Internal Medicine Commons^™

Increasing Use Of Allogeneic Hematopoietic Cell Transplantation In Patients Aged 70 Years And Older In The United States, Lori Muffly, Marcelo C. Pasquini, Michael Martens, Ruta Brazauskas, Xiaochun Zhu, Kehinde Adekola, Mahmoud Aljurf, Karen K. Ballen, Ashish Bajel, Frederic Baron, Minoo Battiwalla, Amer Beitinjaneh, Jean-Yves Cahn, Mathew Carabasi, Yi-Bin Chen, Saurabh Chhabra, Stefan Ciurea, Edward Copelan, Anita D'Souza, John Edwards, James Foran, Cesar O. Freytes, Henry C. Fung, Robert Peter Gale, Sergio Giralt, Shahrukh K. Hashmi, Gerhard C. Hildebrandt, Vincent Ho, Ann Jakubowski, Hillard Lazarus

Internal Medicine Faculty Publications

In this study, we evaluated trends and outcomes of allogeneic hematopoietic cell transplantation (HCT) in adults ≥ 70 years with hematologic malignancies across the United States. Adults ≥ 70 years with a hematologic malignancy undergoing first allogeneic HCT in the United States between 2000 and 2013 and reported to the Center for International Blood and Marrow Transplant Research were eligible. Transplant utilization and transplant outcomes, including overall survival (OS), progression-free survival (PFS), and transplant-related mortality (TRM) were studied. One thousand one hundred and six patients ≥ 70 years underwent HCT across 103 transplant centers. The number and proportion of allografts …

Retrospective Analysis To Describe Associations Between Tumor Necrosis Factor Alpha Inhibitors And Copd-Related Hospitalizations, Neil A. Accortt, James B. Chung, Machaon Bonafede, Brendan L. Limone, David M. Mannino

Preventive Medicine and Environmental Health Faculty Publications

Background: Limited information exists on the impact of tumor necrosis factor inhibition on COPD exacerbations. This retrospective study characterized this impact among COPD patients with underlying autoimmune conditions, exposed to tumor necrosis factor inhibitors (TNFi) and/or non-biologic disease-modifying antirheumatic drugs (DMARDs).
Patients and methods: Adult COPD patients with ≥1 diagnosis for rheumatoid arthritis (RA), psoriasis (PsO), psoriatic arthritis (PsA), or ankylosing spondylitis (AS) before or within 6 months following the index COPD diagnosis were identified from the Truven Health MarketScan^® databases. Patients were required to have a second claim for RA, PsO, PsA, AS, or DMARD use (biologic or …

Demographics, Patterns Of Care, And Survival In Pediatric Medulloblastoma, Emily V. Dressler, Therese A. Dolecek, Meng Liu, John L. Villano

Internal Medicine Faculty Publications

We evaluated the American College of Surgeon’s National Cancer Data Base (NCDB) to describe current hospital-based epidemiologic frequency, survival, and patterns of care of pediatric medulloblastoma. We analyzed NCDB 1998–2011 data on medulloblastoma for children ages 0–19 years using logistic and poisson regression, Kaplan–Meier survival estimates, and Cox proportional hazards models. 3647 cases of medulloblastoma in those aged 0–19 years were identified. Chemotherapy was received by 79 and 74% received radiation, with 65% receiving both therapies. Those who received radiation were more likely to be older than four, while those who received chemotherapy were more likely to be age four …

Gastrointestinal Stromal Tumor Induced Hypercalcemia, Aram Barbaryan, Stefania Bailuc, Padma Poddutoori, Aida Richardson, Aibek E. Mirrakhimov

Internal Medicine Faculty Publications

Hypercalcemia in patients with cancer is a common laboratory finding affecting up to 44% of that patient population. 1,25-Dihydroxyvitamin D₃ mediated hypercalcemia is one of the rare mechanisms of this endocrine emergency in cancer patients. It is even rarer for solid organ neoplasms to present with hypercalcemia mediated through the production of 1,25-dihydroxyvitamin D₃. We report a case of a 77-year-old female who presented to the hospital with hypercalcemia and later was found to have metastatic gastrointestinal stromal tumor. There have been only 5 cases of gastrointestinal stromal tumor described in literature resulting in hypercalcemia. In our …

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

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, …

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 …

Multiorgan Chronic Inflammatory Hepatobiliary Pancreatic Murine Model Deficient In Tumor Necrosis Factor Receptors 1 And 2, Helieh S. Oz

Physiology Faculty Publications

AIM: To provoke persistent/chronic multiorgan inflammatory response and to contribute to stones formation followed by fibrosis in hepatobiliary and pancreatic tissues.

