tbuckley/cabot-search huggingface dataset:
Effect of Moderate to Vigorous Physical Activity on All-Cause Mortality in Middle-aged and Older Australians
Authors: Klaus Gebel, Ding Ding, Tien Chey, Emmanuel Stamatakis, Wendy J. Brown, Adrian E. Bauman
Journal: JAMA Internal Medicine (2015)

<h3>Importance</h3> Few studies have examined how different proportions of moderate and vigorous physical activity affect health outcomes. <h3>Objective</h3> To examine whether the proportion of total moderate to vigorous activity (MVPA) that is achieved through vigorous activity is associated with all-cause mortality independently of the total amount of MVPA. <h3>Design, Setting, and Participants</h3> We performed a prospective cohort study with activity data linked to all-cause mortality data from February 1, 2006, through June 15, 2014, in 204 542 adults aged 45 through 75 years from the 45 and Up population-based cohort study from New South Wales, Australia (mean [SD] follow-up, 6.52 [1.23] years). Associations between different contributions of vigorous activity to total MVPA and mortality were examined using Cox proportional hazards models, adjusted for total MVPA and sociodemographic and health covariates. <h3>Exposures</h3> Different proportions of total MVPA as vigorous activity. Physical activity was measured with the Active Australia Survey. <h3>Main Outcomes and Measures</h3> All-cause mortality during the follow-up period. <h3>Results</h3> During 1 444 927 person-years of follow-up, 7435 deaths were registered. Compared with those who reported no MVPA (crude death rate, 8.34%), the adjusted hazard ratios for all-cause mortality were 0.66 (95% CI, 0.61-0.71; crude death rate, 4.81%), 0.53 (95% CI, 0.48-0.57; crude death rate, 3.17%), and 0.46 (95% CI, 0.43-0.49; crude death rate, 2.64%) for reporting 10 through 149, 150 through 299, and 300 min/wk or more of activity, respectively. Among those who reported any MVPA, the proportion of vigorous activity revealed an inverse dose-response relationship with all-cause mortality: compared with those reporting no vigorous activity (crude death rate, 3.84%) the fully adjusted hazard ratio was 0.91 (95% CI, 0.84-0.98; crude death rate, 2.35%) in those who reported some vigorous activity (but &lt;30% of total activity) and 0.87 (95% CI, 0.81-0.93; crude death rate, 2.08%) among those who reported 30% or more of activity as vigorous. These associations were consistent in men and women, across categories of body mass index and volume of MVPA, and in those with and without existing cardiovascular disease or diabetes mellitus. <h3>Conclusions and Relevance</h3> Among people reporting any activity, there was an inverse dose-response relationship between proportion of vigorous activity and mortality. Our findings suggest that vigorous activities should be endorsed in clinical and public health activity guidelines to maximize the population benefits of physical activity.
Cardiac Expression of a Mini-dystrophin That Normalizes Skeletal Muscle Force Only Partially Restores Heart Function in Aged Mdx Mice
Authors: Brian Bostick, Yongping Yue, Chun Long, Nate Marschalk, Deborah M Fine, Jing Chen, Dongsheng Duan
Journal: Molecular Therapy (2008)

Duchenne muscular dystrophy (DMD) affects both skeletal and cardiac muscle. It is currently unclear whether the strategies developed for skeletal muscle can ameliorate cardiomyopathy. Synthetic mini-/micro-dystrophin genes have yielded impressive skeletal muscle protection in animal models. The 6-kb DeltaH2-R19 minigene is particularly promising because it completely restores skeletal muscle force to wild-type levels. Here, we examined whether expressing this minigene in the heart, but not skeletal muscle, could normalize cardiac function in the mdx model of DMD cardiomyopathy. Transgenic mdx mice were generated to express the DeltaH2-R19 minigene under the control of the alpha-myosin heavy-chain promoter. Heart structure and function were examined in adult and very old mice. The DeltaH2-R19 minigene enhanced cardiomyocyte sarcolemmal strength and prevented myocardial fibrosis. It also restored the dobutamine response and enhanced treadmill performance. Surprisingly, heart-restricted DeltaH2-R19 minigene expression did not completely normalize electrocardiogram and hemodynamic abnormalities. Overall, systolic function and ejection fraction were restored to normal levels but stroke volume and cardiac output remained suboptimal. Our results demonstrate that the skeletal muscle-proven DeltaH2-R19 minigene can correct cardiac histopathology but cannot fully normalize heart function. Novel strategies must be developed to completely restore heart function in DMD.
Prediction of Lifetime Risk for Cardiovascular Disease by Risk Factor Burden at 50 Years of Age
Authors: Donald M. Lloyd-Jones, Eric P. Leip, Martin G. Larson, Ralph B. D’Agostino, Alexa Beiser, Peter W.F. Wilson, Philip A. Wolf, Daniel Levy
Journal: Circulation (2006)

