Medical Pharmacology Commons^™

Frontal White Matter Integrity In Adults With Down Syndrome With And Without Dementia, David K. Powell, Allison Caban-Holt, Greg A. Jicha, William C. Robertson, Roberta Davis, Brian T. Gold, Frederick A. Schmitt, Elizabeth Head

Magnetic Resonance Imaging and Spectroscopy Center Faculty Publications

Adults with Down syndrome (DS) are at high risk for developing Alzheimer's disease after the age of 40 years. To detect white matter (WM) changes in the brain linked to dementia, fractional anisotropy (FA) from diffusion tensor imaging was used. We hypothesized that adults with DS without dementia (DS n = 10), DS with dementia (DSAD n = 10) and age matched non-DS subjects (CTL n = 10) would show differential levels of FA and an association with scores from the Brief Praxis Test and the Severe Impairment Battery. WM integrity differences in DS compared with CTL were found predominantly …

Characterization Of Primary Care Clinicians’ Use Of Genomic And Pharmacogenomic Testing, Brian Stello Md, Heather Bittner-Fagan Md, Mph, Christopher V. Chambers Md, Melanie B. Johnson Mpa, Geoffrey Mills Md, Phd, Michael P. Rosenthal Md, Kyle Shaak Bs

Department of Family Medicine

No abstract provided.

Primary Care Clinicians Use Of Genomics And Pharmacogenomic Testing, Heather Bittner-Fagan Md, Mph, Brian Stello Md, Christopher V. Chambers Md, Geoffrey Mills Md, Phd, Beth Careyva Md, Melanie B. Johnson Mpa, Dierdre B. Axell-House Ba, Michael P. Rosenthal Md

Department of Family Medicine

No abstract provided.

Phosphatidylinositol 3-Kinase (Pi3k) As A Therapeutic Target In Nsclc, Christopher W. Stamatkin

Theses and Dissertations--Pharmacy

Deregulated activation of phosphatidylinositol 3-kinase (PI3K) pathway is central to many human malignancies. The functions of this pathway are critical for normal cell metabolism, proliferation, and survival. In lung cancers, the PI3K pathway activity is often aberrantly driven by multiple mutations, including EGFR, KRAS, and PIK3CA. Molecules targeting the PI3K pathway are intensely investigated as potential anti-cancer agents. Although inhibitors of the pathway are currently in clinical trials, rational and targeted use of these compounds, alone or in combination, requires an understanding of isoform-specific activity in context. We sought to identify class IA PI3K enzyme (p110a/PIK3CA, p110b/PIK3CB, p110d/PIK3CD) activities using …

Radiosensitization Of Head & Neck Carcinoma Cells By Linifanib, A Receptor Tyrosine Kinase Inhibitor, Heng-Wei Hsu

Loma Linda University Electronic Theses, Dissertations & Projects

Tumor angiogenesis is a hallmark of advanced cancers and promotes invasion and metastasis. Over 90% of head and neck squamous cell carcinomas (HNSCC) express angiogenic factors such as vascular endothelial growth factor (VEGF). Since radiotherapy is one of the most commonly used treatments for HNSCC, it is imperative to identify the interactions between antiangiogenic therapy and radiotherapy, and to develop combination therapy to improve clinical outcome. The mechanisms between antiangiogenic agents and ionizing radiation are complicated and involve many interactions between the vasculature, tumor stroma and tumor cells. The proliferation and metastasis of tumor cells rely on angiogenesis/blood vessel formation. …

Intestinal Gucy2c Prevents Tgf-Β Secretion Coordinating Desmoplasia And Hyperproliferation In Colorectal Cancer., Ahmara V Gibbons, Jieru Egeria Lin, Gilbert Won Kim, Glen P Marszalowicz, Peng Li, Brian Arthur Stoecker, Erik S Blomain, Satish Rattan, Adam E. Snook, Stephanie Schulz, Scott A Waldman

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Tumorigenesis is a multistep process that reflects intimate reciprocal interactions between epithelia and underlying stroma. However, tumor-initiating mechanisms coordinating transformation of both epithelial and stromal components are not defined. In humans and mice, initiation of colorectal cancer is universally associated with loss of guanylin and uroguanylin, the endogenous ligands for the tumor suppressor guanylyl cyclase C (GUCY2C), disrupting a network of homeostatic mechanisms along the crypt-surface axis. Here, we reveal that silencing GUCY2C in human colon cancer cells increases Akt-dependent TGF-β secretion, activating fibroblasts through TGF-β type I receptors and Smad3 phosphorylation. In turn, activating TGF-β signaling induces fibroblasts to …

