tbuckley/cabot-search huggingface dataset:
Abstract 5266: A Novel Technique for Assessing the Renal Microvasculature in Chronic Kidney Disease
Authors: Michael A Kuliszewski, Dmitriy Rudenko, Kim A Connelly, Darren Yuen, Judy Trogadis, Andrew Advani, Richard E Gilbert, Howard Leong-Poi
Journal: Circulation (2009)

A variety of factors have been identified as playing an important role in the progression of chronic kidney disease (CKD) to end-stage renal failure. Microvascular loss plays a critical role, being pathologically linked to the development of glomerular sclerosis and tubulointerstitial fibrosis. Thus, we have developed a new and novel post-mortem fixation technique, fluorescent microangiography (FMA), for assessing the microvasculature in animal models of CKD. Methods: 8 week old make Fischer 344 rats underwent subtotal nephrectomy (n=10) (SNX), or sham surgery (n=10). Systolic blood pressure (SBP), serum creatinine, and proteinuria were assessed at baseline and 8 weeks follwing surgery. At sacrifice rats were subjected to FMA. (10% solution of 0.02 μ m fluorescent microspheres) Thick (200 μ m) sections of fixed tissue can then be visualized under confocal microscopy. Stacks of images are collected and 3D reconstruction and visualization carried out in order to quantify the density, size and shape of blood vessels. An automated tracing algorithm was used to connect the tubular microvessels in 3 dimensions, and a solid 3D model was created (Neurolucida). Results : SNX animals showed increased in SBP (192±36 versus 123±4 mm Hg in controls; p &lt; 0.0001), serum creatinine (65±12 versus 32±4 μ M in controls; p &lt; 0.001) and urinary protein (84±26 versus 13±1 mg/d in controls; p &lt; 0.05). FMA analysis demonstrated glomerular hypertrophy (average glomerular diameter [185±7 versus 136±4 μ M in controls; p &lt; 0.01]) with microvascular loss in SNX animals (3.02E-03±2.20E-04 versus 4.45E-03±2.29E-04 μ M in controls; p &lt; 0.01, see figure below). SNX increased total vessel length (9809±627 versus 5879±393 μ M in controls; p &lt; 0.05), average vessel diameter (5.59±0.15 versus 5.24±0.18 μ M in controls; p &lt; 0.05). Conclusion: Fluorescent microangiography (FMA), with a spatial resolution of less than 1 μ M is a practical and quantifiable method for visualizing the microvasculature of the kidney that allows for direct measurements of volume, diameter, length and vascular density. In addition FMA provides visualization of the phenotypic changes in the renal microvasculature associated with CKD.
Promoter hypermethylation of BNIP3 and prognosis in human colorectal cancer
Authors: H. Uetake, S. Iida, K. Sugihara
Journal: Journal of Clinical Oncology (2008)

15025 Background: Promoter hypermethylation plays an important role in the inactivation of tumor suppressor genes and apoptotic genes during tumorigenesis and tumor growth. BNIP3 is a proapoptotic member of the Bcl-2 family and expressed in hypoxic regions of tumors. In the present study, promoter hypermethylation of BNIP3 was investigated in colorectal cancer (CRC) specimen and compared to patient's prognosis. Methods: Methylation status of 145 CRC specimens, all of which were formalin-fixed and paraffin embedded, were studied by methylation specific PCR. Patient characteristics: 52 female and 93 males, 64.5 years old in average, stage0:I:II:III:VI = 6:19:49:49:22. Results: Hypermethylation of BNIP3 was observed 54% of the specimens. Methylation status had no correlation with any clinicopathological factor. Patients with BNIP3 hypermethylated cancer showed significant poorer survival than those with unmethylated cancer in overall survival and disease specific survival (p=0.013 and 0.028, respectively. Log-rank test), but not in relapse free survival (p=0.315) Conclusions: Promoter hypermethylation of BNIP3 were supposed to be negative predictive and prognostic factors in patients with CRC. Possible reasons for poorer prognosis in hypermethylation group are speculated to be prevention of tumor apoptosis in the chemotherapy and resistance to hypoxia-induced cell death in human CRC. No significant financial relationships to disclose.
Post-Transplant Maintenance With The Deacetylase Inhibitor Panobinostat In Patients With High-Risk AML Or MDS: Results Of The Phase I Part Of The Panobest Trial
Authors: Gesine Bug, Andreas Burchert, Kroeger Nicolaus, Sabine Huenecke, Ulrich Duenzinger, Andrea Wolf, Peter Bader, Hubert Serve, Oliver G. Ottmann
Journal: Blood (2013)
Abstract 432: Hypervolemic Hyponatremia Aggravates Myocardial Ischemia/Reperfusion Injury: Normalization with Tolvaptan
Authors: Kairong Zhou, Haiquan Li, Miranda Fong, Junichi Kambayashi, Yongge Liu
Journal: Circulation (2006)

