Medicine and Health Sciences Commons^™

Project Achieve – Using Implementation Research To Guide The Evaluation Of Transitional Care Effectiveness, Jing Li, Jane Brock, Brian Jack, Brian Mittman, Mary Naylor, Joann Sorra, Glen P. Mays, Mark V. Williams, Arnold J. Stromberg, Heather M. Bush, Allison Scott, Robert Duff, Emily R. Clear, Hannah Keeler, Project Achieve

Internal Medicine Faculty Publications

Background: Poorly managed hospital discharges and care transitions between health care facilities can cause poor outcomes for both patients and their caregivers. Unfortunately, the usual approach to health care delivery does not support continuity and coordination across the settings of hospital, doctors’ offices, home or nursing homes. Though complex efforts with multiple components can improve patient outcomes and reduce 30-day readmissions, research has not identified which components are necessary. Also we do not know how delivery of core components may need to be adjusted based on patient, caregiver, setting or characteristics of the community, or how system redesign can be …

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 …

Differences In Rhodococcus Equi Infections Based On Immune Status And Antibiotic Susceptibility Of Clinical Isolates In A Case Series Of 12 Patients And Cases In The Literature, Praveen Gundelly, Yasuhiro Suzuki, Julie A. Ribes, Alice C. Thornton

Internal Medicine Faculty Publications

Rhodococcus equi is an unusual zoonotic pathogen that can cause life-threatening diseases in susceptible hosts. Twelve patients with R. equi infection in Kentucky were compared to 137 cases reported in the literature. Although lungs were the primary sites of infection in immunocompromised patients, extrapulmonary involvement only was more common in immunocompetent patients (P > 0.0001). Mortality in R. equi-infected HIV patients was lower in the HAART era (8%) than in pre-HAART era (56%) (P > 0.0001), suggesting that HAART improves prognosis in these patients. Most (85–100%) of clinical isolates were susceptible to vancomycin, clarithromycin, rifampin, aminoglycosides, ciprofloxacin, and imipenem. …

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-Cat^Ser-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 (p85^ΔIEC) mice develop more severe dextran sodium …

A Multicenter, Open-Label, Controlled Phase Ii Study To Evaluate Safety And Immunogenicity Of Mva Smallpox Vaccine (Imvamune) In 18-40 Year Old Subjects With Diagnosed Atopic Dermatitis, Richard N. Greenberg, Maria Yadira Hurley, Dinh V. Dinh, Serena Mraz, Javier Gomez Vera, Dorothea Von Bredow, Alfred Von Krempelhuber, Siegfried Roesch, Garth Virgin, Nathaly Arndtz-Wiedemann, Thomas Peter Meyer, Darja Schmidt, Richard Nichols, Philip Young, Paul Chaplin

Internal Medicine Faculty Publications

BACKGROUND: Replicating smallpox vaccines can cause severe complications in individuals with atopic dermatitis (AD). Prior studies evaluating Modified Vaccinia Ankara virus (MVA), a non-replicating vaccine in humans, showed a favorable safety and immunogenicity profile in healthy volunteers.

OBJECTIVE: This Phase II study compared the safety and immunogenicity of MVA enrolling groups of 350 subjects with AD (SCORAD ≤ 30) and 282 healthy subjects.

METHODS: Subjects were vaccinated twice with MVA, each dose given subcutaneously 4 weeks apart. Adverse events, cardiac parameters, and the development of vaccinia virus humoral immune responses were monitored.

