Mayo Clinic College Of Medicine Research Articles

The Tipping Point: Academic Careers of Women in Medicine Today

In Reply: We wholeheartedly agree with the call by Arora and Galanos for innovative solutions to the problem of gender disparity in academic medicine. They are correct that the problem is complex, long-standing, and does not appear to be rapidly changing. We also agree that women need both effective mentors to provide hands-on guidance with career development and also positive role models to inspire and lead by example. Considerable research has examined the attributes and impact of mentors and role models in medicine1 and suggests that the two are distinct.2 In settings where there are few gender-concordant mentors and role models, peer mentoring is a creative solution.3 This approach emphasizes collaboration among teams of individuals with shared career goals, which may be particularly appealing to women, who appear to value a collaborative work style.4 In addition to bolstering mentoring, role modeling, and other support for women, we recommend that institutions consider appropriate measures for the recognition and selection of leaders in medicine. Since traditional measures may not align with every individual's goals, personal values, motivations, or career trajectory,5,6 broadening the way accomplishments are recognized and individuals are rewarded may enhance the ability of both women and men to maximally contribute to institutions and the profession. Darcy A. Reed, MD, MPH Assistant professor of medicine, Division of Primary Care Internal Medicine, Mayo Clinic College of Medicine, Rochester, Minnesota; [email protected]. Keith D. Lindor, MD Professor of medicine and dean, Mayo Clinic College of Medicine, Rochester, Minnesota.

Genetic Variants Influencing Human Longevity from Late-Onset Alzheimer’s Disease (LOAD) Genome-Wide Association Studies (GWAS)

P1-262 GENETIC VARIANTS INFLUENCING HUMAN LONGEVITY FROM LATE-ONSETALZHEIMER’S DISEASE (LOAD) GENOME-WIDE ASSOCIATION STUDIES (GWAS) Hui Shi, Christopher Medway, Kristelle Brown, Noor Kalsheker, Alison Goate, Petroula Proitsi, John Powell, Simon Lovestone, Minerva Carrasquillo, Steven Younkin Kevin Morgan (for the ART consortium), University of Nottingham, Nottingham, United Kingdom; University of Nottingham, Nottingham, United Kingdom; Washington University, St Louis, Missouri, United States; Kings College London, London, United Kingdom; Mayo Clinic College of Medicine, Jacksonville, Florida, United States.

A new defined entity among the spectrum of central nervous system inflammation: chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS)

A newly defined CNS inflammatory disease was recently described by Pittock et al. from the Mayo Clinic College of Medicine [1]. They report a series of 8 patients with CNS inflammation with similar clinical, radiological and pathological features, that they named CLIPPERS (Chronic Lymphocytic Inflammation with Pontine Perivascular Enhancement Responsive to Steroids). Since then, other few cases have been reported. The aim of this short review is to outline the general characteristics of the newly defined CLIPPERS, as this new entity should be considered by the clinician for the differential diagnosis of central inflammatory disease.

Interventions to Improve Surgical Safety

From the Department of Surgery, Division of Cardiovascular Surgery, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, MN. Reprints: Thoralf M. Sundt, MD, Department of Surgery, Division of Cardiovascular Surgery, Mayo Clinic College of Medicine, Mayo Clinic, 200 First Street, Rochester, MN. E-mail: [email protected].

