11 results
Synchronous or metachronous lymphoma and metastatic cutaneous squamous cell carcinoma in the head and neck region: a diagnostic and management dilemma
- I Kader, B Leavers, S Shashinder, B Wylie, K-K Chi, P Sundaresan
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- Journal:
- The Journal of Laryngology & Otology / Volume 130 / Issue S4 / July 2016
- Published online by Cambridge University Press:
- 04 August 2016, pp. S45-S49
- Print publication:
- July 2016
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Objective:
To review our experience of managing patients with a dual diagnosis of metastatic cutaneous squamous cell carcinoma in the head and neck region and low-grade non-Hodgkin lymphoma. The secondary aim was to evaluate the utility of 18F-fluorodeoxyglucose positron emission tomography during diagnosis.
Methods:Patients diagnosed with metastatic cutaneous squamous cell carcinoma of the head and neck and low-grade non-Hodgkin lymphoma, in a five-year period, were identified. Patient, tumour and treatment characteristics were identified. 18F-fluorodeoxyglucose positron emission tomography imaging was reviewed and correlated with histopathology findings.
Results:Eight patients were identified. There was a delay in diagnosis of metastatic squamous cell carcinoma in two patients. 18F-fluorodeoxyglucose positron emission tomography differentiated metastatic squamous cell carcinoma from low-grade non-Hodgkin lymphoma with a sensitivity of 88.2 per cent and a specificity of 94.7 per cent. In 38 per cent of patients, compromises in management had to be made.
Conclusion:The management of metastatic squamous cell carcinoma can be challenging in patients with low-grade non-Hodgkin lymphoma. 18F-fluorodeoxyglucose positron emission tomography can be useful in the diagnosis of metastatic squamous cell carcinoma in patients with low-grade non-Hodgkin lymphoma.
Contributors
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- By Mitchell Aboulafia, Frederick Adams, Marilyn McCord Adams, Robert M. Adams, Laird Addis, James W. Allard, David Allison, William P. Alston, Karl Ameriks, C. Anthony Anderson, David Leech Anderson, Lanier Anderson, Roger Ariew, David Armstrong, Denis G. Arnold, E. J. Ashworth, Margaret Atherton, Robin Attfield, Bruce Aune, Edward Wilson Averill, Jody Azzouni, Kent Bach, Andrew Bailey, Lynne Rudder Baker, Thomas R. Baldwin, Jon Barwise, George Bealer, William Bechtel, Lawrence C. Becker, Mark A. Bedau, Ernst Behler, José A. Benardete, Ermanno Bencivenga, Jan Berg, Michael Bergmann, Robert L. Bernasconi, Sven Bernecker, Bernard Berofsky, Rod Bertolet, Charles J. Beyer, Christian Beyer, Joseph Bien, Joseph Bien, Peg Birmingham, Ivan Boh, James Bohman, Daniel Bonevac, Laurence BonJour, William J. Bouwsma, Raymond D. Bradley, Myles Brand, Richard B. Brandt, Michael E. Bratman, Stephen E. Braude, Daniel Breazeale, Angela Breitenbach, Jason Bridges, David O. Brink, Gordon G. Brittan, Justin Broackes, Dan W. Brock, Aaron Bronfman, Jeffrey E. Brower, Bartosz Brozek, Anthony Brueckner, Jeffrey Bub, Lara Buchak, Otavio Bueno, Ann E. Bumpus, Robert W. Burch, John Burgess, Arthur W. Burks, Panayot Butchvarov, Robert E. Butts, Marina Bykova, Patrick Byrne, David Carr, Noël Carroll, Edward S. Casey, Victor Caston, Victor Caston, Albert Casullo, Robert L. Causey, Alan K. L. Chan, Ruth Chang, Deen K. Chatterjee, Andrew Chignell, Roderick M. Chisholm, Kelly J. Clark, E. J. Coffman, Robin Collins, Brian P. Copenhaver, John Corcoran, John Cottingham, Roger Crisp, Frederick J. Crosson, Antonio S. Cua, Phillip D. Cummins, Martin Curd, Adam Cureton, Andrew Cutrofello, Stephen Darwall, Paul Sheldon Davies, Wayne A. Davis, Timothy Joseph Day, Claudio de Almeida, Mario