Digital Commons Network^™

The Line Between Addiction And Medication: Alcohol, Anesthesia, And Analgesia, Priya Joshi, B.S., Emanual Rubin, Md

Department of Pathology Honors Program Student Research Symposium

Alcohol is a particularly dangerous addiction because its consumption is legal even in excess, despite its harmful effects. Because alcohol has a multitude of targets in the central nervous system that are modified during chronic exposure, medications with overlapping targets such as anesthetics and analgesics must be modified when given to alcoholics. Unfortunately, as relatively little is known about the mechanism of addiction, it is difficult to predict how medications will be affected by central adaptation to chronic alcohol exposure. This review summarizes the consequences of alcohol exposure with particular attention to the GABA_Areceptor, and discusses the reasons …

Effects Of Clostridium Difficile On The Human Immune Response, Mike Mcgovern

Honors Projects in Science and Technology

Clostridium difficile is a bacterium that is rapidly becoming a large issue in the medical community due to its tendency to infect hospital patients and its resistance to antibiotics. By studying the way in which the pathogen interacts with the human immune system, it is possible to better understand how the body naturally fights off the disease. This knowledge can allow medical professionals to develop treatments that can help curtail the infection before serious symptoms occur. Working under a grant program alongside Professors Kirsten Hokeness and Chris Reid, I was able to research the effects that exposure to the C. …

Transfusion Related Acute Lung Injury, Nadia Abidi, Jay Herman, Md, Julie Karp, Md

Department of Pathology Honors Program Student Research Symposium

A 74 year old woman presented with hematemesis. Her medical history was significant for pulmonary embolism treated with warfarin anticoagulation, fibromyalgia treated with NSAIDs/steroids, and a prior bleeding event from a gastric ulcer. On admission she was stable with a hemoglobin of 8.7 g/dL and a therapeutic INR of 3.19. A type and screen determined a blood type of AB positive. In anticipation of endoscopy, the patient received one unit of red blood cells and four units of type AB plasma. Following transfusion, her INR was 1.83. The patient received an additional four units of type AB plasma to further …

Morphologic And Endoscopic Evaluation Of Collagenous Gastritis, Annie Ashok, Ashlie L. Burkart, Md, Cm

Department of Pathology Honors Program Student Research Symposium

Collagenous gastritis (CG) is a rare gastrointestinal condition of unknown etiology and pathogenesis characterized by the presence of a gastric subepithelial collagen band of variable thickness. While little is known about the disease, children and young adults often present with anemia, abdominal pain, and nodular gastric mucosa on endoscopy. In contrast, adults often present with chronic watery diarrhea and normal gastric mucosa on endoscopy. Disease associations (usually in adult cases) include celiac disease, collagenous colitis, collagenous sprue, and lymphocytic colitis. This study aims to further characterize the clinical, endoscopic and morphologic spectrum of CG.

Lumbar Chordoma: A Primary Bone Tumor, Andrew N. Fleischman, Bs, Brian O'Hara, Md

Department of Pathology Honors Program Student Research Symposium

INTRODUCTION

• Primary malignant bone tumor of embryonic notochord remnants
• 1-4% of primary bone tumors, <0.1 per 100,000
• Location: Sacral (50%), Skull base (35%), Vertebral column (15%)
• Classic, chondroid (5-15%), and dedifferentiated (5%) variants
• Most commonly in late middle age (50s to 60s)
• Low-grade, slow growing tumor
• But locally aggressive, high rate of local recurrence (20% in 1^st year)
• Local recurrence is most important predictor of mortality
• Metastasis only occurs very late in disease
• Median survival of about 6 years, less than 12 months with mets
• 5 year survival of 70%, 10 year survival of 40%
• Primary therapy- aggressive surgical resection (if possible) …

An Unexpected Immunohistochemical Profile In An Ovarian Lesion, Kate Fritton, Joanna Chan, Md

Department of Pathology Honors Program Student Research Symposium

A 27 year old female presented with pelvic pain and a palpable pelvic mass. Upon histological examination, the cystic mass contained a multi-cellular lining with nuclear grooves. Negative inhibin staining ruled out a follicular cyst and granulosa cell tumor while pan-cytokeratin positivity suggested an epithelial lesion. The lesion stained positive for thrombomodulin, ultimately suggesting a diagnosis of a Brenner cell tumor, although CD56 positivity in the tumor questions the known immunohistochemical profile of Brenner cell tumors. This unusual result opens the door to future research into the role CD56 in the diagnosis of ovarian neoplasms.