METHODS: Tumor necrosis factor receptors 1 and 2 (TNFR1/R2) deficient mice reared in-house were given dibutyltin dichloride (DBTC) twice within 10 d by oral gavage delivery. Sham control animals received vehicle treatment and naïve animals remained untreated throughout the study. Animals were monitored daily for symptoms of pain and discomfort. The abdominal and hindpaw hypersensitivity were assessed with von Frey microfilaments. Exploratory behaviors were recorded at the baseline, after initiation of treatment, and before study termination. Histopathological …

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 …

Selective Induced Altered Coccidians To Immunize And Prevent Enteritis, Helieh S. Oz

Physiology Faculty Publications

Microbiomic flora in digestive tract is pivotal to the state of our health and disease. Antibiotics affect GI, control composition of microbiome, and shift equilibrium from health into disease status. Coccidiosis causes gastrointestinal inflammation. Antibiotic additives contaminate animal products and enter food chain, consumed by humans with possible allergic, antibiotic resistance and enigmatic side effects. Purposed study induced nonpathogenic, immunogenic organisms to protect against disease and abolish antibiotics’ use in food animals and side effects in man. Diverse species of Coccidia were used as model. Immature organisms were treated with serial purification procedure prior to developmental stages to obtain altered …

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.

Transcriptional Repression Of Sodium-Iodide Symporter In Thyroid Carcinoma, Kenneth B. Ain, Wei Li

Internal Medicine Faculty Patents

The present disclosure relates to a sodium iodide symporter (NIS)-repressor binding site (NRBS) consisting of a DNA molecule spanning from −645 to −605 nucleotides (SEQ ID NO:4) or from −648 to −620 nucleotides (SEQ ID NO:5) upstream from the translation start site of human NIS gene. The disclosure further relates to a method of restoring iodide transport to a human thyroid carcinoma cell, including: the steps of: i) contacting the cell expressing and forming a NIS repressor protein complex capable of binding to the NRBS of the disclosure with a modulator of said complex, and ii) administering to the cell …

Region 11 Meld Na Exception Prospective Study, Robert A. Fisher, Douglas M. Heuman, Ann M. Harper, Martha K. Behnke, Alastair D. Smith, Mark W. Russo, Steven Zacks, John W. Mcgillicuddy, James Eason, Michael K. Porayko, Patrick Northup, Michael R. Marvin, Johnathan Hundley, Satheesh Nair

Surgery Faculty Publications

Introduction. Hyponatremia complicates cirrhosis and predicts short term mortality, including adverse outcomes before and after liver transplantation.

Material and methods. From April 1, 2008, through April 2, 2010, all adult candidates for primary liver transplantation with cirrhosis, listed in Region 11 with hyponatremia, were eligible for sodium (Na) exception.

Results. Patients with serum sodium (SNa) less than 130 mg/dL, measured two weeks apart and within 30 days of Model for End Stage Liver Disease (MELD) exception request, were given preapproved Na exception. MELD Na was calculated [MELD + 1.59 (135-SNa/30 days)]. MELD Na was capped at 22, and subject to …

Compositions And Methods For Detecting And Treating Atherosclerosis, Nancy R. Webb, Frederick C. De Beer

Internal Medicine Faculty Patents

Methods for detecting atherosclerotic plaque and quantifying the amount of Group V sPLA₂ in plasma are disclosed. These methods can be used to assess the risk of cardiovascular pathology in a patient.

Sr-Bi Protects Against Endotoxemia In Mice Through Its Roles In Glucocorticoid Production And Hepatic Clearance, Lei Cai, Ailing Ji, Frederick C. De Beer, Lisa R. Tannock, Deneys R. Van Der Westhuyzen

Internal Medicine Faculty Publications

Septic shock results from an uncontrolled inflammatory response, mediated primarily by LPS. Cholesterol transport plays an important role in the host response to LPS, as LPS is neutralized by lipoproteins and adrenal cholesterol uptake is required for antiinflammatory glucocorticoid synthesis. In this study, we show that scavenger receptor B-I (SR-BI), an HDL receptor that mediates HDL cholesterol ester uptake into cells, is required for the normal antiinflammatory response to LPS-induced endotoxic shock. Despite elevated plasma HDL levels, SR-BI–null mice displayed an uncontrollable inflammatory cytokine response and a markedly higher lethality rate than control mice in response to LPS. In addition, …

Iodine Uptake Restoration In Thyroid Cancer, Kenneth B. Ain, Gopalakrishnan Venkataraman

Internal Medicine Faculty Patents

A method of expressing a tumor specific therapeutic response element in a cancerous cell is disclosed in which the response element was previously blocked from expression. The method comprises the step of administering an unblocking agent to the cancerous cell harboring a gene encoding the response element, thereby resulting in the expression of the response element.

