Medicine and Health Sciences Commons^™

Ccl2 Responses To Mycobacterium Tuberculosis Are Associated With Disease Severity In Tuberculosis, Zahra Hasan, Jacqueline M. Cliff, Hazel M. Dockrell, Bushra Jamil, Muhammad Irfan, Mussarat Ashraf, Rabia Hussain

Section of Pulmonary & Critical Care

Background

Leucocyte activating chemokines such as CCL2, CCL3, and CXCL8 together with proinflammatory IFNγ, TNFα and downmodulatory IL10 play a central role in the restriction of M. tuberculosis infections, but is unclear whether these markers are indicative of tuberculosis disease severity.

Methodology

We investigated live M. tuberculosis- and M. bovis BCG- induced peripheral blood mononuclear cell responses in patients with tuberculosis (TB) and healthy endemic controls (ECs, n = 36). TB patients comprised pulmonary (PTB, n = 34) and extrapulmonary groups, subdivided into those with less severe localized extrapulmonary TB (L-ETB, n = 16) or severe disseminated ETB (D-ETB, …

Guyon's Canal Syndrome Due To Tortuous Ulnar Artery With Dequervain Stenosing Tenosynovitis, Ligamentous Injuries And Dorsal Intercalated Segmental Instability Syndrome, A Rare Presentation: A Case Report., Muhammad Zeeshan, Farhan Ahmed, Darakhshan Kanwal, Qazi Saad Bin Khalid, Muhammad Nadeem Ahmed

Department of Radiology

The Guyon's canal syndrome is a well known clinical entity and may have significant impact on Patient's quality of life. We report a case of 43-year-old male who presented with complaints of pain and numbness in right hand and difficulty in writing for past one month. On imaging diagnosis of Guyon's canal syndrome because of tortuous ulnar artery was made with additional findings of DeQuervain's stenosing tenosynovitis and dorsal intercalated segmental instability syndrome with ligamentous injury and subsequently these were confirmed on surgery. Although it is a rare syndrome, early diagnosis and treatment prevents permanent neurological deficits and improve Patient's …

Gbdr Regulates Pseudomonas Aeruginosa Plch And Pchp Transcription In Response To Choline Catabolites, Matthew J. Wargo, Tiffany C. Ho, Maegan J. Gross, Laurie A. Whittaker, Deborah A. Hogan

Dartmouth Scholarship

Pseudomonas aeruginosa hemolytic phospholipase C, PlcH, can degrade phosphatidylcholine (PC) and sphingomyelin in eukaryotic cell membranes and extracellular PC in lung surfactant. Numerous studies implicate PlcH in P. aeruginosa virulence. The phosphorylcholine released by PlcH activity on phospholipids is hydrolyzed by a periplasmic phosphorylcholine phosphatase, PchP. Both plcH gene expression and PchP enzyme activity are positively regulated by phosphorylcholine degradation products, including glycine betaine. Here we report that the induction of plcH and pchP transcription by glycine betaine is mediated by GbdR, an AraC family transcription factor. Mutants that lack gbdR are unable to induce plcH and pchP in media …

T Cell Receptor Cross-Reactivity Directed By Antigen-Dependent Tuning Of Peptide-Mhc Molecular Flexibility, Oleg Y. Borbulevych, Kurt H. Piepenbrink, Brian E. Gloor, Daniel R. Scott, Ruth F. Sommese, David K. Cole, Andrew K. Sewell, Brian M. Baker

Food for Health: Publications

Tell mediated immunity requires T cell receptor (TCR) cross-reactivity, the mechanisms behind which remain incompletely elucidated. The αβ TCR A6 recognizes both the Tax (LLFGYPVYV) and Tel1p (MLWGYLQYV) peptides presented by the human class I MHC molecule HLA-A2. Here we found that although the two ligands are ideal structural mimics, they form substantially different interfaces with A6, with conformational differences in the peptide, the TCR, and unexpectedly, the MHC molecule. The differences between the Tax and Tel1p ternary complexes could not be predicted from the free peptide-MHC structures and are inconsistent with a traditional induced-fit mechanism. Instead, the differences were …

