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Analysis Of Carotid Lumen Surface Morphology Using Three-Dimensional Ultrasound Imaging, Bernard Chiu, Vadim Beletsky, J David Spence, Grace Parraga, Aaron Fenster

Medical Biophysics Publications

Carotid plaque surface irregularity and ulcerations play an important role in the risk of ischemic stroke. Ulcerated or fissured plaque, characterized by irregular surface morphology, exposes thrombogenic materials to the bloodstream, possibly leading to life- or brain-threatening thrombosis and embolization. Therefore, the quantification of plaque surface irregularity is important to identify high-risk plaques that would likely lead to vascular events. Although a number of studies have characterized plaque surface irregularity using subjective classification schemes with two or more categories, only a few have quantified surface irregularity using an objective and continuous quantity, such as Gaussian or mean curvature. In this …

Paracrine Sonic Hedgehog Signalling By Prostate Cancer Cells Induces Osteoblast Differentiation, Samantha M Zunich, Taneka Douglas, Maria Valdovinos, Tiffany Chang

Dartmouth Scholarship

Sonic hedgehog (Shh) and components of its signalling pathway have been identified in human prostate carcinoma and increased levels of their expression appear to correlate with disease progression and metastasis. The mechanism through which Shh signalling could promote metastasis in bone, the most common site for prostate carcinoma metastasis, has not yet been investigated. The present study determined the effect of Shh signalling between prostate cancer cells and pre-osteoblasts on osteoblast differentiation, a requisite process for new bone formation that characterizes prostate carcinoma metastasis.

Genotypic Confirmation Of Transimmunization-Induced Dendritic Cell Maturation, Kristin Elizabeth Hoffmann

Yale Medicine Thesis Digital Library

Transimmunization (TI), a novel modification of the widely used immunotherapy extracorporeal photopheresis (ECP), induces conversion of processed monocytes into cells expressing phenotypic and functional features of dendritic antigen presenting cells (DC). To further characterize TI-induced DC, we analyzed differential gene expression in the monocyte/DC population after TI treatment. Because ECP, the therapy upon which TI is based, has the unique capacity to induce both anti-cancer immune responses in cutaneous T cell lymphoma (CTCL) patients and tolerogenic responses in graft-versus-host disease (GVHD), we studied TI-induced gene expression changes in both of these patient populations as well as in healthy normal control …

Association Of Gucy2c Expression In Lymph Nodes With Time To Recurrence And Disease-Free Survival In Pn0 Colorectal Cancer., Scott A Waldman, Terry Hyslop, Stephanie Schulz, Alan Barkun, Karl Nielsen, Janis Haaf, Christine Bonaccorso, Yanyan Li, David S Weinberg

Department of Pharmacology and Experimental Therapeutics Faculty Papers

CONTEXT: The established relationship between lymph node metastasis and prognosis in colorectal cancer suggests that recurrence in 25% of patients with lymph nodes free of tumor cells by histopathology (pN0) reflects the presence of occult metastases. Guanylyl cyclase 2C (GUCY2C) is a marker expressed by colorectal tumors that could reveal occult metastases in lymph nodes and better estimate recurrence risk.

OBJECTIVE: To examine the association of occult lymph node metastases detected by quantifying GUCY2C messenger RNA, using the reverse transcriptase-polymerase chain reaction, with recurrence and survival in patients with colorectal cancer.

DESIGN, SETTING, AND PARTICIPANTS: Prospective study of 257 patients …

Creb Mediates Prostaglandin F2alpha-Induced Muc5ac Overexpression, Wen-Cheng Chung, Seung-Hee Ryu, Hongxia Sun, Darryl C Zeldin, Ja Seok Koo

Faculty, Staff and Student Publications

Mucus secretion is an important protective mechanism for the luminal lining of open tubular organs, but mucin overproduction in the respiratory tract can exacerbate the inflammatory process and cause airway obstruction. Production of MUC5AC, a predominant gel-forming mucin secreted by airway epithelia, can be induced by various inflammatory mediators such as prostaglandins. The two major prostaglandins involved in inflammation are PGE(2) and PGF(2alpha). PGE(2)-induced mucin production has been well studied, but the effect of PGF(2alpha) on mucin production remains poorly understood. To elucidate the effect and underlying mechanism of PGF(2alpha) on MUC5AC production, we investigated the signal transduction of PGF(2alpha) …

