Digital Commons Network^™

Complexity, Cofactors, And The Failure Of Aids Policy In Africa, Eileen Stillwaggon

Economics Faculty Publications

Global AIDS policy still treats HIV as an exceptional case, abstracting from the context in which infection occurs. Policy is based on a simplistic theory of HIV causation, and evaluated using outdated tools of health economics. Recent calls for a health systems strategy – preventing and treating HIV within a programme of comprehensive health care – have not yet influenced the silo approach of AIDS policy.

Evidence continues to accumulate, showing that multiple factors, such as malnutrition, malaria and helminthes, increase the risk of sexual and vertical transmission of HIV. Moreover, complementary interventions that reduce viral load, improve immune response, …

Genomic Biomarkers For Molecular Imaging: Predicting The Future., Mathew L. Thakur

Department of Radiation Oncology Faculty Papers

Over the past few decades, great strides have been made in anatomical imaging of disease that has led to their diagnosis with minimal invasion. Despite these advances, diseases such as cancer continue to take one human life every minute in the United States. Complimentary approaches that pertain directly to the genesis of the disease might contribute to its early diagnosis and subsequent management. In cancer, an array of molecular abnormalities leading to the modulations in expression of key proteins important in the cellular signaling pathways and cell proliferation has been identified. These specific disease fingerprints, biomarkers, are overexpressed on malignant …

Surgical Management Of Non -Suppurative Brain Lesions (Part I), Muhammad Shahzad Shamim, Syed Ather Enam, Rushna Pervez Ali, Syed Faizan Ali, Mohammad Wasay

Pakistan Journal of Neurological Sciences (PJNS)

No abstract provided.

Metabolic Syndrome And Risk Of Cancer Mortality In Men, Jason R. Jaggers, Xuemei Sui, Steven P. Hooker, Michael J. Lamonte, Charles E. Matthews, Gregory A. Hand, Steven N. Blair

Faculty and Staff Scholarship

Background—Metabolic syndrome (MetS) has been linked with an increased risk of developing cancer; however the association between MetS and cancer mortality remains less clear. Little research has focused on pre-cancer risk factors that may affect the outcome of treatment. The purpose of this study was to examine the association between MetS and all-cancer mortality in men. Methods—The participants included 33,230 men aged 20-88 years who were enrolled in the Aerobics Center Longitudinal Study and free of known cancer at baseline. Results—At baseline 28% of all the participants had MetS. During an average of 14 years followup there were a total …

The Karachi Intracranial Stenosis Study (Kiss) Protocol: An Urban Multicenter Case-Control Investigation Reporting The Clinical, Radiologic And Biochemical Associations Of Intracranial Stenosis In Pakistan., Ayeesha Kamran Kamal, Fawad Taj,, Babar Junaidi, Asif Rasheed, Moazzam Zaidi, Muhammed Murtaza, Naved Iqbal, Fahad Hashmat, Syed Vaqas Alam, Uzma Saleem, Shahan Waheed, Lajpat Bansari, Nabi Shah, Maria Samuel, Madiha Yameen, Sobia Naz, Farrukh Shahab Khan, Naveeduddin Ahmed, Khalid Mahmood, Niaz Sheikh, Karim Ullah Makki, Muhammad Masroor Ahmed, Abdul Rauf Memon, Mohammad Wasay, Nadir Ali Syed, Bhojo A Khealani, Philippe M. Frossard, Danish Saleheen

Department of Medicine

Background: Intracranial stenosis is the most common cause of stroke among Asians. It has a poor prognosis with a high rate of recurrence. No effective medical or surgical treatment modality has been developed for the treatment of stroke due to intracranial stenosis. We aim to identify risk factors and biomarkers for intracranial stenosis and to develop techniques such as use of transcranial doppler to help diagnose intracranial stenosis in a cost-effective manner.

