Medicine and Health Sciences Commons^™

Effects Of Thymus Size And Involution On The Contribution Of Recent Thymic Emigrants To The Peripheral T Cell Pool, Michelle L. Bolner

Dissertations and Theses (Open Access)

The contribution of recent thymic emigrants (RTEs) to the peripheral naïve T cell population is necessary to maintain diversity of the T cell receptor (TCR) repertoire and produce immune responses against newly encountered antigens.

The thymus involutes with age, after irradiation or chemotherapy, and due to severe viral infections. Thymus involution results in decreased thymopoiesis and RTE output leading to a reduced diversity of peripheral T cells. This increases susceptibility to disease and impairs immune responsiveness to vaccines. Therefore, studies aimed at maintaining or regenerating thymic function are integral for maintaining and restoring peripheral TCR diversity.

Mice that express a …

Increased Geranylgeranylated K-Ras Contributes To Antineoplastic Effects Of Farnesyltransferase Inhibitors., Mandy A. Hall

Dissertations and Theses (Open Access)

The Ras family of small GTPases (N-, H-, and K-Ras) is a group of important signaling mediators. Ras is frequently activated in some cancers, while others maintain low level activity to achieve optimal cell growth. In cells with endogenously low levels of active Ras, increasing Ras signaling through the ERK and p38 MAPK pathways can cause growth arrest or cell death. Ras requires prenylation – the addition of a 15-carbon (farnesyl) or 20-carbon (geranylgeranyl) group – to keep the protein anchored into membranes for effective signaling. N- and K-Ras can be alternatively geranylgeranylated (GG’d) if farnesylation is inhibited but are …

Cellular Trafficking Of Single And Multistage Vectors, Silvia Ferrati

Dissertations and Theses (Open Access)

Nanomedicine is an innovative field of science which has recently generated many drug delivery platforms with exciting results. The great potential of these strategies rely on the unique characteristics of the devices at the nano-scale in terms of long time circulation in the blood stream, selective accumulation at the lesions sites, increased solubility in aqueous solutions, etc.

Herein we report on a new drug delivery system known as a multistage system which is comprised of non-spherical, mesoporous silicon particles loaded with second stage nanoparticles. The rationally designed particle shape, the possibility to modulate the surface properties and the degree of …

Novel Phantoms And Post-Processing For Diffusion Spectrum Imaging, Vaibhav Juneja

Dissertations and Theses (Open Access)

High Angular Resolution Diffusion Imaging (HARDI) techniques, including Diffusion Spectrum Imaging (DSI), have been proposed to resolve crossing and other complex fiber architecture in the human brain white matter. In these methods, directional information of diffusion is inferred from the peaks in the orientation distribution function (ODF). Extensive studies using histology on macaque brain, cat cerebellum, rat hippocampus and optic tracts, and bovine tongue are qualitatively in agreement with the DSI-derived ODFs and tractography. However, there are only two studies in the literature which validated the DSI results using physical phantoms and both these studies were not performed on a …

Accuracy Of The Brcapro Risk Assessment Model In Males Presenting To Md Anderson For Brca Testing, Carolyn Garby, Banu Arun M.D, Michelle Jackson M.S., Cgc, Jennifer Litton M.D, Syed Hashmi M.D., Ph.D, Sharon Giordano M.D, Mph, Claire Singletary M.S, Cgc

Dissertations and Theses (Open Access)

ACCURACY OF THE BRCAPRO RISK ASSESSMENT MODEL IN MALES PRESENTING TO MD ANDERSON FOR BRCA TESTING

Publication No. _______

Carolyn A. Garby, B.S.

Supervisory Professor: Banu Arun, M.D.

