Diseases Commons^™

Extracellular Mitochondria Released From Traumatized Brains Induced Platelet Procoagulant Activity, Zilong Zhao, Yuan Zhou, Tristan Hilton, Fanjian Li, Cha Han, Li Liu, Hengjie Yuan, Ying Li, Xin Xu, Xiaoping Wu, Fangyi Zhang, Perumal Thiagarajan, Andrew Cap, Fu-Dong Shi, Jianning Zhang, Jing-Fei Dong

Faculty, Staff and Students Publications

Coagulopathy often develops soon after acute traumatic brain injury and its cause remains poorly understood. We have shown that injured brains release cellular microvesicles that disrupt the endothelial barrier and induce consumptive coagulopathy. Morphologically intact extracellular mitochondria accounted for 55.2% of these microvesicles, leading to the hypothesis that these extracellular mitochondria are metabolically active and serve as a source of oxidative stress that activates platelets and renders them procoagulant. In testing this hypothesis experimentally, we found that the extracellular mitochondria purified from brain trauma mice and those released from brains subjected to freeze-thaw injury remained metabolically active and produced reactive …

Lisinopril-Induced Angioedema In A Patient With Plasma Prekallikrein Deficiency, Swapan K Dasgupta, Stefanie Rivera, Perumal Thiagarajan

Faculty, Staff and Students Publications

Angiotensin-converting enzyme (ACE) inhibitors are extensively prescribed to treat patients with hypertension, congestive heart failure, and diabetic nephropathy. A small fraction of these patients (approximately 0.7%) develop angioedema, manifested by swelling of the lips and oropharynx. Angioedema of oropharynx is a medical emergency that can lead to asphyxiation and death. The angioedema is due to bradykinin generated from high molecular weight kininogen by kallikrein, which is derived from plasma prekallikrein by action of the factor XIIa, factor Xia, or prolylcarboxypeptidase. Bradykinin induces vasodilation and increased vascular permeability. ACE is the major degrading enzyme of bradykinin in the intravascular department. ACE …

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

Associated Data

Metaproteomic Analysis Of Human Gut Microbiome In Digestive And Metabolic Diseases, Sheng Pan, Ru Chen

Faculty, Staff and Students Publications

Metaproteomics, as a subfield of proteomics, has quickly emerged as a pivotal tool for global characterization of a microbiome system at a functional level. It has been increasingly applied in studying human digestive and metabolic diseases, and provides information-rich data to identify the dysbiosis of human gut microbiome related to healthy or disease states to elucidate the molecular events underlying host-microbiota interplays. While significant technical challenges still exist, this emerging technology has been demonstrated to provide essential information in interrogating functional changes in the human gut microbiome, complementary to metagenomics and metatranscriptomics. This chapter overviews the overall metaproteomic work flow …

Prevalence Of Chronic Hepatitis B In Oro Province, Papua New Guinea, Alice Unah Lee, Luke Mair, Bob Kevin, Lily Gandi, Olive Tarumuri, Caroline Lee, Sue Huntley, David Carl Hilmers

Faculty, Staff and Students Publications

Chronic hepatitis B (CHB) affects over 250 million people worldwide. In Papua New Guinea, the prevalence of CHB has been estimated to be over 8%, and it is a leading cause of death. To address this problem, an alliance was formed between the government of Oro Province, a large private employer and an Australian nongovernmental organization, which established a CHB test and treatment programme. Between 2014 and 2019, rapid hepatitis B surface antigen testing was performed on 4068 individuals in Oro Province. The crude prevalence rate was 12.98% and was significantly higher in males (15.26%) than females (10.94%) (P < 0.001). The rate was 4.72% among children aged 10 years and under, 12.81% among women of childbearing age (19–35 years) and 18.48% among health-care workers. These results indicate that the rates of vaccination at birth and later among women of childbearing age and health-care workers must be improved to prevent transmission of CHB.

