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Acute Effects Of Implantable Cardioverter-Defibrillator Shocks On Biomarkers Of Myocardial Injury, Apoptosis, Heart Failure, And Systemic Inflammation, Jordan Brewster, Travis Sexton, Gary Dhaliwal, Richard Charnigo, Gustavo Morales, Kevin Parrott, Yousef Darrat, John C. Gurley, Susan S. Smyth, Claude S. Elayi Apr 2017

Acute Effects Of Implantable Cardioverter-Defibrillator Shocks On Biomarkers Of Myocardial Injury, Apoptosis, Heart Failure, And Systemic Inflammation, Jordan Brewster, Travis Sexton, Gary Dhaliwal, Richard Charnigo, Gustavo Morales, Kevin Parrott, Yousef Darrat, John C. Gurley, Susan S. Smyth, Claude S. Elayi

Internal Medicine Faculty Publications

Background: Implantable cardioverter‐defibrillator (ICD) shocks are potentially associated with myocardial injury, altered hemodynamics, apoptosis, and inflammatory signaling. Their precise cellular impact can be explored after defibrillation testing (DFT) via biomarkers. We evaluated changes in biomarkers after ICD shocks during DFT.

Methods: We prospectively enrolled outpatients presenting for first implantation of a cardiac device. Biomarkers indicative of myocardial injury, inflammation, and apoptosis were measured before and after implantation, and compared between patients receiving DFT (DFT+) to those not (DFT−).

Results: Sixty‐three patients were enrolled, 40 in the DFT+ group and 23 in the DFT− group. Average levels of troponin I, hsCRP, …


Spotlight On Blisibimod And Its Potential In The Treatment Of Systemic Lupus Erythematosus: Evidence To Date, Aleksander Lenert, Timothy B. Niewold, Petar Lenert Mar 2017

Spotlight On Blisibimod And Its Potential In The Treatment Of Systemic Lupus Erythematosus: Evidence To Date, Aleksander Lenert, Timothy B. Niewold, Petar Lenert

Internal Medicine Faculty Publications

B cells in general and BAFF (B cell activating factor of the tumor necrosis factor [TNF] family) in particular have been primary targets of recent clinical trials in systemic lupus erythematosus (SLE). In 2011, belimumab, a monoclonal antibody against BAFF, became the first biologic agent approved for the treatment of SLE. Follow-up studies have shown excellent long-term safety and tolerability of belimumab. In this review, we critically analyze blisibimod, a novel BAFF-neutralizing agent. In contrast to belimumab that only blocks soluble BAFF trimer but not soluble 60-mer or membrane BAFF, blisibimod blocks with high affinity all three forms of BAFF. …


Bioactive Lipids And Circulating Progenitor Cells In Patients With Cardiovascular Disease, Salim S. Hayek, Yuri Klyachkin, Ahmed Asfour, Nima Ghasemzadeh, Mosaab Awad, Iraj Hesaroieh, Hina Ahmed, Brandon Gray, Jinhee Kim, Edmund K. Waller, Arshed A. Quyyumi, Ahmed K. Abdel-Latif Mar 2017

Bioactive Lipids And Circulating Progenitor Cells In Patients With Cardiovascular Disease, Salim S. Hayek, Yuri Klyachkin, Ahmed Asfour, Nima Ghasemzadeh, Mosaab Awad, Iraj Hesaroieh, Hina Ahmed, Brandon Gray, Jinhee Kim, Edmund K. Waller, Arshed A. Quyyumi, Ahmed K. Abdel-Latif

Internal Medicine Faculty Publications

Bone marrow-derived progenitor cells are mobilized into the peripheral blood after acute myocardial injury and in chronic ischemic heart disease. However, the mechanisms responsible for this mobilization are poorly understood. We examined the relationship between plasma levels of bioactive lipids and number of circulating progenitor cells (CPCs) in patients (N = 437) undergoing elective or emergent cardiac catheterization. Plasma levels of sphingosine-1 phosphate (S1P) and ceramide-1 phosphate (C1P) were quantified using mass spectrometry. CPCs were assessed using flow cytometry. S1P levels correlated with the numbers of CD34+, CD34+/CD133+, and CD34+/CXCR4+ CPCs even after adjustment for potential confounding factors. However, …


Roadmap To A Comprehensive Clinical Data Warehouse For Precision Medicine Applications In Oncology, David J. Foran, Wenjin Chen, Huiqi Chu, Evita Sadimin, Doreen Loh, Gregory Riedlinger, Lauri A. Goodell, Shridar Ganesan, Kim Hirshfield, Lorna Rodriguez, Robert S. Dipaola Mar 2017

Roadmap To A Comprehensive Clinical Data Warehouse For Precision Medicine Applications In Oncology, David J. Foran, Wenjin Chen, Huiqi Chu, Evita Sadimin, Doreen Loh, Gregory Riedlinger, Lauri A. Goodell, Shridar Ganesan, Kim Hirshfield, Lorna Rodriguez, Robert S. Dipaola

