Chemicals and Drugs Commons^™

A New Sv2a Ligand For Epilepsy, Michael A. Rogawski

Michael A. Rogawski

The Changing Landscape Of Biosimilars In Rheumatology, Thomas Dorner, Vibeke Strand, Paul Cornes, Joao Goncalves, Laszlo Gulacsi, Jonathan Kay, Tore K. Kvien, Josef S. Smolen, Yoshiya Tanaka, Gerd R. Burmester

Jonathan Kay

Biosimilars remain a hot topic in rheumatology, and some physicians are cautious about their application in the real world. With many products coming to market and a wealth of guidelines and recommendations concerning their use, there is a need to understand the changing landscape and the real clinical and health-economic potential offered by these agents. Notably, rheumatologists will be at the forefront of the use of biosimilar monoclonal antibodies/soluble receptors. Biosimilars offer cost savings and health gains for our patients and will play an important role in treating rheumatic diseases. We hope that these lower costs will compensate for inequities …

Proton Pump Inhibitors: The Perils Of Turning 30, Beth Careyva Md, Katarzyna Jabbour Pharmd, Ahmad Rasheed

Beth A. Careyva, M.D.

No abstract provided.

Which Drugs Cause Cancer?, Andrew Knight, Jarrod Bailey, Jonathan Balcombe

Jarrod Bailey, PhD

Animal tests yield misleading results.

Cancerous Contradictions: The Mis-Regulation Of Human Carcinogens Based On Animal Data, Andrew Knight, Jarrod Bailey, Jonathan Balcombe

Jarrod Bailey, PhD

The regulation of human exposures to potential carcinogens constitutes society’s most important use of animal carcinogenicity data. However, for environmental contaminants of greatest U.S. concern, we found that in most cases (58.1%; 93/160) the U.S. Environmental Protection Agency (EPA) considered the animal data inadequate to support a classification of probable human carcinogen or noncarcinogen.

The World Health Organisation’s International Agency for Research on Cancer (IARC) is a leading international authority on carcinogenicity assessments. For chemicals lacking human exposure data (the great majority), IARC classifications of identical chemicals were significantly more conservative than EPA classifications (p

Tolerability Of Induction Chemotherapy Dosing Practices In Acute Myeloid Leukemia Patients, Kaylene M. Peric, David J. Reeves

David Reeves

For patients with high body surface areas (BSA), differing chemotherapy dosing strategies have been utilized in attempts to reduce toxicity. In a retrospective evaluation, we compared the effects of chemotherapy dosing in acute myeloid leukemia patients with high BSA (>2 m2) who received capped doses (n = 12) to those who received uncapped doses (n = 24), and to patients with BSA ≤ 2 m2 (n = 42). There were no statistically significant differences among groups (BSA ≤ 2 m2, BSA > 2 m2 capped, and BSA > 2 m2 uncapped) in the incidences of febrile neutropenia (85.7, 66.7, and 75.0%, …

Successful Desensitization To Docetaxel After Severe Hypersensitivity Reactions In Two Patients, David J. Reeves, Michael J. Callahan, Gregory P. Sutton

David Reeves

Purpose Two cases of successful desensitization to docetaxel after severe hypersensitivity reactions are reported. Summary Two patients with gynecological malignancies (uterine leiomyosarcoma and ovarian adenocarcinoma) experienced severe hypersensitivity reactions with docetaxel, including flushing, numbness, sharp radiating pain, severe nausea and vomiting, apnea, and unresponsiveness. Both patients received ondansetron before docetaxel. One patient received dexamethasone, diphenhydramine, and famotidine premedication before docetaxel, as she had previously reacted to paclitaxel. Docetaxel infusions were stopped, and the reactions were treated with diphenhydramine and dexamethasone (one patient also received famotidine). After resolution of symptoms, the docetaxel was not reinitiated due to the nature of the …

Drug-Drug Interaction Between Methotrexate And Levetiracetam Resulting In Delayed Methotrexate Elimination, Emily Bain, Ruemu E. Birhiray, David J. Reeves

David Reeves

Objective: To report a case of delayed methotrexate (MTX) elimination while receiving concomitant levetiracetam. Case Report: A 46-year-old man with relapsed osteosarcoma of the base of the skull receiving high-dose MTX tolerated his first cycle of MTX with elimination to nontoxic MTX levels (≤0.1 µmol/L) within 90 hours. After hospital discharge, the patient experienced seizures secondary to brain metastasis and started on levetiracetam, which was continued as maintenance therapy. The patient experienced delayed MTX elimination during cycles 2, 3, and 4 while receiving levetiracetam. On average, elimination to nontoxic MTX levels took 130 hours (106-144 hours). Before the fifth cycle …