Myeloid Sarcoma: Extramedullary Relapse After Allogeneic Bone Marrow Transplant For Chronic Myelogenous Leukemia, Maria Gubbiotti, Alina Dulau Florea, Md, Renu Bajaj, Phd

Department of Pathology Honors Program Student Research Symposium

Myeloid sarcoma (MS) is an extramedullary tumor of myeloid precursor cells, which can precede or occur concomitantly with acute myeloid leukemia, myelodysplastic syndrome, or myeloproliferative neoplasms. Although MS can involve any organ, it is more common in the central nervous system (CNS) and gonads, sites known as “pharmacologic sanctuaries” where leukemic cells can survive despite systemic chemotherapy. Less often, this tumor can be the manner of relapse after allogeneic bone marrow transplantation.

The diagnosis is based on morphology and immunophenotype by either flow cytometry or immunohistochemistry of paraffin-embedded tissue, and confirmed by FISH or molecular studies. Myeloid sarcomas usually express …

A Case Of Hemoglobinopathy-Thalassemia Syndrome, Michele C. Khurana, B.S., Gene Gulati, Ph.D

Department of Pathology Honors Program Student Research Symposium

Patient Presentation

• 43 year-old African American female presents with left lower extremity pain
• Physical exam: unremarkable
• Past medical history:

Anemic since childhood

Avascular necrosis of left hip

DVT

Chronic illnesses: asthma, depression

Surgical history: appendectomy, tubal ligation, splenectomy, cholecystectomy, L hip replacement

• Family history: mother has lupus

Thoracic Dissecting Aneurysm And The Importance Of Genetics, Dan Kramer, Ba, Anthony Prestipino, M.D.

Department of Pathology Honors Program Student Research Symposium

Patient Presentation

• 28 year old white male with a past medical history significant for untreated hypertension
• Presents with 3 day history of chest discomfort, lower extremity weakness, bowel and bladder dysfunction, near-syncopal episodes
• Absent pulse in right femoral artery, weak pulse in left femoral artery
• Echosonography showed acute Type A dissecting aortic aneurysm
• Treatment

Immediately taken to surgery for repair of aorta with a graft and replacement of the aortic valve

• Outcome

Unstable after surgery

Biventricular heart failure

Persistent bleeding into mediastinum due to DIC

Required massive transfusion of RBCs, FFP, Cryoprecipitate, and Platelets

Became anuric and acidotic

Became fluid …

Adenoid Cystic Carcinoma In Unusual Locations – Differential Diagnosis Difficulties, Heather A. Mcmahon, B.S., Madalina Tuluc, Md

Department of Pathology Honors Program Student Research Symposium

Adenoid Cystic Carcinoma (ACC) is an uncommon malignant salivary gland tumor, representing 1% of all malignant tumors of the oral and maxillofacial region and 22% of all salivary gland malignancies. Although in the majority of cases ACC manifests in the major salivary glands, in rare instances it can be found in locations such as the esophagus, larynx, trachea, lacrimal gland, breast, prostate, lungs, or auditory canal. These unusual locations of ACC often pose a diagnostic challenge to the clinician and are associated with poorer outcomes for patients as compared to those ACC of a more typical presentation. In this study …

Correlations Between Gene Amplification And Protein Expression Of Topoisomerase 2a (Top2a) In Squamous Cell Carcinoma Of The Lung, Anita Modi, Msii, Charalambos C. Solomides, Md

Department of Pathology Honors Program Student Research Symposium

Background: While DNA topoisomerase 2A (TOP2A) plays an essential role in maintaining the structural integrity of the double helix during replication and recombination, excessive expression of this enzyme may promote malignant cell transformations. In fact, increased levels of TOP2A have been observed in various cancer cell lines including squamous cell carcinoma of the lung. This study sought to identify correlations between genotypic and phenotypic evidence of TOP2A obtained via in situ hybridization (ISH) and immunohistochemistry (IHC) techniques.

