Medical Specialties Commons^™

Chondrosarcoma Of The Mobile Spine And Sacrum, Ryan M Stuckey, Rex A W Marco

Faculty, Staff and Student Publications

Chondrosarcoma is a rare malignant tumor of bone. This family of tumors can be primary malignant tumors or a secondary malignant transformation of an underlying benign cartilage tumor. Pain is often the initial presenting complaint when chondrosarcoma involves the spine. In the mobile spine, chondrosarcoma commonly presents within the vertebral body and shows a predilection for the thoracic spine. Due to the resistance of chondrosarcoma to both radiation and chemotherapy, treatment is focused on surgery. With en bloc excision of chondrosarcoma of the mobile spine and sacrum patients can have local recurrence rates as low as 20%.

Case Of “Slow” Stroke From Carotid Artery Occlusion Treated By Delayed But Cautious Endovascular Intervention, Kachi Illoh, Emilio Supsupin, Hashem M Shaltoni, Edwin D Cacayorin

Faculty, Staff and Student Publications

In a challenging case of carotid occlusion with slowly evolving stroke, we used brain imaging to facilitate endovascular revascularization resulting in the relief of the patient's symptoms. Patients with carotid occlusion and continued neurological worsening or fluctuations present enormous treatment challenges. These patients may present "slow" strokes with subacute infarcts that present significant challenges and risks during attempts at revascularization of the occluded artery. We present such a case in which we used multimodal imaging techniques, including MR-perfusion, to facilitate endovascular revascularization. Our approach of delayed but cautious intra-arterial thrombolytic therapy, guided by brain imaging, and followed by stent placement …

Enterococcus Faecalis Rnjb Is Required For Pilin Gene Expression And Biofilm Formation, Peng Gao, Kenneth L Pinkston, Sreedhar R Nallapareddy, Ambro Van Hoof, Barbara E Murray, Barrett R Harvey

Faculty, Staff and Student Publications

Pili in Gram-positive bacteria play a major role in the colonization of host tissue and in the development of biofilms. They are promising candidates for vaccines or drug targets since they are highly immunogenic and share common structural and functional features among various Gram-positive pathogens. Numerous publications have helped build a detailed understanding of pilus surface assembly, yet regulation of pilin gene expression has not been well defined. Utilizing a monoclonal antibody developed against the Enterococcus faecalis major pilus protein EbpC, we identified mutants from a transposon (Tn) insertion library which lack surface-exposed Ebp pili. In addition to insertions in …

Peripheral Arterial Disease In Hiv Positive And Negative Subjects At The Aga Khan University Hospital, Nairobi, Farida Kaittany

Master of Medicine in Internal Medicine

Aim: To determine the prevalence of peripheral arterial disease (PAD) amongst HIV positive patients and HIV negative subjects and associated risk factors at Aga Khan Hospital Nairobi Design: Cross-sectional descriptive study Patients and Setting: A group of 125 HIV positive and 120 HIV negative subjects aged between 40 – 70 years were included in the study. HIV negative subjects were sampled from HIV positive patients attending the HIV outpatient clinic while HIV negative subjects were sampled from blood donor unit at theAga KhanUniversityHospital. Methodology: Two separate convenient samples were selected for the study. The first sample was a group of …

A Randomised Comparative Trial Of Seven Versus Fourteen Day Triple Therapy For Helicobacter Pylori Eradication At The Aga Khan University Hospital, Nairobi, Ahmed Sokwala

Master of Medicine in Internal Medicine

Background: Helicobacter is associated with a number of important upper gastrointestinal conditions including chronic gastritis, peptic ulcer disease, and gastric malignancy. Proton pump inhibitor -based triple therapies are considered the standard regimens for Helicobacter pylori eradication, but the optimal duration of these regimens is still controversial. Local studies are required to evaluate the H. pylori eradication rates in a country for adequate eradication to prevent H. pylori infection and complications Objectives: The main objective of this study was to compare 7 day and 14 day regimens and determine the optimum duration of triple therapy for H. pylori eradication. Methods: A …

Histamine Reduces Flash Sensitivity Of On Ganglion Cells In The Primate Retina, Nikolay P Akimov, David W Marshak, Laura J Frishman, Randolph D Glickman, Rafail G Yusupov