Regulation Of Cellular Protein Phosphatase-1 (Pp1) By Phosphorylation Of The Cpi-17 Family, C-Kinase-Activated Pp1 Inhibitors., Masumi Eto

Department of Molecular Physiology and Biophysics Faculty Papers

The regulatory circuit controlling cellular protein phosphatase-1 (PP1), an abundant group of Ser/Thr phosphatases, involves phosphorylation of PP1-specific inhibitor proteins. Malfunctions of these inhibitor proteins have been linked to a variety of diseases, including cardiovascular disease and cancer. Upon phosphorylation at Thr(38), the 17-kDa PP1 inhibitor protein, CPI-17, selectively inhibits a specific form of PP1, myosin light chain phosphatase, which transduces multiple kinase signals into the phosphorylation of myosin II and other proteins. Here, the mechanisms underlying PP1 inhibition and the kinase/PP1 cross-talk mediated by CPI-17 and its related proteins, PHI, KEPI, and GBPI, are discussed.

Giant Synovial Cell Sarcoma Of The Thorax In A 46-Year-Old Man: A Case Report., Saulat Hasnain Fatimi, Taimur Saleem

Department of Surgery

Background:Although synovial cell sarcoma is a common tumor of the extremities, its occurrence in the thorax has been less frequently documented. Case Presentation: A 46-year-old Pakistani man presented with a 2 month history of progressively increasing cough and left lower chest pain. Initial evaluation was done using a chest x-ray, the Patient was found to have a large mass involving the lower portion of the left chest. A computed tomography scan was performed next which showed a large mass involving the left chest wall with invasion into the pericardium and left hemidiaphragm. En bloc surgical resection of the tumor …

Clinical Profile, Outcomes And Improvement In Symptoms And Productivity In Rhinitic Patients In Karachi, Pakistan., Taimur Saleem, Umair Khalid, Ubaid Ur Rehman Sherwani, Shehzad Ghaffar

Section of Otolaryngology, Head & Neck Surgery

Background:Rhinitis can cause a heavy toll on Patients because of its bothersome effects on productivity. This retrospective study was conducted to explore the clinical profile, outcomes and improvement in the symptoms and productivity resulting from treatment of allergic rhinitis in Pakistan.

Methods:

We carried out a retrospective file review of all allergic rhinitis Patients who presented to the Ear, Nose, Throat Consulting Clinic from January, 2006 to June, 2008 using a structured proforma especially designed for this Purpose. Data was entered and analyzed using SPSS v. 16.0.

Results:

The charts of 169 Patients were reviewed. The mean age of …

Addition Of Levalbuterol To A Pediatric Emergency Department Automated Medication Management System Does Not Increase Its Use., Gregory P. Conners, Daniel P. Hays, Thomas Richardson, Frank L. Zwemer

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Although adding a drug to an emergency department-based automated medication management system is known to increase how frequently it is ordered, little is known about this effect when the added drug does not offer substantial benefit over a substitute drug that was already available.

AIMS: We studied the effect of adding nebulized levalbuterol to a pediatric emergency department-based automated medication management system that already included albuterol.

METHODS: All completed orders for nebulized levalbuterol or nebulized albuterol from our academic pediatric emergency department were retrospectively identified using a computerized pharmacy database. We compared ordering of these drugs for the year …

Human Amnion As A Novel Cell Delivery Vehicle For Chondrogenic Mesenchymal Stem Cells, Tunku Kamarul Zaman

Tunku Kamarul Zaman

This study investigates the feasibility of processed human amnion (HAM) as a substrate for chondrogenic differentiation of mesenchymal stem cells (MSCs). HAM preparations processed by air drying (AD) and freeze drying (FD) underwent histological examination and MSC seeding in chondrogenic medium for 15 days. Monolayer cultures were used as control for chondrogenic differentiation and HAMs without cell seeding were used as negative control. Qualitative observations were made using scanning electron microscopy analysis and quantitative analyses were based on the sulfated glycosaminoglycans (GAG) assays performed on day 1 and day 15. Histological examination of HAM substrates before seeding revealed a smooth …

Perioperative Hyperglycemia Increases Risk For Deep Wound Infection After Major Orthopedic Surgery, Boris Mraovic, Md, Orhan Bican, Md, Javad Parvizi, Md, Jeffrey I. Joseph, D.O.