De Caro, Mario De Caro, John Deigh, C. F. Delaney, Daniel C. Dennett, Michael R. DePaul, Michael Detlefsen, Daniel Trent Devereux, Philip E. Devine, John M. Dillon, Martin C. Dillon, Robert DiSalle, Mary Domski, Alan Donagan, Paul Draper, Fred Dretske, Mircea Dumitru, Wilhelm Dupré, Gerald Dworkin, John Earman, Ellery Eells, Catherine Z. Elgin, Berent Enç, Ronald P. Endicott, Edward Erwin, John Etchemendy, C. Stephen Evans, Susan L. Feagin, Solomon Feferman, Richard Feldman, Arthur Fine, Maurice A. Finocchiaro, William FitzPatrick, Richard E. Flathman, Gvozden Flego, Richard Foley, Graeme Forbes, Rainer Forst, Malcolm R. Forster, Daniel Fouke, Patrick Francken, Samuel Freeman, Elizabeth Fricker, Miranda Fricker, Michael Friedman, Michael Fuerstein, Richard A. Fumerton, Alan Gabbey, Pieranna Garavaso, Daniel Garber, Jorge L. A. Garcia, Robert K. Garcia, Don Garrett, Philip Gasper, Gerald Gaus, Berys Gaut, Bernard Gert, Roger F. Gibson, Cody Gilmore, Carl Ginet, Alan H. Goldman, Alvin I. Goldman, Alfonso Gömez-Lobo, Lenn E. Goodman, Robert M. Gordon, Stefan Gosepath, Jorge J. E. Gracia, Daniel W. Graham, George A. Graham, Peter J. Graham, Richard E. Grandy, I. Grattan-Guinness, John Greco, Philip T. Grier, Nicholas Griffin, Nicholas Griffin, David A. Griffiths, Paul J. Griffiths, Stephen R. Grimm, Charles L. Griswold, Charles B. Guignon, Pete A. Y. Gunter, Dimitri Gutas, Gary Gutting, Paul Guyer, Kwame Gyekye, Oscar A. Haac, Raul Hakli, Raul Hakli, Michael Hallett, Edward C. Halper, Jean Hampton, R. James Hankinson, K. R. Hanley, Russell Hardin, Robert M. Harnish, William Harper, David Harrah, Kevin Hart, Ali Hasan, William Hasker, John Haugeland, Roger Hausheer, William Heald, Peter Heath, Richard Heck, John F. Heil, Vincent F. Hendricks, Stephen Hetherington, Francis Heylighen, Kathleen Marie Higgins, Risto Hilpinen, Harold T. Hodes, Joshua Hoffman, Alan Holland, Robert L. Holmes, Richard Holton, Brad W. Hooker, Terence E. Horgan, Tamara Horowitz, Paul Horwich, Vittorio Hösle, Paul Hoβfeld, Daniel Howard-Snyder, Frances Howard-Snyder, Anne Hudson, Deal W. Hudson, Carl A. Huffman, David L. Hull, Patricia Huntington, Thomas Hurka, Paul Hurley, Rosalind Hursthouse, Guillermo Hurtado, Ronald E. Hustwit, Sarah Hutton, Jonathan Jenkins Ichikawa, Harry A. Ide, David Ingram, Philip J. Ivanhoe, Alfred L. Ivry, Frank Jackson, Dale Jacquette, Joseph Jedwab, Richard Jeffrey, David Alan Johnson, Edward Johnson, Mark D. Jordan, Richard Joyce, Hwa Yol Jung, Robert Hillary Kane, Tomis Kapitan, Jacquelyn Ann K. Kegley, James A. Keller, Ralph Kennedy, Sergei Khoruzhii, Jaegwon Kim, Yersu Kim, Nathan L. King, Patricia Kitcher, Peter D. Klein, E. D. Klemke, Virginia Klenk, George L. Kline, Christian Klotz, Simo Knuuttila, Joseph J. Kockelmans, Konstantin Kolenda, Sebastian Tomasz Kołodziejczyk, Isaac Kramnick, Richard Kraut, Fred Kroon, Manfred Kuehn, Steven T. Kuhn, Henry E. Kyburg, John Lachs, Jennifer Lackey, Stephen E. Lahey, Andrea Lavazza, Thomas H. Leahey, Joo Heung Lee, Keith Lehrer, Dorothy Leland, Noah M. Lemos, Ernest LePore, Sarah-Jane Leslie, Isaac Levi, Andrew Levine, Alan E. Lewis, Daniel E. Little, Shu-hsien Liu, Shu-hsien Liu, Alan K. L. Chan, Brian Loar, Lawrence B. Lombard, John Longeway, Dominic McIver Lopes, Michael J. Loux, E. J. Lowe, Steven Luper, Eugene C. Luschei, William G. Lycan, David Lyons, David Macarthur, Danielle Macbeth, Scott MacDonald, Jacob L. Mackey, Louis H. Mackey, Penelope Mackie, Edward H. Madden, Penelope Maddy, G. B. Madison, Bernd Magnus, Pekka Mäkelä, Rudolf A. Makkreel, David Manley, William E. Mann (W.E.M.), Vladimir Marchenkov, Peter Markie, Jean-Pierre Marquis, Ausonio Marras, Mike W. Martin, A. P. Martinich, William L. McBride, David McCabe, Storrs