Methods/Design: The Karachi Intracranial Stenosis Study (KISS) is a prospective, observational, case-control study to describe the clinical features and determine the risk factors of patients with stroke due …

Vegf-A As An Inhibitor Of Angiogenesis And Methods Of Using Same, Jayakrishna Ambati

Ophthalmology and Visual Science Faculty Patents

The invention relates to methods and compositions for the treatment or prevention of ocular angiogenesis and neovascularization associated with neovascular disease. Administration of vascular endothelial growth factor (VEGF)-A into the eye when macrophage infiltration is reduced inhibits ocular angiogenesis.

A Real-Time Prostate Cancer Detection Technique Using Needle Insertion Force And Patient-Specific Criteria During Percutaneous Intervention, Kaiguo Yan, T. Podder, L. Li, J. Joseph, D. R. Rubens, E. M. Messing, L. Liao, Y. Yu

Department of Radiation Oncology Faculty Papers

In this article, the authors present a novel real-time cancer detection technique by using needle insertion forces in conjunction with patient-specific criteria during percutaneous interventions. Needle insertion experiments and pathological analysis were performed for developing a computer-aided detection (CAD) model. Backward stepwise regression method was performed to identify the statistically significant patient-specific factors. A baseline force model was then developed using these significant factors. The threshold force model that estimated the lower bound of the cancerous tissue forces was formulated by adding an adjustable classifier to the baseline force model. Trade-off between sensitivity and specificity was obtained by varying the …

Hibernation-Like State Induced By An Opioid Peptide Protects Against Experimental Stroke, Cesar V. Borlongan, Teruo Hayashi, Peter R. Oeltgen, Tsung-Ping Su, Yun Wang

Pathology and Laboratory Medicine Faculty Publications

BACKGROUND: Delta opioid peptide [D-ala2,D-leU5]enkephalin (DADLE) induces hibernation in summer ground squirrels, and enhances preservation and survival of isolated or transplanted lungs and hearts. In the present study, we investigated the protective effect of DADLE in the central nervous system.

RESULTS: Adult Sprague-Dawley rats were pretreated with DADLE (4 mg/kg every 2 h x 4 injections, i.p.) or saline prior to unilateral occlusion of the middle cerebral artery (MCA). Daily behavioral tests revealed that ischemic animals treated with DADLE did not show any significant behavioral dysfunctions compared with saline-treated ischemic animals. Opioid antagonists only transiently inhibited the protective effect of …

Kinetics And Phenotype Of Vaccine-Induced Cd8+ T-Cell Responses To Toxoplasma Gondii, Kimberly A. Jordan, Emma H. Wilson, Elia D. Tait, Barbara A. Fox, David S. Roos, David J. Bzik

Dartmouth Scholarship

Multiple studies have established that the ability of CD8⁺ T cells to act as cytolytic effectors and produce gamma interferon is important in mediating resistance to the intracellular parasite Toxoplasma gondii. To better understand the generation of the antigen-specific CD8⁺ T-cell responses induced by T. gondii, mice were immunized with replication-deficient parasites that express the model antigen ovalbumin (OVA). Class I tetramers specific for SIINFEKL were used to track the OVA-specific endogenous CD8⁺ T cells. The peak CD8⁺ T-cell response was found at day 10 postimmunization, after which the frequency and numbers of antigen-specific cells …

A Dominant Loss-Of-Function Gja1 (Cx43) Mutant Impairs Parturition In The Mouse, Dan Tong, Xuerong Lu, Hong-Xing Wang, Isabelle Plante, Ed Lui, Dale W. Laird, Donglin Bai, Gerald M. Kidder

Physiology and Pharmacology Publications

Expression of GJA1 (commonly known as connexin43 or Cx43), a major myometrial gap junction protein, is upregulated before the onset of delivery, suggesting an essential role for Cx43-mediated gap junctional intercellular communication (GJIC) in normal uterine contraction during parturition. To determine how a disease-linked Cx43 mutation affects myometrial function, we studied a mutant mouse model carrying an autosomal dominant mutation (Gja1Jrt) in the gene encoding Cx43 that displays features of the human genetic disease oculodentodigital dysplasia. We found that Cx43 level, specifically the phosphorylated species of the protein, is significantly reduced in the myometrium of the mutant mice (Gja1Jrt/+), as …