Department of Anesthesiology Faculty Papers

Total hip and knee replacement surgery are one of the most frequent major surgeries performed in the USA. In 2002, the number of primary hip and knee arthroplasty was 119,000 and 381,000, respectively. By year 2030 the number is projected to increase to 572,000 and 3,481,000 respectively.

Deep wound infection after major orthopedic surgery is one of the most serious complications causing increase in morbidity and mortality and health care costs. Various risk factors for developing infection after hip and knee replacement surgery were described including age, ASA PS status, obesity, patients' comorbidities and surgical technique factors.

Perioperative hyperglycemia may …

Oocyte Peptides As Paracrine Tools For Ovarian Stimulation And Oocyte Maturation., David G Mottershead, Andrew J Watson

Obstetrics & Gynaecology Publications

Recent studies report the production and isolation of a stable bioactive recombinant human bone morphogenetic protein 15 (rhBMP15) that is appropriately processed in HEK-293 cells and activates the SMAD 1/5/8 pathway in mouse granulosa cell cultures. Further, the purified rhBMP15 induces the expression of genes associated with cumulus expansion. Thanks to recent research, we have a greater understanding of the importance of the dialogue that occurs between the oocyte and the granulosa cell layer with regard to regulating folliculogenesis and the acquisition of oocyte developmental competence and maturation. BMP15 is one of the critical components of these intra-follicular communication pathways. …

No Association Of Obesity And Type 2 Diabetes Mellitus Related Genetic Variants With Colon Cancer, Cheryl L. Thompson, Sarah J. Plummer, Thomas C. Tucker, Graham Casey, Li Li

Markey Cancer Center Faculty Publications

Background: Obesity and type 2 diabetes mellitus (T2D) are known risk factors for colon cancer. Recent reports from a number of genome wide association studies (GWAS) have identified several single nucleotide polymorphisms (SNPs) associated with obesity and T2D. Here we tested the hypothesis that these SNPs may also be associated with risk of colon cancer.

Methods: We genotyped nine SNPs reported in GWAS of obesity and/or T2D, including SNPs in HHEX, KCNJ11, SLC30A8, FTO, CDKN2, CDKAL1, TCF2, and the rs9300039 SNP in an intergenic region, in 561 colon cancer cases and 721 population controls.

Results: None of these SNPs were …

Epocrates….Is It Useful At The Neonatal Bedside?, Bobby L. Miller Md

Biochemistry and Microbiology

Most physicians, including residents and medical students have heard of, and many use, a mobile drug database called Epocrates. The purpose of this review is to evaluate Epocrates as a bedside tool from the perspective of a neonatologist on a busy teaching service.

End-Of-Life Issues In The Acute And Critically Ill Patient, Eric A. Savory, Catherine A. Marco

Emergency Medicine Faculty Publications

The challenges of end-of-life care require emergency physicians to utilize a multifaceted and dynamic skill set. Such skills include medical therapies to relieve pain and other symptoms near the end-of-life. Physicians must also demonstrate aptitude in comfort care, communication, cultural competency, and ethical principles. It is imperative that emergency physicians demonstrate a fundamental understanding of end-of-life issues in order to employ the versatile, multidisciplinary approach required to provide the highest quality end-of-life care for patients and their families.

Surgical Tourniquets In Orthopedics, Shahryar Noordin, James A. Mcewen, John F. Kragh, Andrew Eisen, Bassam A. Masri

Section of Orthopaedic Surgery

No abstract provided.

Trauma Registry Needs And Challenges In Developing Countries., Amber Mehmood, Junaid Abdul Razzak

Department of Emergency Medicine

No abstract provided.