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 …

Polypharmacy In Elderly: A Cautious Trail To Tread, Saniya Raghib Sabzwari, Waris Qidwai, Seema Bhanji

Department of Family Medicine

Polypharmacy has now increasingly come into focus as the recipient of healthcare in old age worldwide. In elderly it is associated with frequent adverse drug reactions (ADRs) and drug-drug interactions resulting in significant morbidity. Geriatrics is still an emerging specialty in South Asia, especially in Pakistan, where multiple reasons for polypharmacy exist. An extensive literature review of articles using key words like \'polypharmacy,\' \'elderly\' was conducted. The recently updated Beers Criteria of classification of inappropriate drugs in the elderly was reviewed in detail. Articles of relevance to polypharmacy and evaluation of guidelines for appropriate interventions to minimise inappropriate drug prescribing …

Role Of Garlic Usage In Cardiovascular Disease Prevention: An Evidence-Based Approach, Waris Qidwai, Tabinda Ashfaq

Department of Family Medicine

Introduction:.Rapidly growing prevalence of cardiovascular disease is a major threat for the developed as well as developing world warranting urgent need of intervention. Complementary and alternative medicines are gaining popularity among general population because of their safety profile and easy administration. Garlic, in particular, is considered to be one of the best disease-preventive foods because of its potent and widespread effects. This study was done to find out the role of garlic usage in cardiovascular disease prevention.

Methodology : .Major databases including Google, PubMed,MEDLINE, and Cochrane library view were used for the literature search. Clinical trials conducted on humans assessing …

Rational Use Of Antibiotics--A Quality Improvement Initiative In Hospital Setting, Sidrah Nausheen, Rabia Hammad, Ambreen Khan

Department of Obstetrics & Gynaecology

Objectives: To minimise irrational use of antibiotics by implementing guidelines for antibiotic usage in obstetrics and Gynaeocology.
Methods: The observational study was conducted from January to December 2010 at the maternity unit of Aga Khan Hospital for Women and children, Kharadar, a secondary care facility in Karachi, Pakistan. Data was collected from medical records related to the study period. Prophylactic antibiotics were given according to the American College of Obstetricians and Gynaecologists recommendation 2009. Surveillance was done by surgical site infection rates and infectious morbidity. Data was analysed on SPSS 13.
Results: Therapeutic antibiotic use was rationalized, reducing the use …

Is Administration Of Depot Medroxyprogesterone Acetate Injections Every Three Months Effective In Decreasing Pain Associated With Endometriosis In Premenopausal Women?, Maria Kern

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this systematic EBM review is to determine whether or not the administration of depot medroxyprogesterone acetate injections every three months are effective in decreasing pain associated with endometriosis in premenopausal women.

STUDY DESIGN: A review of two randomized controlled trials and one randomized comparative trial comparing pain improvement from depot medroxyprogesterone acetate (DMPA) injections at different time intervals and/or in comparison to other hormonal birth control methods in premenopausal patients suffering from endometriosis.

DATA SOURCES: Randomized controlled trials and a randomized comparative trial were found using PubMed and Ovid MEDLINE databases.

OUTCOME MEASURED: Outcomes were …

Is Oral Rivaroxaban Safe And Effective In The Treatment Of Patients With Symptomatic Dvt?, Ami A. Patel

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this selective EBM review is to determine whether or not oral rivaroxaban is safe and effective in the treatment of patients with symptomatic DVT.

STUDY DESIGN: Review of three English language primary randomized controlled trial studies published from 2007-2011.

DATA SOURCES: Three randomized controlled trials studying the effectiveness and safety of rivaroxaban in the treatment of patients with symptomatic DVT in comparison to enoxaparin and placebo.

OUTCOMES MEASURED: Outcomes measured were episodes of recurrent DVT and bleeding. Patients were monitored for the proposed treatment period and seen at fixed intervals that were matching …

Are Triptan Drugs Safe And Effective For Use In The Prevention Of Menstrually Related Migraines (Mrms)?, Christina Ponzio

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this selective EBM review is to determine whether or not Triptan drugs are safe and effective for use in the prevention of menstrually related migraines (MRMs).

STUDY DESIGN: Review of two English language randomized controlled trials and one pilot randomized control trial.