Teaching Points With 3-Dimensional Mapping of Cardiac Arrhythmias

Before creating a detailed 3-dimensional map of an arrhythmia, the electrophysiologist should already have a reasonable idea regarding which cardiac chamber contains either the focal site of origin of an automatic tachycardia or the relevant substrate for reentry. Typically, a combination of careful review of the ECG during tachycardia and knowledge of the location of abnormal substrate (such as myocardial infarction, atriotomy scar, etc) will allow focused mapping in the appropriate chamber. Prior teaching points have already discussed1,2 the fact that an isolated “early site of activation” is essentially meaningless for guiding ablation of macroreentry. However, in some circumstances, even for a focal “automatic” tachycardia, the apparently early site is not a suitable site to target for ablation. After constructing the activation map during tachycardia before ablation, especially if the earliest site of activation obtained does not appear to be particularly early compared with the surface ECG reference, the following should be considered. ### Overlapping Cardiac Structures Mapping a chamber other than the actual chamber where the tachycardia originates will clearly lead to a wrong conclusion. For example, when mapping premature ventricular tachycardias or monomorphic ventricular tachycardia in a structurally normal heart, a detailed map of the right ventricular outflow tract may show the “earliest site” of activation to be in the posterior wall of the right ventricular outflow tract. The true site of origin may, however, be in a coronary cusp or the subvalvar anterior left ventricular outflow tract. The posterior right ventricular outflow tract may appear to be early because a far-field signal is detected on the mapping electrode or because of breakthrough in the right ventricular outflow tract from the wave front originating on the other side of the region.3,4 After mapping the left ventricle and coronary cusps and combining the maps, the earliest activation …

Beneficial Plasma Exchange Response in Central Nervous System Inflammatory Demyelination

Plasma exchange (PLEX) is a beneficial rescue therapy for acute, steroid-refractory central nervous system inflammatory demyelinating disease (CNS-IDD). Despite the approximately 45% PLEX response rate reported among patients with CNS-IDD, determinants of interindividual differences in PLEX response are not well characterized. To perform an exploratory analysis of clinical, radiographic, and serological features associated with beneficial PLEX response. Historical cohort study. Neurology practice, Mayo Clinic College of Medicine, Rochester, Minnesota. Patients All Mayo Clinic patients treated with PLEX between January 5, 1999, and November 12, 2007, for a steroid-refractory CNS-IDD attack. The PLEX response in attack-related, targeted neurological deficit(s) assessed within the 6-month period following PLEX. We identified 153 patients treated with PLEX for a steroid-refractory CNS-IDD, of whom 90 (59%) exhibited moderate to marked functional neurological improvement within 6 months following treatment. Pre-PLEX clinical features associated with a beneficial PLEX response were shorter disease duration (P = .02) and preserved deep tendon reflexes (P = .001); post-PLEX variables included a diagnosis of relapsing-remitting multiple sclerosis (P = .008) and a lower Expanded Disability Status Scale score (P < .001) at last follow-up. Plasma exchange was less effective for patients with multiple sclerosis who subsequently developed a progressive disease course (P = .046). Radiographic features associated with a beneficial PLEX response were presence of ring-enhancing lesions (odds ratio = 4.00; P = .03) and/or mass effect (odds ratio = 3.00; P = .02). No association was found between neuromyelitis optica-IgG serostatus and PLEX response. We have identified clinical and radiographic features that may aid in identifying patients with fulminant, steroid-refractory CNS-IDD attacks who are more likely to respond to PLEX.

Meckel's Diverticulum

* Division of Colon and Rectal Surgery, Department of Surgery, Mayo Clinic and Mayo Foundation, Mayo Clinic College of Medicine, Rochester, MN; † Clinical Assistant Professor of Surgery, University of Illinois at Chicago College of Medicine, Chicago, IL. Reprints: Bruce G. Wolff, MD, Division of Colon and Rectal Surgery, Department of Surgery, Mayo Clinic and Mayo Foundation, Mayo Clinic College of Medicine, 200 First St, Gonda 9 South, Rochester, MN 55905. E-mail: [email protected].

