Medical Specialties Commons^™

Changes In Ventricular Depolarisation Vectors During Exercise Caused By Regional Myocardial Ischaemia, Cameruddin Vellani, Satwat Hashmi, Sadia Mahmud, Mohammad Yusuf, Safia Awan, Khawar Kazmi

Section of Cardiology

Research at the Aga Khan University for several years has been directed to find a reliable, low-cost, portable, non-invasive method for identification of coronary artery disease, its location and extent. A new method has been devised to measure the magnitude and direction of cardiac electrical vectors in three perpendicular planes during physical exercise to identify reduction in myocardial excitability as the electrophysiological marker of hypoxia. This report shows that changes in electrical forces due to exercise-induced regional hypoxia serve as indicators of reversible myocardial ischaemia. Changes in the magnitude and direction of vectors at stages of the Bruce protocol were …

Macrophage-Associated Wound Healing Contributes To African Green Monkey Siv Pathogenesis Control, Fredrik Barrenas, Kevin Raehtz, Cuiling Xu, Lynn Law, Richard R. Green, Guido Silvestri, Steven E. Bosinger, Andrew Nishida, Qingsheng Li, Wuxun Lu, Jianshui Zhang, Matthew J. Thomas, Jean Chang, Elise Smith, Jeffrey M. Weiss, Reem A. Dawoud, George H. Richter, Anita Trichel, Dongzhu Ma, Xinxia Peng, Jan Komorowski, Cristian Apetrei, Ivona Pandrea, Michael Gale Jr.

Nebraska Center for Virology: Faculty Publications

Natural hosts of simian immunodeficiency virus (SIV) avoid AIDS despite lifelong infection. Here, we examined how this outcome is achieved by comparing a natural SIV host, African green monkey (AGM) to an AIDS susceptible species, rhesus macaque (RM). To asses gene expression profiles from acutely SIV infected AGMs and RMs, we developed a systems biology approach termed Conserved Gene Signature Analysis (CGSA), which compared RNA sequencing data from rectal AGM and RM tissues to various other species. We found that AGMs rapidly activate, and then maintain, evolutionarily conserved regenerative wound healing mechanisms in mucosal tissue. The wound healing protein fibronectin …

Nearly Complete Genome Sequences Of 17 Enterovirus D68 Strains From Kansas City, Missouri, 2018, Suman B. Pakala, Yi Tan, Ferdaus Hassan, Annie Mai, Robert H. Markowitz, Meghan H. Shilts, Seesandra V. Rajagopala, Rangaraj Selvarangan, Suman R. Das

Manuscripts, Articles, Book Chapters and Other Papers

Here, we report 17 nearly complete genome sequences of enterovirus D68 (EV-D68) isolated from Kansas City, MO, in 2018. Phylogenetic analysis suggests that these strains belong to subclade B3, similar to the ones that caused the 2016 epidemics in the United States but different from the 2014 outbreak B1 strains.

A Physiologically-Based Pharmacokinetic Model For Targeting Calcitriol-Conjugated Quantum Dots To Inflammatory Breast Cancer Cells., James Forder, Mallory Smith, Margot Wagner, Rachel J. Schaefer, Jonathan Gorky, Kenneth L. Van Golen, Anja Nohe, Prasad Dhurjati

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Quantum dots (QDs) conjugated with 1,25 dihydroxyvitamin D3 (calcitriol) and Mucin-1 (MUC-1) antibodies (SM3) have been found to target inflammatory breast cancer (IBC) tumors and reduce proliferation, migration, and differentiation of these tumors in mice. A physiologically-based pharmacokinetic model has been constructed and optimized to match experimental data for multiple QDs: control QDs, QDs conjugated with calcitriol, and QDs conjugated with both calcitriol and SM3 MUC1 antibodies. The model predicts continuous QD concentration for key tissues in mice distinguished by IBC stage (healthy, early-stage, and late-stage). Experimental and clinical efforts in QD treatment of IBC can be augmented by in …

Acute Diagnosis Of Wilson’S Disease In A Teenage Patient, Sarah Irvin, Ryan Mccarthy

