Medicine and Health Sciences Commons^™

Spontaneous Asj-2j Mutant Mouse As A Model For Generalized Arterial Calcification Of Infancy: A Large Deletion/Insertion Mutation In The Enpp1 Gene., Qiaoli Li, C Herbert Pratt, Louise A Dionne, Heather Fairfield, Son Yong Karst, John P Sundberg, Jouni Uitto, Yin Tintut

Department of Dermatology and Cutaneous Biology Faculty Papers

Generalized arterial calcification of infancy (GACI), an autosomal recessive disorder caused by mutations in the ENPP1 gene, manifests with extensive mineralization of the cardiovascular system. The affected individuals in most cases die within the first year of life, and there is currently no effective treatment for this disorder. In this study, we characterized a spontaneous mutant mouse, asj-2J, as a model for GACI. These mice were identified as part of a phenotypic deviant search in a large-scale production colony of BALB/cJ mice at The Jackson Laboratory. They demonstrated a characteristic gait due to stiffening of the joints, with phenotypic similarity …

Kallikrein Family Proteases Klk6 And Klk7 Are Potential Early Detection And Diagnostic Biomarkers For Serous And Papillary Serous Ovarian Cancer Subtypes., Ayala Tamir, Ushma Jag, Sreeja Sarojini, Craig Schindewolf, Takemi Tanaka, Rajendra Gharbaran, Hiren Patel, Anil Sood, Wei Hu, Ruzeen Patwa, Patrick Blake, Polina Chirina, Jin Oh Jeong, Heejin Lim, Andre Goy, Andrew Pecora, K Stephen Suh

Department of Medicine Faculty Papers

BACKGROUND: Early detection of ovarian cancer remains a challenge due to widespread metastases and a lack of biomarkers for early-stage disease. This study was conducted to identify relevant biomarkers for both laparoscopic and serum diagnostics in ovarian cancer.

METHODS: Bioinformatics analysis and expression screening in ovarian cancer cell lines were employed. Selected biomarkers were further validated in bio-specimens of diverse cancer types and ovarian cancer subtypes. For non-invasive detection, biomarker proteins were evaluated in serum samples from ovarian cancer patients.

RESULTS: Two kallikrein (KLK) serine protease family members (KLK6 and KLK7) were found to be significantly overexpressed relative to normal …

Multiple Interventions To Transform A Family Medicine Practice, Nyann Biery Ms, Robin Schroeder Md, Faafp

Department of Family Medicine

No abstract provided.

Toward An Improved Understanding Of The Ionizing Radiation Induced Dna Damage/Response Networks In Human Malignancies., Daphne A Haas-Kogan, David R Raleigh, Adam Paul Dicker

Department of Radiation Oncology Faculty Papers

No abstract provided.

Evaluating The Effectivesness Of Information Sources Regarding Hiv Among Gold Miners In Quảng Nam, Noah Landesberg

Independent Study Project (ISP) Collection

Young migrant males in strenuous manual labor environments represent a high-­‐risk population for the transmission of HIV/AIDS. In Vietnam, gold miners are representative of this high-­‐risk population. Phước Sơn district, Quảng Nam province is home to much of Vietnam’s mining activity and has a comparatively high rate of HIV. Previous studies have been done on HIV/AIDS prevalence in Quảng Nam as well as related knowledge and practices. This analysis of a 2014 questionnaire examines the effects of varying information sources on HIV/AIDS knowledge. The sample of workers was mostly male and between 25 and 49 years old. Migrants made up …

Propranolol Therapy For Infantile Hemangioma Is Less Toxic But Longer In Duration Than Corticosteroid Therapy, Kathryn Sawa, Arjang Yazdani, Michael J. Rieder, Guido Filler

