Medicine and Health Sciences Commons^™

Rapid Onset Hydralazine-Induced Antineutrophil Cytoplasmic Antibody (Anca) Associated Vasculitis Presenting With Hemoptysis And Kidney Failure: Case Report, Rachel E. Easter, Andinet Gizaw, Natalie Klein

Internal Medicine Publications

Hydralazine-induced vasculitis can be challenging to recognize and diagnose as presenting symptoms vary and can mimic other conditions or diseases, however, swift intervention and treatment is key in halting progression of the disease and providing patients with the best possible outcomes. A 71-year-old African American female presented to the emergency department with weakness, fatigue, anemia, blood-streaked sputum, fever, chills, and severe myalgias. Hydralazine was prescribed to treat resistant hypertension eight months prior to presentation. Hydralazine was discontinued on hospital day (HD) 4. Pertinent laboratory values showed elevated inflammatory markers, positive antinuclear antibody (ANA), negative rheumatoid factor (RF), normal complement levels, …

Virtual Infection Prevention And Control In Low- And Middle-Income Countries, Tristan Jones, Kalisvar Marimuthu, Gonzalo Bearman

Internal Medicine Publications

COVID-19 brought new challenges and opportunities for infection prevention and control. Virtual infection prevention and control (VIPC), although nascent, is rapidly becoming a viable and necessary strategy for combatting the COVID-19 pandemic. Benefits of VIPC include extending the impact of globally scarce infectious disease providers and public health practitioners, allowing coordination between disparate professionals to more effectively combat infectious disease, and increasing access to and quality of healthcare. Although mainly applied in developed countries, VIPC may play its greatest role in low- and middle-income countries (LMICs) with fewer healthcare resources. We conducted a brief literature search of VIPC in LMICs …

High-Resolution Mapping And Successful Ablation Of Purkinje Ectopy–Triggered Ventricular Fibrillation Storm, Alexandre Raymond-Paquin, Scott Lovejoy, Kenneth A. Ellenbogen, Santosh K. Padala

Internal Medicine Publications

Catheter ablation is recognized as a central therapeutic option in treating patients with drug-refractory, scar-related monomorphic ventricular tachycardia (VT). Catheter ablation also has a role in selected cases of polymorphic VT (PMVT) and/or ventricular fibrillation (VF). Rarely, premature ventricular contractions (PVCs) originating from the Purkinje network can induce PMVT/VF. Although not completely elucidated, the electrophysiologic mechanisms behind this lethal arrhythmia have generally been thought to be related to abnormal automaticity and triggered activity. Ablation of the triggering PVCs can prevent VF recurrence and is potentially lifesaving

Cystic Fibrosis And Sleep Circadian Rhythms, Mariam Louis, Peter Staiano, Lavender Micalo, Nauman Chaudary

Internal Medicine Publications

Cystic fibrosis (CF) is due to a mutation in the cystic fibrosis transmembrane conductance regulator gene (CFTR), which leads to unusual water and chloride secretion across epithelial surfaces. The lungs are responsible for most morbidity, though other organs are frequently affected. Sleep abnormalities have long been recognized in CF. Abnormal ventilation and oxygenation, sinus disease, deconditioning due to muscle weakness and recurrent infections, and inflammation have been thought to play a role in sleep disorders in CF. However, there is evidence that CFTR gene dysregulation can affect circadian rhythms in CF. Early recognition and treatment of circadian rhythms may improve …

Effect Of Interleukin-1 Blockade With Anakinra On Leukocyte Count In Patients With St-Segment Elevation Acute Myocardial Infarction, Marco Giuseppe Del Buono, Juan I. Damonte, Cory R. Trankle, Dinesh Kadariya, Salvatore Carbone, Georgia Thomas, Jeremy Turlington, Roshanak Markley, Justin M. Canada, Giuseppe G. Biondi‐Zoccai, Michael C. Kontos, Benjamin W. Van Tassell, Antonio Abbate

Internal Medicine Publications

Leukocytosis is a common finding in patients with ST elevation myocardial infarction (STEMI) and portends a poor prognosis. Interleukin 1-β regulates leukopoiesis and pre-clinical studies suggest that anakinra (recombinant human interleukin-1 [IL-1] receptor antagonist) suppresses leukocytosis in myocardial infarction. However, the effect of IL-1 blockade with anakinra on leukocyte count in patients with STEMI is unknown. We reviewed the white blood cell (WBC) and differential count of 99 patients enrolled in a clinical trial of anakinra (n = 64) versus placebo (n = 35) for 14 days after STEMI. A complete blood cell count with differential count were obtained at …

