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Plymouth, MI, United States

Herron T.J.,North Campus Research Complex
Cell Calcium | Year: 2016

The advent of induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs) has revolutionized the cardiovascular research field. Now it is possible to generate a virtually unlimited supply of patient specific pluripotent stem cells and cardiomyocytes that can be used for research purposes, drug toxicity testing and/or regenerative medicine therapies. The most immediate application for this technology is in vitro disease modeling and in vitro drug toxicity testing. To date the majority of disease modeling and drug toxicity testing has been performed on single hiPSC-CMs in culture. However, the study of complex cardiac arrhythmia mechanisms requires a more physiological model system of electrically and mechanically connected hiPSC-CMs that function as a syncytium-like the cardiomyocytes of the adult heart. This review focuses on the work that has been performed recently using hiPSC-CM 2D monolayers for the study of cardiac electrical impulse propagation. © 2016 Elsevier Ltd.

Haymart M.R.,Endocrinology and Diabetes | Haymart M.R.,University of Michigan | Haymart M.R.,North Campus Research Complex | Banerjee M.,University of Michigan | And 4 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2013

Context: Little is known about practice patterns in thyroid cancer, a cancer that is increasing in incidence. Objective: Wesought to identify aspects of thyroid cancer management that have the greatest variation. Design/Setting/Participants: We surveyed 944 physicians involved in thyroid cancer care from 251 hospitals affiliated with the US National Cancer Database. Physicians were asked questions in the following four domains: thyroid surgery, radioactive iodine use, thyroid hormone replacement postsurgery, and long-term thyroid cancer management. We calculated the ratio of observed variation to hypothetical maximum variation under the assumed distribution of the response. Ratios closer to 1 indicate greater variation. Results: We had a 66% response rate. We found variation in multiple aspects of thyroid cancer management, including the role of central lymph node dissections (variation, 0.99; 95% confidence interval [CI], 0.98-1.00), the role of pretreatment scans before radioactive iodine treatment (variation, 1.00; 95% CI, 0.98-1.00), and all aspects of long-term thyroid cancer management, including applications of ultrasound (variation, 0.97; 95% CI, 0.93-0.99) and radioactive iodine scans (variation, 0.99; 95% CI, 0.97-1.00). For the management of small thyroid cancers, variation exists in all domains, including optimal extent of surgery (variation, 0.91; 95% CI, 0.88-0.94) and the role of both radioactive iodine treatment (variation, 0.91; 95% CI, 0.89-0.93) and suppressive doses of thyroid hormone replacement (variation, 1.00; 95% CI, 0.99-1.00). Conclusion: We identified areas of variation in thyroid cancer management. To reduce the variation and improve the management of thyroid cancer, there is a need for more research and more research dissemination. Copyright © 2013 by The Endocrine Society.

Hollingsworth J.M.,University of Michigan | Saigal C.S.,RAND Corporation | Lai J.C.,University of California at Los Angeles | Dunn R.L.,University of Michigan | And 3 more authors.
Journal of Urology | Year: 2012

Purpose: The cost efficiency gains achieved from moving procedures to ambulatory surgery centers and offices may be mitigated if the quality of surgical care at these facilities is not comparable to that at the hospital. Motivated by this, we assessed short-term morbidity and mortality for patients by location of care. Materials and Methods: Using a national sample of Medicare claims (1998 to 2006), we identified elderly beneficiaries who underwent one of 22 common outpatient urological procedures. After determining the facility type where each procedure was performed, we measured 30-day mortality, unexpected admissions and postoperative complications. Finally, we fit multivariable logistic regression models to evaluate the association between occurrence of an adverse event and the ambulatory setting where surgical care was delivered. Results: During the study period, there was a substantial increase in the frequency of nonhospital based outpatient surgery. Compared to ambulatory surgery centers and offices, hospitals treated more women (p <0.001). Those patients also tended to be less healthy (p <0.001). While patients experienced fewer postoperative complications following surgery at an ambulatory surgery center, procedures performed outside the hospital were associated with a higher likelihood of a same day admission (ambulatory surgery centers OR 6.96, 95% CI 4.44-10.90 and offices OR 3.64, 95% CI 2.48-5.36). However, notably with case mix adjustment the probability of any adverse event was exceedingly low across all ambulatory settings. Conclusions: These data indicate that small but measurable variation in surgical quality exists by location of care delivery. © 2012 American Urological Association Education and Research, Inc.

Carlozzi N.E.,North Campus Research Complex | Miciura A.,North Campus Research Complex | Migliore N.,North Campus Research Complex | Dayalu P.,University of Michigan
Journal of Huntington's Disease | Year: 2014

Background: The identification of the gene mutation causing Huntington disease has raised hopes for new treatments to ease symptoms and slow functional decline. As such, there has been a push towards designing efficient pharmacological trials (i.e., drug trials), especially with regard to selecting outcomes measures that are both brief and sensitive to changes across the course of the disease, from subtle prodromal changes, to more severe end-stage changes.Objectives: Recently, to aid in efficient development of new HD research studies, the National Institute of Neurological Disorders and Stroke (NINDS) published recommendations for measurement selection in HD. While these recommendations are helpful, many of the recommended measures have little published data in HD. As such, we conducted a systematic review of the literature to identify the most common outcomes measures used in HD clinical trials.Methods: Major medical databases, including PubMed, Embase, CINAHL, and the Cochrane Central Register of Controlled Trials, were used to identify peer-reviewed journal articles in English from 2001 through April 2013; 151 pharmacological trials were identified.Results: The majority of HD clinical trials employed clinician-reported outcomes measures (93%); patient reported outcome measures (11%) and observer reported outcome measures (3%) were used with much less frequency.Conclusions: We provide a review of the most commonly used measures across these trials, compare these measures to the clinical recommendations made by the NINDS working groups, and provide recommendations for selecting measures for future clinical trials that meet the Food and Drug Administration standards.

Satorius A.E.,North Campus Research Complex | Szafranski J.,North Campus Research Complex | Pyne D.,North Campus Research Complex | Ganesan M.,University of Michigan | And 5 more authors.
Shock | Year: 2013

Biofilms production is a central feature of nosocomial infection of catheters and other medical devices used in resuscitation and critical care. However, the very effective biofilm forming pathogen Staphylococcus epidermidis often produces a modest host inflammatory response and few of the signs and symptoms associated with more virulent pathogens. To examine the impact of bacterial biofilm formation on provocation of an innate immune response, we studied the elaboration of the major complement anaphylatoxin C5a by human serum upon contact with S. epidermidis biofilms. Wild-type S. epidermidis and mutants of sarA (a regulatory protein that promotes synthesis of the biofilm-forming polysaccharide intercellular adhesin [PIA]) and icaB (responsible for postexport processing of PIA) were studied. C5a release, as a function of exposed biofilm surface area, was on the order of 1 fmol · cm · s and was dependent on the presence of PIA. Experimental results were used to inform a physiologically based pharmacokinetic model of C5a release by an infected central venous catheter, one of S. epidermidis' primary means of causing human disease. These simulations revealed that the magnitude of C5a release on a superior vena cava catheter completely covered with S. epidermidis would be lower than necessary to alert circulating leukocytes. Combined, the experimental and computational results are highly consistent with clinical observations in which the clinical signs of central line-associated bloodstream infection are often muted in association with this important pathogen. Copyright © 2013 by the Shock Society.

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