Bone Health Management In Prostate Cancer Patients Receiving Androgen Deprivation Therapy, Vishnuprabha Dhanapal, David J. Reeves

David Reeves

Purpose. Patients receiving androgen deprivation therapy undergo a rapid decline in bone mineral density during the first 6 to 12 months of initiating therapy. The World Health Organization has developed and implemented the Fracture Risk Assessment Tool (FRAX) to predict the ten year risk of a major fracture & hip fracture. Additionally, the National Comprehensive Cancer Network and the National Osteoporosis Foundation have developed osteoporosis guidelines. This study aims to characterize the fracture risk (based on the FRAX tool) and the current management of bone health based on national guidelines compliance. Methods. A retrospective chart review of patients receiving a …

Ascorbic Acid For The Treatment Of Rasburicase Induced Methemoglobinemia In The Setting Of Acute Renal Failure, David J. Reeves, Lindsay Saum, Ruemu Birhiray

David Reeves

Purpose A case of apparent rasburicase-induced methemoglobinemia and acute kidney injury treated with i.v. ascorbic acid because of suspected glucose-6-phosphate dehydrogenase (G6PD) deficiency is reported. Summary A 46-year-old African-American man with a recent diagnosis of multiple myeloma and renal insufficiency was admitted to the hospital with a cough, hemoptysis, and fatigue. His medical history included hypertrophic cardiomyopathy, ventricular tachycardia, attention deficit/hyperactivity disorder, and pleural effusion. No treatments for multiple myeloma were started before hospital admission. Levofloxacin 750 mg orally daily for possible pneumonia, lenalidomide 10 mg orally daily, and dexamethasone 20 mg orally weekly were administered. Plasmapheresis was also initiated. …

Structural And Molecular Analysis Of A Protective Epitope Of Lyme Disease Antigen Ospa And Antibody Interactions, Shivender Shandilya, Nese Kurt Yilmaz, Ejemel Monir, Andrew Sadowski, William D. Thomas, Mark S. Klempner, Celia A. Schiffer, Yan Wang

Celia A. Schiffer

The murine monoclonal antibody LA-2 recognizes a clinically protective epitope on outer surface protein (OspA) of Borrelia burgdorferi, the causative agent of Lyme disease in North America. Human antibody equivalence to LA-2 is the best serologic correlate of protective antibody responses following OspA vaccination. Understanding the structural and functional basis of the LA-2 protective epitope is important for developing OspA-based vaccines and discovering prophylactic antibodies against Lyme disease. Here, we present a detailed structure-based analysis of the LA-2/OspA interaction interface and identification of residues mediating antibody recognition. Mutations were introduced into both OspA and LA-2 based on computational predictions on …

In-Season N Fertilization Strategies Using Active Sensors, Daniel Barker, John Sawyer

John E. Sawyer

The objectives of this project were to measure corn yield response to applied nitrogen (N) fertilizer based on active canopy sensing during the mid-vegetative corn growth stage (V10) and compare yield and N use efficiency between pre-plant N (PP-N), pre-plant + sensor N (PP+S-N), split N strategy (SNS), and rescue N strategy (RNS).

In-Season N Fertilization Strategies Using Active Sensors, Daniel Barker, John Sawyer

John E. Sawyer

The objectives of this project were to measure corn yield response to applied nitrogen (N) fertilizer based on active canopy sensing during the mid-vegetative corn growth stage (V10) and compare yield and N use efficiency between pre-plant N (PP-N), pre-plant + sensor N (PP+S-N), split N strategy (SNS), and rescue N strategy (RNS).

In-Season N Fertilization Strategies Using Active Sensors, Daniel Barker, John Sawyer

John E. Sawyer

The objectives of this project were to measure corn yield response to applied nitrogen (N) fertilizer based on active canopy sensing during the mid-vegetative corn growth stage (V10) and compare yield and N use efficiency between pre-plant N (PP-N), pre-plant + sensor N (PP+S-N), split N strategy (SNS), and rescue N strategy (RNS).

