117 results on '"Simon RJ"'
Search Results
2. ENDGAMES
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Shalchi, Zaid, Lightman, Susan L, Pusey, Charles D, Taylor, Simon RJ, and Sedgwick, Philip
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- 2012
3. Prevalence and causes of phthisis bulbi in a uveitis clinic
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Tan, Lee T., Isa, Hazlita, Lightman, Sue, and Taylor, Simon RJ
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- 2012
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4. Intraocular pressure elevation in uveitis
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Din, Norshamsiah Md, Isa, Hazlita, Taylor, Simon RJ, Barton, Keith, and Lightman, Susan L
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- 2012
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5. Contributors
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Angus, Brian J, Baker, Adam C, Boyle, James G, Campbell, Harry, Soon Chew, Thean, Clifton, Ian J, Clive, Sally, Clunie, Gavin PR, Clutterbuck, Daniel J, Colvin, Lesley A, Connor, Myles D, Conway, Bryan, Cooper, Nicola, Cracknell, Alison L, Culligan, Dominic J, Dockrell, David H, Ellames, Deborah AB, Fallon, Marie, Gibb, Fraser W, Gordon-Walker, Timothy T, Grubb, Neil R, Hunt, David PJ, Ibbotson, Sally H, Jenks, Sara J, Johnston, Sarah L, Lawrie, Stephen M, Lean, Michael EJ, Maartens, Gary, Mackillop, Lucy H, MacMahon, Michael J, Mann, Rebecca J, Manson, Lynn M, Mather, Amanda, Maxwell, Simon RJ, McAllister, David A, Miller-Hodges, Eve, Neuberger, Francesca EM, Newby, David E, Newell-Price, John DC, Olson, John A, Petrie, John R, Phelan, Paul J, Quinn, Terence J, Ralston, Stuart H, Rej, Anupam, Sanders, David S, Sandoe, Jonathan AT, Shand, Alan G, Stares, Mark, Steel, Robby M, Stewart, Grant D, Sullivan, David R, Sundar, Shyam, Tallentire, Victoria R, Tatton-Brown, Katrina, Thomas, Simon HL, Watson, Henry G, White, Julian, Whiteley, William, Williams, Michael J, and Woodfield, Rebecca
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- 2023
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6. Ocular manifestations of Wegenerʼs granulomatosis
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Isa, Hazlita, Lightman, Susan, Pusey, Charles D, and Taylor, Simon RJ
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- 2011
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7. Use of nomogram to predict acute urinary retention
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TANG, VINCENT CY and BOTT, SIMON RJ
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- 2007
8. Creating retroperitoneal space for retroperitoneoscopy using RÜSH® bladder hydrodistension catheter
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TANG, VINCENT CY, BOTT, SIMON RJ, and LE ROUX, PIETER J
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- 2007
9. A better way to insert urethral catheter with guide-wire
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TANG, VINCENT CY and BOTT, SIMON RJ
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- 2006
10. Receptor Functions
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Maxwell, Simon RJ and Webb, David J
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- 2003
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11. Valacyclovir in the treatment of acute retinal necrosis
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Taylor Simon RJ, Hamilton Robin, Hooper Claire Y, Joshi Lavnish, Morarji Jiten, Gupta Nitin, and Lightman Sue L
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Acute retinal necrosis ,Herpetic retinitis ,Acyclovir ,Valacyclovir ,Ophthalmology ,RE1-994 - Abstract
Abstract Background To report the outcome of oral valacyclovir as the sole antiviral therapy for patients with acute retinal necrosis (ARN). Methods This study reports a retrospective, interventional case series of nine consecutive patients with ten eyes with newly diagnosed ARN treated with oral valacyclovir as the sole antiviral agent. Eight patients received oral valacyclovir 2 g tid (Valtrex, GlaxoSmithKline) and one patient with impaired renal function received oral 1 g tid. The main outcome measures were response to treatment, time to initial response to treatment, time to complete resolution of retinitis, best corrected visual acuity (BCVA) at final follow-up, retinal detachment and development of recurrent or second eye disease. Results Retinitis resolved in ten of ten (100%) affected eyes. The median time to initial detectable response was seven days and the median time to complete resolution was 21 days. A final BCVA of 20/40 or better was achieved in 6/10 (60%) of eyes. 3/10 eyes (30%) developed a retinal detachment. No patients developed either disease reactivation or second eye involvement over the course of the study (mean follow up 31 weeks, range 7 to 104 weeks). Conclusions Treatment with oral valacyclovir as the sole antiviral therapy resulted in complete resolution of retinitis. Final BCVA and retinal detachment rate were comparable with previously reported outcomes for intravenous acyclovir.
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- 2012
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12. Contributors
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Angus, Brian J, Anstee, Quentin M, Burnett, Leslie, Byers, Mark, Campbell, Harry, Clunie, Gavin PR, Colvin, Lesley A, Conway, Bryan, Cooper, Nicola, Cracknell, Alison L, Culligan, Dominic J, Dark, Graham G, Davenport, Richard J, Dockrell, David H, El-Omar, Emad, Fallon, Marie, FitzPatrick, David R, Grubb, Neil R, Ibbotson, Sally H, Innes, J Alastair, Jenks, Sara J, Johnston, Sarah L, Jones, David EJ, Langhorne, Peter, Lawrie, Stephen M, Leach, John Paul, Maartens, Gary, Mackillop, Lucy, MacMahon, Michael J, Mann, Rebecca, Manson, Lynn M, Marshall, Sara E, Mather, Amanda, Maxwell, Simon RJ, McAllister, David A, McCrimmon, Rory J, McLean, Mairi H, Neuberger, Francesca EM, Newby, David E, Newell-Price, John DC, Olson, John, Pearson, Ewan R, Phelan, Paul J, Ralston, Stuart H, Reid, Peter T, Sandoe, Jonathan AT, Scott, Gordon R, Shand, Alan G, Steel, Robby M, Stewart, Grant D, Stewart, Peter, Strachan, Mark WJ, Sullivan, David R, Sundar, Shyam, Tallentire, Victoria R, Tatton-Brown, Katrina, Thomas, Simon HL, Watson, Henry G, White, Julian, Wilding, John PH, and Witham, Miles D
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- 2018
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13. Oxygen therapy in acute medical care: the potential dangers of hyperoxia need to be recognised. (Editorials)
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Thomson, Alastair J., Webb, David J., Maxwell, Simon RJ, and Grant, Ian S.