Marshall Journal of Medicine

Wilson’s Disease, a rare autosomal recessive genetic disease, is caused by a mutation in the ATP7B enzyme gene. Without this enzyme, copper builds up in the brain, liver, and cornea causing a multitude of symptoms. It is important to consider Wilson’s disease because the prognosis is dependent on timely diagnosis. This is an interesting case of a 19-year-old male who presented with suicidal thoughts and rapid weight loss. After many months and an extensive work-up, Wilson’s Disease was diagnosed. Due to his rapid decline, he was transferred to a larger university healthcare center where he is currently enrolled in clinical …

Contributing Factors To Diabetic Brain Injury And Cognitive Decline, Nirmal Verma, Florin Despa

Pharmacology and Nutritional Sciences Faculty Publications

The link of diabetes with co-occurring disorders in the brain involves complex and multifactorial pathways. Genetically engineered rodents that express familial Alzheimer's disease-associated mutant forms of amyloid precursor protein and presenilin 1 (PSEN1) genes provided invaluable insights into the mechanisms and consequences of amyloid deposition in the brain. Adding diabetes factors (obesity, insulin impairment) to these animal models to predict success in translation to clinic have proven useful at some extent only. Here, we focus on contributing factors to diabetic brain injury with the aim of identifying appropriate animal models that can be used to mechanistically dissect the …

Drug-Induced Autoimmune Hepatitis From Hydralazine Leading To Acute Liver Failure And Liver Transplantation, Jasleen Grewal, Angela Doan, Annie S. Hong, Arpit Amin, Jason V. Scapa, Ramy Hanna, Francisco Durazo, Beshoy Yanny

School of Medicine Faculty Research

We describe a woman with no previous liver disease who developed drug-induced autoimmune hepatitis from hydralazine prescribed to her for hypertension. Despite the discontinuation of the medication, she developed acute liver failure and subsequently underwent successful liver transplantation. She survived and had a good clinical outcome.

Metformin And Cancer: Pharmacoepidemiology Considerations, Sarah Kradel, Christina Spinaris, Victoria Pennington, Adam Trimble, Lara Long, Natalie Dipietro

Pharmacy and Wellness Review

No abstract provided.

Maternal Characteristics Affect Fetal Growth Response In The Women First Preconception Nutrition Trial., K Michael Hambidge, Carla M Bann, Elizabeth M Mcclure, Jamie E Westcott, Ana Garcés, Lester Figueroa, Shivaprasad S Goudar, Sangappa M Dhaded, Omrana Pasha, Sumera A Ali, Richard J Derman, Robert L Goldenberg, Marion Koso-Thomas, Manjunath S Somannavar, Veena Herekar, Umber Khan, Nancy F Krebs

Global Health Articles

The objective of this secondary analysis was to identify maternal characteristics that modified the effect of maternal supplements on newborn size. Participants included 1465 maternal-newborn dyads in Guatemala, India, and Pakistan. Supplementation commenced before conception (Arm 1) or late 1st trimester (Arm 2); Arm 3 received usual care. Characteristics included body mass index (BMI), stature, anemia, age, education, socio-economic status (SES), parity, and newborn sex. Newborn outcomes were z-scores for length (LAZ), weight (WAZ), and weight to length ratio-for-age (WLRAZ). Mixed-effect regression models included treatment arm, effect modifier, and arm * effect modifier interaction as predictors, controlling for site, …

Comparison Of Long-Term Oral Anticoagulation Therapies Including Newly Approved Reversal Agent For Dabigatran, Mackenzie Devine, Natalie Lennartz, Michaela Wolford, Rebecca Worden, Joelle Farano, Erin Petersen

Pharmacy and Wellness Review

Anticoagulants are a well-known class of agents essential for the prevention of blood clots, which may further develop into deep vein thrombosis, pulmonary embolism or stroke. Individuals at a high risk of clotting, such as those with atrial fibrillation, multiple risk factors or recent hip/knee surgery, are in need of long-term anticoagulation therapy. The purpose of this review is to highlight the pros and cons for each available anticoagulant as well as discuss pivotal clinical trials that evaluated the safety and efficacy of these agents. Warfarin, the oldest anticoagulant, requires the patient to attend frequent appointments with a health care …

