Medicine and Health Sciences Commons^™

Effect Of Chemotherapeutic Treatment Schedule On A Tissue Transport Model, Dan E. Ganz

Masters Theses

Current chemotherapeutic treatment schedule prediction methods rely heavily on PK/PD-based models and overlook the important contribution of tissue-level transport and binding. Tissue-level transport and binding phenomena are essential to understanding drug delivery and efficacy in tumors. Drugs with desirable PK/PD properties often fail in vivo due to poor tissue-level transport. We developed an in silico method to predict the effect of treatment schedule on efficacy that couples PK/PD with tissue-level transport. Treatment schedules were implemented on theoretical drugs with different PK/PD and transport properties. For each drug with a given clearance rate, diffusivity, and binding, treatment schedules consisting of one …

What Is Pfapa And Why Does It Matter?, Dennis J. Baumgardner

Journal of Patient-Centered Research and Reviews

PFAPA, the syndrome of periodic fever, aphthous stomatitis, pharyngitis and cervical lymphadentitis, is an uncommon disease of episodic immune dysregulation that usually begins in early childhood. Symptoms occur at regular, predictable intervals, with healthy periods in between, and generally include the namesake signs and various other constitutional symptoms such as fever and fatigue. The etiology is unknown and there is no definitive diagnostic test or treatment. Uncertainty during the period of searching for a diagnosis may be disconcerting to the family and the clinician. Single-dose prednisone is effective for resolving the fever of PFAPA episodes within just a few hours, …

Antipsychotic Use In Nursing Homes Varies By Psychiatric Consultant, Jennifer Tjia, Terry Field, Celeste Lemay, Kathleen Mazor, Michelle Pandolfi, Ann Spenard, Shih-Yieh Ho, Abir Kanaan, Jennifer Donovan, Jerry Gurwitz, Becky Briesacher

Jennifer Tjia

BACKGROUND: The relationship between psychiatric consultation and antipsychotic prescribing in nursing homes (NH) is unknown. OBJECTIVE: To identify the association between psychiatric consultant groups and NH-level antipsychotic prescribing after adjustment for resident case-mix and facility characteristics. RESEARCH DESIGN AND SUBJECTS: Nested cross-sectional study of 60 NHs in a cluster randomized trial. We linked facility leadership surveys to October 2009-September 2010 Minimum Data Set, Nursing Home Compare, the US Census, and pharmacy dispensing data. MEASURES: The main exposure is the psychiatric consultant group and the main outcome is NH-level prevalence of atypical antipsychotic use. We calculated annual means and interquartile ranges …

Desktop Medicine, Jason Karlawish

Jason Karlawish

No abstract provided.

Derivation And Validation Of Cutoffs For Clinical Use Of Cell Cycle Arrest Biomarkers, Eric A.J. Hoste, Peter A. Mccullough, Kianoush Kashani, Lakhmir S. Chawla, Michael Joannidis, The Sapphire Investigators

Anesthesiology and Critical Care Medicine Faculty Publications

Background

Acute kidney injury (AKI) remains a deadly condition. Tissue inhibitor of metalloproteinases (TIMP)-2 and insulin-like growth factor binding protein (IGFBP)7 are two recently discovered urinary biomarkers for AKI. We now report on the development, and diagnostic accuracy of two clinical cutoffs for a test using these markers.

