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Labrad : Vol 39, Issue 1 - September 2013, Aga Khan University Hospital, Karachi

LABRAD - Departments of Pathology & Laboratory Medicine and Radiology Archives

• Immunophenotyping by Flowcytometry
• Chronic Lymphocytic Leukaemia: Diagnosis and Prognostic Factors
• Tumour Markers
• Role of Chemical Pathology in Screening and Diagnosis of Multiple Myeloma
• 1p/19q Deletion: Favourable Prognostic Marker for Oligodendroglioma
• EGFR Mutation Screening Test for Lung Cancer Patients
• Clinical Utility of BCR-ABL1 Kinase Domain Mutational Analysis
• Molecular Cytogenetic Testing for Acute Myeloid Leukaemia
• Diffuse Large B-Cell Lymphoma (DLBCL) Subgroups have Different Phenotype

Oncolog, Volume 58, Number 09, September 2013, Jill Delsigne, Markeda Wade

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

• Advances in Neuroimaging Help Unveil the Mechanisms of Chemobrain: Chemobrain, a catchall term for the cognitive dysfunction and neurophysiological changes produced bt chemotherapy toxicity, is an important quality-of-life issue for cancer survivors
• Opioid Rotation Can Improve Pain Control and Reduce Neurotoxicity for Cancer Patients: Opioids are a main stay in the relief of pain-especially the chronic cancer-related pain often encountered in the palliative care setting. However, extended opioid use can result in tolerance, dependence, and opioid-induced neurotoxicity
• INBRIEF: Researchers Identity Inhibitor of Cancer-Promoting Protein SKp2/ Change in CA-125 Level Over Time Shows Promise for Ovarian cancer Screening
• HOUSE CALL: Myths …

The Effect Of Malnutrition On Patients Undergoing Elective Joint Arthroplasty., Ronald Huang, Md, Max Greenky, Bs, Glenn J. Kerr, Md, Mathew S. Austin, Md, Javad Parvizi, Md, Frcs

Rothman Institute Papers

Malnutrition has been linked to serious complications in patients undergoing elective total joint arthroplasty (TJA). This study prospectively evaluated 2,161 patients undergoing elective TJA for malnutrition as defined by either an abnormal serum albumin or transferrin. The overall incidence of malnutrition was 8.5% (184 of 2,161) and the rate of overall complications in the malnourished group was 12% as compared to 2.9% in patients with normal parameters (P55years-old undergoing TJA and is associated with a significant increase in post-operative complications.

Managing Data For The International, Multicentre Intergrowth-21st Project, E O. Ohuma, L Hoch, C Cosgrove, H E. Knight, L Cheikh Ismail, L Juodvirsiene, A T. Papageorghiou, H Al-Jabri, M Domingues, P Gilli, N Kunnawar, N Musee, F Roseman, A Carter, M Wu, D G. Altman

Obstetrics and Gynaecology, East Africa

The INTERGROWTH-21st Project data management was structured incorporating both a centralised and decentralised system for the eight study centres, which all used the same database and standardised data collection instruments, manuals and processes. Each centre was responsible for the entry and validation of their country-specific data, which were entered onto a centralised system maintained by the Data Coordinating Unit in Oxford. A comprehensive data management system was designed to handle the very large volumes of data. It contained internal validations to prevent incorrect and inconsistent values being captured, and allowed online data entry by local Data Management Units, as well …

Comparison Of The Virulence Markers Of Helicobacter Pylori And Their Associated Diseases In Patients From Pakistan And Afghanistan, Javed Yakoob, Zaigham Abbas, Wasim Jafri, Muhammad W. Usman, Fatima Jafri, Safia Awan

Section of Gastroenterology

BACKGROUND/AIM: Helicobacter pylori is a Gram-negative bacteria, which is associated with development of gastroduodenal diseases. The prevalence of H. pylori and the virulence markers cytotoxin-associated gene A and E (cagA, cagE) and vacuolating-associated cytotoxin gene (vacA) alleles varies in different parts of the world. H. pylori virulence markers cagA, cagE, and vacA alleles in local and Afghan nationals with H. pylori-associated gastroduodenal diseases were studied.