Use Of Botulinum Toxin In Central Nervous System Disorders, Julie Puvogel, Paige Torbet, Jourdan Ujlaki, Rebecca Worden, Lindsey Peters

Pharmacy and Wellness Review

Botulinum toxin is a neurotoxin that is produced by Clostridium botulinum. At one time, this toxin was only seen as a lethal substance, but now scientists have found many medical uses for it. There are eight distinctive toxins (A-H), but only A and B currently have clinical uses. Botulinum toxin A has three different versions that are U.S. Food and Drug Administration (FDA) approved: onabotulinumtoxinA (Botox®), abobotulinumtoxinA (Dysport®), incobotulinumtoxinA (Xeomin®). Botulinum toxin B is also FDA approved as rimabotulinumtoxinB (Myobloc®). The toxins work by inducing reversible, local, dose-dependent chemodenervation by inhibiting acetylcholine release from presynaptic terminals. These drugs are approved …

Prevention And Treatment Of Glucocorticoid-Induced Osteoporosis, Mackenzie Devine, Anh Dao Le, Julie Puvogel, Victoria Cho, Michelle Musser

Pharmacy and Wellness Review

Osteoporosis is a disease state resulting in decreased bone mineral density (BMD) and increased risk of fracture, specifically of the vertebrae, spine and hip. Risk factors and high risk populations for developing osteoporosis include low BMD, long-term glucocorticoid therapy, genetics, diet, postmenopausal women and patients with inflammatory or chronic disease states. A variety of signaling pathways involving hormones, cytokines and other signaling molecules are involved in bone formation and are affected by long-term glucocorticoid therapy, leading to the development of glucocorticoid-induced osteoporosis (GIO).

There are a variety of drugs that work efficaciously to prevent and treat GIO. Alendronate is a …

Treatment Of Basal Cell Carcinoma With Vismodegib, Sunitha Johns, Katlyn Brown, Emily Loudermilk, Crystal Zheng, Anh Dao Le, Sophocles Chrissobolis

Pharmacy and Wellness Review

The most prevalent nonmelanoma skin cancers are basal cell carcinoma (BCC) and locally advanced basal cell carcinoma (aBCC). Current, effective first-line treatments for BCC aim to remove and destroy cancerous skin cells through excision surgery, Mohs surgery, radiation therapy and cryotherapy, while treatment of aBCC remains limited. An emerging treatment option for aBCC that promotes tumor size reduction is vismodegib, a pharmaceutical product approved in 2012 by the U.S. Food and Drug Administration (FDA). Vismodegib was approved for the treatment of aBCC, metastasized HCC (mBCC) or recurrent BCC after surgery as well as for use in adults who are not …

Triple Therapy Or Triple Threat: An Analysis Of Triple Antiplatelet Therapy Compared To Dual Antiplatelet Therapy, Isabel E. Cwikla, Kara C. Horvath, Elaina Gollmar, Austin Hilverding, Erin Petersen

Pharmacy and Wellness Review

Triple antiplatelet therapy (TAPT, or triple therapy), is an oral medication regimen designed to reduce the risk of major cardiovascular events. It consists of aspirin, clopidogrel or an alternative, and an oral anticoagulant (OAC). It differs from dual antiplatelet therapy (DAPT) due to inclusion of an OAC. Multiple clinical studies have indicated that triple therapy is more effective at clot prevention, when compared to aspirin monotherapy and DAPT, but is associated with a higher risk of major bleeding. Pharmacists have a key role in determining candidates for DAPT and TAPT regimens. Other opportunities for pharmacists include patient monitoring, counseling and …

Programmed Death Pathway Inhibition: Emerging Therapeutic Options For Treatment Of Advanced Or Refractory Cancers, Katherine Elsass, Morgan Homan, Jana Randolph, Brendan Rasor, David Kinder