Lifetime risk for atherosclerotic cardiovascular disease (CVD) has not previously been estimated, and the effect of risk factor burden on lifetime risk is unknown.We included all Framingham Heart Study participants who were free of CVD (myocardial infarction, coronary insufficiency, angina, stroke, claudication) at 50 years of age. Lifetime risks to 95 years of age were estimated for men and women, with death free of CVD as a competing event. We followed up 3564 men and 4362 women for 111,777 person-years; 1757 had CVD events and 1641 died free of CVD. At 50 years of age, lifetime risks were 51.7% (95% CI, 49.3 to 54.2) for men and 39.2% (95% CI, 37.0 to 41.4) for women, with median survivals of 30 and 36 years, respectively. With more adverse levels of single risk factors, lifetime risks increased and median survivals decreased. Compared with participants with > or =2 major risk factors, those with optimal levels had substantially lower lifetime risks (5.2% versus 68.9% in men, 8.2% versus 50.2% in women) and markedly longer median survivals (>39 versus 28 years in men, >39 versus 31 years in women).The absence of established risk factors at 50 years of age is associated with very low lifetime risk for CVD and markedly longer survival. These results should promote efforts aimed at preventing development of risk factors in young individuals. Given the high lifetime risks and lower survival in those with intermediate or high risk factor burden at 50 years of age, these data may be useful in communicating risks and supporting intensive preventive therapy.
Nitric oxide release from porcine mitral valves
Authors: L. Siney, M. J Lewis
Journal: Cardiovascular Research (1993)

Objective: The aim was to investigate the release of nitric oxide (NO) from porcine mitral valves. Methods: The valves were sandwiched between gauze in a chamber constantly perfused by Holman solution. The presence of NO in the perfusate of the valves was detected by two methods: a bioassay cascade system using preconstricted rings of pig coronary artery as the detector tissue, and a chemiluminescent method, specific for NO. Results: Porcine mitral valves release NO under basal conditions. Release can be increased by the agonists ADP, substance P, bradykinin, thrombin, and the calcium ionophore A23187. ADP was by far the most effective. NO release under basal conditions was inhibited by each of the three NO synthase inhibitors studied, but only NG-monomethyl L-arginine (L-NMMA) reduced ADP stimulated release. A reversible inhibition of NO release occurred when valves were perfused with calcium-free Holman solution and NO release was inhibited by removal of the endocardial monolayer. Conclusions: The endocardial endothelium covering the mitral valves releases NO under basal conditions and following stimulation with several agonists. The NO synthase enzyme is calcium dependent. Different mechanisms may exist for the synthesis of basal and agonist dependent NO release in these cells. Cardiovascular Research 1993;27:1657-1661
P322Structure and hemodynamics in the chick chorioallantoic membrane: Murray's law revisited
Authors: M Maibier, B Nitzsche, B Reglin, M Hoepfner, AR Pries
Journal: Cardiovascular Research (2014)

Purpose: Although highly used as in vivo model to study e.g. angiogenesis and tumor development, topology and hemodynamics of the chick chorioallantoic membrane (CAM) vasculature has not been systematically characterized so far. Here, we investigated topological and hemodynamic network characteristics of the CAM by combining intravital microscopy and mathematical simulations.
Design and function of a mechanical assembly for recording echocardiograms during upright exercise
Authors: D. R. REDWOOD, W. L. HENRY, S. GOLDSTEIN, E. R. SMITH
Journal: Cardiovascular Research (1975)

It has proved difficult to record satisfactorily echocardiograms during patient motion. This report describes the design and preliminary results obtained with an echo harness with which the transducer can be held stationary or moved rapidly and predictably by remote control. With this apparatus, recordings can be made during tilting, drug intervention, and during bicycle and treadmill exercise.
HIV-associated cardiomyopathy is not Keshan disease
Authors: G. Barbaro
Journal: Journal of the Royal Society of Medicine (2002)

