Medical Specialties Commons^™

Darkening And Eruptive Nevi During Treatment With Erlotinib, Stephen Hemperly Do, Tanya Ermolovich Do, Nektarios I. Lountzis Md, Hina A. Sheikh Md, Stephen M. Purcell Do

Department of Medicine

No abstract provided.

Clinical Outcome And Cost Effectiveness Of Early Tracheostomy In Isolated Severe Head Injury Patients, Usman Tariq Siddiqui, Muhammad Zubair Tahir, Muhammad Shahzad Shamim, S. Ather Enam

Section of Neurosurgery

Background: Early tracheostomy (ET) has been shown to be effective in reducing complications associated with prolong mechanical ventilation. The study was carried out to evaluate the role of ET in reducing the duration of mechanical ventilation, duration of intensive care unit (ICU) stay, ICU-related morbidities, and its overall effect on outcome, in patients with isolated severe traumatic brain injury (TBI).
Methods: This 7-year review included 100 ICU patients with isolated severe TBI requiring mechanical ventilation. ET was defined as tracheostomy within 7 days of TBI, and prolonged endotracheal intubation (EI) as EI exceeding 7 days of TBI. Of 100 patients, …

Yoga For Burn Survivors: Impact On Range Of Motion, Cardiovascular Function And Quality Of Life, Christina Miller Pt, Dpt, Sandra M. Tremblay Pt, Ms, Cws, Mscs, Elizabeth Dideon-Hess Lsw, Sigrid A. Blome-Eberwein Md

Department of Surgery

No abstract provided.

Improving Patient Satisfaction After Primary Total Knee Arthroplasty Using Nurse Practitioner-Driven Preoperative Education, Jennifer A. White

Doctor of Nursing Practice Scholarly Projects

Total joint arthroplasty is an undisputed option for relieving pain and improving the function of an arthritic joint. The number of patients undergoing total knee arthroplasty (TKA) annually is expected to increase by 600% in the next two decades (Lau, Gandhi, Mahomed, & Mahomed, 2012).

Current research shows that while 81-89% of patients who have had a TKA are satisfied postoperatively, there is room to improve patient satisfaction by providing further education preoperatively. While research cannot agree on a single, specific variable that influences patient dissatisfaction, a review of the literature shows that patients repeatedly note their “unmet expectations” as …

Closed Head Injury In An Age-Related Alzheimer Mouse Model Leads To An Altered Neuroinflammatory Response And Persistent Cognitive Impairment, Scott J. Webster, Linda J. Van Eldik, D. Martin Watterson, Adam D. Bachstetter

Sanders-Brown Center on Aging Faculty Publications

Epidemiological studies have associated increased risk of Alzheimer's disease (AD)-related clinical symptoms with a medical history of head injury. Currently, little is known about pathophysiology mechanisms linked to this association. Persistent neuroinflammation is one outcome observed in patients after a single head injury. Neuroinflammation is also present early in relevant brain regions during AD pathology progression. In addition, previous mechanistic studies in animal models link neuroinflammation as a contributor to neuropathology and cognitive impairment in traumatic brain injury (TBI) or AD-related models. Therefore, we explored the potential interplay of neuroinflammatory responses in TBI and AD by analysis of the temporal …

Role Of Il-16 In Cd4(+) T Cell-Mediated Regulation Of Relapsing Multiple Sclerosis, Dusanka S. Skundric, William W. Cruikshank, Jelena Drulovic

Neurology Faculty Publications

In an important article published in Nature Medicine, Liu and colleagues described a novel CD4⁺ FoxA1⁺ regulatory T (Treg) cell population as distinct regulators of relapsing-remitting multiple sclerosis (RRMS) and experimental autoimmune encephalomyelitis (EAE). CD4⁺ FoxA1⁺ Treg cells appear as key regulators of responsiveness to therapy with interferon beta (IFN-β) in RRMS patients. Data indicate that CD4⁺ FoxA1⁺ FOXP3⁻ Treg cells develop within the central nervous system (CNS), and a potential of cerebellar granule neurons (CGN) in generation of CD4⁺ FoxA1⁺ PD-L1^hiFOXP3⁻ Treg cells from encephalitogenic CD4^{+ …}

