Diseases Commons^™

Acute Tubular Injury In A Patient On A Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitor, June K Pickett, Maulin Shah, Michael Gillette, Peter Jones, Salim Virani, Christie Ballantyne, Vijay Nambi

Faculty, Staff and Students Publications

A 72-year-old man with coronary artery disease, statin intolerance, and chronic kidney disease stage IIIa was initiated on alirocumab, a proprotein convertase subtilisin/kexin type 9 inhibitor, and developed acute kidney injury. A kidney biopsy was performed and suggested acute tubular injury. The serum creatinine returned to baseline after discontinuation of alirocumab. (Level of Difficulty: Intermediate.)

A Genome-Wide Association Study Identifies Two Novel Susceptible Regions For Squamous Cell Carcinoma Of The Head And Neck, Sanjay Shete, Hongliang Liu, Jian Wang, Robert Yu, Erich M Sturgis, Guojun Li, Kristina R Dahlstrom, Zhensheng Liu, Christopher I Amos, Qingyi Wei

Faculty, Staff and Students Publications

To identify genetic variants for risk of squamous cell carcinoma of the head and neck (SCCHN), we conducted a two-phase genome-wide association study consisting of 7,858,089 SNPs in 2,171 cases and 4,493 controls of non-Hispanic white, of which 434,839 typed and 7,423,250 imputed SNPs as the discovery. SNPs with P <1×10–3 were further validated in the OncoArray study of oral and pharynx cancer (5,205 cases and 3,232 controls of European ancestry) from dbGaP. Meta-analysis of the discovery and replication studies identified one novel locus 6p22.1 (P = 2.96×10–9 for the leading rs259919) and two cancer susceptibility loci 6p21.32 (rs3135001, HLA-DQB1) and 6p21.33 (rs1265081, CCHCR1) associated with SCCHN risk. Further stratification by tumor site revealed four known cancer loci (5p15.33, 6p21.32, 6p21.33, and 2p23.1) associated with oral cavity cancer risk and oropharyngeal cancer risk, respectively. In addition, one novel locus 18q22.2 (P = 2.54×10–9 for the leading SNP rs142021700) was identified for hypo-pharynx and larynx cancer risk. For SNPs in those reported or novel loci, we also performed functional annotations by bioinformatics prediction and eQTL analysis. Collectively, our identification of four reported loci (2p23.1, 5p15.33, 6p21.32, and 6p21.33) and two novel loci (6p22.1 and 18q22.2) for SCCHN risk highlight the importance of HLA loci for oropharyngeal cancer risk, suggesting that immunologic mechanisms are implicated in the etiology of this subset of SCCHN.

Wolff-Parkinson-White Syndrome: De Novo Variants And Evidence For Mutational Burden In Genes Associated With Atrial Fibrillation, Zeynep H Coban-Akdemir, Wu-Lin Charng, Mahshid Azamian, Ingrid S Paine, Jaya Punetha, Christopher M Grochowski, Tomasz Gambin, Santiago O Valdes, Bryan Cannon, Gladys Zapata, Patricia P Hernandez, Shalini Jhangiani, Harsha Doddapaneni, Jianhong Hu, Fatima Boricha, Donna M Muzny, Eric Boerwinkle, Yaping Yang, Richard A Gibbs, Jennifer E Posey, Xander H T Wehrens, John W Belmont, Jeffrey J Kim, Christina Y Miyake, James R Lupski, Seema R Lalani

Faculty, Staff and Student Publications

BACKGROUND: Wolff-Parkinson-White (WPW) syndrome is a relatively common arrhythmia affecting ~1-3/1,000 individuals. Mutations in PRKAG2 have been described in rare patients in association with cardiomyopathy. However, the genetic basis of WPW in individuals with a structurally normal heart remains poorly understood. Sudden death due to atrial fibrillation (AF) can also occur in these individuals. Several studies have indicated that despite ablation of an accessory pathway, the risk of AF remains high in patients compared to general population.