Fuzzy Logic In Neurosurgery: Predicting Poor Outcomes After Lumbar Disk Surgery In 501 Consecutive Patients, Muhammad Shahzad Shamim, Ather Enam, Uvais Qidwai

Section of Neurosurgery

Background: Despite a lot of research into Patient selection, a significant number of Patients fail to benefit from surgery for symptomatic lumbar disk herniation. We have used Fuzzy Logic-based fuzzy inference system (FIS) for identifying Patients unlikely to improve after disk surgery and explored FIS as a tool for surgical outcome prediction.
Methods: Data of 501 Patients were retrospectively reviewed for 54 independent variables. Sixteen variables were short-listed based on heuristics and were further classified into memberships with degrees of membership within each. A set of 11 rules was formed, and the rule base used individual membership degrees and their …

Etiology, Functional Status And Short Term Outcome Of Patients With Pituitary Lesions. An Experience From A Developing Country, Osama Ishtiaq, Mansoor Ul Haq, Azra Rizwan, Mohammad Qamar Masood, Saeed Mehar, Abdul Jabbar

Section of Diabetes, Endocrinology and Metabolism

OBJECTIVE: To describe the etiology, functional status and short term outcome of patients with pituitary lesions (PL).

METHODS: Brain or pituitary MRI reports of 3753 patients were analyzed for PL over the period of 2000 to 2007, done at the Aga Khan University Hospital (AKUH), Karachi, Pakistan. MRIs with reported PL and all those ordered by Endocrinologists with or without pituitary abnormalities, were included in the analysis. This made a total of 338 (9%) MRI reports. PL were defined as pituitary tumors, cysts, haemorrhage, hypoplasia; and empty sella. Patients with these PL, were analyzed for symptoms, hormonal profile and short …

Stromal Caveolin-1 Levels Predict Early Ductal Carcinoma In Situ Progression To Invasive Breast Carcinoma, A. K. Witkiewicz, A. Dasgupta, G. F. Schwartz, Kh H. Nguyen, H. R. Rui, M. P. Lisanti

Department of Cancer Biology Faculty Papers

With the increased use of screening mammography, the incidence of ductal carcinoma in situ (DCIS) has increased substantially and it currently accounts for 20-30% of newly diagnosed breast carcinomas in United States. Breast conserving therapy with or without radiotherapy is the accepted treatment for most cases of DCIS. However, the local recurrence rate with such therapy rages from 10 to 40% with half of these patients developing invasive carcinoma. Tamoxifen, used as an adjuvant systemic therapy for DCIS, does not increase overall survival and data on reduction of local recurrence rates are conflicting.

The current classification for DCIS based on …

Admission Creatine Kinase As A Prognostic Marker In Acute Myocardial Infarction, Khawar Abbas Kazmi, Saleem Perwaiz Iqbal, Ayla Bakr, Mohammad Perwaiz Iqbal

Section of Cardiology

OBJECTIVES: To investigate the prognostic significance of creatine kinase (CK) in Pakistani patients suffering from acute myocardial infarction (AMI) and to find out if CK combined with troponin T (TnT) could be a better predictor for long-term adverse cardiac event.

METHODS: One hundred and eighty six consecutive patients with AMI who were eligible for streptokinase (SK) treatment were included in this prospective cohort study. The relationship between their serum/plasma CK and TnT levels at the time of admission and clinical outcome was investigated over a mean follow up of 24.12 +/- 3.75 months.

RESULTS: Admission CK was found to be …

Mitochondrial Mislocalization Underlies Abeta42-Induced Neuronal Dysfunction In A Drosophila Model Of Alzheimer's Disease., Kanae Iijima-Ando, Stephen A Hearn, Christopher Shenton, Anthony Gatt, Lijuan Zhao, Koichi Iijima

Department of Biochemistry and Molecular Biology Faculty Papers

The amyloid-beta 42 (Abeta42) is thought to play a central role in the pathogenesis of Alzheimer's disease (AD). However, the molecular mechanisms by which Abeta42 induces neuronal dysfunction and degeneration remain elusive. Mitochondrial dysfunctions are implicated in AD brains. Whether mitochondrial dysfunctions are merely a consequence of AD pathology, or are early seminal events in AD pathogenesis remains to be determined. Here, we show that Abeta42 induces mitochondrial mislocalization, which contributes to Abeta42-induced neuronal dysfunction in a transgenic Drosophila model. In the Abeta42 fly brain, mitochondria were reduced in axons and dendrites, and accumulated in the somata without severe mitochondrial …