Influence Of Extracellular Volume Fraction On Peak Exercise Oxygen Pulse Following Thoracic Radiotherapy, Justin M. Canada, Elisabeth Weiss, John D. Grizzard, Cory R. Trankle, Leila Rezai Gharai, Franklin Dana, Leo F. Buckley, Salvatore Carbone, Dinesh Kadariya, Anthony Ricco, Jennifer H. Jordan, Ronald K. Evans, Ryan S. Garten, Benjamin W. Van Tassell, W. Gregory Hundley, Antonio Abbate

Internal Medicine Publications

Background

Radiation-induced myocardial fibrosis increases heart failure (HF) risk and is associated with a restrictive cardiomyopathy phenotype. The myocardial extracellular volume fraction (ECVF) using contrast-enhanced cardiac magnetic resonance (CMR) quantifies the extent of fibrosis which, in severe cases, results in a noncompliant left ventricle (LV) with an inability to augment exercise stroke volume (SV). The peak exercise oxygen pulse (O2Pulse), a noninvasive surrogate for exercise SV, may provide mechanistic insight into cardiac reserve. The relationship between LV ECVF and O2Pulse following thoracic radiotherapy has not been explored.

Methods

Patients who underwent thoracic radiotherapy for chest malignancies with significant incidental heart …

Calpain-Mediated Protein Targets In Cardiac Mitochondria Following Ischemia–Reperfusion, Ling Li, Jeremy Thompson, Ying Hu, Edward J. Lesnefsky, Belinda Willard, Qun Chen

Internal Medicine Publications

Calpain 1 and 2 (CPN1/2) are calcium-dependent cysteine proteases that exist in cytosol and mitochondria. Pharmacologic inhibition of CPN1/2 decreases cardiac injury during ischemia (ISC)–reperfusion (REP) by improving mitochondrial function. However, the protein targets of CPN1/2 activation during ISC–REP are unclear. CPN1/2 include a large subunit and a small regulatory subunit 1 (CPNS1). Genetic deletion of CPNS1 eliminates the activities of both CPN1 and CPN2. Conditional cardiomyocyte specific CPNS1 deletion mice were used in the present study to clarify the role of CPN1/2 activation in mitochondrial damage during ISC–REP with an emphasis on identifying the potential protein targets of CPN1/2. …

Cardiac Gene Therapy With Relaxin Receptor 1 Overexpression Protects Against Acute Myocardial Infarction, Teja Devarakonda, Adolfo G. Mauro, Chad Cain, Anindita Das, Fadi N. Salloum

Internal Medicine Publications

Relaxin is a pleiotropic hormone shown to confer cardioprotection in several preclinical models of cardiac ischemia-reperfusion injury. In the present study, the effects of up-regulating relaxin family peptide receptor 1 (RXFP1) via adeno-associated virus serotype 9 (AAV9) vectors were investigated in a mouse model of myocardial infarction. AAV9-RXFP1 vectors were generated and injected in adult male CD1 mice. Up-regulation of Rxfp1 was confirmed via quantitative polymerase chain reaction, and overexpressing animals showed increased sensitivity to relaxin-induced ventricular inotropic response. Overexpressing animals also demonstrated reduced infarct size and preserved cardiac function 24 hours after ischemia-reperfusion. Up-regulation of RXFP1 via AAV9 vectors …

Rpop: Robust Pet-Only Processing Of Community Acquired Heterogeneous Amyloid-Pet Data, Leonardo Iaccarino, Renaud La Joie, Robert Koeppe, Barry A. Siegel, Bruce E. Hilner, Constantine Gatsonis, Rachel A. Whitmer, Maria C. Carrillo, Charles Apgar, Monica R. Camacho, Rachel Nosheny, Gil D. Rabinovici