Internal Medicine Faculty Publications

Leading institutions throughout the country have established Precision Medicine programs to support personalized treatment of patients. A cornerstone for these programs is the establishment of enterprise-wide Clinical Data Warehouses. Working shoulder-to-shoulder, a team of physicians, systems biologists, engineers, and scientists at Rutgers Cancer Institute of New Jersey have designed, developed, and implemented the Warehouse with information originating from data sources, including Electronic Medical Records, Clinical Trial Management Systems, Tumor Registries, Biospecimen Repositories, Radiology and Pathology archives, and Next Generation Sequencing services. Innovative solutions were implemented to detect and extract unstructured clinical information that was embedded in paper/text documents, including synoptic …


Early Gadolinium Enhancement For Area At Risk Determination: A Preclinical Validation Study, Sophia Hammer-Hansen, Steve W. Leung, Li-Yueh Hsu, Joel R. Wilson, Joni Taylor, Anders M. Greve, Jens Jakob Thune, Lars Køber, Peter Kellman, Andrew E. Arai Feb 2017

Early Gadolinium Enhancement For Area At Risk Determination: A Preclinical Validation Study, Sophia Hammer-Hansen, Steve W. Leung, Li-Yueh Hsu, Joel R. Wilson, Joni Taylor, Anders M. Greve, Jens Jakob Thune, Lars Køber, Peter Kellman, Andrew E. Arai

Internal Medicine Faculty Publications

Objectives—The aim of this study was to determine if early gadolinium enhancement (EGE) by cardiovascular magnetic resonance (CMR) imaging in a canine model of reperfused myocardial infarction depicts the area at risk (AAR) as determined by microsphere blood flow analysis.

Background—It remains controversial whether only the irreversibly injured myocardium enhances when performing CMR imaging in the setting of acute myocardial infarction. Recently, EGE has been proposed as a measure of the AAR in acute myocardial infarction as it correlates well with T2-weighted imaging of the AAR, but still requires pathological validation.

Methods—Eleven dogs underwent 2 hours of …


Telotristat Ethyl, A Tryptophan Hydroxylase Inhibitor For The Treatment Of Carcinoid Syndrome, Matthew H. Kulke, Dieter Hörsch, Martyn E. Caplin, Lowell B. Anthony, Emily Bergsland, Kjell Öberg, Staffan Welin, Richard R. P. Warner, Catherine Lombard-Bohas, Pamela L. Kunz, Enrique Grande, Juan W. Valle, Douglas Fleming, Pablo Lapuerta, Phillip Banks, Shanna Jackson, Brian Zambrowicz, Arthur T. Sands, Marianne Pavel Jan 2017

Telotristat Ethyl, A Tryptophan Hydroxylase Inhibitor For The Treatment Of Carcinoid Syndrome, Matthew H. Kulke, Dieter Hörsch, Martyn E. Caplin, Lowell B. Anthony, Emily Bergsland, Kjell Öberg, Staffan Welin, Richard R. P. Warner, Catherine Lombard-Bohas, Pamela L. Kunz, Enrique Grande, Juan W. Valle, Douglas Fleming, Pablo Lapuerta, Phillip Banks, Shanna Jackson, Brian Zambrowicz, Arthur T. Sands, Marianne Pavel

Internal Medicine Faculty Publications

Purpose

Preliminary studies suggested that telotristat ethyl, a tryptophan hydroxylase inhibitor, reduces bowel movement (BM) frequency in patients with carcinoid syndrome. This placebo-controlled phase III study evaluated telotristat ethyl in this setting.

Patients and Methods

Patients (N = 135) experiencing four or more BMs per day despite stable-dose somatostatin analog therapy received (1:1:1) placebo, telotristat ethyl 250 mg, or telotristat ethyl 500 mg three times per day orally during a 12-week double-blind treatment period. The primary end point was change from baseline in BM frequency. In an open-label extension, 115 patients subsequently received telotristat ethyl 500 mg.

Results

Estimated differences …


Retention In Continuous Care And Sustained Viral Suppression: Examining The Association Among Individuals Living With Hiv, Timothy N. Crawford, Alice C. Thornton Jan 2017

Retention In Continuous Care And Sustained Viral Suppression: Examining The Association Among Individuals Living With Hiv, Timothy N. Crawford, Alice C. Thornton

Internal Medicine Faculty Publications

Objectives: To examine the relationship between retention in continuous care and sustained viral suppression.

Methods: The authors retrospectively followed 653 persons who were virally suppressed and seeking care at an infectious disease clinic in Kentucky for an average of 6 years to determine the rates of retention in medical care (≥2 visits separated by ≥3 months within a 12-month period) and sustained viral suppression (<400 copies/mL). A generalized linear mixed model was used to determine an association between retention and suppression over time.

