SECTION OF OTOLARYNGOLOGY 2001-2002 Professor and Chief of SectionClarence T. Sasaki, M.D., Charles W. Ohse Professor
Overview and Accomplishments
The Section of Otolaryngology produced a large number of scientific publicationsreflecting a) its engagement in initiating new and improved models of patient care and b)its leadership position in the investigation of fundamental mechanisms of diseases relatedto auditory function, speech and swallowing behavior, taste and oral pain syndromes,progression of sinonasal inflammatory disease and head and neck cancer. Efforts of theSection have been rewarded by the acquisition of several new grants. Dr. Douglas Rosshas been named co-investigator on a new NIH grant with Dr. James Douglas toinvestigate the pathogenesis of chronic sinusitis. Dr. Clarence Sasaki and Dr. Ross withDr. Richard Satava have also been awarded a new AHRQ grant, subcontracted fromAlbert Einstein School of Medicine for three years, entitled “Identifying and ReducingErrors with Surgical Simulation”.
The Clinical Development Fund of the Yale School of Medicine and Yale-New HavenHospital has agreed to fund Dr. Sasaki’s proposal “Innovations in Head and NeckCancer”, a three year multidisciplinary clinical project allowing the Section to updatemuch needed outpatient equipment, acquire new nursing and clerical staff, and add newprofessional appointments in Head and Neck Surgery, Medical Oncology, andCommunication Disorders.
Both Dr. Steven Leder and Dr. Sasaki have received funding from the Ohse Endowmentfor projects respectively entitled “Comparison of Simultaneous Fiberoptic Endoscopicand Videofluoroscopic Evaluations of Swallowing” and “Supramedullary Facilitation ofthe Glottic Closure Reflex in Humans”.
Finally, Dr. David Karas successfully competed for commercial funding from the ElmonCorporation for a project entitled “Radiofrequency Tympanic Membrane Fenetration inthe Chinchilla Model” and is co-investigator on a new four year NIH grant “PerioperativeBehavioral and Physiological Stress in Children”.
Over the past year the Section has forged a research and clinical alliance with theOtolaryngology Department of the Christian-Albrecht University, Kiel, Germany,providing opportunities for students and residents from either institution to study abroad. Faculties from each institution also travel between the two institutions to conductacademic lectures and clinical courses. Students from Christian-Albrecht currently aredoing research in laboratories of Drs. Santos-Sacchi and Douglas. The Christian-Albrecht University shares an interesting past. Among its members have been suchprominent scientists as Max Planck, Heinrich Herts and Hans Geiger, who built the first“Geiger Counter” in Kiel in 1928. In 1950, the chemist Otto Diels was the latest of six
Nobel Prize winners who have taught at Kiel. Despite its age, the University of Kiel istoday a modern university campus. After being almost completely destroyed in theSecond World War, the university’s planned expansion began on a large site on theformer outskirts of the city. Only the University Hospital has remained on the site of the“Old University” near the city center. With few exceptions, all university departmentsand hospitals are housed in new buildings equipped with the latest technology.
Thus, with the acquisition of new alliances and funding, the Section is poised to enter thenew academic year with a more highly focused vision of its educational, research andclinical missions. Research in Progress and Accomplishments Dr. James C. Alex isan internationally recognized researcher in sentinel noderadiolocalization. Dr. Alex was invited to lecture in Glasgow, Scotland and Cairo, Egypt. He has also recently developed a minimally invasive technique for reanimating the lowerface in patients with facial paralysis. The procedure, which formerly required generalanesthesia and an overnight stay, can now be solely performed as an outpatient procedurewith minimal discomfort and bruising.
In 1992, Dr. Alex co-developed the technique of gamma probe for radiolocalization ofregional lymph nodes in melanoma and breast cancer. Currently he is applying thistechnique to the identification of sentinel node in squamous carcinoma of the head andneck. He hypothesizes that the sentinel node will be predictive of occult nodal diseaseallowing for accurate staging of regional lymphatics and indicating the need for definitivetreatment of the neck whether by surgery or radiation therapy. To validate thishypothesis, he will perform gamma probe radiolocalization in thirty patients with clinicalT1-T4 N0 squamous carcinoma of the head and neck in order to determine the optimummethodology for consistent radiolocalization; to compare the localizing features ofgamma probe to computed tomography and lymphocintigraphy; and finally to determineby histologic evaluation if the occurrence of alignan node micrometastases are predictiveof metastatic spread in the remaining lymphatic bed. Dr. Linda Bartoshuk conducts research on genetic variation in taste perception, oralpains, and taste disorders. Genetic studies focus on PROP (6-n-propylthiouracil) whichtastes extremely bitter to 25% (supertasters), moderately bitter to 50% (medium tasters),and is nearly tasteless to 25% (non tasters) of the population. Supertasters have the mosttaste buds, experience the most intense taste and perceive the most intense oral burn fromirritants like the capsaicin in the chili peppers (taste buds are innervated by both taste andpain neurons). In addition to studying capsaicin as an oral irritant, she studies its abilityto desensitize pain receptors and thus provide clinically effective analgesia. She and Dr. Kveton study taste disorders including taste loss and taste phantoms (akin to tinnitus orphantom limb). In an effort to study the mechanisms of these symptoms, they conductresearch with volunteers in whom taste nerves are temporarily anesthetized usingotolaryngological anesthesia techniques. Paradoxically, anesthesia of one taste nerve can