Accumulation Of Rhodopsin In Late Endosomes Triggers Photoreceptor Cell Degeneration, Yashodhan Chinchore, Amitavo Mitra, Patrick J. Dolph, Norbert Perrimon

Dartmouth Scholarship

Progressive retinal degeneration is the underlying feature of many human retinal dystrophies. Previous work using Drosophila as a model system and analysis of specific mutations in human rhodopsin have uncovered a connection between rhodopsin endocytosis and retinal degeneration. In these mutants, rhodopsin and its regulatory protein arrestin form stable complexes, and endocytosis of these complexes causes photoreceptor cell death. In this study we show that the internalized rhodopsin is not degraded in the lysosome but instead accumulates in the late endosomes. Using mutants that are defective in late endosome to lysosome trafficking, we were able to show that rhodopsin accumulates …

Dna Instability In Replicating Huntington's Disease Lymphoblasts, Milena Cannella, Vittorio Maglione, Tiziana Martino, Giuseppe Ragona, Luigi Frati, Guo-Min Li, Ferdinando Squitieri

Toxicology and Cancer Biology Faculty Publications

BACKGROUND: The expanded CAG repeat in the Huntington's disease (HD) gene may display tissue-specific variability (e.g. triplet mosaicism) in repeat length, the longest mutations involving mitotic (germ and glial cells) and postmitotic (neurons) cells. What contributes to the triplet mutability underlying the development of HD nevertheless remains unknown. We investigated whether, besides the increased DNA instability documented in postmitotic neurons, possible environmental and genetic mechanisms, related to cell replication, may concur to determine CAG repeat mutability. To test this hypothesis we used, as a model, cultured HD patients' lymphoblasts with various CAG repeat lengths.

RESULTS: Although most lymphoblastoid cell lines …

Facilitated Monocyte-Macrophage Uptake And Tissue Distribution Of Superparmagnetic Iron-Oxide Nanoparticles., Arnaud Beduneau, Zhiya Ma, Cassi B. Grotepas, Alexander Kabanov, Barrett E. Rabinow, Nan Gong, R. Lee Mosley, Huanyu Dou, Michael D. Boska, Howard Gendelman

Journal Articles: Radiology

BACKGROUND: We posit that the same mononuclear phagocytes (MP) that serve as target cells and vehicles for a host of microbial infections can be used to improve diagnostics and drug delivery. We also theorize that physical and biological processes such as particle shape, size, coating and opsonization that affect MP clearance of debris and microbes can be harnessed to facilitate uptake of nanoparticles (NP) and tissue delivery.

METHODS: Monocytes and monocyte-derived macrophages (MDM) were used as vehicles of superparamagnetic iron oxide (SPIO) NP and immunoglobulin (IgG) or albumin coated SPIO for studies of uptake and distribution. IgG coated SPIO was …

Endothelial Progenitor Cell Number And Colony-Forming Capacity In Overweight And Obese Adults, O J Maceneaney, E J Kushner, Gary P. Van Guilder, J J Greiner, B L Stauffer, C A Desouza

Health and Nutritional Sciences Faculty Publications

OBJECTIVE: To investigate whether adiposity influences endothelial progenitor cell (EPC) number and colony-forming capacity.
DESIGN: Cross-sectional study of normal weight, overweight and obese adult humans.
PARTICIPANTS: Sixty-seven sedentary adults (aged 45-65 years): 25 normal weight (body mass index (BMI) or=30 kg/m(2); 18 males/6 females). All participants were non-smokers and free of overt cardiometabolic disease.
MEASUREMENTS: Peripheral blood samples were collected and circulating EPC number was assessed by flow cytometry. Putative EPCs were defined as CD45(-)/CD34(+)/VEGFR-2(+)/CD133(+) or CD45(-)/CD34(+) cells. EPC colony-forming capacity was measured in vitro using a colony-forming unit (CFU) assay.
RESULTS: Number of circulating putative EPCs (either CD45(-)/CD34(+)/VEGFR-2(+)/CD133(+) or …

The Future (Or Lack Of Future) Of Personalized Prescription In Psychiatry, Jose De Leon

