Medicine and Health Sciences Commons^™

Nucleic Acid And Non-Nucleic Acid-Based Reprogramming Of Adult Limbal Progenitors To Pluripotency, Sowmya Parameswaran, Sudha Balasubramanian, Norbert Babai, Carolina B. Deldebbio, Donald W. Harms, Channabasavaiah B. Gurumurthy, Mahendra S. Rao, J. Graham Sharp, Iqbal Ahmad

Journal Articles: Ophthalmology

Reprogramming somatic cells to a pluripotent state by nucleic acid based (NAB) approaches, involving the ectopic expression of transcription factors, has emerged as a standard method. We recently demonstrated that limbal progenitors that regenerate cornea are reprogrammable to pluripotency by a non-NAB approach through simple manipulation of microenvironment thus extending the possible therapeutic use of these readily accessible cells beyond the proven treatment of corneal diseases and injury. Therefore, to determine the validity and robustness of non-cell autonomous reprogramming of limbal progenitors for a wider clinical use, here, we have compared their reprogramming by non-NAB and NAB approaches. We observed …

Orientation-Invariant Ecg-Based Virtual Pathology Stethoscope Tracking For Standardized Patient Heart Auscultation, Nahom B. Kidane

Computational Modeling & Simulation Engineering Theses & Dissertations

Cardiac auscultation (CA), the act of listening to the heart sounds, is a critical physician's skill that provides substantial information for diagnosing many cardiovascular disorders; therefore, competent training can be a key for accurate and reliable diagnosis. The teaching of CA has been an area of recognized importance since the inception of the stethoscope. However, recent changes in health-care, such as limited student access to patients and higher reliance on competing technologies have made it challenging to teach bedside CA techniques.

Over the past few decades, standardized patients (SPs), individuals trained to portray real patients, have been widely used for …

Pulmonary Complications In Patients With Severe Brain Injury., Kiwon Lee, Fred Rincon

Department of Neurology Faculty Papers

Pulmonary complications are prevalent in the critically ill neurological population. Respiratory failure, pneumonia, acute lung injury and the acute respiratory distress syndrome (ALI/ARDS), pulmonary edema, pulmonary contusions and pneumo/hemothorax, and pulmonary embolism are frequently encountered in the setting of severe brain injury. Direct brain injury, depressed level of consciousness and inability to protect the airway, disruption of natural defense barriers, decreased mobility, and secondary neurological insults inherent to severe brain injury are the main cause of pulmonary complications in critically ill neurological patients. Prevention strategies and current and future therapies need to be implemented to avoid and treat the development …

Comparison Of Upper Lip Bite Test With Mallampati Test In The Prediction Of Difficult Intubation At A Tertiary Care Hospital Of Pakistan, Muhammad Asghar Ali, Muhammad Qamar-Ul-Hoda, Khalid Samad

Department of Anaesthesia

Objective: To determine the accuracy of the Upper lip bite test and Mallampati test in predicting difficult endotracheal intubation.Methods: The cross-sectional study was conducted at the Aga Khan University Hospital, a tertiary care facility in Karachi, Pakistan. Between June 1,2007 and May 31, 2008, 324 adult patients undergoing elective surgeries requiring general anaesthesia with endotracheal intubations were enrolled. Pre-operatively upper lip bite test and Mallampati test were performed for the assessment of airway by a specifically trained observer. Laryngoscopic view was rated by using Cormack and Lehane laryngoscopic grading once the patient was fully anaesthetised using standard anaesthesia technique. Completed …

Visual Function After Correction Of Distance Refractive Error With Ready-Made And Custom Spectacles: A Randomized Clinical Trial., Christopher J. Brady, Andrea C Villanti, Monica Gandhi, David S Friedman, Lisa Keay

Wills Eye Hospital Papers

PURPOSE: To evaluate patient-reported outcome measures with the use of ready-made spectacles (RMS) and custom spectacles (CS) in an adult population in India with uncorrected refractive error (URE).