Clinical And Translational Implications Of The Caveolin Gene Family: Lessons From Mouse Models And Human Genetic Disorders., Isabelle Mercier, Jean-Francois Jasmin, Stephanos Pavlides, Carlo Minetti, Neal Flomenberg, Richard G Pestell, Philippe G Frank, Federica Sotgia, Michael P Lisanti

Department of Stem Cell Biology and Regenerative Medicine Faculty Papers & Presentations

Here we review the clinical and translational implications of the caveolin gene family for understanding the pathogenesis of human diseases, including breast and prostate cancers, pulmonary hypertension, cardiomyopathy, diabetes, and muscular dystrophy. Detailed phenotypic analysis of caveolin knockout mice has served to highlight the crucial role of a caveolin deficiency in the pathogenesis of many human disease processes. Mutations in the human caveolin genes are associated with a number of established genetic disorders (such as breast cancer, lipodystrophy, muscular dystrophy, and cardiomyopathy), making the caveolins important and novel targets for drug development. The implementation of new strategies for caveolin replacement …

Field Testing Adolescent Females For Cardiovascular Disease Risk, C. Jayne Brahler, Wesley R. Stephens, Betsy Donahoe Fillmore

Physical Therapy Faculty Publications

Over-fatness and poor cardiovascular (CV) fitness are well-documented risk factors for cardiovascular disease (CVD) in adults, but less is known about their association with disease risk in adolescents. This study aimed to determine the relationship between anthropometrics, fitness, and CVD risk.

Six anthropometric indicators of body fatness, seven measures of fitness, and seven metabolic and hemodynamic CVD risk factors were measured in a convenience sample of 28 female high school students (15-18 years of age). A tally was made of the number of factors for which each subject was outside the normal reference range (CVD risk).

Correlation analyses were completed …

Mnte-2-Pyp And Radiation In A Prostate Cancer Model: Implications For Radiotherapy, Adeola Y. Makinde

Loma Linda University Electronic Theses, Dissertations & Projects

A major limitation of successful radiation therapy in cancer treatment is the increase in normal tissue damage as higher doses are used to achieve greater tumor destruction. Radiation dose optimization in cancer therapy requires achieving maximum tumor destruction with minimal damage to normal tissue Antioxidants have been shown to protect normal tissues against radiation damage, as radiation-induced tissue damage results predominantly from reactive oxygen species that directly damage cellular components. However, for effective use as normal tissue radioprotectants in radiotherapy, these antioxidants must not protect the tumors. Mn (III) tetrakis (N-ethylpyridinium-2-yl) porphyrin (MnTE-2-PyP) is a metalloporphyrin antioxidant that has been …

Outbreak Of Dengue Fever In Karachi 2006: A Clinical Perspective, Muhammad Mehmood Riaz, Khalid Mumtaz, Muhammad Shoaib Khan, Junaid Patel, M. Tariq, Harith Hilal, Shaheryar Ahmed Siddiqui, Farrukh Shezad

Section of Internal Medicine

OBJECTIVE: This study reports clinical manifestations and spectrum of severity of dengue fever (DF), dengue haemorrhagic fever (DHF) and dengue shock syndrome (DSS) in adult patients admitted during 2006 outbreak in Karachi. A rough estimation of cost of care was also calculated.

METHODS: A cross-sectional study was done at a tertiary care hospital in Karachi from January to December 2006. Patients suspected of having DF with positive dengue IgM antibodies were included and records were reviewed. Patients were divided into DF, DHF and DSS as per WHO classification, and the severity of clinical manifestations was determined.

RESULTS: A total of …

Intravenous Inoculation Of A Bat-Associated Rabies Virus Causes Lethal Encephalopathy In Mice Through Invasion Of The Brain Via Neurosecretory Hypothalamic Fibers., Mirjam A R Preuss, Marie-Luise Faber, Gene S Tan, Michael Bette, Bernhard Dietzschold, Eberhard Weihe, Matthias J Schnell