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Oxygen therapy -- Dosage and administration ,Oximetry ,Health ,Dosage and administration - Abstract
Oxygen is cheap, widely available, and used in a range of settings and conditions to relieve or prevent tissue hypoxia. Since its discovery by Scheele and Priestley in the 1770s, [...]
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- 2002
14. COX-2 selective inhibitors—important lessons learned
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Maxwell, Simon RJ and Webb, David J
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- 2005
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15. The eye in haematological disease.
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Shalchi, Zaid, Taylor, Simon RJ, and Lightman, Sue
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- 2011
16. The eye and phacomatoses.
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Joshi, Lavnish, Taylor, Simon RJ, and Lightman, Sue
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- 2011
17. The eye in renal disease.
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Muthusamy, Kirithika, Lightman, Sue, and Taylor, Simon RJ
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- 2011
18. The eye in rheumatology.
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Morarji, Jiten, Lightman, Sue, and Taylor, Simon RJ
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- 2011
19. The eye in virology.
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Robins, Julian, Lightman, Sue, and Taylor, Simon RJ
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- 2011
20. Deprivation-based risk scores: the re-emergence of postcode prescribing in the UK?
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Payne, Rupert A and Maxwell, Simon RJ
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- 2009
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21. Transracial placement in adoptions with public agency involvement: what can we learn from the AFCARS data?
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Hansen ME and Simon RJ
- Abstract
The Adoption and Safe Families Act gave incentives to states to promote adoption in a environment in which routine racial matching in adoptive placement was forbidden under the Multiethnic Placement Act/Interethnic Adoption Provisions. Adoptions of many kinds increased after the passage of ASFA. Did transracial adoptive placements also increase under ASFA? Using the public use files of the Adoption and Foster Care Reporting System for fiscal years 1995 through 2001, we calculate the percent of adoptions with state involvement that were transracial. At the national level, there is no evidence of an increase in transracial adoptions after ASFA, but in a group of six states transracial adoption as clearly increased since ASFA. [ABSTRACT FROM AUTHOR]
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- 2004
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22. Practice management guidelines for the optimal timing of long-bone fracture stabilization in polytrauma patients: the EAST Practice Management Guidelines Work Group.
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Dunham CM, Bosse MJ, Clancy TV, Cole FJ Jr., Coles MJM, Knuth T, Luchette FA, Ostrum R, Plaisier B, Poka A, and Simon RJ
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- 2001
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23. Effect of hemorrhage on superior mesenteric artery flow during increased intra-abdominal pressures.
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Friedlander MH, Simon RJ, Ivatury R, DiRaimo R, and Machiedo GW
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- 1998
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24. Intestinal permeability correlates with severity of injury in trauma patients.
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Faries PL, Simon RJ, Martella AT, Lee MJ, and Machiedo GW
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- 1998
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25. Intra-abdominal hypertension after life-threatening penetrating abdominal trauma: prophylaxis, incidence, and clinical relevance to gastric mucosal pH and abdominal compartment syndrome.
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Ivatury RR, Porter JM, Simon RJ, Islam S, John R, and Stahl WM
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- 1998
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26. Hemorrhage lowers the threshold for intra-abdominal hypertension-induced pulmonary dysfunction.
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Simon RJ, Friedlander MH, Ivatury RR, DiRaimo R, and Machiedo GW
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- 1997
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27. Choice of opioid analgesics in postoperative care
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Maxwell, Simon RJ and Bateman, D Nicholas
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- 2007
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28. Clinical pharmacology—too young to die?
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Maxwell, Simon RJ and Webb, David J
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- 2006
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29. Local therapies for inflammatory eye disease in translation: past, present and future.
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Tempest-Roe, Shenzhen, Joshi, Lavnish, Dick, Andrew D, Taylor, Simon Rj, and Taylor, Simon R J
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ADRENOCORTICAL hormones ,INJECTIONS ,ANTI-inflammatory agents ,INTRAOCULAR drug administration ,UVEITIS ,TUMOR necrosis factors ,RESEARCH funding ,IMMUNOSUPPRESSIVE agents ,EYE diseases ,CHEMICAL inhibitors - Abstract
Despite their side-effects and the advent of systemic immunosuppressives and biologics, the use of corticosteroids remains in the management of patients with uveitis, particularly when inflammation is associated with systemic disease or when bilateral ocular disease is present. The use of topical corticosteroids as local therapy for anterior uveitis is well-established, but periocular injections of corticosteroid can also be used to control mild or moderate intraocular inflammation. More recently, intraocular corticosteroids such as triamcinolone and steroid-loaded vitreal inserts and implants have been found to be effective, including in refractory cases. Additional benefits are noted when ocular inflammation is unilateral or asymmetric, when local therapy may preclude the need to increase the systemic medication.Implants in particular have gained prominence with evidence of efficacy including both dexamethasone and fluocinolone loaded devices. However, an appealing avenue of research lies in the development of non-corticosteroid drugs in order to avoid the side-effects that limit the appeal of injected corticosteroids. Several existing drugs are being assessed, including anti-VEGF compounds such as ranibizumab and bevacizumab, anti-tumour necrosis factor alpha antibodies such as infliximab, as well as older cytotoxic medications such as methotrexate and cyclosporine, with varying degrees of success. Intravitreal sirolimus is currently undergoing phase 3 trials in uveitis and other inflammatory pathways have also been proposed as suitable therapeutic targets. Furthermore, the advent of biotechnology is seeing advances in generation of new therapeutic molecules such as high affinity binding peptides or modified high affinity or bivalent single chain Fab fragments, offering higher specificity and possibility of topical delivery. [ABSTRACT FROM AUTHOR]
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- 2013
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30. Exploratory immunogenicity outcomes of peanut oral immunotherapy: Findings from the PALISADE trial.