RESULTS: The overall safety …

Current And Emerging Treatment Options For Anca-Associated Vasculitis: Potential Role Of Belimumab And Other Baff/April Targeting Agents, Aleksander Lenert, Petar Lenert

Internal Medicine Faculty Publications

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) comprises several clinical entities with diverse clinical presentations, outcomes, and nonunifying pathogenesis. AAV has a clear potential for relapses, and shows unpredictable response to treatment. Cyclophosphamide-based therapies have remained the hallmark of induction therapy protocols for more than four decades. Recently, B-cell depleting therapy with the anti-CD20 antibody rituximab has proved beneficial in AAV, leading to Food and Drug Administration approval of rituximab in combination with corticosteroids for the treatment of AAV in adults. Rituximab for ANCA-associated vasculitis and other clinical trials provided clear evidence that rituximab was not inferior to cyclophosphamide for remission …

A Word Of Caution Regarding Proposed Benefits Of Albumin From Albios: A Dose Of Healthy Skepticism, Alexander H. Flannery, Sean P. Kane, Angel O. Coz-Yataco

Internal Medicine Faculty Publications

No abstract provided.

Reduction In Overall Occurrences Of Ischemic Events With Vorapaxar: Results From Tracer, Harvey D. White, Zhen Huang, Pierluigi Tricoci, Frans Van De Werf, Lars Wallentin, Yuliya Lokhnygina, David J. Moliterno, Philip E. Aylward, Kenneth W. Mahaffey, Paul W. Armstrong

Internal Medicine Faculty Publications

BACKGROUND: Clinical trials traditionally use time-to-first-event analysis embedded within the composite endpoint of cardiovascular death (CVD), myocardial infarction (MI), or stroke. However, many patients have >1 event, and this approach may not reflect overall experience. We addressed this by analyzing all cardiovascular events in TRACER.

METHODS AND RESULTS: TRACER randomized 12 944 patients with non-ST-segment elevation acute coronary syndromes to placebo or to protease-activated receptor 1 antagonist vorapaxar with a median follow-up of 502 days (interquartile range, 349 to 667). Analysis of vorapaxar's effect on recurrent CVD, MI, or stroke was prespecified using the Wei, Lin, and Weissfeld approach. Vorapaxar …

Fundamentals Of Lung Auscultation, Abraham Bohadana, Gabriel Izbicki, Steve S. Kraman

Internal Medicine Faculty Publications

Chest auscultation has long been considered a useful part of the physical examination, going back to the time of Hippocrates. However, it did not become a widespread practice until the invention of the stethoscope by René Laënnec in 1816, which made the practice convenient and hygienic.1 During the second half of the 20th century, technological advances in ultrasonography, radiographic computed tomography (CT), and magnetic resonance imaging shifted interest from lung auscultation to imaging studies, which can detect lung disease with an accuracy never previously imagined. However, modern computer-assisted techniques have also allowed precise recording and analysis of lung sounds, prompting …

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

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 …

Autophagy Is Involved In Oligodendroglial Precursor-Mediated Clearance Of Amyloid Peptide, Wenxia Li, Yifen Tang, Zhiqin Fan, Ya Meng, Guang Yang, Jia Luo, Zun-Ji Ke

Internal Medicine Faculty Publications

BACKGROUND: Accumulation of β-amyloid peptides is an important hallmark of Alzheimer's disease (AD). Tremendous efforts have been directed to elucidate the mechanisms of β-amyloid peptides degradation and develop strategies to remove β-amyloid accumulation. In this study, we demonstrated that a subpopulation of oligodendroglial precursor cells, also called NG2 cells, were a new cell type that can clear β-amyloid peptides in the AD transgene mice and in NG2 cell line.

RESULTS: NG2 cells were recruited and clustered around the amyloid plaque in the APPswe/PS1dE9 mice, which is Alzheimer's disease mouse model. In vitro, NG2 cell line and primary NG2 cells engulfed …

Bioactive Lipids And Cationic Antimicrobial Peptides As New Potential Regulators For Trafficking Of Bone Marrow-Derived Stem Cells In Patients With Acute Myocardial Infarction, Anush V. Karapetyan, Yuri M. Klyachkin, Samy Selim, Manjula Sunkara, Khaled M. Ziada, Donald A. Cohen, Ewa K. Zuba-Surma, Janina Ratajczak, Susan S. Smyth, Mariusz Z. Ratajczak, Andrew J. Morris, Ahmed Abdel-Latif