The Effects Of Adderall On Maternal And Fetal Health, Alyson Brady

Honors Theses

Information available for woman prescribed Adderall to treat ADHD and the effects that it may have on her fetus is limited. However, Adderall and methamphetamine have similar pharmacological and addictive qualities. This paper is concerned with whether there is an adequate approach to treatment that balances the needs of the mother and the fetus. With Adderall use becoming more prevalent, it is essential that society is aware of the physiology and pharmacology of this drug, as well as, the need for more research on this subject to be produced.

Diagnosis And Management Of Hyponatremia In Patients With Aneurysmal Subarachnoid Hemorrhage, Neena I. Marupudi, Sandeep Mittal

Neurosurgery Faculty Publications

Hyponatremia is the most common, clinically-significant electrolyte abnormality seen in patients with aneurysmal subarachnoid hemorrhage. Controversy continues to exist regarding both the cause and treatment of hyponatremia in this patient population. Lack of timely diagnosis and/or providing inadequate or inappropriate treatment can increase the risk of morbidity and mortality. We review recent literature on hyponatremia in subarachnoid hemorrhage and present currently recommended protocols for diagnosis and management.

Diabetes Self-Management Education For Adolescent Patients: The Importance Of A Developmentally Sensitive Approach, Laura Mumme

Senior Honors Theses

The attention of healthcare providers to the developmental level of adolescent patients with type one diabetes (T1D) maximizes effective patient education and glycemic control. Due to the dynamic changes that occur in the mind and body during adolescence, self-care for adolescent T1D patients is overwhelming as it envelopes activities of everyday life. The disease process and the unique aspects of adolescence in relation to T1D are important for caregivers to consider. Developmentally appropriate teaching during the initial onset of the disease must inform the patient and the patient’s family of the basics of the disease process and the daily care …

Lymphedema In A Hypertrophic Scar: Treatment With Fractional Co2 Laser, Sigrid A. Blome-Eberwein Md

Department of Surgery

No abstract provided.

Elevated Serum Bicarbonate Concentration In Chronic Kidney Disease: A Call To Find The Cause, Zeid J. Khitan

Internal Medicine

In this issue, Dobre et al1 reported an observational study looking at results of annually measured serum bicarbonate concentration in participants with chronic kidney disease (CKD) enrolled in the Chronic Renal Insufficiency Cohort (CRIC) using the marginal structural model, a validated statistical method,2 to estimate the cumulative effect over the period of the study and their effects on adjudicated heart failure events, atherosclerotic events, renal disease progression, and mortality. In their analysis, they included patients aged 21 to 74 years with estimated glomerular filtration rate of 20 to 70 mL/min per 1.73 m2 and excluded patients with NYHA Class III/IV …

Kinase-Independent Role Of Cyclin D1 In Chromosomal Instability And Mammary Tumorigenesis., Mathew C Casimiro, Gabriele Disante, Marco Crosariol, Emanuele Loro, William Dampier, Adam Ertel, Zuoren Yu, Elizabeth A Saria, Alexandros Papanikolaou, Z Li, Chenguang Wang, Sankar Addya, Michael P. Lisanti, Paolo Fortina, Robert D Cardiff, Aydin Tozeren, Erik S Knudsen, Andrew Arnold, Richard Pestell

Department of Cancer Biology Faculty Papers

Cyclin D1 is an important molecular driver of human breast cancer but better understanding of its oncogenic mechanisms is needed, especially to enhance efforts in targeted therapeutics. Currently, pharmaceutical initiatives to inhibit cyclin D1 are focused on the catalytic component since the transforming capacity is thought to reside in the cyclin D1/CDK activity. We initiated the following study to directly test the oncogenic potential of catalytically inactive cyclin D1 in an in vivo mouse model that is relevant to breast cancer. Herein, transduction of cyclin D1-/- mouse embryonic fibroblasts (MEFs) with the kinase dead KE mutant of cyclin D1 led …

