Medical Specialties Commons^™

The Elucidation Of Metabolic Pathways And Their Improvements Using Stable Optimization Of Large-Scale Kinetic Models Of Cellular Systems, Evgeni V. Nikolaev

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Metabolic engineering of cellular systems to maximize reaction fluxes or metabolite concentrations still presents a significant challenge by encountering unpredictable instabilities that can be caused by simultaneous or consecutive enhancements of many reaction steps. It can therefore be important to select carefully small subsets of key enzymes for their subsequent stable modification compatible with cell physiology. To address this important problem, we introduce a general mixed integer non-linear problem (MINLP) formulation to compute automatically which enzyme levels should be modulated and which enzyme regulatory structures should be altered to achieve the given optimization goal using non-linear kinetic models of relevant …

Multicenter Randomized Phase Ii Study Of Weekly Or Twice-Weekly Bortezomib Plus Rituximab In Patients With Relapsed Or Refractory Follicular Or Marginal-Zone B-Cell Lymphoma, Sven De Vos, André Goy, Shaker R. Dakhil, Mansoor Saleh, Peter Mclaughlin, Robert Belt, Christopher R. Flowers, Mark Knapp, Lowell Hart, Dipti Patel-Donnelly

Haematology and Oncology, East Africa

Purpose: To determine overall response rate (ORR), time to progression (TTP), and duration of response (DOR) with twice-weekly/weekly bortezomib plus rituximab, and evaluate safety/tolerability, in patients with relapsed or refractory CD20+ follicular lymphoma (FL) or marginal-zone lymphoma.

Patients and Methods: Patients were randomly assigned (minimization method) to bortezomib 1.3 mg/m2 twice weekly (days 1, 4, 8, and 11; 21-day cycle, five cycles; arm A) or bortezomib 1.6 mg/m2 weekly (days 1, 8, 15, and 22; 35-day cycle, three cycles; arm B) plus rituximab 375 mg/m2 weekly for 4 weeks (both arms). Response/progression was determined by International Workshop Response Criteria using …

In Reply To Dr. Hurkmans Et Al., Ying Xiao, Phd, Lech S. Papiez, Phd, James M. Galvin, Dsc

Department of Radiation Oncology Faculty Papers

No abstract provided.

Esophageal Polypoidal Mass: Presentation Of An Uncommon Pleomorphic Carcinoma, Javed Yakoob, Z Abbas, Wasim Jafri, Najamul Sahar Azad

Section of Gastroenterology

Pleomorphic carcinomas are primary malignant tumours that are known to arise in the lungs, pancreas, gall bladder and intestine. A patient with polypoid tumour of the esophagus is described in this report. The patient presented with dysphagia. Diagnostic and therapeutic intervention required endoscopic evaluation and treatment. Benign esophageal tumours are rarely seen and originate from the upper third of esophagus. We observed an esophageal tumour which was interpreted as spindle cell carcinoma of the esophagus that caused obstruction. We present the clinical picture and histopathological findings of the tumour. To our knowledge this is the first local report of spindle …

Negative Predictive Value Of Mammography And Sonography In Mastalgia With Negative Physical Findings, Imrana Masroor, Shaista Afzal, Saima Sakhawat, Nadir Khan, Mirza Amanullah Beg, Darakhshan Kawal

Department of Radiology

OBJECTIVE: To determine the negative predictive value of mammography and sonography in patients with focal/ diffuse breast pain with negative physical examination of the breasts.