Department of Microbiology and Immunology Faculty Papers

The majority of rabies virus (RV) infections are caused by bites or scratches from rabid carnivores or bats. Usually, RV utilizes the retrograde transport within the neuronal network to spread from the infection site to the central nervous system (CNS) where it replicates in neuronal somata and infects other neurons via trans-synaptic spread. We speculate that in addition to the neuronal transport of the virus, hematogenous spread from the site of infection directly to the brain after accidental spill over into the vascular system might represent an alternative way for RV to invade the CNS. So far, it is unknown …

Old Disease, New Targets--Part-I, Solid Malignancies, Shiyam Kumar, Nehal Masood, Asim Jamal Shaikh

Department of Radiation Oncology

Targeted agents are now an integral part of treatment regimens for some cancers. Trastuzumab is established in treatment of human epidermal receptor 2 (Her2) positive breast cancers, with improvements in both, the disease free and over all survival. Monoclonal antibody (MoAB) against vascular growth factor receptor (VEGF), bevacizumab and cetuximab a MoAB against epidermal growth factor receptor (EGFR) are establishing their role in a many cancers after making their mark in colorectal cancer. Sorafenib and sunitinib have success stories in renal carcinoma. The Sorafenib Hepatocellular Carcinoma Assessment Randomized Protocol (SHARP) trial has established sorafenib role in advanced hepatocellular carcinoma, while …

Human Cerebral Neuropathology Of Type 2 Diabetes Mellitus, Peter T. Nelson, Charles D. Smith, Erin L. Abner, Frederick A. Schmitt, Stephen W. Scheff, Gregory J. Davis, Jeffrey N. Keller, Gregory A. Jicha, Daron Davis, Wang-Xia Wang, Adria Hartman, Douglas G. Katz, William R. Markesbery

Pathology and Laboratory Medicine Faculty Publications

The cerebral neuropathology of Type 2 diabetes (CNDM2) has not been positively defined. This review includes a description of CNDM2 research from before the ‘Pubmed Era’. Recent neuroimaging studies have focused on cerebrovascular and white matter pathology. These and prior studies about cerebrovascular histopathology in diabetes are reviewed. Evidence is also described for and against the link between CNDM2 and Alzheimer's disease pathogenesis. To study this matter directly, we evaluated data from University of Kentucky Alzheimer's Disease Center (UK ADC) patients recruited while non-demented and followed longitudinally. Of patients who had come to autopsy (N = 234), 139 met …

Vital Signs, Spring/Summer 2009, Boonshoft School Of Medicine

Vital Signs

A fifty-six page newsletter created by the Boonshoft School of Medicine to document the current affairs of the school. This issue includes a variety of feature articles and smaller pieces that focus on faculty, students, milestones and more.

Labrad : Vol 34, Issue 2 - May 2009, Aga Khan University Hospital, Karachi

LABRAD - Departments of Pathology & Laboratory Medicine and Radiology Archives

• Acute Leukemia Immunophenotyping with Pakistani Perspective
• PAX5: Immunohistochemistry Marker for B cell Lymphoproliferative Disorders
• Understanding the Water Deprivation Test
• Gonadotropins Releasing Hormone (GnRH) Stimulation Test
• Haematology Quiz
• Red Cell Mass Study
• Semen Analysis: An Invaluable Tool for Infertility Work-up
• Foetal Anomaly Scan
• Diagnosis of Helicobacter Pylori Infection
• Hepatitis C Virus (HCV) Genotyping
• Answer to Haematology Quiz

Correlates Of Soy Food Consumption In Adventist Health Study-2, Yen Ang

Loma Linda University Electronic Theses, Dissertations & Projects

Much has been discussed about the health benefits and risks of soy consumption but very little is known about who the consumers are. Most of what is known has been observed mainly in Asian populations who consume high levels of soy. Very little is known about soy food intake in the western population who typically has low consumption level. The Seventh-Day Adventist cohort in North America is the only population known in the West with soy food intake that is comparable to the Asian population living in the East.