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Nilsson C, Vereda A, Borres MP, Andersson M, Södergren E, Rudengren M, Smith A, Simon RJ, Ryan R, Fernández-Rivas M, Adelman D, and Vickery BP
- Abstract
Background: Immunoglobulin E (IgE) and immunoglobulin G4 (IgG4) to peanut and its components may influence the clinical reactivity to peanut. Allergen-specific immunotherapy is known for modifying both IgE and IgG4. Peanut oral immunotherapy may influence these serological parameters., Methods: Exploratory analyses of serological data from participants receiving peanut (Arachis hypogaea) allergen powder-dnfp (PTAH) and placebo in the double-blind, randomized, phase 3 PALISADE trial were conducted to evaluate potential relationships between peanut-specific and peanut component-specific (Ara h 1, Ara h 2, Ara h 3, Ara h 6, Ara h 8, and Ara h 9) IgE and IgG4 levels and clinical outcomes., Results: A total of 269 participants (PTAH, n = 202; placebo, n = 67) were analyzed. No relationship was observed between specific IgE and IgG4 levels at screening and maximum tolerated peanut protein dose during screening or response status during exit double-blind placebo-controlled food challenge (DBPCFC). In PTAH-treated participants, no relationship was observed between IgE and IgG4 levels at screening and maximum symptom severity during exit DBPCFC. Postscreening ratios (ie, postscreening/screening) in the PTAH group were significant at the end of updosing and exit visit for most components. Postscreening changes in specific IgE levels were more pronounced with PTAH versus placebo for most components., Conclusions: Specific IgE and IgG4 levels at screening are not correlated with screening or exit DBPCFC results, and are not predictive of clinical response to PTAH. Peanut (Arachis hypogaea) allergen powder-dnfp contains the relevant and immunodominant allergens, inducing immunological changes with the treatment., Clinical Trial Registration: ClinicalTrials.gov identifier: NCT02635776., (© 2024 The Authors. Clinical and Translational Allergy published by John Wiley & Sons Ltd on behalf of European Academy of Allergy and Clinical Immunology.)
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- 2024
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31. IgE and IgG4 epitopes of the peanut allergens shift following oral immunotherapy.
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Rambo IM, Kronfel CM, Rivers AR, Swientoniewski LT, McBride JK, Cheng H, Simon RJ, Ryan R, Tilles SA, Nesbit JB, Kulis MD, Hurlburt BK, and Maleki SJ
- Abstract
Background: Oral immunotherapy (OIT) with peanut ( Arachis hypogaea ) allergen powder-dnfp (PTAH; Aimmune Therapeutics) is an FDA-approved treatment to desensitize peanut allergic participants., Objective: Here we assessed shifts in IgE and IgG4 binding to peanut allergens and their epitopes recognized by United States (US) peanut allergic participants ( n = 20) enrolled in phase 3 PTAH OIT clinical trials., Methods: Pre- and post- trial participant sera were collected approximately 12 months apart and tested for IgE binding to intact peanut proteins via ImmunoCAP ISAC immunoassays. IgE and IgG4 linear epitopes were identified based on binding to synthetic overlapping 15-mer linear peptides of 10 peanut allergens (Ara h 1-11) synthesized on microarray slides., Results: Statistically significant decreases in IgE binding were identified for intact Ara h 2, 3, and 6, and known and newly identified IgE epitopes were shown to exhibit shifts towards IgG4 binding post-OIT, with most linear peptides having increased IgG4 binding after treatment with PTAH. While PTAH does not seem to alter the actual peptide binding patterns significantly after one year of treatment, the IgE and IgG4 binding ratios and intensity are altered., Conclusion: At a population level, the linear IgE and IgG4 epitopes of 10 peanut allergens overlap and that increase in IgG4 with OIT results in displacement of IgE binding to both conformational and linear epitopes. Furthermore, it appears as though the increase in IgG4 is more important to achieve desensitization at the 12-month timepoint than the decrease in IgE. This type of knowledge can be useful in the identification of IgE and IgG4-binding allergen and peptide biomarkers that may indicate desensitization or sustained unresponsiveness of allergic individuals to peanut., Competing Interests: SAT is an employee of Aimmune Nestle Health Science. This study was funded by The United States Department of Agriculture (USDA), Agricultural Research Service and by Aimmune Nestlé Health Science, via a Cooperative Research and Development Agreement (CRADA agreement #58-6054-1-0011). Aimmune Nestlé was involved in performing the OIT study with Palforzia, which is published information, but was not involved in the design and interpretation of this study. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (© 2023 Rambo, Kronfel, Rivers, Swientoniewski, McBride, Cheng, Simon, Ryan, Tilles, Nesbit, Kulis, Hurlburt and Maleki.)
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- 2023
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32. Cryo-EM structure of human PAPP-A2 and mechanism of substrate recognition.
