Medicine and Health Sciences Commons^™

Higher Plasma Cxcl12 Levels Predict Incident Myocardial Infarction And Death In Chronic Kidney Disease: Findings From The Chronic Renal Insufficiency Cohort Study, Nehal N. Mehta, Gregory J. Matthews, Parasuram Krishnamoorthy, Rhia Shah, Catherine Mclaughlin, Dominic S. Raj, +18 Additional Authors

Medicine Faculty Publications

Aims

Genome-wide association studies revealed an association between a locus at 10q11, downstream from CXCL12, and myocardial infarction (MI). However, the relationship among plasma CXCL12, cardiovascular disease (CVD) risk factors, incident MI, and death is unknown.

Methods and Results

We analysed study-entry plasma CXCL12 levels in 3687 participants of the Chronic Renal Insufficiency Cohort (CRIC) Study, a prospective study of cardiovascular and kidney outcomes in chronic kidney disease (CKD) patients. Mean follow-up was 6 years for incident MI or death. Plasma CXCL12 levels were positively associated with several cardiovascular risk factors (age, hypertension, diabetes, hypercholesterolaemia), lower estimated glomerular filtration rate …

Myocarditis After Trimethoprim/Sulfamethoxazole Treatment For Ehrlichiosis, Seema U. Nayak, Gary L. Simon

Medicine Faculty Publications

The manifestations of human monocytic ehrlichiosis range from a mild febrile syndrome to a severe multisystem illness. Myocardial involvement is uncommon. We report a woman, 78 years of age, who was treated with trimethoprim/sulfamethoxazole after a tick bite, in whom myocarditis was subsequently diagnosed. She recovered completely after doxycycline therapy.

Capture Of Lipopolysaccharide (Endotoxin) By The Blood Clot: A Comparative Study, Margaret T. Armstrong, Frederick R. Rickles, Peter B. Armstrong

Medicine Faculty Publications

In vertebrates and arthropods, blood clotting involves the establishment of a plug of aggregated thrombocytes (the cellular clot) and an extracellular fibrillar clot formed by the polymerization of the structural protein of the clot, which is fibrin in mammals, plasma lipoprotein in crustaceans, and coagulin in the horseshoe crab, Limulus polyphemus. Both elements of the clot function to staunch bleeding. Additionally, the extracellular clot functions as an agent of the innate immune system by providing a passive anti-microbial barrier and microbial entrapment device, which functions directly at the site of wounds to the integument. Here we show that, in …

Gastric Electrical Stimulation With Enterra Therapy Improves Symptoms Of Idiopathic Gastroparesis., Richard W. Mccallum, Irene Sarosiek, H. P. Parkaman, William J.S. Snape, Frederick J. Brody, J. Wo, Thomas V. Nowak

Medicine Faculty Publications

No abstract provided.

Cold Atmospheric Plasma For Selectively Ablating Metastatic Breast Cancer Cells, Mian Wang, Benjamin Holmes, Xiaoqian Cheng, Wei Zhu, Michael Keidar, Lijie Grace Zhang

Medicine Faculty Publications

Traditional breast cancer treatments such as surgery and radiotherapy contain many inherent limitations with regards to incomplete and nonselective tumor ablation. Cold atomospheric plasma (CAP) is an ionized gas where the ion temperature is close to room temperature. It contains electrons, charged particles, radicals, various excited molecules, UV photons and transient electric fields. These various compositional elements have the potential to either enhance and promote cellular activity, or disrupt and destroy them. In particular, based on this unique composition, CAP could offer a minimally-invasive surgical approach allowing for specific cancer cell or tumor tissue removal without influencing healthy cells. Thus, …

Determine Tb-Lam Lateral Flow Urine Antigen Assay For Hiv-Associated Tuberculosis: Recommendations On The Design And Reporting Of Clinical Studies, Stephen D. Lawn, Keertan Dheda, Andrew D. Kerkhoff, Jonathan G. Peter, Susan Dorman, Catharina C. Boehme, Mark P. Nicol