Methods

We derived cutoffs based on sensitivity and specificity for prediction of Kidney Disease: Improving Global Outcomes Stages 2–3 AKI within 12 h using data from a previously published multicenter cohort (Sapphire). Next, we verified these cutoffs in a new study (Opal) enrolling 154 critically ill adults from six sites in the …

Nanofluidity Of Fatty Acid Hydrocarbon Chains As Monitored By Benchtop Time-Domain Nuclear Magnetic Resonance, David P. Cistola

David P Cistola

The functional properties of lipid-rich assemblies such as serum lipoproteins, cell membranes, and intracellular lipid droplets are modulated by the fluidity of the hydrocarbon chain environment. Existing methods for monitoring hydrocarbon chain fluidity include fluorescence, electron spin resonance, and nuclear magnetic resonance (NMR) spectroscopy; each possesses advantages and limitations. Here we introduce a new approach based on benchtop time-domain 1H NMR relaxometry (TD-NMR). Unlike conventional NMR spectroscopy, TD-NMR does not rely on the chemical shift resolution made possible by homogeneous, high-field magnets and Fourier transforms. Rather, it focuses on a multiexponential analysis of the time-decay signal. In this study, we …

Intravenous Angiotensin Ii For The Treatment Of High-Output Shock (Athos Trial): A Pilot Study, Lakhmir S. Chawla, Laurence Busse, Ermira Brasha-Mitchell, Danielle L. Davison, Jacqueline R. Honig, Ziyad Alotaibi, Michael G. Seneff

Anesthesiology and Critical Care Medicine Faculty Publications

Introduction: Patients with distributive shock who require high dose vasopressors have a high mortality. Angiotensin II (ATII) may prove useful in patients who remain hypotensive despite catecholamine and vasopressin therapy. The appropriate dose of parenteral angiotensin II for shock is unknown.

Methods: In total, 20 patients with distributive shock and a cardiovascular Sequential Organ Failure Assessment score of 4 were randomized to either ATII infusion (N?=?10) or placebo (N?=?10) plus standard of care. ATII was started at a dose of 20?ng/kg/min, and titrated for a goal of maintaining a mean arterial pressure (MAP) of 65?mmHg. The infusion (either ATII or …

Effects Of Yoga On Arm Volume Among Women With Breast Cancer Related Lymphedema: A Pilot Study, Mary Insana Fisher, Betsy Donahoe-Fillmore, Laura Leach, Colleen O'Malley, Cheryl Paeplow, Tess Prescott, Harold L. Merriman

Physical Therapy Faculty Publications

Lymphedema affects 3–58% of survivors of breast cancer and can result in upper extremity impairments. Exercise can be beneficial in managing lymphedema. Yoga practice has been minimally studied for its effects on breast cancer related lymphedema (BCRL). The purpose of this study was to determine the effect of yoga on arm volume, quality of life (QOL), self-reported arm function, and hand grip strength in women with BCRL. Six women with BCRL participated in modified Hatha yoga 3×/week for 8 weeks. Compression sleeves were worn during yoga sessions. Arm volume, QOL, self-reported arm function, and hand grip strength were measured at …

Cancer Survivorship Care: An Emphasis On Rehabilitation Needs In Maine, Miranda Carlson, Nicole Christine, Charles Dowd, Cassandra Dawley, Irina Fedulow, Lisa Gerhardt, Erin Pike, Kaitlin Powers, Angela Serrani

Disease Prevention and Health Promotion Papers

The first section of this report addresses the evidence of causation concerning impairments developed as a result of a cancer diagnosis and cancer treatment. The second section investigates the evidence regarding rehabilitation and physical activity as an effective intervention in the prevention and treatment of impairments from cancer diagnosis and cancer treatment. The third section discusses the underlying behavioral change theory for incorporation of our Cancer Survivorship Rehabilitation Algorithm (Appendix 1), which details our proposed use of rehabilitation and wellness services in the continuum of cancer care and includes an outline for a survivorship care plan. This section also discusses …

Normative Scores For The Nih Toolbox Dynamic Visual Acuity Test From 3 To 85 Years, Carol Li, Jennifer L. Beaumont, Rose Marie Rine, Jerry Slotkin, Michael C. Schubert

