CWRUmedicine Annual Research Day

Research Day provides an opportunity for researchers in training at the Case Western Reserve University Department of Medicine to present their biomedical research in a public forum.

This group includes trainees at all levels of programming, including graduate, undergraduate, medical and MD/PhD students, as well as postdoctoral fellows and researchers and clinical residents and fellows.

Research Day also presents an opportunity for colleagues and visitors to learn about the cutting edge research occuring at Case Medical Center.

With multiple posters representing a wide array of research topics are displayed throughout the day, with presenters on hand to discuss their projects and research findings with visitors and guests.

Learn more at CWRUmedicine.org

Susan Redline discusses Sleep Apnea Increases Stroke Risk with WebMD

Moderate to Severe Sleep Apnea Triples Stroke Risk in Men, Study Finds

WebMD | April 8, 2010

Obstructive sleep apnea more than doubles the risk of stroke in men and also increases the danger in women, new research indicates.

The finding comes from a major study of 5,422 people aged 40 and older who had no history of stroke. Researchers say increased risk of stroke appeared in men with mild sleep apnea and rose with severity.

Men with moderate to severe sleep apnea were about three times more likely to have a stroke than men with mild or no sleep apnea, researchers say.

The increased risk of stroke in women with obstructive sleep apnea was significant only in cases of severe apnea, according to the study, published in the American Journal of Respiratory and Critical Care Medicine.

Obstructive Sleep Apnea and Stroke
Data were taken from the Sleep Heart Health Study, which is ongoing at a number of locations. The participants in the beginning performed a standard at-home sleep test to determine whether they had sleep apnea, and if so, its severity.

They were followed for about nine years, and during that time, 193 suffered strokes — 85 men out of 2,462 enrolled and 108 women out of 2,960.

“Although more women had strokes, relatively more men with sleep apnea than without sleep apnea had strokes, and less so in women,” study author Susan Redline, MD, MPH, of Case Western Reserve University in Cleveland, tells WebMD in an email. “I think that the relatively greater impact of sleep apnea on risk of stroke in men relates to the likely longer duration of sleep apnea in men than women.”

Researchers say more than 15 million strokes occur worldwide every year, and that about a third are fatal. Increased risk of stroke in people with sleep apnea exists even without other risk factors, such as weight, high blood pressure, race, diabetes, and smoking.

Men may be more at risk because they develop sleep apnea at younger ages, the researchers say, and thus go untreated for longer periods.

Learn more at CWRUmedicine.org

theHeart.org feature CWRUmedicine research on shared molecular pathway identified for cardiac and vascular disease

theHeart.org | US researchers have pinpointed a genetic factor that affects diseases of both the heart and blood vessels and identified a molecular pathway shared between the two. They propose that a subset of human heart and vascular disease may be due to deficiency of this genetic factor, known as Krüppel-like factor 15 (Klf15), and that amending the pathway in some way could help ameliorate both diseases.

Dr Saptarsi M Haldar (Case Western Reserve University, Cleveland, OH) and colleagues report their findings online April 7, 2010 in Science Translational Medicine.

“Often, people think of cardiac disease and vascular disease as separate entities, but they often run together—for example, in Marfan’s syndrome or in aging, when there are degenerative changes to both the heart and blood vessels,” senior author Dr Mukesh K Jain (Case Western Reserve University) explained to heartwire.

Some years ago, his research team identified the genetic factor Klf15 and showed that it was expressed in both the heart and aorta; they also demonstrated that in human tissue from patients with heart failure or aortic aneurysmal disease, the expression of Klf15 was markedly reduced. The new research is an attempt to identify a common molecular pathway for these effects that could represent a potential therapeutic target.

Both heart and blood vessels affected by Klf15 deficiency

“We hypothesized that maybe the absence of Klf15 or its relative deficiency might be unhealthy, so we generated mice to mimic this,” Jain explains. The mice, which were completely deficient in Klf15, were then stressed using angiotensin 2, and they developed heart failure and, “quite unusually,” aneurysms at the same time, he notes, “so we showed that both the heart and blood vessels of the mice were affected by deficiency of Klf15.

“We then wondered whether there was a common molecular mechanism that might explain this shared pathology,” he continued.