Medicine Faculty Publications

Detection of the Mycobacterium tuberculosis cell wall antigen lipoarabinomannan (LAM) in urine permits diagnoses of tuberculosis (TB) to be made in HIV-infected patients with advanced immunodeficiency. This can be achieved at the point-of-care within just 30 minutes using the Determine TB-LAM, which is a commercially available, lateral-flow urine ‘strip test’ assay. The assay has been shown to have useful diagnostic accuracy in patients enrolling in antiretroviral treatment services or in HIV-infected patients requiring admission to hospital medical wards in sub-Saharan Africa. Such patients have high mortality risk and have most to gain from rapid diagnosis of TB and immediate initiation …

Metastatic Castration-Resistant Prostate Cancer: Critical Review Of Enzalutamide, Joelle El-Amm, Nihar Patel, Ashley Freeman, Jeanny B. Aragon-Ching

Medicine Faculty Publications

Enzalutamide, previously known as MDV300, is an oral, second-generation androgen receptor (AR) signaling inhibitor or antagonist that was approved by the Food and Drug Administration in 2012 for the treatment of metastatic castrate-resistant prostate cancer (mCRPC) postdocetaxel. Preclinical studies have demonstrated impressive affinity to the AR compared to the first-generation AR inhibitors. The landmark Phase III AFFIRM trial demonstrated improved overall survival benefit compared to placebo in addition to improvement in all tested parameters. Enzalutamide is currently being studied in several trials prechemotherapy and in earlier settings of prostate cancer. This review will discuss the mechanism of action of enzalutamide, …

Bendamustine Combined With Rituximab For Patients With Relapsed Or Refractory Diffuse Large B Cell Lymphoma, Jeffrey L. Vacirca, Peter I. Acs, Imad A. Tabbara, Peter J. Rosen, Peter Lee, Eric Lynam

Medicine Faculty Publications

Patients with relapsed or refractory diffuse large B cell lymphoma (DLBCL) are treated with salvage regimens and may be considered for high-dose chemotherapy and autologous stem cell transplantation if disease is chemosensitive. Bendamustine is active in indolent B cell lymphomas and chronic lymphocytic leukemia but has not been extensively studied in aggressive lymphomas. This trial examines the combination of bendamustine and rituximab in patients with relapsed and refractory DLBCL. Patients received bendamustine at 90 mg/m2 (n = 2) or 120 mg/m2 (n = 57) on days 1 and 2 and rituximab at 375 mg/m2 on day 1 every …

Calcium, Magnesium And Potassium Intake And Mortality In Women With Heart Failure: The Women's Health Initiative, Emily B. Levitan, James M. Shikany, Ali Ahmed, Linda G. Snetselaar, Lisa W. Martin, J. David Curb, Cora E. Lewis

Medicine Faculty Publications

Although diet is thought to affect the natural history of heart failure (HF), nutrient intake in HF patients has not been well studied. Based on prior research linking high intake of Ca, Mg and K to improved cardiovascular health, we hypothesised that these nutrients would be inversely associated with mortality in people with HF. Of the 161 808 participants in the Women's Health Initiative (WHI), we studied 3340 who experienced a HF hospitalisation. These participants were followed for post-hospitalisation all-cause mortality. Intake was assessed using questionnaires on food and supplement intake. Hazard ratios (HR) and 95 % CI were calculated …

A Multicenter Randomized Controlled Trial Of A Plant-Based Nutrition Program To Reduce Body Weight And Cardiovascular Risk In The Corporate Setting: The Geico Study, S. Mishra, J. Xu, U. Agarwal, J. Gonzales, S. Levin, Neal D. Barnard

Medicine Faculty Publications

Background/objectives:

To determine the effects of a low-fat plant-based diet program on anthropometric and biochemical measures in a multicenter corporate setting.

Subjects/methods:

Employees from 10 sites of a major US company with body mass index 25 kg/m² and/or previous diagnosis of type 2 diabetes were randomized to either follow a low-fat vegan diet, with weekly group support and work cafeteria options available, or make no diet changes for 18 weeks. Dietary intake, body weight, plasma lipid concentrations, blood pressure and glycated hemoglobin (HbA_1C) were determined at baseline and 18 weeks.