McCall, Hugh J. McCann, Robert N. McCauley, John J. McDermott, Sarah McGrath, Ralph McInerny, Daniel J. McKaughan, Thomas McKay, Michael McKinsey, Brian P. McLaughlin, Ernan McMullin, Anthonie Meijers, Jack W. Meiland, William Jason Melanson, Alfred R. Mele, Joseph R. Mendola, Christopher Menzel, Michael J. Meyer, Christian B. Miller, David W. Miller, Peter Millican, Robert N. Minor, Phillip Mitsis, James A. Montmarquet, Michael S. Moore, Tim Moore, Benjamin Morison, Donald R. Morrison, Stephen J. Morse, Paul K. Moser, Alexander P. D. Mourelatos, Ian Mueller, James Bernard Murphy, Mark C. Murphy, Steven Nadler, Jan Narveson, Alan Nelson, Jerome Neu, Samuel Newlands, Kai Nielsen, Ilkka Niiniluoto, Carlos G. Noreña, Calvin G. Normore, David Fate Norton, Nikolaj Nottelmann, Donald Nute, David S. Oderberg, Steve Odin, Michael O’Rourke, Willard G. Oxtoby, Heinz Paetzold, George S. Pappas, Anthony J. Parel, Lydia Patton, R. P. Peerenboom, Francis Jeffry Pelletier, Adriaan T. Peperzak, Derk Pereboom, Jaroslav Peregrin, Glen Pettigrove, Philip Pettit, Edmund L. Pincoffs, Andrew Pinsent, Robert B. Pippin, Alvin Plantinga, Louis P. Pojman, Richard H. Popkin, John F. Post, Carl J. Posy, William J. Prior, Richard Purtill, Michael Quante, Philip L. Quinn, Philip L. Quinn, Elizabeth S. Radcliffe, Diana Raffman, Gerard Raulet, Stephen L. Read, Andrews Reath, Andrew Reisner, Nicholas Rescher, Henry S. Richardson, Robert C. Richardson, Thomas Ricketts, Wayne D. Riggs, Mark Roberts, Robert C. Roberts, Luke Robinson, Alexander Rosenberg, Gary Rosenkranz, Bernice Glatzer Rosenthal, Adina L. Roskies, William L. Rowe, T. M. Rudavsky, Michael Ruse, Bruce Russell, Lilly-Marlene Russow, Dan Ryder, R. M. Sainsbury, Joseph Salerno, Nathan Salmon, Wesley C. Salmon, Constantine Sandis, David H. Sanford, Marco Santambrogio, David Sapire, Ruth A. Saunders, Geoffrey Sayre-McCord, Charles Sayward, James P. Scanlan, Richard Schacht, Tamar Schapiro, Frederick F. Schmitt, Jerome B. Schneewind, Calvin O. Schrag, Alan D. Schrift, George F. Schumm, Jean-Loup Seban, David N. Sedley, Kenneth Seeskin, Krister Segerberg, Charlene Haddock Seigfried, Dennis M. Senchuk, James F. Sennett, William Lad Sessions, Stewart Shapiro, Tommie Shelby, Donald W. Sherburne, Christopher Shields, Roger A. Shiner, Sydney Shoemaker, Robert K. Shope, Kwong-loi Shun, Wilfried Sieg, A. John Simmons, Robert L. Simon, Marcus G. Singer, Georgette Sinkler, Walter Sinnott-Armstrong, Matti T. Sintonen, Lawrence Sklar, Brian Skyrms, Robert C. Sleigh, Michael Anthony Slote, Hans Sluga, Barry Smith, Michael Smith, Robin Smith, Robert Sokolowski, Robert C. Solomon, Marta Soniewicka, Philip Soper, Ernest Sosa, Nicholas Southwood, Paul Vincent Spade, T. L. S. Sprigge, Eric O. Springsted, George J. Stack, Rebecca Stangl, Jason Stanley, Florian Steinberger, Sören Stenlund, Christopher Stephens, James P. Sterba, Josef Stern, Matthias Steup, M. A. Stewart, Leopold Stubenberg, Edith Dudley Sulla, Frederick Suppe, Jere Paul Surber, David George Sussman, Sigrún Svavarsdóttir, Zeno G. Swijtink, Richard Swinburne, Charles C. Taliaferro, Robert B. Talisse, John Tasioulas, Paul Teller, Larry S. Temkin, Mark Textor, H. S. Thayer, Peter Thielke, Alan Thomas, Amie L. Thomasson, Katherine Thomson-Jones, Joshua C. Thurow, Vzalerie Tiberius, Terrence N. Tice, Paul Tidman, Mark C. Timmons, William Tolhurst, James E. Tomberlin, Rosemarie Tong, Lawrence Torcello, Kelly Trogdon, J. D. Trout, Robert E. Tully, Raimo Tuomela, John Turri, Martin M. Tweedale, Thomas Uebel, Jennifer Uleman, James Van Cleve, Harry van der Linden, Peter van Inwagen, Bryan W. Van Norden, René van Woudenberg, Donald Phillip Verene, Samantha Vice, Thomas Vinci, Donald Wayne Viney, Barbara Von