Medical Specialties Commons^™

Oncogenes And Inflammation Rewire Host Energy Metabolism In The Tumor Microenvironment: Ras And Nfκb Target Stromal Mct4., Ubaldo E. Martinez-Outshoorn, Md, Joseph Curry, Md, Ying-Hui Ko, Md, Zhao Lin, Md, Madalina Tuluc, Md, David Cognetti, Md, Ruth Birbe, Md, Edmund A. Pribitkin, Md, Alessandro Bombonati, Richard Pestell, Md, Anthony Howell, Federica Sotgia, Michael P. Lisanti, Md

Kimmel Cancer Center Faculty Papers

Here, we developed a model system to evaluate the metabolic effects of oncogene(s) on the host microenvironment. A matched set of "normal" and oncogenically transformed epithelial cell lines were co-cultured with human fibroblasts, to determine the "bystander" effects of oncogenes on stromal cells. ROS production and glucose uptake were measured by FACS analysis. In addition, expression of a panel of metabolic protein biomarkers (Caveolin-1, MCT1, and MCT4) was analyzed in parallel. Interestingly, oncogene activation in cancer cells was sufficient to induce the metabolic reprogramming of cancer-associated fibroblasts toward glycolysis, via oxidative stress. Evidence for "metabolic symbiosis" between oxidative cancer cells …

Immunopathology Of Cd4+ T Cell-Mediated Autoimmune Responses To Central Nervous System Antigens: Role Of Il-16, Harley Y. Tse, Dusanka S. Skundric, William W. Cruikshank, Paul C. Montgomery, Robert P. Lisak

Neurology Faculty Publications

Multiple sclerosis (MS) is a chronic, inflammatory, demyelinating and degenerative disease of the central nervous system (CNS). While etiology of the disease remains unknown, genetic susceptibility and autoimmune mechanisms in the initiation and progression of the disease have been strongly suggested. Experimental autoimmune encephalomyelitis (EAE) is commonly used to study immune regulation of MS. Infiltration by CD4⁺ T cells, through blood-brain barrier (BBB), precedes the onset and relapses of MS. CNS migration and homing patterns of T cells are tightly synchronized by astrocyte and microglia derived cytokines and chemokines. Autoimmune, CNS antigenreactive, infiltrating T cells produce and locally release …

Pattern Of Emergency Department Visits By Elderly Patients: Study From A Tertiary Care Hospital, Karachi, Jabeen Fayyaz, Munawar Khursheed, Mohammed Umer Mir, Uzma Rahim Khan

Department of Emergency Medicine

Background

Worldwide the proportion of elderly people in the population is increasing. Currently in Pakistan 7.3 million people (5.6% of total population) are more than 60 years old. This age shift has emerged as an important health issue and is associated with an increased utilization of emergency services by the elderly. We carried out this study to assess the pattern of elderly patients (>60 years) who visit emergency departments in comparison to young adults (18–60 years).

Methods

Data was collected retrospectively of patients aged 18 years or more who visited the Emergency Department (ED) of Aga Khan University Hospital, …

Hdl-C: Does It Matter? An Update On Novel Hdl-Directed Pharmaco-Therapeutic Strategies., Ramprasad Gadi, Aman Amanullah, Vincent M. Figueredo

Division of Cardiology Faculty Papers

It has long been recognized that elevated levels of low-density lipoprotein cholesterol (LDL-C) increase the risk of cardiovascular disease (CHD) and that pharmacologic therapy to decrease LDL-C significantly reduces cardiovascular events. Despite the effectiveness of statins for CHD risk reduction, even optimal LDL-lowering therapy alone fails to avert 60% to 70% of CHD cases. A low plasma concentration of high-density lipoprotein cholesterol (HDL-C) is also associated with increased risk of CHD. However, the convincing epidemiologic data linking HDL cholesterol (HDL-C) to CHD risk in an inverse correlation has not yet translated into clinical trial evidence supporting linearity between HDL-C increases …

Adverse Childhood Experiences, Disability And Health-Risk Behaviors, Sophia Miryam Schussler-Fiorenza Rose Md, Phd

Population Health Matters (Formerly Health Policy Newsletter)

No abstract provided.

