Analytical, Diagnostic and Therapeutic Techniques and Equipment Commons^™

Bridging From Intramuscular To Limb Perfusion Delivery Of Raav: Optimization In A Non-Human Primate Study, Alisha Gruntman, Gwladys Gernoux, Qiushi Tang, Guo-Jie Ye, Dave R. Knop, Gensheng Wang, Janet Benson, Kristen E. Coleman, Allison M. Keeler, Christian Mueller, Louis G. Chicoine, Jeffrey D. Chulay, Terence R. Flotte

Christian Mueller

Phase 1 and phase 2 gene therapy trials using intramuscular (IM) administration of a recombinant adeno-associated virus serotype 1 (rAAV1) for replacement of serum alpha-1 antitrypsin (AAT) deficiency have shown long-term (5-year) stable transgene expression at approximately 2% to 3% of therapeutic levels, arguing for the long-term viability of this approach to gene replacement of secreted serum protein deficiencies. However, achieving these levels required 100 IM injections to deliver 135 mL of vector, and further dose escalation is limited by the scalability of direct IM injection. To further advance the dose escalation, we sought to bridge the rAAV-AAT clinical development …

Effect Of Exercise Position On Percent Changes In Serratus Anterior Muscle Thickness, Joseph M. Day

Joseph M. "Matt" Day

Objective: A reliable method for measuring SA thickness with ultrasound imaging has been reported, yet the ability to detect differences in levels of contractility has yet to be established. The purpose of this study was to determine if there are differences in the percent change in thickness of the SA during four different exercise positions performed by healthy individuals.

Design: Observational study

Setting: Laboratory

Participants: Twenty-eight healthy participants, mean age 26 (SD 4, 57% female, 100% right handed)

Methods: Volunteers were positioned in a standardized sitting posture and anatomical landmarks were marked for ultrasound probe positioning. Two resting and two …

Investigation Of Zebrafish Larvae Behavior As Precursor For Suborbital Flights: Feasibility Study, Pedro Llanos, Kristina Andrijauskaite, Mark Rubinstein, Sherine S.L. Chan

Pedro J. Llanos (www.AstronauticsLlanos.com)

Survival Advantage Of Both Human Hepatocyte Xenografts And Genome-Edited Hepatocytes For Treatment Of Alpha-1 Antitrypsin Deficiency, Florie Borel, Qiushi Tang, Gwladys Gernoux, Cynthia Greer, Ziqiong Wang, Adi Barzel, Mark A. Kay, Leonard D. Shultz, Dale L. Greiner, Terence R. Flotte, Michael A. Brehm, Christian Mueller

Christian Mueller

Hepatocytes represent an important target for gene therapy and editing of single-gene disorders. In alpha-1 antitrypsin (AAT) deficiency, one missense mutation results in impaired secretion of AAT. In most patients, lung damage occurs due to a lack of AAT-mediated protection of lung elastin from neutrophil elastase. In some patients, accumulation of misfolded PiZ mutant AAT protein triggers hepatocyte injury, leading to inflammation and cirrhosis. We hypothesized that correcting the Z mutant defect in hepatocytes would confer a selective advantage for repopulation of hepatocytes within an intact liver. A human PiZ allele was crossed onto an immune-deficient (NSG) strain to create …

Disaggregating The Relative Influence Of Genetic, Environmental And Individual Factors On Lcl And Hdl Cholesterols And Bmi For A Sample Of African American (Aa) Mothers And Daughters, C. Jayne Brahler, Jewel Harden, Michelle Mchone, Matthew Soules, Eric Evans, Ann Alyanak, Fred Diakpieng, Paul M. Vanderburgh

Paul M. Vanderburgh

There are many reports about the associations between blood lipids, body mass index (BMI) and dietary cholesterol intakes both within the individual and between related individuals. The purpose of this descriptive research project was to investigate the relationships between LDL and HDL cholesterols, body mass index and dietary cholesterol intakes for a sample of African American (AA) mothers and their daughters and to attempt to separate the contribution of genetic versus environmental factors. Mother and daughter participants (n =42 and 66, respectively) were 12-14-hours fasted when blood samples were drawn, heights and weights measured, and 24 hour food recalls completed.