METHODS: We applied exome sequencing in 305 subjects, including 65 trios, 80 singletons, and 6 multiple affected families. We used de novo analysis, …

Incidental Cannulation Of Left Ventricular Thebesian Vein, Kalyan Chakravarthy Potu, Jay N Patel, Majd Ibrahim, Sujitha Sree Ketineni, Sudhir Mungee

The Texas Heart Institute Journal

No abstract provided.

Surgical Endoepicardial Linear Ablation For Ventricular Tachycardia With Postinfarction Left Ventricular Aneurysm, Changcheng Liu, Zhaoping Su, Liangshan Wang, Bo Li, Jin Wang, Yang Yu, Chengxiong Gu

The Texas Heart Institute Journal

This retrospective study evaluated the feasibility of surgical endoepicardial linear ablation for ventricular tachycardia in patients with postinfarction left ventricular aneurysm. Sixty-four patients with multivessel coronary artery disease and left ventricular aneurysm but no mural thrombosis of the aneurysm or valve disease were treated at our institution from March 2012 through July 2015. All underwent off-pump coronary artery bypass grafting and left ventricular aneurysm repair by linear plication. Twenty-three patients (35.9%) had ventricular tachycardia and underwent surgical endoepicardial linear ablation on the beating heart guided by epicardial substrate mapping with the Carto 3 system. The remaining 41 patients (64.1%) composed …

Altered Mental Status And Hyponatremia After 20 Hours Of Amiodarone Therapy, Andrea Qi, John C Moscona, Justin Reed, Thierry H Le Jemtel

The Texas Heart Institute Journal

A 66-year-old woman with no relevant medical history presented at the emergency department with new-onset atrial fibrillation. We initiated intravenous amiodarone therapy. At 20 hours, the patient experienced severe neurologic symptoms, hyponatremia, and syndrome of inappropriate antidiuretic hormone. We discontinued amiodarone, infused saline solution, and restricted the patient's fluid intake. She recovered in 3 days. This case illustrates that amiodarone-induced syndrome of inappropriate antidiuretic hormone with hyponatremia can occur far earlier than expected during acute amiodarone therapy.

Association Of Intensive Lifestyle Intervention, Fitness, And Body Mass Index With Risk Of Heart Failure In Overweight Or Obese Adults With Type 2 Diabetes Mellitus: An Analysis From The Look Ahead Trial, Ambarish Pandey, Kershaw V Patel, Judy L Bahnson, Sarah A Gaussoin, Corby K Martin, Ashok Balasubramanyam, Karen C Johnson, Darren K Mcguire, Alain G Bertoni, Dalane Kitzman, Jarett D Berry, Look Ahead Research Group

Faculty, Staff and Students Publications

BACKGROUND: Type 2 diabetes mellitus (T2DM) is associated with a higher risk for heart failure (HF). The impact of a lifestyle intervention and changes in cardiorespiratory fitness (CRF) and body mass index on risk for HF is not well established.

METHODS: Participants from the Look AHEAD trial (Action for Health in Diabetes) without prevalent HF were included. Time-to-event analyses were used to compare the risk of incident HF between the intensive lifestyle intervention and diabetes support and education groups. The associations of baseline measures of CRF estimated from a maximal treadmill test, body mass index, and longitudinal changes in these …

Diabetes And Cardiovascular Disease In Women: Current Challenges And New Hope, Efstratios Koutroumpakis, David Aguilar

The Texas Heart Institute Journal

No abstract provided.