Methods Tissue microarrays created from 29 samples of Stage I Squamous Cell Carcinoma of the lung were stained with VENTANA BenchMark ULTRA platform …

Temporal Lobe Ganglioglioma In An Epilepsy Patient With Worsening Seizures: Case Study And Future Directions, Adam M. Olszewski, Mark Curtis, Md Phd.

Department of Pathology Honors Program Student Research Symposium

Gangliogliomas are rare brain tumors that have both neuronal and glial components. They hold a better prognosis than other infiltrative glial tumors, but differentiating between them can be challenging. While molecular markers are being studied, it is currently a histologic diagnosis.

In this case, the patient presented with epilepsy and worsening seizures secondary to a medial temporal lobe mass. Radiology report was inconclusive. Surgical resection was achieved and based on histologic examination the lesion was diagnosed as ganglioglioma, WHO grade I.

In this patient, pathological diagnosis of ganglioglioma offers a favorable prognosis and low risk of recurrence. In the future, …

Diagnostic Yield Of Endobronchial Ultrasound-Guided Fine Needle Aspiration (Ebus-Fna) In Lung Cancer Staging, Subtyping And Diagnosis Of Unexplained Mediastinal Lymphadenopathy, Rino Sato, Rossitza Draganova-Tacheva, Md

Department of Pathology Honors Program Student Research Symposium

INTRODUCTION

• Lung cancer (LC) is the most commonly diagnosed cancer worldwide and the most frequent cause of cancer death in both men and women in the US (more deaths than the next three most common cancers combined)¹
• Clinical staging of LC is an integral part of patient care because it directs therapy and has prognostic value

Patients are routinely investigated with a conventional workup (medical history, PE, lab tests, bronchoscopy), CT and integrated whole-body PET-CT, followed by mediastinal tissue staging for enlarged or PET-positive intrathoracic nodes²

• Mediastinal tissue staging has been classically performed by mediastinoscopy, but they can …

Melanocytoma Of The Cerebellopontine Angle, Pranay Soni, M.D, Lawrence C. Kenyon, Md, Phd

Department of Pathology Honors Program Student Research Symposium

Ms. M.G. is a 46-year-old woman with a history of hypertension and prior bilateral laser eye surgery. In 2009, she presented with vertigo, tinnitus, and decreased hearing in the left ear. An MRI scan revealed an enhancing mass in the posterior fossa that was thought to be an acoustic neuroma. In May of 2009, she underwent gamma-knife radiotherapy for the 2.7 cm mass.

In September of 2012, M.G. noted progressive change in her voice quality as well as a swallowing disturbance and left facial spasms. A subsequent MRI showed significant enlargement of the tumor to a maximal size of 3.7 …

Diffuse Idiopathic Pulmonary Neuroendocrine Cell Hyperplasia (Dipnech) To Carcinoid: Exploring The Link, Jacob D. Mcfadden Msii, Jeffrey P. Baliff Md

Department of Pathology Honors Program Student Research Symposium

Neuroendocrine cells (NECs) play important roles in normal lung development, autonomic regulation of lung function, and response to hypoxia or injury. They are located between the respiratory epithelium and the basement membrane of bronchi and bronchioles (below), often as single cells or small clusters.

NEC proliferation is a common pathologic occurrence, well established as a reactive response to chronic lung injury. Much less commonly, NEC proliferation is observed in the absence of apparent inciting factors. This neoplastic phenomenon is termed “diffuse idiopathic pulmonary neuroendocrine cell hyperplasia” (DIPNECH).

DIPNECH is recognized as a precursor lesion for carcinoid tumors. While the progression …

Ocular Manifestations Of Rosai-Dorfman Disease, Phoebe L. Mellen, B.S., Ralph C. Eagle Jr., M.D.