lead to increased taste perception showing that there are inhibitory interactions amongcranial nerves that play a role in patient’s symptoms. Dr. Carol Fowler’s research over the past year has focused on phonetic perception andhas used the “McGurk effect” and compensation for coarticulation to do so. Whenspeakers talk, they coarticulate that is, they produce the consonants and vowels thatcompose words in overlapping time frames. This makes the acoustic signal forconsonants and vowels highly context sensitive. The question arises how listeners detectconsonants and vowels in such a signal. One thing they do is “compensate” forcoarticulation. That is, they evaluate the acoustic information for a consonant or vowel inthe light of the impact that coarticulation by neighboring segments should have on it. Forexample, ambiguous stimuli along an acoustic continuum that range from /da/ to /ga/ aremore likely to be identified as /ga/ following /l/ than /r/. /l/ has a front place ofarticulation that would pull /ga/ forward; when listeners identify ambiguous continuummembers as /ga/, they are compensating for that fronting effect. We recently used theMcGurk effect to test whether this compensation is, in fact, based on detection ofprobable coarticulatory effects or, instead as some researchers have proposed, is due to alow level auditory process of frequency contrast. In the McGurk effect, an acousticsignal for a syllable that is dubbed on to a face producing a different syllable may beheard differently than in the absence of the facial information. We made syllablesambiguous between /ar/ and /al/ and appended them to members of a /da/-to-/ga/continuum. We dubbed these onto a face mouthing either /al/ or /ar/ followed by amouthed CV syllable consistent with either /da/ or /ga/. In these disyllables the onlyinformation distinguishing the coarticulating contexts (/al/ and /ar/) was visual; the onlyinformation distinguishing /da/ from /ga/ was accustic. We found compensation forcoarticulation and therefore eliminated the auditory contrast account of it. Dr. Barry Green is conducting research on several topics related to somatosensation andtaste. He recently discovered that thermal stimulation of the tongue, in the absence ofchemical stimulation, can produce sensations of taste. This new phenomenon, called‘thermal taste’, may provide insights into how taste qualities (salty, sour, sweet, better)are coded, and how the gustatory system interacts with the somatosensory system. Asecond line of investigation is directed toward describing and understanding the sensoryeffects of chemical irritants (e.g., capsaicin) in the mouth and throat, including whetherchemical irritants such as carbonation can provide sensory signals that aide swallowing indysphasic patients (in collaboration with Dr. Steven Leder). Other research projects inhis laboratory include studies of interactions between touch and taste, spatial factors inperception of temperature on the skin, and the effects of aging on the sensitivity totouch.”
Dr. Pawel J. Jastreboff spent eight years at Yale University and eight years at Universityof Maryland, where he was involved in research on tinnitus and established Tinnitus &Hyperacusis Center. In January 1999, Dr. Jastreboff moved to Emory University tocontinue his basic and clinical research on tinnitus and to create a center of excellence fortinnitus research and patients treatment. In 1988, on the basis of research on thephysiological mechanisms of tinnitus Dr. Jastreboff proposed the neurophysiological
model of tinnitus and Tinnitus Retraining Therapy (TRT). He has also created an animalmodel of tinnitus. His present research is aimed at delineating the mechanisms of tinnitusand designing new methods of tinnitus and hyperacusis alleviation. Dr. Jastreboffreceived a Ph.D. in Neurophysiology and Doctor pf Science Degree (Neuroscience) fromthe Polish Academy of Sciences. He did his Postdoctoral training at the University ofTokyo, Japan. He is presently a Professor and Director of Tinnitus & Hyperacusis Centerat Emory University and he hold Visiting Professor appointments at Yale UniversitySchool of Medicine, University College London, UK and Middlesex Hospital, London,UK. Dr. David E. Karas is interested in the use of radio frequency as a new surgical tool in itsapplications towards the head and neck. He is currently involved in a research studylooking at the use of short-term middle ear ventilation with the use of radio frequency inthe chinchilla model. Radio frequency offers a much less expensive alternative. Dr. Karas other interests include such as ciliary dyskinesia and pediatric airway, swallowingdisorders, and effects of perioperative stress. Dr. John A. Kirchner serves as curator of the 442 laryngeal cancer specimens removed bytotal or partial laryngectomy and displayed in whole-organ serial sections. The collectionis used for instructing residents and postgraduate fellows in Otolaryngology, Pathologyand Radiation Therapy. Dr. Kirchner’s recently published textbook “Atlas on theSurgical Anatomy of Laryngeal Cancer” serves as an authoritative source on larynxcancer. Dr. John F. Kveton is a co-investigator in an NIH-funded project with Dr. LindaBartoshuk to study taste and taste phantoms. Taste alterations are produced in subjectsby a local anesthetic block of the chorda tympani nerve and taste function is manipulatedorally to study the development of taste phantoms. Patients who have suffered damage tothe chorda tympani nerve by surgery or skull base tumors are studied to better understandthe effects on taste and the development of taste phantoms. The insight obtained from thebasic science investigations and clinical assessments of taste function are leading to abetter understanding of the function of the special senses in disease states. Dr. Steven B. Leder is actively engaged in clinical research investigating dysphagiadiagnostics and rehabilitation in the acute care setting, including the effects of head andneck cancer, stroke, and tracheotomy on swallowing function. Efficacy of differentdiagnostic tools to assess dysphagia in the pediatric and adult populations and generationof clinically useful dysphagia diagnostic scales are being pursued. In addition, researchon voice restoration in head and neck cancer, tracheotomized, and ventilator dependentpopulations are under investigation. Dr. Steffen Maune is Professor and Vice Chairman of the Department ofOtorhinolaryngology – Head and Neck Surgery at Christian Albrechts University of Kiel,Germany. He is a renowned and respected leader in the field of Otolaryngology withresearch interests in oncology, rhinology and otology. Since 1996, Dr. Maune has workedwith Yale physicians: Dr. Clarence Sasaki, Dr. Douglas Ross and Dr. Joseph Santos-
Sacchi, in organizing an exchange of medical students and residents from ChristianAlbrechts University to collaborate in research, academic lectures and clinical courses atYale School of Medicine.