PATIENTS AND METHODS:Two hundred and ten patients with upper gastrointestinal symptoms and positive for H. pylori by the urease test and histology were included. One hundred and nineteen were local nationals and 91 were Afghans. …

Ultrasound Methodology Used To Construct The Fetal Growth Standards In The Intergrowth-21st Project, Papageorghiou A. T, Sarris I, Oannou C I, Todros T, Maria Carvalho, Pilu G, Salomon L. J

Imaging & Diagnostic Radiology, East Africa

A unified protocol is essential to ensure that fetal ultrasound measurements taken in multicentre research studies are accurate and reproducible. This paper describes the methodology used to take two-dimensional, ultrasound measurements in the longitudinal, fetal growth component of the INTERGROWTH-21^st Project. These standardised methods should minimise the systematic errors associated with pooling data from different study sites. They represent a model for carrying out similar research studies in the future.

Improvement In Access And Equity For Maternal And Neonatal Health Services: Comparative Advantages Of Contracted-Out Versus Non-Contracted-Out Facilities, Shehla Zaidi, Fauziah Rabbani, Iqbal Azam Syed, Atif Riaz, Peter Hatcher, Gul Nawaz Khan Nawaz Khan, Nousheen Pradhan, Hassan Fazli, Shiraz Shaikh, Yasmeen Khan, Syeda Nida Naim, Unaib Rabbani

Community Health Sciences

No abstract provided.

Pulmonary Arteriovenous Malformation In Cryptogenic Liver Cirrhosis, Noureen Afzal, Saleem Akhtar, Shakeel Ahmed, Mehnaz Atiq

Department of Paediatrics and Child Health

The cause in 10 - 20% cases of liver cirrhosis (LC) cannot be elucidated, and are thus termed cryptogenic. Pulmonary arteriovenous malformations (PAVMs) are relatively rare, but the most common anomaly involving the pulmonary tree. Although the rare correlation between LC and PAVM is well-known, there have been no reports of PAVMs occurring in cryptogenic LC. We report a case of PAVM that occurred in cryptogenic liver cirrhosis in a 3 years old male child. The child presented with complaints of malena, hematemesis and variceal bleed. The examination revealed a child with respiratory distress, irritability, tachycardia, clubbing and abdominal distention. …

Reproducibility Of Cine Displacement Encoding With Stimulated Echoes (Dense) Cardiovascular Magnetic Resonance For Measuring Left Ventricular Strains, Torsion, And Synchrony In Mice, Christopher M. Haggerty, Sage P. Kramer, Cassi M. Binkley, David K. Powell, Andrea C. Mattingly, Richard Charnigo, Frederick H. Epstein, Brandon K. Fornwalt

Pediatrics Faculty Publications

BACKGROUND: Advanced measures of cardiac function are increasingly important to clinical assessment due to their superior diagnostic and predictive capabilities. Cine DENSE cardiovascular magnetic resonance (CMR) is ideal for quantifying advanced measures of cardiac function based on its high spatial resolution and streamlined post-processing. While many studies have utilized cine DENSE in both humans and small-animal models, the inter-test and inter-observer reproducibility for quantification of advanced cardiac function in mice has not been evaluated. This represents a critical knowledge gap for both understanding the capabilities of this technique and for the design of future experiments. We hypothesized that cine DENSE …

Cardiac Fibroblast-Dependent Extracellular Matrix Accumulation Is Associated With Diastolic Stiffness In Type 2 Diabetes., Kirk R. Hutchinson, C. Kevin Lord, T. Aaron West, James A. Stewart

CAS Publications

Cardiovascular complications are a leading cause of death in patients with type 2 diabetes mellitus (T2DM). Diastolic dysfunction is one of the earliest manifestations of diabetes-induced changes in left ventricular (LV) function, and results from a reduced rate of relaxation and increased stiffness. The mechanisms responsible for increased stiffness are not completely understood. Chronic hyperglycemia, advanced glycation endproducts (AGEs), and increased levels of proinflammatory and profibrotic cytokines are molecular pathways known to be involved in regulating extracellular matrix (ECM) synthesis and accumulation resulting in increased LV diastolic stiffness. Experiments were conducted using a genetically-induced mouse model of T2DM generated by …

A Survey Of The Barriers Associated With Academic-Based Cancer Research Commercialization, Nathan L. Vanderford, L. Todd Weiss, Heidi L. Weiss

