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Search Results: 1 - 10 of 303079 matches for " Kevin J. Sullivan "
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Hyperacute Therapies for Childhood Stroke: A Case Report and Review of the Literature
Jose Irazuzta,Kevin J. Sullivan
Neurology Research International , 2010, DOI: 10.1155/2010/497326
Abstract: Objective. The optimal management of pediatric patients with arterial ischemic stroke (AIS) is not known. Despite this, goal-oriented, time-sensitive therapies geared to rapid reestablishment of arterial blood flow are occasionally applied with beneficial effects. The inconsistent approach to AIS is in part due to a lack of knowledge and preparedness. Methods. Case report of a 12-year-old male with right middle cerebral artery (MCA) occlusion resulting in dense left hemiplegia and mutism and review of the literature. Intervention(s). Mechanical thrombectomy, intra-arterial administration of rt-PA, vasodilators, and platelet inhibitors, and systemic anticoagulation and subsequent critical care support. Results. Restoration of right MCA blood flow and complete resolution of neurologic deficits. Conclusion. We report the gratifying outcome of treatment of a case of AIS in a pediatric patient treated with hyperacute therapies geared to arterial recanalization and subsequent neurologic critical care and review the pertinent literature. Guidelines for the emergency room management of pediatric AIS from prospective, randomized trials are needed. 1. Introduction Arterial ischemic stroke (AIS) occurs more commonly in adults than children. In children the clinical presentation is often interpreted as other neurologic conditions or intoxications resulting in a delay in diagnosis due to the lack of awareness of pediatrician or that the symptoms do not systematically evoke a stroke. Adult AIS occurs in the setting of the principal risk factors of hypertension and atherosclerosis, while pediatric risk factors are heterogeneous and include focal intracranial arteriopathies, congenital cardiovascular diseases, and hemoglobinopathies [1, 2]. Recent advances in the management of AIS have emphasized the importance of timely diagnosis and restoration of arterial flow in the affected vascular territories. Adult victims have access to time-sensitive or hyperacute therapies due to an awareness of the severity of the disease, organization of delivery of medical care from the emergency room that includes designation of stroke centers, and protocol-driven preparedness for such emergencies [3–6]. Unfortunately, this is not the case for pediatric victims, because it is not known whether thrombolytic therapies are appropriate. We describe the case of a 12-year-old male with AIS who presented to medical attention with a potentially devastating neurological injury. A resolute strategy utilizing hyperacute therapies aimed at restoring blood flow followed by neurointensive care support
Current Opinions in Pediatric Septic Shock
José Irazuzta,Kevin J. Sullivan
Journal of Pediatric Sciences , 2009,
Abstract: Objectives: Our aim is to describe the current clinical practice related to the management of septic shock (SS). Methods: Review of medical literature using the MEDLINE database. Articles were selected according to their relevancy to the objective and according to the author’s opinion. Summary of the findings: The outcome from SS is dependent on an early recognition and a sequential implementation of time-sensitive goal-directed therapies. The goals of the resuscitation are rapid restoration of micro circulation and improved organ tissue perfusion. Clinical and laboratory markers are needed to assess the adequacy of the treatments. Initial resuscitation involves the use of isotonic solutions (>60ml/kg) either crystalloid (normal saline) or colloid infusion often followed by vasoactive medications. Altered pharmacokinetics and pharmacodynamics responses dictate that vasoactive agents should be adjusted to achieve predetermined goals. An assessment of central venous pressure complements clinical and serological findings to tailor therapies. Elective airway instrumentation and mechanical ventilation as well as adjunctive therapy with stress dose of corticosteroid are indicated in selected populations. In neonates, a special attention to the presence of electrolyte imbalance and increase pulmonary vascular resistance needs to be considered early. Conclusions: Septic shock hemodynamic is a changing process that requires frequent assessment and therapeutic adjustments.