Evolution Of The Alpha-1 Antitrypsin Muscle Gene Therapy: Translation From Clinical Trial To Benchtop And Back Again, Alisha M. Gruntman, Gwladys Gernoux, Gensheng Wang, Janet Benson, Jeff Chulay, Dave Knop, Christian Mueller, Terence R. Flotte

Christian Mueller

Alpha-one antitrypsin (AAT) deficiency is a genetic disease affecting the lungs due to inadequate anti-protease activity in the pulmonary interstitium. On-going human trials use intra-muscular delivery of adeno-associated virus (rAAV1), allowing expressing myofibers to secrete normal (M)AAT protein. In the Phase IIa trial, patients in the highest dose cohort (6x1012vg/kg) were given 100 intra-muscular (IM) injections of undiluted vector, with serum AAT levels still substantially below target levels. Previous work has shown that delivering rAAV vector to the musculature via limb perfusion leads to widespread gene expression in myofibers. We hypothesize that widespread delivery would result in an overall increase …

5 Year Expression And Neutrophil Defect Repair After Gene Therapy In Alpha-1 Antitrypsin Deficiency, Christian Mueller, Gwladys Gernoux, Alisha M. Gruntman, Florie Borel, Emer P. Reeves, Roberto Calcedo, Farshid N. Rouhani, Anthony Yachnis, Margaret Humphries, Martha Campbell-Thompson, Louis M. Messina, Jeffrey D. Chulay, Bruce Trapnell, James M. Wilson, Noel G. Mcelvaney, Terence R. Flotte

Christian Mueller

Alpha-1 antitrypsin deficiency is a monogenic disorder resulting in emphysema due principally to the unopposed effects of neutrophil elastase. We previously reported achieving plasma wild-type alpha-1 antitrypsin concentrations at 2.5%-3.8% of the purported therapeutic level at 1 year after a single intramuscular administration of recombinant adeno-associated virus serotype 1 alpha-1 antitrypsin vector in alpha-1 antitrypsin deficient patients. We analyzed blood and muscle for alpha-1 antitrypsin expression and immune cell response. We also assayed previously reported markers of neutrophil function known to be altered in alpha-1 antitrypsin deficient patients. Here, we report sustained expression at 2.0%-2.5% of the target level from …

Recombinant Aav Serotype And Capsid Mutant Comparison For Pulmonary Gene Transfer Of Alpha-1-Antitrypsin Using Invasive And Noninvasive Delivery, Rejean Liqun Wang, Thomas J. Mclaughlin, Travis Cossette, Qiushi Tang, Kevin Foust, Martha Campbell-Thompson, Ashley Martino, Pedro Cruz, Scott Loiler, Christian Mueller, Terence R. Flotte

Christian Mueller

Recombinant adeno-associated viral (rAAV) vectors have been widely used in pulmonary gene therapy research. In this study, we evaluated the transduction and expression efficiencies of several AAV serotypes and AAV2 capsid mutants with specific pulmonary targeting ligands in the mouse lung. The noninvasive intranasal delivery was compared with the traditional intratracheal lung delivery. The rAAV8 was the most efficient serotype at expressing alpha-1-antitrypsin (AAT) in the lung among all the tested serotypes and mutants. A dose of 1 x 1010 vg of rAAV8-CB-AAT transduced a high percentage of cells in the lung when delivered intratrachealy. The serum and the broncho-alveolar …

Self-Complementary Adeno-Associated Virus Vectors Improve Transduction Efficiency Of Corneal Endothelial Cells, Anja K. Gruenert, Marta Czugala, Christian Mueller, Marco Schmeer, Martin Schleef, Friedrich E. Kruse, Thomas A. Fuchsluger

Christian Mueller

Transplantation of a donor cornea to restore vision is the most frequently performed transplantation in the world. Corneal endothelial cells (CEC) are crucial for the outcome of a graft as they maintain corneal transparency and avoid graft failure due to corneal opaqueness. Given the characteristic of being a monolayer and in direct contact with culture medium during cultivation in eye banks, CEC are specifically suitable for gene therapeutic approaches prior to transplantation. Recombinant adeno-associated virus 2 (rAAV2) vectors represent a promising tool for gene therapy of CEC. However, high vector titers are needed to achieve sufficient gene expression. One of …