Cytotoxicity of naphthoquinones and their capacity to generate reactive oxygen species is quenched when conjugated with gold nanoparticles

Several reports have demonstrated the anticancer activities of plumbagin, a naphthoquinone derivative isolated from plants belonging to Plumbaginaceae family. However, to the best of our knowledge, there are no reports which describe gold nanoconjugation with plumbagin, even though plumbagin is considered to be a promising therapeutic agent. In this report, we demonstrate the fabrication and characterization of gold nanoparticles conjugated with plumbagin (AuPB) that can reduce the toxicity of the latter, and their capacity for cellular localization and generation of reactive oxygen species. The anticancer activity and ability of plumbagin to produce reactive oxygen species was studied and compared with that of bromoderivatives of 1,4 naphthoquinones such as 2-bromo-1,4-naphthoquinone (2-BNQ) and 2,3-dibromo-1, 4-naphthoquinone (2,3-DBNQ) and their gold nanoconjugates. Plumbagin and bromoderivatives of 1,4 naphthoquinones in the form of gold nanoconjugates showed reduced cytotoxicity and apoptosis compared with the pristine compounds, ie, plumbagin, 2-BNQ, and 2,3-DBNQ. Interestingly, we observed that the gold nanoparticles could quench the reactive oxygen species-generating capacity of plumbagin, 2-BNQ, and 2,3-BNQ, which is one of the main mechanisms of action of the naphthoquinones. Therefore, it can be concluded that conjugation with gold nanoparticles can reduce the cytotoxicity of these compounds.

Kelly D. Flemming

The Guest Editor of this issue of Seminars in Neurology is Kelly Flemming, M.D. Dr. Flemming is Assistant Professor in Neurology in the Mayo Clinic College of Medicine and Medical Director of the Mayo Stroke Center. Dr. Flemming is a summa cum laude graduate of Illinois Wesleyan University with a Bachelor of Arts degree in biology. She attended medical school at the University of Wisconsin where her accomplishments were recognized by election into the Alpha Omega Alpha Honor Medical Society, together with the Rasey Medical Scholarship for Academic Excellence, The Francis Forester Award in Neurology, the Charles Russell Bardeen Award for Excellence in Anatomy, and the Mark Gichert Memorial Award in Neurosurgery. She did an internship at the Medical College of Wisconsin and her Neurology Residency and a Fellowship in Cerebrovascular Disease at the Mayo Clinic.

Gene variation may increase lung cancer risk for non‐smokers

A recent study found that variations in the GPC5 gene may significantly increase the risk of developing lung cancer in patients who never smoked.1 The findings indicate the gene may be a target for both drug development and identifying those individuals at high risk for the disease. The study was led by Ping Yang, MD, of the department of health sciences research at the Mayo Clinic College of Medicine in Rochester, Minnesota. Dr.Yang and colleagues studied DNA samples from 754 never-smokers and analyzed 331,918 single-nucleotide polymorphisms (SNP5) in 377 matched case-control pairs to find genetic variations that were most likely to alter the risk of lung cancer. They found 2 specific genetic markers that appeared to be significant. Further studies validated their findings. In addition, they found that the top 2 SNPs were associated with lung cancer in never-smokers through their regulation of GPC5 expression. Additional studies demonstrated that GPC5 expression levels were 50% lower in adenocarcinoma than in matched normal lung tissue, which indicated that reduced GPC5 expression could be specific for adenocarcinoma in never-smokers. Researchers must develop more studies to determine the regulatory effects of the SNPs and the possible role of GPC5 in the development of lung cancer, the research team concluded.

The 19-Amino Acid Insertion in the Tumor-associated Splice Isoform Rac1b Confers Specific Binding to p120 Catenin

The Rac1b splice isoform contains a 19-amino acid insertion not found in Rac1; this insertion leads to decreased GTPase activity and reduced affinity for GDP, resulting in the intracellular predominance of GTP-bound Rac1b. Here, using co-precipitation and proteomic methods, we find that Rac1b does not bind to many common regulators of Rho family GTPases but that it does display enhanced binding to SmgGDS, RACK1, and p120 catenin (p120(ctn)), proteins involved in cell-cell adhesion, motility, and transcriptional regulation. We use molecular modeling and structure analysis approaches to determine that the interaction between Rac1b and p120(ctn) is dependent upon protein regions that are predicted to be unstructured in the absence of molecular complex formation, suggesting that the interaction between these two proteins involves coupled folding and binding. We also find that directed cell movement initiated by Rac1b is dependent upon p120. These results define a distinct binding functionality of Rac1b and provide insight into how the distinct phenotypic program activated by this protein may be implemented through molecular recognition of effectors distinct from those of Rac1.