Psychiatry Faculty Publications

Rapid technological advances in genetics have created conceptual chaos regarding the genetics of drug response. Terms for differing concepts are used interchangeably: pharmacogenetics with pharmacogenomics, personalized medicine with personalized prescription. Biomarker has many definitions. The author prefers the concept of personalized prescription and uses it with implications beyond pharmacogenetics by considering all scientific information valid for prescribing medication. Genetics may not be crucial for all drugs. In this comprehensive view, clinicians must consider genetic, environmental and personal variables when prescribing medication and incorporate some basic pharmacological principles: (1) safety and efficacy, (2) pharmacokinetics and pharmacodynamics, (3) therapeutic window and prescriber's …

Identification Of A Potent Herbal Molecule For The Treatment Of Breast Cancer, Srinivas Koduru, Srinivasan Sowmyalakshmi, Raj Kumar, Rohini Gomathinayagam, Jürgen Rohr, Chendil Damodaran

Pharmaceutical Sciences Faculty Publications

BACKGROUND: Breast cancer (BCa)-related mortality still remains the second leading cause of cancer-related deaths worldwide. Patients with BCa have increasingly shown resistance and high toxicity to current chemotherapeutic drugs for which identification of novel targeted therapies are required.

METHODS: To determine the effect of PDBD on BCa cells, estrogen-receptor positive (ER+)-MCF-7 and estrogen-receptor negative (ER-)-MDA 231 cells were treated with PDBD and the cell viability, apoptotic, cell cycle, Western blot and Promoter assays were performed.

RESULTS: PDBD inhibits cell viability of ER+ and ER- BCa cells by inducing apoptosis without causing significant toxicity in normal breast epithelial cells. While dissecting …

Incompatibility With Formin Cdc12p Prevents Human Profilin From Substituting For Fission Yeast Profilin: Insights From Crystal Structures Of Fission Yeast Profilin., Obidimma Ezezika, Noah S Younger, Jia Lu, Donald A Kaiser, Zachary A Corbin, Bradley J Nolen, David R Kovar, Thomas D Pollard

Health Studies Publications

Expression of human profilin-I does not complement the temperature-sensitive cdc3-124 mutation of the single profilin gene in fission yeast Schizosaccharomyces pombe, resulting in death from cytokinesis defects. Human profilin-I and S. pombe profilin have similar affinities for actin monomers, the FH1 domain of fission yeast formin Cdc12p and poly-L-proline (Lu, J., and Pollard, T. D. (2001) Mol. Biol. Cell 12, 1161-1175), but human profilin-I does not stimulate actin filament elongation by formin Cdc12p like S. pombe profilin. Two crystal structures of S. pombe profilin and homology models of S. pombe profilin bound to actin show how the two profilins bind …

The Specificity Of The Search Template, Mary J. Bravo, Hany Farid

Dartmouth Scholarship

When searching for a target object, observers use an internal representation of the target's appearance as a search template. This study used naturalistic stimuli to examine the specificity of this template. Observers first learned several name-image pairs; they then participated in a search experiment in which the names served as cues and the images served as targets. To test whether the observers searched for the targets using an exact image template, we included targets that were transformations of the studied image and targets that belonged to the same subordinate-level category as the studied image. The same stimuli were also used …

Systems-Level Interactions Between Insulin-Egf Networks Amplify Mitogenic Signaling., Nikolay Borisov, Edita Aksamitiene, Anatoly Kiyatkin, Stefan Legewie, Jan Berkhout, Thomas Maiwald, Nikolai P Kaimachnikov, Jens Timmer, Jan B Hoek, Boris N Kholodenko

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Crosstalk mechanisms have not been studied as thoroughly as individual signaling pathways. We exploit experimental and computational approaches to reveal how a concordant interplay between the insulin and epidermal growth factor (EGF) signaling networks can potentiate mitogenic signaling. In HEK293 cells, insulin is a poor activator of the Ras/ERK (extracellular signal-regulated kinase) cascade, yet it enhances ERK activation by low EGF doses. We find that major crosstalk mechanisms that amplify ERK signaling are localized upstream of Ras and at the Ras/Raf level. Computational modeling unveils how critical network nodes, the adaptor proteins GAB1 and insulin receptor substrate (IRS), Src kinase, …

Mitostatin, A Putative Tumor Suppressor On Chromosome 12q24.1, Is Downregulated In Human Bladder And Breast Cancer., A Vecchione, M Fassan, V Anesti, A Morrione, S Goldoni, G Baldassarre, D Byrne, D D'Arca, J P Palazzo, J Lloyd, L Scorrano, L G Gomella, R V Iozzo, R Baffa