In reply to Dr Cheng's comments (April 2002 JRSM1) I do not question the therapeutic role of selenium supplementation in patients with malnutrition (including selenium deficiency) and dilated cardiomyopathy in those with Keshan disease. However, the role of selenium deficiency in HIV-infected patients with cardiomyopathy is still controversial and controlled prospective clinical trials in this subset of patients are lacking. Cardiac and pulmonary complications of HIV disease are generally late manifestations and may be related to prolonged effects of immunosuppression and a complex interplay of mediator effects from opportunistic infections, viral infections, autoimmune response to viral infection, drug-related cardiotoxicity and nutritional deficiencies (selenium, vitamin B12, carnitine, growth hormone and thyroid hormone, frequently in combination)2,3. Because of its multifactorial pathogenesis, HIV-associated cardiomyopathy should not be compared to Keshan disease, since they are independent nosological entities from both a pathogenetic and a clinical point of view.
Radiation and Cancer
Authors: Mary H. Waziri
Journal: JAMA (1981)

<h3>To the Editor.—</h3> Regular examination of breasts in women previously exposed to radiation, as suggested by Stoffer et al (1981;245:462), is excellent advice. They failed, however, to note the other known risk factors in development of breast cancer.<sup>1</sup>The patient described, and her family, may still be at risk for cancer development. She may have one of several types of familial breast cancer syndromes<sup>2</sup>or, more important, could be a person afflicted with the family cancer syndrome (FCS).<sup>3</sup>The patient displayed a potential for thyroid tumor as well as the actual development of bilateral breast cancer. No mention is made of investigation into other potential tumors in this 28-year-old woman or in other family members. Family cancer syndrome, described by Lynch et al,<sup>3</sup>recognizes groupings of specific cancers found in excess within certain families. In these families the predisposition to cancer seems to be inherited in
The influence of the individual surgeon and of the type of vagotomy upon the insulin test after vagotomy
Authors: D. Johnston, J. C. Goligher
Journal: Gut (1971)

Six hundred and seventy-six insulin tests performed in the early postoperative period after vagotomy and drainage for duodenal ulcer were analysed by the criteria of Hollander. Consultants had done 364 vagotomies, of which 17·6% were shown to be incomplete. Registrars and senior registrars had done 312, of which 12·2% were incomplete. Thus, consultants may not be significantly better, on average, than their juniors at achieving complete gastric vagotomy, even when allowance is made for the fact that they tend to take on the more difficult cases. The ability to achieve a complete vagotomy varied widely from surgeon to surgeon, regardless of his status. Of 515 truncal vagotomies, 15·7% were incomplete compared with 14·3% of 161 bilateral selective vagotomies. An `early-positive9 secretory response within one hour of the insulin injection, which is commonly regarded as indicating inadequate vagotomy, was found in 5·6% of patients after truncal vagotomy and 3·1% of patients after selective vagotomy.
A non-invasive serum fibrosis marker panel can consistently select chronic hepatitis C patients with minimal stage (F0–F1) fibrosis from more advanced disease (F2–F4)
Authors: K. Patel, C. Hezode, S.C. Gordon, I.M. Jacobson, J.-M. Pawlotsky, E. Oh, K.M. Smith, J.G. McHutchison
Journal: Journal of Hepatology (2003)
Augmentation of coronary responsiveness to serotonin at the site of X-ray-induced intimal thickening in miniature pigs
Authors: W. Mitsuoka, S. Egashira, H. Tagawa, T. Kuga, Y. Hayashi, A. Yamada, H. Tomoike, M. Nakamura, A. Takeshita
Journal: Cardiovascular Research (1995)