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Sridar J, Mafi A, Judge RA, Xu J, Kong KA, Wang JCK, Stoll VS, Koukos G, Simon RJ, Eaton D, Bratkowski M, and Hao Q
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Pregnancy-Associated Plasma Protein A isoforms, PAPP-A and PAPP-A2, are metalloproteases that cleave insulin-like growth factor binding proteins (IGFBPs) to modulate insulin-like growth factor signaling. The structures of homodimeric PAPP-A in complex with IGFBP5 anchor peptide, and inhibitor proteins STC2 and proMBP have been recently reported. Here, we present the single-particle cryo-EM structure of the monomeric, N-terminal LG, MP, and the M1 domains (with the exception of LNR1/2) of human PAPP-A2 to 3.13 Å resolution. Our structure together with functional studies provides insight into a previously reported patient mutation that inactivates PAPP-A2 in a distal region of the protein. Using a combinational approach, we suggest that PAPP-A2 recognizes IGFBP5 in a similar manner as PAPP-A and show that PAPP-A2 cleaves IGFBP5 less efficiently due to differences in the M2 domain. Overall, our studies characterize the cleavage mechanism of IGFBP5 by PAPP-A2 and shed light onto key differences with its paralog PAPP-A., (© 2023. The Author(s).)
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- 2023
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33. IgE epitopes of Ara h 9, Jug r 3, and Pru p 3 in peanut-allergic individuals from Spain and the US.
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Kronfel CM, Cheng H, McBride JK, Nesbit JB, Krouse R, Burns P, Cabanillas B, Crespo JF, Ryan R, Simon RJ, Maleki SJ, and Hurlburt BK
- Abstract
Non-specific lipid transfer proteins (LTPs) are well studied allergens that can lead to severe reactions, but often cause oral allergy syndrome in the Mediterranean area and other European countries. However, studies focused on LTP reactivity in allergic individuals from the United States are lacking because they are not considered major allergens. The goal of this study is to determine if differences in immunoglobulin (Ig) E binding patterns to the peanut allergen Ara h 9 and two homologous LTPs (walnut Jug r 3 and peach Pru p 3) between the US and Spain contribute to differences observed in allergic reactivity. Synthetic overlapping 15-amino acid-long peptides offset by five amino acids from Ara h 9, Jug r 3, and Pru p 3 were synthesized, and the intact proteins were attached to microarray slides. Sera from 55 peanut-allergic individuals from the US were tested for IgE binding to the linear peptides and IgE binding to intact proteins using immunofluorescence. For comparison, sera from 17 peanut-allergic individuals from Spain were also tested. Similar IgE binding profiles for Ara h 9, Jug r 3, and Pru p 3 were identified between the US and Spain, with slight differences. Certain regions of the proteins, specifically helices 1 and 2 and the C-terminal coil, were recognized by the majority of the sera more often than other regions of the proteins. While serum IgE from peanut-allergic individuals in the US binds to peptides of Ara h 9 and its homologs, only IgE from the Spanish subjects bound to the intact LTPs. This study identifies Ara h 9, Jug r 3, and Pru p 3 linear epitopes that were previously unidentified using sera from peanut-allergic individuals from the US and Spain. Certain regions of the LTPs are recognized more often in US subjects, indicating that they represent conserved and possible cross-reactive regions. The location of the epitopes in 3D structure models of the LTPs may predict the location of potential conformational epitopes bound by a majority of the Spanish patient sera. These findings are potentially important for development of peptide or protein-targeting diagnostic and therapeutic tools for food allergy., Competing Interests: Author RK and PB were employed by the company Rho Federal Systems Division. Authors RR and RS were employed by the company Aimmune Therapeutics. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Kronfel, Cheng, McBride, Nesbit, Krouse, Burns, Cabanillas, Crespo, Ryan, Simon, Maleki and Hurlburt.)
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- 2023
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34. The Role of Family History and Germline Genetics in Prostate Cancer Disease Profile and Screening
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Raghallaigh HN, Bott SRJ, Barber N, and Ali A
- Abstract
Established risk factors for prostate cancer include age, ethnicity, a family history of prostate cancer or carrying a pathogenic germline variation in a prostate cancer predisposition gene. Approximately 10–15% of men with advanced prostate cancer have a germline genetic predisposition to the disease (i.e., BRCA2 ). Whilst the largest, and most well-known prostate cancer screening studies (i.e., ERSPC) have focused on the use of prostate-specific antigen as a screening tool, the incorporation of tissue and liquid genomic biomarkers alongside modern imaging modalities are being designed to individualize and improve the accuracy of both the screening and diagnostic pathway. The use of a polygenic risk scoring can now also offer a man his personalized prostate cancer risk based on a number of low-risk, common genetic variants and is currently the subject of ongoing research. The mainstreaming of genomics into the prostate cancer screening, diagnostic and treatment pathway will soon become embedded into routine clinical practice. This chapter aims to summarize current knowledge on the topic of men who harbor a genetic predisposition to prostate cancer, how this predisposition arises, its stratification into low-risk common variants vs. high-risk, rare variants, and its impact and incorporation into screening and diagnostic algorithms. The importance of germline genetics beyond screening and diagnostics, its role in the identification of lethal prostate cancer, and in the selection of targeted treatments for advanced disease is also discussed., (Copyright: The Authors.; The authors declare no potential conflict of interest with respect to research, authorship and/or publication of this chapter.)