Department of Urology Faculty Papers

Allelic deletions on human chromosome 12q24 are frequently reported in a variety of malignant neoplasms, indicating the presence of a tumor suppressor gene(s) in this chromosomal region. However, no reasonable candidate has been identified so far. In this study, we report the cloning and functional characterization of a novel mitochondrial protein with tumor suppressor activity, henceforth designated MITOSTATIN. Human MITOSTATIN was found within a 3.2-kb transcript, which encoded a approximately 62 kDa, ubiquitously expressed protein with little homology to any known protein. We found homozygous deletions and mutations of MITOSTATIN gene in approximately 5 and approximately 11% of various cancer-derived …

Genic Regions Of A Large Salamander Genome Contain Long Introns And Novel Genes, Jeramiah J. Smith, Srikrishna Putta, Wei Zhu, Gerald M. Pao, Inder M. Verma, Tony Hunter, Susan V. Bryant, David M. Gardiner, Timothy T. Harkins, S. Randal Voss

Biology Faculty Publications

BACKGROUND: The basis of genome size variation remains an outstanding question because DNA sequence data are lacking for organisms with large genomes. Sixteen BAC clones from the Mexican axolotl (Ambystoma mexicanum: c-value = 32 x 10(9) bp) were isolated and sequenced to characterize the structure of genic regions.

RESULTS: Annotation of genes within BACs showed that axolotl introns are on average 10x longer than orthologous vertebrate introns and they are predicted to contain more functional elements, including miRNAs and snoRNAs. Loci were discovered within BACs for two novel EST transcripts that are differentially expressed during spinal cord regeneration and skin …

The Sleeping Brain's Influence On Verbal Memory: Boosting Resistance To Interference, Jeffrey M. Ellenbogen, Justin C. Hulbert, Ying Jiang, Robert Stickgold

Dartmouth Scholarship

Memories evolve. After learning something new, the brain initiates a complex set of post-learning processing that facilitates recall (i.e., consolidation). Evidence points to sleep as one of the determinants of that change. But whenever a behavioral study of episodic memory shows a benefit of sleep, critics assert that sleep only leads to a temporary shelter from the damaging effects of interference that would otherwise accrue during wakefulness. To evaluate the potentially active role of sleep for verbal memory, we compared memory recall after sleep, with and without interference before testing. We demonstrated that recall performance for verbal memory was greater …

Iatrogenic Bile Duct Injury Associated With Anomalies Of The Right Hepatic Sectoral Ducts: A Misunderstood And Underappreciated Problem, Nitin Babel, Sujit Vijay Sakpal, Prakash Paragi, Jason Wellen, Stephen Feldman, Ronald Scott Chamberlain

Department of Surgery

Although laparoscopic cholecystectomy (LC) has been widely accepted as the standard of care, it continues to have a higher complication rate than open cholecystectomy. Bile duct injury with LC has often been attributed to surgical inexperience, but it is also clear that aberrant bile ducts are present in a significant number of patients who sustain biliary injuries during these procedures. We present three cases of right sectoral hepatic duct injuries which occurred during LC and provide a discussion of the conditions which are likely to lead to these injuries, as part of a strategy to prevent them.

Sand Fly Fever: What Have We Learned In One Hundred Years?, David Brett-Major, David M. Claborn

Journal Articles: Epidemiology

Sand fly fever has severely impacted military missions in southern Europe and the Middle East for hundreds of years. After a brief respite following the malaria eradication programs of World War II, it has returned as a significant disease among residents in and travelers to the Mediterranean rim. It is a more severe disease now, with potential vectors in the United States. Sand fly fever is discussed in terms of its viruses, vectors, disease, control, and potential domestic impact.

Aging And Endothelial Progenitor Cell Telomere Length In Healthy Men, Erich J Kushner, Gary P. Van Guilder, Owen J Maceneaney, Jennifer N Cech, Brian L Stauffer, Christopher A Desouza

Health and Nutritional Sciences Faculty Publications

BACKGROUND: Telomere length declines with age in mature endothelial cells and is thought to contribute to endothelial dysfunction and atherogenesis. Bone marrow-derived circulating endothelial progenitor cells (EPCs) are critical to vascular health as they contribute to both reendothelialization and neovascularization. We tested the hypothesis that EPC telomere length decreases with age in healthy adult humans.