Objective: X-irradiation is known to enhance atherosclerotic change. We tested whether coronary vasoconstrictor responses are augmented at the sites of X-ray-induced intimal thickening in Göttingen miniature pigs. Methods: In 17 pigs, a major branch of the left coronary artery was denuded with a balloon catheter. In 10 pigs, the denuded portion of the left coronary artery was selectively irradiated with 15 Gy of X-rays twice at 3 and 4 months after denudation (group 1). The remaining 7 pigs were not irradiated (group 2). The effects of intracoronary administration of serotonin, histamine and phenylephrine on the coronary diameter were studied 3 (3M) and 5 months (5M) after denudation. After the angiographical study at 5M, the vessels were isolated and isometric tension was measured in an organ chamber. Results: The percent reduction in coronary diameter evoked with 10 μg · kg−1 of serotonin increased from 39(s.e.m. 4)% before X-irradiation (3M) to 75(6)% after X-irradiation (5M) in group 1 (P < 0.01), while it did not differ in group 2 [39(6)% at 3M vs. 33(8)% at 5M]. In group 1, serotonin-induced coronary constriction was frequently accompanied by ischemic ECG changes. Histamine (10 μg · kg−1)-induced vasoconstriction was also augmented but to a smaller degree [47(6)% at 3M vs. 62(4)% at 5M; P < 0.05] in group 1, while it remained unchanged in group 2 [52(5)% at 3M vs. 44(7)% at 5M]. Phenylephrine did not cause detectable contraction in either group at 3M or 5M. Methysergide and ketanserin attenuated serotonin-induced hypercontraction in a dose-dependent fashion. In the in vitro studies, endothelium-dependent relaxation to serotonin was impaired at the denuded site with (group 1) and without (group 2) X-irradiation to a similar extent. Isometric tension of medial smooth muscle developed by serotonin was significantly greater at the denuded site with X-irradiation (group 1) than the control site and the denuded site without X-irradiation (group 2) (P < 0.05). Intimal thickening was significantly greater at the denuded sites with X-irradiation [group 1, 238(45) μm] than at the denuded sites without X-irradiation [group 2, 58(5) μm] (P < 0.05). Conclusions: These results indicate that X-irradiation augments the coronary vasoconstrictor responses to autacoids, predominantly to serotonin, and that this augmentation is accompanied by enhanced intimal thickening. Serotonin-induced hypercontraction after X-irradiation resulted mainly from the hyperreactivity of medial smooth muscle.
Functional significance of cardiac myosin essential light chain isoform switching in transgenic mice.
Authors: J G Fewell, T E Hewett, A Sanbe, R Klevitsky, E Hayes, D Warshaw, D Maughan, J Robbins
Journal: Journal of Clinical Investigation (1998)

The different functions of the ventricular- and atrial-specific essential myosin light chains are unknown. Using transgenesis, cardiac-specific overexpression of proteins can be accomplished. The transgenic paradigm is more useful than originally expected, in that the mammalian heart rigorously controls sarcomeric protein stoichiometries. In a clinical subpopulation suffering from heart disease caused by congenital malformations of the outflow tract, an ELC1v-->ELC1a isoform shift correlated with increases in cross-bridge cycling kinetics as measured in skinned fibers derived from the diseased muscle. We have used transgenesis to replace the ventricular isoform of the essential myosin light chain with the atrial isoform. The ELC1v--> ELC1a shift in the ventricle resulted in similar functional alterations. Unloaded velocities as measured by the ability of the myosin to translocate actin filaments in the in vitro motility assay were significantly increased as a result of the isoform substitution. Unloaded shortening velocity was also increased in skinned muscle fibers, and at the whole organ level, both contractility and relaxation were significantly increased. This increase in cardiac function occurred in the absence of a hypertrophic response. Thus, ELC1a expression in the ventricle appears to be advantageous to the heart, resulting in increased cardiac function.
Organ Preservation for Rectal Cancer
Authors: Nancy N. Baxter, Julio Garcia-Aguilar
Journal: Journal of Clinical Oncology (2007)

Organ preservation with maintenance of function in the treatment of rectal cancer is highly valued by patients. Although most patients with resectable rectal cancer can undergo a sphincter-sparing radical procedure, there are patient, tumor, surgeon, and treatment factors that influence the ability to restore intestinal continuity after radical resection. Although population-based data suggest that the rate of sphincter preservation is lower than could be obtained at expert centers, there are patients in whom low anterior resection with colo-anal anastomosis is not technically feasible and/or oncologically sound. Additionally, resection with ultralow anastomosis results in functional compromise in many patients. Local treatment of rectal cancer aims to decrease the morbidity and the functional sequelae associated with radical resection; however, local excision is associated with a higher rate of local recurrence than is radical resection. Strict selection criteria are essential when considering local excision, and patients should be informed of the risk of local recurrence. The use of adjuvant therapy with local excision, particularly in patients with T2 lesions, has promise but should be considered only as part of a clinical trial.
THE INFLUENCE OF THE SUPRARENAL GLAND ON THE THYMUS
Authors: Henry L. Jaffe
Journal: The Journal of Experimental Medicine (1924)

1. Regeneration of involuted thymuses of old rats follows double suprarenalectomy in this species with great constancy. 2. Partial thymectomy alone does not induce compensatory secondary hyperplasia in involuting glands. 3. Regeneration of the thymus following suprarenalectomy would appear to be completed in most rats in about 2 weeks; and it probably begins in the medulla.
Long-Term Additive Prognostic Value of Thallium-201 Myocardial Perfusion Imaging Over Clinical and Exercise Stress Test in Low to Intermediate Risk Patients
Authors: Gérald Vanzetto, Olivier Ormezzano, Daniel Fagret, Michel Comet, Bernard Denis, Jacques Machecourt
Journal: Circulation (1999)