In 2002, Dr. Maune was appointed Visiting Professor at Yale School of Medicine tofocus on the collaboration of the following: 1) Laser Surgery: transfer of new techniquesfrom the University of Kiel. This includes the capability of validating outcome andquality of life of treated head and neck cancer patients, 2) Application of sentinel lymphnode in N0 neck patients, 3) Brachytherapy in head and neck tumor patients and 4)Chemokines and its receptors in mucosal defense. Dr. Douglas Ross’ research now focuses on the effects of nitric oxide on chronicsinusitis. Chronic sinusitis plagues millions of Americans each year and although it isthought to be caused by chronic bacterial infection, there may be other contributingfactors to the development of the disease. Pathologic specimens are being examined bothhistopathologically, as well as on a molecular basis in order to “better understand”chronic sinusitis.
Another research venture for Dr. Ross is an effort to better understand and improve thetraining of residents in endoscopic sinus surgery. New ways and techniques are beingexamined in order to eventually develop a curriculum for learning endoscopic sinussurgery. Dr. Philip Rubin, Chief Operating Officer at Haskins Laboratories, has beencollaborating with a number of colleagues on the development of computational modelsof audio-visual speech production. These models incorporate photo-realistic simulationsof actual speakers in which the data used to control movements of the articulators isbased on physiological measurements gathered during speech production. Some of thiswork is described on a website called “Talking Heads” which can be found on theHaskins Laboratories and MIT’s COGNET sites. Dr. Rubin is also the founding Directorof AVISA, the Audio-Visual Speech Association, which is part of ESCA (the EuropeanSpeech Community Association). In addition to his administrative responsibilities, hecontinues to supervise the development of research tools for the display and analysis ofmulti-channel physiological data, including data from an electromagnetic articulometer(EMMA) system used to monitor articulator positions during speech production. Withother colleagues, Dr. Rubin is developing a new system called CASY, which is anextension of the standard Haskins articulatory synthesis, a configurable version of hisarticulatory synthesis model. This model (ASY) adds the ability to fit the synthesizer’svocal tract model to midsagittal x-ray and/or MR images. Other research includes workon the dynamics of the temporal patterning of speech and the global principles oforganization in speech perception and production. Dr. Joseph Santos-Sacchi’s research efforts are directed at understanding normalperipheral auditory function so that eventually inner ear deafness can be treatedeffectively. The exquisite sensitivity and frequency resolving power of the mammalianinner ear depends upon interaction between the two receptor cells of the organ of Corti,
inner (IHC) and outer (OHC) hair cells. Whereas inner hair cells appear to functionsolely as receptors of acoustic information, OHCs function both as receptors andeffectors, producing motile responses as a function of transmembrane potentialfluctuations. These motile responses are believed to modify the mechanical input to theinner hair cells, which receive the majority of afferent innervation, thereby enhancing thegross frequency tuning afforded by basilar membrane mechanics. Currently, we arestudying the effector role of the OHC with electrophysiological and displacementmeasurement techniques using isolated OHCs from the guinea pig. In particular, we usethe whole cell voltage clamp to study the voltage dependence of the mechanical response,and the corresponding nonlinear charge associated with the motility voltage sensor. Estimates of the mechanical frequency response are made in order to assess the potentialsignificance of OHC motility in the in vivo feedback scheme. In addition, to the work onOHCs, we are also involved with studies on electrical coupling in the supporting cells, aswell as characterization of the ionic currents in these cells and in spiral ganglion cells. Clarence T. Sasaki, MD: Innervation of the human cricopharyngeus muscle remainshistorically controversial and unclear; encouraging numerous treatments inconsistentlydesigned to pharmacologically or mechanically alter the contractile state of this muscle. Neuroanatomic controversy results from and is perpetuated by 1) use of nonhumanmodels, 2) observational misinterpretation of small-diameter, overlapping nerve fibers,and, most importantly, 3) lack of real-time verification of neural projections. The YaleLarynx Laboratory is seeking to overcome these difficulties by performingmicrodissections in patients undergoing laryngectomy using real-time electomyographicvalidation. We have preliminarily demonstrated 1) dual ipsilateral innervation by thepharyngeal plexus and recurrent laryngeal nerve, 2) segmental projection of the recurrentlaryngeal nerve to anterior motor units, 3) pharyngeal plexus projection to posteriormotor units, 4) absence of a sympathetic or external superior laryngeal nervecontribution, and 5) absence of contralateral innervation. Such dual ipsilateralinnervation, segmentally projected, has not been previously described in any other formof neuromuscular organization.