Results:

Mean body weight fell 2.9 kg …

Increased Brain White Matter Axial Diffusivity Associated With Fatigue, Pain And Hyperalgesia In Gulf War Illness, Rakib U. Rayhan, Benson W. Stevens, Christian R. Timbol, Oluwatoyin Adewuyi, Brian Walitt, John Vanmeter, James N. Baraniuk

Medicine Faculty Publications

Background

Gulf War exposures in 1990 and 1991 have caused 25% to 30% of deployed personnel to develop a syndrome of chronic fatigue, pain, hyperalgesia, cognitive and affective dysfunction.

Methods

Gulf War veterans (n = 31) and sedentary veteran and civilian controls (n = 20) completed fMRI scans for diffusion tensor imaging. A combination of dolorimetry, subjective reports of pain and fatigue were correlated to white matter diffusivity properties to identify tracts associated with symptom constructs.

Results

Gulf War Illness subjects had significantly correlated fatigue, pain, hyperalgesia, and increased axial diffusivity in the right inferior fronto-occipital fasciculus. ROC …

Biomarkers And Bacterial Pneumonia Risk In Patients With Treated Hiv Infection: A Case-Control Study, Sonja M. Bjerk, Jason V. Baker, Sean Emery, Jacqueline Neuhaus, Brian Angus, Fred M. Gordin, Sarah L. Pett, Christoph Stephan, Ken M. Kunisaki

Medicine Faculty Publications

Background

Despite advances in HIV treatment, bacterial pneumonia continues to cause considerable morbidity and mortality in patients with HIV infection. Studies of biomarker associations with bacterial pneumonia risk in treated HIV-infected patients do not currently exist.

Methods

We performed a nested, matched, case-control study among participants randomized to continuous combination antiretroviral therapy (cART) in the Strategies for Management of Antiretroviral Therapy trial. Patients who developed bacterial pneumonia (cases) and patients without bacterial pneumonia (controls) were matched 1:1 on clinical center, smoking status, age, and baseline cART use. Baseline levels of Club Cell Secretory Protein 16 (CC16), Surfactant Protein D (SP-D), …

Gut Hormones, Appetite Suppression And Cachexia In Patients With Pulmonary Tb, Suzanne W. Chang, William S. Pan, Daniel Lozano Beltran, Lizet Oleyda Baldelomar, Marco Antonio Solano, Iskra Tuero, Faustino Torrico, Robert H. Gilman

Medicine Faculty Publications

Background

Cachexia is a hallmark of pulmonary tuberculosis and is associated with poor prognosis. A better understanding of the mechanisms behind such weight loss could reveal targets for therapeutic intervention. The role of appetite-regulatory hormones in tuberculosis is unknown.

Methods and Findings

41 subjects with newly-diagnosed pulmonary TB (cases) were compared to 82 healthy controls. We measured appetite, body mass index (BMI), % body fat (BF), plasma peptide YY (PYY), leptin, ghrelin, and resistin for all subjects. Measurements were taken at baseline for controls and at treatment days 0, 30, and 60 for cases. Baseline appetite, BMI, and BF were …

Vlincrnas Controlled By Retroviral Elements Are A Hallmark Of Pluripotency And Cancer, Georges St. Laurent, Dmitry Shtokalo, Biao Dong, Michael R. Tackett, Xiaoxuan Fan, Sandra Lazorthes, Estelle Nicolas, Nianli Sang, Timothy J. Triche, Timothy A. Mccaffrey, Wendiong Xiao, Philipp Kapranov

Medicine Faculty Publications

Background

The function of the non-coding portion of the human genome remains one of the most important questions of our time. Its vast complexity is exemplified by the recent identification of an unusual and notable component of the transcriptome - very long intergenic non-coding RNAs, termed vlincRNAs.