Internal Medicine Publications

The reference standard for amyloid-PET quantification requires structural MRI (sMRI) for preprocessing in both multi-site research studies and clinical trials. Here we describe rPOP (robust PET-Only Processing), a MATLAB-based MRI-free pipeline implementing non-linear warping and differential smoothing of amyloid-PET scans performed with any of the FDA-approved radiotracers (18F-florbetapir/FBP, 18F-florbetaben/FBB or 18F-flutemetamol/FLUTE). Each image undergoes spatial normalization based on weighted PET templates and data-driven differential smoothing, then allowing users to perform their quantification of choice. Prior to normalization, users can choose whether to automatically reset the origin of the image to the center of mass or proceed with the pipeline with …

Increased C-Reactive Protein Is Associated With The Severity Of Thoracic Radiotherapy-Induced Cardiomyopathy, Justin M. Canada, Georgia K. Thomas, Cory R. Trankle, Salvatore Carbone, Hayley Billingsley, Benjamin W. Van Tassell, Ronald K. Evans, Ryan Garten, Elisabeth Weiss, Antonio Abbate

Internal Medicine Publications

Background: Irradiation of the heart during cancer radiotherapy is associated with a dose-dependent risk of heart failure. Animal studies have demonstrated that irradiation leads to an inflammatory response within the heart as well as a reduction in cardiac reserve. In the current study we aimed to evaluate whether inflammatory biomarkers correlated with changes in cardiac function and reserve after radiotherapy for breast or lung cancer.

Methods and results: We studied 25 subjects with a history of breast or lung cancer without a prior diagnosis of cardiovascular disease or heart failure, 1.8 years [0.4–3.6] post-radiotherapy involving at least 5 …

Vitamin C Intravenous Treatment In The Setting Of Atrial Fibrillation Ablation: Results From The Randomized, Double-Blinded, Placebo-Controlled Citris-Af Pilot Study, Cory R. Trankle, Laura Puckett, Theresa Swift-Scanlan, Christine Dewilde, Anna Priday, Robin Sculthorpe, Kenneth A. Ellenbogen, Alpha Fowler, Jayanthi N. Koneru

Internal Medicine Publications

Background
Catheter ablation is an effective treatment for atrial fibrillation (AF), but high levels of post-procedure inflammation predict adverse clinical events. Ascorbic acid (AA) has shown promise in reducing inflammation but is untested in this population. We sought to test the feasibility, safety, and preliminary effects on inflammatory biomarkers in the CITRIS-AF (Vitamin C Intravenous Treatment In the Setting of Atrial Fibrillation Ablation) pilot study.

Methods and Results
Patients scheduled to undergo AF ablation (N=20) were randomized 1:1 to double-blinded treatment with AA (200 mg/kg divided over 24 hours) or placebo. C-reactive protein and interleukin-6 levels were obtained before the …

Interleukin‐1 Blockade Inhibits The Acute Inflammatory Response In Patients With St‐Segment–Elevation Myocardial Infarction, Antonio Abbate, Cory R. Trankle, Leo F. Buckley, Michael J. Lipinski, Darryn Appleton, Dinesh Kadariya, Justin M. Canada, Salvatore Carbone, Charlotte S. Roberts, Nayef Abouzaki, Ryan Melchior, Sanah Christopher, Jeremy Turlington, George Mueller, James Garnett, Christopher Thomas, Roshanak Markley, George F. Wohlford, Laura Puckett, Horacio Medina De Chazal, Juan G. Chiabrando, Edoardo Bressi, Marco Giuseppe Del Buono, Aaron Schatz, Chau Vo, Dave L. Dixon, Giuseppe G. Biondi-Zoccai, Michael C. Kontos, Benjamin W. Van Tassell

Internal Medicine Publications

Background

ST‐segment–elevation myocardial infarction is associated with an intense acute inflammatory response and risk of heart failure. We tested whether interleukin‐1 blockade with anakinra significantly reduced the area under the curve for hsCRP (high sensitivity C‐reactive protein) levels during the first 14 days in patients with ST‐segment–elevation myocardial infarction (VCUART3 [Virginia Commonwealth University Anakinra Remodeling Trial 3]).