Translation Initiation Complex Eif4f Is A Therapeutic Target For Dual Mtor Kinase Inhibitors In Non-Hodgkin Lymphoma., Christos Demosthenous, Jing Jing Han, Mary J Stenson, Matthew J Maurer, Linda E Wellik, Brian Link, Kristen Hege, Ahmet Dogan, Eduardo Sotomayor, Thomas Witzig, Mamta Gupta

Medicine Faculty Publications

Deregulated mRNA translation has been implicated in disease development and in part is controlled by a eukaryotic initiation complex eIF4F (composed of eIF4E, eIF4G and eIF4A). We demonstrate here that the cap bound fraction from lymphoma cells was enriched with eIF4G and eIF4E indicating that lymphoma cells exist in an activated translational state. Moreover, 77% (110/142) of diffuse large B cell lymphoma tumors expressed eIF4E and this was associated with an inferior event free survival. Over-expression of wild-type eIF4E (eIF4E(WT)) but not cap-mutant eIF4E (eIF4E(cap mutant)) increased the activation of the eIF4F complex. Treatment with the active-site dual mTOR inhibitor …

When Operating On Dead People Saves Lives: Benefits Of Surgical Organ Donor Intensivists, Kristin Long, Cynthia Talley, Rebecca B. Yarrison, Andrew Bernard

Surgery Faculty Publications

Solid organ transplantation has emerged as a life-saving treatment for many patients suffering from end-stage organ failure. Organs have been successfully recovered after a variety of aggressive interventions. We propose that decompressive laparotomy, when clinically indicated, should be considered in the aggressive resuscitation of potential organ donors. A thorough literature review examining aggressive interventions on potential organ donors was conducted after experience with a unique case at this institution. Articles were reviewed for the types of interventions performed as well as the time frame in relation to organ donation. In our case, several ethical issues were raised when considering decompressive …

Implementation Of An Advance Directive Protocol In A Primary Care Setting, Gloria Dillman

Evidence-Based Practice Project Reports

Despite the passage of the Patient Self-Determination Act in 1992, only 15% of the United States population has completed an advance directive (AD). This statistic will be exaggerated with the future growth of older adults in the year 2030, at which time this portion of the population is expected to double to 72.1 million people. Without an AD, patients lose their autonomy and may be subjected to costly, life prolonging treatments that they would never choose for themselves. The unnecessary costs and unwanted treatment are preventable with an AD, and primary care providers are in a prime position to initiate …

Phylogenetic Tree Construction And “Truncal Loss” Analysis Reveal Hidden Associations Between Loss Of Protein Expression In Swi/Snf Complex Components And Tumor Stage And Survival In Clear Cell Renal Cell Carcinoma (Ccrcc), Wei Jiang, Md, Phd, Essel Dulaimi, Karthik Devarajan, Qiong Wang, Raymond O'Neill, Charalambos C. Solomides, Md, Stephen C Peiper, Phd, Robert Uzzo, Joseph R. Testa, Haifeng Yang, Phd

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Background

Polybromo-1 (PBRM1), a targeting subunit of the SWI/SNF chromatin remodeling complex, is mutated at a rate of ~40% in clear cell Renal Cell Carcinoma (ccRCC), second only to VHL. Whether its mutation is correlated with tumor stage is controversial. As other components of the SWI/SNF complex were also reported to be mutated in ccRCC, we aim to examine the protein expression patterns of PBRM1, ARID1A, BRG1, and BRM in ccRCC, and to investigate possible association between their loss of expression and tumor stage, as well as survival. We also included a histone modifier, SETD2, which is recently discovered to …