Large Sinus Of Valsalva Aneurysm Complicated By Thrombus Formation, Milan Ravishankar, Ali Ghergherehchi, Jing Liu, Ernesto Jimenez, Umair Khalid

Faculty, Staff and Students Publications

Sinus of Valsalva aneurysm (SOVA) is an unusual cardiac anomaly that is potentially fatal with rupture. It is often asymptomatic but has various presentations. We describe a case of a 67-year-old male who presented with atypical chest pain. Transthoracic echocardiogram and cardiac computed tomography scan confirmed a large SOVA complicated by thrombus formation and compression of the left atrium and left ventricular outflow tract. The patient successfully underwent a Bentall procedure-surgical aortic aneurysm repair with mechanical aortic valve conduit. We discuss several clinical decision-making branch points to highlight the complexity of managing this condition. Even in asymptomatic or minimally symptomatic …

Hypogonadism, Type-2 Diabetes Mellitus, And Bone Health: A Narrative Review, Vittoria Russo, Rui Chen, Reina Armamento-Villareal

Faculty, Staff and Students Publications

One of the complications from chronic hyperglycemia and insulin resistance due to type 2 diabetes mellitus (T2DM) on the hypothalamic-pituitary-gonadal axis in men is the high prevalence of hypogonadotropic hypogonadism (HH). Both T2DM and hypogonadism are associated with impaired bone health and increased fracture risk but whether the combination results in even worse bone disease than either one alone is not well-studied. It is possible that having both conditions predisposes men to an even greater risk for fracture than either one alone. Given the common occurrence of HH or hypogonadism in general in T2DM, a significant number of men could …

The Longitudinal Parallel Process Analysis Of Biomarkers Of Oxidative Stress, Symptom Clusters, And Cognitive Function In Children With Leukemia, Mary C Hooke, Daniel Hatch, Marilyn J Hockenberry, Susan Whitman, Ida Moore, David Montgomery, Kari Marano, Pauline Mitby, Michael E Scheurer, Olga Taylor, Wei Pan

Faculty, Staff and Students Publications

Background: During treatment for acute lymphoblastic leukemia (ALL), children report co-occurring symptoms of fatigue, sleep disturbance, pain, nausea, and depression as a symptom cluster. Central nervous system–directed ALL therapies also put children at risk for cognitive impairments. Cancer therapies can cause an increase in oxidative stress, which may contribute to treatment-related symptoms. This study examined the longitudinal relationships between biomarkers of oxidative stress in the cerebrospinal fluid, the Childhood Cancer Symptom Cluster–Leukemia (CCSC-L), and cognition, in children over the first year of ALL treatment. Methods: Glutathione (GSH) biomarkers of oxidative stress were measured in cerebrospinal fluid collected during treatment lumbar …

Results Of A Phase 1 Multicentre Investigation Of Dexmedetomidine Bolus And Infusion In Corrective Infant Cardiac Surgery, Athena F Zuppa, Susan C Nicolson, Nicole S Wilder, Juan C Ibla, Erin A Gottlieb, Kristin M Burns, Mario Stylianou, Felicia Trachtenberg, Hua Ni, Tera H Skeen, Dean B Andropoulos

Faculty, Staff and Students Publications

BACKGROUND: Dexmedetomidine (DEX) is increasingly used intraoperatively in infants undergoing cardiac surgery. This phase 1 multicentre study sought to: (i) determine the safety of DEX for cardiac surgery with cardiopulmonary bypass; (ii) determine the pharmacokinetics (PK) of DEX; (iii) create a PK model and dosing for steady-state DEX plasma levels; and (iv) validate the PK model and dosing.

METHODS: We included 122 neonates and infants (0-180 days) with D-transposition of the great arteries, ventricular septal defect, or tetralogy of Fallot. Dose escalation was used to generate NONMEM® PK modelling, and then validation was performed to achieve low (200-300 pg ml …

Infant With Protein C Deficiency And Stroke In The Setting Of Iron Deficiency Anemia, Tahseen Jalal Karim, Dustin J Paul, Regina M Troxell, Rajan Patel, Ian J Butler

Faculty, Staff and Student Publications

We report an 18-month-old infant with ischemic stroke, neurocognitive impairment, and psychomotor retardation in the setting of severe iron deficiency anemia. Although an uncommon outcome in anemic children, stroke is important to consider as a cause for developmental delay in children with iron deficiency anemia.

Oxidative Phosphorylation: A Critical Feature And Novel Therapeutic Target In Melanoma Brain Metastases, Grant Fischer

Dissertations and Theses (Open Access)

We recently showed via RNA-sequencing (RNA-seq) analysis of clinical samples that melanoma brain metastases (MBMs) have higher expression of oxidative phosphorylation (OXPHOS) genes (including PPARGC1A or PGC1α) than patient-matched extracranial metastases (ECMs). Thus, the central hypothesis of this dissertation is that OXPHOS plays a critical role in the pathogenesis of MBMs.