Physical Therapy Faculty Research

As part of the National Institutes of HealthToolbox initiative, a computerized test of dynamic visual acuity (cDVA) was developed and validated as an easy-to-administer, cost- and timeefficient test of vestibular and visual function. To establish normative reference values, 3,992 individuals, aged 3–85 years, without vestibular pathology underwent cDVA testing at multiple clinical research testing facilities across the United States. Test scores were stratified by sociodemographic characteristics. cDVA was worse in males (p <0.001) and those subjects 50 years or older, while there was no difference in dynamic visual acuity across age groups binned from 3 to 49 years. Furthermore, we used these normative cDVA data as a criterion reference to compare both the long (validated) and short versions of the test. Both versions can distinguish between those with and without vestibular pathology (p D0.0002 long; p D0.0025 short). The intraclass correlation coefficient between longand short-cDVA tests was 0.86.

Quantifying The Effect Of A Novel Topical Hyaluronic-Acid Phosphatidylethanolamine Cream On The Epidermis, Caitlin J. Symonette

Electronic Thesis and Dissertation Repository

With aging, keratinocytes have diminished proliferative capacity resulting in atrophic skin with reduced barrier function. This investigation evaluates the effect of daily topical applications of a novel high-molecular weight hyaluronan cream (HA-PE) on keratinocyte renewal and epidermal thickness. Unmodified hyaluronan and HA-PE were mixed separately into a vehicle cream. Each topical formulation was applied daily onto the shaved backs of aged female C57BL6 mice. Full-thickness biopsies of treated skin were obtained for analysis of keratinocyte proliferation, keratinocyte differentiation, and local inflammation at days 1, 5, and 10 of cream application. In addition, a cardiac puncture was performed for serum C-reactive …

Development Of A Fatal Noncompressible Truncal Hemorrhage Model With Combined Hepatic And Portal Venous Injury In Normothermic Normovolemic Swine, Ujwal R. Yanala, Jason M. Johanning, Iraklis I. Pipinos, Gustavo F. Larsen, William H. Velander, Mark A. Carlson

William H. Velander Publications

Noncompressible truncal hemorrhage and brain injury currently account for most early mortality of warfighters on the battlefield. There is no effective treatment for noncompressible truncal hemorrhage, other than rapid evacuation to a surgical facility. The availability of an effective field treatment for noncompressible truncal hemorrhage could increase the number of warfighters salvaged from this frequently-lethal scenario. Our intent was to develop a porcine model of noncompressible truncal hemorrhage with a ,50% one-hour mortality so that we could develop new treatments for this difficult problem. Normovolemic normothermic domestic swine (barrows, 3 months old, 34–36 kg) underwent one of three injury types …

Sorting Reality From What We Think We Know About Breast Cancer In Africa, Sulma I. Mohammed, Joe B. Harford

Department of Comparative Pathobiology Faculty Publications

Much attention has been paid to the features of breast cancer in Africa and the parallels between breast cancer in indigenous Africans and in African American women, including a shift toward earlier onset; a tendency toward poorer outcomes; and an increased likelihood for the tumors to be negative for the estrogen receptor (ER), the progesterone receptor (PR), and/or the human epidermal growth factor receptor-2 (HER2) [1,2]. One of the more aggressive forms of breast cancer is termed ‘‘triple negative,’’ i.e., ER2, PR2, HER22 [3]. Patients with triple negative breast cancer tend to be younger than patients with other forms of …

Ligand-Receptor Interactions For Supramolecular Disassembly With Applications In Screening And Drug Delivery, Diego Amado Torres

Doctoral Dissertations

Proteins have the capacity to bind specific sets of compounds known as ligands, these are small molecules with a recurrent theme in their molecular design that is a characteristic exploited here to (i) identify particular affinities of small molecules for proteins with the aim of using them as ligands, inhibitors, or targeting moieties in more complex systems by means of a methodology that screens small molecules based on protein affinity; (ii) decorate a self-assembling supramolecular system at different positions, making it responsive to a complementary protein with the aim of exploring differences in disassembly and sensitivity of the release of …

Surgical Approach In Total Hip Arthroplasty: Patient Outcomes And Impact On Costs, Stephen M. Petis

Electronic Thesis and Dissertation Repository

Total hip arthroplasty is often renowned as one of the most important surgical advances of the past century. Orthopaedic surgeons must choose a surgical approach to gain access to the hip joint in order to perform the reconstruction. There is debate in the literature as to which surgical approach optimizes patient outcomes, minimizes complications, and reduces costs to hospitals as a high volume procedure.