Assessment For Risk Factors Associated With Local Recurrence In Chordoma, John A. Abraham, Md, Wei Jiang, Md, Phd

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Background

Chordoma is a rare but locally aggressive malignant neoplasm showing notochordal differentiation. The clinical differential diagnoses can be extensive, and definitive diagnosis often relies on histopathologic evaluation. Histologically, chordoma shows dual epithelial and mesenchymal differentiation, with various morphologies. Despite surgical resection and use of adjuvant radiation therapy, the local recurrence rate of chordoma remains high. We aim to establish factors associated with the increased risk of recurrence and help guide treatment decisions.

Polymorphisms In Genes Of Tricarboxylic Acid Cycle Key Enzymes Are Associated With Early Recurrence Of Hepatocellular Carcinoma., Shaogui Wan, Yousheng Wu, Xingchun Zhou, Yibing Chen, Jiaze An, Xiaohe Yu, Huiqing Zhang, Hushan Yang, Jinliang Xing

Department of Medical Oncology Faculty Papers

Alterations of activity and expression in tricarboxylic acid (TCA) cycle key enzymes have been indicated in several malignancies, including hepatocellular carcinoma (HCC). They play an important role in the progression of cancer. However, the impact of single nucleotide polymorphisms (SNPs) in genes encoding these key enzymes on the recurrence of HCC has not been investigated. In this study, we genotyped 17 SNPs in genes encoding TCA cycle key enzymes and analyzed their association with recurrence-free survival (RFS) in a cohort of 492 Chinese HCC patients by Cox proportional hazard model and survival tree analysis. We identified 7 SNPs in SDHC, …

Crosstalk Between Desmoglein 2 And Patched 1 Accelerates Chemical-Induced Skin Tumorigenesis., Donna M Brennan-Crispi, Claudia Hossain, Joya Sahu, Mary Brady, Natalia A Riobo, M G Mahoney

Department of Biochemistry and Molecular Biology Faculty Papers

Aberrant activation of Hedgehog (Hh) signaling is causative of BCCs and has been associated with a fraction of SCCs. Desmoglein 2 (Dsg2) is an adhesion protein that is upregulated in many cancers and overexpression of Dsg2 in the epidermis renders mice more susceptible to squamous-derived neoplasia. Here we examined a potential crosstalk between Dsg2 and Hh signaling in skin tumorigenesis. Our findings show that Dsg2 modulates Gli1 expression, in vitro and in vivo. Ectopic expression of Dsg2 on Ptc1+/lacZ background enhanced epidermal proliferation and interfollicular activation of the Hh pathway. Furthermore, in response to DMBA/TPA, the Dsg2/Ptc1+/lacZ mice developed squamous …

Routine Surveillance Of Patients With Hypertensive Disorders In Pregnancy, Johanna Quist-Nelson, Md, Lauren Cooper, Md, Abigail Wolf, Md

Department of Obstetrics and Gynecology Presentations and Grand Rounds

BACKGROUND

• Hypertensive disorders in pregnancy carry morbidity and mortality for mothers and infants
• Hypertensive disorders include a full spectrum from gestational hypertension and preeclampsia to eclampsia.
• In 2013 the American College of Obstetricians and Gynecologists released an executive summary with new task force recommendations for closer monitoring of patients with hypertensive disorders including:

Twice weekly blood pressure monitoring

Weekly office visits

Ultrasound surveillance of fetal growth

Weekly laboratory surveillance

Delivery at 37 weeks for patients with gestational hypertension and preeclampsia without severe features

Irreversible Electroporation Of Malignant Lesions: An Institution Experience, Benjamin Bates, Minia Hellan, Shannon Kauffman, James R. Ouellette

Department of Surgery Faculty Publications

Background: Irreversible electroporation (IRE) is a tumor ablation technique where short, high-voltage pulses are applied to tumors to permeabilize the cell membranes. Since no thermal energy is created, it can be used near vital structures. We report our experience in a wide array of anatomic locations and on diverse oncologic processes.