DESIGN: Prospective, double-masked, randomized trial with 1-month follow-up.

PARTICIPANTS: A total of 363 adults aged 18 to 45 years with ≥1 diopter (D) of URE (RMS, n = 183; CS, n = 180).

INTERVENTION: All participants received complete refraction and were randomized to receive CS (full sphero-cylindrical correction) or RMS based on the spherical equivalent for the eye with lower refractive error but limited to the powers in the RMS inventory.

MAIN …

Neurosteroid-Mediated Regulation Of Brain Innate Immunity In Hiv/Aids: Dhea-S Suppresses Neurovirulence, Amber Paul, Ferdinand G. Maingat, Maria J. Polyak, Pornpun Vivithanaporn, Farshid Noorbakhsh, Samir Ahboucha, Glen B. Baker, Keir Pearson, Christopher Power

Publications

Neurosteroids are cholesterol-derived molecules synthesized within the brain, which exert trophic and protective actions. Infection by human and feline immunodeficiency viruses (HIV and FIV, respectively) causes neuroinflammation and neurodegeneration, leading to neurological deficits. Secretion of neuroinflammatory host and viral factors by glia and infiltrating leukocytes mediates the principal neuropathogenic mechanisms during, although the effect of neurosteroids on these processes is unknown. We investigated the interactions between neurosteroid mediated effects and lentivirus infection outcomes. Analyses of HIV-infected uninfected human brains disclosed a reduction in neurosteroid synthesis enzyme expression. Human neurons exposed to supernatants from HIV macrophages exhibited suppressed enzyme expression without …

Early Abnormal Sponteneous Activity Findings In Axonal Variant Of Guillain Barre Syndrome: Is This A New Variant Of Guillain Barre Syndrome?, Ghulam Shabbir Dr., Asad Ullah Dr., M.A. Lakhair Dr., Ali Majid Dr., Emran Rashid Dr.

Pakistan Journal of Neurological Sciences (PJNS)

No abstract provided.

Acute Quadriparesis Due To Acute Demyelinating Polyneuropathy In A Patient Newly Diagnosed As A Case Of B -Cell Lymphoma- An Unusual Presentation. A Case Report With Review Of Literature, Sardar M. Alam, Haroon Khan, Rafi Ud Din, Faiqa Filza, Tariq Khan

Pakistan Journal of Neurological Sciences (PJNS)

No abstract provided.

Transfusion Therapy As A Sole Treatment Option In A Thalassemia Patient With Acute Paraplegia – A Case Report And Review Of Literature, Sana Rashid

Pakistan Journal of Neurological Sciences (PJNS)

No abstract provided.

Delayed Diagnosis Of Hand Injuries In Polytrauma Patients (Poster), Joshua M. Adkinson Md, Muhammad Shuja Shafqat Md, Sherrine Eid Mph, Marshall G. Miles Do

Department of Surgery

No abstract provided.

Characterization And Normal Measurements Of The Left Ventricular Outflow Tract By Ecg-Gated Cardiac Ct: Implications For Disorders Of The Outflow Tract And Aortic Valve., Ethan J Halpern, Shiva Gupta, David J Halpern, David H Wiener, Alyson N Owen

Department of Radiology Faculty Papers

RATIONALE AND OBJECTIVES: Studies suggest that electrocardiographically gated coronary computed tomographic angiography provides a clear definition of the left ventricular outflow tract (LVOT), and normal LVOT morphology may not be round, as assumed when the continuity equation is applied during echocardiography. The aims of this study were to demonstrate the morphology of the LVOT on coronary computed tomographic angiography and to establish normal values for LVOT measurements.