Internal Medicine Faculty Publications

Acute myocardial infarction (AMI) triggers mobilization of stem cells from bone marrow (BM) into peripheral blood (PB). Based on our observation that the bioactive sphingophospholipids, sphingosine-1 phosphate (S1P), and ceramide-1 phosphate (C1P) regulate trafficking of hematopoietic stem cells (HSCs), we explored whether they also direct trafficking of non-hematopoietic stem cells (non-HSCs). We detected a 3–6-fold increase in circulating CD34+, CD133+, and CXCR4+ lineage-negative (Lin−)/CD45− cells that are enriched in non-HSCs [including endothelial progenitors (EPCs) and very small embryonic-like stem cells (VSELs)] in PB from AMI patients (P<0.05 vs. controls). Concurrently, we measured a 3-fold increase in S1P and C1P levels in plasma from AMI patients. At the same time, plasma obtained at hospital admission and 6 h after AMI strongly chemoattracted human BM-derived CD34+/Lin− and CXCR4+/Lin− cells in Transwell chemotaxis assays. This effect of plasma was blunted after depletion of S1P level by charcoal stripping and was further inhibited by the specific S1P1 receptor antagonist such as W146 and VPC23019. We also noted that the expression of S1P receptor 1 (S1P1), which is dominant in naïve BM, is reduced after the exposure to S1P at concentrations similar to the plasma S1P levels in patients with AMI, thus influencing the role of S1P in homing to the injured myocardium. Therefore, we examined mechanisms, other than bioactive lipids, that may contribute to the homing of BM non-HSCs to the infarcted myocardium. Hypoxic cardiac tissue increases the expression of cathelicidin and β-2 defensin, which could explain why PB cells isolated from patients with AMI migrated more efficiently to a low, yet physiological, gradient of stromal-derived factor-1 in Transwell migration assays. Together, these observations suggest that while elevated S1P and C1P levels early in the course of AMI may trigger mobilization of non-HSCs into PB, cathelicidin and β-2 defensin could play an important role in their homing to damaged myocardium.

An Acacb Variant Implicated In Diabetic Nephropathy Associates With Body Mass Index And Gene Expression In Obese Subjects, Lijun Ma, Mariana Murea, James A. Snipes, Alejandra Marinelarena, Jacqueline Krüger, Pamela J. Hicks, Kurt A. Langberg, Meredith A. Bostrom, Jessica N. Cooke, Daisuke Suzuki, Tetsuya Babazono, Takashi Uzu, Sydney C. W. Tang, Ashis K. Mondal, Neeraj K. Sharma, Sayuko Kobes, Peter A. Antinozzi, Matthew Davis, Swapan K. Das, Neda Rasouli, Philip A. Kern, Nathan J. Shores, Lawrence L. Rudel, Matthias Blüher, Michael Stumvoll, Donald W. Bowden, Shiro Maeda, John S. Parks, Peter Kovacs, Robert L. Hanson, Leslie J. Baier, Steven C. Elbein, Barry I. Freedman

Internal Medicine Faculty Publications

Acetyl coenzyme A carboxylase B gene (ACACB) single nucleotide polymorphism (SNP) rs2268388 is reproducibly associated with type 2 diabetes (T2DM)-associated nephropathy (DN). ACACB knock-out mice are also protected from obesity. This study assessed relationships between rs2268388, body mass index (BMI) and gene expression in multiple populations, with and without T2DM. Among subjects without T2DM, rs2268388 DN risk allele (T) associated with higher BMI in Pima Indian children (n = 2021; p-additive = 0.029) and African Americans (AAs) (n = 177; p-additive = 0.05), with a trend in European Americans (EAs) (n = 512; p-additive = 0.09), but not Germans (n …