Gastroduodenal Disorders

1Center for Gastroenterological Research, KU Leuven, Leuven, Belgium 2Department of Internal Medicine, Mayo Clinic Florida, Jacksonville, Florida, USA 3Enteric Neuroscience Program, Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA Correspondence: Jan Tack, MD, PhD, Center for Gastroenterological Research, KU Leuven, 49 Herestraat, Leuven 3000, Belgium. E-mail: [email protected]

The USPSTF Recommendation Statement on Coronary Heart Disease Risk Assessment

Letters16 March 2010The USPSTF Recommendation Statement on Coronary Heart Disease Risk AssessmentEric L. Matteson, MD, MPH, Cynthia S. Crowson, MS, and Sherine E. Gabriel, MD, MScEric L. Matteson, MD, MPHFrom Mayo Clinic College of Medicine, Rochester, MN 55905.Search for more papers by this author, Cynthia S. Crowson, MSFrom Mayo Clinic College of Medicine, Rochester, MN 55905.Search for more papers by this author, and Sherine E. Gabriel, MD, MScFrom Mayo Clinic College of Medicine, Rochester, MN 55905.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-152-6-201003160-00018 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:The recently published USPSTF (1) statement and systematic review summary of emerging risk factors for CHD (2) highlight important recognized risk factors but neglect an important and emerging aspect of CHD.In the past decade, it has become increasing clear that accelerated atherosclerosis and CHD are more common in patients with systemic inflammatory diseases, such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Women with SLE have a more than 2-fold increased risk for CVD, including myocardial infarction (MI), compared with women without SLE, and the incidence of CHD in women aged 35 to 44 years ...

Interview: David R Holmes Jr speaks to Laura Dormer, Commissioning Editor

Dr David Holmes is currently a Professor of Medicine at the Mayo Clinic College of Medicine and a consultant in the Division of Cardiovascular Diseases and the Department of Internal Medicine at Mayo Clinic in Rochester, Minnesota. Holmes has also been named the Edward W and Betty Knight Scripps Professor in Cardiovascular Medicine in Honor of George M Gura Jr. In 2009, he was elected Vice President of the American College of Cardiology. His special areas of interest include acute coronary syndromes, interventional cardiology, restenosis, vascular biology, risk outcomes analysis and telemedicine. In addition, he is involved in the development of new catheter design and new approaches for the treatment of a wide variety of patients with coronary artery disease and vein graft disease. Finally, he is involved in the development of continued application of percutaneous coronary intervention technology to noncoronary vascular beds. Holmes received his medical degree at Marquette University Medical School in Mi...

The Role of Ultrasound and Regional Anesthesia

*Mayo Clinic College of Medicine †Division of Regional AnesthesiaMayo Clinic Jacksonville, Florida Reprints: Steven R. Clendenen, MD, Mayo Clinic College of Medicine and Division of Regional Anesthesia, Department of Anesthesiology, 4500 San Pablo Road, Jacksonville Florida, 32224, E-mail: [email protected]

Polymeric Biomaterials for Tissue Engineering Applications

1Department of Materials Science & Engineering, The University of Tennessee, Knoxville, TN 37996, USA 2Departments of Biomedical Engineering and Orthopaedic Surgery, Mayo Clinic College of Medicine, Rochester, MN 55905, USA 3Department of Biomedical Engineering, University of Minnesota, Minneapolis, MN 55455, USA 4Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027, China 5 School of Chemistry, University of Leeds, Leeds LS2 9JT, UK

