tbuckley/cabot-search huggingface dataset:
Abstract 19328: Clinical Predictors of Renal Failure in Heart Transplant Patients Following Initiation of Calcineurin Inhibitor Free Regimen
Authors: Omeed Elboudwarej, Jignesh Patel, Michelle Kittleson, Frank Liou, Jon Kobashigawa
Journal: Circulation (2014)

Purpose: Calcineurin inhibitor (CNI) therapy has been the cornerstone of standard triple-drug immunosuppressive therapy that has significantly improved outcomes after heart transplantation (HTx). However, CNI-induced nephrotoxicity remains a significant cause of morbidity and mortality. Renal-sparing protocols (RSP) using CNI-free regimens have improved renal function in some patients (pts). The clinical variables associated with development of renal failure despite RSP initiation are unknown. We therefore evaluated HTx pts on RSP for possible risk factors associated with renal failure. Methods: Of 1,424 HTx pts between 1/1994 to 1/2011, 61 were identified who underwent RSP. Creatinine values were obtained at time of RSP initiation and ≥3 months post-RSP. The CKD-EPI Cr Equation (2009) was used to estimate GFR. We assessed pts for type of CNI, prednisone use, ACE-inhibitor/ARB use, calcium-channel blocker use, sex, race, hypertension, diabetes mellitus, obesity, and hypercholesterolemia. A logistic regression model was used to determine if there was an association between the clinical variables measured and stage IV renal failure (estimated GFR &lt;30 mL/kg/m2). Results: 40 patients (66%) developed renal failure at an average of 14.4 ± 12.8 months after initiating RSP. Pts with an estimated GFR &lt;30 mL/kg/ m2 at time of RSP initiation had a 5.4-fold (1.69-17.26, p=0.004) higher risk of developing renal failure. By multivariate logistic regression, this relationship remained significant after controlling for potential confounders in the relationship between RSP and renal failure, with a 8.9-fold (1.64-48.4; p=0.01) risk of renal failure in pts with an estimated GFR &lt;30 mL/kg/ m2 at time of RSP initiation. The other clinical variables tested did not significantly affect outcome (Table). Conclusions: RSP does not appear to be effective in pts with advanced renal disease. RSP should be considered in pts with CNI nephrotoxicity at an earlier stage of the disease.
Abstract 822: The histone Methyltransferase MLL is an Upstream Regulator of Endothelial Cell Angiogenic Functions
Authors: Florian Diehl, Michael Potente, Carmen Urbich, Lothar Rossig
Journal: Circulation (2006)

Posttranslational histone modification by acetylation, phosphorylation, or methylation is involved in the regulation of gene expression. Among homeodomain transcription factors, transcriptional act...
CARDIAC PROBLEMS IN WAR TIME
Authors: Paul D. White
Journal: Annals of Internal Medicine (1943)

Article1 March 1943CARDIAC PROBLEMS IN WAR TIMEPAUL D. WHITE, F.A.C.P.PAUL D. WHITE, F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-18-3-323 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptI shall not discuss the cardiac problems in war time which are also those in times of peace and which include the vast bulk of all the problems that both civilian and military doctors have to face, such as the diagnosis of coronary and rheumatic heart disease, the treatment of angina pectoris and myocardial failure, acute pericarditis, and arrhythmias. I shall plunge at once into the specific problems bearing on the heart in this year 1942.First, a brief word about the cardiologist himself. His rôle is not a simple one. If a civilian, he is overburdened with the cardiac... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Boston, Massachusetts*Presented before the Midwest Regional Meeting of the American College of Physicians, Chicago, November 21, 1942, and before the Annual Meeting of the New York Heart Association, Academy of Medicine, New York, January 21, 1943. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byThe influence of age on blood pressureEARLY DIAGNOSIS OF RHEUMATIC VALVULAR DISEASE IN RECRUITSSome observations on the cardiovascular examination for aircrew fitness 1 March 1943Volume 18, Issue 3Page: 323-331KeywordsAnginaArmed forcesArrhythmiaCardiovascular therapyCoronary heart diseaseHeartHeart diseasesHeart failure ePublished: 1 December 2008 Issue Published: 1 March 1943 PDF downloadLoading ...
Clinical Actionability of Multigene Panel Testing for Hereditary Breast and Ovarian Cancer Risk Assessment
Authors: Andrea Desmond, Allison W. Kurian, Michele Gabree, Meredith A. Mills, Michael J. Anderson, Yuya Kobayashi, Nora Horick, Shan Yang, Kristen M. Shannon, Nadine Tung, James M. Ford, Stephen E. Lincoln, Leif W. Ellisen
Journal: JAMA Oncology (2015)