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- 2022
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35. Prostate Cancer
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Bott SRJ and Ng KL
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Prostate cancer is a life-altering diagnosis, not just for patients, but for their loved ones as well. Once, prostate cancer was most frequently diagnosed in men in their 60s and 70s; with increasing use of imaging modalities and PSA testing, the incidence is on the rise, and we are now seeing men in their 40s with the disease. This poses a challenge for clinical management depending on the stage of the disease—from watchful waiting or active surveillance to aggressive treatment with the risk of therapeutic nihilism. Despite being one of the most common cancers in Western men, its natural history, prognosis, and treatment are poorly understood. This book brings together a select faculty of experts to present a comprehensive view of the current state and future perspectives of prostate cancer. There are ten chapters in the book—the first four cover our present knowledge and understanding of the disease, the following three explore new advancements and treatments, particularly looking at overcoming resistance to therapy, and the remaining three chapters focus on specific molecules with the potential to become drug targets. We all have much to learn about prostate cancer. This book is aimed primarily at clinicians and scientists, but many areas will also be of interest to the layperson., (Copyright© 2021 Exon Publications.)
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- 2021
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36. Current Diagnostics for Prostate Cancer
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Whiting D, Bott SRJ, Bott SRJ, and Ng KL
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How prostate cancer is diagnosed and staged is an ever-evolving field. It plays a fundamental role in ensuring the appropriate therapeutic options are offered to the patient whilst preventing overdiagnosis and overtreatment. Despite the numerous advances in the field, a suspicion of prostate cancer continues to arise from digital rectal examination and measurement of serum prostate specific antigen (PSA). Additional derivatives of serum PSA along with urinary biomarkers and multiparametric magnetic resonance imaging can then help to risk stratify patients in order to appropriately counsel them on the risks and benefits of a prostate biopsy. After a diagnosis of prostate cancer is reached, further staging may be required and can be achieved by a variety of imaging techniques such as computed tomography (CT), bone scintigraphy, and prostate specific membrane antigen-based positron-emission tomography/CT. In this chapter, we review the current role of these and other diagnostic tools in prostate cancer., (Copyright: The Authors.)
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- 2021
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37. Effect of weekend admission on geriatric hip fractures.
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Pasternack JB, Ciminero ML, Silver M, Chang J, Simon RJ, and Kang KK
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Background: The care discrepancy for patients presenting to a hospital on the weekend relative to the work week is well documented. With respect to hip fractures, however, there is no consensus about the presence of a so-called "weekend effect". This study sought to determine the effects, if any, of weekend admission on care of geriatric hip fractures admitted to a large tertiary care hospital. It was hypothesized that geriatric hip fracture patients admitted on a weekend would have longer times to medical optimization and surgery and increased complication and mortality rates relative to those admitted on a weekday., Aim: To determine if weekend admission of geriatric hip fractures is associated with poor outcome measures and surgical delay., Methods: A retrospective chart review of operative geriatric hip fractures treated from 2015-2017 at a large tertiary care hospital was conducted. Two cohorts were compared: patients who arrived at the emergency department on a weekend, and those that arrived at the emergency department on a weekday. Primary outcome measures included mortality rate, complication rate, transfusion rate, and length of stay. Secondary outcome measures included time from emergency department arrival to surgery, time from emergency department arrival to medical optimization, and time from medical optimization to surgery., Results: There were no statistically significant differences in length of stay ( P = 0.2734), transfusion rate ( P = 0.9325), or mortality rate ( P = 0.3460) between the weekend and weekday cohorts. Complication rate was higher in patients who presented on a weekend compared to patients who presented on a weekday (13.3% vs 8.3%; P = 0.044). Time from emergency department arrival to medical optimization (22.7 h vs 20.0 h; P = 0.0015), time from medical optimization to surgery (13.9 h vs 10.8 h; P = 0.0172), and time from emergency department arrival to surgery (42.7 h vs 32.5 h; P < 0.0001) were all significantly longer in patients who presented to the hospital on a weekend compared to patients who presented to the hospital on a weekday., Conclusion: This study provided insight into the "weekend effect" for geriatric hip fractures and found that day of presentation has a clinically significant impact on delivered care., Competing Interests: Conflict-of-interest statement: We have no financial relationships to disclose., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)
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- 2020
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38. Getting It Right for Our Patients: The Importance of Collaborative Leadership in the ICU.
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Savel RH, Shiloh AL, Simon RJ, and Kupfer Y
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- Intensive Care Units, Cooperative Behavior, Leadership
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- 2019
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39. Using Big Data to See the Big Picture in Sepsis.
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Savel RH, Shiloh AL, Simon RJ, and Kupfer Y
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- Humans, Big Data, Sepsis
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- 2018
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40. The Intensive Care Unit Perspective of Becoming a Level I Trauma Center: Challenges of Strategy, Leadership, and Operations Management.
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Savel RH, Cohen W, Borgia D, and Simon RJ
- Abstract
The primary purpose of this narrative is to elucidate the numerous significant changes that occur at the intensive care unit (ICU) level as a medical center pursues becoming a Level I trauma center. Specifically, we will focus on the following important areas: (1) leadership and strategy issues behind the decision to move forward with becoming a trauma center; (2) preparation needed to take a highly functioning surgical ICU and align it for the inevitable changes that happen as trauma go-live occurs; (3) intensivist staffing changes; (4) roles for and training of advanced practice practitioners; (5) graduate medical education issues; (6) optimizing interactions with closely related services; (7) nursing, staffing, and training issues; (8) bed allocation issues; and (9) reconciling the advantages of a "unified adult critical care service" with the realities of the central relationship between trauma and surgical critical care., Competing Interests: There are no conflicts of interest.
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- 2018
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41. Unraveling the Mysterious Relationship Between Obesity and Outcomes in Patients With Sepsis.
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Savel RH, Simon RJ, and Kupfer Y
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- Humans, Obesity, Sepsis
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- 2016
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42. Rational prescribing: the principles of drug selection.