Patient Education to Reduce Prehospital Delay Time in Acute Coronary Syndrome

Reducing time from symptom onset to reperfusion therapy decreases infarct size and improves survival in patients with ST-elevation myocardial infarction (STEMI). National quality improvement initiatives, including the Door-to-Balloon (D2B) Quality Alliance, have successfully disseminated evidence-based strategies to reduce door-to-balloon time.1,2 Many hospital systems have achieved the targeted door-to-balloon time <90 minutes for 75% of patients with STEMI presenting directly to a hospital with percutaneous coronary intervention capability.3 However, prehospital delay from time of symptom onset to hospital arrival remains the largest portion of the total delay time and has been refractory to interventions aimed at improving patient responsiveness. Article see p 524 For patients with STEMI, longer prehospital delay is associated with higher in-hospital mortality even after adjusting for patient-, hospital-, and system-level variables including door-to-balloon or door-to-needle time.4,5 In the past 15 years, 2 randomized controlled trials have tested whether educational interventions to improve patient knowledge about acute coronary syndrome (ACS) symptoms and to promote patient action to call 9-1-1 would reduce prehospital delay time. Luepker and colleagues randomized 20 US cities to serve as controls or to receive 18 months of education targeting mass media, community and professional organizations, and patients and clinicians in the Rapid Early Action for Coronary Treatment (REACT) trial.6 The median prehospital delay time was 2.3 hours at baseline and decreased slightly (4.7% per year) during the 18 months in the intervention group; however, this trend was not significantly different to that observed in the control group ( P =0.54). The use of emergency medical services (EMS) increased modestly in the …

Next generation drug-eluting stents: focus on bioabsorbable platforms and polymers

The success of drug-eluting stents in preventing restenosis has shifted the focus of new stent development toward enhancing long term safety and efficacy of these devices, while simultaneously eliminating the need for indefinite dual antiplatelet therapy. A technical advance fulfilling these aims would hold tremendous potential to reduce morbidity, mortality and economic costs associated with the percutaneous treatment of coronary artery disease. An attractive approach is the use of bioabsorbable stent designs. These may include stents with different bioabsorbable drugs, bioabsorbable polymers or even bioabsorbable metallic backbones. A device that could achieve excellent acute and long-term results, but disappear completely within months (thereby avoiding the need for prolonged dual antiplatelet therapy), would be a tremendous advance. Too good to be true? We explore here the scientific rationale and prospects for success with this exciting concept.

Perioperative Nerve Injury: A Silent Scream?

Perioperative Nerve Injury: A Silent Scream?

Cardiovascular Disease Surveillance in the Comparative Effectiveness Landscape

As the leading cause of death in the Western world, cardiovascular disease (CVD) constitutes an enormous public health problem.1 The last 4 decades have been characterized chiefly by the postponement of CVD events and CVD related deaths until older age. Thus, the burden of CVD is increasing in parallel with the increase in life expectancy.2 Within this context, identifying persons with CVD, measuring its incidence and outcome and how these vary over time and across populations is essential. A central goal of this monitoring (otherwise termed surveillance) has been to understand the determinants of the trends in CVD and in particular the respective responsibility of primary prevention versus that of the care of established disease in the genesis of the CVD trends. A direct extension of surveillance is its application to assess the effectiveness of care and the response to interventions designed to improve the quality of care. Articles see pp 414, 475, and 508 Over the first year of its existence, the journal Circulation: Cardiovascular Quality and Outcomes published 3 important articles that illustrate the clinical relevance of surveillance and the applicability of trend studies to care improvement. The article by Lewsey et al constitutes a classic example of CVD surveillance.3 The authors present much needed data on recent (1986 to 2005) trends in the epidemiology of stroke indicating that age- and sex-specific incidence rates of fatal and nonfatal hospitalized strokes in Scotland declined in men from 235 (95% CI, 229 to 242) to 149 (144 to 154) and in women from 299 (292 to 306) to 182 (177 to 188). The decline in incidence of hospitalized stroke varied by age, but overall this equated to a relative reduction in the risk of stroke of 31% in men and 42% in women. Declines in the …