Faculty, Staff and Student Publications

PURPOSE. In Old World primates, the retina receives input from histaminergic neurons in the posterior hypothalamus. They are a subset of the neurons that project throughout the central nervous system and fire maximally during the day. The contribution of these neurons to vision, was examined by applying histamine to a dark-adapted, superfused baboon eye cup preparation while making extracellular recordings from peripheral retinal ganglion cells. METHODS. The stimuli were 5-ms, 560-nm, weak, full-field flashes in the low scotopic range. Ganglion cells with sustained and transient ON responses and two cell types with OFF responses were distinguished; their responses were recorded …

A Direct Role For Secretory Phospholipase A2 And Lyso-Phosphatidylcholine In The Mediation Of Lipopolysaccharide-Induced Gastric Injury, Elizabeth J Dial, Duy M Tran, Jimmy J Romero, Mayssa Zayat, Lenard M Lichtenberger

Faculty, Staff and Student Publications

Endotoxemia from sepsis can injure the gastrointestinal tract through mechanisms that have not been fully elucidated. We have shown that LPS induces an increase in gastric permeability in parallel with the luminal appearance of secretory phospholipase A2 (sPLA2) and its product, lysophosphatidylcholine (lyso-PC). We proposed that sPLA2 acted on the gastric hydrophobic barrier, composed primarily of phosphatidylcholine (PC), to degrade it and produce lyso-PC, an agent that is damaging to the mucosa. In the present study, we have tested whether lyso-PC and/or sPLA2 have direct damaging effects on the hydrophobic barriers of synthetic and mucosal surfaces. Rats were administered LPS …

Progressive Regression Of Left Ventricular Hypertrophy Two Years After Bariatric Surgery, Mohamed F Algahim, Thomas R Lux, Joshua G Leichman, Anthony F Boyer, Charles C Miller, Susan T Laing, Erik B Wilson, Terry Scarborough, Sherman Yu, Brad Snyder, Carol Wolin-Riklin, Ursula G Kyle, Heinrich Taegtmeyer

Faculty, Staff and Student Publications

BACKGROUND: Obesity is a systemic disorder associated with an increase in left ventricular mass and premature death and disability from cardiovascular disease. Although bariatric surgery reverses many of the hormonal and hemodynamic derangements, the long-term collective effects on body composition and left ventricular mass have not been considered before. We hypothesized that the decrease in fat mass and lean mass after weight loss surgery is associated with a decrease in left ventricular mass.

METHODS: Fifteen severely obese women (mean body mass index [BMI]: 46.7+/-1.7 kg/m(2)) with medically controlled hypertension underwent bariatric surgery. Left ventricular mass and plasma markers of systemic …

Cellular Dynamic Simulator: An Event Driven Molecular Simulation Environment For Cellular Physiology, Michael J Byrne, M Neal Waxham, Yoshihisa Kubota

Faculty, Staff and Student Publications

In this paper, we present the Cellular Dynamic Simulator (CDS) for simulating diffusion and chemical reactions within crowded molecular environments. CDS is based on a novel event driven algorithm specifically designed for precise calculation of the timing of collisions, reactions and other events for each individual molecule in the environment. Generic mesh based compartments allow the creation / importation of very simple or detailed cellular structures that exist in a 3D environment. Multiple levels of compartments and static obstacles can be used to create a dense environment to mimic cellular boundaries and the intracellular space. The CDS algorithm takes into …

Thoracic Aortic Disease In Tuberous Sclerosis Complex: Molecular Pathogenesis And Potential Therapies In Tsc2+/- Mice, Jiumei Cao, Limin Gong, Dong-Chuan Guo, Ulrike Mietzsch, Shao-Qing Kuang, Callie S Kwartler, Hazim Safi, Anthony Estrera, Michael J Gambello, Dianna M Milewicz