The sphincteric function of the larynx, essential to lower airway protection, is mostefficiently achieved through strong reflex adduction by both vocal cords. Wehypothesize that central facilitation is an essential component of a bilateral adductorreflex and that its disturbance could result in a weakened sphincteric closure. In the YaleLarynx Laboratory, adult 50-kg pigs underwent evoked response laryngealelectromyography under 0.5 to 1.0 minimal alveolar concentration (MAC) isofluraneanesthesia. The internal branch of the superior laryngeal nerve was stimulated throughbipolar platinum-iridium electrodes, and recording electrodes were positioned in theipsilateral and contralateral thyroarytenoid muscles. Consistent threshold responses wereobtained ipsilaterally from 0.5 to 1.0 MAC anesthesia. However, the contralateral reflexresponses approached 0% in successive trials as anesthetic levels approached 1.0 MAC. Alteration of central facilitation by deepening anesthesia abolishes the crossed adductorreflex, predisposing to a weakened glottic closure response. These observations arecurrently being extended to patients undergoing supraglottic laryngectomy. Preliminaryobservations appear to confirm the above relationships. A precise understanding of these
effects may improve the prevention of aspiration in patients emerging from prolongedsedation or under heavy psychotropic control. Dr. Ilsa R. Schwartz is studying the structure and chemistry of neurons in the mammalianauditory system in normal, developing, and pathological systems. Work is underway todefine neuronal populations in the cochlea and brainstem, especially the cochlear nucleiand superior olivary complex, in terms of: their anatomic features, ultrastructure,relationship to various synaptic terminal inputs upon their surfaces, and chemicalproperties or molecular markers which may relate to their neurotransmitters, glutamatereceptors, or other functional differences. Current studies are focused on ionotropicglutamate receptor subunits and glutamate receptor interacting proteins and how theydiffer in congenic mice with and without the gene for age-related hearing loss, C57BL6and B6Cast respectively. Light and electron microscopic immunocytochemical andmolecular biological methods are used. Active Grants
The Applicability of Gamma Probe Localization in NO Squamous Cell Carcinoma of theHead and Neck, Ohse Endowment, 2001-2002, Dr. James C. Alex
Taste Psychophysics, NIH with a sub-contract to UCONN for five years, Primary Site:Yale, 1999-2004, Dr. Linda Bartoshuk
Nature and Acquisition of the Speech Code and Reading, NIH, 2001-2006, Dr. CarolFowler
Links between Production and Perception in Speech, NIH, 2000-2005, Dr. Carol Fowler
Imitation-A Tool for Studying Speech Perception, NIH, 1999-2003, Dr. Carol Fowler
Spatial Properties of Cutaneous Thermal Sensitivity, NIH, 1999-2003, Dr. Barry Green
Cutaneous Sensitivity and Aging, NIH, 1999-2003, Dr. Barry Green
Oral Somesthesis and Taste, NIH, 2001-2006, Dr. Barry Green
Modification of the Metabolic Activity of the Brain Related to Tinnitus Associated withSound Induced Hearing Loss, American Tinnitus Association, 1996-2002, Dr. Pawl J. Jastreboff
Perioperative behavioral and physiological stress in children, Co-investigator, NIH, 1999-2003, Dr. David Karas
Radiofrequency Tympanic Membrane Fenetration in the Chinchilla Model, ElmonCorporation, 2000-2002, Dr. David Karas
Comparison of Simultaneous Fiberoptic Endoscopic and Videofluoroscopic Evaluationsof Swallowing, Ohse Endowment, 2001-2002, Dr. Steven Leder
The Pathogenesis of Chronic Sinusitis, Co-investigator, Institute of Allergy andInfectious Diseases, 2001-2002, Dr. Douglas Ross
Identifying and Reducing Errors with Surgical Simulation, AHRQ, 2001-2004, Dr. Douglas Ross
Intergovernmental Personnel Act (IPA) Assignment, NIH, 2000-2002, Dr. Philip Rubin
Membrane Properties of Cells Comprising the Outer Hair Cell System, NIH, NIDCD,1984-2005, Dr. Joseph Santos-Sacchi
Supramedullary Facilitation of the Glottic Closure Reflex in Humans, Ohse Endowment,2001-2002, Dr. Clarence Sasaki
McFadden Endowment, Mirikitani Endowment, Harmon Endowment, Dr. ClarenceSasaki
Identifying and Reducing Errors with Surgical Simulation, AHRQ, 2001-2004, Dr. Clarence Sasaki