METHODS: A descriptive study, conducted at Radiology Department ofAga Khan University Hospital from 2006-2007 for a period of 2 years. A total of 207 women were referred for mammography and sonography because of focal or diffuse breast pain. Complete follow-up was available only in 55 patients. The outcome or gold standard was mammograms or ultrasound after an average follow-up period of 18 months with negative/benign findings or histopathology of the suspicious lesion or imaging which …

Effects Of Functional Appliances On Pharyngeal Airway Dimensions: A Cone Beam Computed Tomography Study, Melissa K. Lee

Loma Linda University Electronic Theses, Dissertations & Projects

Introduction: Functional appliances are intended to correct by incremental advancement of the mandible for correction of skeletal Class 11 relationships. Similar in design to functional appliances, mandibular advancing devices (MAD) are used for obstructive sleep apnea (OSA) patients as they increase the size of the airway by drawing the tongue and soft palate forwards, and thus maintain its patency during sleep. It has been shown that significant increases in airway dimensions and decreases in airway resistance were gained in OSA patients while evaluated with a MAD in place. This retrospective study evaluated volumetric, cross-sectional area and linear changes in the …

Observer Reliability Of Cephalometric Landmark Identification On 3-D Mr Images, Michael S. Pollack

Loma Linda University Electronic Theses, Dissertations & Projects

Introduction: Cephalometric analysis is a cornerstone of orthodontic diagnosis, yet much information is lost when 3-dimensional structures are assessed with 2-dimensional methods. CBCT offers 3-dimensional imaging but at the cost of higher levels of ionizing radiation. Magnetic resonance imaging provides 3-dimensional imaging without ionizing radiation and additionally imparts visualization of soft tissue structures. Prior to employing MR images for cephalometric analysis, reliability of landmark identification must be assessed. The purpose of this study was to evaluate intra- and interobserver reliability in 3-dimensional landmark identification using MR images.

Materials and Methods: Fifteen cranial MR images (3.0 T, MP-RAGE) from subjects between …

Advances In Progenitor Cell Therapy Using Scaffolding Constructs For Central Nervous System Injury, Peter A Walker, Kevin R Aroom, Fernando Jimenez, Shinil K Shah, Matthew T Harting, Brijesh S Gill, Charles S Cox

Faculty, Staff and Student Publications

Traumatic brain injury (TBI) is a major cause of morbidity and mortality in the United States. Current clinical therapy is focused on optimization of the acute/subacute intracerebral milieu, minimizing continued cell death, and subsequent intense rehabilitation to ameliorate the prolonged physical, cognitive, and psychosocial deficits that result from TBI. Adult progenitor (stem) cell therapies have shown promise in pre-clinical studies and remain a focus of intense scientific investigation. One of the fundamental challenges to successful translation of the large body of pre-clinical work is the delivery of progenitor cells to the target location/organ. Classically used vehicles such as intravenous and …

A Comparative Study Of The Genotype Mtbdrplus® Assay Against A Standard Culture Method For Diagnosis And Drug Susceptibility Testing Of Tuberculosis, Peris W. Thamaini

Master of Medicine in Clinical Pathology

Background: Nearly one-third of the global population, i.e. two billion people, is infected with Mycobacterium tuberculosis and is at risk of developing the disease. More than eight million people develop active tuberculosis (TB) every year, with about two million dying from the disease annually. Diagnosis of tuberculosis inKenya remains dependent on smear microscopy. New methods of TB diagnosis are needed which have better accuracy and are still cost effective. Molecular methods of TB diagnosis have come under investigation in a lot of studies recently. However, they have their own limitations including the inability to differentiate between active organisms and dead …

Safe Emergency Management Of Acute Ischemic Stroke: An Academic Community Hospital Decade Experience, John Castaldo, Richard S. Mackenzie Md, Peter J. Barbour Md, Lorraine Spikol, Yevgeniy Isayev, Yuebing Li Phd, Gary Clauser Md, John Margraf Md, Glenn Mackin Md, Faan, Facp, David Richardson, Gavin C. Barr, Jr. Md, Donna Jenny, Susan Nevada, Claranne Mathiesen

Department of Emergency Medicine

No abstract provided.