Markey Cancer Center Faculty Publications

Commercialization within the academic setting is associated with many challenges and barriers. Previous studies investigating these challenges/barriers have, in general, broadly focused on multiple disciplines and, oftentimes, several institutions simultaneously. The goal of the study presented here was to analyze a range of barriers that may be broadly associated with commercializing academic-based cancer research. This goal was addressed via a study of the barriers associated with cancer research commercialization at the University of Kentucky (UK). To this end, a research instrument in the form of an electronic survey was developed. General demographic information was collected on study participants and two …

Spectral Discrimination Of Breast Pathologies In Situ Using Spatial Frequency Domain Imaging, Ashley M. Laughney, Venkataramanan Krishnaswamy, Elizabeth J. Rizzo, Mary C. Schwab, Richard J. Barth, David J. Cuccia, Bruce J. Tromberg, Keith D. Paulsen, Brian W. Pogue, Wendy A. Wells

Dartmouth Scholarship

Introduction: Nationally, 25% to 50% of patients undergoing lumpectomy for local management of breast cancer require a secondary excision because of the persistence of residual tumor. Intraoperative assessment of specimen margins by frozen-section analysis is not widely adopted in breast-conserving surgery. Here, a new approach to wide-field optical imaging of breast pathology in situ was tested to determine whether the system could accurately discriminate cancer from benign tissues before routine pathological processing.

Targeting Platelet Thrombin Receptor Signaling To Prevent Thrombosis, Eric L. Wallace, Susan S. Smyth

Gill Heart & Vascular Institute Faculty Publications

Platelets contribute fundamentally to ischemic heart disease, and antiplatelet therapy has been critical to reducing acute thrombotic complications of atherosclerotic disease. Thrombin, by acting on protease activated receptors (PAR), is one of the most potent platelet activators. PAR-1 antagonists may therefore provide more comprehensive antithrombotic effects. We review the pathophysiology of atherothrombosis, platelet activation by thrombin, the role of platelet protease activated receptors (PAR), and the clinical data supporting their use.

Interests In High-Functioning Autism Are More Intense, Interfering, And Idiosyncratic Than Those In Neurotypical Development, Laura G. Anthony, Lauren Kenworthy, Benjamin E. Yerys, Kathryn F. Jankowski, Joette James, Madeline B. Harms, Alex Martin, Gregory L. Wallace

Psychiatry and Behavioral Sciences Faculty Publications

Although circumscribed interests are pathognomonic with autism, much about these interests remains unknown. Using the Interests Scale (IS), this study compares interests between 76 neurotypical (NT) individuals and 109 individuals with high-functioning autism spectrum disorder (HF-ASD) matched groupwise on age, IQ, and gender ratio. Participants and their parents/caregivers completed diagnostic measures (the Autism Diagnostic Interview—Revised and the Autism Diagnostic Observation Schedule; HF-ASD only), cognitive tests (Wechsler IQ Scales), and questionnaires (the Repetitive Behavior Scale—Revised, the Behavior Rating Inventory of Executive Function, and the Social Responsiveness Scale), in addition to the IS. Consistent with previous research, HF-ASD and NT individuals did …

Effect Of Early Release Of Tourniquet In Total Knee Arthroplasty, Kashif Abbas, Hasnain Raza, Masood Umer, Kamran Hafeez

Section of Orthopaedic Surgery

Objective: To evaluate whether tourniquet release intraoperatively is better than postoperative release in reducing overall blood loss, duration of surgery, duration of tourniquet, length of hospital stay, wound related complications and transfusion requirement. Study Design: Comparative study. Place and Duration of Study: Department of Surgery, The Aga Khan University Hospital, Karachi, from January 2004 to June 2007.
Methodology: One hundred and thirty patient files were reviewed retrospectively. Patients were divided into two groups. Group-A consisted of 65 patients with early deflation of tourniquet and group-B comprised of 65 patients with the release of tourniquet after applying compressive dressing. Total blood …

Sentinel Node Localisation Using Pre-Operative Lymphoscintigraphy And Intraoperative Gamma Probe In Early Oral Cavity Cancer, Mubasher Ikram, Shabbir Akhtar, Montasir Junaid, Tariq Dhari, Maseeh-Uz Zaman, Riffat Hussain, Zubair Ahmad