Faculty, Staff and Student Publications

Tuberous sclerosis complex (TSC) is a genetic disorder with pleiotropic manifestations caused by heterozygous mutations in either TSC1 or TSC2. One of the less investigated complications of TSC is the formation of aneurysms of the descending aorta, which are characterized on pathologic examination by smooth muscle cell (SMC) proliferation in the aortic media. SMCs were explanted from Tsc2(+/-) mice to investigate the pathogenesis of aortic aneurysms caused by TSC2 mutations. Tsc2(+/-) SMCs demonstrated increased phosphorylation of mammalian target of rapamycin (mTOR), S6 and p70S6K and increased proliferation rates compared with wild-type (WT) SMCs. Tsc2(+/-) SMCs also had reduced expression of …

Severity Of Acute Hepatitis And Its Outcome In Patients With Dengue Fever In A Tertiary Care Hospital Karachi, Pakistan (South Asia), Om Parkash, Aysha Almas, Wasim Jafri, Saeed Hamid, J. Akhter, Syed H Shah

Department of Medicine

Background: Liver injury due to dengue viral infection is not uncommon. Acute liver injury is a severe complicating factor in dengue, predisposing to life-threatening hemorrhage, Disseminated Intravascular Coagulation (DIC) and encephalopathy. Therefore we sought to determine the frequency of hepatitis in dengue infection and to compare the outcome (length of stay, in hospital mortality, complications) between patients of Dengue who have mild/moderate (ALT 23-300 IU/L) v/s severe acute hepatitis (ALT > 300 IU/L).

Methods: A Cohort study of inpatients with dengue viral infection done at Aga Khan University Hospital Karachi. All patients (≥ 14 yrs age) admitted with diagnosis of Dengue …

Perfusion In Rat Brain At 7 T With Arterial Spin Labeling Using Fair-Truefisp And Quipss, Emilio Esparza-Coss, Jarek Wosik, Ponnada A Narayana

Faculty, Staff and Student Publications

Measurement of perfusion in longitudinal studies allows for the assessment of tissue integrity and the detection of subtle pathologies. In this work, the feasibility of measuring brain perfusion in rats with high spatial resolution using arterial spin labeling is reported. A flow-sensitive alternating recovery sequence, coupled with a balanced gradient fast imaging with steady-state precession readout section was used to minimize ghosting and geometric distortions, while achieving high signal-to-noise ratio. The quantitative imaging of perfusion using a single subtraction method was implemented to address the effects of variable transit delays between the labeling of spins and their arrival at the …

Effect Of Indomethacin On Bile Acid-Phospholipid Interactions: Implication For Small Intestinal Injury Induced By Nonsteroidal Anti-Inflammatory Drugs, Yong Zhou, Elizabeth J Dial, Rand Doyen, Lenard M Lichtenberger

Faculty, Staff and Student Publications

The injurious effect of nonsteroidal anti-inflammatory drugs (NSAIDs) in the small intestine was not appreciated until the widespread use of capsule endoscopy. Animal studies found that NSAID-induced small intestinal injury depends on the ability of these drugs to be secreted into the bile. Because the individual toxicity of amphiphilic bile acids and NSAIDs directly correlates with their interactions with phospholipid membranes, we propose that the presence of both NSAIDs and bile acids alters their individual physicochemical properties and enhances the disruptive effect on cell membranes and overall cytotoxicity. We utilized in vitro gastric AGS and intestinal IEC-6 cells and found …

Synthesis, Biological Evaluation, And Molecular Modeling Studies Of 1-Aryl-1h-Pyrazole-Fused Curcumin Analogues As Anticancer Agents, L Curtis, P Datta, X Liu, N Bogdanova, R Heidelberger, R Janz

Faculty, Staff and Student Publications

Ribbon synapses of the vertebrate retina are specialized synapses that release neurotransmitter by synaptic vesicle exocytosis in a manner that is proportional to the level of depolarization of the cell. This release property is different from conventional neurons, in which the release of neurotransmitter occurs as a short-lived burst triggered by an action potential. Synaptic vesicle exocytosis is a calcium regulated process that is dependent on a set of interacting synaptic proteins that form the so-called SNARE (soluble N-ethylmaleimide sensitive factor attachment protein receptor) complex. Syntaxin 3B has been identified as a specialized SNARE molecule in ribbon synapses of the …

Three-Dimensional Structure Of Tropism-Switching Bordetella Bacteriophage, Wei Dai, Asher Hodes, Wong H Hui, Mari Gingery, Jeff F Miller, Z Hong Zhou