Department of Pathology Honors Program Student Research Symposium

History of Rosai-Dorfman Disease

In 1969, Dr. Juan Rosai and Dr. Ronald F. Dorfman reported four cases of an entity that previously had puzzled pathologists and clinicians. The four cases had failed to fit under any diagnosis, but shared a few common characteristics. Each patient presented with painless, massive lymphadenopathy, most commonly of the cervical lymph nodes¹. Other locations included the inguinal, intra-parotid, and axillary lymph nodes. The patients all presented with fever and leukocytosis¹. The differential diagnosis included malignant lymphoma, malignant histiocytosis, reticuloendotheliosis, and chronic inflammation. However, the histopathological characteristics of the cases did not …

Cavin1; A Regulator Of Lung Function And Macrophage Phenotype., Praveen Govender, Freddy Romero, Dilip Shah, Jesus Paez, Shi-Ying Ding, Libin Liu, Adam Gower, Elizabeth Baez, Sherif Shawky Aly, Paul Pilch, Ross Summer

Center for Translational Medicine Faculty Papers

Caveolae are cell membrane invaginations that are highly abundant in adipose tissue, endothelial cells and the lung. The formation of caveolae is dependent on the expression of various structural proteins that serve as scaffolding for these membrane invaginations. Cavin1 is a newly identified structural protein whose deficiency in mice leads to loss of caveolae formation and to development of a lipodystrophic phenotype. In this study, we sought to investigate the functional role of Cavin1 in the lung. Cavin1 deficient mice possessed dramatically altered distal lung morphology and exhibited significant physiological alterations, notably, increased lung elastance. The changes in distal lung …

Pharmacology And Clinical Potential Of Guanylyl Cyclase C Agonists In The Treatment Of Ulcerative Colitis., Giovanni M Pitari

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Agonists of the transmembrane intestinal receptor guanylyl cyclase C (GCC) have recently attracted interest as promising human therapeutics. Peptide ligands that can specifically induce GCC signaling in the intestine include endogenous hormones guanylin and uroguanylin, diarrheagenic bacterial enterotoxins (ST), and synthetic drugs linaclotide, plecanatide, and SP-333. These agonists bind to GCC at intestinal epithelial surfaces and activate the receptor's intracellular catalytic domain, an event initiating discrete biological responses upon conversion of guanosine-5'-triphosphate to cyclic guanosine monophosphate. A principal action of GCC agonists in the colon is the promotion of mucosal homeostasis and its dependent barrier function. Herein, GCC agonists are …

A Study Of Small Rnas From Cerebral Neocortex Of Pathology-Verified Alzheimer's Disease, Dementia With Lewy Bodies, Hippocampal Sclerosis, Frontotemporal Lobar Dementia, And Non-Demented Human Controls, Sébastien S. Hébert, Wang-Xia Wang, Qi Zhu, Peter T. Nelson

Sanders-Brown Center on Aging Faculty Publications

MicroRNAs (miRNAs) are small (20-22 nucleotides) regulatory non-coding RNAs that strongly influence gene expression. Most prior studies addressing the role of miRNAs in neurodegenerative diseases (NDs) have focused on individual diseases such as Alzheimer's disease (AD), making disease-to-disease comparisons impossible. Using RNA deep sequencing, we sought to analyze in detail the small RNAs (including miRNAs) in the temporal neocortex gray matter from non-demented controls (n = 2), AD (n = 5), dementia with Lewy bodies (n = 4), hippocampal sclerosis of aging (n = 4), and frontotemporal lobar dementia (FTLD) (n = 5) cases, together accounting for the most prevalent …

Holobiont Nutrition: Considering The Role Of The Gastrointestinal Microbiota In The Health Benefits Of Whole Grains, Jens Walter, Ines Martinez, Devin J. Rose

Food for Health: Publications

Intake of whole grains and other food products high in dietary fiber have long been linked to the prevention of chronic diseases associated with inflammation. A contribution of the gastrointestinal microbiota to these effects has been suggested, but little is known on how whole grains interact with gut bacteria. We have recently published the first human trial that made use of next-generation sequencing to determine the effect of whole grains (whole grain barley, brown rice or a mixture of the two) on fecal microbiota structure and tested for associations between the gut microbiota and blood markers of inflammation, glucose and …

Alcohol And The Heart: To Abstain Or Not To Abstain?, Rajesh Movva, Md, Mrcp, Vincent M. Figueredo, M.D.