Soy consumers in a population known for its healthier lifestyle and …

Does Admission Hyperglycemia Predict Intracranial And Extracranial Vasculopathy?, Ather Mohammed Taqui, Ayeesha Kamran Kamal, Saqib Ali Gowani, Bhojo A Khealani, Shafquat Rozi

Community Health Sciences

Objective: To study the association between admission hyperglycaemia and the presence and pattern of intracranial and extracranial vascular disease.
Methods: This retrospective study was conducted at a major tertiary care hospital in Karachi, Pakistan. Patients who had presented with acute stroke and had undergone a carotid ultrasound doppler of the carotids and/or Magnetic Resonance Angiography (MRA) of the brain were included in the study. A multiple logistic regression analysis of variables was done for an abnormal finding on each investigation.
Results: Out of the total of 216 patients, the age of majority of the patients (83.3%) was >50 years …

Does Admission Hyperglycemia Predict Intracranial And Extracranial Vasculopathy?, Ather Mohammed Taqui, Ayeesha Kamran Kamal, Saqib Ali Gowani, Bhojo A. Khealani, Shafquat Rozi

Department of Medicine

Objective: To study the association between admission hyperglycaemia and the presence and pattern of intracranial and extracranial vascular disease.
Methods: This retrospective study was conducted at a major tertiary care hospital in Karachi, Pakistan. Patients who had presented with acute stroke and had undergone a carotid ultrasound doppler of the carotids and/or Magnetic Resonance Angiography (MRA) of the brain were included in the study. A multiple logistic regression analysis of variables was done for an abnormal finding on each investigation.
Results: Out of the total of 216 patients, the age of majority of the patients (83.3%) was >50 years …

Photochemical Delivery Of Bleomycin In Malignant Glioma Cells, Joseph William Blickenstaff Iii

UNLV Theses, Dissertations, Professional Papers, and Capstones

Despite continued efforts, glioblastoma multiforme (GBM) remains an incurable form of primary brain cancer. Surgical resection followed by radiation treatment and chemotherapy have been the most effective modalities in prolonging median survival time to 14 months. This research aims to study the response of two different cell culture models to a novel drug delivery method termed photochemical internalization (PCI). PCI is a technique to improve the utilization of macromolecules (e.g. the chemotherapeutic drug bleomycin) in site-specific cancer therapy. This concept is based on the use of specially designed photosensitizers (e.g. aluminum phthalocyanine disulfonate; AlPcS _2a ) which preferentially localize in …

Using Thermoluminescent Dosimeters To Measure The Dose From High And Low Energy X-Ray Sources, Wesley Leon Boyd

UNLV Theses, Dissertations, Professional Papers, and Capstones

This work focused on using thermoluminescent dosimeters (TLDs) to measure the doses from two x-ray sources, a CT scanner and a linear accelerator (linac). In addition ion chambers were used to determine the isodose contours from the operation of the linac. 1mm x 1mm x 1mm TLD-100 microcubes were placed in a Lawrence Livermore National Laboratory (LLNL) torso phantom and irradiated using a Toshiba Aquilion One 320-Slice CT Scanner. Different thicknesses of shielding composed of antimony and bismuth powder suspended in an ethylene copolymer were used to shield the phantom and the dose reduction was measured. The dose reduction ranged …

Basement Membrane Proteoglycans: Modulators Par Excellence Of Cancer Growth And Angiogenesis., Renato V. Iozzo, Jason J. Zoeller, Alexander Nyström

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Proteoglycans located in basement membranes, the nanostructures underling epithelial and endothelial layers, are unique in several respects. They are usually large, elongated molecules with a collage of domains that share structural and functional homology with numerous extracellular matrix proteins, growth factors and surface receptors. They mainly carry heparan sulfate side chains and these contribute not only to storing and preserving the biological activity of various heparan sulfate-binding cytokines and growth factors, but also in presenting them in a more "active configuration" to their cognate receptors. Abnormal expression or deregulated function of these proteoglycans affect cancer and angiogenesis, and are critical …

State Infant Mortality: An Ecologic Study To Determine Modifiable Risks And Adjusted Infant Mortality Rates., David A. Paul. Md, Amy Mackley, Rnc, Robert G. Locke, Do, John L. Stefano, Md, Charlan Kroelinger, Phd