Robotic-Assisted Percutaneous Coronary Intervention Through Transradial Approach: Experience In 4 Patients With Complex Lesions, Amornpol Anuwatworn, Muhammad Ali Kahn, Tomasz Stys, Marian Petrasko, Adam Stys

The Texas Heart Institute Journal

Robotic-assisted percutaneous coronary intervention can reduce the exposure of interventional cardiologists to radiation and minimize the risk of occupational orthopedic injuries from wearing heavy protective aprons. The PRECISE (Percutaneous Robotically-Enhanced Coronary Intervention) study showed the efficacy and safety of robotic-assisted procedures for relatively low-risk lesions in single coronary arteries. Several reports have described robotic-assisted treatment of complex high-risk lesions, mostly through the transfemoral approach. We report 4 cases of patients in whom we used the transradial approach to treat complex lesions in the left anterior descending coronary artery with bifurcation balloon angioplasty reconstruction (2 cases), in the ostium of the …

Histologic Abnormalities Of The Ascending Aorta: Effects On Aortic Remodeling After Intracardiac Repair Of Tetralogy Of Fallot, Ujjwal Kumar Chowdhury, Lakshmi Kumari Sankhyan, Sheil Avneesh, Ruma Ray, Mani Kalaivani, Suruchi Hasija, Abhinavsingh Chauhan

The Texas Heart Institute Journal

We evaluated aortic tissue specimens from patients undergoing tetralogy of Fallot repair, to determine whether histologic abnormalities affect postsurgical aortic remodeling and other patient-related variables.

Using light microscopy, we studied full-thickness aortic wall tissue operatively excised from 118 consecutive patients undergoing intracardiac repair of tetralogy of Fallot. We performed multiple linear regression analysis to identify independent predictors of change in aortic root dimensions, which we measured with echocardiography after repair and every 3 months thereafter.

Thirty histologically normal specimens were used as controls. Elastic fiber fragmentation was found in 74.6% of the abnormal specimens, mucoid extracellular matrix accumulation in 49.2%, …

Thrombotic, Inflammatory, And Hif-Regulated Genes And Thrombosis Risk In Polycythemia Vera And Essential Thrombocythemia, Radhika Gangaraju, Jihyun Song, Soo Jin Kim, Tsewang Tashi, Brandi N Reeves, Krishna M Sundar, Perumal Thiagarajan, Josef T Prchal

Faculty, Staff and Students Publications

Thrombosis is a major cause of morbidity and mortality in polycythemia vera (PV) and essential thrombocythemia (ET). The pathophysiology of thrombosis in these disorders remains unclear, and we hypothesized that upregulation of thrombotic, inflammatory, and hypoxia-inducible factor (HIF)-regulated genes may play a role in it. We performed unbiased RNA sequencing in granulocytes and platelets of PV patients and found differential expression of several thrombotic, inflammatory, and HIF-regulated genes. The expression of many of these genes positively correlated with JAK2 expression and JAK2V617F allelic burden. We then validated these findings by quantitative polymerase chain reaction analyses of selected gene transcripts in …

The Impact Of Diabetic Foot Ulcers And Unilateral Offloading Footwear On Gait In People With Diabetes, Erica Ling, Brian Lepow, He Zhou, Ana Enriquez, Ashley Mullen, Bijan Najafi

Faculty, Staff and Students Publications

BACKGROUND: Unilateral offloading footwear prescribed to patients with diabetic foot ulcers elevates one limb relative to the other, which may lead to limp and abnormal gait. This study investigated whether the unilateral foot ulcer and offloading combination negatively impacts gait function beyond diabetic peripheral neuropathy.

METHODS: Eighty-six participants were recruited in 3 groups: 12 with diabetic peripheral neuropathy and unilateral foot ulcers wearing offloading footwear (offloading group, age = 55.6 ± 9.5 years, BMI = 30.9 ± 4.5 kg/m

FINDINGS: The offloading group exhibited deteriorated gait function compared to the non-diabetic group (p < 0.005, Cohen's effect size d = 0.90-2.61). They also had decreased gait speed (p < 0.001, d = 1.79) and stride length (p < 0.001, d = 1.76), as well as increased gait cycle time (p < 0.001, d = 1.67) and limp (p < 0.050, d = 0.72-1.49) compared to the neuropathy group. The offloading group showed increased gait unsteadiness compared to the neuropathy group, but the difference did not reach statistical significance in our samples.

