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Labrad : Vol 40, Issue 1 - April 2014, Aga Khan University Hospital, Karachi

LABRAD - Departments of Pathology & Laboratory Medicine and Radiology Archives

• Provocative Testing for Growth Hormone Disorders
• Serum Procalcitonin for Early Sepsis Diagnosis
• Monoclonal Gammopathy of Undetermined Significance (MGUS)
• Understanding Six Sigma Methodology
• Blood Collection for Culture
• Molecular Analysis of Alpha Thalassaemia by Multiple Ligation Probe Assay
• Prognostification of Acute Myeloid Leukemia with FLT 3 Mutation
• Interferon Gamma Release Assay (IGRA) for Detection of Mycobacterium Tuberculosis Infection in the Host
• Meeting Report: The 37th Annual Conference of the Pakistan Association of Pathologists

Pharmaceuticals And Personal Care Products: Emerging Contaminants In Aquatic Ecosystems, Jenny E. Zenobio

Open Access Theses

In recent years, the presence of pharmaceuticals and personal care products (PPCPs) in aquatic systems has led to research on their fate and effects. PPCPs have been found in mixture in wastewater effluents, surface, ground, and drinking water at low concentrations from areas of intense urbanization. Although adverse effects to human health from the current environmental concentrations are unlikely, the impacts to ecological receptors are not clear. We performed field and laboratory studies to quantify and evaluate effects of PPCPs on fish. First, a field study was conducted at the Baca National Wildlife Refuge, Colorado (2010-2012) because a portion of …

Feasibility Of Pulsed Proton Induced Acoustics For 3d Dosimetry, Fahed M. Alsanea

Open Access Theses

Proton therapy has the potential to deposit its energy in tissue with high conformity to the tumor and significantly reduced integral dose to normal tissue compared to conventional radiation, such as x-rays. As a result, local control can be enhanced while reducing side-effects and secondary cancers. This is due to the way charged Particles deposit their energy or dose, where protons form a Bragg peak and establish a well-defined distal edge as a function of depth (range). To date, the dose delivered to a patient from proton therapy remains uncertain, in particular the positioning of the distal edge of the …

Oncolog, Volume 59, Number 04, April 2014, Zach Bohannan, Joe Munch, J. Delsigne

OncoLog MD Anderson's Report to Physicians (All issues) Archives

• New fat Grafting Technique Improves Aesthetic Outcomes Following Head and Neck Reconstructive Surgery: A new gat grafting technique is enabling reconstructive surgeons to maximize aesthetic outcomes following major reconstruction for head and neck cancer treatment-related defects
• INBRIEF: Invasive Bladder Cancer Subtypes Resemble Breast Cancer Subtypes
• New Kinase Inhibitors Hold Promise for Chronic Lymphocytic Leukemia, Other B-Cell Malignancies: New targeted therapies against chronic lymphocytic leukemia (CLL) are eliciting overall response rates similar to those achieved using standard chemoimmunotherapy but with fewer toxic effects
• HOUSE CALL: Animal-Assisted Therapy- Interacting with pets helps recovery

The Intersection Of Depression, Partner Violence And Poverty During The Perinatal Period, Catherine L. Kothari

Dissertations

Problem: Despite the wealth of research documenting the individual links between maternal depression, partner violence, and poverty, important gaps remain regarding their combined interactions, and their variation related to perinatal timing (pregnancy and postpartum). The current dissertation examined the interplay of these phenomena across perinatality.

Methods: This dissertation utilized secondary analysis of telephone survey data from a representative sample of women recruited during their postpartum hospital stay and interviewed four times over the subsequent 18 months. Linear regression was used for predictive modeling of fixed effects, and generalized estimating equation regression was used for multivariate analysis of temporal trends.

