Therapeutics Commons^™

Mechanism Of Fecal Bacteriotherapy In Treating Clostridium Difficile Infection And Gi Tract Disorders, Rivka Steinberg

The Science Journal of the Lander College of Arts and Sciences

Clostridium difficile infection, an increasingly prevalent and virulent condition, is often resistant to treatment. Standard antibiotic therapy is rarely efficient when used to treat recurrent C. difficile infection. Fecal microbiota transplantation (FMT) is a safe, effective and inexpensive treatment that has a cure rate of about 90%, according to clinical trials and reports. This approach may also be applicable in treating ulcerative colitis, a type of inflammatory bowel disease, on the basis of the restoration of flora imbalances. Additionally, recent data suggests that a disproportion in composition of the gut microbiome may contribute to obesity. FMT, may restore a healthy …

Does Music Therapy Reduce Anxiety Levels In End-Stage Renal Disease Patients Undergoing Hemodialysis?, Andrew C. Konopacki

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this selective EBM review is to determine whether or not music therapy reduces anxiety levels in end-stage renal disease patients undergoing hemodialysis.

STUDY DESIGN: Systematic Review of two randomized controlled trials and one crossover study published in English in 2008, 2012 and 2013, respectively.

DATA SOURCES: Two non-blind randomized controlled trials and one cross-over study were found via PubMed and EBSCOhost databases.

OUTCOMES MEASURED: Subjective Anxiety Levels were measured in ESRD patients undergoing hemodialysis pre and posttest via patient self-reporting. An anxiety level survey graded on a scale of 1-10 was used in the study by …

Selective Action Of Aqueous Maté Extract On Human Breast Cancer, Catherine Nguyen, Kenisha Nisbett, Vanessa Halvorsen, Calvin He, Amina Sadik

College of Osteopathic Medicine (TUN) Publications and Research

Ilex paraguariensis, Yerba Maté, is a subtropical plant native to South America, where it is consumed several times daily as a tea made with roasted leaves. Several studies have been conducted to elucidate the beneficial effects of this plant. A recent study has shown that saponins isolated from Yerba Maté extract induce apoptosis in human colon cancer cells, while another study indicated that the consumption of Maté tea causes higher incidence of esophageal cancer. Our study looked into the effects Yerba Maté extract have on human breast cancer cells and non-cancer cells from the same tissue. The findings show …

The Effect Of Neurostimulation On Ischemic Pain And Methods Of Assessing Pain, Kaylee Keck

Biomedical Engineering

Peripheral arterial disease (PAD) impacts approximately eight million people in the United States [1]. Disease progression leads to chronic ischemic pain, hindering quality of life. Pharmaceuticals are a typical treatment for pain associated with PAD; but as few as 30% of patients have a significant reduction of pain (≥50%) [2].

Neurostimulation is commonly used as a treatment for various diseases and injuries, including Parkinson’s disease and sports-related back and knee injuries [2]. The objective of the study was to explore neurostimulation and its effect on pain and paresthesia for a model of acute peripheral ischemia in young college students.

Pain …

Mice Null For The Deubiquitinase Usp18 Spontaneously Develop Leiomyosarcomas, Fadzai Chinyengetere, David J. Sekula, Yun Lu, Andrew J. Giustini, Aarti Sanglikar, Masanori Kawakami, Tian Ma

Dartmouth Scholarship

USP18 (ubiquitin-specific protease 18) removes ubiquitin-like modifier interferon stimulated gene 15 (ISG15) from conjugated proteins. USP18 null mice in a FVB/N background develop tumors as early as 2 months of age. These tumors are leiomyosarcomas and thus represent a new murine model for this disease.

Alkali Therapy In Lactic Acidosis, Zeid J. Khitan, Md, Deepak Malhotra, Md, Dominic S. Raj, Md, Antonios H. Tzamaloukas, Md, Joseph I. Shapiro, Md

Marshall Journal of Medicine

This report attempts to frame the debate about clinical administration of sodium bicarbonate in the setting of lactic acidosis in terms of simple questions. Specifically, we address why we develop lactic acidosis in some circumstances, how acute lactic acidosis impairs cardiovascular function and why sodium bicarbonate may have deleterious effects which limit its utility. We also attempt to explore treatment alternatives to sodium bicarbonate.