Targeted Gene Delivery To The Enteric Nervous System Using Aav: A Comparison Across Serotypes And Capsid Mutants, Matthew J. Benskey, Nathan C. Kuhn, James J. Galligan, Joanna Garcia, Shannon E. Boye, William W. Hauswirth, Christian Mueller, Sanford L. Boye, Fredric P. Manfredsson

Christian Mueller

Recombinant adeno-associated virus (AAV) vectors are one of the most widely used gene transfer systems in research and clinical trials. AAV can transduce a wide range of biological tissues, however to date, there has been no investigation on targeted AAV transduction of the enteric nervous system (ENS). Here, we examined the efficiency, tropism, spread, and immunogenicity of AAV transduction in the ENS. Rats received direct injections of various AAV serotypes expressing green fluorescent protein (GFP) into the descending colon. AAV serotypes tested included; AAV 1, 2, 5, 6, 8, or 9 and the AAV2 and AAV8 capsid mutants, AAV2-Y444F, AAV2-tripleY-F, …

Therapeutic Raavrh10 Mediated Sod1 Silencing In Adult Sod1(G93a) Mice And Nonhuman Primates, Florie Borel, Gwladys Gernoux, Brynn Cardozo, Jake P. Metterville, Gabriela Toro Cabrera, Lina Song, Qin Su, Guang Ping Gao, Mai K. Elmallah, Robert H. Brown Jr., Christian Mueller

Christian Mueller

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease; survival in ALS is typically 3-5 years. No treatment extends patient survival by more than three months. Approximately 20% of familial ALS and 1-3% of sporadic ALS patients carry a mutation in the gene encoding superoxide dismutase 1 (SOD1). In a transgenic ALS mouse model expressing the mutant SOD1(G93A) protein, silencing the SOD1 gene prolongs survival. One study reports a therapeutic effect of silencing the SOD1 gene in systemically treated adult ALS mice; this was achieved with a short hairpin RNA, a silencing molecule that has raised multiple safety concerns, and …

Serum Levels Of Alpha-1 Antitrypsin Following Vascular Limb Or Intra-Muscular Delivery Of Aav1 Or Aav8 Gene Therapy Vectors In Rhesus Macaques, Alisha M. Gruntman, Gwladys Gernoux, Gensheng Wang, Janet M. Benson, Jeffrey D. Chulay, David R. Knop, Christian Mueller, Terence R. Flotte

Christian Mueller

Alpha-one antitrypsin (AAT) deficiency is a genetic disease that results in both lung disease and potentially liver failure in affected patients. In un-affected people AAT is produced in the liver and secreted to act as an anti-protease (primarily counteracting the effects of neutrophil elastase) in the lung. On-going human clinical trials have focused on intra-muscular delivery of adeno-associated virus (AAV1) to patients. The goal of delivery to the muscle is to have the myocytes serve as bio-factories to produce normal AAT protein and secrete it into the blood where it can exert its normal function in the lung. In the …

Sustained Expression With Partial Correction Of Neutrophil Defects 5 Years After Intramuscular Raav1 Gene Therapy For Alpha-1 Antitrypsin Deficiency, Terence R. Flotte, Christian Mueller, Gwladys Gernoux, Alisha Gruntman, Jeffrey D. Chulay, David R. Knop, Noel G. Mcelvaney, Martha Campbell-Thompson, James M. Wilson

Christian Mueller

Alpha-1 antitrypsin (AAT) deficiency is a common monogenic disorder resulting in emphysema, which is currently treated with weekly infusions of protein replacement. We previously reported achieving plasma wild-type (M) AAT concentrations at 2.5-3.8% of the therapeutic level at 1 year after intramuscular (IM) administration of 6×1012vg/kg of a recombinant adeno-associated virus serotype 1 (rAAV1)-AAT vector in AAT-deficient patients, with an associated regulatory T cell (Treg) response to AAV1 capsid epitopes in the absence of any exogenous immune suppression. Here, we report sustained expression at greater than 2% of the therapeutic level for 5 years after one-time treatment with rAAV1-AAT in …

Oncology Edge Task Force On Prostate Cancer Outcomes: A Systematic Review Of Outcome Measures For Functional Mobility, Claire Davies, Genevieve Colon, Hannah Geyer, Lucinda Pfalzer, Mary Insana Fisher