MATERIALS AND METHODS: Two independent readers retrospectively measured anterior-posterior (AP) and transverse diameters of the LVOT and performed LVOT planimetry on coronary computed tomographic angiographic studies of 106 consecutive patients with normal aortic …

Parenthood With Exposure To Mycophenolic Acid Products, Sophia M. Termimi, Megan Clary, Lisa Coscia, Carolyn Mcgrory, Vincent T. Armenti

Department of Surgery Faculty Papers

Successful pregnancy outcomes have been reported in all solid-organ transplant recipients on a variety of immunosuppressive medication regimes. In October 2007, the FDA pregnancy category of mycophenolic acid products (MPA) was changed from category C to D, based on registry and post-marketing data which revealed a higher incidence of spontaneous abortions and structural birth defects. The purpose of this abstract is to describe pregnancy outcomes with exposure to MPA and pregnancies fathered by male transplant recipients conceived while taking MPA. Data were collected by the National Transportation Pregnancy Registry (NTPR) via questionnaires, telephone interview and medical records. There were 152 …

Compliance With Surgical Care Improvement Project Blood Glucose--A Marker For Euglycemia, But Does It Put Our Patients At Risk?, Isaac R Whitman, Maura Murphy, Marta M Gilson, Amy Campfield, Michel Haddad, Elizabeth Moxey, Glenn J R Whitman

Department of Surgery Faculty Papers

To improve outcomes in open heart surgery (OHS) patients, the Surgical Care Improvement Project (SCIP) requires 6 am postoperative day (POD) 1 and 2 blood glucose (BG) to be ≤200mg/dL. This study examined risk factors for SCIP noncompliance when using an insulin infusion protocol (IIP) and evaluated this SCIP metric as a surrogate for glycemic control. The authors divided 99 consecutive OHS patients, all subjected to 1 uniform IIP, into 2 groups: Group 1-SCIP compliant (n=79) and Group 2-SCIP noncompliant (n=20). They determined mean BG for the first 48 postoperative hours, percent of total time with hyperglycemia (% time BG …

Pediatric Pharmacogenomics: A Systematic Assessment Of Ontogeny And Genetic Variation To Guide The Design Of Statin Studies In Children., Jonathan B. Wagner, J Steven Leeder

Manuscripts, Articles, Book Chapters and Other Papers

The dose-exposure-response relationship for drugs may differ in pediatric patients compared with adults. Many clinical studies have established drug dose-exposure relationships across the pediatric age spectrum; however, genetic variation was seldom included. This article applies a systematic approach to determine the relative contribution of development and genetic variation on drug disposition and response using HMG-CoA reductase inhibitors as a model. Application of the approach drives the collection of information relevant to understanding the potential contribution of ontogeny and genetic variation to statin dose-exposure-response in children, and identifies important knowledge deficits to be addressed through the design of future studies.

Cause, Timing, And Location Of Death In The Single Ventricle Reconstruction Trial., Richard G. Ohye, Julie V. Schonbeck, Pirooz Eghtesady, Peter C. Laussen, Christian Pizarro, Peter Shrader, Deborah U. Frank, Eric M. Graham, Kevin D. Hill, Jeffrey P. Jacobs, Kirk R. Kanter, Joel A. Kirsh, Linda M. Lambert, Alan B. Lewis, Chitra Ravishankar, James S. Tweddell, Ismee A. Williams, Gail D. Pearson, Pediatric Heart Network Investigators, Girish S. Shirali

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVES: The Single Ventricle Reconstruction trial randomized 555 subjects with a single right ventricle undergoing the Norwood procedure at 15 North American centers to receive either a modified Blalock-Taussig shunt or right ventricle-to-pulmonary artery shunt. Results demonstrated a rate of death or cardiac transplantation by 12 months postrandomization of 36% for the modified Blalock-Taussig shunt and 26% for the right ventricle-to-pulmonary artery shunt, consistent with other publications. Despite this high mortality rate, little is known about the circumstances surrounding these deaths.

