Medicine and Health Sciences Commons^™

Current Therapeutic Research Is Now Indexed On Pubmed., John N Van Den Anker, Karel Allegaert, Walter K. Kraft

Department of Pharmacology and Experimental Therapeutics Faculty Papers

No abstract provided.

Impact Of Preadmission Beta-Blocker Use On Cardiac Abnormalities And In-Hospital Mortality In Patients With Aneurysmal Subarachnoid Hemorrhage, Toshimasa Okabe, Md, Anushya Jeyabalan, Md, Benjamin E. Leiby, Phd, Fred Rincon, Md, Walter K. Kraft, Md

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Introduction:

Various cardiac abnormalities, including dysrhythmias, left ventricular (LV) dysfunction, and myocardial injury, are commonly seen after subarachnoid hemorrhage (SAH). In patients taking a beta-blocker (BB) chronically, the medication is generally discontinued after hospitalization due to the concern of compromising cerebral perfusion. We hypothesized that sudden BB discontinuation might inadvertently lead to an increased incidence of composite cardiac abnormalities and higher in-hospital mortality in patients presenting with nontraumatic SAH.

Gucy2c Lysosomotropic Endocytosis Delivers Immunotoxin Therapy To Metastatic Colorectal Cancer., Glen P Marszalowicz, Adam E. Snook, Michael Sullivan Magee, Dante Merlino, Lisa D Berman-Booty, Scott A Waldman

Department of Pharmacology and Experimental Therapeutics Faculty Papers

The emergence of targeted cancer therapy has been limited by the paucity of determinants which are tumor-specific and generally associated with disease, and have cell dynamics which effectively deploy cytotoxic payloads. Guanylyl cyclase C (GUCY2C) may be ideal for targeting because it is normally expressed only in insulated barrier compartments, including intestine and brain, but over-expressed by systemic metastatic colorectal tumors. Here, we reveal that GUCY2C rapidly internalizes from the cell surface to lysosomes in intestinal and colorectal cancer cells. Endocytosis is independent of ligand binding and receptor activation, and is mediated by clathrin. This mechanism suggests a design for …

Ethanol Pharmacokinetics In Neonates And Infants, Elizabeth Marek, Pharmd., Walter K. Kraft, Md

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Introduction:

Ethanol has been used for years in neonatal and infant liquid medications, yet the pharmacokinetics, pharmacodynamics, and safety of ethanol in this vulnerable population have not been well characterized. The purpose of this review is to raise awareness of ethanol use as an excipient in neonatal and infant medications and to provide insight, based on the available evidence, into clearance rates of ethanol in babies. We also discuss ethanol pharmacokinetics in adults, theoretical pharmaco-kinetic changes in neonates and infants as it may apply to ethanol disposition, and case reports involving ethanol exposure in neonates and infants.

Materials and methods: …

Obesity And Mortality: Are The Risks Declining? Evidence From Multiple Prospective Studies In The United States., Tapan S. Mehta, Kevin R. Fontaine, Scott W. Keith, Sripal S. Bangalore, Gustavo De Los Campos, Alfred Bartolucci, Nicholas M. Pajewski, David B. Allison

Department of Pharmacology and Experimental Therapeutics Faculty Papers

We evaluated whether the obesity-associated years of life lost (YLL) have decreased over calendar time. We implemented a meta-analysis including only studies with two or more serial body mass index (BMI) assessments at different calendar years. For each BMI category (normal weight: BMI 18.5 to <25 >[reference]; overweight: BMI 25 to60, YLL for grade 1 obesity decreased by 1.02 years (P < 0.001) and increased by 0.63 years for grade 2-3 obesity (P = 0.63). Among women aged ≤60, YLL for grade 1 obesity decreased by 4.21 years (P < 0.001) and by 4.97 years (P < 0.001) for grade 2-3 obesity. In women aged >60, YLL for grade 1 obesity decreased by 3.98 years (P < 0.001) and by 2.64 years (P = 0.001) for grade 2-3 obesity. Grade 1 obesity's association with decreased longevity has reduced for older Caucasian men. For Caucasian women, there is evidence of a decline in the obesity YLL association across all ages.

Posaconazole Tablet Pharmacokinetics: Lack Of Effect Of Concomitant Medications Altering Gastric Ph And Gastric Motility In Healthy Subjects., Walter K. Kraft, Peter S. Chang, Marlou L P S Van Iersel, Hetty Waskin, Gopal Krishna, Wendy M Kersemaekers

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Posaconazole oral suspension is an extended-spectrum triazole that should be taken with food to maximize absorption. A new posaconazole tablet formulation has demonstrated improved bioavailability over the oral suspension in healthy adults in a fasting state. This study evaluated the effects of concomitant medications altering gastric pH (antacid, ranitidine, and esomeprazole) and gastric motility (metoclopramide) on the pharmacokinetics of posaconazole tablets. This was a prospective open-label 5-way crossover study in 20 healthy volunteers. In each treatment period, a single 400-mg dose (4 100-mg tablets) of posaconazole was administered alone or with 20 ml antacid (2 g of aluminum hydroxide and …

Asa Section On Teaching Of Statistics In The Health Sciences: 25 Years Later, Constantine Daskalakis, Scd

Department of Pharmacology and Experimental Therapeutics Faculty Papers

ASA's Section on Teaching of Statistics in the Health Sciences was established as a subsection of the Section on Statistical Education in 1970, and became an independent section in 1991. Stephen Looney, Todd Nick, Ralph O'Brien, Bob Oster and others led the section's early growth in the mid-to-late 1990s. Sessions and continuing education courses were organized at JSM, the newsletter was modernized, and a first website was established. In the early-to-mid 2000s, Ruth Mickey, Walter Ambrosius, Cyndy Long, Ed Gracely, the late Patrick Arbogast, Jodi Lapidus, and Scott Evans added their own efforts in strengthening section activities. It was during …

Tumor Radiation Therapy Creates Therapeutic Vaccine Responses To The Colorectal Cancer Antigen Gucy2c., Matthew Witek, Erik S Blomain, Michael Sullivan Magee, Bo Xiang, Scott A Waldman, Adam E. Snook

Department of Pharmacology and Experimental Therapeutics Faculty Papers

PURPOSE: Radiation therapy (RT) is thought to produce clinical responses in cancer patients, not only through direct toxicity to cancer cells and supporting tumor stroma cells, but also through activation of immunologic effectors. More recently, RT has potentiated the local and systemic effects of cancer immunotherapy (IT). However, combination regimens that maximize immunologic and clinical efficacy remain undefined.

METHODS AND MATERIALS: We evaluated the impact of local RT on adenoviral-mediated vaccination against the colorectal cancer antigen GUCY2C (Ad5-GUCY2C) in a murine subcutaneous tumor model using mouse CT26 colon cancer cells (CT26-GUCY2C). Immune responses were assessed by ELISpot, and clinical responses …

Managing The Innovation Supply Chain To Maximize Personalized Medicine., Scott A. Waldman, Andre Terzic

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Personalized medicine epitomizes an evolving model of care tailored to the individual patient. This emerging paradigm harnesses radical technological advances to define each patient's molecular characteristics and decipher his or her unique pathophysiological processes. Translated into individualized algorithms, personalized medicine aims to predict, prevent, and cure disease without producing therapeutic adverse events. Although the transformative power of personalized medicine is generally recognized by physicians, patients, and payers, the complexity of translating discoveries into new modalities that transform health care is less appreciated. We often consider the flow of innovation and technology along a continuum of discovery, development, regulation, and application …