In the current studies, patient reported outcomes were compared at short-term follow-up using a prospective study design across the anterior, posterior, and lateral approach. A micro-costing method was used to acquire costs related to each procedure, …

Design And Development Of A Miniature In Vivo Surgical Robot With Distributed Motor Control For Laparoendoscopic Single-Site Surgery, Eric J. Markvicka

Department of Mechanical and Materials Engineering: Dissertations, Theses, and Student Research

Paradigm shifts in invasiveness, recovery time, cosmesis, and cost have been seen within the field of general surgery through major advances in surgical technology. Some of the most advanced types of general surgery now include Minimally Invasive Surgery (MIS), LaparoEndoscopic Single-Site (LESS) surgery, and Natural Orifice Translumenal Endoscopic Surgery (NOTES). One of the newest and rapidly developing catalysts is robotic platforms. Such platforms have improved ergonomics and control, increased workspace and dexterity, and have surpassed the efficacy of many non-robotic platforms such as traditional laparoscopic surgical tools. This thesis presents the design and development of a four-degree-of-freedom (4- DOF) miniature …

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 …

Evaluating Human Performance For Image-Guided Surgical Tasks, Matthew Kenneth Kramers

Electronic Thesis and Dissertation Repository

The following work focuses on the objective evaluation of human performance for two different interventional tasks; targeted prostate biopsy tasks using a tracked biopsy device, and external ventricular drain placement tasks using a mobile-based augmented reality device for visualization and guidance. In both tasks, a human performance methodology was utilized which respects the trade-off between speed and accuracy for users conducting a series of targeting tasks using each device. This work outlines the development and application of performance evaluation methods using these devices, as well as details regarding the implementation of the mobile AR application. It was determined that the …

Towards Highly-Integrated Stereovideoscopy For In Vivo Surgical Robots, Jay Carlson

Department of Electrical and Computer Engineering: Dissertations, Theses, and Student Research

When compared to traditional surgery, laparoscopic procedures result in better patient outcomes: shorter recovery, reduced post-operative pain, and less trauma to incisioned tissue. Unfortunately, laparoscopic procedures require specialized training for surgeons, as these minimally-invasive procedures provide an operating environment that has limited dexterity and limited vision. Advanced surgical robotics platforms can make minimally-invasive techniques safer and easier for the surgeon to complete successfully. The most common type of surgical robotics platforms -- the laparoscopic robots -- accomplish this with multi-degree-of-freedom manipulators that are capable of a diversified set of movements when compared to traditional laparoscopic instruments. Also, these laparoscopic robots …

Utilizing Haplotypes For Sensitive Snp Array-Based Discovery Of Somatic Chromosomal Mutations, Selina M. Vattathil

Dissertations & Theses (Open Access)

Somatic copy-number (CN) gains and losses and copy-neutral loss of heterozygosity (CNLOH) frequently occur in tumors and play a major role in the progression of disease by altering gene dosage and unmasking deleterious recessive variants. Characterizing these mutations in an individual tumor sample is therefore critical for research on the relationship of specific mutations to disease outcome and for clinical decision-making based on mutations with known impact. A pervasive hindrance to sensitive detection of these mutations is genetic heterogeneity and high levels of contaminating normal cells in tumor samples, which limit the fraction of cells carrying informative mutations. The method …

Joint Reaction Force And Contributions Of Surrounding Muscles To Knee Joint Load During Stair Ascent In Total Knee Replacement Patients And Healthy Individuals, Robert Jacob Rasnick