Bile Laryngitis: Fact or Fiction, Ohse Edowment, 2002-2003, Dr. Clarence Sasaki
Publications Abrahams JJ. Dental CT imaging: a look at the jaw, Radiology, 219:334-345, 2001 Abrahams JJ. Radiology of the sinuses, Sasaki CT (ed), Kveton JF, Ross DA, Karas DE, Leder SB (assoc. ed), The Yale Manual on Management of Ear, Nose, and Throat, Disorders in Primary Care Practice, Humana Press, Totowa, NJ (in press) Abrahams JJ. Radiology of the throat, Sasaki CT (ed), Kveton JF, Ross DA, Karas DE, Leder SB (assoc. ed), The Yale Manual on Management of Ear, Nose, and Throat, Disorders in Primary Care Practice, Humana Press, Totowa, NJ (in press) Abrahams JJ. Dental CT and pathologic conditions of the jaw, Radiologe, (in press) Alberti P, Loeffler J. Nasal foreign body, Sasaki CT (ed), Kveton JF, Ross DA, Karas DE, Leder SB (assoc. ed), The Yale Manual on Management of Ear, Nose, and Throat, Disorders in Primary Care Practice, Humana Press, Totowa, NJ (in press) Alex JC, Bhattacharyya TK, O’Grady K, Smyrniotis G, Konior R, Toriumi D. A histomorphic analysis of 3-dimensional versus 2-dimensional tissue expansion in the porcine model, Laryngoscope, 111:36-43, 2001
Argiris A, Heald P, Kuzel T, Foss FM, DiStasio S, Cooper DL, Arbuck S, Murren JR. Phase II trial of 9-AC as a 72-hours infusion in cutaneous T-cell lymphoma, Investigative New Drugs (in press) Ariyan S. Principles of cancer management, Mathes S (ed), In: Plastic Surgery, second edition, WB Saunders, Philadelphia (in press) Ariyan S. Radiation injuries, Mathes S (ed), In: Plastic Surgery, second edition, WB Saunders, Philadelphia (in press) Ariyan S. Cutaneous melanoma. Mathes S (ed), In: Plastic Surgery, second edition, WB Saunders, Philadelphia (in press) Ariyan S. Narayan D, Ariyan CD. Salivary gland tumors, Mathes S (ed), In: Plastic Surgery, second edition, WB Saunders, Philadelphia (in press) Ariyan S. Management of metastatic disease of the head and neck. Mathes S (ed), In: Plastic Surgery, second edition, WB Saunders, Philadelphia (in press) Astrachan D, Sasaki CT. Tracheotomy, Sasaki CT (ed) Kveton JF, Ross DA, Karas DE, Leder SB (assoc. ed), The Yale Manual on Management of Ear, Nose, and Throat, Disorders in Primary Care Practice, Humana Press, Totowa, NJ. (in press) Bartoshuk LM. Disorder of smell and taste, Sasaki CT (ed) Kveton JF, Ross DA, Karas DE, Leder SB (assoc. ed), The Yale Manual on Management of Ear, Nose, and Throat, Disorders in Primary Care Practice, Humana Press, Totowa, NJ (in press) Bartoshuk LM, Duffy VB, Fast K, Green BG, Snyder DJ. Hormones, age, genes and pathology: How do we assess variation in sensation and preference? Food Selection: From Genes to Culture, Danone Institute, Paris, France, 2001 (in press) Bartoshuk LM. Autobiography, O’Connell A (ed), Models of Achievement: Reflections of Eminent Women in Psychology,Volume 3, Lawrence Erlbaum Associates, Mahwah, NJ, 169-183, 2001 Bartoshuk, LM, Duffy VB, Fast K., Green BG, Snyder DJ. Hormones, age, genes and pathology: How do we assess variation in sensation and preference? Food Selection: From Genes to Culture, Paris, France, Danone Institute, 2002. Bartoshuk LM. Self reports and across-group comparisons: A way out of the box. APS Observer, 15, 7, 26-28, 2002, Bartoshuk LM, Duffy VB, Fast K., Green BG, Prutkin J, Snyder DJ. Labeled scales (e.g., category, Likert, VAS) and invalid across-group comparisons: What we have learned from genetic variation in taste. Journal Bhanot S, Alex JC, Lowlicht RA, Sasaki CT, et al, The efficacy of resorbable plates in head and neck reconstruction, Laryngoscope, 112(5):890-898, 2002 Bhanot S, Alex JC. Current applications of blood products and platelet gels in facial plastic surgery, Facial Plastic Surgery, 18:27-33, 2002 Bianchi M, Oliver R. Neck Mass, Sasaki CT (ed) Kveton JF, Ross DA, Karas DE, Leder SB (assoc. ed), The Yale Manual on Management of Ear, Nose, and Throat, Disorders in Primary Care Practice, Humana Press, Totowa, NJ (in press)
Breslin PAS, Gingrich TN, Green BG. Psychophysical investigations of oral ibuprofen: basic sensory characteristics, Chemical Senses. 26:55-65, 2001
Chen T, Yan W, Wells RG, Rimm DL, McNiff J, Leffell DJ, Reiss M: Novel Inactivating Mutations of Transforming Growth Factor-B Type I Receptor Gene In Head- And-Neck Cancer Metastases. Internal Journal of Cancer, May 2001