Paediatrics Publications

BACKGROUND: Infantile hemangioma is the most common benign, self-limiting tumour of childhood. Treatment is reserved for hemangiomas that obstruct vital structures or cause significant disfigurement. Traditionally, corticosteroids have been the medical treatment of choice. Since 2008, however, propranolol has been rapidly adopted as an effective pharmacological treatment for infantile hemangioma. Published data regarding the long-term side effects of propranolol are currently lacking. OBJECTIVE: To describe the long-term effects of propranolol and corticosteroids on anthropometric measurements (height, body mass index [BMI]) and blood pressure in children. METHODS: A prospective database analysis of all infantile hemangioma patient visits to the pediatric vascular …

The Health Initiative Program For Kids (Hip Kids): Effects Of A 1-Year Multidisciplinary Lifestyle Intervention On Adiposity And Quality Of Life In Obese Children And Adolescents -- A Longitudinal Pilot Intervention Study, Dirk E. Bock, Tracy Robinson, Jamie A Seabrook, Meghan Rombeek, Kambiz Norozi, Guido Filler, Ralf Rauch, Cheril L Clarson

Paediatrics Publications

BACKGROUND: Though recent data suggest that multidisciplinary outpatient interventions can have a positive effect on childhood obesity, it is still unclear which program components are most beneficial and how they affect quality of life (QoL). The aim of this study was to determine if a 1-year multidisciplinary, family-centered outpatient intervention based on social cognitive theory would be effective in (i) preventing further increases in BMI and BMI z-score, and (ii) improving QoL in obese children and adolescents.

METHODS: Obese children and adolescents 8-17 years of age and their families participated in this 1-year longitudinal pilot intervention study. The intervention consisted …

Effects Of Video Enhancement In A Stated-Choice Experiment On Medical Decision Making, Susanne Hoffmann, Joachim Winter, Francis G. Caro, Alison Gottlieb

Gerontology Institute Publications

Background. The internet can be useful in administering stated-choice experiments to understand medical decision making and refine the content of patient decision aids. In internet-based stated-choice experiments, video and audio files can be used to provide information to respondents. Quality of data may or may not be affected.

Objectives. In a methodological experiment concerned with administration of a stated-choice experiment on the internet concerned with knee-replacement surgery, we compared the data quality obtained with video-enhanced and conventional text formats.

Methods. Members of the RAND Corporation’s American Life Panel and 50 years of age or older (n=1616) were randomly assigned to …

Suppression Of Invasion And Metastasis Of Triple-Negative Breast Cancer Lines By Pharmacological Or Genetic Inhibition Of Slug Activity., Giovanna Ferrari-Amorotti, Claudia Chiodoni, Fei Shen, Sara Cattelani, Angela Rachele Soliera, Gloria Manzotti, Giulia Grisendi, Massimo Dominici, Francesco Rivasi, Mario Paolo Colombo, Alessandro Fatatis, Bruno Calabretta

Department of Cancer Biology Faculty Papers

Most triple-negative breast cancers (TNBCs) exhibit gene expression patterns associated with epithelial-to-mesenchymal transition (EMT), a feature that correlates with a propensity for metastatic spread. Overexpression of the EMT regulator Slug is detected in basal and mesenchymal-type TNBCs and is associated with reduced E-cadherin expression and aggressive disease. The effects of Slug depend, in part, on the interaction of its N-terminal SNAG repressor domain with the chromatin-modifying protein lysine demethylase 1 (LSD1); thus, we investigated whether tranylcypromine [also known as trans-2-phenylcyclopropylamine hydrochloride (PCPA) or Parnate], an inhibitor of LSD1 that blocks its interaction with Slug, suppresses the migration, invasion, and metastatic …

Utilizing Weightlifting For Cycling Performance, Nicholas J. Fiolo, Christopher B. Taber, Caleb D. Bazyler, Cody T. Haun, Robert Duncan, Aaron M. Thomas, Michael W. Ramsey, Michael H. Stone

ETSU Faculty Works

Abstract available in the 9th Annual Coaches and Sport Science College.