Division of Cardiology Faculty Papers

Alcohol has been consumed by most societies over the last 7000 years. Abraham Lincoln said "It has long been recognized that the problems with alcohol relate not to the use of a bad thing, but to the abuse of a good thing." Light to moderate alcohol consumption reduces the incidence of coronary heart disease (CHD), ischemic stroke, peripheral arterial disease, CHD mortality, and all-cause mortality, especially in the western populations. However, heavy alcohol consumption is detrimental causing cardiomyopathy, cardiac arrhythmias, hepatic cirrhosis, pancreatitis, and hemorrhagic stroke. In this article, we review the effects of alcohol on CHD, individual cardiovascular risk …

Smooth Muscle Fascicular Reorientation Is Required For Esophageal Morphogenesis And Dependent On Cdo., Anthony I Romer, Jagmohan Singh, Satish Rattan, Robert S Krauss

Department of Medicine Faculty Papers

Postnatal maturation of esophageal musculature involves proximal-to-distal replacement of smooth muscle with skeletal muscle by elusive mechanisms. We report that this process is impaired in mice lacking the cell surface receptor Cdo and identify the underlying developmental mechanism. A myogenic transition zone containing proliferative skeletal muscle precursor cells migrated in a proximal-distal direction, leaving differentiated myofibers in its wake. Distal to the transition zone, smooth muscle fascicles underwent a morphogenetic process whereby they changed their orientation relative to each other and to the lumen. Consequently, a path was cleared for the transition zone, and smooth muscle ultimately occupied only the …

Comparison Study Of Airway Reactivity Outcomes Due To A Pharmacologic Challenge Test: Impulse Oscillometry Versus Least Mean Squared Analysis Techniques., Elena Rodriguez, Charrell M Bullard, Milena H Armani, Thomas L Miller, Thomas H Shaffer

Department of Medicine Faculty Papers

The technique of measuring transpulmonary pressure and respiratory airflow with manometry and pneumotachography using the least mean squared analysis (LMS) has been used broadly in both preclinical and clinical settings for the evaluation of neonatal respiratory function during tidal volume breathing for lung tissue and airway frictional mechanical properties measurements. Whereas the technique of measuring respiratory function using the impulse oscillation technique (IOS) involves the assessment of the relationship between pressure and flow using an impulse signal with a range of frequencies, requires less cooperation and provides more information on total respiratory system resistance (chest wall, lung tissue, and airways). …

Caveolar Fatty Acids And Acylation Of Caveolin-1, Qian Cai, Ling Guo, Haiqing Gao, Xiang-An Li

Pediatrics Faculty Publications

PURPOSE: Caveolae are cholesterol and sphingolipids rich subcellular domains on plasma membrane. Caveolae contain a variety of signaling proteins which provide platforms for signaling transduction. In addition to enriched with cholesterol and sphingolipids, caveolae also contain a variety of fatty acids. It has been well-established that acylation of protein plays a pivotal role in subcellular location including targeting to caveolae. However, the fatty acid compositions of caveolae and the type of acylation of caveolar proteins remain largely unknown. In this study, we investigated the fatty acids in caveolae and caveolin-1 bound fatty acids.

METHODS: Caveolae were isolated from Chinese hamster …

Bortezomib (Ps-341) Treatment Decreases Inflammation And Partially Rescues The Expression Of The Dystrophin-Glycoprotein Complex In Grmd Dogs., Karla P C Araujo, Gloria Bonuccelli, Caio N Duarte, Thais P Gaiad, Dayson F Moreira, David Feder, José E Belizario, Maria A Miglino, Michael P Lisanti, Carlos E Ambrosio

Department of Stem Cell Biology and Regenerative Medicine Faculty Papers & Presentations

Golden retriever muscular dystrophy (GRMD) is a genetic myopathy corresponding to Duchenne muscular dystrophy (DMD) in humans. Muscle atrophy is known to be associated with degradation of the dystrophin-glycoprotein complex (DGC) via the ubiquitin-proteasome pathway. In the present study, we investigated the effect of bortezomib treatment on the muscle fibers of GRMD dogs. Five GRMD dogs were examined; two were treated (TD- Treated dogs) with the proteasome inhibitor bortezomib, and three were control dogs (CD). Dogs were treated with bortezomib using the same treatment regimen used for multiple myeloma. Pharmacodynamics were evaluated by measuring the inhibition of 20S proteasome activity …

Early Prediction Of Trauma Patient Discharge Disposition, Ronald Beaulieu, Priti Parikh, Akpofure Peter Ekeh, Ronald J. Markert, Mary C. Mccarthy