Hereditary Breast and Ovarian Cancer (HBOC) syndrome is due to mutations in BRCA1 and BRCA2 genes. Women with HBOC have high risks to develop breast and ovarian cancers. Males with HBOC are commonly overlooked because male breast cancer is rare and other male cancer risks such as prostate and pancreatic cancers are relatively low. BRCA genetic testing is indicated for men as it is currently estimated that 4-40% of male breast cancers …

Regulation Of Protein Degradation In The Heart By Amp-Activated Protein Kinase, Kedryn K. Baskin

Dissertations and Theses (Open Access)

The degradation of proteins by the ubiquitin proteasome system is essential for cellular homeostasis in the heart. An important regulator of metabolic homeostasis is AMP-activated protein kinase (AMPK). During nutrient deprivation, AMPK is activated and intracellular proteolysis is enhanced through the ubiquitin proteasome system (UPS). Whether AMPK plays a role in protein degradation through the UPS in the heart is not known. Here I present data in support of the hypothesis that AMPK transcriptionally regulates key players in the UPS, which, under extreme conditions can be detrimental to the heart. The ubiquitin ligases MAFbx /Atrogin-1 and MuRF1, key regulators of …

Predictors Of Contralateral Breast Cancer In Brca Negative Women, Ann E. Simmons

Dissertations and Theses (Open Access)

Breast cancer is the most common cancer diagnosis and second leading cause of death in women. Risk factors associated with breast cancer include: increased age, alcohol consumption, cigarette smoking, white race, physical inactivity, benign breast conditions, reproductive and hormonal factors, dietary factors, and family history. Hereditary breast and ovarian cancer syndrome (HBOC) is caused by mutations in the BRCA1 and BRCA2 genes. Women carrying a mutation in these genes are at an increased risk to develop a second breast cancer. Contralateral breast cancer is the most common second primary cancer in patients treated for a first breast cancer. Other risk …

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 …

A Pre-Clinical Assessment Of Minocycline For Treatment Of Chronic Neuropathic Pain After Spinal Cord Injury, Alissa R. Poteete

Dissertations and Theses (Open Access)

Patients living with a spinal cord injury (SCI) often develop chronic neuropathic pain (CNP). Unfortunately, the clinically approved, current standard of treatment, gabapentin, only provides temporary pain relief. This treatment can cause numerous adverse side effects that negatively affect the daily lives of SCI patients. There is a great need for alternative, effective treatments for SCI-dependent CNP.

Minocycline, an FDA-approved antibiotic, has been widely prescribed for the treatment of acne for several decades. However, recent studies demonstrate that minocycline has neuroprotective properties in several pre-clinical rodent models of CNS trauma and disease. Pre-clinical studies also show that short-term minocycline treatment …

Pathologic Markers Of Prognosis In Ampullary Carcinoma, Rachna T. Shroff

Dissertations and Theses (Open Access)

Ampullary cancer is a rare gastrointestinal malignancy that can be curable with surgical resection of localized disease. The benefit of adjuvant therapy, however, remains unknown in these patients partly because of difficulty in stratifying which patients are at high risk for recurrence. To better identify those patients who may benefit from adjuvant therapy, I conducted a retrospective analysis the pathology reports from 176 patients with surgically resected ampullary cancer who had not received any neoadjuvant therapy, the systemic therapy given, and the patient outcomes. A tissue microarray (TMA) of 95 surgically resected ampullary specimens was also constructed to examine whether …

Evidence Of Human Endogenous Retrovirus K Involvement In Human Cancer, Joshua B. Plummer

Dissertations and Theses (Open Access)

Many lines of clinical and experimental evidence indicate a viral role in carcinogenesis (1-6). Our access to patient plasma, serum, and tissue samples from invasive breast cancer (N=19), ductal carcinoma

in situ (N=13), malignant ovarian cancer (N=12), and benign ovarian tumors (N=9), via IRB-approved and informed consent protocols through M.D. Anderson Cancer Center, as well as normal donor plasmas purchased from Gulf Coast Regional Blood Center (N=6), has allowed us to survey primary patient blood and tissue samples, healthy donor blood from the general population, as well as commercially available human cell lines for the presence of human endogenous retrovirus …

Regulation Of Protein Degradation In The Heart By Amp-Activated Protein Kinase, Kedryn K. Baskin, Kedryn K. Baskin

Dissertations and Theses (Open Access)

The degradation of proteins by the ubiquitin proteasome system is essential for cellular homeostasis in the heart. An important regulator of metabolic homeostasis is AMP-activated protein kinase (AMPK). During nutrient deprivation, AMPK is activated and intracellular proteolysis is enhanced through the ubiquitin proteasome system (UPS). Whether AMPK plays a role in protein degradation through the UPS in the heart is not known. Here I present data in support of the hypothesis that AMPK transcriptionally regulates key players in the UPS, which, under extreme conditions can be detrimental to the heart. The ubiquitin ligases MAFbx /Atrogin-1 and MuRF1, key regulators of …