DATA SOURCES: Randomized controlled trials comparing Triptan drugs to a placebo group were found using Medline, PubMed, and OVID.

OUTCOMES MEASURED: Incidence of MRM based on patient self-report; number of relapses; patients’ subjective evaluations of effectiveness based on questionnaire; adverse effects of Triptan treatment.

RESULTS: Two randomized controlled trials …

Is Pramipexole Safe And Effective In Reducing Depressive Symptoms In Patients With Mild To Moderate Parkinson’S Disease And Depression?, Corinne J. Kern

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this selective EBM review is to determine whether or not pramipexole (Mirapex) is a safe and effective drug to treat depression in patients with mild to moderate Parkinson’s Disease (PD).

STUDY DESIGN: Review of three English language primary randomized controlled trials and one randomized prospective, observational study published between 2003-2010.

DATA SOURCES: Three randomized controlled trials and one randomized prospective, observational study comparing the efficacy of pramipexole to placebo, sertraline (an SSRI) and other dopamine agonists (pergolide) in the treatment of PD related depression symptoms were found using PubMed.

OUTCOME(S) MEASURED: Each of the …

Does The Addition Of Muramyl Tripeptide To Chemotherapy Improve Overall Survival For Patients With Osteosarcoma?, Jennifer Jones

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this selective EBM review is to determine whether or not “Does the addition of muramyl tripeptide to chemotherapy improve overall survival for patients with osteosarcoma?”

STUDY DESIGN: Review of three English language primary randomized controlled trials published between 2005 and 2009.

DATA SOURCES: Randomized controlled trials evaluating the addition of muramyl tripeptide (MTP) to chemotherapy for patients with osteosarcoma were found using Medline/PubMed databases.

OUTCOMES MEASURED: Event-free survival (EFS) and overall survival were the outcome measures used to determine the effectiveness of the additional chemotherapy treatment in osteosarcoma patients. EFS was defined as …

Is Dabigatran Superior To Warfarin In Treating Patients With Atrial Fibrillation?, Kelly Higgins

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this selective EBM review is to determine whether or not Dabigatran is superior to Warfarin in patients with atrial fibrillation.

STUDY DESIGN: Review of three English language primary studies published in 2007, 2009, and 2010.

DATA SOURCES: Three randomized control trials found using Cochrane Database.

OUTCOME(S) MEASURED: Outcomes measured were presence or absence of stroke or systolic embolism and intracranial hemorrhage. The absence of these events preserved neurologic function in patients with atrial fibrillation.

RESULTS: In both VKA-naïve and VKA-experienced patients, Dabigatran 150 mg was superior to Warfarin in both the prevention of stroke …

Does Daily Intake Of Glucosamine Supplements Prevent The Need For Knee Replacements Later In Life For Adult Patients Predisposed To Osteoarthritis?, Nancy Helmy

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this selective EBM review is to determine whether or not daily intake of glucosamine supplements prevents the need for knee replacements later in life for adults predisposed to osteoarthritis.

STUDY DESIGN: Review of three English language primary randomized controlled trial studies published between 2001 and 2008

DATA SOURCES: Three double blind randomized control trials comparing glucosamine supplements to placebo were found using PubMed.

OUTCOMES MEASURED: Outcomes were measured using radiographic studies of the knees, joint space measurements, and symptoms were evaluated using Lequesne and WOMAC indexes.

RESULTS: The Reginster (2001) and Pavelka (2002) studies demonstrated no …

Is Fentanyl Pectin Nasal Spray Safe And Effective For Patients With Breakthrough Cancer Pain?, Salina G. Elengical

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this systematic review is to determine whether fentanyl pectin nasal spray (FPNS) is safe and effective treatment for patients with breakthrough cancer pain.

STUDY DESIGN: Review of three English language primary randomized controlled trials published 2010-2011.

DATA SOURCES: Multicenter, randomized, double-blind, double-dummy, placebo-controlled trials comparing fentanyl pectin nasal spray, immediate-release morphine sulfate, and/or nasal spray placebo were found using PubMed, COCHRANE, and Medline databases.

OUTCOME MEASURED: All three studies essentially used similar parameters to measure effectiveness and safety of fentanyl pectin nasal spray compared to oral immediate-release morphine sulfate and/or placebo. Baseline pain intensity …

Is Omalizumab A Safe And Effective Treatment For Chronic Urticaria?, Ashley L. Davis

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this selective EBM review is to determine whether or not omalizumab is a safe and effective treatment for chronic urticaria.