Findings: …

Numerical And Experimental Investigation Of Orthopaedic Fracture Fixation, Bipinchandra Patel

Dissertations

Poor bone fracture fixation leads to malunion, delayed union, non-union, or infection. These malunited fractures affect a bone’s ability to carry loads. Patient outcomes regarding fixation quality can be affected by the healing environment and human factors such as bone quality and surgeons’ perception. Furthermore, the stiffness and strength of the screw-plate construct affect the healing environment. Therefore, this dissertation investigates the stiffness and strength of the non-locking (conventional) and locking (fixed angle) type screw-plate constructs and the factors that contribute to them, such as screw-plate interface, screw design, bone density, cortical bone thickness and load orientation. Additionally, the surgeon’s …

Metformin Inhibits Androgen-Induced Igf-Ir Up-Regulation In Prostate Cancer Cells By Disrupting Membrane-Initiated Androgen Signaling., Roberta Malaguarnera, Antonella Sacco, Alaide Morcavallo, Sebastiano Squatrito, Antimo Migliaccio, Andrea Morrione, Marcello Maggiolini, Antonino Belfiore

Department of Urology Faculty Papers

We have previously demonstrated that, in prostate cancer cells, androgens up-regulate IGF-I receptor (IGF-IR) by inducing cAMP-response element-binding protein (CREB) activation and CREB-dependent IGF-IR gene transcription through androgen receptor (AR)-dependent membrane-initiated effects. This IGF-IR up-regulation is not blocked by classical antiandrogens and sensitizes cells to IGF-I-induced biological effects. Metformin exerts complex antitumoral functions in various models and may inhibit CREB activation in hepatocytes. We, therefore, evaluated whether metformin may affect androgen-dependent IGF-IR up-regulation. In the AR(+) LNCaP prostate cancer cells, we found that metformin inhibits androgen-induced CRE activity and IGF-IR gene transcription. CRE activity requires the formation of a CREB-CREB …

Brain Blast 2014 Speakers Poster, Annie Leslie

Brain Blast

Poster from UNE's Brain Blast 2014 listing the presenters at this event.

Tumor Radiation Therapy Creates Therapeutic Vaccine Responses To The Colorectal Cancer Antigen Gucy2c., Matthew Witek, Erik S Blomain, Michael Sullivan Magee, Bo Xiang, Scott A Waldman, Adam E. Snook

Department of Pharmacology and Experimental Therapeutics Faculty Papers

PURPOSE: Radiation therapy (RT) is thought to produce clinical responses in cancer patients, not only through direct toxicity to cancer cells and supporting tumor stroma cells, but also through activation of immunologic effectors. More recently, RT has potentiated the local and systemic effects of cancer immunotherapy (IT). However, combination regimens that maximize immunologic and clinical efficacy remain undefined.

METHODS AND MATERIALS: We evaluated the impact of local RT on adenoviral-mediated vaccination against the colorectal cancer antigen GUCY2C (Ad5-GUCY2C) in a murine subcutaneous tumor model using mouse CT26 colon cancer cells (CT26-GUCY2C). Immune responses were assessed by ELISpot, and clinical responses …

Neuroradiological Manifestations Of Tuberculous Meningitis, Sumaira Nabi, Sadaf Khattak, Mazhar Badshah, Haris Majid Rajput

Pakistan Journal of Neurological Sciences (PJNS)

Tuberculous meningitis (TBM) represents the most severe form of extra pulmonarytuberculosis (1).The early and exact diagnosis of TBM is important but difficult due to time consuming definitive microbiological procedures (2).Neuroimaging is an important initial investigation in tuberculous meningitis(3).This study was conducted to evaluate the neuroradiological findings in patients with tuberculous meningitis, as a useful modality for itsearly diagnoses and prompt treatment.