Carotid Artery Disease In Patients Undergoing Elective Coronary Artery Bypass Surgery, Waseem Akhtar, Ayan Sabih, Arif Ali, Mubashir Aslam, Nadeem Ahmad

Department of Radiology

OBJECTIVE: To determine frequency of carotid artery disease in patients undergoing elective coronary artery bypass grafting (CABG) using Doppler sonography.STUDY DESIGN: Observational study.

PLACE AND DURATION OF STUDY: Radiology Department, The Aga Khan University Hospital, Karachi, from January 2005 to September 2008.

METHODOLOGY: Patients with known cardiovascular disease waiting for CABG surgery were enrolled for carotid artery Doppler sonography. A predefined data entry form was used for data collection. Coronary angiography findings, carotid artery findings and other associated factors were noted from medical and radiological records. Frequency and pattern of carotid artery disease along with associated risk factors were evaluated. …

Improved Inter-Rater Reliability For Sah Ct Grading Scales Through Application Of A Formal Definition Of Clot Thickness, William Mcbride, Md, Valerie Dechant, Md, Michael Moussouttas, Md

Department of Neurology Faculty Papers

Various scales have been devised for the prediction of vasospasm following aneurysmal rupture.

Especially prominent in these scales is their reliance upon a subjective assessment of clot thickness which introduces variability in grading across raters.

The current study seeks to compare the inter-rater reliability of the traditional Fisher and newer "Frontera" scale (Modified Fisher) when a rigid definition of thick clot is employed.

Effect Of Donor Ethnicity On Kidney Survival In Different Recipient Pairs: An Analysis Of The Optn/Unos Database., C O. Callender, W S. Cherikh, P Traverso, A Hernandez, Tolulope A. Oyetunji, D Chang

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Previous multivariate analysis performed between April 1, 1994, and December 31, 2000 from the Organ Procurement Transplant Network/United Network for Organ Sharing (OPTN/UNOS) database has shown that kidneys from black donors were associated with lower graft survival. We compared graft and patient survival of different kidney donor-to-recipient ethnic combinations to see if this result still holds on a recent cohort of US kidney transplants.

METHODS: We included 72,495 recipients of deceased and living donor kidney alone transplants from 2001 to 2005. A multivariate Cox regression method was used to analyze the effect of donor-recipient ethnicity on graft and patient …

Paroxysmal Atrial Fibrillation Presenting As Anterior Wall Stemi In An Elderly Woman, Muhammad Asim Shabbir, Muhammad Hamza Saad Shaukat, Lance Sullenberge, Mikhail Torosof

Section of Internal Medicine

A 77-year-old woman without traditional risk factors for coronary artery disease (CAD) underwent coronary CT-angiography for evaluation of palpitations after negative Holter monitoring and non-diagnostic ECG exercise stress test. Coronary artery calcium score was reported zero; 1 day later, she was admitted with anterior-wall ST elevation myocardial infarction. Acute left anterior descending artery thrombus was treated with mechanical thrombectomy and Percutaneous Coronary Intervention (PCI). Interestingly, the coronary arteries were angiographically normal. During hospitalisation, paroxysmal atrial fibrillation was noted followed by initiation of anticoagulation. Echocardiogram did not show thrombus or atrial shunt. Cardioversion with Sotalol was successful. Myocardial infraction was most …

Initial Tumor Metabolic Parameters (Maximum Suv And Metabolic Volume) Predict Death From Lung Cancer And Rapid Suv Decline Is Associated With Local Control, Maria Werner-Wasik, Edward Pequignot, Terry Hyslop, Brian Shulli, Ying Xiao, Mitchell Machtay, Amy Taylor, Walter Curran, Rita Axelrod

Department of Radiation Oncology Faculty Papers

Factors associated with local failure and death from lung cancer were evaluated based on post-treatment FDG-PET imaging in patients (pts) with non-small cell lung cancer (NSCLC).