RNA-seq analysis identified increased expression of OXPHOS genes in intracranial (ICr) vs. subcutaneous (SQ) xenografts of 4 different human melanoma cell lines. Increased OXPHOS in the ICr xenografts was confirmed by direct metabolite analysis and [U-¹³C]-glucose tracing analysis. Together, these studies indicate that the brain TME …

Tracking Treatment Response And Resistance To Parp Inhibition (Talazoparib) In Hereditary Pancreatic Cancer., Jennifer Goldstein

Dissertations and Theses (Open Access)

polyADP ribose polymerase (PARP) inhibitors are a class of drugs that block the PARP enzymes, involved in the repair of singe-stranded DNA breaks through the base excision repair pathway. PARP inhibition leads to replication-associated double stranded DNA breaks, which are repaired by homologous recombination (HR). In tumors with HR defects (i.e. BRCA mutants), there is a shift to error-prone DNA repair and subsequent genomic instability and cell death.

In 2014, Olaparib became the first FDA-approved PARP inhibitor for the treatment of BRCA-mutant ovarian cancer. In the phase III POLO (Pancreas cancer OLaparib Ongoing) trial presented at the American Society …

Role Of Nudt21 Mediated Alternative Polyadenylation And Hyaluronan In The Development Of Pulmonary Hypertension, Scott Dale Collum

Dissertations and Theses (Open Access)

Pulmonary hypertension (PH) is a progressive disease with serious effects on quality of life and life expectancy of patients. PH is a complex disease that likely develops due to multiple influences, and no curative treatments exist for this disease. It has been shown that alternative polyadenylation (APA) due to depletion of Nudix Hydrolase 21(NUDT21) is involved in several disease states including the chronic lung disease idiopathic pulmonary fibrosis (IPF). Additionally, hyaluronan, an extracellular matrix glycosaminoglycan has been associated with PH. The role and mechanism of NUDT21 and hyaluronan have not yet been described in this disease. My results reveal that …

In Vitro Characterization Of Sonothrombolysis And Echocontrast Agents To Treat Ischemic Stroke, Himanshu Shekhar, Robert T Kleven, Tao Peng, Arunkumar Palaniappan, Kunal B Karani, Shaoling Huang, David D Mcpherson, Christy K Holland

Faculty, Staff and Student Publications

The development of adjuvant techniques to improve thrombolytic efficacy is important for advancing ischemic stroke therapy. We characterized octafluoropropane and recombinant tissue plasminogen activator (rt-PA)-loaded echogenic liposomes (OFP t-ELIP) using differential interference and fluorescence microscopy, attenuation spectroscopy, and electrozone sensing. The loading of rt-PA in OFP t-ELIP was assessed using spectrophotometry. Further, it was tested whether the agent shields rt-PA against degradation by plasminogen activator inhibitor-1 (PAI-1). An in vitro system was used to assess whether ultrasound (US) combined with either Definity or OFP t-ELIP enhances rt-PA thrombolysis. Human whole blood clots were mounted in a flow system and visualized …

Incidence And Predictors Of Obstructive Coronary Artery Disease And The Role Of Cardiac Troponin Assays In Patients With Unstable Angina, Sushan Yang, Nirmanmoh Bhatia, Meng Xu, John A Mcpherson

The Texas Heart Institute Journal

In a time when cardiac troponin assays are widely used to detect myocardial injury, data remain scarce concerning the incidence and predictors of substantial obstructive coronary artery disease that causes unstable angina. This retrospective single-center study included consecutive patients hospitalized for unstable angina from January 2015 through January 2016. Patients with troponin I levels above the upper reference limit and those who did not undergo angiography were excluded. Multivariate logistic regression analysis was used to identify predictors of obstructive coronary artery disease that warranted revascularization and of major adverse cardiac events up to 6 months after discharge from the hospital. …

Goosebumps, Efrain Rodriguez

The Texas Heart Institute Journal

No abstract provided.