Faculty, Staff and Student Publications

Bacteriophage BPP-1, which infects Bordetella species, can switch its specificity by mutations to the ligand-binding surface of its major tropism-determinant protein, Mtd. This targeted mutagenesis results from the activity of a phage-encoded diversity-generating retroelement. Purified Mtd binds its receptor with low affinity, yet BPP-1 binding and infection of Bordettella cells are efficient because of high-avidity binding between phage-associated Mtd and its receptor. Here, using an integrative approach of three-dimensional (3D) structural analyses of the entire phage by cryo-electron tomography and single-prticle cryo-electron microscopy, we provide direct localization of Mtd in the phage and the structural basis of the high-avidity binding …

Tips And Tricks For The Trauma Patient., Anthony D Goei, Brian H Ching, Mark W Meyermann, Timothy Nunez, David Sacks

Reading Hospital Interventional Radiology

Interventions on the trauma patient are an essential component of the complete scope of care that is provided to the multiply injured patient today. The active participation by the interventional radiologist along the entire spectrum of clinical care is very important to optimize patient outcomes. Suggestions on how to establish a clinical presence are presented. A few of the newer concepts and terminology applicable to trauma care are reviewed. Tips useful in the trauma room, in the interventional radiology suite, and during the postprocedural period are discussed.

Maternal And Neonatal Outcomes By Labor Onset Type And Gestational Age, Jennifer L Bailit, Kimberly D Gregory, Uma M Reddy, Victor H Gonzalez-Quintero, Judith U Hibbard, Mildred M Ramirez, D Ware Branch, Ronald Burkman, Shoshana Haberman, Christos G Hatjis, Matthew K Hoffman, Michelle Kominiarek, Helain J Landy, Lee A Learman, James Troendle, Paul Van Veldhuisen, Isabelle Wilkins, Liping Sun, Jun Zhang

Faculty, Staff and Student Publications

OBJECTIVE: We sought to determine maternal and neonatal outcomes by labor onset type and gestational age.

STUDY DESIGN: We used electronic medical records data from 10 US institutions in the Consortium on Safe Labor on 115,528 deliveries from 2002 through 2008. Deliveries were divided by labor onset type (spontaneous, elective induction, indicated induction, unlabored cesarean). Neonatal and maternal outcomes were calculated by labor onset type and gestational age.

RESULTS: Neonatal intensive care unit admissions and sepsis improved with each week of gestational age until 39 weeks (P < .001). After adjusting for complications, elective induction of labor was associated with a lower risk of ventilator use (odds ratio [OR], 0.38; 95% confidence interval [CI], 0.28-0.53), sepsis (OR, 0.36; 95% CI, 0.26-0.49), and neonatal intensive care unit admissions (OR, 0.52; 95% CI, 0.48-0.57) compared to spontaneous labor. The relative risk of hysterectomy at term was 3.21 (95% CI, 1.08-9.54) with elective induction, 1.16 (95% CI, 0.24-5.58) with indicated induction, and 6.57 (95% CI, 1.78-24.30) with cesarean without labor compared to spontaneous labor.

CONCLUSION: Some neonatal outcomes improved until 39 weeks. Babies born with elective induction …

Emergency Evaluation Of Acute Chest Pain., Aysha Almas, Om Parkash, Aamir Hameed, Muhammad Islam

Department of Medicine

Objective: To determine the sensitivity and specificity of initial clinical assessment about the diagnosis of acute coronary syndrome (ACS) in patients presenting with acute chest pain by a cardiology resident in the emergency room and assess the 30-day outcome of patients with ACS and non ACS.

Study Design: Cohort study.

Place and Duration of Study: The study was conducted in the emergency department and cardiac care units of the Aga Khan University in 2006-07.

Methodology: A total of 202 patients, who presented to the emergency room with chest pain, were given an initial ECG and troponin check. Patients were assigned …

Elevated Albumin In Retinas Of Monkeys With Experimental Glaucoma, Louvenia Carter-Dawson, Yujin Zhang, Ronald S Harwerth, Ricky Rojas, Pramod Dash, Xinping C Zhao, Elizabeth Woldemussie, Guadalupe Ruiz, Alice Chuang, William P Dubinsky, John B Redell

Faculty, Staff and Student Publications

PURPOSE: To establish the identity of a prominent protein, approximately 70 kDa, that is markedly increased in the retina of monkeys with experimental glaucoma compared with the fellow control retina, the relationship to glaucoma severity, and its localization in the retina.