Masters Theses

Total knee replacement (TKR) is commonly used to correct end stage knee osteoarthritis (OA) of the knee joint. Unfortunately, difficulty with stair climbing has been seen to exist, prolonging the challenges of TKR patents. Complete understanding of loading at the knee is of great interest in order to aid patient populations, implant manufacturers, rehabilitation, and future research. The outcome of a TKR is intended to reestablish normal motion and loading of the knee. Musculoskeletal modeling provides a means to accurately approximate joint loading and the corresponding muscle contributions during a movement.

The purpose of the present study was to examine …

Determination Of The Functional Relationship Between Lumbar Lordosis And Pelvic Tilt, Casey Tyler Hebert

Theses and Dissertations (ETD)

Americans are undergoing spinal fusion surgery (SFS) at an ever increasing rate; in 2008 over 400,000 Americans underwent SFS with a national cost of approximately $33.9 billion. During SFS it is difficult for the surgeon to properly align the spine’s s-shape, as viewed from the patient’s side. Abnormal alignment of the spine then alters the position of the pelvis and hip joints, which may impact the function and hip contact patterns. Several studies have shown that patients with spinal pathology, such as arthritis, often have a coexisting hip pathology or subsequently develop hip pathology, and it is estimated that 18% …

Fluid Powered Miniature In-Vivo Robots For Minimally Invasive Surgery (Mis), Abolfazl Pourghodrat

Department of Mechanical and Materials Engineering: Dissertations, Theses, and Student Research

Minimizing the invasiveness of surgery is believed to improve patient outcomes. Bleeding, infection, and pain are major concerns in surgery afflicting patients for decades. Minimally invasive techniques have come into play to reduce these concerns and smooth the evolution of abdominal surgery to a scarless process where nearly all surgeries can be performed without a skin incision. Technology continually advances the frontier of development of novel surgical devices to implement less invasive surgical techniques.

Fusion of robotics and Minimally Invasive Surgery (MIS) has created new opportunities to develop diagnostic and therapeutic tools. Surgical robotics is advancing from externally actuated systems …

The Kras/Mapk Pathway And Ligand Independent Activation Of Erα: Implications For The Treatment Of Endometrial Cancer, Kari Ring

Dissertations & Theses (Open Access)

Hormonal therapy remains a first line option for the treatment of recurrent endometrial cancer (EC), however, many tumors demonstrate de novo or acquired resistance. Member kinases of the PI3K/AKT and Ras/MAPK pathways activate estrogen receptor α (ERα) independent of estrogen, however, few studies have evaluated the role of the Ras/MAPK pathway in predicting response to hormonal therapy in EC. The aims of this project were to evaluate the role of ligand independent activation of ERα in EC and to explore therapeutic implications for the treatment of recurrent EC.

A xenograft model for recurrent EC was used to evaluate the effect …

Nerve Fiber Diameter Measurements Using Hematoxylin And Eosin Staining And Brightfield Microscopy To Assess The Novel Method Of Characterizing Peripheral Nerve Fiber Distributions By Group Delay, Jorge Arturo Vazquez

Master's Theses

Peripheral neuropathies are a set of common diseases that affect the peripheral nervous system, causing damage to vital connections between various parts of the body and the brain and spinal cord. Different clinical conditions are known to selectively impact various size nerve fibers, which often makes it difficult to diagnose which peripheral neuropathy a patient might have. The nerve conduction velocity diagnostic test provides clinically useful information in the diagnosis of some peripheral neuropathies. This method is advantageous because it tends to be minimally invasive yet it provides valuable diagnostic information. However, this test does not determine characteristics of peripheral …

Development Of A Molecular Gram-Stain Assay For The Diagnosis Of Blood Stream Infections Associated With Sepsis, Douglas Bryan Litwin