IMPORTANCEThe practice of genetic testing for hereditary breast and/or ovarian cancer (HBOC) is rapidly evolving owing to the recent introduction of multigene panels.While these tests may identify 40% to 50% more individuals with hereditary cancer gene mutations than does testing for BRCA1/2 alone, whether finding such mutations will alter clinical management is unknown.OBJECTIVE To define the potential clinical effect of multigene panel testing for HBOC in a clinically representative cohort. DESIGN, SETTING, AND PARTICIPANTSObservational study of patients seen between 2001 and 2014 in 3 large academic medical centers.We prospectively enrolled 1046 individuals who were appropriate candidates for HBOC evaluation and who lacked BRCA1/2 mutations. INTERVENTIONSWe carried out multigene panel testing on all participants, then determined the clinical actionability, if any, of finding non-BRCA1/2 mutations in these and additional comparable individuals. MAIN OUTCOMES AND MEASURESWe evaluated the likelihood of (1) a posttest management change and (2) an indication for additional familial testing, considering gene-specific consensus management guidelines, gene-associated cancer risks, and personal and family history.RESULTS Among 1046 study participants, 40 BRCA1/2-negative patients (3.8%; 95% CI, 2.8%-5.2%)harbored deleterious mutations, most commonly in moderate-risk breast and ovarian cancer genes (CHEK2, ATM, and PALB2) and Lynch syndrome genes.Among these and an additional 23 mutation-positive individuals enrolled from our clinics, most of the mutations (92%) were consistent with the spectrum of cancer(s) observed in the patient or family, suggesting that these results are clinically significant.Among all 63 mutation-positive patients, additional disease-specific screening and/or prevention measures beyond those based on personal and family history alone would be considered for most (33 [52%] of 63; 95% CI, 40.3%-64.2%).Furthermore, additional familial testing would be considered for those with first-degree relatives (42 [72%] of 58; 95% CI, 59.8%-82.2%)based on potential management changes for mutation-positive relatives.This clinical effect was not restricted to a few of the tested genes because most identified genes could change clinical management for some patients. CONCLUSIONS AND RELEVANCEIn a clinically representative cohort, multigene panel testing for HBOC risk assessment yielded findings likely to change clinical management for substantially more patients than does BRCA1/2 testing alone.Multigene testing in this setting is likely to alter near-term cancer risk assessment and management recommendations for mutation-affected individuals across a broad spectrum of cancer predisposition genes.
Abstract 4920: Luminol-based <i>in situ</i> photodynamic therapy for breast adenocarcinoma
Authors: Hamad S. Alshetaiwi, Tej B. Shrestha, Sivasai Balivada, Matthew T. Basel, Marla Pyle, Hongwang Wang, Stefan H. Bossmann, Deryl L. Troyer
Journal: Cancer Research (2014)

Abstract Photodynamic therapy (PDT) is a cancer treatment that uses a photosensitizer and a specific wavelength of light. When tumor cells which have absorbed photosensitizer are exposed to the correct wavelength of light, reactive oxygen species are generated, resulting in tumor cell death. Poor tissue penetration of light is a major limitation in PDT, restricting its use to treatment of localized tumors. Light generation at the tumor area might increase the effectiveness of PDT and can expand its use for metastatic tumors. Infiltration of tumor-activated polymorphonuclear neutrophils (PMNs) produces luminescence in the presence of luminol; this bioluminescence has been used for tumor detection in pre-clinical trials. Based on this rationale, we hypothesized that luminol-based bioluminescence can cause targeted PDT in breast adenocarcinoma tumors in the presence of the photosensitizer 5-aminolevulinic acid (ALA). To test this hypothesis, BALB/c mice were transplanted with 4T1 mammary adenocarcinoma cells to establish a breast adenocarcinoma model. After tumor formation, ALA and luminol were administered to mice through intraperitoneal and intravenous routes, respectively. This treatment regimen was repeated six times and ALA alone/luminol alone/saline treated tumor-bearing mice were used as controls. Relative differences in the increase of tumor volume and final tumor weights were analyzed to test the treatment hypothesis. Analysis of the data showed that treatment with a combination of luminol and ALA as well as treatment with luminol alone results in breast adenocarcinoma tumor growth attenuation. This study gives evidence for the antitumor activity of luminol on breast adenocarcinoma, possibly through PDT. Citation Format: Hamad S. Alshetaiwi, Tej B. Shrestha, Sivasai Balivada, Matthew T. Basel, Marla Pyle, Hongwang Wang, Stefan H. Bossmann, Deryl L. Troyer. Luminol-based in situ photodynamic therapy for breast adenocarcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4920. doi:10.1158/1538-7445.AM2014-4920
Triggering of Acute Myocardial Infarction by Heavy Physical Exertion -- Protection against Triggering by Regular Exertion
Authors: Murray A. Mittleman, Malcolm Maclure, Geoffrey H. Tofler, Jane B. Sherwood, Robert J. Goldberg, James E. Muller
Journal: New England Journal of Medicine (1993)