METHODS: Retinal extracts were subjected to 2-D gel electrophoresis to identify differentially expressed proteins. Purified peptides from the abundant 70 kDa protein were analyzed and identified by liquid chromatography/mass spectrometry/mass spectrometry (LC/MS/MS) separation, and collision-induced dissociation sequencing. Protein identity was performed on MASCOT (Matrix Science, Boston, MA) and confirmed by Western blot. The relationship between the increase in this …

Cardiomyocyte Pdgfr-Beta Signaling Is An Essential Component Of The Mouse Cardiac Response To Load-Induced Stress, Vishnu Chintalgattu, Di Ai, Robert R Langley, Jianhu Zhang, James A Bankson, Tiffany L Shih, Anilkumar K Reddy, Kevin R Coombes, Iyad N Daher, Shibani Pati, Shalin S Patel, Jennifer S Pocius, George E Taffet, L Maximillian Buja, Mark L Entman, Aarif Y Khakoo

Faculty, Staff and Student Publications

PDGFR is an important target for novel anticancer therapeutics because it is overexpressed in a wide variety of malignancies. Recently, however, several anticancer drugs that inhibit PDGFR signaling have been associated with clinical heart failure. Understanding this effect of PDGFR inhibitors has been difficult because the role of PDGFR signaling in the heart remains largely unexplored. As described herein, we have found that PDGFR-beta expression and activation increase dramatically in the hearts of mice exposed to load-induced cardiac stress. In mice in which Pdgfrb was knocked out in the heart in development or in adulthood, exposure to load-induced stress resulted …

Humoral Immunity In Tuberculin Skin Test Anergy And Its Role In High-Risk Persons Exposed To Active Tuberculosis, Liliana Encinales, Joaquin Zuñiga, Julio Granados-Montiel, Maria Yunis, Julio Granados, Ingrid Almeciga, Olga Clavijo, Carlos Awad, Vilma Collazos, María Inés Vargas-Rojas, José Luis Bañales-Mendez, Lilia Vazquez-Castañeda, Joel N Stern, Viviana Romero, Masha Fridkis-Hareli, Masha Frindkis-Hareli, Daniel Terreros, Marcelo Fernandez-Viña, Edmond J Yunis

Faculty, Staff and Student Publications

The most common test to identify latent tuberculosis is the tuberculin skin test that detects T cell responses of delayed type hypersensitivity type IV. Since it produces false negative reactions in active tuberculosis or in high-risk persons exposed to tuberculosis patients as shown in this report, we studied antibody profiles to explain the anergy of such responses in high-risk individuals without active infection. Our results showed that humoral immunity against tuberculin, regardless of the result of the tuberculin skin test is important for protection from active tuberculosis and that the presence of high antibody titers is a more reliable indicator …

A Woman With Hiv Infection, Brain Abscesses, And Eosinophilia, Marcela Campo, Man K Phung, Rehan Ahmed, Paul Cantey, Henry Bishop, Tanvir K Bell, Carolyn Gardiner, Cesar A Arias

Faculty, Staff and Student Publications

No abstract provided.

Future Prospects For The Utility Of Interferon Assays In Tuberculosis Diagnosis, Taimur Saleem, Madiha Syed, Bushra Jamil

Department of Medicine

No abstract provided.

H1n1 2009 In Karachi: A Situational Analysis, Bushra Jamil, Syed Faisal Mahmood

Department of Medicine

No abstract provided.