Adverse Effects Of Asparaginase In Pediatric Patients With Acute Lymphoblastic Leukemia, Chengcheng Liu

Theses and Dissertations (ETD)

Acute lymphoblastic leukemia (ALL) is the most common type of childhood cancer. Asparaginase is a critical treatment component for ALL. However, its use is complicated by adverse effects, such as hypersensitivity, osteonecrosis and pancreatitis.

Hypersensitivity to asparaginase typically requires discontinuation of current formulation and substitution with other formulations, but the differential diagnosis can be challenging, and the diagnostic utility of antibody tests is unclear. We comprehensively analyzed anti-Elspar (native E.coli asparaginase) IgG antibodies in 410 pediatric patients treated on an asparaginaseintensive front-line clinical trial. Of 169 patients (41.2%) who exhibited clinical allergy, 147 (87.0%) were positive for anti-Elspar antibody. Of …

A Novel Caspase 8 Selective Small Molecule Potentiates Trail-Induced Cell Death, Octavian Bucur, Gabriel Gaidos, Achani Yatawara, Bodvael Pennarun, Chamila Rupasinghe, Jérémie Roux, Stefan Andrei, Bingqian Guo, Alexandra Panaitiu, Maria Pellegrini, Dale Mierke, Roya Khosravi-Far

Dartmouth Scholarship

Recombinant soluble TRAIL and agonistic antibodies against TRAIL receptors (DR4 and DR5) are currently being created for clinical cancer therapy, due to their selective killing of cancer cells and high safety characteristics. However, resistance to TRAIL and other targeted therapies is an important issue facing current cancer research field. An attractive strategy to sensitize resistant malignancies to TRAIL-induced cell death is the design of small molecules that target and promote caspase 8 activation. For the first time, we describe the discovery and characterization of a small molecule that directly binds caspase 8 and enhances its activation when combined with TRAIL, …

Site-Specific Immunomodulator: A Novel Treatment For Crohn's Disease, Brian Bressler, Kevin P. Bethel, Ralf Kleef, Sophie L. Reynolds, Simon Sutcliffe, David W. Mullins, Hal Gunn

Dartmouth Scholarship

We investigated the mechanism of action, safety, and efficacy of the Site-Specific Immunomodulator (SSI) QBECO, a novel immunotherapy for Crohn’s disease (CD). Using human monocytic THP-1 cells, we demonstrate that SSI QBECO (derived from the common colon bacteria E. coli) activates macrophages to an M1 phenotype (associated with enhanced capacity to eliminate bacteria and activate innate immune responses). We assessed SSI QBECO in a compassionate use protocol of ten adult patients with active CD. Patients with moderate to severe clinical symptoms receiving conventional CD treatments and/or complementary therapies were included, except patients receiving anti-TNF medications. SSI QBECO was self-administered subcutaneously …

The Role Of Occupational Therapy In The Prevention Of Infant Torticollis & Plagiocephaly, Anne H. Zachry

Faculty Presentations

AOTA includes health promotion as an Intervention approach in the Occupational Therapy Practice Framework: Domain and Process. As health care professionals, occupational therapy practitioners are responsible for promoting public health and wellness. Occupational therapists need to educate parents and caregivers about the importance of varying infant positions, providing tummy time, and limiting infant time spent in baby gear.

Assessment Of Three Acute Responses To Traumatic Brain Injury, Shoshana Fireworker

The Science Journal of the Lander College of Arts and Sciences

Traumatic brain injury has a devastating effect on millions worldwide each year. As yet, there are no methods which have been proven to improve recovery from the trauma. Current treatment protocols revolve around reducing secondary insult, such as hypoxia, hypotension, and cerebral edema, which raises intracranial pressure. The purpose of this study is to assess the efficacy of three responses to traumatic brain injury. Two of them, the administration of hypertonic saline and the administration of progesterone, are pharmacologic, while the third, the performance of a decompressive craniectomy, is surgically invasive. A number of original studies have been analyzed to …

Active Immunotherapy And Adoptive Cell Transfer As An Effective Cancer Treatment, Philip Jay Cynamon

The Science Journal of the Lander College of Arts and Sciences

There are many ways to fight cancer using the body’s own immune system. Some methods include the administration of vaccines while others involve stimulatory factors injected near tumors. One promising method is enlisting the help of T cells. To fight cancer effectively, T cells must be able to recognize cancerous antigens and the environment in which these T cells reside must be conducive to their function, survival, and proliferation. This paper discusses a method of providing such an environment called adoptive cell transfer, as well as the elements that effect this protocol and the ways in which the environment can …

Tuberculosis As A Metaphor For Isolation: An Interdisciplinary Examination Of Tuberculosis, Stefanie Pavlick 15

Honor Scholar Theses

No abstract provided.