A Phase Ii Study Of Pulse Dose Imatinib Mesylate And Weekly Paclitaxel In Patients Aged 70 And Over With Advanced Non-Small Cell Lung Cancer, Julie E. Bauman, Keith D. Eaton, Sarah G. Wallace, Laurie L. Carr, Sang-Joon Lee, Dennie V. Jones, Hugo Arias-Pulido, Lisa A. Cerilli, Renato G. Martins

Internal Medicine Faculty Publications

BACKGROUND: In non-small cell lung cancer (NSCLC), interstitial hypertension is a barrier to chemotherapy delivery, and is mediated by platelet derived growth factor receptor (PDGFR). Antagonizing PDGFR with imatinib may improve intra-tumoral delivery of paclitaxel, increasing response rate (RR).

METHODS: This single-stage, open-label phase II study evaluated pulse dose imatinib and weekly paclitaxel in elderly patients with advanced NSCLC. Eligible patients were aged ≥ 70 with untreated, stage IIIB-IV NSCLC and ECOG performance status 0-2. Primary endpoint was RR. Secondary endpoints included median progression free and overall survival (PFS, OS) and correlatives of PDGFR pathway activation. Baseline Charlson Comorbidity Index …

Latexin Is Down-Regulated In Hematopoietic Malignancies And Restoration Of Expression Inhibits Lymphoma Growth, Yi Liu, Dianna Howard, Kyle Rector, Carol Swiderski, Jason Brandon, Lawrence Schook, Jayesh Mehta, J. Scott Bryson, Subbarao Bondada, Ying Liang

Internal Medicine Faculty Publications

Latexin is a negative regulator of hematopoietic stem cell number in mice. Its dysregulated expression in other tumors led us to hypothesize that latexin may have tumor suppressor properties in hematological malignancies. We found that latexin was down-regulated in a variety of leukemia and lymphoma cell lines as well as in CD34+ cells from the blood and marrow of patients with these malignancies. 5-aza-2'-deoxycytodine treatment and bisulfite sequencing revealed hypermethylation of latexin promoter in tumor cells. Retrovirus-mediated latexin overexpression in A20 mouse lymphoma cells inhibited their in vitro growth by 16 fold and in vivo tumor volume by 2 fold. …

Efficacy And Safety Characteristics Of Mometasone Furoate/Formoterol Fumarate Fixed-Dose Combination In Subjects With Moderate To Very Severe Copd: Findings From Pooled Analysis Of Two Randomized, 52-Week Placebo-Controlled Trials, Donald P. Tashkin, Dennis E. Doherty, Edward Kerwin, Carlos E. Matiz-Bueno, Barbara Knorr, Tulin Shekar, Davis Gates, Heribert Staudinger

Internal Medicine Faculty Publications

Background:

The clinical efficacy and safety of a mometasone furoate/formoterol fumarate (MF/F) fixed-dose combination formulation administered via a metered-dose inhaler was investigated in patients with moderate to very severe chronic obstructive pulmonary disease (COPD).

Methods:

Two 52-week, multicenter, double-blind, placebo-controlled trials with identical study designs were conducted in current or ex-smokers (aged =40 years), and pooled study results are presented herein. Subjects (n = 2251) were randomized to 26 weeks of twice-daily treatment with MF/F 400/10 µg, MF/F 200/10 µg, MF 400 µg, F 10 µg, or placebo. After the 26-week treatment period, placebo subjects completed the trial and 75% …

Effects Of Mometasone Furoate/Formoterol Fumarate Fixed-Dose Combination Formulation On Chronic Obstructive Pulmonary Disease (Copd): Results From A 52-Week Phase Iii Trial In Subjects With Moderate-To-Very Severe Copd, Dennis E. Doherty, Donald P. Tashkin, Edward Kerwin, Barbara Knorr, Tulin Shekar, Sibabrata Banerjee, Heribert Staudinger

Internal Medicine Faculty Publications

RATIONALE: The purpose of this study was to investigate the clinical efficacy and safety of a fixed-dose combination of mometasone furoate/formoterol fumarate (MF/F) administered via a metered-dose inhaler in subjects with moderate-to-very severe chronic obstructive pulmonary disease (COPD).

