. The etiology of these diseases is beginning to be elucidated, and premature aging or cellular senescence through increased oxidative stress and DNA damage to telomeric ends may be initiators of these disease processes. This paper will explore the areas where telomere and telomerase biology can have significant effects on various tissues in the body in IUGR outcomes.

Medical Physics Staffing For Radiation Oncology: A Decade Of Experience In Ontario, Canada., Jerry J. Battista Dr., Brenda G Clark, Michael S Patterson, Luc Beaulieu, Michael B Sharpe, L John Schreiner, Miller S Macpherson, Jacob Van Dyk

Oncology Publications

The January 2010 articles in The New York Times generated intense focus on patient safety in radiation treatment, with physics staffing identified frequently as a critical factor for consistent quality assurance. The purpose of this work is to review our experience with medical physics staffing, and to propose a transparent and flexible staffing algorithm for general use. Guided by documented times required per routine procedure, we have developed a robust algorithm to estimate physics staffing needs according to center-specific workload for medical physicists and associated support staff, in a manner we believe is adaptable to an evolving radiotherapy practice. We …

Optimal Strategy For Prophylactic Cranial Irradiation In Limited Stage Small Cell Lung Cancer, Edward Yu, Patricia Tai, Avi Assouline, Kurian Joseph

Data and Test Instruments

No abstract provided.

The Life Of John Wishart (1850-1926): Study Of An Academic Surgical Career Prior To The Flexner Report., Emily Claydon, Vivian Mcalister

Data and Test Instruments

BACKGROUND: The 1910 Flexner Report on Medical Education in the United States and Canada is often taken as the point when medical schools in North America took on their modern form. However, many fundamental advances in surgery, such as anesthesia and asepsis, predated the report by decades. To understand the contribution of educators in this earlier period, we investigated the forgotten career of John Wishart, founding Professor of Surgery at Western University, London Ontario. METHODS: Archives at the University of Western Ontario, University of Toronto, London City Library, and Wellington County Museum were searched for material about Wishart and his …