Risk Of Contrast Induced Nephropathy In Hiv Patients Receiving Radiographic Contrast At Three Aga Khan Hospitals, Sitna A. Mwanzi

Master of Medicine in Internal Medicine

Aim: To study the influence of HIV infection on the development of contrast induced nephropathy in patients receiving radio contrast material Design: Prospective cohort study Patients and setting:One hundred and twenty five (125) HIV positive patients and one hundred and fifty five (155) HIV negative patients selected from in and out patient departments of the Aga Khan University Hospital, Nairobi and Aga Khan Hospitals in Mombasa and Kisumu, were evaluated for the study between August 2008 and August 2009. Methodology: Eligible patients undergoing radiological evaluation requiring the use of radio contrast material were consecutively recruited for the study after which …

Calcium Homeostasis And Cone Signaling Are Regulated By Interactions Between Calcium Stores And Plasma Membrane Ion Channels., Tamas Szikra, Peter Barabas, Theodore M. Bartoletti, Wei Huang, Abram Akopian, Wallace B. Thoreson, David Krizaj

Journal Articles: Ophthalmology

Calcium is a messenger ion that controls all aspects of cone photoreceptor function, including synaptic release. The dynamic range of the cone output extends beyond the activation threshold for voltage-operated calcium entry, suggesting another calcium influx mechanism operates in cones hyperpolarized by light. We have used optical imaging and whole-cell voltage clamp to measure the contribution of store-operated Ca(2+) entry (SOCE) to Ca(2+) homeostasis and its role in regulation of neurotransmission at cone synapses. Mn(2+) quenching of Fura-2 revealed sustained divalent cation entry in hyperpolarized cones. Ca(2+) influx into cone inner segments was potentiated by hyperpolarization, facilitated by depletion of …

Relating Visual To Verbal Semantic Knowledge: The Evaluation Of Object Recognition In Prosopagnosia, Jason J. S. Barton, Hashim-M Hanif, Sohi Ashraf

Section of Neurology

Assessment of face specificity in prosopagnosia is hampered by difficulty in gauging pre-morbid expertise for non-face object categories, for which humans vary widely in interest and experience. In this study, we examined the correlation between visual and verbal semantic knowledge for cars to determine if visual recognition accuracy could be predicted from verbal semantic scores. We had 33 healthy subjects and six prosopagnosic Patients first rated their own knowledge of cars. They were then given a test of verbal semantic knowledge that presented them with the names of car models, to which they were to match the manufacturer. Lastly, they …

Mechanisms Of Primary Axonal Damage In A Viral Model Of Multiple Sclerosis., Jayasri Das Sarma, Lawrence C. Kenyon, Susan T. Hingley, Kenneth S. Shindler

Department of Neurology Faculty Papers

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the CNS. Recent studies have demonstrated that significant axonal injury also occurs in MS patients and correlates with neurological dysfunction, but it is not known whether this neuronal damage is a primary disease process, or occurs only secondary to demyelination. In the current studies, neurotropic strains of mouse hepatitis virus (MHV) that induce meningitis, encephalitis, and demyelination in the CNS, an animal model of MS, were used to evaluate mechanisms of axonal injury. The pathogenic properties of genetically engineered isogenic spike protein recombinant demyelinating and nondemyelinating strains of MHV were compared. …

Dronedarone., Chinmay Patel, Gan-Xin Yan, Peter R Kowey

Department of Medical Genetics Faculty Papers

Amiodarone is the most effective antiarrhythmic drug for maintaining sinus rhythm for patients with atrial fibrillation. Extra-cardiac side effects have been a limiting factor, especially during chronic use, and may offset its benefits. Dronedarone is a noniodinated benzofuran derivative of amiodarone that has been developed for the treatment of atrial fibrillation and atrial flutter. Similar to amiodarone, dronedarone is a potent blocker of multiple ion currents, including the rapidly activating delayed-rectifier potassium current, the slowly activating delayed-rectifier potassium current, the inward rectifier potassium current, the acetylcholine activated potassium current, peak sodium current, and L-type calcium current, and exhibits antiadrenergic effects. …