Mary Insana Fisher

Background: The medical treatment of prostate cancer results in multiple impairments in body structure and declines functional abilities, resulting in activity limitations and participation restrictions. Measurement of functional mobility is an essential outcome measure in survivorship care. Purpose: The purpose of this systematic review is to make recommendations of the best measurement tools to assess functional mobility in men treated for prostate cancer based on psychometric properties and clinical utility. Methods: Multiple electronic databases were searched from February to March 2014. Studies of tools used to assess functional mobility were included if they met the following criteria: reported psychometric properties, …

Research Roundup From The Research Committee, Mary Insana Fisher, Shana Harrington

Mary Insana Fisher

With the expectations of accountability by consumers and third party payors for the efficacy of physical therapy practice, there has been a significant increase in the push to develop outcome measures in rehabilitation. One type of these measures, patient-reported outcome measures (PROs), are becoming increasingly more common in clinical practice. The American Physical Therapy Association’s Guide to Physical Therapist Practice 3rd edition includes outcomes assessment as an integral part of the Patient and Client Management model, and delineates that appropriate tests and measures depend upon established psychometric properties of the measurement.1 The Section on Research formed the Evidence Database to …

Oncology Section Edge Task Force On Breast Cancer Outcomes: A Systematic Review Of Outcome Measures For Functional Mobility, Mary Insana Fisher, Jeannette Lee, Claire Davies, Hannah Geyer, Genevieve Colon, Lucinda Pfalzer

Mary Insana Fisher

Background: Breast cancer treatments in women with breast cancer often result in physical impairments that lead to activity limitations and participation restrictions. These limitations and restrictions manifest in impaired functional mobility skills that may impact survivorship. Thus, evaluation of functional mobility is an important part of survivorship care. Purpose: To identify functional mobility outcome measures that possess strong psychometric properties and are clinically useful for examination of women treated for breast cancer. Methods: Multiple electronic databases were searched for articles published after 1995. Studies were included if they reported psychometric properties, used clinically feasible methods, were performed on adults, and …

Knee Range Of Motion: Reliability And Agreement Of 3 Measurement Methods, Paul G. Peters, Michael A. Herbenick, Philip A. Anloague, Ronald J. Markert, L. Joseph Rubino

Philip A. Anloague

We conducted a study to compare 3 methods of measuring knee range of motion: visual estimation by physicians, hand goniometry by physical therapists, and radiographic goniometry. We hypothesized that reliability would be high within and across all techniques. We found intrarater and interrater reliability to be satisfactory for visual estimation, hand goniometry, and radiographic goniometry. Interrater reliability across methods did not agree satisfactorily. Between-methods differences in estimating knee range of motion may result from variations in technique among physicians and physical therapists.

The Association Between Critical Thinking And Scholastic Aptitude On First-Time Pass Rate Of The National Physical Therapy Examination, Daniel W. Suckow, C. Jayne Brahler, Betsy Donahoe-Fillmore, Mary Insana Fisher, Philip A. Anloague

Philip A. Anloague

Objectives: 1) To investigate the relationships among critical thinking (CT) abilities, overall academic performance in the Doctorate of Physical Therapy (DPT) program as measured by cumulative grade point average (GPA), and National Physical Therapy Examination (NPTE) licensure scores, and 2) To determine if NPTE scores were significantly different between groups of students who were classified as having low, moderate or high CT abilities. Background: It is well-established that physical therapy practice requires good clinical reasoning skills. Passage of the NPTE is required for licensure. Research to date has been mixed as to whether CT abilities or GPA can predict success …

Chronic Elbow Dislocation Treated With Open Reduction And Lateral Ulnar Collateral Ligament Reconstruction, Louis Joseph Rubino, Michael A. Herbenick, Ryan P. Finnan, Philip A. Anloague

Philip A. Anloague

In the United States, chronic unreduced elbow dislocations are rare injuries. We report the successful short-term outcome of a chronic elbow dislocation treated with open reduction and lateral ulnar collateral ligament reconstruction using a split semitendinosus allograft in a figure-of-8 technique without use of hinged external fixation. The authors have obtained the patient’s written informed consent for print and electronic publication of the case report.