STUDY DESIGN: Review of two randomized controlled studies and one crossover study. All three studies are published in English between 2008-2011.

DATA SOURCES: Two randomized, double blind, placebo controlled studies and one crossover study found using PubMed and EBSCOhost.

OUTCOMES MEASURED: Each trial measured the duration, size, number and/or intensity of wheals. This was done by using the urticaria activity score (UAS). Quality of life was also measured using Dermatology Life Quality Index (DLQI), …

Is Local Infiltration Analgesia (Lia) A Safe And Effective Method For Post-Operative Pain Management After A Unilateral Total Knee Arthroplasty (Tka)?, Brooke A. Bonnette

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this systematic review is to determine whether or not local infiltration analgesia (LIA) is a safe and effective method for post-operative pain management after a unilateral total knee arthroplasty (TKA).
STUDY DESIGN: Review of three English language primary studies published in 2010 and 2011.

DATA SOURCES: Three randomized controlled trials comparing local infiltration analgesia to three separate controls: epidural analgesia, placebo infiltration and femoral nerve block found using PubMed.

OUTCOMES MEASURED: Clinical outcome was measured by total morphine use postoperatively and average knee pain intensity at rest and upon movement postoperatively. Total morphine use …

What Is The Effectiveness Of Onabotulinumtoxina (Botox®) In Reducing The Number Of Chronic Migraines (Cm) In Patients 18-65 Years Old?, Kristin A. Beddingfield

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this selective EBM review is to determine whether or not onabotulinumtoxinA (Botox®) is effective in reducing the number of chronic migraines (CM) in patients 18-65 years old? Study Design: Review of three published, double blind randomized controlled trials were used for this review, which were found on PubMed; were selected based on their relevance to the clinical question and if they included patient oriented outcomes.

OUTCOMES MEASURED: The outcomes measured were headache/migraine free days measured by >50% responder rate analysis, the Treatment Responder Rate based on Physician Global Assessment, and total adverse events reported by …

Is Phlogenzym Effective In Reducing Moderate To Severe Osteoarthritis Pain In Adults?, Vanessa K. Wood

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this selective EBM review is to determine whether or not Phlogenzym (or ERC) effective in reducing moderate to severe osteoarthritis pain in adults.

STUDY DESIGN: Review of three randomized controlled trials in the English language from 2001 to 2006.

DATA SOURCES: Two double blind RCTs and one open RCT was found using Cochrane Library EBM Online Database, Ovid Medline, and PubMed Online.

OUTCOMES MEASURED: Each of the three studies measured for pain at rest, pain with motion, and restricted function at baseline assessing efficacy using the Lequesne’s Algofunctional Index, visual analog scales, and …

Is Topiramate Effective In Preventing Pediatric Migraines?, Krystina Zeliff

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this selective EBM review is to determine whether or not Topiramate is effective in the prevention of pediatric migraines.
Study Design: Review of three English language randomized control trials published in 2005, 2007, and 2009.

DATA SOURCES: Three double-blind, placebo-controlled, randomized trials comparing various doses of Topiramate to placebo were found using PubMed, OVID, and Cochrane Library databases.

OUTCOME(S) MEASURED: The frequency of migraines in patients under the age of 18 years old was documented with headache diaries. The patient’s parent would record the number, severity, duration, associated symptoms, and use of acute …

Is Transdermal Glyceryl Trinitrate A Safe And Effective Treatment For Primary Dysmenorrhea?, Sarah E. Visich

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this selective evidence based medicine review is to determine whether or not transdermal glyceryl trinitrate is a safe and effective treatment for primary dysmenorrhea.

STUDY DESIGN: Review of two English language randomized control trials (RCTs) published in 1996 and 1999 and one English language pilot study in 1997.

DATA SOURCES: Two double-blind, randomized, placebo-controlled cross-over studies and one pilot study comparing transdermal glyceryl trinitrate to placebo were found using PubMed, Medline and OVID.

OUTCOME MEASURED: Outcomes measured were based on pain intensity scores (PID) assessed on a visual analog scale and the …

Does Etravirine Decrease Central Nervous System (Cns)/Neuropsychiatric (Nps) Adverse Events Compared To Efavirenz, In Hiv Positive Patients?, Angelo D. T. Smith

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this selective EBM review is to determine whether or not Etravirine (ETR) decreases adverse reactions on the central nervous system (CNS) compared to Efavirenz (EFV) in Human Immunodeficiency Virus (HIV) positive patients.