Eckardt, Peter B. M. Vranas, Steven J. Wagner, William J. Wainwright, Paul E. Walker, Robert E. Wall, Craig Walton, Douglas Walton, Eric Watkins, Richard A. Watson, Michael V. Wedin, Rudolph H. Weingartner, Paul Weirich, Paul J. Weithman, Carl Wellman, Howard Wettstein, Samuel C. Wheeler, Stephen A. White, Jennifer Whiting, Edward R. Wierenga, Michael Williams, Fred Wilson, W. Kent Wilson, Kenneth P. Winkler, John F. Wippel, Jan Woleński, Allan B. Wolter, Nicholas P. Wolterstorff, Rega Wood, W. Jay Wood, Paul Woodruff, Alison Wylie, Gideon Yaffe, Takashi Yagisawa, Yutaka Yamamoto, Keith E. Yandell, Xiaomei Yang, Dean Zimmerman, Günter Zoller, Catherine Zuckert, Michael Zuckert, Jack A. Zupko (J.A.Z.)
- Edited by Robert Audi, University of Notre Dame, Indiana
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- Book:
- The Cambridge Dictionary of Philosophy
- Published online:
- 05 August 2015
- Print publication:
- 27 April 2015, pp ix-xxx
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Contributors
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- By Ainsworth Shaaron, Ayres Paul, Azevedo Roger, Bediou Benoit, Britt Anne, Kirsten R. Butcher, Chen Fei, Michelene T. H. Chi, Richard E. Clark, Ruth Colvin Clark, Sharon J. Derry, David F. Feldon, Fiorella Logan, J. D. Fletcher, Arthur C. Graesser, Hegarty Mary, HU Xiangen, Allison J. Jaeger, Janssen Jeroen, Cheryl I. Johnson, Ton De Jong, Kalyuga Slava, Kester Liesbeth, Kirschner Femke, Paul A. Kirschner, Susanne P. Lajoie, Ard W. Lazonder, Leutner Detlev, Low Renae, Richard K. Lowe, Richard E. Mayer, Benjamin D. Nye, Paas Fred, Pilegard Celeste, Jan L. Plass, Heather A. Priest, Renkl Alexander, Rouet Jean-FranÇois, Christopher A. Sanchez, Scheiter Katharina, Schmeck Annett, Schnotz Wolfgang, Ruth N. Schwartz, Bruce L. Sherin, Miriam Gamoran Sherin, Sweller John, Tobias Sigmund, Tamara Van Gog, Jeroen J. G. Van MerriËNboer, Jennifer Wiley, Alexander P. Wind, Ruth Wylie
- Edited by Richard E. Mayer, University of California, Santa Barbara
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- Book:
- The Cambridge Handbook of Multimedia Learning
- Published online:
- 05 August 2014
- Print publication:
- 28 July 2014, pp ix-x
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On climbing fiber signals and their consequence(s)
- J. I. Simpson, D. R. Wylie, C. I. De Zeeuw
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- Journal:
- Behavioral and Brain Sciences / Volume 19 / Issue 3 / September 1996
- Published online by Cambridge University Press:
- 19 May 2011, pp. 384-398
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The persistence of many contrasting notions of climbing fiber function after years of investigation testifies that the issue of climbing fiber contributions to cerebellar transactions is still unresolved. The proposed capabilities of the climbing fibers cover an impressive spectrum. For many researchers, the climbing fibers signal errors in motor performance, either in the conventional manner of frequency modulation or as a single announcement of an “unexpected event”. More controversial is the effect of these signals on the simple spike modulation of Purkinje cells. In some hands, they lead to a long-term depression of the strength of parallel fiber synapses, while, in other hands, they lead to a short-lasting enhancement of the responsiveness of Purkinje cells to mossy fiber inputs or contribute to the often-seen reciprocal relation between complex and simple spike modulation. For still other investigators, the climbing fibers serve internal timing functions through their capacity for synchronous and rhythmic firing. The above viewpoints are presented in the spirit of trying to reach some consensus about climbing fiber function. Each point of view is introduced by summarizing first the key observations made by the respective proponents; then the issues of short-lasting enhancement, reciprocity between complex and simple spikes, and synchrony and rhythmicity are addressed in the context of the visual climbing fiber system of the vestibulocerebellum.
