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Effects Of Hyperthermia On Photochemical Internalization-Mediated Delivery Of Bleomycin, Christina Schlazer

UNLV Theses, Dissertations, Professional Papers, and Capstones

Standard treatment protocols for high-grade gliomas, such as glioblastoma multiforme (GBM), are highly ineffective due to their inability to eradicate infiltrating tumor cells. Improvements in overall survival are likely to be realized only with the development of more effective localized therapies capable of eradicating tumor cells in the surgical resection margin and beyond. Photochemical internalization (PCI) is a localized light-based therapeutic modality that enhances the efficacy of therapeutic macromolecules including chemotherapeutic agents such as bleomycin. A number of studies have shown that this photodynamic therapy (PDT) - based modality may prove effective in the treatment of high-grade gliomas.

Three-dimensional multicell …

Use Of Continuous Glucose Monitors In Type-1 Diabetes: An Analysis Of Wave Form Versus Glycemic Values In The Improvement Of Glucose Control And Fear Of Hypoglycemia, Tomas Charles Walker

UNLV Theses, Dissertations, Professional Papers, and Capstones

Type-1 diabetes is a disease of subtle complexities. Patients struggle to understand glucose patterns and their responses to insulin or food intake while maintaining hectic lifestyles. Minor misjudgments in treatments can result in disastrous consequences with significant hypo- or hyperglycemic excursions.

Despite improvements in technologies available for diabetes management, including home monitoring of blood glucose, more predictable insulin therapies, and improved insulin delivery via insulin pump, the average HbA1c has remained relatively unchanged. Poor diabetes control is recognized as contributing to long-term diabetes comorbidities including neuropathy, nephropathy, retinopathy, and micro- and macrovascular disease.

Real-time continuous glucose monitors, such as the …

Population-Based Survey Of Lumbar Surgery Beliefs In The United States, Amanda Elyse Mccauley, Zachery Clark Rasmussen

UNLV Theses, Dissertations, Professional Papers, and Capstones

Purpose/Hypothesis: Studies have shown that poor lumbar surgery outcomes may be influenced by a person’s preconceived perceptions of low back surgery (LBS). However, the perceptions of the general population about issues related to lumbar surgery are not known. Therefore, the purpose of this study was to investigate the general population’s perceptions regarding LBS.

Number of Subjects: This study included 262 participants (Average age: 46.1, SD=16.9; 125 Males, 137 Females) who completed the questionnaire from the general population in the Las Vegas area.

Materials/Methods: Questionnaire development involved expert panel feedback from three physical therapists, three spine surgeons, two surgeon assistants/nurses, two …

Stabilization Of The Cardiac Nervous System During Cardiac Stress Induces Cardioprotection, David D. Gibbons

Electronic Theses and Dissertations

The cardiac nervous system consists of nested reflex feedback loops that interact to regulate regional heart function. Cardiac disease affects multiple components of the cardiac nervous system and the myocytes themselves. This study aims to determine: 1) how select components of the cardiac nervous system respond to acute cardiac stress, including myocardial ischemia (MI) and induced neural imbalance leading to cardiac electrical instability, and 2) how neuromodulation can affect neural-myocyte interactions to induce cardioprotection. Thoracic spinal cord stimulation (SCS) is recognized for its anti-anginal effects and ability to reduce apoptosis in response to acute MI, primarily via modulation of adrenergic …

Acetaminophen Induced Steven Johnson Syndrome-Toxic Epidermal Necrolysis Overlap, Ali Khuwaja, Ahmed Shahab, Syed Ather Hussain

Section of Internal Medicine

Steven Johnson Syndrome and Toxic Epidermal Necrolysis are rare but severe form of hypersensitivity inflammatory reactions to multiple offending agents including drugs. Acetaminophen is extensively used due to its analgesic and anti-pyretic properties. It is rendered to be relatively safe, with hepatotoxicity considered to be the major adverse effect. However, very few cases of Steven Johnson Syndrome and Toxic Epidermal Necrolysis have been reported with acetaminophen usage in the past. We present the case of a 40 years old lady who developed an overlap of the two condition after taking several doses of acetaminophen for fever. She presented with widespread …

