Medicine and Health Sciences Commons^™

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 …

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.

A Pilot Trial Comparing The Effects Of Onabotulinumtoxina And Standard Oxybutynin Therapy As First Line Treatment For The Poorly Compliant Pediatric Neurogenic Bladder, Sumit Dave

Electronic Thesis and Dissertation Repository

Research question

Is it feasible to conduct a phase III RCT to compare OnabotulinumtoxinA injections to oxybutynin as primary therapy in pediatric neurogenic bladder?

Methods

Patients on a stable oxybutynin regimen were recruited for a pilot RCT and underwent randomization to either OnabotulinumtoxinA or continuation of oxybutynin. Primary outcomes included an a priori defined feasibility and acceptability assessment. Secondary outcomes included continence, urodynamic parameters, side effects and QOL.

Results

The study enrolled 8 subjects in the OnabotulinumtoxinA group and 6 in the oxybutynin group. The recruitment rate was 75 % and the dropout rate was 6.6 %. There were 2 …

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 …

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 …

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 …

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 …

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 …

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.

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 …