Site-Specific Mutation Of The Sensor Kinase Gras In Staphylococcus Aureus Alters The Adaptive Response To Distinct Cationic Antimicrobial Peptides, Ambrose L. Cheung, Arnold S. Bayer, Michael R. Yeaman, Yan Q. Xiong, Alan J. Waring, Guido Memmi, Niles Donegan

Dartmouth Scholarship

The Staphylococcus aureus two-component regulatory system, GraRS, is involved in resistance to killing by distinct host defense cationic antimicrobial peptides (HD-CAPs). It is believed to regulate downstream target genes such as mprF and dltABCD to modify the S. aureus surface charge. However, the detailed mechanism(s) by which the histidine kinase, GraS, senses specific HD-CAPs is not well defined. Here, we studied a well-characterized clinical methicillin-resistant S. aureus (MRSA) strain (MW2), its isogenic graS deletion mutant (ΔgraS strain), a nonameric extracellular loop mutant (ΔEL strain), and four residue-specific ΔEL mutants (D37A, P39A, P39S, and D35G D37G D41G strains). The ΔgraS and …

Integrative Therapy Use For Management Of Side Effects And Toxicities Experienced By Pediatric Oncology Patients, Shana Jacobs

Pediatrics Faculty Publications

Integrative Therapies (IT), otherwise known as Complementary and Alternative Medicine, are widely used among pediatric oncology patients, despite a paucity of available evidence. This review summarizes surveys that describe the prevalence of IT use by pediatric oncology patients, both during therapy and in survivorship, as well as the modalities being used. Additionally, the evidence that exists for specific treatments that appear to be efficacious in controlling specific symptoms is described. Finally, there are recommendations for practitioners on how to best counsel patients about IT use.

Food Choices And Practices During Pregnancy Of Immigrant Women With High-Risk Pregnancies In Canada: A Pilot Study, Gina M A. Higginbottom, Helen Vallianatos, Joan Forgeron, Donna Gibbons, Fabiana Mamede, Rubina Barolia

School of Nursing & Midwifery

Background: Immigrant women may be regarded as a vulnerable population with respect to access and navigation of maternity care services. They may encounter difficulties when accessing culturally safe and appropriate maternity care, which may be further exacerbated by language difficulties and discriminatory practices or attitudes. The project aimed to understand ethnocultural food and health practices and how these intersect in a particular social context of cultural adaptation and adjustment in order to improve the care-giving capacities of health practitioners working in multicultural perinatal clinics.
Methods: This four-phase study employed a case study design allowing for multiple means of data collection …

A Study Protocol: Using Demand-Side Financing To Meet The Birth Spacing Needs Of The Underserved In Punjab Province In Pakistan, Syed Khurram Azmat, Moazzam Ali, Waqas Hameed, Ghulam Mustafa, Ghazanfer Abbas, Muhammad Ishaque, Mohsina Bilgrami, Marleen Temmerman

Obstetrics and Gynaecology, East Africa

Background: High fertility rates, unwanted pregnancies, low modern contraceptive prevalence and a huge unmet need for contraception adversely affect women’s health in Pakistan and this problem is compounded by limited access to reliable information and quality services regarding birth spacing especially in rural and underserved areas. This paper presents a study protocol that describes an evaluation of a demand-side financing (DSF) voucher approach which aims to increase the uptake of modern contraception among women of the lowest two wealth quintiles in Punjab Province, Pakistan.

Methods/Design: This study will use quasi-experimental design with control arm and be implemented in: six government …

A Combined Therapeutic Regimen Of Buspirone And Environmental Enrichment Is More Efficacrious Than Either Alone In Enhancing Spatial Learning In Brain-Injured Rats, Christina M. Monaco, Kory M. Gebhardt, Sarah M. Chlebowski, Kaitlyn E. Shaw, Jeffrey P. Cheng

PCOM Scholarly Papers

Abstract Buspirone, a 5-HT1A receptor agonist, and environmental enrichment (EE) enhance cognition and reduce histopathology after traumatic brain injury (TBI) in adult rats, but have not been fully evaluated after pediatric TBI, which is the leading cause of death in children. Hence, the aims of this study were to assess the efficacy of buspirone alone (Experiment 1) and in combination with EE (Experiment 2) in TBI postnatal day-17 male rats. The hypothesis was that both therapies would confer cognitive and histological benefits when provided singly, but their combination would be more efficacious. Anesthetized rats received a cortical impact or sham …

Takotsubo Cardiomyopathy: Ten Year Experience At A Tertiary Care Hospital In Pakistan., Abid Laghari, Aamir Hameed, K. Kazmi

Department of Medicine

Objective: There is very little literature regarding Takotsubo Cardiomyopathy (TTC) from the Asian Countries other than Japan and Korea. We conducted this study to determine the demographics, clinical presentations, complications and recovery of left ventricular (LV) systolic function in TTC patients of Pakistani origin.