Unraveling The Mechanism Of 2,4-Dinitrofluorobenzene-Associated Cell Death, Franklin Thelmo

Summer Training Program in Cancer Immunotherapy

The mechanism by which the hapten 2,4-dinitrophenyl (DNP) mediates cell death is unclear according to current literature. To determine how DNP mediates death in the B16F10 murine melanoma cell line in vitro, cells were modified with 2,4-dinitro-1-fluorobenzene (DNFB). Following modification, cell lysates were collected and analyzed via Western blottings with known apoptotic or necrotic markers. Our results indicated that DNFB treated cells do not express the apoptotic marker Cleaved Caspase-3 and have no change in levels of the necrotic marker Cyclophilin A. We conclude that DNFB is not inducing apoptosis in B16F10 cells. Future research will further examine the …

Adoptive T Cell Therapy For Metastatic Colorectal Cancer, Shauna Ebanks

Summer Training Program in Cancer Immunotherapy

Colorectal cancer is the second leading cause of cancer-related death in US (1). Most of the mortality reflects local, regional and distant metastatic tumors. Cancers that are confined within the wall of the colon are often curable with surgery while tumor cells that have spread into other organs like liver and lung has low curable possibility, even though the chemotherapies and monoclonal antibodies can extend the person's life and improve quality of life(2, 3). Surgery is the main treatment for primary colorectal tumors but recurrence can happen and develop into metastasis. In addition, colorectal cancer …

Coupling S100a4 To Rhotekin Alters Rho Signaling Output In Breast Cancer Cells, Min Chen, Anne R. Bresnick, Kathleen L. O'Connor

Markey Cancer Center Faculty Publications

Rho signaling is increasingly recognized to contribute to invasion and metastasis. In this study, we discovered that metastasis-associated protein S100A4 interacts with the Rho-binding domain (RBD) of Rhotekin, thus connecting S100A4 to the Rho pathway. Glutathione S-transferase pull-down and immunoprecipitation assays demonstrated that S100A4 specifically and directly binds to Rhotekin RBD, but not the other Rho effector RBDs. S100A4 binding to Rhotekin is calcium-dependent and uses residues distinct from those bound by active Rho. Interestingly, we found that S100A4 and Rhotekin can form a complex with active RhoA. Using RNA interference, we determined that suppression of both S100A4 and …

Increased Reticulocytosis During Infancy Is Associated With Increased Hospitalizations In Sickle Cell Anemia Patients During The First Three Years Of Life, Emily Riehm Meier, Colleen Byrnes, Y. Terry Lee, Elizabeth C. Wright, Alan N. Schechter, Naomi L. Luban, Jeffrey L. Miller

Pediatrics Faculty Publications

Objective

Among older children with sickle cell anemia, leukocyte counts, hemoglobin, and reticulocytosis have previously been suggested as disease severity markers. Here we explored whether these blood parameters may be useful to predict early childhood disease severity when tested in early infancy, defined as postnatal ages 60–180 days.

Study Design

Data from fifty-nine subjects who were followed at Children’s National Medical Center’s Sickle Cell Program for at least three years was retrospectively analyzed. Comparisons were made between white blood cell counts, hemoglobin and reticulocyte levels measured at ages 60–180 days and the clinical course of sickle cell anemia during infancy …

The Effect Of Heart Failure Education On Reducing Readmissions, Mayola Lara Villarruel

Evidence-Based Practice Project Reports

Management of heart failure is a significant financial challenge for the health care industry, costing approximately $33.2 billion annually. Common reasons for preventable heart failure readmissions include inadequate discharge education and lack of self-care and health management activities. Education at discharge is a vital component of improving heart failure outcomes. Following a review of the literature, high quality evidence supports that heart failure education should focus on medication adherence, sodium and fluid restriction, daily weights, activity tolerance, identification of deteriorating signs and symptoms of heart failure, and smoking cessation. The purpose of this EBP project was to reduce heart failure …