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Maxwell SR
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- Humans, Precision Medicine, Drug Prescriptions, Drug Therapy methods, Drug Therapy standards
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Prescribing is the most important tool used by physicians to cure illness, relieve symptoms and prevent future disease. It is also a complex intellectual task that requires formulation of an appropriate treatment regimen from the many thousands available, taking into account the infinite variation in the patients they encounter. Unfortunately, the selection of a medicine and dosage regimen is sometimes suboptimal, leading to poor patient outcomes (eg treatment failure, avoidable adverse reactions). This article will highlight some of the common prescribing errors and will develop a rational approach that includes making a diagnosis, estimating prognosis, establishing the goals of therapy, selecting the most appropriate treatment and monitoring the effects of the treatment., (© Royal College of Physicians 2016. All rights reserved.)
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- 2016
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43. Fatal Falls in New York City: An Autopsy Analysis of Injury Patterns.
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Obeid NR, Bryk DJ, Lee T, Hemmert KC, Frangos SG, Simon RJ, Pachter HL, and Cohen SM
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- Accidents, Occupational mortality, Adolescent, Adult, Age Distribution, Female, Forensic Medicine, Hemorrhage mortality, Humans, Male, Middle Aged, New York City epidemiology, Personal Protective Equipment adverse effects, Prospective Studies, Sex Distribution, Young Adult, Accidental Falls mortality, Suicide statistics & numerical data, Wounds and Injuries mortality
- Abstract
Introduction: Falls from heights are an important cause of unintentional fatal injury. We investigated the relationship between the characteristics of fatal falls and resulting injury patterns., Materials and Methods: We reviewed prospectively collected data from the Office of Chief Medical Examiner in New York City between 2000 and 2010. Data included fall height, work or non-work related, use of safety equipment, intentionality, specific organ injuries, and death on impact. The primary outcome was organ injury based on fall height., Results: Higher falls were associated with hemorrhage as well as rib and various organ injuries. Organ injury pattern did not differ based on work status. The presence of equipment misuse or malfunction was associated with more deaths upon impact. Victims of falls from 200 ft or higher were 11.59 times more likely to die on impact than from lower than 25 ft., Conclusions: Fall height and work-related falls were significantly associated with death on impact. This is a public health issue, as 13% of falls were work related and 4% of falls were due to improper use of safety equipment. Some work-related falls are potentially preventable with proper safety equipment use. Understanding patterns of injury may play a role in prevention and management of survivors in the acute period.
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- 2016
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44. A High-Affinity Native Human Antibody Disrupts Biofilm from Staphylococcus aureus Bacteria and Potentiates Antibiotic Efficacy in a Mouse Implant Infection Model.
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Estellés A, Woischnig AK, Liu K, Stephenson R, Lomongsod E, Nguyen D, Zhang J, Heidecker M, Yang Y, Simon RJ, Tenorio E, Ellsworth S, Leighton A, Ryser S, Gremmelmaier NK, and Kauvar LM
- Subjects
- Amino Acid Sequence, Animals, Anti-Bacterial Agents biosynthesis, Anti-Bacterial Agents isolation & purification, Antibodies, Monoclonal biosynthesis, Antibodies, Monoclonal isolation & purification, Antibody Specificity, B-Lymphocytes chemistry, B-Lymphocytes cytology, B-Lymphocytes immunology, Bacterial Proteins antagonists & inhibitors, Bacterial Proteins genetics, Bacterial Proteins metabolism, Biofilms growth & development, DNA-Binding Proteins antagonists & inhibitors, DNA-Binding Proteins genetics, DNA-Binding Proteins metabolism, Daptomycin pharmacology, Disease Models, Animal, Drug Therapy, Combination, Epitope Mapping, Female, Foreign Bodies microbiology, Gene Expression, Injections, Intraperitoneal, Integration Host Factors antagonists & inhibitors, Integration Host Factors genetics, Integration Host Factors metabolism, Methicillin-Resistant Staphylococcus aureus genetics, Methicillin-Resistant Staphylococcus aureus growth & development, Methicillin-Resistant Staphylococcus aureus metabolism, Mice, Mice, Inbred C57BL, Models, Molecular, Plankton drug effects, Plankton genetics, Plankton growth & development, Plankton metabolism, Sequence Alignment, Single-Cell Analysis, Staphylococcal Infections microbiology, Anti-Bacterial Agents pharmacology, Antibodies, Monoclonal pharmacology, Biofilms drug effects, Foreign Bodies drug therapy, Methicillin-Resistant Staphylococcus aureus drug effects, Staphylococcal Infections drug therapy
- Abstract
Many serious bacterial infections are difficult to treat due to biofilm formation, which provides physical protection and induces a sessile phenotype refractory to antibiotic treatment compared to the planktonic state. A key structural component of biofilm is extracellular DNA, which is held in place by secreted bacterial proteins from the DNABII family: integration host factor (IHF) and histone-like (HU) proteins. A native human monoclonal antibody, TRL1068, has been discovered using single B-lymphocyte screening technology. It has low-picomolar affinity against DNABII homologs from important Gram-positive and Gram-negative bacterial pathogens. The disruption of established biofilm was observedin vitroat an antibody concentration of 1.2 μg/ml over 12 h. The effect of TRL1068in vivowas evaluated in a murine tissue cage infection model in which a biofilm is formed by infection with methicillin-resistantStaphylococcus aureus(MRSA; ATCC 43300). Treatment of the established biofilm by combination therapy of TRL1068 (15 mg/kg of body weight, intraperitoneal [i.p.] administration) with daptomycin (50 mg/kg, i.p.) significantly reduced adherent bacterial count compared to that after daptomycin treatment alone, accompanied by significant reduction in planktonic bacterial numbers. The quantification of TRL1068 in sample matrices showed substantial penetration of TRL1068 from serum into the cage interior. TRL1068 is a clinical candidate for combination treatment with standard-of-care antibiotics to overcome the drug-refractory state associated with biofilm formation, with potential utility for a broad spectrum of difficult-to-treat bacterial infections., (Copyright © 2016, American Society for Microbiology. All Rights Reserved.)