Dissertations & Theses (Open Access)

Sepsis is a serious medical condition resulting from the severe dysregulation of the immune response that is generally triggered by infection. It affects more than 1.1 million Americans, has an average mortality rate of 30%, and is estimated to cost $24.3 billion annually. Currently, blood culture followed by Gram-stain analysis is the gold standard for diagnosing bacterial infections associated with sepsis. This method generates a high rate of false negative results and, in general, requires 20 to 48 hr to provide results. Both of these problems are related to the requirement that the bacterial pathogens grow under defined laboratory conditions. …

Production Of Recombinant Human Coagulation Factor Ix By Transgenic Pig, Weijie Xu

Department of Chemical and Biomolecular Engineering: Theses and Student Research

Hemophilia B is the congenital bleeding disorder caused by deficiency in functional coagulation factor IX (FIX) and about 28,000 patients worldwide in 2012. And current treatment is restricted to protein-replacement therapy, which required FIX concentrates for patients’ life-time. Approximately 1 billion units FIX were consumed in 2012. However, still about 70-80% patients, mostly in developing countries, received inadequate or no treatment because of the unavailable and/or unaffordable FIX concentrates. Considering safety reasons, e.g. transmission of blood-borne diseases, the recombinant human FIX (rFIX) is recommended other than the plasma-derived FIX. However, only one rFIX is currently available on the market. The …

Quantitative Ultrasound: Measurement Considerations For The Assessment Of Muscular Dystrophy And Sarcopenia, Michael O. Harris-Love, Reza Monfaredi, Catheeja Ismail, Marc R. Blackman, Kevin Cleary

Exercise and Nutrition Sciences Faculty Publications

Diagnostic musculoskeletal ultrasound has potential clinical utility in characterizing pathological muscle tissue. Sonography has been long proposed as method of assessing muscle damage due to neuromuscular diseases such as muscular dystrophy, and more recently, changes in body and tissue composition associated with muscle wasting disorders such as sarcopenia. The use of quantitative ultrasound as an adjunct diagnostic procedure has different technical challenges than the traditional use of ultrasound in clinical medicine. Operator-dependent technique and variation are critical considerations when obtaining measures of echointensity (i.e., tissue composition estimates) and tissue dimensions (i.e., muscle thickness) – key elements of the ultrasound assessment …

Development Of A Short Version Of The Modified Yale Preoperative Anxiety Scale, Brooke N. Jenkins, Michelle Fortier, Sherrie H. Kaplan, Linda C. Mayes, Zeev N. Kain

Psychology Faculty Articles and Research

BACKGROUND: The modified Yale Preoperative Anxiety Scale (mYPAS) is the current “criterion standard” for assessing child anxiety during induction of anesthesia and has been used in >100 studies. This observational instrument covers 5 items and is typically administered at 4 perioperative time points. Application of this complex instrument in busy operating room (OR) settings, however, presents a challenge. In this investigation, we examined whether the instrument could be modified and made easier to use in OR settings.

METHODS: This study used qualitative methods, principal component analyses, Cronbach αs, and effect sizes to create the mYPAS-Short Form (mYPAS-SF) and reduce time …

Two Brief Interventions For Acute Pain, Stephen Bruehl, Charles Carlson, James Mccubbin

James A. McCubbin

This study evaluated two brief (3–5 min) interventions for controlling responses to acute pain. Eighty male subjects were randomly assigned to 1 of 2 intervention groups (Positive Emotion Induction (PEI) or Brief Relaxation (BR)) or to 1 of 2 control groups (No-instruction or Social Demand). The PEI focused on re-creating a pleasant memory, while the BR procedure involved decreasing respiration rate and positioning the body in a relaxed posture. All subjects underwent a 60-sec finger pressure pain trial. Analyses indicated that the PEI subjects reported lower ratings of pain, fear, and anxiety, and experienced greater finger temperature recovery than controls. …