Interactions Of Nitric Oxide And Superoxide Pathways In Hyperglycemic Endothelial Cells, Steven Clay Rogers

Graduate Theses and Dissertations

Cardiovascular complications arising from diabetic hyperglycemia represents one of the leading causes of death and greatest public health challenges of modern societies. Despite state-of-the-art glucose control, diabetic patients remain at a markedly increased risk of cardiovascular disease. The loss of endothelial function (the development of diabetic endothelial dysfunction) has been implicated in the development of numerous diabetic cardiovascular diseases. The endothelial cell produces many vasoactive substances, hormones and cytoprotective biological factors. Endothelial cells are also involved in and affected by the initiation of inflammatory responses through the release and interaction of cytokines and other immune system molecules. Therefore, regulation of …

Role Of Endovascular Treatment In Vascular Injuries, Muhammad Misbah Tahir, Tanveer-Ul-Haq

Department of Radiology

OBJECTIVE: To evaluate retrospectively the results, complications and follow-up of patients after endovascular treatment of vascular injuries.

METHODS: Fifty transcatheter embolisation procedures (TCE) were performed in 46 patients between 1999 and 2008 at the Aga Khan University Hospital, Karachi. Injuries in 14 (30.4%) patients were due to road traffic accident; iatrogenic in 13 (28%); accidental in 6 (13%). Firearms, bomb blasts and earthquake contributed to injuries in 8(17%), 4(8.8%) and 1(2.2%) patients respectively. All patients underwent angiography and had evidence of either active haemorrhage, pseudo-aneurysm, abnormal vascularity or arteriovenous fistula. Followup ranged from 1 day to 6 years with mean …

Coronary Artery Bypass Grafting After Percutaneous Coronary Intervention, Syed Shahabuddin, Syed Ahmed Sami, Junaid Alam Ansari, Shazia Perveen, Shumaila Furnaz, Saulat H. Fatimi, Hasanat Sharif

Section of Cardiothoracic Surgery

Following percutaneous intervention (PCI), restenosis, progression of disease and multi-vessel involvement may require further intervention in the form of surgical revascularization. Patients with coronary artery bypass grafting (CABG) done after PCI were evaluated to find out the reason for the need of surgical revascularization. Over a period of 12 months, 610 patients underwent CABG. Out of them, 34 patients had previous PCI/stenting. Coronary risk factors including hypertension in 85%, diabetes mellitus in 60%, dyslipidemia in 60%, tobacco use in 50% and a positive family history was present in 53% of the patients. All patients were symptomatic. Multi-vessel disease was present …

Knowledge, Attitudes, And Utilization Of Brca Testing Among Obstetricians And Gynecologists, Salma Nassef

Dissertations and Theses (Open Access)

Hereditary breast and ovarian cancer (HBOC) is an inherited cancer syndrome that is associated with mutations in the BRCA1 and BRCA2 genes. Carriers of BRCA mutations, both men and women, are at an increased risk for developing certain cancers. Carriers are most notably at an increased risk to develop breast and ovarian cancers; however an increased risk for prostate cancer, melanoma, and pancreatic cancers has also been associated with these mutations. In 2009 the American Congress of Obstetricians and Gynecologists (ACOG) released a practice bulletin stating that evaluating a patient’s risk for HBOC should be a routine part of obstetric …

Progesterone And Preterm Birth Prevention: Translating Clinical Trials Data Into Clinical Practice, Vincenzo Berghella

Department of Obstetrics and Gynecology Faculty Papers

OBJECTIVE:

We sought to provide evidence-based guidelines for using progestogens for the prevention of preterm birth (PTB).