Tolvaptan (OPC-41061) is a selective vasopressin V2 antagonist. It generates increased, dose-dependent production of diluted urine without altering serum electrolyte balance, and without activation...
Gene expression profiling from blood for early detection of breast cancer
Authors: Alexander Krause, Laurent Bracco, Jonathan Kearsey, Malick Paye, Anne-Kim Isnard, Veronique Barbalat, Christelle Compagnon, Bernard Miramand, Daniel Serin, Farhat Ben Ayed, Laurent Mineur, Philippe Leissner, Bruno Mougin
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

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It is now well established that early detection of breast cancer improves survival rates and increases the probability of successful treatment. To date, mammographic screening is the most reliable method to detect breast cancer in asymptomatic women. However, mammography has significant limitations: it often fails to detect very small tumors in absence of microcalcifications and is difficult to interpret with dense breast in young women. These limitations lead us to evaluate an alternative method for screening breast cancers based on the identification of a molecular signature in peripheral blood cells. ExonHit’s gene profiling technology DATAS (Differential Analysis of Transcripts with Alternative Splicing) allowed the isolation of a set of messengers and alternatively spliced mRNA sequences that were differentially expressed between the blood of healthy women and early stage breast cancer patients. A customised Affymetrix Genechip array has then been set up for the validation of those DATAS clones. Total RNA extracted from whole blood samples of 37 controls and 55 breast cancer stage I/II (i.e. train group) were amplified, labeled and hybridized on the custom array in order to identify the most significant diagnostic markers. Monoparametric and multiparametric approaches have been carried out, leading to the identification of a 54-gene signature capable of clearly distinguishing healthy women from early stage breast cancers. By applying this method to the train group, 86.5% of the controls and 92.7% of the breast cancers were correctly classified. A first, limited validation with 21 independent blood samples (5 healthy controls vs 16 early stage-breast cancers) showed that this expression profile in blood kept its diagnostic power. The confirmation of the robustness of the blood-molecular signature is underway using a larger independent cohort of 1000 patients. In parallel, blood samples of patients suffering from benign breast diseases, inflammatory diseases or other types of cancer are processed in order to evaluate the specificity of the gene signature for breast cancer. Taken together, our results show that a gene expression-based assay can be developed for the early detection of breast cancer through the use of 5ml of whole blood and that such assay will rely on transcripts very unlikely to be expressed from circulating tumor cells.
Abstract 8422: Cardiac Protein Abnormalities of Human Left Ventricular Tissue in Ischemic and Dilated Cardiomyopathy
Authors: Miguel Rivera, Esther Rosello-Lleti, Antonio Salvador, Raquel Cortes, Luis Martinez-Dolz, Luis Almenar, Francisca Lago, Inmaculada Azorin, Jose Gonzalez-Juanatey, Ignacio Sanchez-Lazaro, Vicente Bertomeu, Anastasio Montero, Leif Hove, Juan Cinca, Manuel Portoles, Jana Alonso
Journal: Circulation (2011)