INTERPRETATION: This study demonstrated that while diabetic …

Orthostatic Hypotension, Cardiovascular Outcomes, And Adverse Events: Results From Sprint, Stephen P Juraschek, Addison A Taylor, Jackson T Wright, Gregory W Evans, Edgar R Miller, Timothy B Plante, William C Cushman, Tanya R Gure, William E Haley, Imran Moinuddin, John Nord, Suzanne Oparil, Carolyn Pedley, Christianne L Roumie, Jeff Whittle, Alan Wiggers, Ciarán Finucane, Rose Anne Kenny, Lawrence J Appel, Raymond R Townsend

Faculty, Staff and Students Publications

Orthostatic hypotension (OH) is frequently observed with hypertension treatment, but its contribution to adverse outcomes is unknown. The Systolic Blood Pressure Intervention Trial (SPRINT) was a randomized trial of adults, age ≥50years at high risk for cardiovascular disease (CVD) with a seated systolic BP (SBP) of 130–180 mmHg and a standing SBP ≥110 mmHg. Participants were randomized to a SBP treatment goal of either <120 mmHg or <140 mmHg. OH was defined as a drop in SBP≥20 or diastolic BP ≥10 mmHg one minute after standing from a seated position. We used Cox models to examine the association of OH with CVD or adverse study events by randomized BP goal. During the follow-up period (median 3years), there were 1,170 (5.7%) instances of OH among those assigned a standard BP goal, and 1,057 (5.0%) among those assigned the intensive BP goal. OH was not associated with higher risk of CVD events (primary outcome: HR 1.06; 95%CI: 0.78,1.44). Moreover, OH was not associated with syncope, electrolyte abnormalities, injurious falls, or acute renal failure. OH was associated with hypotension-related hospitalizations or emergency department visits (HR 1.77; 1.11,2.82) and bradycardia (HR 1.94; 1.19,3.15), but these associations did not differ by BP treatment goal. OH was not associated with a higher risk of CVD events and BP treatment goal had no effect on OH’s association with hypotension and bradycardia. Symptomless OH during hypertension treatment should not be viewed as a reason to down-titrate therapy even in the setting of a lower BP goal.

Probable African Tick Bite Fever In The United States, Kami Lowery, Theodore Rosen

Faculty, Staff and Students Publications

African tick bite fever (ATBF) is a tick-borne rickettsial disease most often observed in North American and European tourists returning home from the southern portion of Africa. Ticks infected with Rickettsia africae transmit this parasitic bacterium to humans, who subsequently develop an influenza-like illness, one or more inoculation eschars, and in some cases, a cutaneous rash. Because ATBF often presents with non-specific symptoms that suggest other infectious diseases, establishing the diagnosis may be difficult. Confirmatory assays, including serology and nucleic acid amplification, may take weeks to return and cannot help with acute treatment decisions. We present a case of a …

Comparison Of Microneutralization And Histo-Blood Group Antigen-Blocking Assays For Functional Norovirus Antibody Detection, Robert L Atmar, Khalil Ettayebi, B Vijayalakshmi Ayyar, Frederick H Neill, Ralph P Braun, Sasirekha Ramani, Mary K Estes

Faculty, Staff and Students Publications

BACKGROUND: The development of an in vitro cultivation system for human noroviruses allows the measurement of neutralizing antibody levels.

METHODS: Serum neutralizing antibody levels were determined using a GII.4/Sydney/2012-like virus in human intestinal enteroids in samples collected before and 4 weeks after administration of an investigational norovirus vaccine and were compared with those measured in histo-blood group antigen (HBGA)-blocking assays.

RESULTS: Neutralizing antibody seroresponses were observed in 71% of 24 vaccinated adults, and antibody levels were highly correlated (r = 0.82, P < .001) with those measured by HBGA blocking.