Results: Approximately 61% of the study population were retained in continuous care and 75% had sustained viral suppression for all patient-years. Persons retained in care were 3 times the odds of sustaining viral suppression over …


Using Low-Dose Radiation To Potentiate The Effect Of Induction Chemotherapy In Head And Neck Cancer: Results Of A Prospective Phase 2 Trial, Susanne M. Arnold, Mahesh Kudrimoti, Emily V. Dressler, John F. Gleason, Natalie L. Silver, William F. Regine, Joseph Valentino Oct 2016

Using Low-Dose Radiation To Potentiate The Effect Of Induction Chemotherapy In Head And Neck Cancer: Results Of A Prospective Phase 2 Trial, Susanne M. Arnold, Mahesh Kudrimoti, Emily V. Dressler, John F. Gleason, Natalie L. Silver, William F. Regine, Joseph Valentino

Internal Medicine Faculty Publications

Purpose: Low-dose fractionated radiation therapy (LDFRT) induces effective cell killing through hyperradiation sensitivity and potentiates effects of chemotherapy. We report our second investigation of LDFRT as a potentiator of the chemotherapeutic effect of induction carboplatin and paclitaxel in locally advanced squamous cell cancer of the head and neck (SCCHN).

Experimental Design: Two cycles of induction therapy were given every 21 days: paclitaxel (75 mg/m2) on days 1, 8, and 15; carboplatin (area under the curve 6) day 1; and LDFRT 50 cGy fractions (2 each on days 1, 2, 8, and 15). Objectives included primary site complete response …


A Case Of Pituitary Abscess Presenting Without A Source Of Infection Or Prior Pituitary Pathology, Derick Adams, Philip A. Kern Aug 2016

A Case Of Pituitary Abscess Presenting Without A Source Of Infection Or Prior Pituitary Pathology, Derick Adams, Philip A. Kern

Internal Medicine Faculty Publications

Pituitary abscess is a relatively uncommon cause of pituitary hormone deficiencies and/or a suprasellar mass. Risk factors for pituitary abscess include prior surgery, irradiation and/or pathology of the suprasellar region as well as underlying infections. We present the case of a 22-year-old female presenting with a spontaneous pituitary abscess in the absence of risk factors described previously. Her initial presentation included headache, bitemporal hemianopia, polyuria, polydipsia and amenorrhoea. Magnetic resonance imaging (MRI) of her pituitary showed a suprasellar mass. As the patient did not have any risk factors for pituitary abscess or symptoms of infection, the diagnosis was not suspected …


Samarium-153-Edtmp (Quadramet®) With Or Without Vaccine In Metastatic Castration-Resistant Prostate Cancer: A Randomized Phase 2 Trial, Christopher R. Heery, Ravi A. Madan, Mark N. Stein, Walter M. Stadler, Robert S. Dipaola, Myrna Rauckhorst, Seth M. Steinberg, Jennifer L. Marté, Clara C. Chen, Italia Grenga, Renee N. Donahue, Caroline Jochems, William L. Dahut, Jeffrey Schlom, James L. Gulley Jul 2016

Samarium-153-Edtmp (Quadramet®) With Or Without Vaccine In Metastatic Castration-Resistant Prostate Cancer: A Randomized Phase 2 Trial, Christopher R. Heery, Ravi A. Madan, Mark N. Stein, Walter M. Stadler, Robert S. Dipaola, Myrna Rauckhorst, Seth M. Steinberg, Jennifer L. Marté, Clara C. Chen, Italia Grenga, Renee N. Donahue, Caroline Jochems, William L. Dahut, Jeffrey Schlom, James L. Gulley

Internal Medicine Faculty Publications

PSA-TRICOM is a therapeutic vaccine in late stage clinical testing in metastatic castration-resistant prostate cancer (mCRPC). Samarium-153-ethylene diamine tetramethylene phosphonate (Sm-153-EDTMP; Quadramet®), a radiopharmaceutical, binds osteoblastic bone lesions and emits beta particles causing local tumor cell destruction. Preclinically, Sm-153-EDTMP alters tumor cell phenotype facilitating immune-mediated killing. This phase 2 multi-center trial randomized patients to Sm-153-EDTMP alone or with PSA-TRICOM vaccine. Eligibility required mCRPC, bone metastases, prior docetaxel and no visceral disease. The primary endpoint was the proportion of patients without radiographic disease progression at 4 months. Secondary endpoints included progression-free survival (PFS), overall survival (OS), and immune responses. …


Dasatinib-Loaded Albumin Nanoparticles Possess Diminished Endothelial Cell Barrier Disruption And Retain Potent Anti-Leukemia Cell Activity, Chunling Dong, Bo Li, Zhenyu Li, Sreerama Shetty, Jian Fu Jul 2016