Choi EC, Koh YW, Kim MS, Kim HJ, Chung TY, Choi JJ, Kim CH, Kim Y-H. Invasions and metastases of facial and neck skin by head and neck cancer. Korean J Otolaryngol, 44:517-521, 2001
Choi EC, Kim CH, Kim SH, Kim Y-H, Kim KM. The role of pectoralis major myocutaneous flap in the era of free flap, Korean J Head Neck Oncology, 17(2):190-193, 2001
Choi HS, Jung EJ, Chun HS, Moon IS, Kim Y-H, Kim KM. Development of cannula- typed silicone voice prosthesis (So-Mang®), J. Korean Soc Logoped Phoniatr, 12(2):152- 157, 2001
Christmas DA, Yanagisawa E, Mirante JP. Powered endoscopic maxillary sinusotomy. In: Yanagisawa E, Christmas DA, Mirante JP. Powered Instrumentation in Otolaryngology – Head and Neck Surgery, Chapter 5, San Diego, Singular, 2001
Christmas DA, Yanagisawa E, Mirante JP. Powered endoscopic ethmoid sinusotomy. In: Yanagisawa E, Christmas DA, Mirante Jp. Powered Instrumentation in Otolaryngology – Head and Neck Surgery, Chapter 6, San Diego, Singular, 2001
Christmas DA, Yanagisawa E, Mirante JP. Powered endoscopic sphenoid sinusotomy. In: Yanagisawa E, Christmas DA, Mirante JP. Powered Instrumentation in Otolaryngology – Head and Neck Surgery, Chapter 7, San Diego, Singular, 2001
Christmas DA, Yanagisawa E, Mirante JP. Powered instrumentation with computer- aided navigation in otolaryngology – head and neck surgery. In: Yanagisawa E,
Christmas DA, Mirante JP. Powered Instrumentation in Otolaryngology – Head andNeck Surgery, Chapter 13, San Diego, Singular, 2001
Coffey T, Hernandez J. Parotid and other salivary masses, Sasaki CT (ed) Kveton JF, Ross DA, Karas DE, Leder SB (assoc. ed), The Yale Manual on Mangement of Ear, Nose, and Throat, Disorders in Primary Care Practice, Humana Press, Totowa, NJ. (in press) Cooper DL, Seropian S. Hodgkin’s disease, In: Annual of Lymphoid Malignancies, Cavalli F, Armitage J, Longo D (eds), Martin Dunitz Ltd, 31-46, 2001 Cooper DL, Seropian S. Autologous stem cell transplantation, In: Cancer: Principles and Practices of Oncology, DeVita VT, Hellman S, Rosenberg SA (eds), sixth edition, Lippincott-Raven, Philadelphia, 2767-2778, 2001 Cooper DL. Early stage Hodgkin’s disease, In: Malignant Lymphomas. ACS Atlas of Clinical Oncology, Grossbard M (ed) (in press) Cooper DL, Tumor Makers, Bennett JC and Plum F (ed) Cecil Textbook of Medicine, 21st ed. W.B. Saunders, Philadelphia. (in press) Cooper DL, Seropian S. Autologous hematopoietic progenitor cell transplants, Principles and Practices of Oncology, DeVita VT, Hellman S, Rosenberg SA (ed), 6th edition, Lippincott-Raven, Philadelphia. (in press) Dowaliby, J. What is Otolaryngology?, Sasaki CT (ed), Kveton JF, Ross DA, Karas DE, Leder SB (assoc. ed), The Yale Manual on Management of Ear, Nose, and Throat, Disorders in Primary Care Practice, Humana Press, Totowa, NJ (in press) Duffy VB, Cain WS, Ferris AM. Measurement of sensitivity to olfactory flavor: Application in a study of aging and dentures, Chemical Senses (in press) Duffy VB, Phillips MN, Peterson JM, Bartoshuk LM. Bitterness of 6-n- propylthiouracil (PROP) associates with bitter sensations and intake of vegetables, Appetite (in press) Duffy VB, Bartoshuk LM, Peterson JM, Phillips MN. Are nontasters at risk for coronary heart disease (CHD)? Chemical Senses (in press) Duffy VB, Fast K, Cohen Z, Bartoshuk LM. Genetic taste status associates with fat food acceptance and body mass index in adults. Presented at A ChemS XXI, Chemical Senses, (in press) Duffy VB, Phillips MN, Peterson JM, Bartoshuk LM. Bitterness of 6-n- propylthiouracil (PROP) associates with bitter sensations and intake of vegetables, Appetite (in press) Duffy VB, Bartoshuk LM, Peterson JM, Phillips MN. Are nontasters at risk for coronary heart disease (CHD)? Chemical Senses (in press)
Fast K, Duffy VB, Bartoshuk LM. Individual differences in taste psychophysics. In: Rouby C, Schaal B, Dubois D, Gervais R, Holley A (eds), Olfaction, Taste and Cognition, CNRS UPRESA, 2001 (in press)
Fast K, Duffy VB, Bartoshuk LM. New psychophysical insights in evaluating genetic variation in taste. Rouby C, Schaal B, Dubois D, Gervais R, Holley A (eds) In: Olfaction, Taste and Cognition, Cambridge, U.K.: Cambridge University Press, 2002.