METHODS:

Relevant documents, in particular randomized trials, were identified using PubMed (US National Library of Medicine, 1983 through February 2012) publications, written in English, which evaluate the effectiveness of progestogens for prevention of PTB. Progestogens evaluated were, in particular, vaginal progesterone and 17-alpha-hydroxy-progesterone caproate. Additionally, the Cochrane Library, organizational guidelines, and studies identified through review of the above were utilized to identify relevant articles. Data were evaluated according to population studied, with separate analyses for singleton vs multiple gestations, prior PTB, or short …

Cardiac G-Protein-Coupled Receptor Kinase 2 Ablation Induces A Novel Ca2+ Handling Phenotype Resistant To Adverse Alterations And Remodeling After Myocardial Infarction., Philip W Raake, Xiaoying Zhang, Leif E Vinge, Henriette Brinks, Erhe Gao, Naser Jaleel, Yingxin Li, Mingxin Tang, Patrick Most, Gerald W Dorn, Steven R Houser, Hugo A Katus, Xiongwen Chen, Walter J Koch

Center for Translational Medicine Faculty Papers

BACKGROUND: G-protein-coupled receptor kinase 2 (GRK2) is a primary regulator of β-adrenergic signaling in the heart. G-protein-coupled receptor kinase 2 ablation impedes heart failure development, but elucidation of the cellular mechanisms has not been achieved, and such elucidation is the aim of this study.

METHODS AND RESULTS: Myocyte contractility, Ca(2+) handling and excitation-contraction coupling were studied in isolated cardiomyocytes from wild-type and GRK2 knockout (GRK2KO) mice without (sham) or with myocardial infarction (MI). In cardiac myocytes isolated from unstressed wild-type and GRK2KO hearts, myocyte contractions and Ca(2+) transients were similar, but GRK2KO myocytes had lower sarcoplasmic reticulum (SR) Ca(2+) content …

Comparison Of Different Craniofacial Patterns With Pharyngeal Widths, Sarwat Memon, Mubassar Fida, Attiya Shaikh

Section of Dental-Oral Maxillofacial Surgery

OBJECTIVE: To compare different craniofacial patterns with pharyngeal widths.

STUDY DESIGN: Cross-sectional analytical study.

PLACE AND DURATION OF STUDY: Orthodontic Clinic at the Aga Khan University Hospital, Karachi, from June 2002 to June 2010.

METHODOLOGY: Data were collected using pre-treatment records including orthodontic files and pre-treatment lateral cephalographs of 360 orthodontic patients. The inclusion criteria were subjects of Pakistani origin, aged between 14-20 years and having no pharyngeal pathology or complaints of nasal obstruction at the initial visit. The sample comprised a total of 360 subjects divided into 2 groups: skeletal Class I (n=180) and skeletal Class II (n=180) subdivided …

Management Of Sexual Disorders In Spinal Cord Injured Patients., Vafa Rahimi-Movaghar, Alexander R Vaccaro

Department of Neurosurgery Faculty Papers

Spinal cord injured (SCI) patients have sexual disorders including erectile dysfunction (ED), impotence, priapism, ejaculatory dysfunction and infertility. Treatments for erectile dysfunction include four steps. Step 1 involves smoking cessation, weight loss, and increasing physical activity. Step 2 is phosphodiesterase type 5 inhibitors (PDE5I) such as Sildenafil (Viagra), intracavernous injections of Papaverine or prostaglandins, and vacuum constriction devices. Step 3 is a penile prosthesis, and Step 4 is sacral neuromodulation (SNM). Priapism can be resolved spontaneously if there is no ischemia found on blood gas measurement or by Phenylephrine. For anejaculatory dysfunction, massage, vibrator, electrical stimulation and direct surgical biopsy …

Taz As A Regulator Of Mesenchymal Transformation And Clinical Aggressiveness In Gliomas, Katrina Salazar

Dissertations and Theses (Open Access)

Glioblastoma multiforme (GBM) is an aggressive, high grade brain tumor. Microarray studies have shown a subset of GBMs with a mesenchymal gene signature. This subset is associated with poor clinical outcome and resistance to treatment. To establish the molecular drivers of this mesenchymal transition, we correlated transcription factor expression to the mesenchymal signature and identified transcriptional co-activator with PDZ-binding motif (TAZ) to be highly associated with the mesenchymal shift. High TAZ expression correlated with worse clinical outcome and higher grade. These data led to the hypothesis that TAZ is critical to the mesenchymal transition and aggressive clinical behavior seen in …