Effects Of Two Inhaled Corticosteroid/Long-Acting Beta-Agonist Combinations On Small-Airway Dysfunction In Mild Asthmatics Measured By Impulse Oscillometry, Bill Diong, Kshitiz Singh, Rogelio Menendez

Faculty Articles

Background: We previously showed that the long-acting beta agonist (LABA) salmeterol as inhalation powder or metered-dose inhaler improves lung-function parameters assessed by impulse oscillometry (IOS) in 2- to 5-year-old children with reversible-airway disease within 15 minutes. Objective: We studied 12- to 45-year-olds with mild persistent asthma in order to compare the onset and extent of peripheral airway effects following the first dose and after 4 weeks dosing with two inhaled corticosteroid (ICS)/LABA combinations: fluticasone propionate/salmeterol 115/21 and budesonide/formoterol 160/4.5. Methods: Thirty subjects with mild persistent asthma using only an as-needed short-acting beta-agonist (albuterol) who had at least a 40% change …

Spectral Discrimination Of Breast Pathologies In Situ Using Spatial Frequency Domain Imaging, Ashley M. Laughney, Venkataramanan Krishnaswamy, Elizabeth J. Rizzo, Mary C. Schwab, Richard J. Barth, David J. Cuccia, Bruce J. Tromberg, Keith D. Paulsen, Brian W. Pogue, Wendy A. Wells

Dartmouth Scholarship

Introduction: Nationally, 25% to 50% of patients undergoing lumpectomy for local management of breast cancer require a secondary excision because of the persistence of residual tumor. Intraoperative assessment of specimen margins by frozen-section analysis is not widely adopted in breast-conserving surgery. Here, a new approach to wide-field optical imaging of breast pathology in situ was tested to determine whether the system could accurately discriminate cancer from benign tissues before routine pathological processing.

Targeting Platelet Thrombin Receptor Signaling To Prevent Thrombosis, Eric L. Wallace, Susan S. Smyth

Gill Heart & Vascular Institute Faculty Publications

Platelets contribute fundamentally to ischemic heart disease, and antiplatelet therapy has been critical to reducing acute thrombotic complications of atherosclerotic disease. Thrombin, by acting on protease activated receptors (PAR), is one of the most potent platelet activators. PAR-1 antagonists may therefore provide more comprehensive antithrombotic effects. We review the pathophysiology of atherothrombosis, platelet activation by thrombin, the role of platelet protease activated receptors (PAR), and the clinical data supporting their use.

Department Of Surgery Update, August 2013, Wright State University Department Of Surgery

Department of Surgery Updates

A three page newsletter created by the Department of Surgery documenting changes to the department. This issue contains a message from the chair, a list of important dates, committee meetings, scholarly activity and more.

Ereply. Re: Balancing The Pulmonary Circulation In Tricuspid Atresia With An Aortopulmonary Window, Pranava Sinha, Syed Murfad Peer, Mary T. Donofrio

Pediatrics Faculty Publications

No abstract provided.

Appendicitis Is Like A Box Of Chocolates, Clint D. Cappiello, Phillip C. Guzzetta, Faisal G. Qureshi

Pediatrics Faculty Publications

Appendicitis is the most commonly encountered abdominal emergency in pediatric surgery. However, the presentation of acute appendicitis is as diverse as the patient population. We present here a case of appendicitis presenting as an intra-abdominal mass consistent with lymphoma. Our patient is a 3 year old male with an atypical presentation of acute appendicitis. Additionally, he was found to have malrotation at the time of surgery. A delayed presentation, coupled with anomalous laboratory findings and aberrant anatomy made for a difficult diagnosis and overall interesting case of appendicitis.