Methods: A ten years retrospective case series study of TTC was conducted at the Aga Khan University Hospital. Patients were followed for up to six months after presentation, with special emphasis on the recovery of LV function.

Conclusion: TTC is classically triggered by an acute illness or by extreme stress and a triggering incident may not …

Better Physician-Patient Communication; An Important Milestone In Control Of Hypertension, A Multicenter Study From Karachi, Pakistan., Aysha Almas Almas, Faridah Bhamani, Aamir Hameed

Department of Medicine

Control of hypertension is an important cornerstone in prevention of cardiovascular morbidity and mortality. This study was designed to compare physician encounter score in patients with controlled and uncontrolled hypertension. It was conducted at three tertiary care hospitals in Karachi. Patients were categorized into controlled and uncontrolled hypertension based on their initial blood pressure readings on presentation. Primary outcome variable was control of hypertension and physician encounter score (a composite score of 12 item question) was the main candidate variable. Higher scores reflected favorable encounter with physician. Mean age of participants was 57.7 ± 12 years; 224 (50.1%) were men. …

New Onset Refractory Status Epilepticus As An Unusual Presentation Of A Suspected Organophosphate Poisoning, Shahan Waheed, Amber Sabeen, Nadeem Ullah Khan

Department of Medicine

New onset refractory status epilepticus (NORSE) is a new entity in medical literature. It has different infectious and noninfectious etiologies showing a devastating impact onto the clinical outcome of patients. Therapy with anaesthetic and antiepileptic agents often fails to improve the condition, unless the primary cause is rectified. Here is presented the case of a young female with a history of depression who after a recent bereavement came to the Emergency Department of Aga Khan University Hospital with complaints of drowsiness that lasted for few hours. Though she had no history of organophosphate poisoning, her physical examination and further investigations …

Interventions To Promote Adherence To Antiretroviral Therapy In Africa: A Network Meta-Analysis, Edward J. Mills, Richard Lester, Kristian Thorlund, Maria Lorenzi, Katherine Muldoon, Steve Kanters, Sebastian Linnemayr, Robert Gross, Yvette Calderon, K Rivet Amico, Harsha Thirumurthy, Cynthia Pearson, Robert H. Remien, Lawrence Mbuagbaw, Lehana Thabane, Michael Chung, Ira B. Wilson, Albert Liu, Olalekan A. Uthman, Jane Simoni, David Bangsberg, Sanni Yaya, Till Bärnighausen, Nathan Ford, Jean B. Nachega

Internal Medicine, East Africa

Background: Adherence to antiretroviral therapy (ART) is necessary for the improvement of the health of patients and for public health. We sought to determine the comparative effectiveness of different interventions for improving ART adherence in HIV-infected people living in Africa.

Methods: We searched for randomised trials of interventions to promote antiretroviral adherence within adults in Africa. We searched AMED, CINAHL, Embase, Medline (via PubMed), and ClinicalTrials.gov from inception to Oct 31, 2014, with the terms “HIV”, “ART”, “adherence”, and “Africa”. We created a network of the interventions by pooling the published and individual patients' data for comparable treatments and comparing …

Adults With Intellectual Disability Or Autism Spectrum Disorder. Executive Summary, Kimberly I. Snow Mhsa, Ba, Stuart Bratesman Mpp, Taryn Bowe, Julie T. Fralich Mba

Disability & Aging

This chartbook describes Maine’s historical trends in meeting the needs of adults with ID/ASD through institutional and community based services in comparison to other states; a detailed analysis of the population’s utilization of different types of services and their costs in SFY 2010; the implementation of the Supports Intensity Scale (SIS) as a means of identifying the supports needs of the adults with ID/ASD; and the complement of providers serving this population in Maine.