PET-CT scans were obtained 6-8 weeks after thoracic RT and approximately every 3 months thereafter.

Mepe/Of45 Protects Cells From Dna Damage Induced Killing Via Stabilizing Chk1., Shuang Liu, Hongyan Wang, Xiang Wang, Lin Lu, Ning Gao, Peter S N Rowe, Baocheng Hu, Ya Wang

Department of Radiation Oncology Faculty Papers

Matrix extracellular phosphoglycoprotein/osteoblast factor 45 (MEPE/OF45) was cloned in 2000 with functions related to bone metabolism. We identified MEPE/OF45 for the first time as a new co-factor of CHK1 in mammalian cells to protect cells from DNA damage induced killing. We demonstrate here that MEPE/OF45 directly interacts with CHK1. Knocking down MEPE/OF45 decreases CHK1 levels and sensitizes the cells to DNA damage inducers such as ionizing radiation (IR) or camptothicin (CPT)-induced killing. Over-expressing wild-type MEPE/OF45, but not the mutant MEPE/OF45 (depleted the key domain to interact with CHK1) increases CHK1 levels in the cells and increases the resistance of the …

Fluorescent Protein Markers To Tag Collagenous Proteins: The Paradigm Of Procollagen Vii, Hye J. Chung, Andrzej Steplewski, Jouni Uitto, Andrzej Fertala

Department of Dermatology and Cutaneous Biology Faculty Papers

Fluorescent proteins are powerful markers allowing tracking expression, intracellular localization, and translocation of tagged proteins but their effects on the structure and assembly of complex extracellular matrix proteins has not been investigated. Here, we analyzed the utility of fluorescent proteins as markers for procollagen VII, a triple-helical protein critical for the integrity of dermal-epidermal junction. DNA constructs encoding a red fluorescent protein-tagged wild type mini-procollagen VII α chain and green fluorescent protein-tagged α chains harboring selected mutations were genetically engineered. These DNA constructs were co-expressed in HEK-293 cells and the assembly of heterogeneous triple-helical mini-procollagen VII molecules was analyzed. Immunoprecipitation …

Outcome And Haemato-Toxicity Of Two Chemotherapy Regimens For Childhood Non-Hodgkin's Lymphoma In A Kenyan Hospital, William Macharia

Paediatrics and Child Health, East Africa

Background: Effectiveness and toxicity of childhood cancer treatments have never been evaluated in Kenya since introduction of structured care in the early seventies.

Objective:To evaluate effectiveness and toxicity of two treatment protocols for Non- Hodgkin’s lymphoma (NHL).

Design: Historical cohort study using medical records.

Setting: Kenyatta National Hospital, a tertiary care and medical teaching hospital.

Subjects: Children ≤ 15 years with diagnosis of non-Hodgkin’s Lymphoma.

Main outcome measures: Primary outcomes were median survival, event free survival and toxicity.

Results: Out of 101 records, only 26 (25.7%) met inclusion criteria. Baseline characteristics were similar in the two treatment arms. …

Identification And Genotyping Of Bacteria From Paired Vaginal And Rectal Samples From Pregnant Women Indicates Similarity Between Vaginal And Rectal Microflora, Nabil Abdullah El Aila, Inge Tency, Geert Claeys, Hans Verstraelen, Bart Saerens, Guido Lopes Dos Santos Santiago, Ellen De Backer, Piet Cools, Marleen Temmerman, Rita Verhelst

Obstetrics and Gynaecology, East Africa

Background: The vaginal microflora is important for maintaining vaginal health and preventing infections of the reproductive tract. The rectum has been suggested as the major source for the colonisation of the vaginal econiche.

Methods: To establish whether the rectum can serve as a possible bacterial reservoir for colonisation of the vaginal econiche, we cultured vaginal and rectal specimens from pregnant women at 35-37 weeks of gestation, identified the isolates to the species level with tRNA intergenic length polymorphism analysis (tDNA-PCR) and genotyped the isolates for those subjects from which the same species was isolated simultaneously vaginally and rectally, by RAPD-analysis. …