Results

Here we identify 2,147 vlincRNAs covering 10 percent of our genome. We show they are present not only in cancerous cells, but also in primary cells and normal human tissues, and are controlled by canonical promoters. Furthermore, vlincRNA promoters frequently originate from within endogenous retroviral sequences. Strikingly, the number of vlincRNAs expressed …

Changing Behavior Among Nurses To Track Indwelling Urinary Catheters In Hospitalized Patients, Bona Yoon, Samantha D. Mcintosh, Leslie Rodriguez, Alma Holley, Charles Faselis, Angelike P. Liappis

Medicine Faculty Publications

Catheter-associated urinary tract infections (CAUTIs) are preventable complications of hospitalization. An interdisciplinary team developed a curriculum to increase awareness of the presence of indwelling urinary catheters (IUCs) in hospitalized patients, addressed practical, primarily nurse-controlled inpatient risk-reduction interventions, and promoted the use of the IUC labels (“tags”). Five thirty-minute educational sessions were cycled over three daily nursing shifts on two inpatient medical floors over a 1-year period; participants were surveyed to elicit feedback and provide real-time insight on the learning objectives. Nurse self-reported IUC tagging was early and sustained; after the IUC tag was introduced, there was a significant increase in …

Genomic Profiling Reveals The Potential Role Of Tcl1a And Mdr1 Deficiency In Chemotherapy-Induced Cardiotoxicity, Timothy A. Mccaffrey, Constantine Tziros, Jannet Lewis, Richard Katz, Robert S. Siegel, William B. Weglicki, Jay H. Kramer, I. Tong Mak, Ian Toma, Liang Chen, Elizabeth Benas, Alexander Lowitt, Shruti Rao, Linda Witkin, Yi Lian, Zhaoqing Yang, Sidney W. Fu

Medicine Faculty Publications

Background: Anthracyclines, such as doxorubicin (Adriamycin), are highly effective chemotherapeutic agents, but are well known to cause myocardial dysfunction and life-threatening congestive heart failure (CHF) in some patients.

Methods: To generate new hypotheses about its etiology, genome-wide transcript analysis was performed on whole blood RNA from women that received doxorubicin-based chemotherapy and either did, or did not develop CHF, as defined by ejection fractions (EF)≤40%. Women with non-ischemic cardiomyopathy unrelated to chemotherapy were compared to breast cancer patients prior to chemo with normal EF to identify heart failure-related transcripts in women not receiving chemotherapy. Byproducts of oxidative stress in plasma …

Comparing Hormone Therapy Effects In Two Rcts And Two Large Observational Studies That Used Similar Methods For Comprehensive Data Collection And Outcome Assessment, Arthur Hartz, Tao He, Robert Wallace, John H. Powers

Medicine Faculty Publications

Objectives Prospective observational studies (OSs) that collect adequate information about confounders can validly assess treatment consequences. However, what constitutes adequate information is unknown. This study investigated whether the extensive information collected by the Women's Health Initiative (WHI) in two OSs and two randomised controlled trials (RCTs) was adequate.

Design Secondary analysis of WHI data. Cox regression was used to select from all baseline risk factors those that best predicted outcome. Cox regression that included these risk factors was used for two types of analyses: (1) comparing RCT and OS assessments of the effects of hormone therapy on outcome for participants …

Self-Perceived Physical Health Predicts Cardiovascular Disease Incidence And Death Among Postmenopausal Women, Nazmus Saquib, Robert Brunner, Jessica Kubo, Hilary Tindle, Candyce Kroenke, Manisha Desai, Marsha L. Daviglus, Norrina Allen, Lisa W. Martin, Jennifer Robinson, Marcia L. Stefanick

Medicine Faculty Publications

Background

Physical and Mental Component Summary (PCS, MCS, respectively) scales of SF- 36 health-related-quality-of-life have been associated with all-cause and cardiovascular disease (CVD) mortality. Their relationships with CVD incidence are unclear. This study purpose was to test whether PCS and/or MCS were associated with CVD incidence and death.