Section of Otolaryngology, Head & Neck Surgery

Objectives: To assess the diagnostic value of sentinel lymph node localisation using pre-operative lymphoscintigraphy and intra-operative gamma probe radio localisation in Pakistani patients suffering from early stage squamous cell carcinoma of the oral cavity.
Methods: The prospective case series was conducted between September 2007 and April 2010 at the Aga Khan University Hospital, Karachi. It comprised patients with T1and T2 oral cavity cancer with clinically and radiologically negative neck. Pre-operative lymphoscintigraphy was performed one day before surgery and intra-operative gamma probe was used to detect sentinel node. Final histo-pathological evaluation was taken as the gold standard.
Results: The study comprised …

Improving Function In Age-Related Macular Degeneration: A Randomized Clinical Trial., Barry W. Rovner, Robin J Casten, Mark T Hegel, Robert W Massof, Benjamin E. Leiby, Allen C. Ho, William S. Tasman

Department of Psychiatry and Human Behavior Faculty Papers

PURPOSE: To compare the efficacy of problem-solving therapy (PST) with supportive therapy (ST) to improve targeted vision function (TVF) in age-related macular degeneration (AMD).

DESIGN: Single-masked, attention-controlled, randomized clinical trial with outcome assessments at 3 months (main trial endpoint) and 6 months (maintenance effects).

PARTICIPANTS: Patients with AMD (n = 241) attending retina practices.

INTERVENTIONS: Whereas PST uses a structured problem-solving approach to reduce vision-related task difficulty, ST is a standardized attention-control treatment.

MAIN OUTCOME MEASURES: We assessed TVF, the 25-item National Eye Institute Vision Function Questionnaire plus Supplement (NEI VFQ), the Activities Inventory (AI), and vision-related quality of life …

Early Echocardiographic Changes After Percutaneous Implantation Of The Edwards Sapien Transcatheter Heart Valve In The Pulmonary Position., Shahryar M. Chowdhury, Ziyad M. Hijazi, John Rhodes, Saibal Kar, Raj Makkar, Michael Mullen, Qi-Ling Cao, Lydia King, Jodi Akin, Girish S. Shirali

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVES: To evaluate echocardiographic changes after SAPIEN valve implantation in the pulmonary position.

BACKGROUND: The feasibility of the SAPIEN transcatheter pulmonary valve (TPV) has recently been demonstrated. We evaluated changes in pulmonary valve function and the right ventricle after SAPIEN TPV placement.

METHODS: We evaluated echocardiograms at baseline, discharge, 1 and 6 months after TPV placement in 33 patients from 4 centers. Pulmonary insufficiency severity was graded 0-4. TPV peak and mean gradients were measured. Right ventricular (RV) size and function were quantified using routine measures derived from color, spectral, and tissue Doppler indices and two-dimensional echocardiography.

RESULTS: At baseline, …

Nutri One-On-One: The Assessment And Evaluation Of A Single One-On-One Nutritional Coaching In Patients Affected By Metabolic Syndrome, Jennifer L. King

PCOM Biomedical Studies Student Scholarship

The Nutri One-on-One Program's aim was to positively modify participants' nutritional habits and lifestyles through a brief one-on-one health coaching session, which was conducted within a primary healthcare setting at the Philadelphia College of Osteopathic Medicine's Clinics. It is documented that 70% of deaths in the U.S. result from complications secondary to chronic diseases of metabolic syndrome. The participants were selected by physicians and classified as suffering from one or more of the five indicators of metabolic syndrome: abdominal obesity, elevated serum triglycerides, low HDL-cholesterol, elevated blood pressure, and insulin resistance. Evidence shows that health coaching positively assists individuals in …

Coping With Pediatric Cancer: Conversational Methods Utilized By Parents And Children When Dealing With Pediatric Cancer, Chelsi Morgan Walls

UNLV Theses, Dissertations, Professional Papers, and Capstones

This study analyzed how people perceived parents should communicate with their child regarding pediatric cancer treatments. When dealing with pediatric cancer, it is vital that parents and their child communicate about the illness in order to effectively cope with the cancer. Using Uncertainty Management Theory, appraisals, inferences, and illusions, are examined in this study to discover how much affect-management and buffering would be used to manage the illness. Under UMT, the coping mechanisms of affect-management (i.e., religious coping and behavioral disengagement), and buffering (avoidance and child distraction) depend upon how individuals appraise the uncertain situation (positive vs. negative), the inferences …

