Campus & alumni news

Boston University Medicine was published by the Boston University Medical Campus, and presented stories on events and topics of interest to members of the BU Medical Campus community. It followed the discontinued publication Centerscope as Boston University Medicine from 1991-2005, and was continued as Campus & Alumni News from 2006-2013 before returning to the title Boston University Medicine from 2014-present

Left ventricular assist device implantation augments nitric oxide dependent control of mitochondrial respiration in failing human hearts

AbstractOBJECTIVESThe objective of the study was to evaluate nitric oxide (NO) mediated regulation of mitochondrial respiration after implantation of a mechanical assist device in end-stage heart failure.BACKGROUNDVentricular unloading using a left ventricular assist device (LVAD) can improve mitochondrial function in end-stage heart failure. Nitric oxide modulates the activity of the mitochondrial electron transport chain to regulate myocardial oxygen consumption (MVO2).METHODSMyocardial oxygen consumption was measured polarographically using a Clark-type oxygen electrode in isolated left ventricular myocardium from 26 explanted failing human hearts obtained at the time of heart transplantation.RESULTSThe rate of decrease in oxygen concentration was expressed as a percentage of baseline. Results of the highest dose of drug are shown. Decrease in MVO2 was greater in LVAD hearts (n = 8) compared with heart failure controls (n = 18) in response to the following drugs: bradykinin (−34 ± 3% vs. −24 ± 5%), enalaprilat (−37 ± 5% vs. −23 ± 5%) and amlodipine (−43 ± 13% vs. −16 ± 5%; p < 0.05 from controls). The decrease in MVO2 in LVAD hearts was not significantly different from controls in response to diltiazem (−22 ± 5% in both groups) and exogenous NO donor, nitroglycerin (−33 ± 7% vs. −30 ± 3%). Nw-nitro-L-arginine methyl ester, inhibitor of NO synthase, attenuated the response to bradykinin, enalaprilat and amlodipine. Reductions in MVO2 in response to diltiazem and nitroglycerin were not altered by inhibiting NO.CONCLUSIONSChronic LVAD support potentiates endogenous NO-mediated regulation of mitochondrial respiration. Use of medical or surgical interventions that augment NO bioavailability may promote myocardial recovery in end-stage heart failure

Multicenter clinical evaluation of the HeartMate vented electric left ventricular assist system in patients awaiting heart transplantation

AbstractBackground: Despite advances in heart transplantation and mechanical circulatory support, mortality among transplant candidates remains high. Better ways are needed to ensure the survival of transplant candidates both inside and outside the hospital. Methods: In a prospective, multicenter clinical trial conducted at 24 centers in the United States, 280 transplant candidates (232 men, 48 women; median age, 55 years; range, 11-72 years) unresponsive to inotropic drugs, intra-aortic balloon counterpulsation, or both, were treated with the HeartMate Vented Electric Left Ventricular Assist System (VE LVAS). A cohort of 48 patients (40 men, 8 women; median age, 50 years; range, 21-67 years) not supported with an LVAS served as a historical control group. Outcomes were measured in terms of laboratory data (hemodynamic, hematologic, and biochemical), adverse events, New York Heart Association functional class, and survival. Results: The VE LVAS–treated and non–VE LVAS–treated (control) groups were similar in terms of age, sex, and distribution of patients by diagnosis (ischemic cardiomyopathy, idiopathic cardiomyopathy, and subacute myocardial infarction). VE LVAS support lasted an average of 112 days (range, < 1-691 days), with 54 patients supported for > 180 days. Mean VE LVAS flow (expressed as pump index) throughout support was 2.8 L · min–1 · m–2. Median total bilirubin values decreased from 1.2 mg/dL at baseline to 0.7 mg/dL (P =.0001); median creatinine values decreased from 1.5 mg/dL at baseline to 1.1 mg/dL (P =.0001). VE LVAS–related adverse events included bleeding in 31 patients (11%), infection in 113 (40%), neurologic dysfunction in 14 (5%), and thromboembolic events in 17 (6%). A total of 160 (58%) patients were enrolled in a hospital release program. Twenty-nine percent of the VE LVAS-treated patients (82/280) died before receiving a transplant, compared with 67% of controls (32/48) (P <.001). Conversely, 71% of the VE LVAS–treated patients (198/280) survived: 67% (188/280) ultimately received a heart transplant, and 4% (10/280) had the device removed electively. One-year post-transplant survival of VE LVAS–treated patients was significantly better than that of controls (84% [158/188] vs 63% [10/16]; log rank analysis P =.0197). Conclusion: The HeartMate VE LVAS provides adequate hemodynamic support, has an acceptably low incidence of adverse effects, and improves survival in heart transplant candidates both inside and outside the hospital. The studies of the HeartMate LVAS (both pneumatic and electric) for Food and Drug Administration approval are the only studies with a valid control group to show a survival benefit for cardiac transplantation