Frese KA, Reker U, Maune S. Klinische Aspekte zur Arbeitsfähigkeit bei vestibulären Störungen. Norddeutsche Gesellschaft für Otorhinolaryngologie und zervikofaziale Chirurgie 4: 32-34, 2001
Frese KA, Reker U, Maune S. Pseudoemissionen und falsch positive Befunde in der Messung transitorisch evozierter otoakustischer Emissionen (TEOAE). Laryngo-Rhino- Otol 80: 734-739, 2001
Frese K, Reker U, Maune S. Der beidseitige Vestibularisausfall – Diagnostik und Krankheitsverlauf. HNO, 2002 (in press)
Friedman S. Otitis Media. Sasaki CT (ed), Kveton JF, Ross DA, Karas DE, Leder SB (assoc. ed), The Yale Manual on Management of Ear, Nose, and Throat, Disorders in Primary Care Practice, Humana Press, Totowa, NJ (in press)
Göbel H, Baloh R, Heinze-Kuhn K, Heinze A, Maune S. Kopfschmerzen bei Erkrankungen der Ohren, Nasen und Nasennebenhöhlen. Deutsches Ärzteblatt 98(7): 333-338, 2001 Goravalingappa, R, Kveton, JF. Physiologic changes in the ear and nose and throat (Chapter) Rosenthal RA, Zenilman ME, and Katlic MR (eds) Principles and Practice of Geriatric Surgery. (in press)
Görögh T, Maune S, Lippert BM, Rudert H, Gottschlich S, Hoffmann M, Meyer JE, Heidorn K, Werner JA. Transciptional repression of the human fibronectin gene in laryngeal squamous cell carcinoma cells. J Cancer Res Clin Oncol 127: 166-172, 2001
Gottschlich S, Koch R, Görögh T, Holtmeyer C, Hoffmann M, Rudert H, Maune S. Kollagenase-3 mRNA-Expression in Plattenepithelkarzinomen des Oropharynx. HNO 50(1): 43-47, 2002
Gottschlich S, Hoffmann M, Görögh T, Maaß JD, Rudert H, Maune S. p53 serum antibodies as tumor marker in head and neck cancer. Anticancer Research, 2002 (in press) Green BG. Psychophysical measurement of oral chemesthesis. In: Simon SA, Nicolelis MAI (eds), Methods and Frontiers in Neuroscience, Boca Raton, FL, CRC Press (in press) Green BG, Zaharchuk R. Spatial variation in sensitivity as a factor in measurements of spatial summation of warmth and cold, Somatosensory and Motor Research (in press) Green BG. Studying Taste as a Cutaneous Sense, J. Food Quality and Preference (in press)
Guttenberg I. Earache. Sasaki CT (ed), Kveton JF, Ross DA, Karas DE, Leder SB (assoc. ed), The Yale Manual on Management of Ear, Nose, and Throat, Disorders in Primary Care Practice, Humana Press, Totowa, NJ (in press)
Hasbun R, Abrahams JJ, Jekel J, Quagliarello VJ. Computed tomography of the head before lumbar puncture in adults with suspected meningitis. N Engl J Med, 345:1727- 1733, 2001
Higgins TF, DeLuca PA, Ariyan S. Salvage of open tibial fracture with segmental loss of tibial nerve, Case report and review of literature, J Orthop Trauma (in press) Hirokawa RH, Scher DA, Yanagisawa E. Unusual cartilaginous lesion of the torus tubarius as a cause of otalgia, ENT J, 80:136-137, 2001
Holland D, Behrendt S, Maune S, Kovács G. Metastatic tumors of the orbit –a retrospective study. Orbit, 2002 (in press)
Hoffmann-Fazel A, Gottschlich S, Hoffmann M, Maaß JD, Rudert H, Maune S. The value of CYFRA 21-1 serum levels for detection of distant metastases in head and neck cancer. Anticancer Research, 2002 (in press)
Hoffmann M, Scheunemann D, Rudert H, Maune S. Zenker’s Diverticulotomy with the CO2-Laser – Perioperative Management and Long-term Results. Annals of Otology, Rhinology & Laryngology, 2002 (in press)
Höft S, Muhle C, Brenner W, Sprenger E, Maune S. Fine needle aspiration cytology of the sentinel lymph node in head and neck cancer. J Nucl Med, 2002 (in press)
Huh JW, Han SJ, Kim Y-H, Kim MJ, Lee KY, Kim JE, Han A, Hwang EH. A successful slide cricotracheoplasty in congenital cricotracheal stenosis. J Korean Assoc Pediatric Surgeons, 7(1):54-58, 2001
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Khan AJ, DiGiovanna MP, Ross DA, Sasaki CT, Carter D, Son YH, Haffty BG: Adenoid cystic carcinoma: a retrospective clinical review, Int. J. Cancer, 96:149-158, 2001
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Mayne ST, Cartmel B, Baum M, Shor-Posner G, Fallon BG, Briskin K, Bean J, Zheng T, Cooper D, Friedman C, Goodwin WJ. Randomized trial of supplemental B-Carotene to prevent second head and neck cancer, Cancer Res, 61:1457-1463, 2001
McGuirk J, Seropian S, Howe G, Smith B, Krause D, Cooper DL. Use of Rituximab and irradiated donor derived lymphocytes to control Epstein-Barr virus associated lymphoproliferation in patients undergoing related haplo-identical stem cell transplantation, Bone Marrow Transplant (in press)
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Mirante JP, Christmas DA, Yanagisawa E. History and development of powered instrumentation in otolaryngology-head and neck surgery. In: Yanagisawa E, Christmas DA, Mirate JP. Powered instrumentation in Otolaryngology – Head and Neck Surgery. Chapter 1, San Diego, Singular, 2001