STUDY DESIGN: Review of three, English language, primary randomized controlled trial studies published in 2011.

DATA SOURCES: Three randomized controlled trials studying the possible decrease of ADR’s in HIV positive patients who are taking Efavirenz compared to study medication Etravirine.

OUTCOME(S) MEASURED: Outcomes measured were by surveys from patients that assess the development or cessation of CNS ADR’s. The self …

In Adults With Acute Diarrhea, Which Treatment Is More Effective Between Loperamide And Racecadotril?, Lorena A. Castillo

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this selective EBM review is to determine which treatment is more effective between loperamide and racecadotril to treat acute diarrhea in adults.

STUDY DESIGN: Review of three English language primary randomized controlled studies published from 1999-2005.

DATA SOURCES: First study was a RCT that was double blinded, double placebo, parallel study group and second and third study was RCT single blinded, comparative parallel group that all compared efficacy of loperamide and racecadotril. These were all found by using PubMed, COCHRANE and NCBI.

OUTCOMES MEASURED: Each of the studies measured the efficacy of each …

Nevirapine Hepatotoxicity: Case Report And Discussion, Matt Baichi

The Medicine Forum

Nevirapine (viramune) is a nonnucleoside reverse transcriptase inhibitor commonly used in combination with other antiretroviral medicines in the treatment of HIV/AIDS. The safety profile of nevirapine, as determined by review of prospective clinical trials, reports rash with an incidence of 16% as the most common side effect. Clinical hepatitis is reported to occur with an incidence of 1%. A review of the literature shows many case reports of nevirapine-induced hepatotoxicity in patients receiving both treatment and prophylaxis for HIV. The purpose of this case report is to stress the importance of early recognition and withdrawal of the offending drug.

Pediatric Pharmacogenomics: A Systematic Assessment Of Ontogeny And Genetic Variation To Guide The Design Of Statin Studies In Children., Jonathan B. Wagner, J Steven Leeder

Manuscripts, Articles, Book Chapters and Other Papers

The dose-exposure-response relationship for drugs may differ in pediatric patients compared with adults. Many clinical studies have established drug dose-exposure relationships across the pediatric age spectrum; however, genetic variation was seldom included. This article applies a systematic approach to determine the relative contribution of development and genetic variation on drug disposition and response using HMG-CoA reductase inhibitors as a model. Application of the approach drives the collection of information relevant to understanding the potential contribution of ontogeny and genetic variation to statin dose-exposure-response in children, and identifies important knowledge deficits to be addressed through the design of future studies.

Inhibition Of Soluble Tumor Necrosis Factor Ameliorates Synaptic Alterations And Ca2+ Dysregulation In Aged Rats, Diana M. Sama, Hafiz Mohmmad Abdul, Jennifer L. Furman, Irina A. Artiushin, David E. Szymkowski, Stephen W. Scheff, Christopher M. Norris

Graduate Center for Gerontology Faculty Publications

The role of tumor necrosis factor α (TNF) in neural function has been investigated extensively in several neurodegenerative conditions, but rarely in brain aging, where cognitive and physiologic changes are milder and more variable. Here, we show that protein levels for TNF receptor 1 (TNFR1) are significantly elevated in the hippocampus relative to TNF receptor 2 (TNFR2) in aged (22 months) but not young adult (6 months) Fischer 344 rats. To determine if altered TNF/TNFR1 interactions contribute to key brain aging biomarkers, aged rats received chronic (4-6 week) intracranial infusions of XPro1595: a soluble dominant negative TNF that preferentially inhibits …

Chemosensitization Of Hepatocellular Carcinoma To Gemcitabine By Non-Invasive Radiofrequency Field-Induced Hyperthermia, Mustafa Raoof

Dissertations and Theses (Open Access)

Gemcitabine is a potent nucleoside analogue against solid tumors however drug resistance rapidly emerges. Removal of gemcitabine incorporated in the DNA by repair mechanisms could potentially contribute to resistance in chemo-refractory solid tumors. In this study, we evaluated homologous recombination repair of gemcitabine-stalled replication forks as a potential mechanism contributing to resistance. We also studied the effect of hyperthermia on homologous recombination pathway to explain the previously reported synergy between gemcitabine and hyperthermia. We found that hyperthermia degrades and inhibits localization of Mre11 to gemcitabine-stalled replication forks. Furthermore, gemcitabine-treated cells that were also treated with hyperthermia demonstrate a prolonged passage …