They went on to show that enhancement of the activity of p53—a protein most often associated with protection against cancer—appeared to be causing the adverse effects in the setting of Klf15 deficiency.

Furthermore, they showed that Klf15 functions as a “molecular brake” on p53 function by inhibiting p53 acetylation, which is a critical “on” switch for this protein.

These molecular effects were operative both in the Klf15-deficient mice and in human tissues from heart-failure patients, which were also found to be Klf15 deficient.

Boosting Klf15 production or blocking p53 acetylation may be of benefit

“This now lends us the opportunity to try to identify a chemical compound that might either boost the activity of Klf15 or somehow block the acetylation of p53, which might help ameliorate diseases affecting both the heart and blood vessels,” Jain noted. As well as aging and Marfan’s syndrome, this includes peripartum cardiomyopathy and in particular a subset of women who develop aortic dilatation as well as heart failure in the setting of pregnancy, he explained.

The discovery of new molecular pathways that are amenable to therapeutic manipulation is of immense clinical value,” he says, adding that research into compounds targeting Klf15 or p53 is already under way. Researchers have already demonstrated that a compound called curcumin, the active constituent of the spice turmeric that is often used in Asian cooking, is able to block the acetylation of p53, and they are actively trying to identify other compounds that could enhance the expression of Klf15.

Read the abstract on CWRUmedicine.org

Journal of Lipid Research publish Dr Charles Hoppels recent work on the inner mitochondrial membrane

“Separation and characterization of cardiolipin molecular species by reverse-phase ion pair high-performance liquid chromatography-mass spectrometry”

J Lipid Res. 2010 Apr
Minkler PE, Hoppel CL.

Center for Mitochondrial Diseases, Division of Pharmacology, Department of Medicine, Case Medical Center, University Hospitals, Cleveland

Read the full abstract on CWRUmedicine.org

Message from Richard A. Walsh, MD

We have over 250 full time faculty, 120 medical housestaff, 80 fellows and 400 support staff working at the CWRU School of Medicine, University Hospitals Case Medical Center and the Cleveland VA Medical Center Wade Park Campus.

We are proud of our premier, extramurally funded research programs, our delivery of high-quality, cost-effective patient care at University Hospitals (ranked as a Top Ten Health Care System by Thompson Reuters) and our VA Hospital (ranked first in the entire VA system for Health Care Delivery Measures).

We are also deeply committed to medical student, graduate student and post graduate training.

Our faculty, trainees and staff are committed to the highest standard of excellence in all of our activities in a collegial, integrated and interactive work environment.

We invite you to navigate our website to learn more about who we are and what we do. Visit us at CWRUmedicine.org
If we can be of help, please contact us.

Richard A. Walsh, MD

Chair, Department of Medicine

Which social tool do you use?

It doesn’t take much effort to see the impact social media is having on almost every avenue of our lives, both professionally and personally. Tools such as LinkedIn, Twitter and Facebook, just to name a few, are changing the way and frequency in which we communicate. It should be no surprise, then, that even Healthcare would find itself impacted by the influence and immediacy that social media provides.

We value your opinion and want to know what tools you use to stay up with the latest news and information. Give us your thoughts. Take our poll on social media in healthcare, and let us know what tool(s) you use.

Take the Poll and see results at CWRUmedicine.org

Cleveland ranked 16 on Real Simple’s Top Time-Saving Cities in America List

The report, in the magazine’s April issue, highlighted urban areas across the nation that offer convenient, timesaving services to residents.

To learn more and review Clevelands scorecard visit us at CWRUmedicine.org

The Survey
Takeout on every corner. Easy access to a doctor. Timed traffic lights. These conveniences can ease even the most chaotic days. To assess which places help you make the most of your precious hours, we sorted through reams of data on dozens of large American cities, ranked each on various criteria in five categories (see below) on a scale of 1 to 5, and added up those categories to get an overall score.

Category 1 :: Getting Around
Includes average commute, walkability, traffic congestion, airport on-time performance.

Category 2 :: Health and Safety
Includes average wait to get a doctor’s appointment, physicians per capita, response times of emergency medical services.

Category 3 :: Information and Technology
Includes broadband and wireless availability, bookstores and libraries per capita, helpful resources such as 311 hotlines.