Uncoupling Scavenger Receptor A-Mediated Phagocytosis Of Bacteria From Endotoxic Shock Resistance, Eyal Amiel, Julie L. Acker, Ryan M. Collins, Brent Berwin

Dartmouth Scholarship

Unresolved infection by gram-negative bacteria can result in the potentially lethal condition known as endotoxic shock, whereby uncontrolled inflammation can lead to multiple organ failure and death of the infected host. Previous results have demonstrated that animals deficient in class A scavenger receptor (SRA), a trafficking receptor for bacteria and bacterium-derived molecules, are more susceptible to endotoxic shock. This has been proposed to be a result of impaired SRA-dependent phagocytic clearance of bacteria resulting in stronger proinflammatory stimuli. In this report, we test the hypothesis that there is an obligate reciprocal relationship between SRA-mediated phagocytosis of bacteria and susceptibility to …

Expression Of An Alternate Splice Form Of Bmi-1 In Multiple Myeloma, Adam Austin, Kristine Veys, Debbie Wong, James Tung

Undergraduate Research Opportunities Program (UROP)

The concept of “tumor stem cells” has garnered much attention in the last few years. Tumor stem cells are believed to exist among a heterogeneous group of cells that constitute a tumor. These tumor stem cells often express genes that are important for stem cell function, cell division, and maintenance of pluripotent state in stem cells. Stem cell or stem cell maintenance genes such as SALL 4 and Bmi-1 are often seen in these cancer cells and contribute to self-renewing divisions and cancer cell survival. In particular, high expression of Bmi-1 (B lymphoma mouse Moloney leukemia virus insertion region), a …

Pdest Fg12-Cmv Dsred Vector, Jarod Wolffis, Sheri L. Holmen

Undergraduate Research Opportunities Program (UROP)

Melanoma is the most rapidly increasing malignancy among young people in the United States. If detected early, the disease is easily treated; however, once the disease has metastasized it is largely refractory to conventional therapies and is associated with a high mortality rate. The development of human cancer from a pre-malignant primary tumor to a metastatic lesion that develops at secondary sites is thought to be a multi-step process, requiring many genetic and epigenetic events that provide a growth advantage to cells. It is still unclear which of the many genetic changes in human cancers are required for metastasis. Therefore, …

Incomplete, Atypical Kawasaki Disease Or Evolving Systemic Juvenile Idiopathic Arthritis: A Case Report., Shakeel Shaikh, Sidra Ishaque, Taimur Saleem

Department of Paediatrics and Child Health

Kawasaki disease is an acute febrile condition seen in children. However, it is also well recognized that some Patients do not fulfill the classic diagnostic criteria for the diagnosis of kawasaki disease. The incomplete form of kawasaki disease is termed as 'Incomplete KD' or 'Atypical KD'. We present a case of a 6 year old child with a history of prolonged fever, periorbital, oral and lip changes, changes in the extremities and an erythamatous, maculopapular rash. Based on the physical exam and her echocardiogram that showed right coronary artery dilatation, Intravenous immune globulin was administered in this Patient. This Patient …

Median Values For Second-Trimester Maternal Serum Αlpha Fetoprotein And Human Chorionic Gonadotrophin (Double Test) At Aga Khan University Hospital-Nairobi, Nancy A. Okinda

Master of Medicine in Clinical Pathology

Aim To establish median values for second trimester maternal serum human chorionic gonadotrophin (HCG) and alpha fetoprotein (AFP) at Aga Khan University Hospital- Nairobi (AKUH-N) using the Abbott Micro particle Enzyme immunoassay. Specific objectives •To perform measurements of second trimester maternal serum human chorionic gonadotrophin (HCG) and alpha fetoprotein (AFP) and to establish observed and regressed median values. •To establish regression coefficients for regressed medians of AFP and HCG. •To compare these data with data obtained from other geographical regions. Methodology 330 serum samples from women of gestational ages 15 to 20 weeks were analyzed for AFP and HCG. Observed …