Radiosurgery: Current Recommendations For Intracranial Lesions And Practices In Pakistan, Hussain Shallwani, Sohaib Tariq, Muhammad E Bari

Pakistan Journal of Neurological Sciences (PJNS)

Radiosurgery is defined as the use of high-dose ionizing radiation for precise and total destruction of a chosen target, avoiding concomitant or delayed harm to adjacent tissues. The three types of radiations include gamma rays (GammaKnife) by Cobalt-60, X8 rays using linear accelerator (LINAC) system, and charged-particles generated from synchocyclotron. Recommendations: Based on current evidence, radiosurgery has proven benefits as the treatment of certain brain metastases, vestibular schwannomas, meningiomas, and some skull base tumors. Conclusion: This review describes the current recommendations for use of radiosurgery for intracranial pathologies. Radiosurgery is a relatively newer modality in the developing country of Pakistan. …

Isoflavones And Alzheimer’S Disease: The Effects Of Soy In Diet, Sara Habib, Asad Ali Khan Afridi, Mohammad Wasay, Romaina Iqbal

Pakistan Journal of Neurological Sciences (PJNS)

Pathologically, Alzheimer’s disease is a result of aggregation of amyloid peptides and protein tau in the brain forming neurofibrillary tangles which are highly toxic to neuronal circuits in the brain. Recent evidences report that apart from aging, estrogen deficiency is one of the risk factors predisposing to the development of Alzheimer’s disease. Isoflavones, also known as phytoestrogens, are metabolized by the body forming compounds that are known to interfere with neurotoxic pathways and through their anti-fibrillization effects they play a role in reducing apoptosis of neurons and glial cells and promote axonal regeneration. Experimental studies on transgenic models with Alzheimer’s …

Attendance At Cervical Cancer Screening And Use Of Diagnostic And Therapeutic Procedures On The Uterine Cervix Assessed From Individual Health Insurance Data (Belgium, 2002-2006), Marc Arbyn, Valérie Fabri, Marleen Temmerman, Cindy Simoens

Obstetrics and Gynaecology, East Africa

Objective: To assess the coverage for cervical cancer screening as well as the use of cervical cytology, colposcopy and other diagnostic and therapeutic interventions on the uterine cervix in Belgium, using individual health insurance data.

Methods: The Intermutualistic Agency compiled a database containing 14 million records from reimbursement claims for Pap smears, colposcopies, cervical biopsies and surgery, performed between 2002 and 2006. Cervical cancer screening coverage was defined as the proportion of women aged 25-64 that had a Pap smear within the last 3 years.

Results: Cervical cancer screening coverage was 61% at national level, for the target population of …

Barriers To Successful Cervical Cancer Screening In Rural Kwazulu-Natal, Cato Manor, And Cape Town, Amanda Comai

Independent Study Project (ISP) Collection

In 2000, the South African Department of Health produced a nationwide policy intended to combat the growing crisis of cervical cancer. Nearly fifteen years later, however, the disease remains a significant cause of death among certain female populations, especially those who are rural, poor, and HIV-positive. It is undeniable that challenges of access, awareness, resource demand, and stigmatization stand in the way of complete policy enactment.

In this study, I explore in detail the barriers that prevent successful implementation of the policy. My research combines interviews with a variety of individuals and participant observation at the Cancer Association of South …

Quality Of Emergency Departments In Amman Evaluated By The Availability Of Essential Emergency Equipment, Seif Laeth Sari Nasir

Independent Study Project (ISP) Collection

The present study aims to determine the quality of emergency health care in Jordan by assessing the availability of essential emergency equipment in emergency departments in Amman. This study uses a cross-­‐sectional questionnaire assessing the accessibility of equipment and medication in emergency departments, as well as eliciting the opinions of the participants regarding the future development of the emergency medical sector in Jordan. The questionnaires were distributed to the physician directors of every participating hospital emergency department in Amman, and completed by the physician director excepting two cases, one of which was completed by the head staff nurse, and the …

Promoter Hypermethylation Of Tumor Suppressor Genes Correlates With Tumor Grade And Invasiveness In Patients With Urothelial Bladder Cancer, Shumaila M. Bilgrami, Sohail A. Qureshi, Shahid Pervez, Farhat Abbas