Despite anecdotal evidence suggesting that heavy physical exertion can trigger the onset of acute myocardial infarction, there have been no controlled studies of the risk of myocardial infarction during and after heavy exertion, the length of time between heavy exertion and the onset of symptoms (induction time), and whether the risk can be modified by regular physical exertion. To address these questions, we collected data from patients with confirmed myocardial infarction on their activities one hour before the onset of myocardial infarction and during control periods.
January 7/14, 2003
Authors: James T. Willerson
Journal: Circulation (2003)

is the Section Editor for Circulation's newest section, Mini-Reviews: Expert Opinions.Expert opinions and advice will be solicited from internationally recognized thought-leaders for topics in cardiovascular medicine that are of interest to the cardiovascular clinician.In addition, health-care policy and patient care issues will be examined attempting to improve clinical care and resource utilization.Mini-
Decreased colony formation of high proliferative potential colony-forming cells and granulocyte-macrophage colony-forming units and increased Hes-1 expression in bone marrow mononuclear cells from patients with psoriasis
Authors: K. Zhang, R. Hou, X. Niu, J. Zhang, G. Yin, X. Li, Y. Jia
Journal: British Journal of Dermatology (2010)

Background Psoriasis is a chronic inflammatory disease of the skin. The dysfunctional immunity experienced by patients with psoriasis is believed to influence the bone marrow haematopoietic cells and their surrounding microenvironment. Phagocytes derived from the bone marrow of patients with active psoriasis exhibit enhanced monocytopoietic activity and hyperplasia in vitro. However, direct evidence supporting the hypothesis that bone marrow is involved in the pathogenesis of psoriasis has yet to be established. Objectives To investigate the involvement of bone marrow in the pathogenesis of psoriasis. Methods Bone marrow mononuclear cells (BMMNCs) were isolated from patients with psoriasis and healthy individuals. The high proliferative potential colony-forming cells (HPP-CFCs), granulocyte-macrophage colony-forming units (CFU-GM) and erythroid colony-forming units (CFU-E) were cultured in the presence of defined cytokines, and the effects of secreted factors from psoriatic peripheral blood mononuclear cells (PBMCs) on colony formation of normal haematopoietic cells were analysed. Furthermore, the telomere activity of psoriatic and normal BMMNCs was determined using the polymerase chain reaction (PCR)-based telomeric repeat amplification protocol, while the expression of human telomerase reverse transcriptase (hTERT) and HES1 mRNA was detected by reverse transcription-PCR assay. Results The numbers of HPP-CFCs and CFU-GM, but not CFU-E, were significantly reduced in cultured haematopoietic cells from patients with psoriasis. The culture supernatant of PBMCs from patients with psoriasis was found to inhibit the colony formation capacity of HPP-CFCs, CFU-GM and CFU-E of normal haematopoietic cells. We also detected low levels of telomerase activity and hTERT gene expression in psoriatic and control BMMNCs that was statistically similar between the two groups. In contrast, the HES1 gene expression appeared to be significantly elevated in psoriatic BMMNCs (P < 0·05). Conclusions Together, our results indicate the involvement of bone marrow in the immunopathogenesis of psoriasis, and suggest a mechanism mediated by certain inflammatory or haematopoietic cytokines present in the bone marrow microenvironment. Elevated expression levels of HES1 mRNA suggest a potential role for the Notch signalling pathway in this process.
Brief Report: Connecting Two Pathways Through Ca<sup>2+</sup> Signaling: NLRP3 Inflammasome Activation Induced by a Hypermorphic <i>PLCG2</i> Mutation
Authors: Jae Jin Chae, Yong Hwan Park, Chung Park, Il‐Young Hwang, Patrycja Hoffmann, John H. Kehrl, Ivona Aksentijevich, Daniel L. Kastner
Journal: Arthritis & Rheumatology (2014)