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- 2016
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45. Risky behaviors associated with pediatric pedestrians and bicyclists struck by motor vehicles.
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Glass NE, Frangos SG, Simon RJ, Bholat OS, Todd SR, Wilson C, Jacko S, Slaughter D, Foltin G, and Levine DA
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- Adolescent, Adult, Child, Child, Preschool, Cohort Studies, Female, Humans, Infant, Male, New York City, Prospective Studies, Risk Factors, Trauma Centers, Accidents, Traffic statistics & numerical data, Bicycling injuries, Motor Vehicles statistics & numerical data, Risk-Taking
- Abstract
Objective: Road safety constitutes a crisis with important health and economic impacts. In 2010, 11,000 pedestrians and 3500 bicyclists were injured by motor vehicles in New York City (NYC). Motor vehicle injuries represent the second leading cause of injury-related deaths in NYC children aged 5 to 14 years. To better target injury prevention strategies, we evaluated demographics, behaviors, environmental factors, injuries, and outcomes of pediatric pedestrians and bicyclists struck by motor vehicles in NYC., Methods: Pediatric data were extracted from a prospectively collected database of pedestrians and bicyclists struck by motor vehicles and treated at a level I regional trauma center between December 2008 and June 2011. Patients, guardians, and first responders were interviewed and medical records were reviewed. Institutional review board approval was granted and verbal consent was obtained., Results: Of the 1457 patients, 168 (12%) were younger than 18 years. Compared with injured adults, children were more likely to be in male sex (69% vs 53%), to have minor injuries (83% vs 73% for injury severity scores of <9), and to be discharged without admission (69% vs 67%). Midblock crossings were more common in children pedestrians than in adults (37% vs 19%), often despite supervision (48%). Electronic device use among teenagers aged 13 to 17 years was nearly 3 times that of adults (28% vs 11%)., Conclusions: Risky behaviors are common among pediatric pedestrians and bicyclists injured by motor vehicles. Road safety education and prevention strategies must stress compliance with traffic laws, readdress the importance of supervision, and reinforce avoidance of common distractors including electronic devices.
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- 2014
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46. Birdshot uveitis: current and emerging treatment options.
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Menezo V and Taylor SR
- Abstract
Birdshot chorioretinopathy is a relatively uncommon subtype of idiopathic posterior uveitis with distinct clinical characteristics and a strong genetic association with the Human Leukocyte Antigen (HLA)-A29 allele. The diagnosis remains clinical and is based on the presence of typical clinical features, including multiple, distinctive, hypopigmented choroidal lesions throughout the fundus. The long-term visual prognosis of this disorder, however, remains guarded - central visual acuity can be preserved until late in the disease and it is not uncommon for patients to receive inadequate immunosuppressive treatment, leading to a poor long-term outcome in which peripheral retinal damage eventually leads to visual deterioration. Birdshot chorioretinopathy has proven a particularly attractive area of study within the field of uveitis, as it is a relatively easily defined disease with an associated human leukocyte antigen haplotype. Despite this, however, the immune mechanisms involved in its pathogenesis remain unclear, and some patients continue to lose retinal function despite therapy with corticosteroids and conventional immunosuppressive agents. Laboratory research continues to investigate the underlying mechanisms of disease, and clinical research is now being driven to improve the phenotyping and monitoring of this condition as, in the era of so-called personalized medicine, it is becoming increasingly important to identify patients at risk of visual loss early so that they can be treated more aggressively with targeted therapies such as the newer biological agents. This approach requires the formation of collaborative groups, as the relative rarity of the condition makes it difficult for one center to accumulate enough patients for worthwhile studies. Nevertheless, results obtained with newer therapies, such as biological agents directed against particular cytokines or cell-surface receptors, demonstrate ever improving control of the inflammation in refractory cases, providing hope that the outlook for visual function in this condition can only improve.
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- 2014
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47. The (f)utility of flexion-extension C-spine films in the setting of trauma.
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Sim V, Bernstein MP, Frangos SG, Wilson CT, Simon RJ, McStay CM, Huang PP, Pachter HL, and Todd SR
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- Adult, Cervical Vertebrae diagnostic imaging, Female, Humans, Male, Retrospective Studies, Algorithms, Cervical Vertebrae injuries, Spinal Injuries diagnostic imaging, Tomography, X-Ray Computed methods, X-Ray Film statistics & numerical data
- Abstract
Background: Flexion-extension radiographs are often used to assess for removal of the cervical collar in the setting of trauma. The objective of this study was to evaluate their adequacy. We hypothesized that a significant proportion is inadequate., Methods: This was a retrospective review of C-spine clearance at a level 1 trauma center. A trauma-trained radiologist interpreted all flexion-extension radiographs for adequacy. Studies performed within 7 days of injury were considered acute., Results: Three hundred fifty-five flexion-extension radiographs were examined. Ninety-five percent% of these studies were inadequate (51% because of the inability to visualize the top of T1, whereas 44% had less than 30° of angulation from neutral). Two hundred ten studies were performed acutely; of these, 97% were inadequate. When performed 7 days or longer from injury, 91% were inadequate., Conclusions: Injury to the C-spine may harbor significant consequences; therefore, its proper evaluation is critical. The majority of flexion-extension films are inadequate. As such, they should not be included in the algorithm for removal of the cervical collar. If used, adequacy must be verified and supplemental radiographic studies obtained as indicated., (Copyright © 2013 Elsevier Inc. All rights reserved.)
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- 2013
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48. Helmet use is associated with safer bicycling behaviors and reduced hospital resource use following injury.