CONCLUSIONS: HBGA-blocking antibodies are a surrogate for neutralization in human noroviruses.

A Ten-Year Retrospective Evaluation Of Acute Flaccid Myelitis At 5 Pediatric Centers In The United States, 2005-2014., Margaret M. Cortese, Anita K. Kambhampati, Jennifer E. Schuster, Zaid Alhinai, Gary R. Nelson, Gloria J. Guzman Perez-Carrillo, Arastoo Vossough, Michael A. Smit, Robert C. Mckinstry, Timothy Zinkus, Kevin R. Moore, Jeffrey M. Rogg, Meghan S. Candee, James J. Sejvar, Sarah E. Hopkins

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Acute flaccid myelitis (AFM) is a severe illness similar to paralytic poliomyelitis. It is unclear how frequently AFM occurred in U.S. children after poliovirus elimination. In 2014, an AFM cluster was identified in Colorado, prompting passive US surveillance that yielded 120 AFM cases of unconfirmed etiology. Subsequently, increased reports were received in 2016 and 2018. To help inform investigations on causality of the recent AFM outbreaks, our objective was to determine how frequently AFM had occurred before 2014, and if 2014 cases had different characteristics.

METHODS: We conducted a retrospective study covering 2005-2014 at 5 pediatric centers in 3 …

A Retrospective Matched-Cohort Study Of 3994 Lower Extremity Wounds Of Multiple Etiologies Across 644 Institutions Comparing A Bioactive Human Skin Allograft, Theraskin, Plus Standard Of Care, To Standard Of Care Alone, Geoff C Gurtner, Aimee D Garcia, Katie Bakewell, Jason B Alarcon

Faculty, Staff and Students Publications

Most chronic wounds are related to comorbidities, for which no clinical trials are performed. This retrospective propensity matched-cohort study examined data from 2 074 000 lower extremity wounds across 644 institutions to determine the effectiveness of TheraSkin plus standard of care (SOC; n = 1997) versus SOC alone (n = 1997). Multivariate modelling comparing outcomes such as healing rates, percent area reductions (PARs), amputations, recidivism, treatment completion, and medical transfers were evaluated. A higher proportion of wounds in the treatment group compared with the controls were more likely to close (68.3% versus 60.3%), particularly wounds with exposed structures (64% versus …

Whole Exome Sequencing Of Highly Aggregated Lung Cancer Families Reveals Linked Loci For Increased Cancer Risk On Chromosomes 12q, 7p, And 4q, Anthony M Musolf, Bilal A Moiz, Haiming Sun, Claudio W Pikielny, Yohan Bossé, Diptasri Mandal, Mariza De Andrade, Colette Gaba, Ping Yang, Yafang Li, Ming You, Ramaswamy Govindan, Richard K Wilson, Elena Y Kupert, Marshall W Anderson, Ann G Schwartz, Susan M Pinney, Christopher I Amos, Joan E Bailey-Wilson

Faculty, Staff and Students Publications

BACKGROUND: Lung cancer kills more people than any other cancer in the United States. In addition to environmental factors, lung cancer has genetic risk factors as well, though the genetic etiology is still not well understood. We have performed whole exome sequencing on 262 individuals from 28 extended families with a family history of lung cancer.

METHODS: Parametric genetic linkage analysis was performed on these samples using two distinct analyses-the lung cancer only (LCO) analysis, where only patients with lung cancer were coded as affected, and the all aggregated cancers (AAC) analysis, where other cancers seen in the pedigree were …

Benefit Of Contact Force-Guided Catheter Ablation For Treating Premature Ventricular Contractions, Ziming Zhao, Xiaowei Liu, Lianjun Gao, Yutao Xi, Qi Chen, Dong Chang, Xianjie Xiao, Jie Cheng, Yanzong Yang, Yunlong Xia, Xiaomeng Yin

The Texas Heart Institute Journal

We evaluated whether an irrigated contact force–sensing catheter would improve the safety and effectiveness of radiofrequency ablation of premature ventricular contractions originating from the right ventricular outflow tract.