Pupillometry: A Non-Invasive Technique For Pain Assessment In Paediatric Patients., Mark A. Connelly, Jacob T. Brown, Gregory L. Kearns, Rawni A. Anderson, Shawn D. St Peter, Kathleen A. Neville

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVE: Pupillometry has been used to assess pain intensity and response to analgesic medications in adults. The aim of this observational study was to explore proof of concept for the use of this technique in paediatric patients. Changes in pupil parameters before and after opioid exposure also were evaluated.

DESIGN AND SETTING: This was a single-centre, prospective study conducted at an academic paediatric medical centre.

PATIENTS: Children 9-17 years of age undergoing elective surgical correction of pectus excavatum were enrolled into a protocol approved by the human ethical committee (institutional review board).

INTERVENTIONS: Pupil size and reactivity were measured using …

Comprehensive Management Of The Paranasal Sinuses In Patients Undergoing Endoscopic Endonasal Skull Base Surgery., Gurston G Nyquist, Md, Marc R Rosen, Md, Mark E. Friedel, Md, D David Beahm, Md, Christopher J Farrell, Md, James J. Evans, Md

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

OBJECTIVE: The endonasal route often provides the most direct and safe approach to skull base pathology. In this article we review the literature with regard to management of the paranasal sinuses in the setting of skull base surgery.

METHODS: We describe our institutional experience and review the literature of concurrent management of the sinusitis in patients undergoing endoscopic skull base surgery.

RESULTS: Patients should be optimized preoperatively to ensure the endonasal route is a safe corridor to enter the intracranial cavity. Often the paranasal sinuses can be surgically addressed at the same time as endoscopic skull base surgery. We describe …

Social Support From The Athletic Trainer And Symptoms Of Depression And Anxiety At Return To Play, Jingzhen Yang, Julie T. Schaefer, Ni Zhang, Tracey Covassin, Kele Ding, Erin Heiden

Faculty Research, Scholarly, and Creative Activity

No abstract provided.

Use Of Fresh Parental Fibular Allograft For Reconstruction Of Skeletal Defects After Limb Salvage Surgery, Muhammad Masood Kadir, Raza Askari, Sher Baz

Department of Surgery

Abstract

OBJECTIVE:

To share early experience with paediatric patients having undergone skeletal reconstruction after limb salvage surgery.

METHODS:

A reterorespective audit study was conducted at Aga Khan University Hospital, Karachi, from 1994 to 2011 An audit of the institutional tumour registry was done and relevant cases of paediatric patients having undergone skeletal reconstruction after limbsalvage surgery were tracked. Outcomes were objectively assessed through Musculoskeletal Tumour Society score. International Society of Limb Salvage grading was used to measure union of the graft to the host bone.

RESULTS:

Of the total 9 patients, 5(55.6%) were males and 4(44.4%) were females with an …

Our Experience With Van Nes Rotationplasty For Locally Advanced Lower Extremity Tumours, Raza Askari, Masood Umer, Mohsin-E-Azam, Haroon Rashid

Department of Surgery

Abstract

OBJECTIVE:

To present an early experience with the time-tested technique of Van Ness Rotationplasty to save distal lmbs.

METHODS:

Van Nes Rotationplasty for locally advanced lower extremity tumours. A reterorespective audit was conducted at Aga Khan University Hospital, Karachi, and comprised cases of bone and soft tissue sarcoma who underwent Van Ness Rotationplasty over seven years from January 2005 to December 2011. Demographic data, family history, past history, co-morbids, date since diagnosis, duration of symptoms, type of tumour, metastasis, pre-op and post-op functional status, recurrence and survival were collected.