Department of Surgery Faculty Publications

Objective: Do pre-injury and early hospital admission characteristics help predict patient discharge disposition? Background: Total one-year treatment cost of adult major trauma in the United States is estimated at $30 billion annually, with 58% of the cost due to the index hospitalization. Increased length of stay (LOS) increases morbidity and delays rehabilitation. Prediction of discharge to a location other than home through univariate risk factor methodology and development of a multivariable binary logistic regression model allows early discharge planning. Methods: A one-year Level 1 trauma center registry dataset was used to develop a predictive model of discharge disposition using 2836 …

The Effect Of Network Transitions On Spontaneous Activity And Sycnhrony In Devloping Neural Networks, Jude P. J. Savarraj

Doctoral Dissertations

Connectivity patterns of developing neural circuits and the effects of its dynamics on network behavior, particularly the emergence of spontaneous activity and synchrony, are not clear. We attempt to quantify anatomical connectivity patterns of rat cortical cultures during different stages of development. By culturing the networks on dishes embedded with micro electrode arrays, we simultaneously record electrical activity from multiple regions of the developing network and monitor its electrical behavior, particularly its tendency to fire spontaneously and to synchronize under certain conditions. We investigate possible correlations between changes in the network connectivity patterns and spontaneous electrical activity and synchrony. Cocultures …

Single Stage Oncologic Resection And Reconstruction: A Step Toward Development Of Sarcoma Service In Resource Constrained Country, Haroon Ur Rashid, Kashif Abbas, Masood Umer

Section of Orthopaedic Surgery

Tumor free-margin surgical resection remains the single most important treatment in the curative therapy of musculoskeletal tumor of limbs. Refinements in surgical techniques have led to increased function preservation and limb salvage.
Patients and Methods: The records of patients (n = 24) who underwent microsurgical soft tissue reconstruction subsequent to resection of limb tumour during the period 2006 to 2011 were reviewed. Primary outcome i.e. uptake of the flap was evaluated. Perioperative morbidities were also noted including donor as well as recipient site complications. Assessment of Functional outcome (Musculoskeletal Tumor Society score, MSTS) local recurrence, free survival, and disease-specific …

The Tweak Receptor Fn14 Is A Therapeutic Target In Melanoma: Immunotoxins Targeting Fn14 Receptor For Malignant Melanoma Treatment., Hong Zhou, Suhendan Ekmekcioglu, John W Marks, Khalid A Mohamedali, Kaushal Asrani, Keeley K Phillips, Sharron A N Brown, Emily Cheng, Michele B Weiss, Walter N Hittelman, Nhan L Tran, Hideo Yagita, Jeffrey A Winkles, Michael G Rosenblum

Department of Cancer Biology Faculty Papers

Fibroblast growth factor-inducible protein 14 (Fn14), the cell surface receptor for tumor necrosis factor-like weak inducer of apoptosis (TWEAK), is overexpressed in various human solid tumor types and can be a negative prognostic indicator. We detected Fn14 expression in ∼60% of the melanoma cell lines we tested, including both B-Raf WT and B-Raf(V600E) lines. Tumor tissue microarray analysis indicated that Fn14 expression was low in normal skin, but elevated in 173/190 (92%) of primary melanoma specimens and in 86/150 (58%) of melanoma metastases tested. We generated both a chemical conjugate composed of the recombinant gelonin (rGel) toxin and the anti-Fn14 …

Performance And Measurement Of A Community-Based Distribution Model Of Family Planning Services In Pakistan, Syed Khurram Azmat, Shirin Ahmed, Waqas Hameed, Mohsina Bilgrami, Ayesha Khan, Adnan Ahmad Khan, Ghulam Mustafa

Community Health Sciences

Introduction: Community-based distribution (CBD) has been successfully applied to family planning (FP) services worldwide. It forms the basis for the large lady health worker (LHW) programme in Pakistan which serves a limited number of women with contraception services. Thus, the concept has seen limited application in Pakistan. We present the outcomes of a CBD model that was implemented in 49 districts across Pakistan by a non-government organization (NGO).
Methods: The Marie Stopes Society (MSS) developed a CBD model around its fixed centres and reached around half a million married women of reproductive age (MWRA) with services. The services provided included …