Beca J.,Starship Childrens Hospital |
Mcsharry B.,Starship Childrens Hospital |
Erickson S.,Princess Margaret Hospital |
Yung M.,Women and Childrens Hospital |
And 7 more authors.
Critical Care Medicine | Year: 2015
Objectives: To perform a pilot study to assess the feasibility of performing a phase III trial of therapeutic hypothermia started early and continued for at least 72 hours in children with severe traumatic brain injury. Design: Multicenter prospective randomized controlled phase II trial. Setting: All eight of the PICUs in Australia and New Zealand and one in Canada. Patients: Children 1-15 years old with severe traumatic brain injury and who could be randomized within 6 hours of injury. Interventions: The control group had strict normothermia to a temperature of 36-37°C for 72 hours. The intervention group had therapeutic hypothermia to a temperature of 32-33°C for 72 hours followed by slow rewarming at a rate compatible with maintaining intracranial pressure and cerebral perfusion pressure. Measurements and Main Results: Of 764 children admitted to PICU with traumatic brain injury, 92 (12%) were eligible and 55 (7.2%) were recruited. There were five major protocol violations (9%): three related to recruitment and consent processes and two to incorrect temperature management. Rewarming took a median of 21.5 hours (16-35 hr) and was performed without compromise in the cerebral perfusion pressure. There was no increase in any complications, including infections, bleeding, and arrhythmias. There was no difference in outcomes 12 months after injury; in the therapeutic hypothermia group, four (17%) had a bad outcome (pediatric cerebral performance category, 4-6) and three (13%) died, whereas in the normothermia group, three (12%) had a bad outcome and one (4%) died. Conclusions: Early therapeutic hypothermia in children with severe traumatic brain injury does not improve outcome and should not be used outside a clinical trial. Recruitment rates were lower and outcomes were better than expected. Conventional randomized controlled trials in children with severe traumatic brain injury are unlikely to be feasible. A large international trials group and alternative approaches to trial design will be required to further inform practice. © 2015 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc.
Hagemeier J.,State University of New York at Buffalo |
Yeh E.A.,Women and Childrens Hospital |
Brown M.H.,State University of New York at Buffalo |
Bergsland N.,State University of New York at Buffalo |
And 4 more authors.
Multiple Sclerosis Journal | Year: 2013
Objective: The objective of this paper is to assess abnormal phase values, indicative of increased iron content, using susceptibility-weighted imaging (SWI)-filtered phase of the subcortical deep gray matter (SDGM) in adolescent multiple sclerosis (MS) and other neurological disorders (OND) patients, and in healthy controls (HC). Methods: Twenty adolescent MS and eight adolescent OND patients and 21 age- and sex-matched HC were scanned on a 3T GE scanner. Mean phase of abnormal phase tissue (MP-APT), MP-APT volume, normal phase tissue volume (NPTV) and normalized volume measurements were obtained for total SDGM, as well as specific structures separately. Results: Significantly increased MP-APT (28.2%, p<.001) and MP-APT volume (82.7%, p<.001), and decreased NPTV (-23.3%, p<.001) and normalized volume (-15.5%, p<.001) in the pulvinar nucleus of the thalamus was found in MS patients compared to HC. MP-APT in MS patients was also increased in total SDGM (p=.012) and thalamus (p=.044). Compared to OND patients, MS patients had increased MP-APT volume in the pulvinar nucleus of the thalamus (p=.044) and caudate (p=.045). Increased MP-APT of the SDGM structures were associated with increased T2 and T1 lesion burden and brain atrophy in MS patients. Conclusion: Adolescent MS patients showed increased iron content in the SDGM compared to OND patients and HC. © The Author(s) 2012.
O'Loughlin J.,Royal Adelaide Hospital |
Millwood I.Y.,University of New South Wales |
McDonald H.M.,Women and Childrens Hospital |
Price C.F.,Starpharma Pty Ltd. |
And 2 more authors.