Effects Of Training On Physical Performance Wearing Personal Protective Equipment, David P. Swain, James A. Onate, Stacie I. Ringleb, Dayanand N. Naik, Marlene Demaio

Human Movement Studies & Special Education Faculty Publications

We evaluated the effects of wearing a weighted vest during 6 weeks of military-style training. Forty-three subjects were randomly assigned to a control group or a vest group (carrying 4-5 kg for 2 weeks, and 8-10 kg for 4 weeks), with 37 completing the study (17 vest, 20 control). Both groups performed stair climbing in addition to standard Marine Corps training for 1 hour, four times per week. Pre- and post-tests were performed while wearing military personal protective equipment, with the exception of the Marine Physical Readiness Test (PRT). Both groups significantly improved PRT scores (8.4% 3-mile run, 28-38% calisthenics) …

Safety, Tolerability, And Efficacy Of Fixed Combination Therapy With Dorzolamide Hydrochloride 2% And Timolol Maleate 05% In Glaucoma And Ocular Hypertension, Nicholas P Bell, José L Ramos, Robert M Feldman

Faculty, Staff and Student Publications

Glaucoma is a collection of diseases characterized by multifactorial progressive changes leading to visual field loss and optic neuropathy most frequently due to elevated intraocular pressure (IOP). The goal of treatment is the lowering of the IOP to prevent additional optic nerve damage. Treatment usually begins with topical pharmacological agents as monotherapy, progresses to combination therapy with agents from up to 4 different classes of IOP-lowering medications, and then proceeds to laser or incisional surgical modalities for refractory cases. The fixed combination therapy with the carbonic anhydrase inhibitor dorzolamide hydrochloride 2% and the beta blocker timolol maleate 0.5% is now …

3d Visualization Of Hiv Virions By Cryoelectron Tomography, Jun Liu, Elizabeth R Wright, Hanspeter Winkler

Faculty, Staff and Student Publications

The structure of the human immunodeficiency virus (HIV) and some of its components have been difficult to study in three-dimensions (3D) primarily because of their intrinsic structural variability. Recent advances in cryoelectron tomography (cryo-ET) have provided a new approach for determining the 3D structures of the intact virus, the HIV capsid, and the envelope glycoproteins located on the viral surface. A number of cryo-ET procedures related to specimen preservation, data collection, and image processing are presented in this chapter. The techniques described herein are well suited for determining the ultrastructure of bacterial and viral pathogens and their associated molecular machines …

Subacute Neural Stem Cell Therapy For Traumatic Brain Injury, Mikhail Bogdanov, Philip N Heacock, William Dowhan

Faculty, Staff and Student Publications

A protocol is described using lipid mutants and thiol-specific chemical reagents to study lipid-dependent and host-specific membrane protein topogenesis by the substituted-cysteine accessibility method as applied to transmembrane domains (SCAM). SCAM is adapted to follow changes in membrane protein topology as a function of changes in membrane lipid composition. The strategy described can be adapted to any membrane system.

More Than Synaptic Plasticity: Role Of Nonsynaptic Plasticity In Learning And Memory, Riccardo Mozzachiodi, John H Byrne

Faculty, Staff and Student Publications

Decades of research on the cellular mechanisms of memory have led to the widely held view that memories are stored as modifications of synaptic strength. These changes involve presynaptic processes, such as direct modulation of the release machinery, or postsynaptic processes, such as modulation of receptor properties. Parallel studies have revealed that memories might also be stored by nonsynaptic processes, such as modulation of voltage-dependent membrane conductances, which are expressed as changes in neuronal excitability. Although in some cases nonsynaptic changes can function as part of the engram itself, they might also serve as mechanisms through which a neural circuit …

Bicarbonate Enhances Expression Of The Endocarditis And Biofilm Associated Pilus Locus, Ebpr-Ebpabc, In Enterococcus Faecalis, Agathe Bourgogne, L Charlene Thomson, Barbara E Murray

Faculty, Staff and Student Publications

BACKGROUND: We previously identified ebpR, encoding a potential member of the AtxA/Mga transcriptional regulator family, and showed that it is important for transcriptional activation of the Enterococcus faecalis endocarditis and biofilm associated pilus operon, ebpABC. Although ebpR is not absolutely essential for ebpABC expression (100-fold reduction), its deletion led to phenotypes similar to those of an ebpABC mutant such as absence of pili at the cell surface and, consequently, reduced biofilm formation. A non-piliated ebpABC mutant has been shown to be attenuated in a rat model of endocarditis and in a murine urinary tract infection model, indicating an important participation …