Interleukin Expression After Injury And The Effects Of Interleukin-1 Receptor Antagonist, Connie S. Chamberlain, Ellen M. Leiferman, Kayt E. Frisch, Stacey L. Brickson, William L. Murphy, Geoffrey S. Baer

Faculty Publications - Biomedical, Mechanical, and Civil Engineering

Ligament and tendon repair involves a complex series of coordinated events orchestrated by various cell types, cytokines and other factors. The repair process extends months to years and results in scar tissue mechanically inferior to native tissue. This is in clear contrast to tissue "regeneration" which would recapitulate the native tissue. Numerous approaches to stimulate a regenerative scenario have been attempted, including tissue-engineering, non-steroidal anti-inflammatories, ultrasonic, or electrical stimulation, but none have resulted in complete regeneration. In pursuit of a more regenerative outcome, it is important to understand the fundamentals of the normal healing process. Previous work from our lab …

Analysis Of Lmnb1 Duplications In Autosomal Dominant Leukodystrophy Provides Insights Into Duplication Mechanisms And Allele-Specific Expression, Elisa Giorgio, Harshvardhan Rolyan, Laura Kropp, Anish Baswanth Chakka, Svetlana Yatsenko, Adeline Vanderver, +31 Additional Authors

Neurology Faculty Publications

Autosomal dominant leukodystrophy (ADLD) is an adult onset demyelinating disorder that is caused by duplications of the lamin B1 (LMNB1) gene. However, as only a few cases have been analyzed in detail, the mechanisms underlying LMNB1 duplications are unclear. We report the detailed molecular analysis of the largest collection of ADLD families studied, to date. We have identified the minimal duplicated region necessary for the disease, defined all the duplication junctions at the nucleotide level and identified the first inverted LMNB1 duplication. We have demonstrated that the duplications are not recurrent; patients with identical duplications …

Interests In High-Functioning Autism Are More Intense, Interfering, And Idiosyncratic Than Those In Neurotypical Development, Laura G. Anthony, Lauren Kenworthy, Benjamin E. Yerys, Kathryn F. Jankowski, Joette James, Madeline B. Harms, Alex Martin, Gregory L. Wallace

Psychiatry and Behavioral Sciences Faculty Publications

Although circumscribed interests are pathognomonic with autism, much about these interests remains unknown. Using the Interests Scale (IS), this study compares interests between 76 neurotypical (NT) individuals and 109 individuals with high-functioning autism spectrum disorder (HF-ASD) matched groupwise on age, IQ, and gender ratio. Participants and their parents/caregivers completed diagnostic measures (the Autism Diagnostic Interview—Revised and the Autism Diagnostic Observation Schedule; HF-ASD only), cognitive tests (Wechsler IQ Scales), and questionnaires (the Repetitive Behavior Scale—Revised, the Behavior Rating Inventory of Executive Function, and the Social Responsiveness Scale), in addition to the IS. Consistent with previous research, HF-ASD and NT individuals did …

Metastatic Castration-Resistant Prostate Cancer: Critical Review Of Enzalutamide, Joelle El-Amm, Nihar Patel, Ashley Freeman, Jeanny B. Aragon-Ching

Medicine Faculty Publications

Enzalutamide, previously known as MDV300, is an oral, second-generation androgen receptor (AR) signaling inhibitor or antagonist that was approved by the Food and Drug Administration in 2012 for the treatment of metastatic castrate-resistant prostate cancer (mCRPC) postdocetaxel. Preclinical studies have demonstrated impressive affinity to the AR compared to the first-generation AR inhibitors. The landmark Phase III AFFIRM trial demonstrated improved overall survival benefit compared to placebo in addition to improvement in all tested parameters. Enzalutamide is currently being studied in several trials prechemotherapy and in earlier settings of prostate cancer. This review will discuss the mechanism of action of enzalutamide, …

Effect Of Early Release Of Tourniquet In Total Knee Arthroplasty, Kashif Abbas, Hasnain Raza, Masood Umer, Kamran Hafeez

Section of Orthopaedic Surgery

Objective: To evaluate whether tourniquet release intraoperatively is better than postoperative release in reducing overall blood loss, duration of surgery, duration of tourniquet, length of hospital stay, wound related complications and transfusion requirement. Study Design: Comparative study. Place and Duration of Study: Department of Surgery, The Aga Khan University Hospital, Karachi, from January 2004 to June 2007.
Methodology: One hundred and thirty patient files were reviewed retrospectively. Patients were divided into two groups. Group-A consisted of 65 patients with early deflation of tourniquet and group-B comprised of 65 patients with the release of tourniquet after applying compressive dressing. Total blood …