Department of Pathology and Laboratory Medicine

Purpose: To investigate the promoter methylation status at selected loci which encode for key proteins involved in apoptosis, DNA repair, cell cycle control and progression in urothelial cell carcinoma of bladder and compare the findings from tissue samples with that of plasma.
Methods: Total genomic DNA was isolated from 43 non-muscle invasive (low grade) and 33 muscle invasive (high grade) urothelial bladder cancer samples along with 10 control cases of normal bladder mucosa. Promoter methylation status was investigated for RASSF1A, APC, MGMT, CDKN2A and CDKN2B genes using real-time methylation-specific PCR with SYBR® green. Plasma samples from 16 patients with muscle …

Serum Levels Of Soluble Icam-1 In Children With Pulmonary Artery Hypertension, Melahat Melek Oguz, Ayse Deniz Oguz, Cihat Sanli, Ayhan Cevik

The Texas Heart Institute Journal

This prospective cross-sectional study attempted to determine both the usefulness of the serum intercellular adhesion molecule-1 (ICAM-1) as a biomarker for pulmonary artery hypertension secondary to congenital heart disease and the nature of this marker's association with catheter angiographic findings.

Our study included a total of 70 male and female children, comprising 30 patients with both pulmonary artery hypertension and congenital heart disease, 20 patients with congenital heart disease alone, and 20 healthy control subjects. Levels of ICAM-1 in plasma samples from all groups were measured by the enzyme-linked immunosorbent assay method. Cardiac catheterization was also performed in all patients. …

Ultrasound-Enhanced Ocular Delivery Of Dexamethasone Sodium Phosphate: An In Vivo Study, Marjan Nabili, Aditi Shenoy, Shawn Chawla, Sankaranarayana P. Mahesh, Craig Geist, Vesna Zderic

Ophthalmology Faculty Publications

Background

The eye's unique anatomy and its physiological and anatomical barriers can limit effective drug delivery into the eye.

Methods

An in vivo study was designed to determine the effectiveness and safety of ultrasound application in enhancing drug delivery in a rabbit model. Permeability of a steroid ophthalmic drug, dexamethasone sodium phosphate, was investigated in ultrasound- and sham-treated cases. For this study, an eye cup filled with dexamethasone sodium phosphate was placed on the cornea. Ultrasound was applied at intensity of 0.8 W/cm² and frequency of 400 or 600 kHz for 5 min. The drug concentration in aqueous humor …

A Novel Multivalent, Single-Domain Antibody Targeting Tcda And Tcdb Prevents Fulminant Clostridium Difficile Infection In Mice, Zhiyong Yang, Diane Schmidt, Weilong Liu, Shan Li, Lianfa Shi, Jinliang Sheng, Kevin Chen, Hua Yu, Jacqueline M. Tremblay, Xinhua Chen, Kurt H. Piepenbrink, Eric J. Sundberg, Ciaran P. Kelly, Guang Bai, Charles B. Shoemaker, Hanping Feng

Food for Health: Publications

The incidence of Clostridium difficile infection (CDI) and associated mortality have increased rapidly worldwide in recent years. Therefore, it is critical to develop new therapies for CDI. In this study, we generated a novel, potently neutralizing, tetravalent, and bispecific antibody composed of 2 heavy-chain-only V_H (V_HH) binding domains against both TcdA and TcdB (designated “ABA”) that reverses fulminant CDI in mice infected with an epidemic 027 strain after a single injection of the antibody. We demonstrated that ABA bound to both toxins simultaneously and displayed a significantly enhanced neutralizing activity both in vitro and in vivo. Additionally, …

A Novel Curcumin Analog (H-4073) Enhances The Therapeutic Efficacy Of Cisplatin Treatment In Head And Neck Cancer, Bhavna Kumar, Arti Yadav, Kalman Hideg, Periannan Kuppusamy

Dartmouth Scholarship

Chemotherapy constitutes the standard modality of treatment for localized head and neck squamous cell carcinomas (HNSCC). However, many patients fail to respond and relapse after this treatments due to the acquisition of chemo- resistance. Therefore, there is an urgent need to develop novel drugs that could reverse the resistant phenotype. Curcumin, the constituent of the spice turmeric has been shown to have anti-inflammatory, anti-oxidant and anti-proliferative properties in several tumor types. However, use of curcumin has been limited due to its poor bio-absorption. Recently, a novel class of curcumin analogs, based on diarylidenylpiperidones (DAP), has been developed by incorporating a …