Empagliflozin In The Treatment Of Type 2 Diabetes: Evidence To Date, Jay H. Shubrook, Babak Baradar Bokaie, Sarah E. Adkins

Faculty Publications & Research of the TUC College of Osteopathic Medicine

In the last decade, researchers have gained a greater understanding of the pathophysiologic mechanisms of type 2 diabetes as a chronic and progressive disease. One of the more recent treatment targets is the kidney. The kidneys become maladaptive in diabetes by increasing the reabsorption of glucose above the normal physiologic renal threshold. This discovery has led to the development of the sodium/glucose cotransporter 2 inhibitors (SGLT2). These agents readjust the renal threshold for glucose reabsorption to a lower level and decrease glucose reabsorption, while increasing urinary glucose when the glucose is above the renal threshold and subsequently lowering plasma glucose. …

The Effect Of Statin Therapy On Heart Failure Events: A Collaborative Meta-Analysis Of Unpublished Data From Major Randomized Trials, David Preiss, Ross T. Campbell, Heather M. Murray, Ian Ford, Chris J. Packard, Naveed Sattar, Michael B. Clearfield

Faculty Publications & Research of the TUC College of Osteopathic Medicine

Aims: The effect of statins on risk of heart failure (HF) hospitalization and HF death remains uncertain. We aimed to establish whether statins reduce major HF events.

Methods and results: We searched Medline, EMBASE, and the Cochrane Central Register of Controlled Trials for randomized controlled endpoint statin trials from 1994 to 2014. Collaborating trialists provided unpublished data from adverse event reports. We included primary- and secondary-prevention statin trials with >1000 participants followed for >1 year. Outcomes consisted of first non-fatal HF hospitalization, HF death and a composite of first non-fatal HF hospitalization or HF death. HF events occurring(MI) were excluded. …

What To Do After Basal Insulin: 3 Tx Strategies For Type 2 Diabetes, Lubaina Presswala, Jay H. Shubrook

Faculty Publications & Research of the TUC College of Osteopathic Medicine

While many family physicians have become comfortable with using once-daily basal insulin such as glargine or detemir, what to do after basal insulin is much more complex. This review builds upon an earlier article in this journal, “Insulin for type 2 diabetes: How and when to get started,” by explaining 3 strategies to consider when basal insulin alone isn't enough.

Effect Of Tai Chi Exercise Combined With Mental Imagery Theory In Improving Balance In A Diabetic And Elderly Population, Abdulrahman Alsubiheen, Jerrold S. Petrofsky, Noha S. Daher, Everett Lohman, Edward Balbas

College of Health & Human Services (TUN) Publications and Research

BACKGROUND: One of the effects of diabetes mellitus (DM), peripheral neuropathy, affects the sensation in the feet and can increase the chance of falling. The purpose of the study was to investigate the effect of 8 weeks of Tai Chi (TC) training combined with mental imagery (MI) on improving balance in people with diabetes and an age matched control group.
MATERIAL AND METHODS: Seventeen healthy subjects and 12 diabetic sedentary subjects ranging from 40–80 years of age were recruited. All subjects in both groups attended a Yang style of TC class using MI strategies, 2 sessions a week …

Treating Acute Migraines: Triptans Vs. Antiemetics, Samuel Reisman

The Science Journal of the Lander College of Arts and Sciences

Influential American medical organizations and publications have published guidelines for the treatment of acute migraine headaches that omit antiemetics, usually suggesting triptans as the first line of treatment. A review of the few comparative studies directly contrasting clinical outcomes of triptans and antiemetics in the treatment of acute migraines suggest that both treatment options are relatively equal in efficaciousness. The added burden of triptan usage, including an added risk of adverse effects and a high cost per dose, would seem to warrant an antiemetic-first approach to migraine treatment, as recommended by several international health communities. Possible reasons for the prominent …