METHODS: This multicenter, double-blind, placebo-controlled trial had a 26-week treatment period and a 26-week safety extension. Subjects (n = 1196), at least 40 years old, were current or ex-smokers randomized to twice-daily inhaled MF/F 400/10 μg, MF/F 200/10 μg, MF 400 μg, F 10 μg, or placebo. The trial's co-primary endpoints were mean changes from baseline, as area under the curve (AUC), …

Efficacy And Safety Characteristics Of Mometasone Furoate/Formoterol Fumarate Fixed-Dose Combination In Subjects With Moderate To Very Severe Copd: Findings From Pooled Analysis Of Two Randomized, 52-Week Placebo-Controlled Trials, Donald P. Tashkin, Dennis E. Doherty, Edward Kerwin, Carlos E. Matiz-Bueno, Barbara Knorr, Tulin Shekar, Sibabrata Banerjee, Heribert Staudinger

Internal Medicine Faculty Publications

Background: A clinical trial of mometasone furoate/formoterol fumarate (MF/F) administered via a metered-dose inhaler in subjects with moderate to very severe chronic obstructive pulmonary disease (COPD) investigated the efficacy and safety of a fixed-dose combination of MF/F.

Methods: This multicenter, double-blind, placebo-controlled trial had a 26-week treatment period and a 26-week safety extension. Subjects (n = 1055; ≥40 years) were current or ex-smokers randomized to twice-daily treatment with inhaled MF/F 400/10 µg, MF/F 200/10 µg, MF 400 µg, F 10 µg, or placebo. The coprimary endpoints of the trial were mean changes from baseline in forced expiratory volume in 1 …

Predictors Of Survival In A Cohort Of Patients With Polymyositis And Dermatomyositis: Effect Of Corticosteroids, Methotrexate And Azathioprine, Elena Schiopu, Kristine Phillips, Paul M. Macdonald, Leslie J. Crofford, Emily C. Somers

Internal Medicine Faculty Publications

INTRODUCTION: The idiopathic inflammatory myopathies are rare diseases for which data regarding the natural history, response to therapies and factors affecting mortality are needed. We performed this study to examine the effects of treatment and clinical features on survival in polymyositis and dermatomyositis patients.

METHODS: A total of 160 consecutive patients (77 with polymyositis and 83 with dermatomyositis) seen at the University of Michigan from 1997 to 2003 were included. Medical records were abstracted for clinical, laboratory and therapeutic data, including initial steroid regimen and immunosuppressive use. State vital records were utilized to derive mortality and cause of death data. …

Academic Detailing To Increase Colorectal Cancer Screening By Primary Care Practices In Appalachian Pennsylvania, William J. Curry, Eugene J. Lengerich, Brenda C. Kluhsman, Marie A. Graybill, Jason Z. Liao, Eric W. Schaefer, Angela M. Spleen, Mark B. Dignan

Internal Medicine Faculty Publications

BACKGROUND: In the United States, colorectal cancer (CRC) is the third most frequently diagnosed cancer and second leading cause of cancer death. Screening is a primary method to prevent CRC, yet screening remains low in the U.S. and particularly in Appalachian Pennsylvania, a largely rural area with high rates of poverty, limited health care access, and increased CRC incidence and mortality rates. Receiving a physician recommendation for CRC screening is a primary predictor for patient adherence with screening guidelines. One strategy to disseminate practice-oriented interventions is academic detailing (AD), a method that transfers knowledge or methods to physicians, nurses or …

Intestinal Epithelial Serum Amyloid A Modulates Bacterial Growth In Vitro And Pro-Inflammatory Responses In Mouse Experimental Colitis, Erik R.M. Eckhardt, Jassir Witta, Jian Zhong, Razvan Arsenescu, Violeta Arsenescu, Yu Wang, Sarbani Ghoshal, Marcielle C. De Beer, Frederick C. De Beer, Willem J.S. De Villiers