METHODS: Peripheral blood samples were collected from 40 healthy, non-obese, sedentary men: 12 young (age 21-34 years), 12 middle-aged (43-55 years) and 16 older (57-68 years). Putative EPCs were isolated from peripheral blood mononuclear cells and telomere length was determined using genomic DNA preparation and …

The Root Of Dental Anatomy: A Case For Naming Eustachius The "Father Of Dental Anatomy"., Gregory W. Bennett

Journal Articles: College of Dentistry

When one considers the names of those whose affect on dentistry reached far beyond their lifetimes, one may think of Fauchard, Wells, Morton and Black. One name that deserves to be called among the pantheon of the greats is Bartholomaeus Eustachius. Eustachius was not the first to study the anatomy of the teeth and jaws, having been preceded by Da Vinci; however, he was the first to publish a treatise devoted entirely to this subject, Libellus de Dentibus, in 1563. As Sir William Osler, the father of modern medicine, stated: "In Science, the credit goes to the man who convinces …

Stat5 Regulation Of Bcl10 Parallels Constitutive Nfkappab Activation In Lymphoid Tumor Cells., Zsuzsanna S Nagy, Matthew J Lebaron, Jeremy A Ross, Abhisek Mitra, Hallgeir Rui, Robert A Kirken

Department of Cancer Biology Faculty Papers

BACKGROUND: Signal Transducer and Activator of Transcription 5 A and B (STAT5) are key survival factors in cells of the lymphoid lineage. Identification of novel, tissue-specific STAT5 regulated genes would advance the ability to combat diseases due to aberrant STAT5 signaling. In the present work a library of human STAT5 bound genomic elements was created and validated. RESULTS: Of several STAT5 responsive genomic regulatory elements identified, one was located within the first intron of the human BCL10 gene. Chromatin immuno-precipitation reactions confirmed constitutive in vivo STAT5 binding to this intronic fragment in various human lymphoid tumor cell lines. Interestingly, non-phosphorylated …

Genetic And Hormonal Factors Modulate Spreading Depression And Transient Hemiparesis In Mouse Models Of Familial Hemiplegic Migraine Type 1, Katharina Eikermann-Haerter, Ergin Dileköz, Chiho Kudo, Sean I Savitz, Christian Waeber, Michael J Baum, Michel D Ferrari, Arn M J M Van Den Maagdenberg, Michael A Moskowitz, Cenk Ayata

Faculty, Staff and Student Publications

Familial hemiplegic migraine type 1 (FHM1) is an autosomal dominant subtype of migraine with aura that is associated with hemiparesis. As with other types of migraine, it affects women more frequently than men. FHM1 is caused by mutations in the CACNA1A gene, which encodes the alpha1A subunit of Cav2.1 channels; the R192Q mutation in CACNA1A causes a mild form of FHM1, whereas the S218L mutation causes a severe, often lethal phenotype. Spreading depression (SD), a slowly propagating neuronal and glial cell depolarization that leads to depression of neuronal activity, is the most likely cause of migraine aura. Here, we have …

Interface Pressure Profile Analysis For Patellar Tendon-Bearing Socket And Hydrostatic Socket, E.K. Moo, Noor Azuan Abu Osman, Belinda Pingguan-Murphy, Wan Abu Bakar Wan Abas, W.D. Spence, S.E. Solomonidis

Research Publications (2006 to 2010)

Conventionally, patellar tendon-bearing (PTB) sockets, which need high dexterity of prosthetist, are widely used. Lack of chartered and experienced prosthetist has often led to painful experience of wearing prosthesis and this will in turn deter the patients to wear the prosthesis, which will further aggravate stump shrinkage. Thus, the hydrostatic socket which demands relatively lower level of fabricating skill is proposed to replace the PTB socket in order to produce the equivalent, if not better, quality of support to the amputee patients. Both sockets' pressure profiles are studied and compared using finite element analysis (FEA) software. Three-dimensional models of both …

Osteoarthritis Associated With Estrogen Deficiency., Jorge A Roman-Blas, Santos Castañeda, Raquel Largo, Gabriel Herrero-Beaumont

Jefferson Institute of Molecular Medicine Papers and Presentations

Osteoarthritis (OA) affects all articular tissues and finally leads to joint failure. Although articular tissues have long been considered unresponsive to estrogens or their deficiency, there is now increasing evidence that estrogens influence the activity of joint tissues through complex molecular pathways that act at multiple levels. Indeed, we are only just beginning to understand the effects of estrogen deficiency on articular tissues during OA development and progression, as well as on the association between OA and osteoporosis. Estrogen replacement therapy and current selective estrogen receptor modulators have mixed effectiveness in preserving and/or restoring joint tissue in OA. Thus, a …

Polyethylenimine-Based Sirna Nanocomplexes Reprogram Tumor-Associated Dendritic Cells Via Tlr5 To Elicit Therapeutic Antitumor Immunity, Juan R. Cubillos-Ruiz, Xavier Engle, Uciane K. Scarlett, Diana Martinez

Dartmouth Scholarship

No abstract provided.