Hippocampal Functional Connectivity Patterns During Spatial Working Memory Differ In Right Versus Left Temporal Lobe Epilepsy., Gaelle Eve Doucet, Karol Osipowicz, Ashwini Sharan Md, Michael R Sperling, Joseph I Tracy

Department of Neurology Faculty Papers

Temporal lobe epilepsy (TLE), affecting the medial temporal lobe, is a disorder that affects not just episodic memory but also working memory (WM). However, the exact nature of hippocampal-related network activity in visuospatial WM remains unclear. To clarify this, we utilized a functional connectivity (FC) methodology to investigate hippocampal network involvement during the encoding phase of a functional magnetic resonance imaging (fMRI) visuospatial WM task in right and left TLE patients. Specifically, we assessed the relation between FC within right and left hippocampus-seeded networks, and patient performance (rate of correct responses) during the encoding phase of a block span WM …

Disease Patterns And Outcomes Of Neonatal Admissions At A Secondary Care Hospital In Pakistan, Syed R. Ali, Shakeel Ahmed, Heeramani Lohana

Department of Paediatrics and Child Health

Objectives: This study aimed to determine the disease patterns and outcome of patients admitted to the neonatal unit of a secondary care hospital in Pakistan from January to December 2009.
Methods: Retrospective data from the medical records of all neonates admitted during the study period were reviewed and analysed for age, weight, sex, reason for admission, duration of hospital stay, diagnosis and final outcome. Trends were examined to identify the indicators of inpatient neonatal deaths.
Results: The total number of neonates admitted during the study period was 1,554; 979 were male (63%), and 575 were female (37%). A total of …

Evaluating The Utility Of Clinical Criteria For The Identification Of Lynch Syndrome Among Endometrial Cancer Patients, Amanda S. Bruegl

Dissertations and Theses (Open Access)

Background: Lynch Syndrome (LS) is a familial cancer syndrome with a high prevalence of colorectal and endometrial carcinomas among affected family members. Clinical criteria, developed from information obtained from familial colorectal cancer registries, have been generated to identify individuals at elevated risk for having LS. In 2007, the Society of Gynecologic Oncology (SGO) codified criteria to assist in identifying women presenting with gynecologic cancers at elevated risk for having LS. These criteria have not been validated in a population-based setting.

Materials and Methods: We retrospectively identified 412, unselected endometrial cancer cases. Clinical and pathologic information were obtained from the electronic …

Body Mri Artifacts In Clinical Practice: A Physicist's And Radiologist's Perspective., Martin J Graves, Donald Mitchell

Department of Radiology Faculty Papers

The high information content of MRI exams brings with it unintended effects, which we call artifacts. The purpose of this review is to promote understanding of these artifacts, so they can be prevented or properly interpreted to optimize diagnostic effectiveness. We begin by addressing static magnetic field uniformity, which is essential for many techniques, such as fat saturation. Eddy currents, resulting from imperfect gradient pulses, are especially problematic for new techniques that depend on high performance gradient switching. Nonuniformity of the transmit radiofrequency system constitutes another source of artifacts, which are increasingly important as magnetic field strength increases. Defects in …

Efficacy Of Gold Silica Nanoshells And Gold Nanorods For Photothermal Therapy Of Human Glioma Spheroids, Suyog Jung Chhetri

UNLV Theses, Dissertations, Professional Papers, and Capstones

Gold-based nanoparticles including gold-silica nano-spheres and gold nano-rods have been investigated for a number of therapeutic and diagnostic applications. The ability of these nanoparticles to convert light into heat energy makes them particularly appealing for photothermal therapy in which cancer cells are destroyed via light-induced heat generation. The overall objective of the study is to compare the efficacy of gold-silica nano-spheres and gold nano-rods in an in vitro system consisting of human brain tumor (glioma) spheroids.