Methods and Results

We conducted a randomized, placebo‐controlled, double‐blind, clinical trial in 99 patients with ST‐segment–elevation myocardial infarction in which patients were assigned to 2 weeks treatment with anakinra once daily (N=33), anakinra twice daily (N=31), or placebo (N=35). hsCRP area under the …

Association Of Anti-Mullerian Hormone With C-Reactive Protein In Men, Dinesh Kadariya, Nargiza Kurbanova, Rehan Qayyum

Internal Medicine Publications

While serum anti-mullerian hormone (AMH) levels are inversely associated with all-cause mortality in men, the underlying mechanisms are unclear. Elevated levels of inflammation, also associated with all-cause mortality, and may be the link between AMH and mortality. Hence, we examined the association of AMH with serum c-reactive protein (CRP), a biomarker of inflammation, in men. We included men ≥20 years from the National Health and Nutrition Examination Survey (1999–2004). We used survey weight-adjusted linear regression to examine the association between AMH and CRP without and with adjustment for age, race, body mass index (BMI), smoking, hypertension, diabetes, cholesterol, glomerular filtration …

Unsaturated Fatty Acids To Improve Cardiorespiratory Fitness In Patients With Obesity And Hfpef, Salvatore Carbone, Hayley E. Billingsley, Justin M. Canada, Dinesh Kadariya, Horacio Medina De Chazal, Brando Rotelli, Nicola Potere, Bishal Paudel, Roshi Markley, Dave L. Dixon, Cory R. Trankle, Benjamin W. Van Tassell, Francesco S. Celi, Antonio Abbate

Internal Medicine Publications

No abstract provided.

The Association Between Urinary Genistein Levels And Mortality Among Adults In The United States, Carolyn Marcelo, Melissa Warwick, Catherine Marcelo, Rehan Qayyum

Internal Medicine Publications

Background
Current research on the relationship between phytoestrogens and mortality has been inconclusive. We explored the relationship between genistein, a phytoestrogen, and mortality in a large cohort representative of the United States population.


Methods: Data were analyzed from the National Health and Nutrition Examination Survey (NHANES) from 1999–2010. Normalized urinary genistein (nUG) was analyzed as a log-transformed continuous variable and in quartiles. Mortality data were obtained from the National Death Index and matched to the NHANES participants. Survival analyses were conducted using the Kaplan-Meier analysis. Cox proportional hazard models were constructed for all-cause and cause-specific mortality without and with …

Remote Ischemic Pre-Conditioning Attenuates Adverse Cardiac Remodeling And Mortality Following Doxorubicin Administration In Mice, Zachary M. Gertz, Chad Cain, Donatas Kraskauskas, Teja Devarakonda, Adolfo G. Mauro, Jeremy Thompson, Arun Samidurai, Qun Chen, Sarah W. Gordon, Edward J. Lesnefsky, Anindita Das, Fadi N. Salloum

Internal Medicine Publications

Objectives

Because of its multifaceted cardioprotective effects, remote ischemic pre-conditioning (RIPC) was examined as a strategy to attenuate doxorubicin (DOX) cardiotoxicity.

Background

The use of DOX is limited by dose-dependent cardiotoxicity and heart failure. Oxidative stress, mitochondrial dysfunction, inflammation, and autophagy modulation have been proposed as mediators of DOX cardiotoxicity.

Methods

After baseline echocardiography, adult male CD1 mice were randomized to either sham or RIPC protocol (3 cycles of 5 min femoral artery occlusion followed by 5 min reperfusion) 1 h before receiving DOX (20 mg/kg, intraperitoneal). The mice were observed primarily for survival over 85 days (86 mice). An …

Low Nt-Probnp Levels In Overweight And Obese Patients Do Not Rule Out A Diagnosis Of Heart Failure With Preserved Ejection Fraction, Leo F. Buckley, Justin M. Canada, Marco G. Del Buono, Salvatore Carbone, Cory R. Trankle, Hayley Billingsley, Dinesh Kadariya, Ross Arena, Benjamin W. Van Tassell, Antonio Abbate

Internal Medicine Publications

Background Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome that presents clinicians with a diagnostic challenge. The use of natriuretic peptides to exclude a diagnosis of HFpEF has been proposed. We sought to compare HFpEF patients with N-terminal pro-brain natriuretic peptide (NT-proBNP) level above and below the proposed cut-off.