Methods: We performed a retrospective review of all IRE cases performed at our institution from September 2010 to September 2013. Patients were evaluated for peri-operative morbidity, mortality, and oncologic outcome.

Results: Twenty-seven patients underwent IRE during 16 laparotomies and 12 CT guided percutaneous procedures. Anatomic locations: 9 liver, 7 …

Management Of The Hospitalized Transplant Patient., Brian P. Boerner, Vijay Shivaswamy, Whitney Goldner, Jennifer Larsen

Journal Articles: Diabetes, Endocrinology & Metabolism

Significant hyperglycemia is commonly observed immediately after solid organ and bone marrow transplant as well as with subsequent hospitalizations. Surgery and procedures are well known to cause pain and stress leading to secretion of cytokines and other hormones known to aggravate insulin action. Immunosuppression required for transplant and preexisting risk are also major factors. Glucose control improves outcomes for all hospitalized patients, including transplant patients, but is often more challenging to achieve because of frequent and sometimes unpredictable changes in immunosuppression doses, renal function, and nutrition. As a result, risk of hypoglycemia can be greater in this patient group when …

What Did We Learn About Vads In 2014?, Maya Guglin

The VAD Journal

No abstract provided.

Urine Proteomics Identifies Preeclampsia Subphenotypes, Michelle R. Axe

Undergraduate Honors Thesis Projects

Preeclampsia is a perinatal complication of unknown etiology, resulting in 76,000 maternal deaths and 500,000 infant deaths annually₁. The Nationwide Children’s Center for Perinatal Research was the first cohort to propose that preeclampsia is rooted in protein misfolding. We aimed to characterize the misfolded protein components of maternal urine samples and to determine if distinct molecular profiles exist for clinical preeclampsia phenotypes. A total of 86 maternal urine samples from Yale-New Haven Hospital were analyzed for this study, from six clinical preeclampsia subphenotypes- pregnant control (n=10), idiopathic proteinuria (n=15), mild preeclampsia (n=14), superimposed preeclampsia (n=12), typical severe preeclampsia …

Targeting Human Central Nervous System Protein Kinases: An Isoform Selective P38Αmapk Inhibitor That Attenuates Disease Progression In Alzheimer's Disease Mouse Models, Saktimayee M. Roy, Valerie L. Grum-Tokars, James P. Schavocky, Faisal Saeed, Agnieszka Staniszewski, Andrew F. Teich, Ottavio Arancio, Adam D. Bachstetter, Scott J. Webster, Linda J. Van Eldik, George Minasov, Wayne F. Anderson, Jeffrey C. Pelletier, D. Martin Watterson

Spinal Cord and Brain Injury Research Center Faculty Publications

The first kinase inhibitor drug approval in 2001 initiated a remarkable decade of tyrosine kinase inhibitor drugs for oncology indications, but a void exists for serine/threonine protein kinase inhibitor drugs and central nervous system indications. Stress kinases are of special interest in neurological and neuropsychiatric disorders due to their involvement in synaptic dysfunction and complex disease susceptibility. Clinical and preclinical evidence implicates the stress related kinase p38αMAPK as a potential neurotherapeutic target, but isoform selective p38αMAPK inhibitor candidates are lacking and the mixed kinase inhibitor drugs that are promising in peripheral tissue disease indications have limitations for neurologic indications. Therefore, …

Chaperone Hsp47 Drives Malignant Growth And Invasion By Modulating An Ecm Gene Network, Jieqing Zhu, Gaofeng Xiong, Hanjiang Fu, B. Mark Evers, Binhua P. Zhou, Ren Xu