Isolated cutaneous metastasis of uterine leiomyosarcoma: case report and review of literature
Shane Corcoran, Aisling M Hogan, Tamas Nemeth, Fadel Bennani, Francis J Sullivan, Waqar Khan, Kevin Barry
Diagnostic Pathology , 2012, DOI: 10.1186/1746-1596-7-85
Abstract: She noticed an uncomfortable and unsightly cystic swelling on her occiput four years after hysterectomy and was referred for routine excision of what was believed to be a benign lesion. The lesion was excised and sent for histopathological examination. Microscopic analysis including immuno-histochemistry demonstrated an ER and PR positive metastatic deposit of leiomyosarcoma. The margins of excision were histologically clear of disease.At Multi-Disciplinary Team (MDT) discussion a diagnosis of metastatic scalp deposit from previous uterine leiomyosarcoma was made. Re-staging CT brain, thorax, abdomen and pelvis and MRI brain were negative for local recurrence or distant metastases. She is currently undergoing radiotherapy to the scalp and surrounding tissues and will be followed up closely by the involved teams.To the best of our knowledge, this is the first case described in the worldwide literature of isolated cutaneous metastasis to the scalp of uterine leiomyosarcoma without evidence of disseminated disease at other sites.The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1311834987345566. webciteA 54 year old lady was referred to the surgical day ward of our institution for routine excision of a scalp lesion thought clinically to represent a sebaceous cyst of the right occiput. She had presented 4 years earlier with menorrhagia, fatigue and iron-deficiency anaemia and was diagnosed with a 9 cm fibroid uterus on ultrasound examination after inconclusive diagnostic laparoscopy. She underwent total abdominal hysterectomy and right salpingo-oophorectomy for 3 large uterine fibroids. Histo-pathological examination of the hysterectomy specimen revealed an incidental low-grade leiomyosarcoma (Figure 1). Staging CT thorax, abdomen and pelvis was negative for metastatic disease. She made an uneventful recovery and was treated further by adjuvant pelvic radiotherapy. Clinical and radiological follow up continued under t
Suporte farmacológico a lactentes e crian?as com choque séptico
Irazuzta, José;Sullivan, Kevin J.;Garcia, Pedro Celiny R.;Piva, Jefferson Pedro;
Jornal de Pediatria , 2007, DOI: 10.1590/S0021-75572007000300005
Abstract: objectives: septic shock (ss) is a frequent cause for admission to the pediatric intensive care unit, requiring prompt recognition and intervention to improve outcome. our aim is to review the relevant literature related to the diagnosis and management of ss and present a sequential management for its treatment. sources: non-systematic review of medical literature using the medline database. articles were selected according to their relevance to the objective and according to the authors’ opinions. summary of the findings: the outcome of sepsis and ss is dependent on the early recognition and implementation of time-sensitive goal-directed therapies. these include rapid aggressive fluid resuscitation followed by a well-designed pharmacotherapy. the goals of the resuscitation are the restoration of microcirculation and improved organ tissue perfusion. clinical and laboratory markers are needed to assess the adequacy of the treatments. altered pharmacokinetic and pharmacodynamic responses dictate that vasoactive agents should be adjusted to achieve the predetermined goals. in initial resuscitation with isotonic solutions (> 60 ml/kg), either crystalloid (normal saline) or colloid infusion could be used. despite adequate fluid resuscitation, if: (a) wide pulse pressure, low blood pressure, or bounding pulses (high cardiac output, low systemic vascular resistance - svr) are present, norepinephrine should be considered; (b) prolonged capillary refill, weak pulses, narrow pulse pressure, normotensive (low cardiac output, high svr), dopamine, epinephrine or dobutamine should be considered. adjunctive therapy with stress dose of corticosteroid is indicated in selected populations. conclusions: septic shock hemodynamics is a changing process that requires frequent assessment and therapeutic adjustments.