Pharmacy and Wellness Review

The programmed death-1 (PD-1) pathway has a significant role in the promotion of immune tolerance. The PD-1 receptor ligands are normally expressed on various inactive immune cells. When cancer cells express these ligands, they are able to interact with active T and B lymphocytes to induce this tolerance. Nivolumab and pembrolizumab are two recently approved agents that act to disrupt this binding and facilitate an immune response against cancer cells. Numerous trials, including KEYNOTE-002 and CheckMate 063, have demonstrated the superior safety and efficacy of these drugs in patients with advanced or refractory cancers. Initially approved for the treatment of …

Pcsk9 Inhibitors: A Novel Class Of Pharmacotherapy For Hypercholesterolemia, Angela Chu, Austin Hilverding, Elizabeth Kramer, Brendan Rasor, Boyd Rorabaugh

Pharmacy and Wellness Review

The recent U.S. Food and Drug Administration (FDA) approval of two new drugs, alirocumab (Praluent®) and evolocumab (Repatha®) is a breakthrough in the treatment of familial hypercholesterolemia. These drugs are a part of a new class called the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors that act by increasing the number of low density lipoprotein receptors (LDL-R) recycled to hepatocyte membranes. The increased density of LDL-R facilitates greater clearance of low density lipoproteins from the blood. Numerous clinical trials have demonstrated the efficacy of these agents, particularly for patients in whom standard cholesterol-lowering therapy is insufficient. However, data on long-term …

Belsomra®: A Novel Dual Orexin Receptor Antagonist For The Treatment Of Insomnia, Shane Bogusz, Steven Blake, Michaela Wolford, Victoria Cho, Manoranjan D'Souza

Pharmacy and Wellness Review

Insomnia is a disease state characterized by a persistent difficulty in falling asleep, and results in enormous health-related and economic costs to both the individual and society. Several medications are currently available for the treatment of insomnia; however, these medications are associated with several limitations including anterograde amnesia, dependence, withdrawal symptoms upon stopping the medication and rebound insomnia. The U.S. Food and Drug Administration recently approved suvorexant (Belsomra®) as a treatment for insomnia. Suvorexant is a first-in-class dual orexin receptor antagonist for the treatment of insomnia. This review will first describe the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) …

Dose Effects Of Recombinant Adenovirus Immunization In Rodents, Eric A. Weaver

Nebraska Center for Virology: Faculty Publications

Recombinant adenovirus type 5 (rAd) has been used as a vaccine platform against many infectious diseases and has been shown to be an effective vaccine vector. The dose of the vaccine varies significantly from study to study, making it very diffcult to compare immune responses and vaccine effcacy. This study determined the immune correlates induced by serial dilutions of rAd vaccines delivered intramuscularly (IM) and intranasally (IN) to mice and rats. When immunized IM, mice had substantially higher antibody responses at the higher vaccine doses, whereas, the IN immunized mice showed a lower response to the higher rAd vaccine doses. …

Pain Management In Dementia Patients In Nursing Homes, Tiffany Kneuss, Kelsey Weisenburger, Hannah Stewart, Kelly Reilly Kroustos

Pharmacy and Wellness Review

Pain in the elderly, especially those with dementia, is often undertreated and misdiagnosed by health care professionals in the long-term care setting. Communication barriers in patients with cognitive impairment force pain assessment to rely heavily on subjective interpretation of behavioral factors due to the inability of patients to self-report pain symptoms. It is important for clinicians to develop a standard method of identifying and assessing signs of pain in patients with dementia in order to appropriately treat those experiencing discomfort. Patients with dementia who present with a sudden onset of behavioral changes should receive a comprehensive evaluation that includes a …

The Effects Of Long-Term Benzodiazepine Use And Withdrawal In The Elderly, Lydia Suchecki, Hannah Granger, Jamie Kellner, Mary Ellen Hethcox

Pharmacy and Wellness Review

Benzodiazepines remain a commonly prescribed medication in the United States, and the high usage of this drug class is especially a concern in the elderly population for several reasons. First, elderly patients metabolize drugs differently, leading to varying responses. Age-related changes also have a significant impact on the effects of benzodiazepines. Second, elderly patients are more likely to be taking multiple centrally-acting drugs, which can further exacerbate negative effects. In regard to long-term benzodiazepine use, elderly patients experience an increased risk of cognitive impairment, motor vehicle accidents, decline in physical performance, falls and subsequent fractures, and sleep disturbances. Withdrawal is …