Impacts Of Cover Crops On Phosphorus And Nitrogen Loss With Surface Runoff, Antonio Mallarino, Richard Cruse, Dan Jaynes, John Sawyer, Pablo Barbieri

John E. Sawyer

Iowa research has demonstrated that cover crops can improve soil productivity and water quality by increasing soil organic matter and reducing nitrate nitrogen (N) leaching. Other research has investigated and is investigating the agronomic and economic viability of using cereal rye cover crops in continuous corn or corn-soybean rotations. However, no Iowa research has evaluated under natural rainfall the impact of cover crops on phosphorus (P) and N loss with surface runoff interacting with other management practices. The need for this type of research was indicated in the Iowa Nutrient Reduction Strategy documents. This effort assessed what would be needed …

Impact Of 4r Management On Crop Production And Nitrate-Nitrogen Loss In Tile Drainage, Matthew Helmers, John Sawyer, Josh Sievers

John E. Sawyer

Corn Belt corn and soybean producers are increasingly challenged to maximize crop production while addressing the contributions farm practices make to Gulf hypoxia. Based on the need for nitrate-N reductions to meet water quality goals, new management practices are needed to reduce nitrate-N losses at minimal cost and maximum economic benefits. This three-year field research and demonstration project is evaluating various promising N management methods and technologies by documenting the nitrate-N export and crop yield from various systems.

The Crisis Of Opiates In Appalachia, James B. Becker Md

James Becker

No abstract provided.

Biosimilars In Rheumatology: What The Clinician Should Know, Gilberto Castaneda-Hernandez, Rodrigo Gonzalez-Ramirez, Jonathan Kay, Morton A. Scheinberg

Jonathan Kay

Biosimilars are now a reality in rheumatology. Although analytical and non-clinical procedures to establish similarity have evolved significantly, clinical trials demonstrating equivalent efficacy and safety are absolutely required for all biosimilars. The design of such trials, including equivalence and non-inferiority statistical approaches, are discussed. Clinical evidence on biosimilars that have been approved recently or are presently being developed for use in rheumatology is also reviewed and contrasted with that available for biomimics (or intended copies), which are non-innovator biologics that are marketed in several countries but have not undergone review according to a regulatory pathway for biosimilars.

A Meta-Analysis Of Incidence And Risk Factors Of Trastuzumab-Induced Cardiotoxicity In Breast Cancer, Zeeshan Ali Jawa, Ruth M. Perez, Lydia Garlie, Maharaj Singh, Rubina Qamar, Bijoy K. Khandheria, Arshad Jahangir, Yang Shi

Maharaj Singh

Background: A monoclonal antibody, trastuzumab targets the human epidermal growth factor receptor 2 (HER2) oncogene that is overexpressed in 25–30% of breast cancers. In combination with first-line therapy, trastuzumab resulted in significant improvement in survival outcomes for those with HER2-positive metastatic breast cancer. Due to its improvement in outcome and prolonged survival, trastuzumab has been established as standard of care in both adjuvant and metastatic settings. However, along with common adverse events, trastuzumab has been found to be associated with cardiotoxicity. An estimated 1–4% of patients treated with trastuzumab will develop heart failure and ~10% of patients will experience a …

Which Drugs Cause Cancer?, Andrew Knight, Jarrod Bailey, Jonathan Balcombe

Andrew Knight, Ph.D.

Animal tests yield misleading results.

Cancerous Contradictions: The Mis-Regulation Of Human Carcinogens Based On Animal Data, Andrew Knight, Jarrod Bailey, Jonathan Balcombe

Andrew Knight, PhD

The regulation of human exposures to potential carcinogens constitutes society’s most important use of animal carcinogenicity data. However, for environmental contaminants of greatest U.S. concern, we found that in most cases (58.1%; 93/160) the U.S. Environmental Protection Agency (EPA) considered the animal data inadequate to support a classification of probable human carcinogen or noncarcinogen.

The World Health Organisation’s International Agency for Research on Cancer (IARC) is a leading international authority on carcinogenicity assessments. For chemicals lacking human exposure data (the great majority), IARC classifications of identical chemicals were significantly more conservative than EPA classifications (p

Vitamin D Deficiency: "At Risk" Patient Populations And Potential Drug Interactions, Dana Lycans Md, Elias Salloum Md, Matthew K. Wingate Md, Thomas Melvin Md, Grant S. Buchanan Md, Franklin D. Shuler Md, Phd

Franklin D. Shuler

Vitamin D is known to play an essential role in calcium homeostasis; however, excessive amounts can have harmful effects. Calcium and vitamin D levels are known to be influenced by drug interactions and pathology ranging from of cancer to cardiovascular disease. Vitamin D supplementation has become widespread, and it is important for clinicians to understand the way that certain conditions and medications interact with vitamin D and calcium homeostasis. The purpose of this review is to outline the benefits and adverse effects of vitamin D and how its levels are affected by certain pathologic and pharmacologic interactions.