Sexually Transmitted Diseases | Year: 2010
OBJECTIVES:: To evaluate safety, tolerability and systemic pharmacokinetics of escalating doses of SPL7013 Gel in healthy women. DESIGN:: Randomized, double-blind, placebo-controlled dose-escalation trial. Methods: Thirty-seven healthy women were randomized to receive 3.5 g of 0.5% (N = 8), 1% (N = 8), or 3% (N = 9) SPL7013 Gel or placebo gel (N = 12), applied vaginally once daily for 7 consecutive days. Genital toxicity was determined by interview, physical examination, assessment of vaginal microflora and colposcopy. Systemic toxicity was determined by nongenital adverse events (AEs) and laboratory assessments. Plasma was collected for pharmacokinetic analysis. Results: Genital AEs considered potentially product-related were all mild and reported by 5 (20%) women receiving SPL7013 Gel and 2 (17%) women receiving placebo gel. The most common were abdominal pain or discomfort, with no reports of vaginal burning or malodour, or genital-tract pain. There were no clinically significant colposcopic findings, including of genital inflammation or epithelial disruption. Lower concentrations of normal lactobacillary flora occurred during SPL7013 Gel and placebo gel use, with a decrease in anaerobes in the SPL7013 Gel groups. There were no reported cases of bacterial vaginosis, and lactobacilli returned to predose levels in most women after treatment. All nongenital AEs were of mild or moderate severity, expect for a severe tension headache in a woman receiving placebo. There was no absorption of SPL7013 into the systemic circulation. Conclusions: SPL7013 Gel applied vaginally once daily for 7 days at concentrations of 0.5% to 3% was safe and well tolerated in healthy, sexually abstinent women, with no evidence of systemic toxicity or absorption. © Copyright 2010 American Sexually Transmitted Diseases Association.
Jolly R.D.,Massey University |
Marshall N.R.,Massey University |
Marshall J.,Massey University |
Hartman A.,Massey University |
And 2 more authors.
Neuropathology and Applied Neurobiology | Year: 2013
Aims: To investigate routes of dispersal of enzyme, its regional uptake and the effect of posture when replacement enzyme is administered directly into the cerebrospinal fluid (CSF). Methods: Dispersal pathways of particles and solutes were investigated using intracisternal injections of india ink with visual assessment, and a contrast medium (Iohexol) with computer tomography (CT). Replacement enzyme was measured at 46 loci within the central nervous system (CNS) in four groups of dogs subjected to different post-injection postural changes. Results: India ink and CT studies showed dispersal pathways for CSF to be mainly via cisterns and sulci. Replacement enzyme reached all areas of the CNS tested, although mean concentrations varied 49-fold over different areas of the brain. Posttreatment posture had only modest effects on enzyme uptake in limited anatomical sites. Conclusions: Dispersal of solutes after injection is rapid and initially enhanced by the injection process. Preferential pathways for CSF flow in the subarachnoid spaces of the brain involve cisterns and sulci. The splenial and suprasplenial sulci in particular appear important conduits for dispersal to more dorsal and rostral areas of the brain. Expansion and contraction of these sulci during brain pulsation is considered important to the forward flow of solutes in CSF through these compartments. Following intracisternal enzyme replacement therapy, enzyme reached all areas of the brain, but there was considerable disparity of enzyme uptake with some areas recording much higher levels than others. Posttreatment posture made only modest differences to enzyme uptake. © 2012 British Neuropathological Society.
Kalra J.,University of British Columbia |
Sutherland B.W.,University of British Columbia |
Stratford A.L.,Women and Childrens Hospital |
Dragowska W.,University of British Columbia |
And 5 more authors.
Oncogene | Year: 2010
In a previous study it was found that the therapeutic effects of QLT0267, a small molecule inhibitor of integrin-linked kinase (ILK), were influenced by Her2/neu expression. To understand how inhibition or silencing of ILK influences Her2/neu expression, Her2/neu signaling was evaluated in six Her2/neu-positive breast cancer cell lines (LCC6 Her2, MCF7 Her2, SKBR3, BT474, JIMT-1 and KPL-4). Treatment with QLT0267 engendered suppression (32-87%) of total Her2/neu protein in these cells. Suppression of Her2/neu was also observed following small interfering RNA-mediated silencing of ILK expression. Time course studies suggest that ILK inhibition or silencing caused transient decreases in P-AKT ser473, which were not temporally related to Her2/neu downregulation. Attenuation of ILK activity or expression was, however, associated with decreases in YB-1 (Y-box binding protein-1) protein and transcript levels. YB-1 is a known transcriptional regulator of Her2/neu expression, and in this study it is demonstrated that inhibition of ILK activity using QLT0267 decreased YB-1 promoter activity by 50.6%. ILK inhibition was associated with changes in YB-1 localization, as reflected by localization of cytoplasmic YB-1 into stress granules. ILK inhibition also suppressed TWIST (a regulator of YB-1 expression) protein expression. To confirm the role of ILK on YB-1 and TWIST, cells were engineered to overexpress ILK. This was associated with a fourfold increase in the level of YB-1 in the nucleus, and a 2- and 1.5-fold increase in TWIST and Her2/neu protein levels, respectively. Taken together, these data indicate that ILK regulates the expression of Her2/neu through TWIST and YB-1, lending support to the use of ILK inhibitors in the treatment of aggressive Her2/neu-positive tumors. © 2010 Macmillan Publishers Limited All rights reserved.