We retrospectively reviewed the charts of patients with symptomatic premature ventricular contractions who underwent ablation with a contact force–sensing catheter (56 patients, SmartTouch) or conventional catheter (59 patients, ThermoCool) at our hospital from August 2013 through December 2015. During a mean follow-up of 16 ± 5 months, 3 patients in the conventional group had recurrences, compared with none in the contact force group. Complications occurred only in the conventional group (one steam …

Prognostic Value Of 6-Minute Walk Distance In Patients Undergoing Percutaneous Coronary Intervention: A Veterans Affairs Prospective Study, Tarun W Dasari, Bhavin Patel, Siddharth A Wayangankar, David Alexander, Yan D Zhao, Joann Schlegel, Cheuk Leung, Pedro Lozano, Faisal Latif, Udho Thadani

The Texas Heart Institute Journal

The 6-minute walk distance (6MWD) test is a useful prognostic tool in chronic heart failure. Its usefulness after percutaneous coronary intervention is unknown.

In a prospective observational study, patients underwent a 6MWD test within 2 weeks after percutaneous coronary intervention. The primary endpoint was major adverse cardiovascular events (MACE) (death, acute coronary syndrome, and heart failure admission) at one year. Receiver operating characteristic curves and area under the curve were used to determine the 6MWD test's predictive power, and the Youden index was used to measure its effectiveness.

A total of 212 patients were enrolled (98% men; mean age, 65 …

Modified Pull-Through Technique For Cardiac Resynchronization Therapy Upgrades In Patients With Occluded Access Veins, Guram Imnadze, Khaled Awad, Wolfgang Kranig, Irakli Giorgberidze

The Texas Heart Institute Journal

The number of procedures for upgrading implantable devices for cardiac resynchronization therapy has increased considerably during the last decade. A major challenge that operators face in these circumstances is occlusion of the access vein. We have modified a pull-through method to overcome this obstacle. Six consecutive patients with occluded access veins and well-developed collateral networks underwent a procedure in which the occluded vein was recanalized by snaring the existing atrial lead via transfemoral access. Upgrading the device was successful in all patients; none had intraprocedural complications. Our experience shows that our modified pull-through technique may be a feasible alternative for …

Obstruction Of 2 Coronary Arteries From Different Causes Immediately After Transapical Transcatheter Aortic Valve Replacement, Umihiko Kaneko, Ryuji Koshima, Hirosato Doi, Tsutomu Fujita

The Texas Heart Institute Journal

Coronary obstruction, a rare complication of transcatheter aortic valve replacement, can be fatal. Few data exist on this phenomenon, and, to date, authors have reported only single coronary lesions. We present a case in which 2 coronary arteries obstructed immediately after transapical transcatheter aortic valve replacement. The patient was an 81-year-old woman with symptomatic severe aortic stenosis who underwent transapical transcatheter aortic valve replacement. Immediately after an Edwards Sapien XT valve was deployed, she experienced sudden cardiogenic shock resulting from obstruction of the left main coronary artery ostium and the distal left anterior descending coronary artery. The left main obstruction …

Assessing Lymphatic Route Of Csf Outflow And Peripheral Lymphatic Contractile Activity During Head-Down Tilt Using Near-Infrared Fluorescence Imaging, John C Rasmussen, Sunkuk Kwon, Amanda Pinal, Alexander Bareis, Fred C Velasquez, Christopher F Janssen, John R Morrow, Caroline E Fife, Ron J Karni, Eva M Sevick-Muraca

Faculty, Staff and Student Publications

Evidence overwhelmingly suggests that the lymphatics play a critical role in the clearance of cerebrospinal fluid (CSF) from the cranial space. Impairment of CSF outflow into the lymphatics is associated with a number of pathological conditions including spaceflight-associated neuro-ocular syndrome (SANS), a problem that limits long-duration spaceflight. We used near-infrared fluorescence lymphatic imaging (NIRFLI) to dynamically visualize the deep lymphatic drainage pathways shared by CSF outflow and disrupted during head-down tilt (HDT), a method used to mimic the cephalad fluid shift that occurs in microgravity. After validating CSF clearance into the lymph nodes of the neck in swine, a pilot …