A Generalized Beta Model For The Age Distribution Of Cancers: Application To Pancreatic And Kidney Cancer., Tengiz Mdzinarishvili, Michael X. Gleason, Leo Kinarsky, Simon Sherman

Journal Articles: Eppley Institute

The relationships between cancer incidence rates and the age of patients at cancer diagnosis are a quantitative basis for modeling age distributions of cancer. The obtained model parameters are needed to build rigorous statistical and biological models of cancer development. In this work, a new mathematical model, called the Generalized Beta (GB) model is proposed. Confidence intervals for parameters of this model are derived from a regression analysis. The GB model was used to approximate the incidence rates of the first primary, microscopically confirmed cases of pancreatic cancer (PC) and kidney cancer (KC) that served as a test bed for …

Inaugural Target Discovery World Congress 2009: Interactive Cardiovascular And Thoracic Surgery, Michael Holinstat, Ph.D.

Department of Medicine Faculty Papers

Dr. Michael Holinstat advocated a preferred therapeutic approach to treatment of platelet clot formation: to target signaling components downstream of receptor activation.

Use Of Magnetic Resonance Spectroscopy (Mrs) To Improve Magnetic Resonance Imaging (Mri) In The Diagnosis Of Intracranial Pathology, Done At Aga Khan University, Joyce Sande

Master of Medicine in Imaging and Diagnostic Radiology

Introduction: Magnetic Resonance Spectroscopy (MRS)is a potentially useful adjunct to Magnetic Resonance Imaging (MRI) in thecharacterization of focal brain lesions. This study was aimed at showing that by the additional use of MRS (MRI, MRS), the characterization of a focal brain lesion into neoplastic, or non- neoplastic (infective, or degenerative) can be improved, as compared to the use of MRI alone. Study question: Does the additional use of MRS improve MRI differentiation of neoplastic from non- neoplastic (infective or degenerative) focal brain lesions? Methods: The design was prospective, analytical and comparative. 80 consecutive patients were enrolled. Conventional MRI of the …

Evaluating The Diagnostic Performance Of An Initial Transvaginal Sonogram (Tvs) In Patients With Suspected Ectopic Pregnancy, Zablon Bett

Master of Medicine in Imaging and Diagnostic Radiology

Purpose of the study: To evaluate the diagnostic performance of an initial transvaginal sonogram (TVS) in patients with suspected ectopic pregnancy (EP). Objectives: 1) To determine the accuracy, sensitivity, specificity, positive and negative predictive values of an initial TVS scan in patients with suspected EP. 2) To determine the diagnostic utility of TVS findings as predictors of EP. Methodology: This was a descriptive, prospective study of 131 consecutive mothers who had TVS for clinical suspicion of EP at the Aga Khan University hospital over a 12 month period between November 2007 and October 2008. The scans were performed in our …

Flagellum-Mediated Biofilm Defense Mechanisms Of Pseudomonas Aeruginosa Against Host-Derived Lactoferrin, Jeff G. Leid, Mathias Kerr, Candice Selgado, Chelsa Johnson, Gabriel Moreno, Alyssa Smith, Mark E. Shirtliff, Georg A. O'Toole, Emily K. Cope

Dartmouth Scholarship

Chronic infection with the gram-negative organism Pseudomonas aeruginosa is a leading cause of morbidity and mortality in human patients, despite high doses of antibiotics used to treat the various diseases this organism causes. These infections are chronic because P. aeruginosa readily forms biofilms, which are inherently resistant to antibiotics as well as the host's immune system. Our laboratory has been investigating specific mutations in P. aeruginosa that regulate biofilm bacterial susceptibility to the host. To continue our investigation of the role of genetics in bacterial biofilm host resistance, we examined P. aeruginosa biofilms that lack the flgK gene. This mutant …