Evaluation Of Knowledge Regarding Diagnostic Strategies For Genetic Diseases In Select Residents, Samantha Penney

Dissertations and Theses (Open Access)

Genetics education for physicians has been a popular publication topic in the United States and in Europe for over 20 years. Decreasing numbers of medical genetics professionals and an increasing volume of genetic information has created a dire need for increased genetics training in medical school and in clinical practice. This study aimed to assess how well pediatrics-focused primary care physicians apply their general genetics knowledge to clinical genetic testing using scenario-based questions. We chose to specifically focus on knowledge of the diagnostic applicability of Chromosomal Microarray (CMA) technology in pediatrics because of its recent recommendation by the International Standard …

Salud &Saludos: The E-News Of The College Of Health Sciences, College Of Health Sciences

College of Health Sciences

Monthly e-newsletter of the College of Health Sciences.

Structural Changes In Glaucoma: A Volumetric Mri Study, John Lackey, Alice L. Williams, Srinivas Gatla, Sheryl S. Wizov, Thomas Chia, George Spaeth, Song Lai

Department of Radiology Faculty Papers

Purpose: To investigate brain structural changes in patients with glaucoma.

Methods: High resolution 3D T1-weighted MP-RAGE MRI images were collected in 11 glaucoma patients (5 female, 6 male, 65+/-11 yrs), and 11 age- and gender-matched controls (64+/-12 yrs). The images were first analyzed using an automatic voxel-based morphometry technique which combines a fully automated spatial normalization approach, dubbed HAMMER [1], in conjunction with a tissue mass preserving framework called RAVENS [2]. Four consecutive steps were carried out: removal of non-brain voxels, tissue segmentation, spatial normalization to a standardized template, and generation of a mass-preserving tissue density map (i.e. RAVENS map) …

Effectiveness Of Premedication At The Time Of Separation From Parent And Mask Induction In Paediatric Patients Coming For Congenital Heart Disease Surgery, Mohammad Hamid, Mansoor Ahmed Khan, Aftab Khatri, Irfan Akhtar

Department of Anaesthesia

OBJECTIVE: To compare the effectiveness of oral midazolam and chloral hydrate on anxiety and sedation at various stages of pre-operative period in congenital heart surgery patients.

STUDY DESIGN: Cross-sectional comparative study.

PLACE AND DURATION OF STUDY: Operating rooms of The Aga Khan University Hospital, Karachi, from October 2009 to December 2010.

METHODOLOGY: Sixty-six patients between the ages of 6 months and 6 years received either chloral hydrate (Group C) or midazolam (Group M) pre-operatively. All congenital heart disease patients coming for cardiac surgeries were included while cases of emergency surgery and those patients in whom premedication was not given were …

Border Hispanics’ Physical Activity Improvement In A Chronic Disease Prevention Program, Lu Xu

Theses and Dissertations - UTB/UTPA

In seeking of effective prevention programs to improve physical activities, we want to examine the factors related to physical activities improvement in Alliance for a Healthy Border, a chronic disease prevention program with pre-post-post evaluations through 12 federally qualified community health centers serving primarily Hispanics in communities along the U.S.- Mexico border. Logistic regression was performed to examine the association between physical activity and twenty predictors at baseline. Multinomial regression was used to examine the determinants of physical activities improvement at two time points: program end and post six-months. Socio-demographic, baseline health condition factors, and determination of doing physical activity …

Validating Dose Rate Calibration Of Radiotherapy Photon Beams Through Iaea/Who Postal Audit Dosimetry Service, Abdul Qadir Jangda, Sherali Hussein

Department of Radiation Oncology

In external beam radiation therapy (EBRT), the quality assurance (QA) of the radiation beam is crucial to the accurate delivery of the prescribed dose to the patient. One of the dosimetric parameters that require monitoring is the beam output, specified as the dose rate on the central axis under reference conditions. The aim of this project was to validate dose rate calibration of megavoltage photon beams using the International Atomic Energy Agency (IAEA)/World Health Organisation (WHO) postal audit dosimetry service. Three photon beams were audited: a 6 MV beam from the low-energy linac and 6 and 18 MV beams from …

E-Stimulation: An Effective Modality To Facilitate Wound Healing, Pamela Scarborough, Luther C. Kloth

Physical Therapy Faculty Research and Publications

No abstract provided.