Diagnostic Criteria For Detection Of Retinal Nerve Fibre Layer Thickness And Neuroretinal Rim Width Abnormalities In Glaucoma, Feihui Zheng, Marco Yu, Christopher Kai-Shun Leung

Faculty, Staff and Student Publications

BACKGROUND/AIMS: Although measurements of the Bruch's membrane opening minimum rim width (BMO-MRW) and retinal nerve fibre layer thickness (RNFLT) with optical coherence tomography (OCT) have been widely adopted in the diagnostic evaluation of glaucoma, there is no consensus on the diagnostic criteria to define BMO-MRW and RNFLT abnormalities. This study investigated the sensitivities and specificities of different diagnostic criteria based on the OCT classification reports for detection of glaucoma.

METHODS: 340 eyes of 137 patients with glaucoma and 87 healthy individuals, all with axial length ≤26mm, had global and sectoral BMO-MRW and RNFLT measured with Spectralis OCT (Heidelberg Engineering). Six …

Losartan Rescues Inflammation-Related Mucociliary Dysfunction In Relevant Models Of Cystic Fibrosis, Michael D Kim, Nathalie Baumlin, Makoto Yoshida, Deepika Polineni, Sebastian F Salathe, Joseph K David, Charles A Peloquin, Adam Wanner, John S Dennis, Juliette Sailland, Philip Whitney, Frank T Horrigan, Juan R Sabater, William M Abraham, Matthias Salathe

Faculty, Staff and Students Publications

Rationale: Despite therapeutic progress in treating cystic fibrosis (CF) airway disease, airway inflammation with associated mucociliary dysfunction remains largely unaddressed. Inflammation reduces the activity of apically expressed large-conductance Ca²⁺-activated and voltage-dependent K⁺ (BK) channels, critical for mucociliary function in the absence of CFTR (CF transmembrane conductance regulator).

Objectives: To test losartan as an antiinflammatory therapy in CF using CF human bronchial epithelial cells and an ovine model of CF-like airway disease.

Methods: Losartan’s antiinflammatory effectiveness to rescue BK activity and thus mucociliary function was tested in vitro using primary, fully redifferentiated human airway epithelial cells homozygous for …

Metabolic Dysregulation In The Atp7b-/- Wilson's Disease Mouse Model, Clavia Ruth Wooton-Kee, Matthew Robertson, Ying Zhou, Bingning Dong, Zhen Sun, Kang Ho Kim, Hailan Liu, Yong Xu, Nagireddy Putluri, Pradip Saha, Cristian Coarfa, David D Moore, Alli M Nuotio-Antar

Faculty, Staff and Students Publications

Inactivating mutations in the copper transporter Atp7b result in Wilson’s disease. The Atp7b−/− mouse develops hallmarks of Wilson’s disease. The activity of several nuclear receptors decreased in Atp7b−/− mice, and nuclear receptors are critical for maintaining metabolic homeostasis. Therefore, we anticipated that Atp7b−/− mice would exhibit altered progression of diet-induced obesity, fatty liver, and insulin resistance. Following 10 wk on a chow or Western-type diet (40% kcal fat), parameters of glucose and lipid homeostasis were measured. Hepatic metabolites were measured by liquid chromatography–mass spectrometry and correlated with transcriptomic data. Atp7b−/− mice fed a chow diet presented …