Dong Y.,Chongqing Medical University |
Yue G.,Women and childrens Hospital |
Yu J.,Chongqing Medical University
Iranian Journal of Pediatrics | Year: 2012
Objective: Mortality of very low birth weight premature infants is of great public health concern. To better guide local intervention program, it is essential that current and reliable statistics be collected to understand the factors associated with mortality of these infants. Methods: Data of very low birth weight premature infants admitted to a neonatal unit during 2002-2009 was retrospectively collected. Changes in perinatal care between two halves of the study period (2002-2005 and 2006-2009) were identified. Factors associated with in-hospital mortality were found by logistic regression and a predictive score model was established. Findings: A total of 475 cases were enrolled. In-hospital mortality decreased from 29.8% in 2002-2005 to 28.1% in 2006-2009 (P>0.05). More infants born<28 gestational weeks survived to discharge in the latter epoch (38.1% vs 8.3%, P<0.05). Persistent pulmonary hypertension of newborn, pulmonary hemorrhage, birth weight <000 grams, gestational age <33 weeks, feeding before 3 postnatal days and enteral feeding were found predictors of in-hospital mortality by logistic regression. The discriminating ability of the predictive model was 82.4% and the cutoff point was -0.56. Conclusion: Survival of very low birth weight premature neonates was not significantly improved in 2006- 2009 than 2002-2005. Infants with a score higher than -0.56 were assessed to be at high risk of in-hospital mortality. Multi-center studies of planned follow-up are needed to develop a comprehensive and applicable score system. © 2012 by Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences, All rights reserved.
An B.,Women And Childrens Hospital |
Ning H.,Women And Childrens Hospital
International Journal of Clinical and Experimental Medicine | Year: 2015
Infiltration remains the commonest iatrogenic injury within infants care. We report a series of 6 infants affected by accidental infusion leakage occurring in subgalea. They were applied wet-hot compresses by sterile gauze, and topically administrated mucopolysaccharide polysulfate (MPS) cream following hot compress. There was no skin impairment in all cases. Early recognition and appropriate care for topical skin are essential to minimize the extent of accidental infusion leakage. © 2015, E-Century Publishing Corporation. All rights reserved.
Horswell B.B.,Women and Childrens Hospital |
Istfan S.,Child Advocacy Center
Oral and Maxillofacial Surgery Clinics of North America | Year: 2012
Oral and maxillofacial surgeons are in a unique position to identify and report child abuse. In the career of any practitioner, maltreated children (both physically abused and neglected) will present for management of injuries and infections. There must be a high level of vigilance for, and understanding of, mechanisms of injury and skill in sorting out inflicted injuries or evidence of neglect. Because of this, the medical community, society, state law, and the legal system place oral and maxillofacial surgeons in a position of expertise and accountability in the care of children. © 2012 Elsevier Inc.
Horswell B.B.,Women and Childrens Hospital
The West Virginia medical journal | Year: 2011
Dog bites of the facial region are increasing in children according to the Center for Disease Control. To evaluate the epidemiology of such injuries in our medical provider region, we undertook a retrospective review of those children treated for facial, head and neck dog bite wounds at a level 1 trauma center. Most dog bites occurred in or near the home by an animal known to the child/family. Most injuries were soft tissue related, however more severe bites and injuries were observed in attacks from the pit-bull and Rottweiler breeds. Younger (under five years) children sustained more of the injuries requiring medical treatment. Injury Severity Scales were determined as well as victim and payer mix demographics, type and characteristics of injury, and complications from the attack.
Curtis W.,Women and Childrens Hospital |
Horswell B.B.,Women and Childrens Hospital
Oral and Maxillofacial Surgery Clinics of North America | Year: 2013
Panfacial fractures are defined as fractures involving the lower, middle, and upper face. Treatment can be challenging and requires an individualized treatment plan. A firm understanding of the treatment principles of each individual fracture is necessary before attempting to tackle the patient with panfacial fractures. Advances in rigid fixation, wide exposure, primary bone grafting, and attention to soft tissue reattachment have significantly improved the treatment of the patient with panfacial fractures. © 2013 Elsevier Inc.