Functional Interactions Between Distinct Sodium Channel Cytoplasmic Domains Through The Action Of Calmodulin, F. Potet, B. Chagot, Mircea Anghelescu, P. Viswanathan, S. J. Stepanovic, S. Kuperschmidt, W. J. Chazin, J. R. Balser

PCOM Scholarly Works

Sodium channels are fundamental signaling molecules in excitable cells, and are molecular targets for local anesthetic agents and intracellular free Ca2+ ([Ca2+]i). Two regions of NaV1.5 have been identified previously as [Ca2+]i-sensitive modulators of channel inactivation. These include a C-terminal IQ motif that binds calmodulin (CaM) in different modes depending on Ca2+ levels, and an immediately adjacent C-terminal EF-hand domain that directly binds Ca2+. Here we show that a mutation of the IQ domain (A1924T; Brugada Syndrome) that reduces CaM binding stabilizes NaV1.5 inactivation, similarly and more extensively than even reducing [Ca2+]i. Because the DIII-DIV linker is an essential structure …

Mrn Complex Function In The Repair Of Chromosomal Rag-Mediated Dna Double-Strand Breaks, Beth A. Helmink, Andrea L. Bredemeyer, Baeck-Seung Lee, Ching-Yu Huang, Girdhar G. Sharma, Laura M. Walker, Jeffrey J. Bednarski, Wan-Ling Lee, Tej K. Pandita, Craig H. Bassing, Barry P. Sleckman

Open Access Publications

The Mre11-Rad50-Nbs1 (MRN) complex functions in the repair of DNA double-strand breaks (DSBs) by homologous recombination (HR) at postreplicative stages of the cell cycle. During HR, the MRN complex functions directly in the repair of DNA DSBs and in the initiation of DSB responses through activation of the ataxia telangiectasia-mutated (ATM) serine-threonine kinase. Whether MRN functions in DNA damage responses before DNA replication in G0/G1 phase cells has been less clear. In developing G1-phase lymphocytes, DNA DSBs are generated by the Rag endonuclease and repaired during the assembly of antigen receptor genes by the process of V(D)J recombination. Mice and …

Aging And Endothelial Progenitor Cell Telomere Length In Healthy Men, Erich J Kushner, Gary Van Guilder, Owen J Maceneaney, Jennifer N Cech, Brian L Stauffer, Christopher A Desouza

Health and Nutritional Sciences Faculty Publications

BACKGROUND: Telomere length declines with age in mature endothelial cells and is thought to contribute to endothelial dysfunction and atherogenesis. Bone marrow-derived circulating endothelial progenitor cells (EPCs) are critical to vascular health as they contribute to both reendothelialization and neovascularization. We tested the hypothesis that EPC telomere length decreases with age in healthy adult humans.
METHODS: Peripheral blood samples were collected from 40 healthy, non-obese, sedentary men: 12 young (age 21-34 years), 12 middle-aged (43-55 years) and 16 older (57-68 years). Putative EPCs were isolated from peripheral blood mononuclear cells and telomere length was determined using genomic DNA preparation and …

Unusual Fibrosclerotic Lesion Of The Laryngotracheal Complex Presenting As Subglottic Stenosis., Douglas R. Johnston, Joseph M. Curry, Raphael Rubin, Marc R. Rosen

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

We present a case report that describes the pathology, presentation, and management complexities of an unusual, destructive fibrosclerotic lesion of the laryngotracheal complex. An otherwise healthy 21-year-old man presented with a 1-year history of progressive shortness of breath and stridor. The initial examination revealed a 3-cm, grade III subglottic stenosis. Nodular fibrosis of the strap muscles, laryngotracheal cartilages, and trachea was evident. Biopsies revealed dense peritracheal desmoplastic reaction with focal erosion of cartilage. However, features diagnostic for relapsing polychondritis, desmoid tumor, or orbital pseudotumor were absent. The disease progressed to involve severe stenosis and thickening of the trachea and main …