Load Carriage Distance Run And Pushups Tests: No Body Mass Bias And Occupationally Relevant, Paul M. Vanderburgh, Nicholas S. Mickley, Philip A. Anloague, Kimber Lucius

Philip A. Anloague

Recent research has demonstrated body mass (M) bias in military physical fi tness tests favoring lighter, not just leaner, service members. Mathematical modeling predicts that a distance run carrying a backpack of 30 lbs would eliminate M-bias. The purpose of this study was to empirically test this prediction for the U.S. Army push-ups and 2-mile run tests. Two tests were performed for both events for each of 56 university Reserve Offi cer Training Corps male cadets: with (loaded) and without backpack (unloaded). Results indicated signifi cant M-bias in the unloaded and no M-bias in the loaded condition for both events. …

Acute Effects Of Whole-Body Vibration On Lower Extremity Muscle Performance In Persons With Multiple Sclerosis, Kurt Jackson, Harold L. Merriman, Paul M. Vanderburgh, C. Jayne Brahler

Harold L. Merriman

Background and Purpose: Whole-body vibration (WBV) is a relatively new form of exercise training that may influence muscle performance. This study investigated the acute effects of high (26 Hz) and low (2 Hz) frequency WBV on isometric muscle torque of the quadriceps and hamstrings in persons with multiple sclerosis (MS). Participants and Method: Fifteen individuals (mean age = 54.6 years, SD = 9.6) with MS and Expanded Disability Status Scale (EDSS) scores ranging from 0-6.5 (mean = 4.2, SD = 2.3) participated in this randomized cross-over study. Following baseline measures of isometric quadricep and hamstring torque, subjects were exposed to …

Breast Cancer Rehabilitation: Clinical Examination And Outcomes Assessment, Nicole L. Stout, Shana Harrington, Lucinda Pfalzer, Mary Insana Fisher

Mary Insana Fisher

Breast cancer is the most commonly diagnosed cancer in women in the United States. The treatment for breast cancer occurs along a protracted time period and includes many different disease treatment modalities. These treatments carry with them a large number of adverse effects that negatively impact function in both the short term and long term. It is necessary for rehabilitation providers to interface with patients being treated for breast cancer throughout the continuum of care so that interval assessments can be conducted to identify emerging impairments and alleviate disability. To achieve this, the rehabilitation provider must have an understanding of …

Oncology Section Edge Task Force On Prostate Cancer Outcomes: A Systematic Review Of Clinical Measures Of Strength And Muscular Endurance, Mary Insana Fisher, Claire Davies, Genevieve Colon, Hannah Geyer, Lucinda Pfalzer

Mary Insana Fisher

Background: Strength deficits are a common morbidity following treatment for prostate cancer. Accurate assessment of strength and muscular endurance following prostate cancer treatments is essential to identify deficits and plan rehabilitation. Purpose: To identify strength and muscular endurance outcome measures that possess strong psychometric properties and are clinically useful for examination of men treated for prostate cancer. Methods: Multiple electronic databases were searched for articles published after 1995. Studies of tools used to assess strength and muscular endurance were included if they reported psychometric properties, were clinically feasible methods, performed on adults, and published in the English language. Each outcome …

Clinical Anesthesia And Analgesia In Fish, Lynne U. Sneddon

Lynne Sneddon, PhD

Fish have become a popular experimental model and companion animal, and are also farmed and caught for food. Thus, surgical and invasive procedures in this animal group are common, and this review will focus on the anesthesia and analgesia of fish. A variety of anesthetic agents are commonly applied to fish via immersion. Correct dosing can result in effective anesthesia for acute procedures as well as loss of consciousness for surgical interventions. Dose and anesthetic agent vary between species of fish and are further confounded by a variety of physiological parameters (e.g., body weight, physiological stress) as well as environmental …

A Comparison Of Upper Extremity Function Between Female Breast Cancer Survivors And Healthy Controls: Typical Self-Report Of Function, Motion, Strength, And Muscular Endurance, Mary Insana Fisher

Mary Insana Fisher

Many women who have experienced breast cancer (BC) report continued impairments in upper extremity (UE) function beyond the time required for normal healing after surgical treatment. Most research supporting this has not made comparisons between survivors of breast cancer (BCS) to a sample of healthy women. This lack of comparison to a healthy cohort prevents an understanding of whether continued deficits in UE function are due to normal aging or the BC treatment. The purpose of this research was to compare quality of life (QOL) and UE function among long term breast cancer survivors and similar aged women without cancer. …