Internal Medicine Faculty Publications

BACKGROUND: Serum Amyloid A (SAA) is a major acute phase protein of unknown function. SAA is mostly expressed in the liver, but also in other tissues including the intestinal epithelium. SAA reportedly has anti-bacterial effects, and because inflammatory bowel diseases (IBD) result from a breakdown in homeostatic interactions between intestinal epithelia and bacteria, we hypothesized that SAA is protective during experimental colitis.

METHODS: Intestinal SAA expression was measured in mouse and human samples. Dextran sodium sulfate (DSS) colitis was induced in SAA 1/2 double knockout (DKO) mice and in wildtype controls. Anti-bacterial effects of SAA1/2 were tested in intestinal epithelial …

Cyanidin-3-Glucoside Inhibits Ethanol-Induced Invasion Of Breast Cancer Cells Overexpressing Erbb2, Mei Xu, Kimberly A. Bower, Siying Wang, Jacqueline A. Frank, Gang Chen, Min Ding, Shiow Wang, Xianglin Shi, Zunji Ke, Jia Luo

Internal Medicine Faculty Publications

BACKGROUND: Ethanol is a tumor promoter. Both epidemiological and experimental studies suggest that ethanol may enhance the metastasis of breast cancer cells. We have previously demonstrated that ethanol increased the migration/invasion of breast cancer cells expressing high levels of ErbB2. Amplification of ErbB2 is found in 20-30% of breast cancer patients and is associated with poor prognosis. We sought to identify agents that can prevent or ameliorate ethanol-induced invasion of breast cancer cells. Cyanidin-3-glucoside (C3G), an anthocyanin present in many vegetables and fruits, is a potent natural antioxidant. Ethanol exposure causes the accumulation of intracellular reactive oxygen species (ROS). This …

Diaphragm Weakness And Mechanical Ventilation – What's The Critical Issue?, Leigh Ann Callahan, Gerald S. Supinski

Internal Medicine Faculty Publications

While animal studies indicate that controlled mechanical ventilation (MV) induces diaphragm weakness and myofiber atrophy, there are no data in humans that confirm MV per se produces diaphragm weakness. Whether or not diaphragm weakness results from MV, sepsis, corticosteroids, hyperglycemia, or a combination of these factors, however, is not the most important issue raised by the recent study from Hermans and colleagues. This study makes an important contribution by providing additional evidence that many critically ill patients have profound diaphragm weakness. If diaphragm weakness of this magnitude is present in most mechanically ventilated patients, a strong argument can be made …

Chylomicrons Promote Intestinal Absorption And Systemic Dissemination Of Dietary Antigen (Ovalbumin) In Mice, Yuehui Wang, Sarbani Ghoshal, Martin Ward, Willem De Villiers, Jerold Woodward, Erik Eckhardt

Internal Medicine Faculty Publications

BACKGROUND: A small fraction of dietary protein survives enzymatic degradation and is absorbed in potentially antigenic form. This can trigger inflammatory responses in patients with celiac disease or food allergies, but typically induces systemic immunological tolerance (oral tolerance). At present it is not clear how dietary antigens are absorbed. Most food staples, including those with common antigens such as peanuts, eggs, and milk, contain long-chain triglycerides (LCT), which stimulate mesenteric lymph flux and postprandial transport of chylomicrons through mesenteric lymph nodes (MLN) and blood. Most dietary antigens, like ovalbumin (OVA), are emulsifiers, predicting affinity for chylomicrons. We hypothesized that chylomicron …

Documentation Of Body Mass Index And Control Of Associated Risk Factors In A Large Primary Care Network, Stephanie A. Rose, Alexander Turchin, Richard W. Grant, James B. Meigs

Internal Medicine Faculty Publications

BACKGROUND: Body mass index (BMI) will be a reportable health measure in the United States (US) through implementation of Healthcare Effectiveness Data and Information Set (HEDIS) guidelines. We evaluated current documentation of BMI, and documentation and control of associated risk factors by BMI category, based on electronic health records from a 12-clinic primary care network.