Adam Christian Thebesius' Channels Into The Human Heart: The Thebesian Veins And The Thebesian Valve, Magdalena Mazurak, Jacek Kusa

The Texas Heart Institute Journal

In 1708, Adam Christian Thebesius, a 22-year-old student at Leiden University, presented his graduate thesis, Disputatio medica inauguralis de circulo sanguinis in corde. More than a doctoral dissertation, this groundbreaking work opened new channels into the study of the human coronary venous system. Thebesius' theory about the vascular communication between the coronary arteries and the chambers of the heart helped to advance understanding of hemodynamic principles and to clarify the physiologic pathways of the coronary circulation. The following article—the third in a trilogy about Lower Silesian scientists—provides an overview of the life story and achievements of this Silesian physician …

Osborn Waves: Differential Diagnosis, Akriti G Jain, Hammad Zafar, Sanjay Jain, Jason D'Souza

The Texas Heart Institute Journal

No abstract provided.

Percutaneous Coronary Intervention For Interposed Coronary Graft Stenosis After Modified Bentall Procedure In A Teenaged Boy With Takayasu Arteritis, Hiroki Ikenaga, Satoshi Kurisu, Yasuki Kihara

The Texas Heart Institute Journal

Anastomotic occlusion of an interposed coronary artery graft after a Bentall procedure is rare and catastrophic. It can lead to myocardial infarction or sudden cardiac death. We found several reports of occlusion and stenosis of a coronary-graft anastomosis, but few describe occlusion of the interposed coronary graft itself, as evaluated with use of intracoronary ultrasonography and computed tomography. We report the case of a 17-year-old boy with Takayasu arteritis who had a myocardial infarction caused by severe ostial stenosis in an interposed left coronary graft. The graft occlusion was confirmed by results of electrocardiography, aortography, and intracoronary ultrasonography. The patient …

Endoanchors Minimize Endoleaks In Chimney-Graft Endovascular Repair Of Juxtarenal Abdominal Aortic Aneurysms, Edgar Luis Galiñanes, Eduardo A Hernandez-Vila, Zvonimir Krajcer

The Texas Heart Institute Journal

Juxtarenal abdominal aortic aneurysms (AAAs) are difficult to treat because they often have little or no proximal aortic neck. Patients with this complex anatomy are not usually candidates for an endovascular aneurysm repair (EVAR). Chimney-graft EVAR has been introduced, but type Ia endoleak is a typical risk. We have begun using EndoAnchors to determine whether this risk can be reduced. From July 2013 through July 2014, we used the chimney-graft EVAR technique in 5 patients whose juxtarenal AAAs had a short or no proximal aortic neck. During the procedure, we implanted EndoAnchors as needed. Postprocedurally, at 30 days, and through …

Anomalous Origin Of The Right Coronary Artery From The Pulmonary Artery In A Neonate With Turner Syndrome And Aortic Arch Hypoplasia, Bryan P Stefek, Jason R Imundo, Joseph B Clark

The Texas Heart Institute Journal

Anomalous origin of the right coronary artery from the pulmonary artery, a rare congenital cardiac defect, is typically not diagnosed during infancy. On the other hand, Turner syndrome is usually diagnosed early, and it is classically associated with bicuspid aortic valve and aortic coarctation. Individuals with Turner syndrome are also at increased risk for coronary artery anomalies. We present a case of anomalous right coronary artery from the pulmonary artery in a week-old neonate who also had Turner syndrome, patent ductus arteriosus, transverse aortic arch hypoplasia, and impaired ventricular function. Prostaglandin therapy through the ductus increased the patient's myocardial perfusion. …

The Man With 2 Hearts: 25 Years From Heterotopic To Orthotopic Heart Transplantation, Elizabeth L Godfrey, Michael L Kueht, Abbas Rana, O H Frazier

The Texas Heart Institute Journal

Substantial technological advances in mechanical circulatory support have caused a shift in the management of end-stage heart failure. From the 1970s through the 1990s, heterotopic heart transplantation was routinely performed in patients in whom orthotopic transplantation was likely to fail. Heterotopic heart transplantation is now performed less often because modern mechanical circulatory assist devices are routinely used as bridges to orthotopic transplantation; regardless, the operation has helped numerous patients who would not otherwise have received adequate allografts. We describe the case of a man with idiopathic nonischemic cardiomyopathy who, at age 17, was given an ABO- and size-matched heterotopic allograft …

Surgical Thrombectomy For Pulmonary Embolism: Updated Performance Rates And Outcomes, Fahad Alqahtani, Muhammad Bilal Munir, Sami Aljohani, Abdul Tarabishy, Ahmad Almustafa, Mohamad Alkhouli

The Texas Heart Institute Journal

Treatments for pulmonary embolism are numerous and often complex. Current data on surgical thrombectomy are important but are not readily available. We studied the National Inpatient Sample to evaluate trends in the performance rates and outcomes of surgical thrombectomy in the United States from 2003 through 2014. We think that our findings have meaningful application to the triage and risk stratification of patients who have hemodynamically significant pulmonary embolism.