Early Developmental Outcome In Children With Hypoplastic Left Heart Syndrome And Related Anomalies: The Single Ventricle Reconstruction Trial., Jane W. Newburger, Lynn A. Sleeper, David C. Bellinger, Caren S. Goldberg, Sarah Tabbutt, Minmin Lu, Kathleen A. Mussatto, Ismee A. Williams, Kathryn E. Gustafson, Seema Mital, Nancy Pike, Erica Sood, William T. Mahle, David S. Cooper, Carolyn Dunbar-Masterson, Catherine Dent Krawczeski, Alan Lewis, Shaji C. Menon, Victoria L. Pemberton, Chitra Ravishankar, Teresa W. Atz, Richard G. Ohye, J William Gaynor, Pediatric Heart Network Investigators, Girish S. Shirali

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Survivors of the Norwood procedure may experience neurodevelopmental impairment. Clinical trials to improve outcomes have focused primarily on methods of vital organ support during cardiopulmonary bypass.

METHODS AND RESULTS: In the Single Ventricle Reconstruction trial of the Norwood procedure with modified Blalock-Taussig shunt versus right-ventricle-to-pulmonary-artery shunt, 14-month neurodevelopmental outcome was assessed by use of the Psychomotor Development Index (PDI) and Mental Development Index (MDI) of the Bayley Scales of Infant Development-II. We used multivariable regression to identify risk factors for adverse outcome. Among 373 transplant-free survivors, 321 (86%) returned at age 14.3 ± 1.1 (mean ± SD) months. Mean …

Predictive Prognosis Value Of Baseline Volumetric Mri, Song Lai, John Lackey

Department of Radiology Faculty Papers

Atrophic changes have been proposed as biomarkers for differential diagnosis of Alzheimer's disease (AD) and amnestic mild cognitive impairment (MCI), and different atrophic rates have been observed in AD, MCI-tp-AD converters (cMRI), stable MCI (sMCI), and normal healthy controls[1]. Measurement of atrophic changes, however, requires longitudinal MRI studies. The purpose of this study was to investigate the following questions: 1. Is it possible to use baseline volumetric MRI to predict MCI conversion to AD, i.e., to tell if a MCI patient is a cMCI or a sMCI? 2. What are the predictive values of APOE genotype, and clinical cognitive …

Patient And Nurse Considerations In Home Health Routing With Remote Monitoring Devices, Jessica Spicer

Graduate Theses and Dissertations

We build on the current consistent vehicle routing problem literature by formulating a novel multi- objective mathematical model of the home health scheduling and routing problem that includes the option of assigning some patient visits to remote monitoring devices, with the objectives of mini- mizing total cost, achieving nurse consistency and creating balanced nurse workloads. A heuristic solution approach that approximates the efficient frontier of this multiobjective problem is pre- sented and validated, and the results of using this methodology to solve several realistic instances are included. We also analyze the assignment of patients to devices and present some managerial …

Daycare Adeno-Tonsillectomy: Is It Safe In Developing Countries, Aria Masoom, Shabbir Akhtar, Hassan Nabeel Humayun, Mubasher Ikram

Section of Otolaryngology, Head & Neck Surgery

OBJECTIVE: To determine the safety of daycare adeno-tonsillectomy in a tertiary care centre.