Noncoding deletions reveal a gene that is critical for intestinal function.

Large-scale genome sequencing is poised to provide a substantial increase in the rate of discovery of disease-associated mutations, but the functional interpretation of such mutations remains challenging. Here we show that deletions of a sequence on human chromosome 16 that we term the intestine-critical region (ICR) cause intractable congenital diarrhoea in infants1,2. Reporter assays in transgenic mice show that the ICR contains a regulatory sequence that activates transcription during the development of the gastrointestinal system. Targeted deletion of the ICR in mice caused symptoms that recapitulated the human condition. Transcriptome analysis revealed that an unannotated open reading frame (Percc1) flanks the regulatory sequence, and the expression of this gene was lost in the developing gut of mice that lacked the ICR. Percc1-knockout mice displayed phenotypes similar to those observed upon ICR deletion in mice and patients, whereas an ICR-driven Percc1 transgene was sufficient to rescue the phenotypes found in mice that lacked the ICR. Together, our results identify a gene that is critical for intestinal function and underscore the need for targeted in vivo studies to interpret the growing number of clinical genetic findings that do not affect known protein-coding genes

Evidence-Based Guidelines for Cardiovascular Disease Prevention in Women

Significant advances in our knowledge about interventions to prevent cardiovascular disease (CVD) have occurred since publication of the first female-specific recommendations for preventive cardiology in 1999.1 Despite research-based gains in the treatment of CVD, it remains the leading killer of women in the United States and in most developed areas of the world.2–3 In the United States alone, more than one half million women die of CVD each year, exceeding the number of deaths in men and the next 7 causes of death in women combined. This translates into approximately 1 death every minute.2 Coronary heart disease (CHD) accounts for the majority of CVD deaths in women, disproportionately afflicts racial and ethnic minorities, and is a prime target for prevention.1–2 Because CHD is often fatal, and because nearly two thirds of women who die suddenly have no previously recognized symptoms, it is essential to prevent CHD.2 Other forms of atherosclerotic/thrombotic CVD, such as cerebrovascular disease and peripheral arterial disease, are critically important in women. Strategies known to reduce the burden of CHD may have substantial benefits for the prevention of noncoronary atherosclerosis, although they have been studied less extensively in some of these settings

Development and validation of HERWIG 7 tunes from CMS underlying-event measurements

This paper presents new sets of parameters (“tunes”) for the underlying-event model of the HERWIG7 event generator. These parameters control the description of multiple-parton interactions (MPI) and colour reconnection in HERWIG7, and are obtained from a fit to minimum-bias data collected by the CMS experiment at s=0.9, 7, and 13Te. The tunes are based on the NNPDF 3.1 next-to-next-to-leading-order parton distribution function (PDF) set for the parton shower, and either a leading-order or next-to-next-to-leading-order PDF set for the simulation of MPI and the beam remnants. Predictions utilizing the tunes are produced for event shape observables in electron-positron collisions, and for minimum-bias, inclusive jet, top quark pair, and Z and W boson events in proton-proton collisions, and are compared with data. Each of the new tunes describes the data at a reasonable level, and the tunes using a leading-order PDF for the simulation of MPI provide the best description of the dat