Metabolic Control, Quality Of Life, And Body Image In Patients With Glycogen Storage Disease Type Ia, Alexa Bream

Dissertations and Theses (Open Access)

Glycogen storage disease is a group of inborn errors of metabolism, with type Ia being the most common form of the disorder. Glycogen storage disease type Ia (GSDIa) is a multisystemic condition in which individuals have various complications secondary to an inability to properly break down glycogen and to perform gluconeogenesis. Complex management is then necessary for patients and includes dietary modification, frequent cornstarch usage, and evaluation for additional complications such as hepatic adenomas, hypertriglyceridemia, and kidney disease. Previous studies have found lower scores in quality of life and body image in GSDIa patients; however, the specific factors influencing this …

Unconventional 2:1 Ventricular Pacing In A Neonate With Congenital Heart Block And Biventricular Noncompaction, Andrew E Schneider, Philip L Wackel

The Texas Heart Institute Journal

Congenital complete heart block with concomitant biventricular noncompaction cardiomyopathy has been reported once previously. Although not universal, when restrictive physiology is present, impaired diastolic filling may pose a distinct challenge to pacing during the neonatal period. We present the case of a neonate with congenital complete heart block and biventricular noncompaction that resulted in severe diastolic dysfunction and atrioventricular dyssynchrony. We intentionally used 2:1 ventricular pacing to provide atrioventricular synchrony with every paced beat, and this resulted in hemodynamic and clinical improvement. This unconventional pacing technique may be beneficial in other neonates who have complete heart block and diastolic dysfunction.

Effectiveness Of Artificial Neochordae Implantation In Tricuspid Valve Repair, Salih Salihi, H Tarik Kiziltan, Ahmad Huraibat, Askin Ali Korkmaz, Ibrahim Kara, Mustafa Guden

The Texas Heart Institute Journal

Various techniques for treating tricuspid regurgitation have been described; however, because of scarce data about the long-term outcomes of different repairs, the optimal technique has not been established. We evaluated the effectiveness and durability of artificial neochordae implantation in the treatment of tricuspid regurgitation. From 2009 through 2014, 507 patients underwent tricuspid valve repair at our institution. Of those, 48 patients implanted with artificial neochordae were included in our study. The median age of the participants was 62 years (range, 4-77 yr) and 50% were women. Thirty patients (63%) were in New York Heart Association functional class III, and 11 …

More On Waiting For Test Results: When A Doctor Is The Patient, Herbert L Fred

The Texas Heart Institute Journal

No abstract provided.

An Unusual Case Of Takotsubo Cardiomyopathy In Pheochromocytoma, Paolo Angelini

The Texas Heart Institute Journal

No abstract provided.

Effect Of Percutaneous Suction Thromboembolectomy On Improved Right Ventricular Function, Akbarshakh Akhmerov, Heidi Reich, James Mirocha, Danny Ramzy

The Texas Heart Institute Journal

Venous thromboembolism is a leading cause of cardiovascular death. Historically, surgical intervention has been associated with high morbidity rates. Pharmacologic therapy alone can be inadequate for patients with substantial hemodynamic compromise, so minimally invasive procedures are being developed to reduce clot burden. We describe our initial experience with using the AngioVac system to remove thromboemboli percutaneously. We reviewed all suction thromboembolectomy procedures performed at our institution from March 2013 through August 2015. The main indications for the procedure were failed catheter-directed therapy, contraindication to thrombolysis, bleeding-related complications, and clot-in-transit phenomena. We collected details on patient characteristics, procedural indications, thrombus location, …

Transapical Implantation Of Edwards Sapien Xt Valve To Close A Left Ventricular Outflow Tract Pseudoaneurysm, Jorge Peñalver, Wassim Shatila, Francisco Y Macedo, Guilherme V Silva

The Texas Heart Institute Journal

No abstract provided.