Human cytomegalovirus infection inhibits CXCL12- mediated migration and invasion of human extravillous cytotrophoblasts
Warner Jessica A,Zwezdaryk Kevin J,Day Bonita,Sullivan Deborah E
Virology Journal , 2012, DOI: 10.1186/1743-422x-9-255
Abstract: Background During the first trimester of pregnancy, a series of tightly regulated interactions govern the formation of a highly invasive population of fetal-derived extravillous cytotrophoblasts (EVT). Successful pregnancy is dependent on efficient invasion of the uterine wall and maternal spiral arteries by EVT. Dysregulated trophoblast invasion is associated with intrauterine growth restriction, birth defects, spontaneous abortion and preeclampsia. A number of soluble growth factors, cytokines, and chemokines modulate this process, fine-tuning the temporal and spatial aspects of cytotrophoblast invasion. In particular, the CXCL12/CXCR4 axis has been shown to specifically modulate cytotrophoblast differentiation, invasion, and survival throughout early pregnancy. Infection with human cytomegalovirus (HCMV) has been associated with impaired differentiation of cytotrophoblasts down the invasive pathway, specifically dysregulating the response to mitogens including epidermal growth factor (EGF) and hepatocyte growth factor (HGF). In this study, the effect of HCMV infection on the CXCL12-mediated migration and invasion of the EVT cell line SGHPL-4 was investigated. Results Infection with HCMV significantly decreased secretion of CXCL12 by SGHPL-4 cells, and induced a striking perinuclear accumulation of the chemokine. HCMV infection significantly increased mRNA and total cell surface expression of the two known receptors for CXCL12: CXCR4 and CXCR7. Functionally, HCMV-infected SGHPL-4 cells were unable to migrate or invade in response to a gradient of soluble CXCL12 in transwell assays. Conclusions Collectively, these studies demonstrate that HCMV impairs EVT migration and invasion induced by CXCL12. As HCMV has the ability to inhibit EVT migration and invasion through dysregulation of other relevant signaling pathways, it is likely that the virus affects multiple signaling pathways to impair placentation and contribute to some of the placental defects seen in HCMV-positive pregnancies.
Urban Tree Effects on Soil Organic Carbon
Jill L. Edmondson, Odhran S. O'Sullivan, Richard Inger, Jonathan Potter, Nicola McHugh, Kevin J. Gaston, Jonathan R. Leake
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0101872
Abstract: Urban trees sequester carbon into biomass and provide many ecosystem service benefits aboveground leading to worldwide tree planting schemes. Since soils hold ~75% of ecosystem organic carbon, understanding the effect of urban trees on soil organic carbon (SOC) and soil properties that underpin belowground ecosystem services is vital. We use an observational study to investigate effects of three important tree genera and mixed-species woodlands on soil properties (to 1 m depth) compared to adjacent urban grasslands. Aboveground biomass and belowground ecosystem service provision by urban trees are found not to be directly coupled. Indeed, SOC enhancement relative to urban grasslands is genus-specific being highest under Fraxinus excelsior and Acer spp., but similar to grasslands under Quercus robur and mixed woodland. Tree cover type does not influence soil bulk density or C:N ratio, properties which indicate the ability of soils to provide regulating ecosystem services such as nutrient cycling and flood mitigation. The trends observed in this study suggest that genus selection is important to maximise long-term SOC storage under urban trees, but emerging threats from genus-specific pathogens must also be considered.
DNA Damage Responses following Exposure to Modulated Radiation Fields
Colman Trainor, Karl T. Butterworth, Conor K. McGarry, Stephen J. McMahon, Joe M. O’Sullivan, Alan R. Hounsell, Kevin M. Prise
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0043326
Abstract: During the delivery of advanced radiotherapy treatment techniques modulated beams are utilised to increase dose conformity across the target volume. Recent investigations have highlighted differential cellular responses to modulated radiation fields particularly in areas outside the primary treatment field that cannot be accounted for by scattered dose alone. In the present study, we determined the DNA damage response within the normal human fibroblast AG0-1522B and the prostate cancer cell line DU-145 utilising the DNA damage assay. Cells plated in slide flasks were exposed to 1 Gy uniform or modulated radiation fields. Modulated fields were delivered by shielding 25%, 50% or 75% of the flask during irradiation. The average number of 53BP1 or γH2AX foci was measured in 2 mm intervals across the slide area. Following 30 minutes after modulated radiation field exposure an increase in the average number of foci out-of-field was observed when compared to non-irradiated controls. In-field, a non-uniform response was observed with a significant decrease in the average number of foci compared to uniformly irradiated cells. Following 24 hrs after exposure there is evidence for two populations of responding cells to bystander signals in-and out-of-field. There was no significant difference in DNA damage response between 25%, 50% or 75% modulated fields. The response was dependent on cellular secreted intercellular signalling as physical inhibition of intercellular communication abrogated the observed response. Elevated residual DNA damage observed within out-of-field regions decreased following addition of an inducible nitric oxide synthase inhibitor (Aminoguanidine). These data show, for the first time, differential DNA damage responses in-and out-of-field following modulated radiation field delivery. This study provides further evidence for a role of intercellular communication in mediating cellular radiobiological response to modulated radiation fields and may inform the refinement of existing radiobiological models for the optimization of advanced radiotherapy treatment plans.