Bim Mediates Imatinib-Induced Apoptosis Of Gastrointestinal Stromal Tumors: Translational Implications, David Reynoso

Dissertations and Theses (Open Access)

Gastrointestinal stromal tumors (GISTs) are oncogene-addicted cancers driven by activating mutations in the genes encoding receptor tyrosine kinases KIT and PDGFR-α. Imatinib mesylate, a specific inhibitor of KIT and PDGFR-α signaling, delays progression of GIST, but is incapable of achieving cure. Thus, most patients who initially respond to imatinib therapy eventually experience tumor progression, and have limited therapeutic options thereafter. To address imatinib-resistance and tumor progression, these studies sought to understand the molecular mechanisms that regulate apoptosis in GIST, and evaluate combination therapies that kill GISTs cells via complementary, but independent, mechanisms. BIM (Bcl-2 interacting mediator …

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 …

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 …

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 …

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 …

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.

Adult Ecmo And Gastrointestinal Bleeding From Small Bowel Arteriovenous Malformations: A Novel Treatment Using Spiral Enteroscopy., Konrad Sarosiek, Hitoshi Hirose, Harrison T Pitcher, Nicholas C. Cavarocchi

Department of Surgery Faculty Papers

Hemorrhagic complications on extracorporeal membrane oxygenation (ECMO) are common because of the need for anticoagulation to maintain the oxygenator and circuitry. Gastrointestinal bleeding (GIB) is reported to occur in 3-6% of ECMO patients, ¹ requiring frequent transfusions as well as multiple diagnostic and therapeutic interventions. Multiple transfusions can result in volume overload, coagulopathies and infections leading to significant morbidity and mortality. We present the first published case of GIB from an arteriovenous malformation (AVM) treated with a novel therapy termed spiral enteroscopy while the patient remained on venoarterial (VA) ECMO.

Infiltrating Ductal Carcinoma Of Breast Presenting As Areolar Dermal Lesion, Gulnaz Shafqat, Shaista Khan, Khurram Minhas, Shaista Afzal

Department of Radiology

Infiltrating ductal carcinoma is the most common form of invasive breast cancer. It accounts for 80% of all types of breast cancer. We report an unusual presentation of histologically proven case of infiltrating ductal carcinoma of breast presented clinically as a small palpable areolar dermal lesion. Well defined hypoechoic cystic lesion in areolar dermis was present on ultrasound with a negative mammogram.

What Is The Role Of Free Radical Scavengers In Acute Stroke?, Muhammad Faisal Wadiwala, Ambreen Sonawalla, Ayeesha Kamran Kamal

Section of Neurology

No abstract provided.

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 …

Ministry Of Memories: Keys To Pastoral Care Of Non-Cognitive Persons, Reginald Corfield

Doctoral Dissertations and Projects

This work is intended to examine and study the theological and moral reasons to provide pastoral care to persons who have limited or no cognition. Dementia, Alzheimer's, certain other medical conditions and the aging process cause a loss of brain function that affects memory, thinking, behavior and judgment. Most Clergy wrestle with the fact as to whether there is any purpose in ministering to such persons especially when there is no verbal or non-verbal response. This paper involves surveys, research, collection of historical and biblical data and medical science to evaluate the disease process and explore ways in which to …

Rotational Vs. Standard Smooth Laryngeal Mask Airway Insertion In Adults, Dileep Kumar, Mueenullah Khan, Muhammad Ishaq

Department of Anaesthesia

OBJECTIVE: To compare the ease of insertion between rotational laryngeal mask airway (LMA) insertion and Brain's LMA insertion technique in terms of number of LMA insertion attempts, time duration of LMA insertion and complications: trauma, laryngospasm, and hypoxaemia.

STUDY DESIGN: Randomized control study.

PLACE AND DURATION OF STUDY: The Aga Khan University Hospital, Karachi, from September 2006 to May 2007.

METHODOLOGY: One hundred ASA I and II adults undergoing short elective surgical procedures requiring general anaesthesia with spontaneous breathing were enrolled. Following pre-oxygenation, anaesthesia was induced with propofol 2 mg/kg and fentanyl 2 mug/kg. Patients were randomly assigned into one …