2014 Massachusetts Family Impact Seminar: A Lot On Our Plate; Chronic Health Threats In Massachusetts, Ira S. Ockene M.D., Christina D. Economos Ph.D, Barbara Goldoftas Ph.D, Denise A. Hines Ph.D., Caitlin Alcorn, Jacqueline A. Daigneault, Jordan R. Daley, Maura A. Flanagan, Carsten-Hendrik Rasche, Heather Rios, Julia Tran, Liam Kelly Fleming

Mosakowski Institute for Public Enterprise

A Lot on Our Plate: Chronic Health Threats in Massachusetts is the fifth Massachusetts Family Impact Seminar, and is designed to emphasize a family perspective in policymaking on issues related to childhood obesity, cardiovascular disease, and type 2 diabetes. In general, Family Impact Seminars analyze the consequences an issue, policy, or program may have for families.

Physiology And Advancements In Wound Healing, Adam Baker, Md

Department of Otolaryngology - Head and Neck Surgery Presentations and Grand Rounds

Outline of presentation:

Fundamentals

Advances

• -Growth Factors
• -Platelet Rich Plasma
• -Engineered skin
• -Hyperbaric Oxygen Therapy

Research

Characterization Of Iron Response In Gynecological Cell Lines, Kyle A. Bauckman

USF Tampa Graduate Theses and Dissertations

Ovarian carcinoma afflicts over 22,000 women each year with a 5 year survival rate of only 18% for stage IV patients [23]. Current treatment options are limited due to high rates of drug resistance and recurrence. Further, the identity of "precursor lesions" which give rise to various subclasses of epithelial ovarian cancer has been evasive. This is due to discovery of the cancer at already an advanced stage. Interestingly, endometriosis a benign but invasive gynecological disease has been described as a "precursor lesion" in the development of specific subtypes of ovarian cancer. Endometriotic cyst development involves the accumulation of "old …

Current Pathophysiological Concepts In Cerebral Small Vessel Disease., Fred Rincon, Clinton B Wright

Department of Neurology Faculty Papers

The association between cerebral small vessel disease (SVD) - in the form of white matter lesions, infarctions, and hemorrhages - with vascular cognitive impairment (VCI), has mostly been deduced from observational studies. Pathological conditions affecting the small vessels of the brain and leading to SVD have suggested plausible molecular mechanisms involved in vascular damage and their impact on brain function. However, much still needs to be clarified in understanding the pathophysiology of VCI, the role of neurodegenerative processes such as Alzheimer's disease, and the impact of aging itself. In addition, both genetic predispositions and environmental exposures may potentiate the development …

Aging Aggravates Nitrate-Mediated Ros/Rns Changes., Qian Fan, Lifen Chen, Shujuan Cheng, Fang Li, Wayne Bond Lau, Le Feng Wang, Jing Hua Liu

Department of Emergency Medicine Faculty Papers

Nitrates are the most frequently prescribed and utilized drugs worldwide. The elderly are a major population receiving nitrate therapy. Both nitrates and aging can increase in vivo reactive oxygen species (ROS) and reactive nitrogen species (RNS). To date, the effects of aging upon nitrate-induced ROS/RNS alteration are unknown. The present study tested the effects of aging upon nitrate-induced ROS/RNS alteration in vivo. 32 adults and 43 elderly unstable angina (UA) patients were subjected to 48 hours of isosorbide dinitrate intravenous injection (50  μg/minutes) in this clinical study. Blood samples were obtained at baseline and conclusion. Outcome measures of oxidative stress …

Microfluidic-Enabled Liposomes Elucidate Size-Dependent Transdermal Transport, Renee R. Hood, Eric L. Kendall, Mariana Junqueira, Wyatt N. Vreeland, Zenaide M.N. Quezado, Julia C. Finkel, Don L. Devoe