We previously reported that p.Ser707Tyr, a novel variant in phospholipase Cγ2 (PLCγ2), is the cause of a dominantly inherited autoinflammatory disease, autoinflammation and PLCγ2-associated antibody deficiency and immune dysregulation (APLAID). The hypermorphic mutation enhances PLCγ2 activity and causes an increase in intracellular Ca2+ release from endoplasmic reticulum stores. Because increased intracellular Ca2+ signaling has been associated with NLRP3 inflammasome activation, we studied the role of the NLRP3 inflammasome in the pathogenesis of APLAID.Human peripheral blood mononuclear cells (PBMCs) were isolated from healthy control subjects and 2 patients with APLAID. Inflammasome activation was analyzed by Western blotting. Intracellular Ca2+ levels were measured with a FLIPR Calcium 4 assay kit.Cells from the patients had elevated basal levels of intracellular Ca2+, and the intracellular Ca2+ flux triggered by extracellular CaCl2 was substantially enhanced. Patient PBMCs secreted interleukin-1β in response to lipopolysaccharide priming alone, and this effect was attenuated by treatment with a PLC inhibitor, intracellular Ca2+ blockers, or an adenylate cyclase activator.Our findings suggest that the inflammation in patients with APLAID is partially driven by activation of the NLRP3 inflammasome. These data link 2 seemingly distinct molecular pathways and provide new insights into the pathogenesis of APLAID and autoinflammation.
Eyelid Tumors: Clinical Diagnosis and Surgical Treatment.
Authors: Jay Justin Older
Journal: Annals of Internal Medicine (1988)

Diagnosis and Management Differential Diagnosis of Eyelid Tumours Malignant Tumours Benign Tumours and Related Conditions Treatment of Eyelid Tumors Reconstruction of the Eyelids Surgical Anatomy General Principles of Eyelid Reconstruction and Radiosurgery Lower Eyelid Reconstruction Upper Eyelid Reconstruction Repair of Defects that do not involve Eyelid Margins Reconstruction of the Medial and Lateral Canthi References Index
Antimetastatic activity of the extract of Pleurospermum kamtschaticum and its active component, Buddlejasaponin IV through the induction of detachment-mediated apoptosis(Anoikis) and the expression of nonsteroidal anti-inflammatory drug-activated gene(NAG-1)
Authors: Jin Eun Kim, Won Yoon Chung, Kwang Kyun Park
Journal: Cancer Research (2005)

Proc Amer Assoc Cancer Res, Volume 46, 2005

2464 

The Pleurospermum kamtschaticum HOFFM,. a native plant in Korea, has been known to work for digestion and stomachache while stimulating appetite. Buddlejasaponin IV(BS-IV) is one of the active components of the P. kamtschaticum . Apoptosis is the process of programmed cell death or cell suicide. Anoikis is a poorly characterized form of apoptosis that occurs when adherent cells lose their integrin-mediated attachment to the extracellular matrix. Anoikis has been suggested to act as a physiological barrier to metastasis. NAG-1, a TGF-β superfamily member also has antitumorigenic activity and stimulates apoptosis in colon cancer and other cell lines. Cell viability was assessed using a MTT and Trypan Blue exclusion assay. Apoptosis was investigated in terms of DAPI staining, DNA laddering and a flow cytometry analysis. The expression of NAG-1, MAPKs and Bcl-2 family members were assessed by western blotting. In this study, we found that the methanolic extract of P. kamtschaticum and BS-IV inhibited the viability of HT-29 cells in a dose-related manner. The extract of P. kamtschaticum and BS-IV induced apoptosis, showing nuclear condensation, DNA fragmentation and the increment of annexin V-FITC-positive fluorescent cells. In particular, the extract of P. kamtschaticum and BS-VI reduced the adhesion of HT-29cells on culture flask and detached the cells within two hours. Moreover the extract of P. kamtschaticum and BS-IV dose-dependently upregulated the expression of NAG-1. Based on these data, to investigate the molecular mechanisms underlying the induction of anoikis and NAG-1 upregulation by the extract of P. kamtschaticum and BS-IV, we assessed the expression and/or activation of integrin-dependent kinases, MAPKs and Bcl-2 family, especially BH3 only proteins. Antimetastatic effect was confirmed in spontaneous mouse lung metastatis model. These results suggest that the extract of P. kamtschaticum and BS-IV may possess antimetastatic potential by inducing anoikis and upregulating NAG-1 expression.
Correction: Corrigendum: Kynurenine is an endothelium-derived relaxing factor produced during inflammation
Authors: Yutang Wang, Hanzhong Liu, Gavin McKenzie, Paul K Witting, Johannes-Peter Stasch, Michael Hahn, Dechaboon Changsirivathanathamrong, Ben J Wu, Helen J Ball, Shane R Thomas, Vimal Kapoor, David S Celermajer, Andrew L Mellor, John F Keaney, Nicholas H Hunt, Roland Stocker
Journal: Nature Medicine (2010)
Abstract P257: Common Genetic Variations in the Vitamin D Pathway in Relation to Blood Pressure
Authors: Lu Wang, Audrey Chu, Julie E Buring, Paul M Ridker, Daniel I Chasman, Howard D Sesso
Journal: Circulation (2014)