Methods Stable patients (n = 30) with left ventricular (LV) ejection fraction ≥ 50% were eligible if they had a diagnosis of HF according to the European Society of Cardiology diagnostic criteria. Characteristics of patients with NT-proBNP below (≤125 pg/mL) and above (>125 pg/mL) the diagnostic …

Intestine‐Specific Expression Of Human Chimeric Intestinal Alkaline Phosphatase Attenuates Western Diet‐Induced Barrier Dysfunction And Glucose Intolerance, Siddhartha S. Ghosh, Hongliang He, Jing Wang, William Korzun, Paul J. Yannie, Shobha Ghosh

Internal Medicine Publications

Intestinal epithelial cell derived alkaline phosphatase (IAP) dephosphorylates/detoxifies bacterial endotoxin lipopolysaccharide (LPS) in the gut lumen. We have earlier demonstrated that consumption of high‐fat high‐cholesterol containing western type‐diet (WD) significantly reduces IAP activity, increases intestinal permeability leading to increased plasma levels of LPS and glucose intolerance. Furthermore, oral supplementation with curcumin that increased IAP activity improved intestinal barrier function as well as glucose tolerance. To directly test the hypothesis that targeted increase in IAP would protect against WD‐induced metabolic consequences, we developed intestine‐specific IAP transgenic mice where expression of human chimeric IAP is under the control of intestine‐specific villin promoter. …

Screening For Gynecologic Conditions With Pelvic Examination Us Preventive Services Task Force Recommendation Statement, Kirsten Bibbins-Domingo, David C. Grossman, Susan J. Curry, Michael J. Barry, Karina W. Davidson, Chyke A. Doubeni, John W. Epling Jr, Francisco A. R. García, Alex R. Kemper, Alex H. Krist, Ann E. Kurth, C. Seth Landefeld, Carol M. Mangione, William R. Phillips, Maureen G. Phipps, Michael Silverstein, Melissa Simon, Albert L. Siu, Chien-Wen Tseng

Internal Medicine Publications

IMPORTANCE Many conditions that can affect women's health are often evaluated through pelvic examination. Although the pelvic examination is a common part of the physical examination, it is unclear whether performing screening pelvic examinations in asymptomatic women has a significant effect on disease morbidity and mortality.

OBJECTIVE To issue a new US Preventive Services Task Force(USPSTF) recommendation on screening for gynecologic conditions with pelvic examination for conditions other than cervical cancer, gonorrhea, and chlamydia, for which the USPSTF has already made specific recommendations.

EVIDENCE REVIEW The USPSTF reviewed the evidence on the accuracy, benefits, and potential harms of performing screening …

Mutant P53 Establishes Targetable Tumor Dependency By Promoting Unscheduled Replication, Shilpa Singh, Catherine Vaughan, Rebecca Anne Frum, Steven R. Grossman, Sumitra Deb, Swati Palit Deb

Internal Medicine Publications

Gain-of-function (GOF) p53 mutations are observed frequently in most intractable human cancers and establish dependency for tumor maintenance and progression. While some of the genes induced by GOF p53 have been implicated in more rapid cell proliferation compared with p53-null cancer cells, the mechanism for dependency of tumor growth on mutant p53 is unknown. This report reveals a therapeutically targetable mechanism for GOF p53 dependency. We have shown that GOF p53 increases DNA replication origin firing, stabilizes replication forks, and promotes micronuclei formation, thus facilitating the proliferation of cells with genomic abnormalities. In contrast, absence or depletion of GOF p53 …

Reversal Of Hepatorenal Syndrome Type 1 With Terlipressin Plus Albumin Vs. Placebo Plus Albumin In A Pooled Analysis Of The Ot-0401 And Reverse Randomised Clinical Studies, A. J. Sanyal, T. D. Boyer, R. T. Frederick, F. Wong, L. Rossaro, V. Araya, H. E. Vargas, K. R. Reddy, S. C. Pappas, P. Teuber, S. Escalante, K. Jamil

Internal Medicine Publications

Background

The goal of hepatorenal syndrome type 1 (HRS-1) treatment is to improve renal function. Terlipressin, a synthetic vasopressin analogue, is a systemic vasoconstrictor used for the treatment of HRS-1, where it is available.

Aim

To compare the efficacy of terlipressin plus albumin vs. placebo plus albumin in patients with HRS-1.