Optimized PCR Conditions and Increased shRNA Fold Representation Improve Reproducibility of Pooled shRNA Screens
?aklina Strezoska, Abel Licon, Josh Haimes, Katie Jansen Spayd, Kruti M. Patel, Kevin Sullivan, Katarzyna Jastrzebski, Kaylene J. Simpson, Devin Leake, Anja van Brabant Smith, Annaleen Vermeulen
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0042341
Abstract: RNAi screening using pooled shRNA libraries is a valuable tool for identifying genetic regulators of biological processes. However, for a successful pooled shRNA screen, it is imperative to thoroughly optimize experimental conditions to obtain reproducible data. Here we performed viability screens with a library of ~10 000 shRNAs at two different fold representations (100- and 500-fold at transduction) and report the reproducibility of shRNA abundance changes between screening replicates determined by microarray and next generation sequencing analyses. We show that the technical reproducibility between PCR replicates from a pooled screen can be drastically improved by ensuring that PCR amplification steps are kept within the exponential phase and by using an amount of genomic DNA input in the reaction that maintains the average template copies per shRNA used during library transduction. Using these optimized PCR conditions, we then show that higher reproducibility of biological replicates is obtained by both microarray and next generation sequencing when screening with higher average shRNA fold representation. shRNAs that change abundance reproducibly in biological replicates (primary hits) are identified from screens performed with both 100- and 500-fold shRNA representation, however a higher percentage of primary hit overlap between screening replicates is obtained from 500-fold shRNA representation screens. While strong hits with larger changes in relative abundance were generally identified in both screens, hits with smaller changes were identified only in the screens performed with the higher shRNA fold representation at transduction.
An assessment of medical students’ awareness of radiation exposures associated with diagnostic imaging investigations
Jennifer O’Sullivan,Owen J. O’Connor,Kevin O’Regan,Bronagh Clarke,Louise N. Burgoyne,Max F. Ryan,Michael M. Maher
Insights into Imaging , 2010, DOI: 10.1007/s13244-010-0009-8
Abstract: Assessment of students’ awareness of radiation exposures in diagnostic imaging demonstrates improved performance with increasing years in medical school and/or increasing exposure to CICR. Findings support the Euroatom 97 directive position, advocating implementation of radiation protection instruction into the undergraduate medical curriculum.
A Kinetic-Based Model of Radiation-Induced Intercellular Signalling
Stephen J. McMahon, Karl T. Butterworth, Colman Trainor, Conor K. McGarry, Joe M. O’Sullivan, Giuseppe Schettino, Alan R. Hounsell, Kevin M. Prise
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0054526
Abstract: It is now widely accepted that intercellular communication can cause significant variations in cellular responses to genotoxic stress. The radiation-induced bystander effect is a prime example of this effect, where cells shielded from radiation exposure see a significant reduction in survival when cultured with irradiated cells. However, there is a lack of robust, quantitative models of this effect which are widely applicable. In this work, we present a novel mathematical model of radiation-induced intercellular signalling which incorporates signal production and response kinetics together with the effects of direct irradiation, and test it against published data sets, including modulated field exposures. This model suggests that these so-called “bystander” effects play a significant role in determining cellular survival, even in directly irradiated populations, meaning that the inclusion of intercellular communication may be essential to produce robust models of radio-biological outcomes in clinically relevant in vivo situations.
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