Markey Cancer Center Faculty Publications

The extracellular matrix (ECM) is a determining factor in the tumor microenvironment that restrains or promotes malignant growth. In this report, we show how the molecular chaperone protein Hsp47 functions as a nodal hub in regulating an ECM gene transcription network. A transcription network analysis showed that Hsp47 expression was activated during breast cancer development and progression. Hsp47 silencing reprogrammed human breast cancer cells to form growth-arrested and/or noninvasive structures in 3D cultures, and to limit tumor growth in xenograft assays by reducing deposition of collagen and fibronectin. Coexpression network analysis also showed that levels of microRNA(miR)-29b and -29c were …

Polymeric Nanoparticle-Based Delivery Of Microrna-199a-3p Inhibits Proliferation And Growth Of Osteosarcoma Cells, Linlin Zhang, Arun K. Iyer, Xiaoqian Yang, Eisuke Kobayashi, Yuqi Guo, Henry Mankin, Francis J. Hornicek, Mansoor M. Amiji, Zhenfeng Duan

Pharmaceutical Sciences Faculty Publications

Our prior screening of microRNAs (miRs) identified that miR-199a-3p expression is reduced in osteosarcoma cells, one of the most common types of bone tumor. miR-199a-3p exhibited functions of tumor cell growth inhibition, suggesting the potential application of miR-199a-3p as an anticancer agent. In the study reported here, we designed and developed a lipid-modified dextran-based polymeric nanoparticle platform for encapsulation of miRs, and determined the efficiency and efficacy of delivering miR-199a-3p into osteosarcoma cells. In addition, another potent miR, let-7a, which also displayed tumor suppressive ability, was selected as a candidate miR for evaluation. Fluorescence microscopy studies and real-time polymerase chain …

The Correlation Between Usmle And Comlex Exam Scores For Applicants To A Dually- Approved Emergency Medicine Residency: An Eight-Year Experience, Kathleen E. Kane Md, Dawn M. Yenser Pgme, Laura Semler Ms, Kevin Weaver Do, Gavin Barr Jr. Md, Terrence E. Goyke Do, Andre Burckhart Do, Adam Leonetti Do, Isamu Yoshioka, Bryan Kane Md

Department of Emergency Medicine

No abstract provided.

Attenuation Of Traumatic Brain Injury-Induced Cognitive Impairment In Mice By Targeting Increased Cytokine Levels With A Small Molecule Experimental Therapeutic, Adam D. Bachstetter, Scott J. Webster, Danielle S. Goulding, Jonathan E. Morton, D. Martin Watterson, Linda J. Van Eldik

Sanders-Brown Center on Aging Faculty Publications

BACKGROUND: Evidence from clinical studies and preclinical animal models suggests that proinflammatory cytokine overproduction is a potential driving force for pathology progression in traumatic brain injury (TBI). This raises the possibility that selective targeting of the overactive cytokine response, a component of the neuroinflammation that contributes to neuronal dysfunction, may be a useful therapeutic approach. MW151 is a CNS-penetrant, small molecule experimental therapeutic that selectively restores injury- or disease-induced overproduction of proinflammatory cytokines towards homeostasis. We previously reported that MW151 administered post-injury (p.i.) is efficacious in a closed head injury (CHI) model of diffuse TBI in mice. Here we test …

Surgical Outcomes Of Sequential Versus Concomitant Glaucoma Drainage Implant And Boston Keratoprosthesis Type 1, Varum Patel, Marlene R. Moster, Louis J. Kishfy, Julian Barkan, Tingting Zhan, Irving M. Raber, Brandon D. Ayers, Michael J. Pro, Michael Waisbourd

Wills Eye Hospital Papers

BACKGROUND

The Boston Keratoprosthesis Type 1 (KPro) is a surgical device used in patients who have failed traditional corneal transplant treatment or are poor candidates for it.¹ Candidates for KPro often have advanced anterior segment disease that predisposes them to developing glaucoma.² As a result, these patients may require both a KPro, to treat their corneal pathology, and a glaucoma drainage implant (GDI), to treat their glaucoma. To date, there have been no long-term studies comparing the order of GDI placement with KPro surgery and how it affects surgical outcomes.