Department of Pediatrics Faculty Papers

OBJECTIVE: To determine factors contributing to state infant mortality rates (IMR) and develop an adjusted IMR in the United States for 2001 and 2002. DESIGN/METHODS: Ecologic study of factors contributing to state IMR. State IMR for 2001 and 2002 were obtained from the United States linked death and birth certificate data from the National Center for Health Statistics. Factors investigated using multivariable linear regression included state racial demographics, ethnicity, state population, median income, education, teen birth rate, proportion of obesity, smoking during pregnancy, diabetes, hypertension, cesarean delivery, prenatal care, health insurance, self-report of mental illness, and number of in-vitro fertilization …

The Pakistan Risk Of Myocardial Infarction Study: A Resource For The Study Of Genetic, Lifestyle And Other Determinants Of Myocardial Infarction In South Asia, Danish Saleheen, Moazzam Zaidi, Asif Rasheed, Usman Ahmad, Abdul Hakeem, Muhammed Murtaza, Waleed Kayani, Rashid Jooma, Nadir Khan, Nabi Shah, Asad Ali Shah, Maria Samuel, Farina Hanif, Madiha Yameen, Sobia Naz, Aisha Sultana, Aisha Nazir, Shehzad Raza, Muhammad Shazad, Sana Nasim, Muhammad Ahsan Javed, Syed Saadat Ali, Mehmood Jafree, Muhammad Imran Nisar, Altaf Hussain, Ayeesha Kamran Kamal, Philippe M. Frossard

Department of Biological & Biomedical Sciences

The burden of coronary heart disease (CHD) is increasing at a greater rate in South Asia than in any other region globally, but there is little direct evidence about its determinants. The Pakistan Risk of Myocardial Infarction Study (PROMIS) is an epidemiological resource to enable reliable study of genetic, lifestyle and other determinants of CHD in South Asia. By March 2009, PROMIS had recruited over 5,000 cases of first-ever confirmed acute myocardial infarction (MI) and over 5,000 matched controls aged 30-80 years. For each participant, information has been recorded on demographic factors, lifestyle, medical and family history, anthropometry, and a …

Nonlinear Tube-Fitting For The Analysis Of Anatomical And Functional Structures, Jeff Goldsmith, Brian S. Caffo, Ciprian Crainiceanu, Daniel Reich, Yong Du, Craig Hendrix

Johns Hopkins University, Dept. of Biostatistics Working Papers

We are concerned with the estimation of the exterior surface of tube-shaped anatomical structures. This interest is motivated by two distinct scientific goals, one dealing with the distribution of HIV microbicide in the colon and the other with measuring degradation in white-matter tracts in the brain. Our problem is posed as the estimation of the support of a distribution in three dimensions from a sample from that distribution, possibly measured with error. We propose a novel tube-fitting algorithm to construct such estimators. Further, we conduct a simulation study to aid in the choice of a key parameter of the algorithm, …

Compositions And Methods For Detecting And Treating Atherosclerosis, Nancy R. Webb, Frederick C. De Beer

Internal Medicine Faculty Patents

Methods for detecting atherosclerotic plaque and quantifying the amount of Group V sPLA₂ in plasma are disclosed. These methods can be used to assess the risk of cardiovascular pathology in a patient.

An Adrenal Beta-Arrestin 1-Mediated Signaling Pathway Underlies Angiotensin Ii-Induced Aldosterone Production In Vitro And In Vivo., Anastasios Lymperopoulos, Giuseppe Rengo, Carmela Zincarelli, Jihee Kim, Stephen Soltys, Walter J Koch

Center for Translational Medicine Faculty Papers

Aldosterone produces a multitude of effects in vivo, including promotion of postmyocardial infarction adverse cardiac remodeling and heart failure progression. It is produced and secreted by the adrenocortical zona glomerulosa (AZG) cells after angiotensin II (AngII) activation of AngII type 1 receptors (AT(1)Rs). Until now, the general consensus for AngII signaling to aldosterone production has been that it proceeds via activation of G(q/11)-proteins, to which the AT(1)R normally couples. Here, we describe a novel signaling pathway underlying this AT(1)R-dependent aldosterone production mediated by beta-arrestin-1 (betaarr1), a universal heptahelical receptor adapter/scaffolding protein. This pathway results in sustained ERK activation and subsequent …