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Webman R, Dultz LA, Simon RJ, Todd SR, Slaughter D, Jacko S, Bholat O, Wall S, Wilson C, Levine DA, Roe M, Pachter HL, and Frangos SG
- Subjects
- Accidents, Traffic mortality, Craniocerebral Trauma psychology, Follow-Up Studies, Humans, Injury Severity Score, Prospective Studies, Survival Rate trends, United States epidemiology, Accidents, Traffic prevention & control, Bicycling injuries, Craniocerebral Trauma prevention & control, Head Protective Devices statistics & numerical data, Health Resources trends, Risk-Taking, Trauma Centers statistics & numerical data
- Abstract
Background: While the efficacy of helmet use in the prevention of head injury is well described, helmet use as it relates to bicyclists' behaviors and hospital resource use following injury is less defined. The objective of this study was to compare the demographics, behaviors, hospital workups, and outcomes of bicyclists based on helmet use., Methods: This study was a subset analysis of a 2.5-year prospective cohort study of vulnerable roadway users conducted at Bellevue Hospital Center, a New York City Level 1 trauma center. All bicyclists with known helmet status were included. Demographics, insurance type, traffic law compliance, alcohol use, Glasgow Coma Scale (GCS) score, initial imaging studies, Abbreviated Injury Scale (AIS) score, Injury Severity Score (ISS), admission status, length of stay, disposition, and mortality were assessed. Information was obtained primarily from patients; witnesses and first responders provided additional information., Results: Of 374 patients, 113 (30.2%) were wearing helmets. White bicyclists were more likely to wear helmets; black bicyclists were less likely (p = 0.037). Patients with private insurance were more likely to wear helmets, those with Medicaid or no insurance were less likely (p = 0.027). Helmeted bicyclists were more likely to ride with the flow of traffic (97.2%) and within bike lanes (83.7%) (p < 0.001 and p = 0.013, respectively). Nonhelmeted bicyclists were more likely to ride against traffic flow (p = 0.003). There were no statistically significant differences in mean GCS score, AIS score, and mean ISS for helmeted versus nonhelmeted bicyclists. Nonhelmeted patients were more likely to have head computed tomographic scans (p = 0.049) and to be admitted (p = 0.030)., Conclusion: Helmet use is an indicator of safe riding practices, although most injured bicyclists do not wear them. In this study, helmet use was associated with lower likelihood of head CTs and admission, leading to less hospital resource use. Injured riders failing to wear helmets should be targeted for educational programs., Level of Evidence: Epidemiologic study, level III.
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- 2013
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49. Clinical and molecular features associated with cystic visceral lesions in von hippel-lindau disease.
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Taylor SR, Singh J, Sagoo MS, and Lightman SL
- Abstract
Background: Von Hippel-Lindau (VHL) is an uncommon oncogenic disorder which occurs as a result of genetic mutations on chromosome 3p. Retinal capillary haemangiomas and CNS haemangioblastomas have been well-characterised in genotypic-phenotypic analyses, but cystic visceral lesions are less common and have been less frequently studied. The aim of this study was to perform genotypic and phenotypic analysis of a cohort of VHL patients that developed cystic visceral lesions to determine whether their genotype differs from that seen in other manifestations of VHL and whether the ocular manifestations differ., Methods: This study reports a prospective case series of twenty-one patients identified from the Hammersmith Hospital Genetics Service database as having VHL mutations. Patients underwent regular ocular and systemic screening as well as genotypic analysis. The main outcome measures were the development of VHL lesions, either ocular or systemic., Results: Cystic visceral lesions were detected in six of the 21 patients from the clinic (29%). These included renal cysts in four patients, pancreatic cysts in three patients, and an epididymal cystadenoma in one patient. Renal cysts were not associated with any specific genotype. Pancreatic cysts appeared to occur in association with VHL gene deletions and all developed CNS haemangioblastomas. Only one patient developed ocular manifestations, which occurred in this patient in the form of two retinal capillary haemangiomas., Conclusions: VHL gene deletions appeared to be associated with pancreatic cysts and the development of CNS haemangioblastomas. Ocular manifestations are uncommon in this group of patients.
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- 2012
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50. Topical prostaglandin analogues and conjunctival inflammation in uveitic glaucoma.
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Taylor SR, Gurbaxani A, Sallam A, and Lightman S
- Abstract
Purpose: A pilot study to determine whether topical prostaglandin analogues alter the expression of conjunctival inflammatory markers in patients with uveitic glaucoma., Methods: Prospective, single-masked case series of 20 patients with uveitis and secondary raised intraocular pressure. Participants were divided into four groups of five patients dependent on their use of topical medication: (1) prostaglandin analogues only, (2) corticosteroids only, (3) both prostaglandin analogues and corticosteroids, (4) no topical medication. Conjunctival cells were harvested by impression cytology and were examined for inflammatory markers (CD3, CD54, HLA-DR, CCR4, CCR5) by flow cytometry. A tear fluid sample was also examined for inflammatory cytokines (IL-12p70, IL-2, IL-10, IL-8, IL-6, IL-4, IL-5, IFN-gamma, IL-1beta, IFN-alpha, IFN-beta) by multiplex bead arrays., Results: All groups demonstrated increased markers of conjunctival inflammation. There was no significant difference in levels of any inflammatory markers between the four groups, suggesting that the use of topical prostaglandin analogues does not increase conjunctival levels of inflammation beyond those already seen in uveitis., Conclusions: The use of topical prostaglandins does not appear to induce conjunctival inflammation over that which is already present in patients with uveitic glaucoma. This supports the use of topical prostaglandin analogues in patients with uveitic glaucoma, indicating that their use is unlikely to adversely affect subsequent glaucoma filtration surgery through the induction of chronic conjunctival inflammation.
- Published
- 2012
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