Delivery of the nanoparticles to the spheroids was accomplished using murine macrophages. Nanoparticles (spheres or rods) were incubated with macrophages for 24 hours. Thereafter, …

Crystal Structure Of The N-Acetyltransferase Domain Of Human N-Acetyl-L-Glutamate Synthase In Complex With N-Acetyl-L-Glutamate Provides Insights Into Its Catalytic And Regulatory Mechanisms, Gengxiang Zhao, Zhongmin Jin, Norma M. Allewell, Mendel Tuchman, Dashuang Shi

Pediatrics Faculty Publications

N-acetylglutamate synthase (NAGS) catalyzes the conversion of AcCoA and L-glutamate to CoA and N-acetyl-L-glutamate (NAG), an obligate cofactor for carbamyl phosphate synthetase I (CPSI) in the urea cycle. NAGS deficiency results in elevated levels of plasma ammonia which is neurotoxic. We report herein the first crystal structure of human NAGS, that of the catalyticN-acetyltransferase (hNAT) domain with N-acetyl-L-glutamate bound at 2.1 Å resolution. Functional studies indicate that the hNAT domain retains catalytic activity in the absence of the amino acid kinase (AAK) domain. Instead, the major functions of the AAK domain appear to be providing …

Creation And Implementation Of An Emergency Medicine Education And Training Program In Turkey: An Effective Educational Intervention To Address The Practitioner Gap, Jennifer Whitfield Bellows, Katherine A. Douglass, Atilla Ridvan, Jeffrey Smith, G. Bobby Kapur

Emergency Medicine Faculty Publications

Background

The specialty of Emergency Medicine has enjoyed recognition for nearly 20 years in Turkey. However, the majority of underserved and rural Turkish emergency departments are staffed by general practitioners who lack formal training in the specialty and have few opportunities to increase emergency medicine-specific knowledge and skills.

Methods

To address this “practitioner gap,” the authors developed a four-phase comprehensive emergency medicine education and training program for general practitioners practicing in government hospitals in Turkey.

Results

From April 2006 until June 2009, 42 courses were taught by 62 trainers across seven regions in Turkey. A total of 2,262 physicians were …

Effect Of Variable Dose Rate On Biologically Effective Dose, Vadim Y. Kuperman, Gregory S. Spradlin

Publications

Purpose: to investigate the effect of variable dose rate on biologically effective dose ( BED ).

Materials and methods: by using the linear-quadratic (LQ) model with bi-exponential repair, we analytically determine the time-dependent dose rate R ~ which minimizes the effective protraction factor ( eff G ) and BEDunder the condition of fixed fraction time and dose per fraction.  Because normal tissue complication probability ( NTCP) monotonically decreases with decreasingBED , the dose rate R ~ also minimizes NTCP.

Results: the dependences of Geff, BED, and NTCP on fraction time were determined for different radiobiological parameters and two different …

Single-Trial Decoding Of Auditory Novelty Responses Facilitates The Detection Of Residual Consciousness, J. R. King, F. Faugeras, A. Gramfort, Aaron Schurger, I. El Karoui, J. D. Sitt, B. Rohaut, C. Wacongne, E. Labyt, T. Bekinschtein, L. Cohen, L. Naccache, S. Dehaene

Psychology Faculty Articles and Research

Detecting residual consciousness in unresponsive patients is a major clinical concern and a challenge for theoretical neuroscience. To tackle this issue, we recently designed a paradigm that dissociates two electro-encephalographic (EEG) responses to auditory novelty. Whereas a local change in pitch automatically elicits a mismatch negativity (MMN), a change in global sound sequence leads to a late P300b response. The latter component is thought to be present only when subjects consciously perceive the global novelty. Unfortunately, it can be difficult to detect because individual variability is high, especially in clinical recordings. Here, we show that multivariate pattern classifiers can extract …

A Synthetic Model Of Human Beta-Thalassemia Erythropoiesis Using Cd34+ Cells From Healthy Adult Donors, Y. Terry Lee, Ki-Soon Kim, Colleen Byrnes, Jaira F. De Vasconcellos, Seung-Jae Noh, Antoinette Rabel, Emily Riehm Meier, Jeffrey L. Meier

Pediatrics Faculty Publications

Based upon the lack of clinical samples available for research in many laboratories worldwide, a significant gap exists between basic and clinical studies of beta-thalassemia major. To bridge this gap, we developed an artificially engineered model for human beta thalassemia by knocking down beta-globin gene and protein expression in cultured CD34+ cells obtained from healthy adults. Lentiviral-mediated transduction of beta-globin shRNA (beta-KD) caused imbalanced globin chain production. Beta-globin mRNA was reduced by 90% compared to controls, while alpha-globin mRNA levels were maintained. HPLC analyses revealed a 96% reduction in HbA with only a minor increase in HbF. During the terminal …