Current Trials And Therapies For The Treatment Of Amyotrophic Lateral Sclerosis And Frontotemporal Dementia, Adam Smith, Angela Chu, Lucy Wagala, Hannah Stewart, Lindsey Peters

Pharmacy and Wellness Review

An area of health care that provides many more questions than answers includes neurodegenerative disorders. Amyotrophic lateral sclerosis (ALS), commonly known as Lou Gehrig's disease, and frontotemporal dementia (FTD) are both diseases about which we know very little. However, ALS and FTD affect nearly 30,000 and 60,000 Americans respectively. Currently, there is not a cure for ALS or FTD and treatment options are aimed toward symptom management. Much of the pathophysiology of these diseases is unknown, but we do know there are genetic implications, specifically in SOD1, TARDBP and c90RF72. These mutations lead to cognitive deficits, muscle weakness and, eventually, …

Testosterone Replacement Therapy In Aging Males, Alexandra Dimit, Joelle Farano, Haley Armstrong, Michelle Musser

Pharmacy and Wellness Review

The U.S. Food and Drug Administration (FDA) cautions health care providers and patients regarding the use of testosterone replacement therapy products for the aging process, including a decrease in muscle strength, muscle mass, and lack of energy or sexual desire, due to an increased risk of heart attacks and strokes. Testosterone replacement therapy products are indicated for genetic defects, chemotherapy damage, or damage to the hypothalamus or pituitary gland, where testosterone is produced. A patient and his team of health care professionals must seriously consider the risks and benefits when using these products for other indications. Use of testosterone replacement …

Combined Neprilysin And Angiotensin Inhibitor For The Treatment Of Heart Failure, Albert Bui, Victoria Cho, Rebecca Worden, Haley Armstrong, Rachel Pucel, Lindsey Peters

Pharmacy and Wellness Review

Heart failure (HF) is a highly prevalent disease state worldwide that can progress into a disabling condition. It is pertinent to have a treatment regimen that is effective in lowering the number of HF exacerbations and, therefore, hospital readmission rates. A novel medication currently in clinical trials, LCZ696, blocks both neprilysin and angiotensin type I receptors. The overall effects are an inhibition of the breakdown of natriuretic peptides which leads to a decrease in renin and aldosterone release. This, combined with the antagonization of angiotensin type I receptors, leads to a decrease in blood pressure, blood volume and systemic vascular …

Potential Use Of Dopamine And Dopamine Agonists As Angiogenesis Inhibitors In The Treatment Of Cancer, Benjamin Finley, Katherine Liu, Daniel Powell, Jamie Kellner, David H. Kinder

Pharmacy and Wellness Review

In recent years, there have been numerous developments in monoclonal antibodies used as anticancer drugs with a focus on reducing the ability of cancers to metastasize and produce new vasculature. These agents are called angiogenesis inhibitors and although these agents have been proven effective in treating certain types of cancers, production and administration of monoclonal antibodies comes at a steep cost with a severe side effect profile. Under normal physiologic conditions, angiogenesis is an important mechanism to create new blood vessels from preexisting vessels, usually occurring in adults. Tumor cells can hijack the angiogenesis pathway to produce new distant tumors …

New Cholesterol Guidelines: An Update For Pharmacists, Emily Limberg, Benjamin Finley, Stacy Henthorne, Sarah Kradel, David Bright

Pharmacy and Wellness Review

The American College of Cardiology and American Heart Association published new blood cholesterol guidelines in November 2013. The new guidelines place an emphasis on evidence-based treatment of dyslipidemias and primarily use randomized controlled trials to create recommendations for health care providers. Major changes from the previous guidelines include eliminating low-density lipoprotein goals, the classification of statins by lipid-lowering potential and the creation of four major statin benefit groups. The new guidelines also establish the role of non-statins in dyslipidemias and use the Pooled Cohort Risk Assessment Equations to calculate patients' risk for cardiovascular events and the need for cholesterol-lowering medications. …