RESULTS:

Of the 351 cases of bone and soft tissue …

Effect Of Teriparatide On Bone Regenerate After Distraction Osteogenesis, Masood Umer, Tashfeen Ahmad, Sadia Habib, Rasham Rehman, Mahmood Ahmed, Irfan Qadir

Department of Surgery

Abstract

OBJECTIVE:

To determine the effect of teriparatide on new bone formation in a rat model of distraction osteogenesis.

METHODS:

The experimental study was conducted at the Aga Khan University Hospital, Karachi, in November-December 2010, and comprised male Sprague-Dawley rats weighing 250gm each who were allocated to two treatment groups, teriparatide and saline, both given subcutaneously for 7 weeks. Femoral distraction was done for 3 weeks at the rate of 0.4mm/day, followed by a further 4 weeks for consolidation. New bone formation was assessed using X-ray scoring system, bone densitometry and histology.

RESULTS:

The 12 rats in the study were …

Formulating Effective And Accessible Population-Based Colorectal Cancer Screening Programs, Danielle Luffman

Independent Study Project (ISP) Collection

Colorectal cancer, a type of carcinoma originating in cells of the colon or rectum, continues to rank as the third most prevalent cancer worldwide with 1.36 million cases and the fourth most fatal with 693,881 deaths during 2012. In an attempt to alleviate the burden of colorectal cancer throughout society, governments and non-governmental organizations continue to implement population-based cancer screening programs. These programs, typically designed by a federal authority, offer free screening tests to a given population for a certain type of cancer on a routine basis. National systematic screening programs have effectively reduced the incidence of and mortality from …

The End Of An Era: The Cancer Stem Cell Hypothesis And Its Therapeutic Implications, Emily Paton

Independent Study Project (ISP) Collection

Cancer, a leading cause of death in many developed countries, has become a global health burden. Much of the drain on healthcare systems has resulted from the high cost and ineffectiveness of conventional cancer treatments, which often lead to cancer relapse or metastasis. The failures of chemotherapy, radiation, and surgery have been elucidated by the cancer stem cell (CSC) hypothesis, which postulates that a small percentage of tumor cells drive tumorigenesis. These cells can sustain cancer through their capacity to self-renew and differentiate into specialized tumor cell types, similar to how healthy stem cells maintain healthy tissues. Conventional cancer treatments …

Treatment Updates Regarding Anaplastic Oligodendroglioma And Anaplastic Oligoastrocytoma, Khurshid Ahmed Khan, Ahmed Nadeem Abbasi, Nasir Ali

Department of Radiation Oncology

Anaplastic Oligodendroglioma / Anaplastic Oligoastrocytoma (AO/AOA) is a WHO Grade-III primary brain tumor. These tumors comprise about 5 - 10% of all gliomas, which make them the third most common primary brain tumors after glioblastoma multiforme and astrocytomas. For many years standard of treatment remained Maximum Safe Resection (MSR) followed by Radiotherapy (RT). These tumors have also been known to be sensitive to alkylator-based chemotherapy particularly the subset having 1p/19q co-deletion signature. There is robust data showing that these tumors are responsive to chemotherapy in recurrent or progressive setting. Recently, up front chemotherapy has been added to standard post-surgery RT. …

Transfusion Practice In Orthopedic Patients: Do We Really Need It?, Kashif Abbas, Raza Askari, Masood Umer, Kamran Hafeez

Department of Surgery

Abstract

OBJECTIVE:

To determine the proportion of inappropriate transfusions in patients undergoing orthopaedic surgery at a tertiary care university hospital, and factors associated with inappropriate transfusions.

METHODS:

The prospective study was conducted at Aga Khan University Hospital, Karachi, from December 2008 to September 2009, and comprised patients admitted to the Orthopaedic Department and received transfusion of at least one packed cell. Patients were divided into four groups: A, those with haemoglobin < 7, B, haemoglobin 7.1-10 without ischemic heart disease, C, haemoglobin 7.1-10 with ischemic heart disease, and D, haemoglobin >10. Variables recorded were, pre-transfusion haemoglobin level, co-morbids, symptoms of hypovolemia, pre-transfusion volume replacement with fluids, transfusion reactions, and haemoglobin after 48 hours. Indications of transfusion were assessed in …