Current Smoking With Or Without Chronic Bronchitis Is Independently Associated With Goblet Cell Hyperplasia In Healthy Smokers And Copd Subjects, Victor Kim, Stephanie Jeong, Huaqing Zhao, Mehmet Kesimer, Richard C. Boucher, J. Michael Wells, Stephanie A. Christenson, Meilan K. Han, Mark Dransfield, Robert Paine, Christopher B. Cooper, Igor Barjaktarevic, Russell Bowler, Jeffrey L. Curtis, Robert J. Kaner, Sarah L. O'Beirne, Wanda K. O'Neal, Stephen I. Rennard, Fernando J. Martinez, Prescott G. Woodruff

Journal Articles: Pulmonary & Critical Care Med

COPD, chronic bronchitis (CB) and active smoking have all been associated with goblet cell hyperplasia (GCH) in small studies. Active smoking is strongly associated with CB, but there is a disconnect between CB clinical symptoms and pathology. Chronic cough and sputum production poorly correlate with the presence of GCH or COPD. We hypothesized that the primary determinant of GCH in ever smokers with or without airflow obstruction is active smoking. Goblet Cell Density (GCD) was measured in 71 current or former smokers [32 subjects without COPD and 39 COPD subjects]. Endobronchial mucosal biopsies were stained with Periodic Acid Schiff-Alcian Blue, …

Heme Metabolism Genes Downregulated In Copd Cachexia, Ava C. Wilson, Preeti L. Kumar, Sool Lee, Margaret M. Parker, Itika Arora, Jarrett D. Morrow, Emiel F.M. Wouters, Richard Casaburi, Stephen I. Rennard, David A. Lomas, Alvar Agusti, Ruth Tal-Singer, Mark T. Dransfield, J. Michael Wells, Surya P. Bhatt, George Washko, Victor J. Thannickal, Hemant K. Tiwari, Craig P. Hersh, Peter J. Castaldi, Edwin K. Silverman, Merry-Lynn N. Mcdonald

Journal Articles: Pulmonary & Critical Care Med

INTRODUCTION: Cachexia contributes to increased mortality and reduced quality of life in Chronic Obstructive Pulmonary Disease (COPD) and may be associated with underlying gene expression changes. Our goal was to identify differential gene expression signatures associated with COPD cachexia in current and former smokers.

METHODS: We analyzed whole-blood gene expression data from participants with COPD in a discovery cohort (COPDGene, N = 400) and assessed replication (ECLIPSE, N = 114). To approximate the consensus definition using available criteria, cachexia was defined as weight-loss > 5% in the past 12 months or low body mass index (BMI) (<  20 kg/m

RESULTS: The prevalence of …

Targeting The Tumor Core: Hypoxia-Responsive Nanoparticles For The Delivery Of Chemotherapy To Pancreatic Tumors, Matthew I. Confeld, Babak Mamnoon, Li Feng, Heather Jensen Smith, Priyanka Ray, James Froberg, Jiha Kim, Michael A. Hollingsworth, Mohiuddin Quadir, Yongki Choi, Sanku Mallik

Journal Articles: Eppley Institute

In pancreatic ductal adenocarcinoma (PDAC), early onset of hypoxia triggers remodeling of the extracellular matrix, epithelial-to-mesenchymal transition, increased cell survival, the formation of cancer stem cells, and drug resistance. Hypoxia in PDAC is also associated with the development of collagen-rich, fibrous extracellular stroma (desmoplasia), resulting in severely impaired drug penetration. To overcome these daunting challenges, we created polymer nanoparticles (polymersomes) that target and penetrate pancreatic tumors, reach the hypoxic niches, undergo rapid structural destabilization, and release the encapsulated drugs. In vitro studies indicated a high cellular uptake of the polymersomes and increased cytotoxicity of the drugs under hypoxia compared to …

A Remarkable Response Of Granulomatous Hypophysitis To Infliximab In A Patient With A Background Of Crohn's Disease-A Case Report, Bahar K Force, Tiphanie P Vogel, Dang M Nguyen, Kent A Heck, Sherly Sebastian, Mas Takashima, Daniel Yoshor, Susan L Samson

Faculty, Staff and Students Publications

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