Background: Vitamin D is involved in the regulation of blood pressure (BP) through multiple mechanisms. Genetic variation may influence the effect of vitamin D on BP, but data from epidemiologic studies remain limited. Methods: We conducted a comprehensive genetic association study to investigate the variants in an expanded vitamin D metabolism and signaling pathway in relation to BP. Analyses were conducted in the Women’s Genome Health Study (WGHS) with genome-wide genotype data among 23,294 women of European ancestry and in the International Consortium of Blood Pressure (ICBP) with published genome-wide meta-analysis results from 69,395 men and women of European ancestry. Results: Analyses were conducted in three stages. First, among 5 candidate single-nucleotide polymorphisms (SNPs) in the vitamin D related genes that were previously found associated with BP, none was associated with systolic (SBP) or diastolic BP (DBP) in the WGHS or ICBP. Second, in an expanded set of 61 SNPs involved in vitamin D metabolism and signaling pathway, rs1507023 (in RBFOX1 ) and rs2296241 (in CYP24A1 ) showed nominally significant associations with SBP, DBP, mean arterial pressure (MAP), or pulse pressure (PP) in the WGHS, but the associations were no longer significant after correction for multiple hypothesis testing. Similarly, nominally significant associations found in the ICBP were also not significant after multiple testing corrections. Third , among 24 candidate genes across the vitamin D pathway, associations with BP traits that meet gene-wide significance level (gene-based empirical p&lt;0.05) were found in the WGHS for NCOA3 (rs2235734), RXRA (rs875444), DHCR7 (rs1790370), VDR (rs2544037), and NCOR2 (rs1243733 and rs1147289). Similar gene-wide significant associations (gene-based p&lt;0.05) with SBP or DBP were found in the ICBP for NCOR1 , TP53BP1 and TYRP1 . After further correction for number of genes in the pathway, however, only the association of TYRP1 with SBP in the ICBP reached significance threshold. Further, the WGHS observed associations were not replicated in the ICBP, and vice versa. Conclusions: Our study in large samples of Caucasian population did not replicate several previously observed associations of candidate SNPs in the vitamin D pathway with BP. However, we found suggestive evidence for associations of other vitamin D pathway gene variants with BP traits. Future studies are needed to replicate our findings.
Abstract 16418: The Impact of MitraClip® Procedure on Left Atrial Strain and Strain Rate
Authors: Esra Gucuk Ipek, Atif Qasim, Esperanza Viloria, Ted Feldman, Paul A Grayburn, Elyse Foster
Journal: Circulation (2014)

Background: Left atrial (LA) remodeling due to mitral regurgitation (MR) is associated with abnormal LA strain parameters which may correlate with degree of fibrosis. Although reverse atrial remodeling has been shown after MitraClip placement, changes in LA strain and strain rate have not been evaluated in these patients or compared with mitral valve repair (MVr). Methods: We measured peak positive LA strain (ε) and strain rates [peak systolic (SRp), peak early diastolic (SRe) and peak late diastolic (SRa)] in 107 subjects (mean age 61±12 yrs) with degenerative MR enrolled in the randomized EVEREST II trial. Individuals with paced rhythm, atrial fibrillation, functional MR and poor image quality were excluded. LA strain measures were obtained from 4-chamber and 2-chamber views and averaged at baseline and at 1 year follow up. Results: At one year all 44 MVr subjects had ≤2+ MR, whereas 22 of the 63 MitraClip had &gt;2+ MR. Baseline average ε, SRp, SRe and SRa values were similar in MitraClip and MVr groups (Table 1). At one year follow up there was a significant decrease in LA volumes in the surgical group and in those with MR ≤2+ after MitraClip. Overall average ε was significantly reduced after MVr. There was a small decrease or no change in average ε after MitraClip. SRe was significantly decreased 1 year after MVr and also in the MitraClip arm, regardless of whether there was significant MR reduction. There were no changes in SRp and SRa at 1 year in either group. Conclusion: Average peak positive LA strain either decreased modestly or did not change after treatment of MR in chronic degenerative MR subjects. There was a significant decrease in SRe in both treatment arms at 1 year. This occurred despite evidence of reverse LA remodeling. Further investigation and replication in additional cohorts is needed to explore these findings, which may suggest persistence of LA dysfunction after correction of chronic MR, or irreversible fibrosis. Disclosure: EVEREST II was funded by Abbott Vascular.