Safety Of Untreated Autologous Cranioplasty After Extracorporeal Storage At -26 Degrees Celsius, Muhammad Zubair Tahir, Muhammad Shahzad Shamim, Zain-Ul-Abdeen Sobani, Syed Nabeel Zafar, Mohsin Qadeer, Muhammad Ehsan Bari

Section of Neurosurgery

Background: Given the improved survival of patients requiring decompressive craniectomies, the frequency of subsequent cranioplasties are on the rise. The most feared complication of autologous cranioplasty is infection and one method for reducing the rate of infection, is to store the bone flaps at subnormal temperatures. However, to date there is no defined temperature for flap storage and temperature ranges from - 18 to - 83°C have been described in literature. Considering our limited resources it has been the practice at our center to store bone flaps at - 26°C. In this study, we have retrospectively reviewed our practice and …

Effects Of Prior Acute Exercise On Circulating Cytokine Concentration Responses To A High-Fat Meal, Josef Brandauer, Rian Q. Landers-Ramos, Nathan T. Jenkins, Espen E. Spangenburg, James M. Hagberg, Steven J. Prior

Health Sciences Faculty Publications

High-fat meal consumption alters the circulating cytokine profile and contributes to cardiometabolic diseases. A prior bout of exercise can ameliorate the triglyceride response to a high-fat meal, but the interactive effects of exercise and high-fat meals on cytokines that mediate cardiometabolic risk are not fully understood. We investigated the effects of prior exercise on the responses of circulating tumor necrosis factor-a (TNF-a), interleukin-6 (IL-6), IL-8, leptin, retinol-binding protein 4 (RBP4), vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), placental growth factor (PlGF), and soluble fms-like tyrosine kinase-1 (sFlt-1) to a high-fat meal. Ten healthy men were studied before …

A Statement On Vemurafenib-Resistant Melanoma., Edward J Hartsough, A E Aplin

Department of Cancer Biology Faculty Papers

Despite recent advancements in the treatment of late-stage mutant BRAF (V600E/K) melanomas, a major hurdle continues to be acquired resistance to BRAF inhibitors such as vemurafenib. The mechanisms for resistance have proven to be heterogeneous, emphasizing the need to use broad therapeutic approaches. In this issue, the study "Stat3-targeted therapies overcome the acquired resistance to vemurafenib in melanomas" by Liu et al. proposes that signal transducer and activator of transcription 3 (STAT3)-paired box 3 (PAX3) signaling may be a mechanism that is used by melanomas to resist RAF inhibitors.

The Relationship Between Prenatal Stress, Depression, Cortisol And Preterm Birth: A Review, Kiran Shaikh, Shahirose Premji, Khurshid Khowaja, Suzanne Tough, Ambreen Kazi, Shaneela Khowaj

School of Nursing & Midwifery

Preterm birth is one of the most common adverse pregnancy outcomes. Maternal risk factors such as stress and depression have been associated with preterm birth. Preterm infants are at a higher risk of poor growth and neuro developmental outcomes. The objective of this paper is to examine the relationship between maternal stress, depression, cortisol level, and preterm birth. Preterm birth is one of the most common adverse pregnancy outcomes with a global prevalence of 9.6% and one of the major contributors to infant mortality and morbidity. The association between psychosocial stress and preterm birth, although examined for more than 25 …

Metabolic Syndrome Increases Risk For Pulmonary Embolism After Hip And Knee Arthroplasty., Boris Mraovic, Md, Brian R Hipszer, Md, Richard H. Epstein, Md, Javad Parvizi, Md, Edward C Pequignot, Md, Inna Chervoneva, Md, Jeffrey Joseph, Md

Department of Anesthesiology Faculty Papers

AIM: To investigate whether patients with metabolic syndrome (MetS) undergoing total hip or knee replacement have an increased risk for pulmonary embolism (PE).