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Paulsen F, Thale A, Maune S, Tillmann B. New Insights into the Pathophysiology of Primary Aquired Dacryostenosis. Ophthamology 108(12): 2329-2336, 2001
Paulsen F, Maune S, Thale A,Schaudig U, Tillmann B. Lacrimal drainage immunity: the role of tear duct associated lymphoid tissue. Invest Ophthalmol Vis Sci, 2002 (in press)
Phillips MN, Bartoshuk LM, Peterson JM, Duffy VB. 6-n-propylthiouracil (PROP) bitterness: associations with creamy sensations, preference for and intake of high fat foods, Chemical Senses (in press)
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Smith BD, Smith GL, Carter D, Giovanna MP, Kasowitz KM, Sasaki CT, Haffty BG. Molecular marker expression in oral and oropharyngeal squamous cell carcinoma, Arch Otolaryngology Head and Neck Surg, 127:780-785, 2001 Smith-Bruno N. Hearing Tests, Sasaki CT (ed), Kveton JF, Ross DA, Karas DE, Leder SB (assoc. ed). The Yale Manual on Management of Ear, Nose, and Throat, Disorders in Primary Care Practice, Humana Press, Totowa, NJ (in press)
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Weise JB, Görögh T, Meyer JE, Maune S. A comparative study of chemokine RANTES detection using ELISA and western blood. 110 (1&2): 139 – 142, 2001
Weise JB, Meyer JE, Helmer H, Wittrock H, Maune S. A new discovered function of palatine tonsils in immune defence: the expression of defensins. Otolaryngol Pol, 2002 (in press)
Wierzbicka M, Kusnierkiewicz M, Wojtowicz JG, Maune S, Szyfter W. The quality of life in head and neck cancer patients: description of randomized examination formula based on standardized questionnaires EORTC QLQ C-30, EORTC QTQ-H-N35 and Kiel Questionnaire. Otolaryngol Pol 55(3): 287-292, 2001
Wilson LD. Kacinski BM, Heald PW, Jones GW. Mycosis Fungoides, Gunderson LLand Tepper JE (ed) Clinical Radiation Oncology, Churchill Livingston, (in press). Wilson LD, Jones GW, Kacinski BM, Edelson RL, Heald P. Cutaneous T-cell Lymphoma, Devita VT, Hellman S, Rosenberg SA (eds), In: Cancer, Principles and Practice of Oncology, 6th edition, Lippincott, Philadelphia, PA, 2316-2329, 2001 Yanagisawa E, Ho SY, Mirante JP, Yanagisawa K, Powered endoscopic choanal polypectomy. In: Yanagisawa E, Christmas DA, Mirante JP. Powered Instrumentation in Otolaryngology – Head and Neck Surgery. Chapter 4, San Diego, Singular, 2001 Yanagisawa E, YanagisawaK, Mirante JP. Powered endoscopic mini Caldwell-Luc procedure. In: Yanagisawa K, Christmas DA, Mirante JP. Powered Instrumentation in Otolaryngology –Head and Neck Surgery, Chapter 8, San Diego, Singular, 2001 Yanagisawa E, Sims HS, Mirante JP. Powered endoscopic transnasal repair of choanal atresia, . In: Yanagisawa K, Christmas DA, Mirante JP. Powered Instrumentation in Otolaryngology –Head and Neck Surgery, Chapter 16, San Diego, Singular, 2001 Yanagisawa E, Ho SY, Mirante JP. Powered transnasal adenoidectomy, In: Yanagisawa K, Christmas DA, Mirante JP. Powered Instrumentation in Otolaryngology –Head and Neck Surgery, Chapter 24, San Diego, Singular, 2001 Yanagisawa E, Joe JK. Anterior and posterior nasal fontanelles, ENT J 80:10-12, 2001 Yanagisawa E. Endoscopic view of a high septal deviation, ENT J 80:68-70, 2001 Yanagisawa E, Yanagisawa K. Endoscopic view of the basal lamella, ENT J 80:192, 2001 Yanagisawa E, Yanagisawa K. Endoscopic view of a concha bullosa of the middle turbinate, ENT J 80:298, 2001 Yanagisawa E, Marotta JC, Yanagisawa K. Endoscopic view of a mucocele in an infraorbital ethmoid cell (Haller cell). ENT J 80:364, 368, 2001 Yangagisawa E. Altas of Rhinoscopy, San Diego, Singular Publishing Group, (in press) Yanagisawa E, Yanagisawa K. Hoarseness and Cough, Sasaki CT (ed) Kveton JF, Ross DA, Karas DE, Leder SB (assoc. ed), The Yale Manual on Management of Ear, Nose, and Throat, Disorders in Primary Care Practice, Humana Press, Totowa, NJ. (in press)
Universidad REGLAMENTO DE BIBLIOTECA INDICE Título Primero: Definición, Función y Organización Art. 1 Definición 3 Art. 2 Funciones 3 Art. 3 Organización 3 Art. 4 Relaciones Externas 4 Título Segundo: Deberes del Ejecutivo, Asistente y Becarios Bibliotecarios Art. 5 Deberes del Ejecutivo Bibliotecario 4 Art. 6 Deberes del Asistente y Becarios Bibliotecarios 5 Art. 7 Nombramie
the binding of the dye coated with cotinine conjugate to the antibodies on References the membrane. This prevents the formation of a line on the membrane. 1. U.S. Department of Health and Human Services, Public Health Service,Therefore, a cotinine-positive urine sample will not generate a line at theCenters for Disease Control: Reducing the Health Consequences of Smoking, 25 Years of Pr