METHODS: There were 164 deaths within 12 months postrandomization. A committee adjudicated all deaths for cause and recorded the …

Variation In Perioperative Care Across Centers For Infants Undergoing The Norwood Procedure., Sara K. Pasquali, Richard G. Ohye, Minmin Lu, Jonathan Kaltman, Christopher A. Caldarone, Christian Pizarro, Carolyn Dunbar-Masterson, J William Gaynor, Jeffrey P. Jacobs, Aditya K. Kaza, Jane Newburger, John F. Rhodes, Mark Scheurer, Eric Silver, Lynn A. Sleeper, Sarah Tabbutt, James Tweddell, Karen Uzark, Winfield Wells, William T. Mahle, Gail D. Pearson, Pediatric Heart Network Investigators, Girish S. Shirali

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVES: In the Single Ventricle Reconstruction trial, infants undergoing the Norwood procedure were randomly allocated to undergo a right ventricle-to-pulmonary artery shunt or a modified Blalock-Taussig shunt. Apart from shunt type, subjects received the local standard of care. We evaluated variation in perioperative care during the Norwood hospitalization across 14 trial sites.

METHODS: Data on preoperative, operative, and postoperative variables for 546 enrolled subjects who underwent the Norwood procedure were collected prospectively on standardized case report forms, and variation across the centers was described.

RESULTS: Gestational age, birth weight, and proportion with hypoplastic left heart syndrome were similar across sites. …

Anaesthetic Management Of Neonatal Primary Hyperparathyroidism, Anwar-Ul-Huda, Sanam Dost Mohammad, Tauseef Ahmed

Department of Anaesthesia

Neonatal primary hyperparathyroidism (NPHP) is a rare disease that presents in the first 6 months of life. It is almost invariably fatal unless a prompt diagnosis is made and urgent surgical intervention is instituted. Patients with hyperparathyroidism require special preoperative considerations. They require proper work-up from cardiac, renal and neurological point of view, correction of intravenous volume and electrolytes irregularities. We are presenting a case of an infant who started to have cyanosis and lethargy at 21st day of life. Initial diagnosis of pneumonia was made but later on diagnosed as hyperparathyroidism. He was planned for parathyroidectomy under general anaesthesia. …

Phase Ii Evaluation Of Dasatinib In The Treatment Of Recurrent Or Persistent Epithelial Ovarian Or Primary Peritoneal Carcinoma: A Gynecologic Oncology Group Study., Russell J Schilder, William E Brady, Heather A Lankes, James V Fiorica, Mark S Shahin, Xun C Zhou, Robert S Mannel, Harsh B Pathak, Wei Hu, R Katherine Alpaugh, Anil K Sood, Andrew K Godwin

Department of Medical Oncology Faculty Papers

OBJECTIVES: Preclinical data suggest an important role for the sarcoma proto-oncogene tyrosine kinase (SRC) in the oncogenesis of epithelial ovarian cancer (EOC) or primary peritoneal carcinoma (PPC). The Gynecologic Oncology Group (GOG) conducted a Phase II trial to evaluate the efficacy and safety of dasatinib, an oral SRC-family inhibitor in EOC/PPC, and explored biomarkers for possible association with clinical outcome.

METHODS: Eligible women had measurable, recurrent or persistent EOC/PPC and had received one or two prior regimens which must have contained a platinum and a taxane. Patients were treated with 100mg orally daily of dasatinib continuously until progression of disease …

Mri Findings In Methanol Intoxication: A Report Of Three Cases, Muhammad Azeemuddin, Rohana Naqi

Department of Radiology

Methanol is a highly toxic substance and acute methanol poisoning produces severe metabolic acidosis and serious neurological symptoms, including severe visual impairment, extrapyramidal signs and coma. We present three cases of accidental methanol intoxication and discuss the MRI findings.

Non-Compaction Of The Left Ventricle And Associated Ventricular Septal Defect., Abid Laghari, Javed Tai, Sumaira Saleem

Department of Medicine

A case report of a 28-year-old patient, who presented with symptoms and signs of congestive heart failure and had clinical signs of ventricular septal defect as well. On further work-up echocardiogram showed non-compaction of the left ventricle with severe left ventricular systolic dysfunction and a ventricular septal defect. He was treated with standard treatment of heart failure and is doing well.