METHODS: We studied patients undergoing total hip or total knee replacement from January 2001 to April 2006. The diagnosis of PE was based on a positive finding with a chest CT or a lung scan. Components of MetS were defined as 1) BMI≥30 kg/m(2) , 2) non-fasting preadmission glucose ≥11.1 mmol/L or diagnosis of diabetes, 3) hypertension, and 4) dyslipidemia. MetS was diagnosed if at least three of these components were present.

RESULTS: Of 7282 patients, 107 …

Improving Function In Age-Related Macular Degeneration: A Randomized Clinical Trial., Barry W. Rovner, Robin J Casten, Mark T Hegel, Robert W Massof, Benjamin E. Leiby, Allen C. Ho, William S. Tasman

Department of Psychiatry and Human Behavior Faculty Papers

PURPOSE: To compare the efficacy of problem-solving therapy (PST) with supportive therapy (ST) to improve targeted vision function (TVF) in age-related macular degeneration (AMD).

DESIGN: Single-masked, attention-controlled, randomized clinical trial with outcome assessments at 3 months (main trial endpoint) and 6 months (maintenance effects).

PARTICIPANTS: Patients with AMD (n = 241) attending retina practices.

INTERVENTIONS: Whereas PST uses a structured problem-solving approach to reduce vision-related task difficulty, ST is a standardized attention-control treatment.

MAIN OUTCOME MEASURES: We assessed TVF, the 25-item National Eye Institute Vision Function Questionnaire plus Supplement (NEI VFQ), the Activities Inventory (AI), and vision-related quality of life …

Disease Patterns And Outcomes Of Neonatal Admissions At A Secondary Care Hospital In Pakistan, Syed R. Ali, Shakeel Ahmed, Heeramani Lohana

Department of Paediatrics and Child Health

Objectives: This study aimed to determine the disease patterns and outcome of patients admitted to the neonatal unit of a secondary care hospital in Pakistan from January to December 2009.
Methods: Retrospective data from the medical records of all neonates admitted during the study period were reviewed and analysed for age, weight, sex, reason for admission, duration of hospital stay, diagnosis and final outcome. Trends were examined to identify the indicators of inpatient neonatal deaths.
Results: The total number of neonates admitted during the study period was 1,554; 979 were male (63%), and 575 were female (37%). A total of …

Illuminating The Dark Side--Vitamin D Status In Different Localities Of Karachi, Romaina Iqbal, Lena Jafri, Ali Haroon, Aysha Habib Khan

Department of Medicine

This study was conducted to determine the association between place of residence (grouped into neighbourhoods), and 25-hydroxy D (25[OH]D) levels of individuals of Karachi. Addresses of 4788 individuals tested for 25[OH]D at the clinical laboratory of the Aga Khan University (AKU), Karachi, from January 2007 to June 2008 were reviewed. The neighbourhoods were categorized into ten, based on locality attributes. A high overall prevalence (74%) of vitamin D deficiency (VDD) was observed. There was a significant difference (p-value < 0.01) between mean log 25[OH]D levels amongst neighbourhoods grouped according to distinct housing structure attributes and localities. A high frequency of VDD in all the studied localities of an urban city warrant dietary vitamin D supplementation and food fortification.

Oncolog, Volume 58, Number 08, August 2013, Bryan Tutt, Sarah Bronson

OncoLog MD Anderson's Report to Physicians (All issues) Archives

• Specialized Care Improves Lives of patients With Head and Neck Lymphedema: A unique program is producing dramatic results for patients with head and neck lymphedema, a side effect of cancer treatment that can interfere with patient's ability to speak, swallow, or breath
• Targeted Cancer Therapies May Help Overcome Resistance to Radiation Therapy: Some cancer cells are resilient enough to withstand and recover from the damage to their DNA caused by radiation therapy. But recent studies have shown that adding molecularly targeted agents to radiation therapy can prevent the repair of this radiation-induced damage and therapy improve the treatment response of …