METHODS: We conducted a cross-sectional analysis of 79,947 active network patients greater than 18 years of age seen between 7/05 - 12/06. We defined BMI category as normal weight (NW, 18-24.9 kg/m²), overweight (OW, 25-29.9), and obese (OB, ≥ 30). We measured documentation …

Hyperglycemia And Acquired Weakness In Critically Ill Patients: Potential Mechanisms, Leigh Ann Callahan, Gerald S. Supinski

Internal Medicine Faculty Publications

Critical illness polyneuropathy/critical illness myopathy (CIP/CIM) is a major cause of mortality and long-term morbidity in critically ill patients, but the true incidence and prevalence of these syndromes are not known. Hermans and colleagues show that when intensive insulin therapy is used as part of routine clinical practice in the intensive care unit, the incidence of CIP/CIM as determined by electrophysiologic testing is reduced. Our understanding of the mechanisms responsible for inducing prolonged weakness in intensive care unit patients is limited, and the role of hyperglycemia in modulating these processes is unknown. Intensive insulin therapy currently remains the only effective …

Life Expectancy And Years Of Life Lost In Chronic Obstructive Pulmonary Disease: Findings From The Nhanes Iii Follow-Up Study, Robert M. Shavelle, David R. Paculdo, Scott J. Kush, David M. Mannino, David J. Strauss

Internal Medicine Faculty Publications

RATIONALE: Previous studies have demonstrated that chronic obstructive pulmonary disease (COPD) causes increased mortality in the general population. But life expectancy and the years of life lost have not been reported.

OBJECTIVES: To quantify mortality, examine how it varies with age, sex, and other risk factors, and determine how life expectancy is affected.

METHODS: We constructed mortality models using the Third National Health and Nutrition Examination Survey, adjusting for age, sex, race, and major medical conditions. We used these to compute life expectancy and the years of life lost.

MEASUREMENTS AND MAIN RESULTS: Pulmonary function testing classified patients as having …

Biology And Therapy Of Fibromyalgia. Evidence-Based Biomarkers For Fibromyalgia Syndrome, Dina Dadabhoy, Leslie J. Crofford, Michael Spaeth, I. Jon Russell, Daniel J. Clauw

Internal Medicine Faculty Publications

Researchers studying fibromyalgia strive to identify objective, measurable biomarkers that may identify susceptible individuals, may facilitate diagnosis, or that parallel activity of the disease. Candidate objective measures range from sophisticated functional neuroimaging to office-ready measures of the pressure pain threshold. A systematic literature review was completed to assess highly investigated, objective measures used in fibromyalgia studies. To date, only experimental pain testing has been shown to coincide with improvements in clinical status in a longitudinal study. Concerted efforts to systematically evaluate additional objective measures in research trials will be vital for ongoing progress in outcome research and translation into clinical …

Preventing Cardiovascular Disease In Kentucky: Epidemiology, Trends, And Strategies For The Future, Sarah Sartini Rugg, Alison L. Bailey, Steven R. Browning

Internal Medicine Faculty Publications

Cardiovascular disease (CVD) is the leading cause of death in the United States despite dramatic improvements in the treatment of heart disease in recent years. Kentucky leads the nation in the prevalence of several individual risk factors for cardiovascular disease, the prevalence of multiple risk factors, and in cardiovascular mortality. While trends in the prevalence of some of these cardiac risk factors have shown improvement, others have remained unchanged or have worsened. The increased prevalence of obesity and diabetes, especially among young persons, is one of the most worrisome trends. The prevalence of smoking in Kentucky remains high, and has …