The exercise treadmill test (ETT) and Tl201 single proton emission computed tomography (SPECT) are of short- to medium-term prognostic value in coronary heart disease. We assessed the long-term prognostic value of these tests in a large population of patients with low- to intermediate risk of cardiac events.One thousand one hundred thirty-seven patients (857 men, age 55+/-9 years) referred for typical (62.1%) or atypical (22.4%) chest pain, or suspected silent ischemia (15.5%), were followed up for 72+/-18 months. Overall mortality was higher after strongly positive (ST depression >2 mm, or >1 mm for a workload </=75 W) (2. 36%/y) or nondiagnostic ETT (1.63%/y) than after normal (0.85%/y) or positive ETT (1.37%/y) (P=0.002), and after abnormal SPECT than after normal SPECT (1.60%/y versus 0.68%/y, P=0.001). The major cardiac event rate (cardiac death or myocardial infarction [MI]) was 0.88%, 1.59%, 2.10%, and 2.13%/y after negative, positive, strongly positive, and nondiagnostic ETT, respectively (P=0.003), and 0.56%, 1.43%, and 2.05%/y in patients with 0, 1 to 2, and >/=3 abnormal segments on SPECT, respectively (P<0.002). An abnormal SPECT was predictive of MI (P<0.001), whereas ETT was not. In multivariate analysis, SPECT was of incremental prognostic value over clinical and ETT data for predicting overall mortality and major cardiac events.The incremental predictive value of SPECT is maintained over 6 years and is particularly relevant after positive, strongly positive, and nondiagnostic ETT.
Differences in MicroRNA Expression Profiles of Adrenocortical Tumors – Letter
Authors: Zsófia Tömböl, Peter M. Szabó, Attila Patócs, Károly Rácz, Peter Igaz
Journal: Clinical Cancer Research (2010)

In their elegant study published in the December 15, 2009 issue of  Clinical Cancer Research , Soon and colleagues described differences in the microRNA expression profiles of adrenocortical tumors (ACT) and established predictors for poor prognosis. Twenty-three microRNAs were found to be significantly differentially expressed between adrenocortical adenomas (ACA) and carcinomas (ACC) but only two between normal adrenal cortices (NA) and ACTs by microarray analysis. Four microRNAs were validated by quantitative real-time PCR (1).  In our previous study published in the September 2009 issue of  Endocrine-Related Cancer  (epub 22 June; ref. 2), we have performed an integrative bioinformatic analysis on ACTs including parallel microRNA (Taqman TLDA Panel) and mRNA profiling and pathway analysis. We have found 22 microRNAs with significant differences in expression among NA, hormonally inactive ACA, cortisol-producing ACA, and ACC. Six microRNAs were validated by quantitative real-time PCR. dCT miR-511  − dCT miR-503  (dCT, delta cycle threshhold) was identified as the best predictor of malignancy.  Whereas the number of significantly differentially expressed microRNAs was highly similar in the two studies, only two were common in both: miR-503 and miR-181b (both overexpressed in ACCs).  There are several differences between the structures of the two studies that might have accounted for these discrepancies. Although the number of tumors included in the study by Soon et al. was higher (27 ACA and 22 ACC) than in ours (19 ACA and 7 ACC), the groups have not been subdivided based on hormone secretion in the former. We have studied only cortisol-secreting ACCs, and ACAs have been subdivided into inactive ACA ( n  = 10) and cortisol-producing ACA ( n  = 9) groups. Both ACAs and ACCs express glucocorticoid receptors that are even overexpressed in ACCs (3). Adrenocortical microRNA expression patterns might be influenced by glucocorticoids. 1    1 A. Patocs, Z. Tombol, P.M. Szabo, P. Igaz, K. Racz, unpublished results.   This might argue against the establishment of tumor groups irrespective of their hormonal activity.  Furthermore, we have studied intact NA ( n  = 10) removed from patients operated for malignant kidney tumors, whereas Soon et al. used NA samples ( n  = 6) from adrenalectomy specimens away from the site of the adenoma. He et al. reported that the overexpression of miR-221 characteristic for papillary thyroid cancer can be detected in the unaffected, histologically normal tissue surrounding the tumor (4). It is possible that a similar phenomenon might also exist in ACTs, and this could be related to the finding that only two microRNAs were significantly differentially expressed between NA and tumors.  Further studies will be necessary to clarify the relevance and potential diagnostic applicability of microRNAs for adrenocortical tumors.  Disclosure of Potential Conflicts of Interest  No potential conflicts of interest were disclosed.