Dasatinib-Loaded Albumin Nanoparticles Possess Diminished Endothelial Cell Barrier Disruption And Retain Potent Anti-Leukemia Cell Activity, Chunling Dong, Bo Li, Zhenyu Li, Sreerama Shetty, Jian Fu

Internal Medicine Faculty Publications

Dasatinib (DAS), a second-generation tyrosine kinase inhibitor, is highly effective in treating chronic myeloid leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia. However, its clinical use is limited due to serious adverse effects. DAS can disrupt endothelial barrier integrity and increase endothelial permeability which may cause peripheral edema and pleural effusion. Albumin nanoparticles (NPs) as a drug carrier may serve as a useful tool for cell-selective drug delivery to reduce DAS-induced endothelial hyperpermeability and maintain endothelial barrier integrity. In this study, we reported that DAS-loaded NPs exhibited potent anti-leukemia efficacy as DAS alone. Importantly, albumin NPs as a drug carrier markedly …


Early Goal-Directed Therapy In Severe Sepsis And Septic Shock: Insights And Comparisons To Process, Promise, And Arise, H. Bryant Nguyen, Anja Kathrin Jaehne, Namita Jayaprakash, Matthew W. Semler, Sara Hegab, Angel Coz-Yataco, Geneva Tatem, Dhafer Salem, Steven Moore, Kamran Boka, Jasreen Kaur Gill, Jayna Gardner-Gray, Jacqueline Pflaum, Juan Pablo Domecq, Gina Hurst, Justin B Belsky, Raymond Fowkes, Ronald B. Elkin, Steven Q. Simpson, Jay L. Falk, Daniel J. Singer, Emanuel P. Rivers Jul 2016

Early Goal-Directed Therapy In Severe Sepsis And Septic Shock: Insights And Comparisons To Process, Promise, And Arise, H. Bryant Nguyen, Anja Kathrin Jaehne, Namita Jayaprakash, Matthew W. Semler, Sara Hegab, Angel Coz-Yataco, Geneva Tatem, Dhafer Salem, Steven Moore, Kamran Boka, Jasreen Kaur Gill, Jayna Gardner-Gray, Jacqueline Pflaum, Juan Pablo Domecq, Gina Hurst, Justin B Belsky, Raymond Fowkes, Ronald B. Elkin, Steven Q. Simpson, Jay L. Falk, Daniel J. Singer, Emanuel P. Rivers

Internal Medicine Faculty Publications

Prior to 2001 there was no standard for early management of severe sepsis and septic shock in the emergency department. In the presence of standard or usual care, the prevailing mortality was over 40-50 %. In response, a systems-based approach, similar to that in acute myocardial infarction, stroke and trauma, called early goal-directed therapy was compared to standard care and this clinical trial resulted in a significant mortality reduction. Since the publication of that trial, similar outcome benefits have been reported in over 70 observational and randomized controlled studies comprising over 70,000 patients. As a result, early goal-directed therapy was …


Immunoglobulin G4-Related Disease: A Rare Disease With An Unusual Presentation, Muhammad Waqas Khan, Terrance Hadley, Melissa Kesler, Zartash Gul Jul 2016

Immunoglobulin G4-Related Disease: A Rare Disease With An Unusual Presentation, Muhammad Waqas Khan, Terrance Hadley, Melissa Kesler, Zartash Gul

Internal Medicine Faculty Publications

IgG4-RD can also present in the skeletal muscle, mimicking several other diseases. It is unusual for this relatively new classification of diseases to present in the muscles and can be mistakenly diagnosed as other autoimmune diseases rendering a delay in the appropriate management and progression of the disease.


Correlation Of Maximal Inspiratory Pressure To Transdiaphragmatic Twitch Pressure In Intensive Care Unit Patients, Gerald S. Supinski, Philip M. Westgate, Leigh Ann Callahan Mar 2016

Correlation Of Maximal Inspiratory Pressure To Transdiaphragmatic Twitch Pressure In Intensive Care Unit Patients, Gerald S. Supinski, Philip M. Westgate, Leigh Ann Callahan

Internal Medicine Faculty Publications

Background: Respiratory muscle weakness contributes to respiratory failure in ICU patients. Unfortunately, assessment of weakness is difficult since the most objective test, transdiaphragmatic pressure in response to phrenic nerve stimulation (PdiTw), is difficult to perform. While most clinicians utilize maximum inspiratory pressure (Pimax) to assess strength, the relationship of this index to PdiTw has not been evaluated in a large ICU population. The purpose of the present study was to assess both PdiTw and Pimax in ICU patients to determine how these indices correlate with each other, what factors influence these indices, and how well these indices predict outcomes.