Methods And Apparatus For In Vivo Identification And Characterization Of Vulnerable Atherosclerotic Plaques, Pedro Moreno, Robert A. Lodder, William O'Connor, James E. Muller

Internal Medicine Faculty Patents

Methods and apparatus for analyzing the chemical composition of vulnerable plaques with an intravascular catheter having a near-infrared light source, a fiber-optic probe, a mechanism for directing the light from the light source into a blood vessel, and detectors for detecting light reflected or scattered by the tissue. The light source may be a tunable laser, and may transmit an incident beam having a wavelength ranging from 1400 to 4100 nm. A computer may be included to receive and process the spectral data in the analysis of the vulnerable plaques. A catheter system may be configured to provide near-IR spectrometric …

Methods To Impair Hematologic Cancer Progenitor Cells And Compounds Related Thereto, Craig Jordan

Internal Medicine Faculty Patents

Primitive or progenitor hematologic cancer cells have been implicated in the early stages and development of leukemia and malignant lymphoproliferative disorders, including acute myelogenous leukemia (AML), chronic myelogenous leukemia (CML) and chronic lymphoid leukemia (CLL). Interleukin-3 receptor alpha chain (IL-3Rα or CD123) is strongly expressed on progenitor hematologic cancer cells, but is virtually undetectable on normal bone marrow cells. The present invention provides methods of impairing progenitor hematologic cancer (e.g., leukemia and lymphomic) cells by selectively targeting cells expressing CD123. These methods are useful in the detection and treatment of leukemias and malignant lymphoproliferative disorders. Also provided are compounds useful …

Flexible Recording/High Energy Electrode Catheter With Anchor For Ablation Of Atrial Flutter By Radio Frequency Energy, Chien-Suu Kuo, John G. Gurley

Internal Medicine Faculty Patents

An electrode catheter is provided having a predetermined flexibility throughout the entire length or at least at the contact portion, such as the electrode region, to allow for the molding of the contact portion such that it conforms to the shape of the heart at a preselected desired target area, such as the isthmus between the inlet of inferior vena cava and posterior tricuspid annulus. The catheter also includes a guiding sheath that is preferably semirigid and may be pre-shaped with at least one bend or angulation to assist in molding to ensure that the electrode region overlies the desired …

Combination Anti-Leukimic Therapy By Utilizing Suramin And Biologic Response Modifiers, Michael A. Doukas

Internal Medicine Faculty Patents

A method of treating leukemia which includes administering an effective amount of composition comprising suramin and a biological response modifier, wherein the suramin and the biological response modifier show synergistic or additive anti-leukemic activity. A pharmaceutical composition is also disclosed.

Metabolically Inactive Insulin Analog Prevents Type I Diabetes In Prediabetic Nod Mice, Dennis G. Karounos, J. Scott Bryson, D. A. Cohen

Internal Medicine Faculty Publications

The purpose of this study was to determine the relative importance of the metabolic effects of insulin for diabetes prevention by administering insulin or an inactive insulin analog by daily subcutaneous injections to prediabetic mice. A recombinant monomeric human insulin analog, which does not bind to the insulin receptor as a consequence of an alteration of a single amino acid at position 25 of the B chain, was shown to be equally effective at diabetes prevention as was intact insulin. In contrast to native insulin, the insulin analog did not cause hypoglycemia after subcutaneous injection. The insulin analog, however, protected …

Plasma Native And Peptidase-Derivable Met-Enkephalin Responses To Restraint Stress In Rats. Adaptation To Repeated Restraint, K. Pierzchala, G. R. Van Loon

Internal Medicine Faculty Publications

Met-enkephalin and related proenkephalin A-derived peptides circulate in plasma at picomolar concentration as free, native pentapeptide and at nanomolar concentration in cryptic forms. We have optimized conditions for measurement of immunoreactive Met-enkephalin in plasma and for generation by trypsin and carboxypeptidase B of much greater amounts of total peptidase-derivable Met-enkephalin in plasma of rats, dogs, and humans. Free Met-enkephalin (11 pM) is constituted by native pentapeptide and its sulfoxide. Characterization of plasma total Met-enkephalin derived by peptidic hydrolysis revealed a small amount (38 pM) of Met-enkephalin associated with peptides of molecular mass less than 30,000 D, and probably derived from …

Simple Capsule Pneumograph, Steve S. Kraman

Internal Medicine Faculty Patents

A capsule pneumograph includes an electret microphone connected to a capsule chestpiece attached to a sleeping subject. The output of the microphone is connected to the input of a recorder or monitor in order to provide a system for the detection of respiratory movements in subjects during polysomnographic sleep monitoring. A tube connecting the capsule chestpiece to the microphone functions as a low pass filter to pass only low frequency signals in the range of respiratory movements from the chestpiece to the microphone.