Pediatrics Faculty Publications

Microfluidic synthesis of small and nearly-monodisperse liposomes is used to investigate the size-dependent passive transdermal transport of nanoscale lipid vesicles. While large liposomes with diameters above 105 nm are found to be excluded from deeper skin layers past the stratum corneum, the primary barrier to nanoparticle transport, liposomes with mean diameters between 31–41 nm exhibit significantly enhanced penetration. Furthermore, multicolor fluorescence imaging reveals that the smaller liposomes pass rapidly through the stratum corneum without vesicle rupture. These findings reveal that nanoscale liposomes with well-controlled size and minimal size variance are excellent vehicles for transdermal delivery of functional nanoparticle drugs.

Redox-Mediated And Ionizing-Radiation-Induced Inflammatory Mediators In Prostate Cancer Development And Treatment, Lu Miao, Aaron K. Holley, Yanming Zhao, William H. St. Clair, Daret K. St. Clair

Toxicology and Cancer Biology Faculty Publications

SIGNIFICANCE: Radiation therapy is widely used for treatment of prostate cancer. Radiation can directly damage biologically important molecules; however, most effects of radiation-mediated cell killing are derived from the generated free radicals that alter cellular redox status. Multiple proinflammatory mediators can also influence redox status in irradiated cells and the surrounding microenvironment, thereby affecting prostate cancer progression and radiotherapy efficiency.

RECENT ADVANCES: Ionizing radiation (IR)-generated oxidative stress can regulate and be regulated by the production of proinflammatory mediators. Depending on the type and stage of the prostate cancer cells, these proinflammatory mediators may lead to different biological consequences ranging from …

Microbiota, Oral Microbiome, And Pancreatic Cancer, Dominique S. Michaud, Jacques Izard

Department of Food Science and Technology: Faculty Publications

Only 30% of patients diagnosed with pancreatic cancer survive one year post-diagnosis. Progress in understanding the causes of pancreatic cancer has been made, including solidifying the associations with obesity and diabetes, and a proportion of cases should be preventable through lifestyle modifications. Unfortunately, identifying reliable biomarkers of early pancreatic cancer has been extremely challenging, and no effective screening modality is currently available for this devastating form of cancer. Recent data suggest the microbiota may play a role in the disease process, but many questions remain. Future studies focusing on the human microbiome, both etiologically and as a marker of disease …

Prevalence And Risk Factors Of Depressive Symptoms In A Canadian Palliative Home Care Population: A Cross Sectional Study, Kathryn A. Fisher, Hsien Seow, Kevin Brazil, Shannon Freeman, Trevor Frise Smith, Dawn M. Guthrie

Kinesiology and Physical Education Faculty Publications

Background: Depression in palliative care patients is important because of its intrinsic burden and association with elevated physical symptoms, reduced immunity and increased mortality risk. Identifying risk factors associated with depression can enable clinicians to more readily diagnose it, which is important since depression is treatable. The purpose of this cross-sectional study was to determine the prevalence of depressive symptoms and risk factors associated with them in a large sample of palliative home care patients.

Methods: The data come from interRAI Palliative Care assessments completed between 2006 and 2012. The sample (n = 5144) consists of adults residing …

Cd46-Mediated Transduction Of A Species D Adenovirus Vaccine Improves Mucosal Vaccine Efficacy, Zenaido T. Camacho, Michael A. Barry, Eric A. Weaver

Nebraska Center for Virology: Faculty Publications

The high levels of preexisting immunity against Adenovirus type 5 (Ad5) have deemed Ad5 unusable for translation as a human vaccine vector. Low seroprevalent alternative viral vectors may be less impacted by preexisting immunity, but they may also have significantly different phenotypes from that of Ad5. In this study we compare species D Ads (26, 28, and 48) to the species C Ad5. In vitro transduction studies show striking differences between the species C and D viruses. Most notably, Ad26 transduced human dendritic cells much more effectively than Ad5. In vivo imaging studies showed strikingly different transgene expression profiles. The …