Methods

Postmenopausal women (aged 50–79 years) in control groups of the Women’s Health Initiative clinical trials (n = 20,308) completed the SF-36 and standardized questionnaires at trial entry. Health outcomes, assessed semi-annually, were verified with medical records. Cox regressions assessed time to selected outcomes during the trial phase (1993–2005).

Results

A total …

Acromegaloid Facial Appearance: Case Report And Literature Review, Adline Ghazi, Shikha Khosla, Kenneth L. Becker

Medicine Faculty Publications

Pseudoacromegaly is characterized by an acromegalic appearance without any abnormality of growth hormone function. It may be caused by several congenital and acquired conditions. One such condition is the acromegaloid facial appearance (AFA) syndrome. This condition has been described in approximately eight cases/families. It encompasses a spectrum of acromegaloid physical findings, normal growth hormone (GH) and insulin-like growth factor one (IGF-1) levels, and variable mode of inheritance. The most common physical findings are coarse facies, bulbous nose, and thickened lips. We present a case and a review of the literature on this illness. The patient is a 57-year-old woman who …

Procalcitonin Beyond The Acute Phase: Novel Biomediator Properties?, Carolina Panico, Eric S. Nylen

Medicine Faculty Publications

Since inflammation has been linked to carcinogenic events, discovery of relevant biomarkers may have important preventative implications. Procalcitonin (ProCT) has been shown to be an important prognostic biomarker in severe inflammatory conditions, but there is no data regarding its biomarker role, if any, beyond the acute phase. In a recent study published in BMC Medicine, Cotoi et al. analyzed whether serum ProCT levels in healthy individuals are associated with mortality outcomes. The results are affirmative in that baseline ProCT was shown to be strongly and independently associated with all-cause and cancer mortality and with the incidence of colon …

Bone-Targeted Therapies In Metastatic Castration-Resistant Prostate Cancer: Evolving Paradigms, Joelle El-Amm, Ashley Freeman, Nihar Patel, Jeanny B. Aragon-Ching

Medicine Faculty Publications

Majority of patients with metastatic castrate resistant prostate cancer (mCRPC) develop bone metastases which results in significant morbidity and mortality as a result of skeletal-related events (SREs). Several bone-targeted agents are either in clinical use or in development for prevention of SREs. Bisphosphonates were the first class of drugs investigated for prevention of SREs and zoledronic acid is the only bisphosphonate that is FDA-approved for this indication. Another bone-targeted agent is denosumab which is a fully humanized monoclonal antibody that binds to the RANK-L thereby inhibiting RANK-L mediated bone resorption. While several radiopharmaceuticals were approved for pain palliation in mCRPC …

Endothelin Receptor Antagonists (Era) In Hypertension And Chronic Kidney Disease: A Rose With Many Thorns, Michael N. Doumas, V. Athyros, N. Katsiki, A. Reklou, A. Lazaridis, A. Karagiannis

Medicine Faculty Publications

The discovery of endothelin created a lot of enthusiasm and paved new therapeutic avenues for the treatment of arterial hypertension. Endothelin plays a significant role in blood pressure regulation through pronounced vasoconstriction and modulation of sodium and water reabsorption in the kidneys. Endothelin receptor antagonists have been tested in many clinical trials in patients with arterial hypertension, heart failure, pulmonary arterial hypertension, systemic sclerosis, chronic kidney disease, and diabetic nephropathy. However, the results were usually disappointing, except in pulmonary hypertension and scleroderma digital ulcers. The future of ERAs for the treatment of arterial hypertension and chronic kidney disease does not …

Nutrient Intake In The Geico Multicenter Trial: The Effects Of A Multicomponent Worksite Intervention, S. Mishra, Neal D. Barnard, J. Gonzales, J. Xu, U. Agarwal, S. Levin

Medicine Faculty Publications

Background/objectives:

To assess the effects on macro- and micronutrient intake of a nutrition intervention program in corporate settings across the United States.