Expression Of Cpi-17 In Smooth Muscle During Embryonic Development And In Neointimal Lesion Formation., Jee In Kim, Garbo D Young, Li Jin, Avril V Somlyo, Masumi Eto

Department of Molecular Physiology and Biophysics Faculty Papers

Ca(2+) sensitivity of smooth muscle (SM) contraction is determined by CPI-17, an inhibitor protein for myosin light chain phosphatase (MLCP). CPI-17 is highly expressed in mature SM cells, but the expression level varies under pathological conditions. Here, we determined the expression of CPI-17 in embryonic SM tissues and arterial neointimal lesions using immunohistochemistry. As seen in adult animals, the predominant expression of CPI-17 was detected at SM tissues on mouse embryonic sections, whereas MLCP was ubiquitously expressed. Compared with SM alpha-actin, CPI-17 expression doubled in arterial SM from embryonic day E10 to E14. Like SM alpha-actin and other SM marker …

Tuberculous And Cryptococcal Meningitis In A Setting With High Tb And Low Hiv Prevalence, Afrasyab Khan, Bushra Jamil, Rahmat Ali, Sana Sultan

Section of Pulmonary & Critical Care

OBJECTIVE: To compare the differences in presentation and outcome of patients with tuberculous meningitis (TBM) and cryptococcal meningitis (CCM).

STUDY DESIGN: Case series.

PLACE AND DURATION OF STUDY: The Aga Khan University Hospital, Karachi, from December 1995 to December 2005.

METHODOLOGY: Patients with a confirmed diagnosis of TBM or CCM were included in this study. The signs and symptoms, laboratory findings and other variables of patients were entered and analyzed by Statistical Package for Social Sciences (SPSS) Software version 14.

RESULTS: We compared 16 patients of TBM with 11 of CCM. None of the patients with TBM were Human Immunodeficiency …

Dynamic Mechanical (Brush) Allodynia In Cluster Headache: A Prevalence Study In A Tertiary Headache Clinic., Michael J Marmura, Muhammad Abbas, Avi Ashkenazi

Department of Jefferson Headache Center Papers and Presentations

Cutaneous allodynia (CA) has been described in migraine and has been related to treatment failure. There are little data about the incidence of CA in other primary headache syndromes such as cluster headache (CH). The objectives of this study are to evaluate the prevalence of dynamic mechanical (brush) allodynia (BA) in CH patients attending a tertiary headache clinic, and to assess its relation to disease characteristics. Adult patients with episodic or chronic CH were recruited. We obtained demographic data and data on disease characteristics through a structured questionnaire, and tested the patients for brush allodynia BA by applying a 4 …

A Large Chorioangioma Causing Intrauterine Foetal Demise, Aamer Imdad, Lumaan Sheikh, Ayesha Malik

Department of Obstetrics & Gynaecology

Chorioangioma is a benign tumour of the placenta consisting of blood vessels and stroma that proliferates beyond normally developing chorionic villi. Most of the small tumours are asymptomatic but large placental tumours are associated with unfavourable outcomes for foetus and mother. We present a case of a 23 year old primigravida who had a large chorioangioma that lead to intrauterine foetal demise. Major complications and diagnostic tools for chrioangioma have been discussed.

Clinical Profile And Outcome In A Paediatric Intensive Care Unit In Pakistan, Anwarul Haque, Surraiya Bano

Department of Paediatrics and Child Health

Paediatric critical care medicine is a relatively new subspecialty in Pakistan. The clinical profile and outcomes of children admitted in the PICU (paediatric intensive care unit) were retrospectively reviewed from January to December 2007. Mean age of the studied 314 patients was 24 months; 37% were less than one-year-old and 66% was male. Mean PRISM score was 13.2. There were almost equal distribution of medical (46%) and surgical (54%) cases. Ninety percent of patients received mechanical ventilation, while more than 50% received vasoactive drugs. The rate of nosocomial infection was 4.7%. The average length of PICU stay was 3.2 (1-49) …