Methods

Pooled patient-level data from two large phase 3, randomised, placebo-controlled studies were analysed for HRS reversal [serum creatinine (SCr) value ≤133 μmol/L], 90-day survival, need for renal replacement therapy and predictors of HRS reversal. Patients received intravenous terlipressin 1–2 mg every 6 hours plus albumin or placebo plus …

Role Of Tissue And Systemic Hypoxia In Obesity And Type 2 Diabetes, Lei Xi, Chin-Moi Chow, Xingxing Kong

Internal Medicine Publications

Human lifestyle in most modern and developing societies has dramatically changed over past decades. Physical inactivity along with unrestricted access to calorie dense foods has established an “obesogenic” environment and contributed to a serious epidemic of obesity and type 2 diabetes (T2D), associated with increased morbidity and mortality. In 2005 a population-based study conducted by Reichmuth et al. of University of Wisconsin with a cross-sectional and longitudinal analysis identified that among 1387 participants the odds ratio for T2D with an apnea-hypopnea index (AHI) > 15 versus an AHI < 5 was 2.30 (1.28–4.11; p < 0.01) after adjustment for age, sex, and body habitus. Therefore it has been assumed that intermittent hypoxic periods associated with obstructive sleep apnea (OSA) may play a pathogenic role in inducing insulin resistance and T2D. At organ/tissue levels, in 2007–2009 Ye and colleagues first proposed a central role played by adipose tissue hypoxia resulting from adipocyte expansion in promoting chronic inflammation, adiponectin reduction, adipocyte dysfunction, and death in obese individuals. This group of researchers later identified the mediator roles played by hypoxia inducible factor 1α (HIF-1α) and other hypoxia-triggered signaling mechanisms that may promote free fatty acid release and inhibit glucose uptake in adipocytes by inhibition of the insulin-signaling pathway and induction of cell death.

Development And Pilot Of A Checklist For Management Of Acute Liver Failure In The Intensive Care Unit, Oren K. Fix, Iris Liou, Constantine J. Karvellas, Daniel R. Ganger, Kinberly A. Forde, Ram M. Subramanian, Alice Boylan, James Hanje, R. Todd Stravitz, William M. Lee, Acute Liver Failure Study Group

Internal Medicine Publications

Introduction

Acute liver failure (ALF) is an ideal condition for use of a checklist. Our aims were to develop a checklist for the management of ALF in the intensive care unit (ICU) and assess the usability of the checklist among multiple providers.

Methods

The initial checklist was developed from published guidelines and expert opinion. The checklist underwent pilot testing at 11 academic liver transplant centers in the US and Canada. An anonymous, written survey was used to assess the usability and quality of the checklist. Written comments were used to improve the checklist following the pilot testing period.

Results

We …

Intravenous Vitamin C Administered As Adjunctive Therapy For Recurrent Acute Respiratory Distress Syndrome, Amit Bharara, Catherine Grossman, Daniel Grinnan, Aamer Syed, Bernard Fisher, Christine Dewilde, Ramesh Natarajan, Alpha A. (Berry) Fowler

Internal Medicine Publications

This case report summarizes the first use of intravenous vitamin C employed as an adjunctive interventional agent in the therapy of recurrent acute respiratory distress syndrome (ARDS). The two episodes of ARDS occurred in a young female patient with Cronkhite-Canada syndrome, a rare, sporadically occurring, noninherited disorder that is characterized by extensive gastrointestinal polyposis and malabsorption. Prior to the episodes of sepsis, the patient was receiving nutrition via chronic hyperalimentation administered through a long-standing central venous catheter. The patient became recurrently septic with Gram positive cocci which led to two instances of ARDS. This report describes the broad-based general critical …

Regulation Of Reactive Oxygen Species And The Antioxidant Protein Dj-1 In Mastocytosis, Do-Kyun Kim, Michael A. Beaven, Joseph M. Kulinski, Avanti Desai, Geethani Bandara, Yun Bai, Calman Prussin, Lawrence B. Schwartz, Hirsh Komarow, Dean D. Metcalfe, Ana Olivera

Internal Medicine Publications

Neoplastic accumulation of mast cells in systemic mastocytosis (SM) associates with activating mutations in the receptor tyrosine kinase KIT. Constitutive activation of tyrosine kinase oncogenes has been linked to imbalances in oxidant/antioxidant mechanisms in other myeloproliferative disorders. However, the impact of KIT mutations on the redox status in SM and the potential therapeutic implications are not well understood. Here, we examined the regulation of reactive oxygen species (ROS) and of the antioxidant protein DJ-1 (PARK-7), which increases with cancer progression and acts to lessen oxidative damage to malignant cells, in relationship with SM severity. ROS levels were increased in both …