METHOD: A retrospective chart review of 207 patients who had undergone tonsillectomy and/or adenoidectomy as daycare procedure in Aga Khan University Hospital, Karachi, between January 2008 to March 2009 was done. Demographic data as well as complications requiring unplanned admissions were recorded. Any emergency room visit in the first 24 hours was also noted. Telephonic calls were then made to collect the first 24-hour, postoperative data in order to know if there were any complications requiring visit to some nearby health facility. All data was analysed using …

The Rationality Of Prescribing Antibiotics After Tonsillectomy, Maqbool Ahmed Baloch, Shabbir Akhtar, Mubasher Ikram, Hassan Nabeel Humayun

Section of Otolaryngology, Head & Neck Surgery

Objective: To compare the antibiotic therapy with the absence of antibiotic therapy in reducing post-tonsillectomy morbidities
Methods: The quasi-experimental study was conducted at the Aga Khan University Hospital, Karachi, from November 2006 to September 2007. It involved 60 patients fulfilling the criteria for recurrent tonsillitis who were divided in two groups based on the different practice of two sets of surgeons. In one group antibiotics were used, while in the other group, no antibiotic was given. Patients filled a questionnaire about pain, post-operative bleeding, day of normal diet intake, day of normal activity and any consultation received during the first …

Prelamin A Influences A Program Of Gene Expression In Regulation Of Cell Cycle Control, Christina N. Bridges

Electronic Theses and Dissertations

The A-type lamins are intermediate filament proteins that constitute a major part of the eukaryotic nuclear lamina—a tough, polymerized, mesh lining of the inner nuclear membrane, providing shape and structural integrity to the nucleus. Lamin A (LA) filaments also permeate the nucleoplasm, providing additional structural support, but also scaffolding numerous tethered molecules to stabilize, organize, and facilitate molecular interactions to accomplish critical functions of cellular metabolism. Over the past 2 decades, much attention has been focused on roles of LA in maintenance of nuclear structural integrity. Only since the late 1990s have scientists discovered the devastating effects of LA gene …

Influence Of Upper Extremity Assistance On Lower Extremity Force Application Symmetry In Individuals Post–Hip Fracture During The Sit-To-Stand Task, Janet A. Kneiss, Jeff R. Houck, Susan A. Bukata, J. Edward Puzas

Faculty Publications - College of Physical Therapy

STUDY DESIGN: Controlled laboratory study using a cross-sectional design.

OBJECTIVES: To compare lower extremity force applications during a sit-to-stand (STS) task with and without upper extremity assistance in older individuals post–hip fracture to those of age matched controls.

BACKGROUND: A recent study documented the dependence on upper extremity assistance and the uninvolved lower limb during an STS task in individuals post–hip fracture. This study extends this work by examining the effect of upper extremity assistance on symmetry of lower extremity force applications.

METHODS: Twenty-eight community-dwelling elderly subjects, 14 who had recovered from a hip fracture and 14 controls, participated in …

Primary Billiary Cirrhosis (Antimitochondrial Antibody Negative) Leading To Secondary Amyloidosis, Om Parkash, Aysha Almas

Section of Gastroenterology

A 49 years old lady presented with low-grade fever (99-100degreesF) for 2 years. During this time she was extensively worked-up for pyrexia of unknown origin but no diagnosis could be established. Her Initial blood work-up was all negative except high alkaline phosphatase and gamma GT (374 IU and 195 IU respectively). She later presented to our tertiary care centre with facial swelling, flushing and bilateral pedal swelling for 3 months. Along with generalized body swelling she had frothy urine. She was diagnosed as nephrotic syndrome on the basis of nephrotic range proteinuria. Her Renal biopsy done for workup of nephrotic …

High Clarithromycin Resistance And A Low Rate Of Recurrence And Reinfection Of Helicobacter Pylori Infection In Pakistan, Shahab Abid, Javed Yakoob, Wasim Jafri, Z Abbas, Khalid Mumtaz, Saeed Hamid, Rashida Ahmed

Section of Gastroenterology

No abstract provided.

Iraq And Afghanistan Veterans’ Experiences Living With Their Parents After Separation From The Military, Miranda E. Worthen, M Moos, R Ahem

Faculty Publications

When military service members separate from the military, many return to their families of origin, living with their parents for a period of several weeks to years. While research with veterans and their spouses has documented the particular strain of this reintegration period on veterans and their partners, little research to date has examined veterans’ experiences living with their parents. The present study sought to fill this research gap by investigating veterans’ experiences living with their parents using qualitative, in-depth interviews with Iraq and Afghanistan veterans in California. Overall, veterans appreciated the instrumental and emotional support their parents provided when …

Hydra Vulgaris As A High Throughput Invertebrate For Anti-Epilepsy Drugs, Bianca Marie Lauro

Senior Honors Projects

No abstract provided.