Cabergoline Therapy For Macroprolactinoma During Pregnancy: A Case Report., Hira Shahzad, Aisha Sheikh, Lumaan Sheikh

Department of Medicine

Background: We assessed the safety of Cabergoline therapy during pregnancy in a lady with hyperprolactinemia intolerant to Bromocriptine.

Case presentation: We report the case of a 31 year old lady who presented to us with uncontrolled hyperprolactinemia. A pituitary Macroadenoma was demonstrated by MRI. Due to intolerance to Bromocriptine, Cabergoline was started. The patient improved and subsequently conceived. MRI in the second trimester demonstrated further reduction in the tumor size. It was decided to continue Cabergoline throughout pregnancy to ensure further reduction in tumor size until delivery and to hold Cabergoline during postpartum period to allow for an adequate interval …

Situation Analysis Of Child Labour In Karachi, Pakistan: A Qualitative Study, Asaad Ahmed Nafees, Kausar S. Khan, Zafar Fatmi, Mubashir Aslam

Community Health Sciences

In Karachi, large employment opportunities, burgeoning population and the availability of cheap labour might be the contributing factors for the increasing prevalence of child labour. A literature review was conducted in 2007 that included published and unpublished literature since 2000. Various organizations working in the field were also covered, while the perception of the child labourers was covered through three focus group discussions. Common health issues among the child labourers in Karachi included respiratory illnesses, fever and generalised pains, as well as drug and sexual abuse. Organisations working for child labour could be broadly categorised into those working for legal …

Are Robots Any Better In Stroke Rehabilitation?, Muhammad Faisal Wadiwala, Ayeesha Kamran Kamal

Department of Medicine

No abstract provided.

Recurrent Non-Aneurysmal, Metastatic Intraparenchymal Haemorrhages Following Resection Of Atrial Myxoma - Case Report And Literature Review., Emmon Raza, Ayeesha Kamran Kamal

Department of Medicine

Atrial myxomas are the commonest cardiac neoplasms. The most common extra-cardiac manifestations are embolic infarcts from tumour embolisation. Infrequently, aneurysm formation and intracranial haemorrhages also occur. Incredibly rare are space-occupying lesions and malignant transformation. The authors report a case of a previously healthy middle-aged lady who developed recurrent and expanding intraparenchymal haemorrhages following resection of a left atrial myxoma without any primary disease recurrence. The case described is completely different from the described literature in that her intracranial vasculature was free of aneurysms on angiography despite central nervous system haemorrhage and no myxomatous or malignant features were seen on histology …

Conventional Isolated Aortic Valve Replacement In Octogenarians: A 10-Year Single Center Experience, James K. Wu Md, Justin D. Roberts Do, Gregory S. Troutman Bs, Michael J. Weiss Mph, Sanjay M. Mehta Md, Theodore G. Phillips Md, Michael F. Szwerc Md, Gary W. Szydlowski Md, Timothy S. Misselbeck, Raymond L. Singer Md

Department of Surgery

No abstract provided.

Determining The Absolute Requirement Of G Protein-Coupled Receptor Kinase 5 For Pathological Cardiac Hypertrophy: Short Communication., Jessica I Gold, Erhe Gao, Xiying Shang, Richard T Premont, Walter J Koch

Center for Translational Medicine Faculty Papers

RATIONALE: Heart failure (HF) is often the end phase of maladaptive cardiac hypertrophy. A contributing factor is activation of a hypertrophic gene expression program controlled by decreased class II histone deacetylase (HDAC) transcriptional repression via HDAC phosphorylation. Cardiac-specific overexpression of G proteinen-coupled receptor kinase-5 (GRK5) has previously been shown to possess nuclear activity as a HDAC5 kinase, promoting an intolerance to in vivo ventricular pressure overload; however, its endogenous requirement in adaptive and maladaptive hypertrophy remains unknown.