Effects Of Yoga On Arm Volume Among Women With Breast Cancer Related Lymphedema: A Pilot Study, Mary Insana Fisher, Betsy Donahoe-Fillmore, Laura Leach, Colleen O'Malley, Cheryl Paeplow, Tess Prescott, Harold L. Merriman

Mary Insana Fisher

Lymphedema affects 3–58% of survivors of breast cancer and can result in upper extremity impairments. Exercise can be beneficial in managing lymphedema. Yoga practice has been minimally studied for its effects on breast cancer related lymphedema (BCRL). The purpose of this study was to determine the effect of yoga on arm volume, quality of life (QOL), self-reported arm function, and hand grip strength in women with BCRL. Six women with BCRL participated in modified Hatha yoga 3×/week for 8 weeks. Compression sleeves were worn during yoga sessions. Arm volume, QOL, self-reported arm function, and hand grip strength were measured at …

The Association Between Critical Thinking And Scholastic Aptitude On First-Time Pass Rate Of The National Physical Therapy Examination, Daniel W. Suckow, C. Jayne Brahler, Betsy Donahoe-Fillmore, Mary Insana Fisher, Philip A. Anloague

Mary Insana Fisher

Objectives: 1) To investigate the relationships among critical thinking (CT) abilities, overall academic performance in the Doctorate of Physical Therapy (DPT) program as measured by cumulative grade point average (GPA), and National Physical Therapy Examination (NPTE) licensure scores, and 2) To determine if NPTE scores were significantly different between groups of students who were classified as having low, moderate or high CT abilities. Background: It is well-established that physical therapy practice requires good clinical reasoning skills. Passage of the NPTE is required for licensure. Research to date has been mixed as to whether CT abilities or GPA can predict success …

Breast Cancer Edge Task Force Outcomes - Clinical Measures Of Strength And Muscular Endurance: A Systematic Review, Mary Insana Fisher, Claire Davies, Christine Beuthin, Genevieve Colon, Brittany Zoll, Lucinda Pfalzer

Mary Insana Fisher

Background: Muscular strength deficits are a common morbidity following treatment for breast cancer. Accurate assessment of strength and muscular endurance following breast cancer treatments is essential in identifying deficits and planning rehabilitation strategies.

Purpose: The purpose of this systematic review was to identify strength and muscular endurance outcome measures for use with women treated for breast cancer that possess strong psychometric properties and are clinically useful.

Methods: Multiple electronic databases were searched between February and June 2013. Included studies of tools used to assess strength and muscular endurance met the following criteria: reported psychometric properties, clinically feasible methods, adults (preferably …

The Importance Of Managing Psychosocial Health: A Case Study, Mary Insana Fisher, Harold L. Merriman

Mary Insana Fisher

Managing the physical aspects of lymphedema requires an individual to be committed to daily treatment of this chronic condition. Performing manual lymph drainage, using compression bandaging or compression garments, exercising, and caring for the skin all take time and a high level of dedication. This commitment to self-care can be emotionally and psychologically exhausting. When coupled with other emotional stressors in a patient’s life, successful treatment of lymphedema is challenging. We present a case demonstrating how the physical and psychological aspects of care interplay, and, when well-managed, can positively affect the outcome.

A Comparison Of The Upper Limb Lift Test Between Women With Breast Cancer And Healthy Control Subjects, Mary Insana Fisher, Lucinda Pfalzer, Ellen W. Levy, Shana Harrington, Lynn H. Gerber, Nicole L. Stout

Mary Insana Fisher

Presentation at the World Confederation for Physical Therapy Congress, held May 1-4, 2015, in Singapore. Background: Objective measures of upper limb (UL) function specific to breast cancer survivors (BC) are limited. Motion, strength, and muscular endurance are measurable components of UL function. A clinical test that quantifies these components is needed. Purpose: This study compares the Upper Limb Lift Test (ULLT) between women with BC and healthy control subjects (HC) at baseline, 1-3 months, and 12+ months post-operatively enrolled in a prospective surveillance trial with early intervention. A secondary purpose was to validate the ULLT by comparing findings to self-reported …