Crohn's Disease: Management, Emerging Therapies And The Role Of The Pharmacist, Sarah Turley, Tiffany Kneuss, Lydia Suchecki, Alison Steinbrunner, Kristen Timperman

Pharmacy and Wellness Review

Crohn's disease is a relapsing-remitting disorder of the gastrointestinal tract caused by a mixture of genetic and environmental factors. Pharmacologic treatment of Crohn's disease is patient-specific, and regimens vary widely between individuals. Drug regimens are typically based on 5-aminosalicylate therapy and may include a combination of steroids, histamine 2 receptor antagonists, proton pump inhibitors, immunomodulators, antibiotics, biologic agents and other medications aimed at symptom relief. A new medication, vedolizumab, is currently in phase III clinical trials awaiting U.S. Food and Drug Administration (FDA) approval for use in Crohn's disease. Vedolizumab is an alpha-integrin inhibitor, which is anticipated to have a …

Advances In Treatment Of Chronic Hepatitis C Virus (Hcv) Infection, Halle Orlinski, Kimberly Loughlin, Haley Armstrong, Emily Blum, Andrew M. Roecker

Pharmacy and Wellness Review

Hepatitis C virus (HCV) infection is a prominent cause of chronic liver disease and may lead to serious complications such as liver failure and need for a transplant. The virus is transmitted via exposure to blood and is classified into various genotypes based on genetic mutations in the virus. Current treatment options for HCV infection are not effective in all patients, and there are limited options for patients infected with a genotype other than genotype 1. Two new medications have been approved recently for treatment of HCV infection. Simeprevir (Olysio®) gained U.S. Food and Drug Administration (FDA) approval in November …

Lbrutinib (Lmbruvica™) For Treatment Of Mantle Cell Lymphoma, Brittany Crowe, Joy Hoffman, Hannah Stewart, Alison Steinbrunner, Mark E. Olah

Pharmacy and Wellness Review

Mantle cell lymphoma (MCL) is a rare and moderately aggressive form of non-Hodgkin's lymphoma (NHL) that predominantly presents at an advanced stage in older males. Patients often present with multiple involvement in the lymph nodes, blood, spleen, bone marrow and gastrointestinal tract (GIT). Some patients may be asymptomatic in early stages or present with an incurable, indolent (slow progressing) form, while other patients display rapid growth of more aggressive lymphomas. Overall survival for patients diagnosed with MCL is four to five years and treatment should be initiated in those who are symptomatic. Mantle cell lymphoma responds well to first-line treatment, …

Dapagliflozin: A Newly Approved Sglt2 Inhibitor For The Treatment Of Type 2 Diabetes Mellitus, Ann Marie Ruhe, Rachel Muhlenkamp, Austin Brown, Emily Blum, Sandra L. Hrometz

Pharmacy and Wellness Review

Type 2 diabetes mellitus (T2DM) is a chronic disease in which a hyperglycemic state is induced by insulin resistance. While there are numerous treatment options available to manage T2DM, many patients require changes in therapy throughout treatment, as well as multiple medications. The sodium/glucose cotransporter 2 (SGLT2) inhibitors, canagliflozin and dapagliflozin, offer a therapeutic alternative in T2DM management through the utilization of a unique mechanism of action to provide intensified glycemic control. This article will evaluate the safety and efficacy of dapagliflozin in the management ofT2DM.

Trametinib And Dabrafenib: New Agents For Advanced Stage Melanoma, Kelsey Weisenburger, Kevin Krivanek, Armond Cosiano, Kasie Bellmann, Mark E. Olah

Pharmacy and Wellness Review

Melanoma, the deadliest form of skin cancer, is caused primarily by exposure to ultraviolet radiation. Tumor formation occurs early in disease progression and can easily metastasize. The development of the disease can be described by one of four stages, characterized by tumor size and risk of spreading. The B-rafprotein plays an important role in cell proliferation and has the ability to develop a mutation for continuous activation, resulting in uncontrolled cell growth. Sixty percent of melanomas possess a V600E mutation in the BRAF gene. Recently, drug developers have turned the focus of melanoma treatments toward preventing the activation of the …