OBJECTIVE: We used mouse models with global or cardiomyocyte-specific GRK5 gene deletion to determine the absolute requirement of endogenous GRK5 for cardiac hypertrophy …

Doxycycline Does Not Influence Established Abdominal Aortic Aneurysms In Angiotensin Ii-Infused Mice, Xiaojie Xie, Hong Lu, Jessica J. Moorleghen, Deborah A. Howatt, Debra L. Rateri, Lisa A. Cassis, Alan Daugherty

Saha Cardiovascular Research Center Faculty Publications

Background: There is no proven medical approach to attenuating expansion and rupture of abdominal aortic aneurysms (AAAs). One approach that is currently being investigated is the use of doxycycline. Despite being primarily used as an antimicrobial drug, doxycycline has been proposed to function in reducing AAA expansion. Doxycycline is effective in reducing the formation in the most commonly used mouse models of AAAs when administered prior to the initiation of the disease. The purpose of the current study was to determine the effects of doxycycline on established AAAs when it was administered at a dose that produces therapeutic serum …

Weight Gain, Metabolic Syndrome, And Breast Cancer Recurrence: Are Dietary Recommendations Supported By The Data?, Colin E Champ, Jeff S Volek, Joshua Siglin, Lianjin Jin, Nicole L Simone

Department of Radiation Oncology Faculty Papers

Metabolic syndrome, which can include weight gain and central obesity, elevated serum insulin and glucose, and insulin resistance, has been strongly associated with breast cancer recurrence and worse outcomes after treatment. Epidemiologic and prospective data do not show conclusive evidence as to which dietary factors may be responsible for these results. Current strategies employ low-fat diets which emphasize supplementing calories with increased intake of fruit, grain, and vegetable carbohydrate sources. Although results thus far have been inconclusive, recent randomized trials employing markedly different dietary strategies in noncancer patients may hold the key to reducing multiple risk factors in metabolic syndrome …

The Effect Of Iliac Crest Autograft On The Outcome Of Fusion In The Setting Of Degenerative Spondylolisthesis: A Subgroup Analysis Of The Spine Patient Outcomes Research Trial (Sport)., Kristen Radcliff, Raymond Hwang, Alan Hilibrand, Harvey E Smith, Jordan Gruskay, Jon D Lurie, Wenyan Zhao, Todd Albert, James Weinstein

Rothman Institute Papers

BACKGROUND: There is considerable controversy about the long-term morbidity associated with the use of posterior autologous iliac crest bone graft for lumbar spine fusion procedures compared with the use of bone-graft substitutes. The hypothesis of this study was that there is no long-term difference in outcome for patients who had posterior lumbar fusion with or without iliac crest autograft.

METHODS: The study population includes patients enrolled in the degenerative spondylolisthesis cohort of the Spine Patient Outcomes Research Trial who underwent lumbar spinal fusion. Patients were divided according to whether they had or had not received posterior autologous iliac crest bone …

Perlecan Domain V Induces Vegf Secretion In Brain Endothelial Cells Through Integrin Α5Β1 And Erk-Dependent Signaling Pathways., Douglas N Clarke, Abraham Al Ahmad, Boyeon Lee, Christi Parham, Lisa Auckland, Andrezj Fertala, Michael Kahle, Courtney S Shaw, Jill Roberts, Gregory J Bix

Department of Dermatology and Cutaneous Biology Faculty Papers

Perlecan Domain V (DV) promotes brain angiogenesis by inducing VEGF release from brain endothelial cells (BECs) following stroke. In this study, we define the specific mechanism of DV interaction with the α(5)β(1) integrin, identify the downstream signal transduction pathway, and further investigate the functional significance of resultant VEGF release. Interestingly, we found that the LG3 portion of DV, which has been suggested to possess most of DV's angio-modulatory activity outside of the brain, binds poorly to α(5)β(1) and induces less BEC proliferation compared to full length DV. Additionally, we implicate DV's DGR sequence as an important element for the interaction …