Mitochondrial Membrane Permeability Inhibitors In Acute Myocardial Infarction Still Awaiting Translation, Cory Trankle, Clinton J. Thurber, Stefano Toldo, Antonio Abbate

Internal Medicine Publications

Despite therapeutic advances, acute myocardial infarction (AMI) remains a leading cause of morbidity and mortality worldwide. One potential limitation of the current treatment paradigm is the lack of effective therapies to optimize reperfusion after ischemia and prevent reperfusion-mediated injury. Experimental studies indicate that this process accounts for up to 50% of the final infarct size, lending it importance as a potential target for cardioprotection. However, multiple therapeutic approaches have shown potential in pre-clinical and early phase trials but a paucity of clear clinical benefit when expanded to larger studies. Here we explore this history of trials and errors of the …

Donor Ifnl4 Genotype Is Associated With Early Post-Transplant Fibrosis In Recipients With Hepatitis C, Taylor Aiken, Ari Garber, Dawn Thomas, Nicole Hamon, Rocio Lopez, Rajesh Konjeti, Arthur Mccullough, Nizar Zein, John Fung, Medhat Askar, Binu V. John

Internal Medicine Publications

Background and Aims

Early post-transplant hepatic fibrosis is associated with poor outcomes and may be influenced by donor/recipient genetic factors. The rs368234815 IFNL4 polymorphism is related to the previously described IL28B polymorphism, which predicts etiology-independent hepatic fibrosis. The aim of this study was to identify the impact of donor and/or recipient IFNL4 genotype on early fibrosis among patients transplanted for hepatitis C (HCV).

Methods

Clinical data were collected for 302 consecutive patients transplanted for HCV. 116 patients who had available liver biopsies and donor/recipient DNA were included. 28% of these patients with stage 2 fibrosis or greater were compared to …

Increased Pleiotrophin Concentrations In Papillary Thyroid Cancer, Youn Hee Jee, Samira M. Sadowsk, Francesco S. Celi, Liqiang Xi, Mark Raffeld, David B. Sacks, Alan T. Remaley, Anton Wellstein, Electron Kebebew, Jeffrey Baron

Internal Medicine Publications

Background Thyroid nodules are common, and approximately 5% of these nodules are malignant. Pleiotrophin (PTN) is a heparin-binding growth factor which is overexpressed in many cancers. The expression of PTN in papillary thyroid cancer (PTC) is unknown. Method and Findings 74 subjects (age 47 ± 12 y, 15 males) who had thyroidectomy with a histological diagnosis: 79 benign nodules and 23 PTCs (10 classic, 6 tall cell, 6 follicular variant and 1 undetermined). Fine-needle aspiration (FNA) samples were obtained ex vivo from surgically excised tissue and assayed for PTN and thyroglobulin (Tg). Immunohistochemistry (IHC) was performed on tissue sections. In …

Pulmonary Hypertension Is A Manifestation Of Congestive Heart Failure And Left Ventricular Diastolic Dysfunction In Octogenarians With Severe Aortic Stenosis, Amresh Raina, Zachary M. Gertz, William T. O'Donnell, Howard C. Herrmann, Paul R. Forfia

Internal Medicine Publications

Previous studies have suggested that pulmonary hypertension (PH) in severe aortic stenosis (AS) is a risk factor for operative mortality with aortic valve replacement (AVR). Conversely, others have shown that patients with AS and PH extract a large symptomatic and survival benefit from AVR compared with those patients not treated surgically. We sought to evaluate the prevalence, severity, and mechanism of PH in an elderly patient cohort with severe AS. We prospectively evaluated 41 patients aged ≥80 years with severe AS. All patients underwent cardiac catheterization and transthoracic echocardiography within 24 hours. We found that PH was common in this …

Peritoneal Mesothelioma: An Unusual Cause Of High-Protein Ascites, Matthew Kaspar

Internal Medicine Publications

We present a case illustrating the workup and diagnosis of peritoneal sarcomatous mesothelioma as an unusual etiology of intestinal obstruction and high-protein ascites in an otherwise healthy man. This rare disorder is diagnosed based on immunohistochemistry, which is necessary to differentiate it from other rare sarcomatous carcinomas. In many cases, localized disease can be treated to cure with surgery and intraperitoneal chemotherapy. Advanced disease is often treated for palliation of symptoms.