Methods: …


Differential Expression Of Pancreatic Protein And Chemosensing Receptor Mrnas In Nkcc1-Null Intestine, Emily M. Bradford, Kanimozhi Vairamani, Gary E. Shull Feb 2016

Differential Expression Of Pancreatic Protein And Chemosensing Receptor Mrnas In Nkcc1-Null Intestine, Emily M. Bradford, Kanimozhi Vairamani, Gary E. Shull

Internal Medicine Faculty Publications

AIM: To investigate the intestinal functions of the NKCC1 Na+-K+-2Cl cotransporter (SLC12a2 gene), differential mRNA expression changes in NKCC1-null intestine were analyzed.

METHODS: Microarray analysis of mRNA from intestines of adult wild-type mice and gene-targeted NKCC1-null mice (n = 6 of each genotype) was performed to identify patterns of differential gene expression changes. Differential expression patterns were further examined by Gene Ontology analysis using the online Gorilla program, and expression changes of selected genes were verified using northern blot analysis and quantitative real time-polymerase chain reaction. Histological staining and immunofluorescence were performed …


Radiation-Induced Breast Cancer: The Question Of Early Breast Cancer Screening In Hodgkin's Lymphoma Survivors, Talal Hilal, David W. Rudy Feb 2016

Radiation-Induced Breast Cancer: The Question Of Early Breast Cancer Screening In Hodgkin's Lymphoma Survivors, Talal Hilal, David W. Rudy

Internal Medicine Faculty Publications

Chest irradiation is associated with numerous early and late complications that arise from ionizing radiation-induced damage to cellular structures within the field of therapy. In patients exposed to chest irradiation at an early age as part of the treatment of childhood cancer, specifically Hodgkin's lymphoma, the increased risk of breast cancer in the long run should be considered. A case of a 35-year-old woman who exposed to chest irradiation as part of the treatment of Hodgkin's lymphoma at the age of 20 years is presented here and serves as a reminder of this somewhat overlooked complication. The article presents the …


High-Altitude Pulmonary Hypertension: An Update On Disease Pathogenesis And Management, Aibek E. Mirrakhimov, Kingman P. Strohl Feb 2016

High-Altitude Pulmonary Hypertension: An Update On Disease Pathogenesis And Management, Aibek E. Mirrakhimov, Kingman P. Strohl

Internal Medicine Faculty Publications

High-altitude pulmonary hypertension (HAPH) affects individuals residing at altitudes of 2,500 meters and higher. Numerous pathogenic variables play a role in disease inception and progression and include low oxygen concentration in inspired air, vasculopathy, and metabolic abnormalities. Since HAPH affects only some people living at high altitude genetic factors play a significant role in its pathogenesis.

The clinical presentation of HAPH is nonspecific and includes fatigue, shortness of breath, cognitive deficits, cough, and in advanced cases hepatosplenomegaly and overt right-sided heart failure. A thorough history is important and should include a search for additional risk factors for lung disease and …


A Combination Of Two Rare Coronary Anomalies Makes It Even Rarer: Right Sided Single Coronary Artery With Dual Left Anterior Descending Artery, Aram Barbaryan, Theodore Addai, Monahar Kola, Muhammad Wajih Raqeem, Sergey Barsamyan, Aibek E. Mirrakhimov Jan 2016

A Combination Of Two Rare Coronary Anomalies Makes It Even Rarer: Right Sided Single Coronary Artery With Dual Left Anterior Descending Artery, Aram Barbaryan, Theodore Addai, Monahar Kola, Muhammad Wajih Raqeem, Sergey Barsamyan, Aibek E. Mirrakhimov

Internal Medicine Faculty Publications

An 82-year-old female with history of hyperlipidemia and hypertension presented to the clinic with chief complaint of nonradiating chest tightness accompanied by exertional dyspnea. Cardiac catheterization showed the absence of left coronary system; the entire coronary system originated from the right aortic sinus as a common trunk which then gave off the right coronary artery and the left main coronary artery. Cardiac catheterization demonstrated also another rare coronary anomaly: dual left anterior descending artery. Patient underwent percutaneous coronary intervention and subsequent multidetector computed tomography angiography confirmed the above angiography findings. Patient was subsequently discharged home on double antiplatelet therapy with …


The Role Of Renal Replacement Therapy In The Management Of Pharmacologic Poisonings, Aibek E. Mirrakhimov, Aram Barbaryan, Adam Gray, Taha Ayach Jan 2016

The Role Of Renal Replacement Therapy In The Management Of Pharmacologic Poisonings, Aibek E. Mirrakhimov, Aram Barbaryan, Adam Gray, Taha Ayach

Internal Medicine Faculty Publications

Pharmacologic toxicities are common and range from mild to life-threatening. The aim of this study is to review and update the data on the role of renal replacement therapy (RRT) in the management of various pharmacologic poisonings. We aim to provide a focused review on the role of RRT in the management of pharmacological toxicities. Relevant publications were searched in MEDLINE with the following search terms alone or in combination: pharmacologic toxicity, hemodialysis, hemofiltration, renal replacement therapy, toxicology, poisonings, critical illness, and intensive care. The studies showed that a pharmacologic substance should meet several prerequisites to be deemed dialyzable. These …


