Medicine and Health Sciences Commons^™

Classic Virilizing Congenital Adrenal Hyperplasia Presenting Late: Case Series From Pakistan, Aysha Habib Khan, Muniba Aban, Rameez-Ul-Hassan, Naeem-Ul-Haq, Jamal Raza, Abdul Jabbar, Tariq Moatter

Department of Pathology and Laboratory Medicine

Deficiency of 21 hydroxylase enzyme deficiency (21OH) activity accounts for 90% cases of congenital adrenal hyperplasia (CAH). This results in deficient cortisol, increased ACTH, adrenal hyperplasia and increased adrenal androgen secretion. There is marked virilization in genetic females which is the hallmark of this disorder. Genetic heterogeneity in 21 OHD is well recognized, and both severe and mild forms occur. We present three cases of adult females with the disease from a larger study to establish genotype, phenotype correlation of Pakistani patients with congenital adrenal hyperplasia (CAH) and to highlight issues such as diagnostic delay, inappropriate gender assignment at birth, …

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 …

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 …

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.

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.

Solar Water Disinfection In Household Settings:Hype Or Hope?, Zulfiqar Ahmed Bhutta

Woman and Child Health

No abstract provided.

Assessing Stakeholder Opinions Of Medical Review Of Impaired Drivers And Fitness To Drive: Recommendations For Massachusetts, Nina M. Silverstein, Kelli Barton

Gerontology Institute Publications

Driving is the main mode of travel for Americans age 65 and older, and although older adults are generally found to be safe drivers, aging often brings about functional limitations and an increase in medications that can impede safe driving and fitness to drive (Rosenbloom, 2003; Kissinger, 2008; Adler & Silverstein, 2008). Effective licensing policies and Medical Advisory Board practices are critical components in identifying medically at-risk drivers and may even have a role in the transition to alternative transportation options; yet, states vary greatly in their approach to licensing and renewal practices and in the utilization, composition, and function …

Modern Approaches To Pediatric Brain Injury Therapy, Peter A Walker, Matthew T Harting, James E Baumgartner, Stephen Fletcher, Nathan Strobel, Charles S Cox

Faculty, Staff and Student Publications

Each year, pediatric traumatic brain injury (TBI) accounts for 435,000 emergency department visits, 37,000 hospital admissions, and approximately 2,500 deaths in the United States. TBI results in immediate injury from direct mechanical force and shear. Secondary injury results from the release of biochemical or inflammatory factors that alter the loco-regional milieu in the acute, subacute, and delayed intervals after a mechanical insult. Preliminary preclinical and clinical research is underway to evaluate the benefit from progenitor cell therapeutics, hypertonic saline infusion, and controlled hypothermia. However, all phase III clinical trials investigating pharmacologic monotherapy for TBI have shown no benefit. A recent …

The Time Has Come For Physicians To Take Notice: The Impact Of Psychosocial Stressors On The Heart., Vincent M. Figueredo, M.D.

Division of Cardiology Faculty Papers

A rapidly growing body of evidence supports a relationship between psychosocial factors and cardiovascular disease. In this article, a review of the epidemiologic and clinical research investigating this relationship concludes that psychosocial stressors can be both a cause and a consequence of cardiovascular disease events. Furthermore, recent data have shown that stress management might reduce future cardiac events in patients with cardiovascular disease. Unfortunately, the influence of psychosocial risk factors on cardiovascular disease remains underrecognized compared with traditional cardiac risk factors. Physicians and their associates should screen for psychosocial stressors and recognize potential symptoms. Consideration should be given to developing …

Vaginal Clear Cell Adenocarcinoma With Associated Mullerian Duct Anomalies, Renal Agenesis And Situs Inversus: Report Of A Case With No Known In-Utero Exposure With Diethyl Stilboestrol, Zeeshan-Ud-Din, Aamir Ahsan

Department of Pathology and Laboratory Medicine

A 27 year old female presented with two months history of continuous vaginal bleeding. On evaluation, she was diagnosed as a case of vaginal clear cell adenocarcinoma (VCCA) along with associated Mullerian duct anomalies including didelphys uterus with double vagina; left sided renal agenesis and situs inversus. Although VCCA is strongly linked to in-utero exposure with Diethyl stillboestrol (DES), this patient had no known history regarding such exposure. Also, only a few cases have been described in the literature in which this tumour was seen in association with Mullerian duct anomalies and renal agenesis; in the absence of known DES …

Shoulder Arthroscopy Positioning: Lateral Decubitus Versus Beach Chair., Christina M. Peruto, Md, Michael G. Ciccotti, Md, Steven B. Cohen, Md

Department of Orthopaedic Surgery Faculty Papers

Since the introduction of the beach chair position for shoulder arthroscopy, orthopaedic surgeons have debated whether the beach chair or lateral decubitus is superior. Most surgeons use the same patient position to perform all of their arthroscopic shoulder procedures, regardless of the pathology. Each position has its advantages and disadvantages. The evidence regarding the efficiency, efficacy, and risks of the lateral decubitus and the beach chair positions for shoulder arthroscopy does not show one position to be superior. This review presents a comparison of these positions with regard to setup, surgical visualization, access, and patient risk.

Clinical Radiology Research In Pakistan: From Evidence To Practice, Waseem Akhtar, Arif Ali, Mubashir Aslam, Gul-E-Khanda

Department of Radiology

OBJECTIVE: To assess the clinical radiology research productivity in Pakistan by type of publication, sources of funding and name of journals.

METHODS: A systematic search strategy using key words related to techniques and type of clinical radiology was carried out to identify various studies published in Indexed (Medline) and non-indexed (Pakmedinet) medical journals.

RESULTS: Total of 397 studies were identified out of which 173(43%) from Medline (indexed database) and 220 (57%) from pakmedinet (Indexed and non- indexed database of Pakistan Medical journals). Original articles were 294 (74%) but most of them (68%) were published in non-indexed journals and significantly different …

Functional State Following The Fontan Procedure., Ismee A. Williams, Lynn A. Sleeper, Steven D. Colan, Minmin Lu, Elizabeth A. Stephenson, Jane W. Newburger, Welton M. Gersony, Meryl S. Cohen, James F. Cnota, Andrew M. Atz, Richard V. Williams, Renee Margossian, Andrew J. Powell, Mario P. Stylianou, Daphne T. Hsu, Pediatric Heart Network Investigators, Girish S. Shirali

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Despite improvements in outcomes after completion of the Fontan circulation, long-term functional state varies. We sought to identify pre- and postoperative characteristics associated with overall function.

METHODS AND RESULTS: We analyzed data from 476 survivors with the Fontan circulation enrolled in the Pediatric Heart Network Fontan Cross-sectional Study. Mean age at creation of the Fontan circulation was 3.4 plus or minus 2.1 years, with a range from 0.7 to 17.5 years, and time since completion was 8.7 plus or minus 3.4 years, the range being from 1.1 to 17.3 years. We calculated a functional score for the survivors by …