Category 4 :: Green Time-Savers
Includes recycling access and cost, number of farmers’ markets and community gardens, bike friendliness.

Category 5 :: Lifestyle
Includes number of personal trainers and organizers, restaurants offering takeout per capita, miscellaneous time-saving services.

Learn more at CWRUmedicine.org

New Research Published on Antibiotic resistance determinants in Acinetobacter spp

We explored the association of antibiotic-resistant phenotypes and genotypes in Acinetobacter spp with clinical outcomes and characteristics in 75 patients from a major military treatment facility. Amikacin resistance was associated with nosocomial acquisition of A baumannii, and carbapenem resistance and bla(OXA-23) were associated with the need for mechanical ventilation. The presence of bla(OXA-23) also correlated with longer hospital and ICU stay. Associations between bla(OXA-23) and complexity, duration, and changes made to antibiotic regimens also existed. Copyright 2010.

Learn more at CWRUmedicine.org

Read why Cushing’s syndrome: Why is diagnosis so difficult?

Practicing and perfecting the art of medicine demands recognition that uncertainty permeates all clinical decisions. When delivering clinical care, clinicians face a multiplicity of potential diagnoses, limitations in diagnostic capacity, and “sub-clinical” disease identified by tests rather than by clinical manifestations. In addition, clinicians must recognize the rapid changes in scientific knowledge needed to guide decisions. Cushing’s syndrome is one of several disorders in which there may be considerable difficulty and delay in diagnosis. This article describes a current model of clinical reasoning, some of its challenges, and the application of the principles of clinical epidemiology to meet some of those challenges.

Learn more at CWRUmedicine.org

New Research on Older Patients with Acute Myeloid Leukemia in their first complete remission

“Effect of Age on Outcome of Reduced-Intensity Hematopoietic Cell Transplantation for Older Patients With Acute Myeloid Leukemia in First Complete Remission or With Myelodysplastic Syndrome”

McClune BL, Weisdorf DJ, Pedersen TL, da Silva GT, Tallman MS, Sierra J, Dipersio J, Keating A, Gale RP, George B, Gupta V, Hahn T, Isola L, Jagasia M, Lazarus H, Marks D, Maziarz R, Waller EK, Bredeson C, Giralt S.
J Clin Oncol. 2010 Mar 8

PURPOSE:
Acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS) primarily afflict older individuals. Hematopoietic cell transplantation (HCT) is generally not offered because of concerns of excess morbidity and mortality. Reduced-intensity conditioning (RIC) regimens allow increased use of allogeneic HCT for older patients. To define prognostic factors impacting long-term outcomes of RIC regimens in patients older than age 40 years with AML in first complete remission or MDS and to determine the impact of age, we analyzed data from the Center for International Blood and Marrow Transplant Research (CIBMTR).

PATIENTS AND METHODS:
We reviewed data reported to the CIBMTR (1995 to 2005) on 1,080 patients undergoing RIC HCT. Outcomes analyzed included neutrophil recovery, incidence of acute or chronic graft-versus-host disease (GVHD), nonrelapse mortality (NRM), relapse, disease-free survival (DFS), and overall survival (OS).

RESULTS:
Univariate analyses demonstrated no age group differences in NRM, grade 2 to 4 acute GVHD, chronic GVHD, or relapse. Patients age 40 to 54, 55 to 59, 60 to 64, and >/= 65 years had 2-year survival rates as follows: 44% (95% CI, 37% to 52%), 50% (95% CI, 41% to 59%), 34% (95% CI, 25% to 43%), and 36% (95% CI, 24% to 49%), respectively, for patients with AML (P = .06); and 42% (95% CI, 35% to 49%), 35% (95% CI, 27% to 43%), 45% (95% CI, 36% to 54%), and 38% (95% CI, 25% to 51%), respectively, for patients with MDS (P = .37). Multivariate analysis revealed no significant impact of age on NRM, relapse, DFS, or OS (all P > .3). Greater HLA disparity adversely affected 2-year NRM, DFS, and OS. Unfavorable cytogenetics adversely impacted relapse, DFS, and OS. Better pre-HCT performance status predicted improved 2-year OS. CONCLUSION: With these similar outcomes observed in older patients, we conclude that older age alone should not be considered a contraindication to HCT.