Acute Liver And Renal Failure: A Rare Adverse Effect Exclusive To Intravenous Form Of Amiodarone, Robin Paudel, Prerna Dogra, Saurav Suman, Saurav Acharya, Jyoti Matta Jan 2016

Acute Liver And Renal Failure: A Rare Adverse Effect Exclusive To Intravenous Form Of Amiodarone, Robin Paudel, Prerna Dogra, Saurav Suman, Saurav Acharya, Jyoti Matta

Internal Medicine Faculty Publications

Amiodarone is an antiarrhythmic drug which is highly effective against a wide spectrum of ventricular tachyarrhythmias making it irreplaceable in certain group of patients. We report an unusual case of acute liver and renal failure within 24 hours of initiation of intravenous (IV) amiodarone which resolved after stopping the medication. The mechanism of acute liver and renal toxicity is not clearly known but is believed to be secondary to amiodarone induced (relative) hypotension, idiosyncratic reaction to the drug, and toxicity of the vector that carries the medication, polysorbate-80. In this case review, we discuss the hyperacute drug toxicity caused by …


Telomerase Inhibition By Everolimus Suppresses Smooth Muscle Cell Proliferation And Neointima Formation Through Epigenetic Gene Silencing, Jun Aono, Ernesto Ruiz-Rodriguez, Hua Qing, Hannes M. Findeisen, Karrie L. Jones, Elizabeth B. Heywood, Dennis Bruemmer Jan 2016

Telomerase Inhibition By Everolimus Suppresses Smooth Muscle Cell Proliferation And Neointima Formation Through Epigenetic Gene Silencing, Jun Aono, Ernesto Ruiz-Rodriguez, Hua Qing, Hannes M. Findeisen, Karrie L. Jones, Elizabeth B. Heywood, Dennis Bruemmer

Internal Medicine Faculty Publications

Proliferation of smooth muscle cells (SMCs) during neointima formation is prevented by drug-eluting stents. The replicative capacity of mammalian cells is enhanced by telomerase expression; however, the contribution of telomerase to the proliferative response underlying neointima formation and its potential role as a pharmacological target are unknown. The present study investigated the mechanisms underlying the mitogenic function of telomerase, and tested the hypothesis that everolimus, which is commonly used on drug-eluting stents, suppresses SMC proliferation by targeting telomerase. Inhibition of neointima formation by everolimus was lost in mice overexpressing telomerase reverse transcriptase (TERT), indicating that repression of telomerase confers the …


A Cytosolic Multiprotein Complex Containing P85Α Is Required For Β-Catenin Activation In Colitis And Colitis-Associated Cancer, Tatiana Goretsky, Emily M. Bradford, Hyunji Ryu, Maryam Tahir, Mary Pat Moyer, Tianyan Gao, Linheng Li, Terrence A. Barrett Nov 2015

A Cytosolic Multiprotein Complex Containing P85Α Is Required For Β-Catenin Activation In Colitis And Colitis-Associated Cancer, Tatiana Goretsky, Emily M. Bradford, Hyunji Ryu, Maryam Tahir, Mary Pat Moyer, Tianyan Gao, Linheng Li, Terrence A. Barrett

Internal Medicine Faculty Publications

Wnt/β-catenin signaling is required for crypt structure maintenance. We previously observed nuclear accumulation of Ser-552 phosphorylated β-catenin (pβ-CatSer-552) in intestinal epithelial cells (IEC) during colitis and colitis-associated cancer. Data here delineate a novel multiprotein cytosolic complex (MCC) involved in β-catenin signaling in the intestine. The MCC contains p85α, the class IA subunit of PI3K, along with β-catenin, 14-3-3ζ, Akt, and p110α. MCC levels in IEC increase in colitis and colitis-associated cancer patients. IEC-specific p85α-deficient (p85ΔIEC) mice develop more severe dextran sodium …


A Prospective Analysis Of Factors Associated With Decreased Physical Activity In Patients With Cirrhosis Undergoing Transplant Evaluation, Anna Christina Dela Cruz, Valery Vilchez, Sooyeon Kim, Benjamin Barnes, Abhishek Ravinuthala, Anthony Zanni, Roberto Galuppo, Achuthan Sourianarayanane, Trushar Patel, Erin Colleen Maynard, Malay B. Shah, Michael F. Daily, Timothy L. Uhl, Karyn A. Esser, Roberto Gedaly Nov 2015

A Prospective Analysis Of Factors Associated With Decreased Physical Activity In Patients With Cirrhosis Undergoing Transplant Evaluation, Anna Christina Dela Cruz, Valery Vilchez, Sooyeon Kim, Benjamin Barnes, Abhishek Ravinuthala, Anthony Zanni, Roberto Galuppo, Achuthan Sourianarayanane, Trushar Patel, Erin Colleen Maynard, Malay B. Shah, Michael F. Daily, Timothy L. Uhl, Karyn A. Esser, Roberto Gedaly

Internal Medicine Faculty Publications

BACKGROUND: Physical activity has been associated with improved recovery time after transplantation. Handgrip strength has been related to post-transplant outcomes.