Essentials Of Herb-Drug Interactions In The Elderly With Cardiovascular Disease, Sulaiman Sultan, Maria Viqar, Rabaiya Ali, A. Jamil Tajik, Arshad Jahangir

Arshad Jahangir, MD

As the number of individuals, particularly the elderly, using herbal products with prescription drugs continues to grow, the risk for adverse interactions increases but remains poorly recognized. The true incidence and nature of adverse herb reactions or herb-drug interactions remains unknown since no postmarketing surveillance mechanism exists. Adverse events are greatly underreported, and information regarding safety mainly comes from case reports and suboptimally conducted studies in a limited number of healthy young volunteers or patients with limited comorbidities. Therefore, convincing evidence for the safety of herbal products in the elderly is lacking, and the true magnitude of problems that herb-drug …

A Meta-Analysis Of Incidence And Risk Factors Of Trastuzumab-Induced Cardiotoxicity In Breast Cancer, Zeeshan Ali Jawa, Ruth Perez, Lydia Garlie, Maharaj Singh, Rubina Qamar, Bijoy Khandheria, Arshad Jahangir, Yang Shi

Arshad Jahangir, MD

Background: A monoclonal antibody, trastuzumab targets the human epidermal growth factor receptor 2 (HER2) oncogene that is overexpressed in 25–30% of breast cancers. In combination with first-line therapy, trastuzumab resulted in significant improvement in survival outcomes for those with HER2-positive metastatic breast cancer. Due to its improvement in outcome and prolonged survival, trastuzumab has been established as standard of care in both adjuvant and metastatic settings. However, along with common adverse events, trastuzumab has been found to be associated with cardiotoxicity. An estimated 1–4% of patients treated with trastuzumab will develop heart failure and ~10% of patients will experience a …

Stinging Nettle: The Bad, The Good, The Unknown, Dennis J. Baumgardner

Dennis J. Baumgardner, MD

Stinging nettle (Urtica dioica) is native to most of the United States. It has a characteristic description and distribution in the environment. Physical contact with numerous tiny needlelike hairs present on leaves and stems of this plant may result in a contact urticarial dermatitis due to chemical and mechanical irritation triggered by skin penetration of the hairs. The manifestations are self-limited in humans and may be treated by washing the skin, topical preparations and oral antihistamines. Explanation of the natural history of these encounters to the patient is helpful in reducing the sometimes significant anxiety. Preparations and extracts of stinging …

Assessing The Effectiveness Of Implementation Of Unified Workflow In Improvement Of Medication Reconciliation For Aurora St. Luke’S Family Medicine Residency Outpatients, Katherine Meyers, Jessica Konarske, Jessica J.F. Kram, Dennis J. Baumgardner

Dennis J. Baumgardner, MD

Background: Medication errors are the most common errors occurring in hospitals. Preventable adverse drug events are linked with 1 in 5 injuries or deaths; 23% of medication errors in primary care occur due to inaccuracies in the medication list. Quality improvement projects designed to improve accuracy of outpatient medication reconciliations may decrease the number of medication errors and increase patient safety by preventing adverse drug events. Purpose: To determine whether a unified workflow for medication reconciliation improves the accuracy of ambulatory, electronic medical record (EMR)-based patient medication records. Methods: Retrospective study of random sample of patients from Aurora Family Medicine …

Methyl Transfer By Substrate Signaling From A Knotted Protein Fold, Thomas Christian, Reiko Sakaguchi, Agata P. Perlinska, George Lahoud, Takuhiro Ito, Erika A. Taylor, Shigeyuki Yokoyama, Joanna I. Sulkowska, Ya-Ming Hou

Erika A. Taylor, Ph.D.

Interrogating Metabolism In Brain Cancer, Travis Salzillo, Jingzhe Hu, Linda Nguyen, Nicholas Whiting, Jaehyuk Lee, Joseph Weygand, Prasanta Dutta, Shivanand Pudakalakatti, Niki Zacharias Millward, Seth Gammon, Frederick F. Lang, Amy B. Heimberger, Pratip Bhattacharya

Nicholas Whiting