Transposon Based Gene Therapy As A Treatment For Cancer, Jacob Stauber

The Science Journal of the Lander College of Arts and Sciences

Gene therapy is the use of genes to treat or prevent diseases. Diseases such as cancer, which are difficult to treat using conventional methods, can be treated using gene therapy. The transport of the therapeutic transgene can be accomplished using viral or non-viral methods. However, widespread use of viral vectors is limited due to its high cost of manufacture and safety concern. Non-viral vectors are limited in their effectiveness. The use of transposons such as the Sleeping Beauty transposon system can effectively deliver the transgene with less concern than viral vectors. This review discusses the various vectors and treatment strategies …

Is Proton Beam Therapy More Effective Than Intensity-Modulated Radiotherapy In Prostate Cancer Treatment?, Daniel Zelefsky

The Science Journal of the Lander College of Arts and Sciences

Prostate cancer is the most common form of cancer found in American males. Breaking technological advances in prostate cancer treatment continue to develop to help fight this disease, one such is proton beam therapy. Proton beam therapy is theorized to spare even more healthy tissue than photon radiotherapy because it delivers a majority of its radiation during the Bragg peak. Since this technology is substantially costlier than any other form of radiation therapy, physicians are assessing its effectiveness and determining if it is worth the cost. Currently, there is no significant difference seen in patient quality of life between recipients …

Is The Neuraminidase Inhibitor Tamiflu Effective In The Treatment Of Influenza?, Eliyakim Hershkop

The Science Journal of the Lander College of Arts and Sciences

Influenza is a disease that has caused the deaths of tens of millions people in the last century alone. The influenza neuraminidase protein is essential in the mechanism infection. It enables the virus to leave the infected cell and proliferate. Antiviral neuraminidase inhibitor drugs can be used for treatment. The drug Tamiflu is the standard of care for both treatment and prophylaxis of influenza. The Cochrane reports of 2009 and 2014 conclude that evidence is lacking to support this. Numerous bodies disagree. Cochrane also question the accuracy and credibility of many studies and agencies in support of Tamiflu. This paper …

Biological Therapy In The Treatment Of Ulcerative Colitis, Tzipora Glanzman

The Science Journal of the Lander College of Arts and Sciences

Ulcerative colitis (UC), a subdivision of inflammatory bowel disease, is a chronic disease of the large intestines. Ulcerative colitis is normally a lifelong chronic illness with times of intense flairs and remission. During a flare, the lining of the colon becomes inflamed, and develops small ulcers causing patients to experience rectal bleeding, vomiting, anemia and diarrhea. The treatment options available to treat colitis are very small, causing many patients to need a total colectomy with in the first five years of their diagnosis. However, recent advancement in bio-technology has led to the development of a large array of new therapeutic …

Program Active Ii: Design And Methods For A Multi-Center Community-Based Depression Treatment For Rural And Urban Adults With Type 2 Diabetes, Mary De Groot, Jay H. Shubrook, Frank Schwartz, W. Guyton Hornsby Jr., Yegan Pillay, Chandan Saha

Faculty Publications & Research of the TUC College of Osteopathic Medicine

Objective: Depression affects one in four adults with type 2 diabetes (T2DM) and is associated with worsened diabetes complications, increased health care costs and early mortality. Rural and low-income urban areas, including the Appalachian region, represent an epicenter of the T2DM epidemic. Program ACTIVE II is a comparative effectiveness treatment trial designed to test whether a combination of cognitive behavioral therapy (CBT) and community-based exercise (EXER) will offer greater improvements in diabetes and depression outcomes compared to individual treatment approaches and usual care (UC). The secondary aims are to assess changes in cardiovascular risk factors across groups and to …

Is Yoga Effective In Reducing Fibromyalgia-­Related Symptoms In Women With Fibromyalgia?, Molly R. Beckmann

PCOM Physician Assistant Studies Student Scholarship

Objective: The objective of this selective EBM review is to determine whether or not yoga is effective in reducing fibromyalgia-related symptoms in women with fibromyalgia.

Study Design: Review of two published double blind, randomized controlled trials published in 2010 and one before-after study published in 2012 were used for this review and selected based on their relevance to the clinical question

Data Source: Studies were found using PubMed, AMED, and CINAHL Plus.

Outcomes Measured: All three studies measured improvement of fibromyalgia symptoms based on a variety of well-validated measures, most notably the Fibromyalgia Impact Questionnaire, the Quality of Life Profile …

Does Balneotherapy Effectively Reduce Non-Specific Chronic Low Back Pain In Adults?, Jenna Srebnik

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this selective EBM review is to determine whether or not balneotherapy effectively reduces non-specific chronic low back pain in adults.