AIM: To evaluate predictors of physical activity and grip strength in cirrhotic patients undergoing liver transplant evaluation.

METHODS: Single center, prospective analysis.

RESULTS: A hundred patients were evaluated (54% male, mean age 53 ± 9). Common etiologies of liver disease were non-alcoholic hepatitis (27%), hepatitis C (22%), and alcoholic liver disease (21%). Mean MELD score was 13.5. Forty one percent had a history of smoking. Ninety-three patients completed the International Physical Activity Questionnaire. The median total physical activity score of …


Coffee: A Selected Overview Of Beneficial Or Harmful Effects On The Cardiovascular System?, Thomas F. Whayne Jr. Jan 2015

Coffee: A Selected Overview Of Beneficial Or Harmful Effects On The Cardiovascular System?, Thomas F. Whayne Jr.

Internal Medicine Faculty Publications

With a history that began in 800 A.D., coffee is the most popular drink known and as a result, the issues regarding its physiologic effects deserve attention. Maintaining alertness is a well-known benefit and in addition, the cardiovascular (CV) effects of the active compounds, which include polyphenols and caffeine, must be considered. Genetics are relevant and where slow caffeine metabolism is inherent, the risk of nonfatal myocardial (MI) has been shown to be increased. Overall risk for coronary heart disease (CHD) is not supported and unless there is excessive intake, congestive heart failure (CHF) is not adversely affected; in moderation, …


Pioglitazone Treatment Reduces Adipose Tissue Inflammation Through Reduction Of Mast Cell And Macrophage Number And By Improving Vascularity, Michael L. Spencer, Lin Yang, Akosua Adu, Brian S. Finlin, Beibei Zhu, Lindsey Rae Shipp, Neda Rasouli, Charlotte A. Peterson, Philip A. Kern Jul 2014

Pioglitazone Treatment Reduces Adipose Tissue Inflammation Through Reduction Of Mast Cell And Macrophage Number And By Improving Vascularity, Michael L. Spencer, Lin Yang, Akosua Adu, Brian S. Finlin, Beibei Zhu, Lindsey Rae Shipp, Neda Rasouli, Charlotte A. Peterson, Philip A. Kern

Internal Medicine Faculty Publications

Context and Objective

Adipose tissue in insulin resistant subjects contains inflammatory cells and extracellular matrix components. This study examined adipose pathology of insulin resistant subjects who were treated with pioglitazone or fish oil.

Design, Setting and Participants

Adipose biopsies were examined from nine insulin resistant subjects before/after treatment with pioglitazone 45 mg/day for 12 weeks and also from 19 subjects who were treated with fish oil (1,860 mg EPA, 1,500 mg DHA daily). These studies were performed in a clinical research center setting.

Results

Pioglitazone treatment increased the cross-sectional area of adipocytes by 18% (p = 0.01), and also increased …


Phosphoinositides: Minor Lipids Make A Major Impact On Photoreceptor Cell Functions, Raju V. S. Rajala, Ammaji Rajala, Andrew J. Morris, Robert E. Anderson Jun 2014

Phosphoinositides: Minor Lipids Make A Major Impact On Photoreceptor Cell Functions, Raju V. S. Rajala, Ammaji Rajala, Andrew J. Morris, Robert E. Anderson

Internal Medicine Faculty Publications

Activation of the phosphoinositide (PI) cycle generates the second messengers that control various aspects of cellular signaling. We have previously shown that two PI cycle enzymes, type II phosphatidylinositol 5-phosphate 4-kinase (PIPK IIα) and phosphoinositide 3-kinase (PI3K), are activated through light stimulation. In our earlier studies, we measured enzyme activities, instead of directly measuring the products, due to lack of sensitive analytical techniques. Cells have very low levels of PIs, compared to other lipids, so special techniques and sensitive analytical instruments are necessary for their identification and quantification. There are also other considerations, such as different responses in different cell …


Metastatic Angiosarcoma And Kasabach-Merritt Syndrome, Suleiman Massarweh, Aun Munis, Rouzan Karabakhtsian, Edward Romond, Jessica Moss Jun 2014

Metastatic Angiosarcoma And Kasabach-Merritt Syndrome, Suleiman Massarweh, Aun Munis, Rouzan Karabakhtsian, Edward Romond, Jessica Moss

Internal Medicine Faculty Publications

Angiosarcomas are exceedingly rare tumors that are often difficult to diagnose. Exceptionally unusual is the presentation of these tumors with Kasabach-Merritt Syndrome, a curious form of intratumoral coagulation that can be impossible to distinguish from intravascular coagulation, which is more common. Instant recognition of this clinical association can help making a prompt diagnosis and timely initiation of therapy.