Subjects/methods:

Two hundred and ninety-two individuals who were overweight or had type 2 diabetes were recruited from 10 sites of a US insurance company. Two hundred and seventy-one participants completed baseline diet recalls, and 183 participants completed dietary recalls at 18 weeks. Sites were randomly assigned to an intervention group (five sites) or to a control group (five sites) for 18 weeks. At intervention sites, participants were asked to follow a low-fat vegan diet and attend weekly group …

Diagnostic Error - Mini Review And Case Report Of Patient Death Resulting From Delayed Diagnosis Of Acute Prostatitis, Dragica K. Mrkoci, Katherine C. Chretien

Medicine Faculty Publications

A 57-year old man presenting with frequent and painful urination and negative initial urinalysis for infection was given a diagnosis of benign prostate hypertrophy, which was never revised by subsequent providers. Instead, the patient continued to be treated for urinary retention and pain. A potent NSAID, Toradol (ketorolac), was included in his regimen. One day prior to his demise, the patient was diagnosed with prostatic abscess and admitted for treatment with intravenous antibiotics. However the patient died on hospital day one from massive GI bleeding. Autopsy revealed an underlying peptic ulcer.

This case shines a light on diagnostic error: missed, …

No-Pharmacological Intervention: Pomegranate Juice For The Management Of Hypertension And The Improvement Of Cardiovascular Health, Konstantinos Tzimalos, Michael N. Doumas, Vasilios Athyros

Medicine Faculty Publications

No abstract provided.

The Emergence Of Ambulatory Measurement Of Arterial Stiffness And Central Blood Pressure: A Promising Novelty Of Clinical Importance Or Just Another Marker?, Antonios Lazaridis, Aristotle University Of Thessaloniki, Michael N. Doumas, Andromachi Reklou, A. Karagiannis

Medicine Faculty Publications

Whereas brachial blood pressure (BP) is still considered the gold standard for the estimation of cardiovascular risk in all clinical trials and guidelines, scientific interest is shifting towards central hemodynamics and the scientific community is experiencing a whole new revolution with the emergence of novel cardiovascular markers such as the ambulatory measurement of central BP and arterial stiffness. Central BP has already started to demonstrate its superiority over peripheral BP as a better and more reliable predictor of end-organ damage in cardiovascular diseases. Furthermore, ambulatory measurement of central BP and pulse wave velocity are expected to add much more useful …

Foreign Body Aspiration Presenting With Asthma-Like Symptoms, Jennifer C. Kam, Vikram Doriswamy, Javier F. Dieguez, Joan Dabu, Matthew Cholankeril, Mayur Govind, Richard Miller, Marc Adelman

Medicine Faculty Publications

Aspiration of a foreign body into the tracheobronchial tree is rare in adults. In the majority of these cases there is an underlying condition such as mental retardation, depressed mental status, impairment in the swallowing reflex, neurological impairment, alcohol or sedative abuse, or complications from dental manipulations that contributed to the aspiration. These patients are commonly misdiagnosed with asthma and typically do not respond to mainstay anti-inflammatory and/or bronchodilator therapy. We describe the case of a patient with a foreign body aspiration in the upper trachea not recognized by radiographic studies that presented with asthma-type symptoms.

The Effect Of Antihypertensive Drugs On Arterial Stiffness And Central Hemodynamics: Not All Fingers Are Made The Same, Michael N. Doumas, Eugenia Gkaliagkousi, N. Katsiki, Andromachi Reklou, Antonios Lazaridis, Konstantinos Karagiannis

Medicine Faculty Publications

Arterial stiffness and central hemodynamics attract increasing scientific interest within the hypertensive community during the last decade. Accumulating evidence indicates that aortic stiffness is a strong and independent predictor of cardiovascular events and all-cause mortality in hypertensive patients, and its predictive value extends beyond traditional risk factors. The role of central hemodynamics and augmentation index (a marker of reflected waves), remains less established and requires further investigation. Several lines of evidence indicate that antihypertensive therapy results in significant reductions of pulse wave velocity and central hemodynamics. However, beta-blockers seem to be the only exception with significant within-class differences. Conventional beta-blockers, …