More on climbing fiber signals and their consequence(s)
- J. I. Simpson, D. R. W. Wylie, C.I. De Zeeuw
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- Journal:
- Behavioral and Brain Sciences / Volume 19 / Issue 3 / September 1996
- Published online by Cambridge University Press:
- 19 May 2011, pp. 496-498
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Several themes can be identified in the commentaries. The first is that the climbing fibers may have more than one function; the second is that the climbing fibers provide sensory rather than motor signals. We accept the possibility that climbing fibers may have more than one function – hence ‘consequence(s)’ in the title. Until we know more about the function of the inhibitory input to the inferior olive from the cerebellar nuclei, which are motor structures, we have to keep open the possibility that the climbing fiber signals can be a combination of sensory and motor signals.
Field Experiments in Ayrshire on Control of Heterodera schachtii by the use of Chloroacetates
- D. G. O'Brien, A. R. Gemmell, I. W. Prentice, S. M. Wylie
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- Journal:
- Journal of Helminthology / Volume 17 / Issue 1 / January 1939
- Published online by Cambridge University Press:
- 18 November 2009, pp. 41-50
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The effect of calcium and ammonium chloroacetates in increasing the yield of potatoes grown in Ayrshire fields infected with Heterodera schachtii is demonstrated.
From the examination of roots of treated and untreated plants it is believed that this increase in yield is due to a reduction in the eelworm infection, and from hatching experiments this reduction is thought to be the result of the action of calcium chloroacetate in retarding and reducing the hatching of larvae from the cysts.
Effects of secondary nematode infection on anorexia and leptin levels in growing lambs of two different breeds
- K. Zaralis, B.J. Tolkamp, A.R.G. Wylie, J.G.M Houdijk, I. Kyriazakis
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- Journal:
- Proceedings of the British Society of Animal Science / Volume 2007 / April 2007
- Published online by Cambridge University Press:
- 23 November 2017, p. 91
- Print publication:
- April 2007
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A primary infection of a parasite naïve animal has detrimental effects on intake (anorexia), which in turn results in impaired animal productivity. Recent studies have indicated that anorexia in nematode infected lambs is a direct consequence of the acquisition of immunity (Greer et al., 2005). In many models of disease, immune system activation results in elevated leptin levels and these have been associated with anorexia. However, whether the expression of acquired immunity following a secondary nematode infection results in elevated leptin levels and/or anorexia in growing lambs it is not known. In addition, it is not known whether the expression of acquired immunity differs between breeds that differ in production potential. The aim of the present study was to test the hypotheses a) that a secondary nematode infection results in increased leptin levels and anorexia in growing lambs and b) that lambs of a high production potential breed exhibit a higher degree of anorexia than lambs of a low production potential.