Prognosis Of Differentiated Thyroid Cancer In Relation To Serum Thyrotropin And Thyroglobulin Antibody Status At Time Of Diagnosis, Donald S. A. Mcleod, David S. Cooper, Paul W. Ladenson, Kenneth B. Ain, James D. Brierley, Henry G. Fein, Bryan R. Haugen, Jacqueline Jonklaas, James Magner, Douglas S. Ross, Monica C. Skarulis, David L. Steward, Harry R. Maxon, Steven I. Sherman Jan 2014

Prognosis Of Differentiated Thyroid Cancer In Relation To Serum Thyrotropin And Thyroglobulin Antibody Status At Time Of Diagnosis, Donald S. A. Mcleod, David S. Cooper, Paul W. Ladenson, Kenneth B. Ain, James D. Brierley, Henry G. Fein, Bryan R. Haugen, Jacqueline Jonklaas, James Magner, Douglas S. Ross, Monica C. Skarulis, David L. Steward, Harry R. Maxon, Steven I. Sherman

Internal Medicine Faculty Publications

BACKGROUND: Serum thyrotropin (TSH) concentration and thyroid autoimmunity may be of prognostic importance in differentiated thyroid cancer (DTC). Preoperative serum TSH level has been associated with higher DTC stage in cross-sectional studies; data are contradictory on the significance of thyroid autoimmunity at the time of diagnosis.

OBJECTIVE: We sought to assess whether preoperative serum TSH and perioperative antithyroglobulin antibodies (TgAb) were associated with thyroid cancer stage and outcome in DTC patients followed by the National Thyroid Cancer Treatment Cooperative Study, a large multicenter thyroid cancer registry.

METHODS: Patients registered after 1996 with available preoperative serum TSH (n=617; the TSH cohort) …


New Oral Anticoagulants Are Not Superior To Warfarin In Secondary Prevention Of Stroke Or Transient Ischemic Attacks, But Lower The Risk Of Intracranial Bleeding: Insights From A Meta-Analysis And Indirect Treatment Comparisons, Partha Sardar, Saurav Chatterjee, Wen-Chih Wu, Edgar Lichstein, Joydeep Ghosh, Shamik Aikat, Debabrata Mukherjee Oct 2013

New Oral Anticoagulants Are Not Superior To Warfarin In Secondary Prevention Of Stroke Or Transient Ischemic Attacks, But Lower The Risk Of Intracranial Bleeding: Insights From A Meta-Analysis And Indirect Treatment Comparisons, Partha Sardar, Saurav Chatterjee, Wen-Chih Wu, Edgar Lichstein, Joydeep Ghosh, Shamik Aikat, Debabrata Mukherjee

Internal Medicine Faculty Publications

PURPOSE: Patients with Atrial Fibrillation (AF) and prior stroke are classified as high risk in all risk stratification schemes. A systematic review and meta-analysis was performed to compare the efficacy and safety of New Oral Anticoagulants (NOACs) to warfarin in patients with AF and previous stroke or transient ischemic attack (TIA).

METHODS: Three randomized controlled trials (RCTs), including total 14527 patients, comparing NOACs (apixaban, dabigatran and rivaroxaban) with warfarin were included in the analysis. Primary efficacy endpoint was ischemic stroke, and primary safety endpoint was intracranial bleeding. Random-effects models were used to pool efficacy and safety data across RCTs. RevMan …


Atypical Clinical And Diagnostic Features In Ménétrier's Disease In A Child, Michael Chung, Jaime Pittenger, Deborah Flomenhoft, Jeffrey Bennett, Eun Young Lee, Harohalli Shashidhar Sep 2011

Atypical Clinical And Diagnostic Features In Ménétrier's Disease In A Child, Michael Chung, Jaime Pittenger, Deborah Flomenhoft, Jeffrey Bennett, Eun Young Lee, Harohalli Shashidhar

Internal Medicine Faculty Publications

Ménétrier's disease is one of the rarest protein-losing gastropathies in childhood. It is characterized clinically by non-specific gastrointestinal symptoms and edema, biochemically by hypoalbuminemia, and pathologically by enlarged gastric folds. In adults, this disease can be devastating with significant morbidity and mortality. In childhood, it is a self-limiting, transient and benign illness. Its treatment is largely supportive with total parenteral nutrition (TPN) while oral intake is encouraged. Acute onset of vomiting in healthy school age children can be initially explained by acute viral gastroenteritis. However, persistent vomiting associated with hematemesis and severe abdominal pain should warrant further work-up. This case …