STUDY DESIGN: Review of three single blind, follow up randomized controlled trials (RCT), published in 2012 and 2005.

DATA SOURCES: Three peer reviewed RCTs were found using PubMed and all compared balneotherapy against various control groups.

OUTCOMES MEASURED: Low back pain of patients was assessed using dose of analgesic consumed, visual analog pain scale (VAS) and Oswestry Low Back Pain Disability Questionnaire (OSWDQ). The tools used to assess significance of outcomes measured were Pvalues, change in …

Dysregulation Of Micrornas In Blood As Biomarkers For Diagnosing Prostate Cancer, Rhonda W. Daniel

Theses and Dissertations

Prostate cancer is the most common noncutaneous cancer among men, yet current diagnostic methods are insufficient and more reliable diagnostic markers need to be developed. The answer that can bridge this gap and enable more efficient diagnoses may lie in microRNAs. These small, single stranded RNA molecules impact protein expression at the translational level and regulate important cellular pathways. Dysregulation of these small RNA molecules can have tumorigenic effects on cells and lead to many types of cancers.

Currently the Prostate-Stimulating Antigen (PSA) is used as a diagnostic marker for prostate cancer. However, many factors can elevate PSA levels such …

Effects Of Pde4 Pathway Inhibition In Rat Experimental Stroke, Fan Yang, Rachita K. Sumbria, Dong Xue, Chuanhui Yu, Dan He, Shuo Liu, Annlia Paganini-Hill, Mark J. Fisher

Pharmacy Faculty Articles and Research

PURPOSE: The first genomewide association study indicated that variations in the phosphodiesterase 4D (PDE4D) gene confer risk for ischemic stroke. However, inconsistencies among the studies designed to replicate the findings indicated the need for further investigation to elucidate the role of the PDE4 pathway in stroke pathogenesis. Hence, we studied the effect of global inhibition of the PDE4 pathway in two rat experimental stroke models, using the PDE4 inhibitor rolipram. Further, the specific role of the PDE4D isoform in ischemic stroke pathogenesis was studied using PDE4D knockout rats in experimental stroke. METHODS: Rats were subjected to either the …

Characterizing The Response Of Multidrug-Resistant Klebsiella Pneumoniae Species To The Application Of A Phage Cocktail, Steven Liu

Symposium

Project Summary: The application of bacteriophages to treat bacterial infections is known as phage therapy, which takes advantage of bacteriophage’s natural ability to infect and lyse bacterial hosts. Phages have been shaped by billions of years of evolution to be highly specialized deliverers of bactericidal agents to the cytoplasm of their target bacteria. Ever since discovery of bacteriophages in 1915, phage therapy was recognized as a potentially powerful tool for eliminating bacterial infections. The effectiveness of phage therapy can be increased by creating a mixture of multiple phages to target a wider variety of bacterial strains. Furthermore, phage therapy has …

Endothelial And Smooth Muscle-Dependent Vascular Reactivity In Immature Arterialized Collateral Capillaries, Caitlin Koeroghlian

Biomedical Engineering

Peripheral arterial occlusive disease (PAOD) occurs due to the build up of atherosclerotic plaque and reduces blood flow to cause chronic ischemia. Patients with PAOD may experience intermittent claudication, or the pain in limb skeletal muscles due to a decease in blood flow. Collateral arteries can act as a natural bypass and improve blood flow to hypoxic tissue by creating an alternate route for blood to flow, but not all patients with PAOD have pre-existing collateral networks. Animal studies indicate that tissues without pre-existing collateral networks can form de novo collaterals from capillaries following occlusion of a feed artery. Unfortunately, …

Predicting Targeted Drug Combinations Based On Pareto Optimal Patterns Of Coexpression Network Connectivity, Nadia M. Penrod, Casey S. Greene, Jason H. Moore

Dartmouth Scholarship

Molecularly targeted drugs promise a safer and more effective treatment modality than conventional chemotherapy for cancer patients. However, tumors are dynamic systems that readily adapt to these agents activating alternative survival pathways as they evolve resistant phenotypes. Combination therapies can overcome resistance but finding the optimal combinations efficiently presents a formidable challenge. Here we introduce a new paradigm for the design of combination therapy treatment strategies that exploits the tumor adaptive process to identify context-dependent essential genes as druggable targets. We have developed a framework to mine high-throughput transcriptomic data, based on differential coexpression and Pareto optimization, to investigate drug-induced …