Characterization of Si in a W matrix Using Diffraction Contrast in the TEM
- B.I. Prenitzer, B.W. Kempshall, J.M. McKinley, W.H. Stinebaugh, I. Wylie
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- Journal:
- Microscopy and Microanalysis / Volume 8 / Issue S02 / August 2002
- Published online by Cambridge University Press:
- 01 August 2002, pp. 790-791
- Print publication:
- August 2002
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4 - The ear and auditory pathways
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- By P. Butler, The Royal Hospitals of St Bartholomew, I. G. Wylie, The Royal Hospitals of St Bartholomew
- Edited by Paul Butler, The Royal London Hospital, Adam W. M. Mitchell, Charing Cross Hospital, London, Harold Ellis, University of London
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- Book:
- Applied Radiological Anatomy
- Published online:
- 05 February 2015
- Print publication:
- 14 October 1999, pp 85-94
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6 - On climbing fiber signals and their consequence(s)
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- By J. I. Simpson, D. R. Wylie, C. I. De Zeeuw, Department of Physiology and Neuroscience, New York University Medical Center, New York, NY 10016
- Edited by Paul J. Cordo, Curtis Calvin Bell, Stevan R. Harnad, University of Southampton
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- Book:
- Motor Learning and Synaptic Plasticity in the Cerebellum
- Published online:
- 04 August 2010
- Print publication:
- 28 November 1997, pp 46-60
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Summary
Abstract: The persistence of many contrasting notions of climbing fiber function after years of investigation testifies that the issue of climbing fiber contributions to cerebellar transactions is still unresolved. The proposed capabilities of the climbing fibers cover an impressive spectrum. For many researchers, the climbing fibers signal errors in motor performance, either in the conventional manner of frequency modulation or as a single announcement of an “unexpected event.” More controversial is the effect of these signals on the simple spike modulation of Purkinje cells. In some hands, they lead to a long-term depression of the strength of parallel fiber synapses, while, in other hands, they lead to a short-lasting enhancement of the responsiveness of Purkinje cells to mossy fiber inputs or contribute to the often-seen reciprocal relation between complex and simple spike modulation. For still other investigators, the climbing fibers serve internal timing functions through their capacity for synchronous and rhythmic firing. The above viewpoints are presented in the spirit of trying to reach some consensus about climbing fiber function. Each point of view is introduced by summarizing first the key observations made by the respective proponents; then the issues of short-lasting enhancement, reciprocity between complex and simple spikes, and synchrony and rhythmicity are addressed in the context of the visual climbing fiber system of the vestibulocerebellum.
Keywords: cerebellum; complex spikes; eye movements; flocculus; inferior olive; mossy fibers; movement; nodulus; posture; Purkinje cells; simple spikes; synchrony.
The value of CT scanning in chronic suppurative otitis media
- B. J. O'Reilly, E. B. Chevretton, I. Wylie, C. Thakkar, P. Butler, N. Sathanathan, G. A. Morrison, G. S. Kenyon
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- Journal:
- The Journal of Laryngology & Otology / Volume 105 / Issue 12 / December 1991
- Published online by Cambridge University Press:
- 29 June 2007, pp. 990-994
- Print publication:
- December 1991
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High definition CT has been advocated for the evaluation of chronic suppurative otitis media (CSOM) either generally or in selected cases. It is said to be capable of producing the fine detail needed to detect lateral canal fistulae, exposed dura and facial canal dehiscences, and to demonstrate the ossicular chain. At present there is no agreement on either the indications for CT scanning in CSOM or the most appropriate scanning plane. To determine the value of high definition CT in CSOM and to decide a unit policy for its application, 36 cases of CSOM underwent pre-operative CT scanning and their scans were compared with the operative findings.
Our results show CT to be highly sensitive to the presence of soft tissue disease and bone erosion, moderately sensitive to the presence of lateral canal fistulae but less sensitive to the presence of small areas of exposed dura, ossicular continuity and facial canal dehiscence. Axial scans were better able to demonstrate the lateral canal but otherwise coronal scans were superior; ideally patients should be scanned in both planes. The principle value of CT in CSOM is its ability to demonstrate disease which is not clinically apparent.