Introduction: The development of heart failure (HF) is characterized by progressive alteration of left ventricle structure and function. A proteomic approach could lead to the detection of variations in protein expression of left ventricular tissue from patients with ischemic (ICM) and dilated cardiomyopathy (DCM). Methods: 24 explanted human hearts, 12 from patients with ICM and 12 with DCM undergoing cardiac transplantation and 6 non-diseased donor hearts (CNT) were analyzed by 2DE. Proteins of interest were identified by mass spectrometry and validated by Western blotting and immunofluorescence. Results: We encountered 35 differentially regulated spots in the comparison CNT vs. ICM, and 33 in CNT vs. DCM. We identified G3P up-regulation in both ICM (2.53-fold, p&lt;0.0001) and DCM (2.89-fold, p&lt;0.0001). HSP71 was up-regulated only in ICM (3.31-fold, p&lt;0.0001). G3P was related with ventricular function parameters (left ventricular end-systolic diameter (p=0.001), end-diastolic diameter (p=0.001)) in our HF patients. HSP71 was also related with these functional parameters (p&lt;0.05). Conclusions: We have shown by proteomics analysis that HF is associated with changes in proteins involved in the cellular stress response, respiratory chain and cardiac metabolism. Although we found altered expression of proteins common to both ischemic and dilated etiology, we also found different proteins altered in both groups. In addition, for the first time left ventricular function was related with changes in G3P and HSP71.
Abstract 6129: COURAGE Revisited: Can Noninvasive Identification of Ischemia Identify a Long-term Therapeutic Benefit of CABG or PCI versus Medical Therapy
Authors: Rory Hachamovitch, Alan Rozanski, Louise E Thomson, Xingping Kang, Sean W Hayes, Ishac Cohen, John D Friedman, Romalisa Miranda-Peats, Guido Germano, Daniel S Berman
Journal: Circulation (2008)
Retinal Arteriolar Narrowing and Left Ventricular Remodeling
Authors: Ning Cheung, David A. Bluemke, Ronald Klein, A. Richey Sharrett, F.M. Amirul Islam, Mary Frances Cotch, Barbara E.K. Klein, Michael H. Criqui, Tien Yin Wong
Journal: Journal of the American College of Cardiology (2007)
Microarray gene expression analysis reveals molecular activities of bexarotene in in vitro models of non-dmall vell lung cancer (NSCLC) and in tumors of NSCLC patients
Authors: T. Hermann, K. H. Dragnev, J. R. Rigas, W. J. Petty, E. Dmitrovsky, A. Negro-Vilar, W. Lamph
Journal: Journal of Clinical Oncology (2005)

7234 Background: Bexarotene (Targretin) is a selective retinoid X receptor (RXR) agonist with clinical activity in NSCLC. Expression levels of RXR in NSCLC have been shown to be independent predictors of survival. The study was designed to determine the molecular activities of this compound in NSCLC and identify biomarkers of RXR activity for prognosis of survival. Methods: NSCLC cell lines and primary cultures derived from human NSCLC tumor specimens were treated with vehicle or bexarotene followed by microarray gene expression analysis. In addition, gene expression profiles were studied in NSCLC tumor samples obtained from patients treated with bexarotene (Targretin capsules) and compared with profiles in tumors and normal lung tissue from untreated patients by hierarchical clustering. Results: All cell lines and primary tumor cultures showed changes in gene expression in response to bexarotene to various degrees, indicating a universal capacity of bexarotene to elicit a molecular response in NSCLC. Genes affected play roles in cell proliferation, apoptosis, differentiation, metastasis, angiogenesis, and small molecule metabolism and transport. Some of the genes responded to bexarotene treatment in a majority or even all of the specimens, with stearoyl-CoA desaturase being the most prominently affected. When comparing NSCLC patients based on the gene expression profiles in the resected tumors, the majority of the cases separated into two distinct clusters, treated or untreated. This indicated that bexarotene may have caused relatively broad molecular changes. In addition, a set of markers identified in the in vitro experiments were also significantly overexpressed in the tumors from bexarotene-treated cases, confirming the molecular activity of the drug in the patients. Interestingly, these genes were significantly under-expressed in the untreated tumors when compared to normal lung tissue. Conclusions: These data suggest that the NSCLC tumors may exhibit reduced RXR transcriptional activity compared to normal lung tissue, which can be normalized by treatment with bexarotene, a selective RXR modulator. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Ligand Ligand Ligand Ligand Ligand
Abstract 5100: Vulnerability of Atherosclerotic Plaque in Relation to Blood Flow Direction: Mechanisms of Increased Plaque Rupture at the Upstream Region
Authors: Iwona Cicha, Anja Woerner, Katharina Osterode, Dorette Raaz, WG Daniel, Christoph Garlichs
Journal: Circulation (2009)

Objectives: Rupture of atherosclerotic plaque, the leading cause of acute coronary syndromes and ischemic strokes, occurs mainly at the upstream (proximal) shoulder of the lesion. We investigated the mechanisms leading to plaque rupture in relation to blood flow direction. Methods: The occurrence of ulceration, endothelial erosion, intimal neovascularization, and intraplaque hemorrhage were histologically determined in 70 human carotid specimens. Longitudinal sections of the plaques were immunohistochemically analyzed for cathepsin L, mast cell chymase, 5-lipoxygenase, Bax, VEGF, and connective tissue growth factor (CTGF) using specific monoclonal antibodies. Results: In &gt;70% of ulcerated plaques, ulceration/rupture was observed at the upstream region of the plaque. Similarly, the occurrence of active intimal neovascularization and intraplaque hemorrhage was increased in upstream region (p&lt;0.01), whereas endothelial erosion was more frequent downstream. The mean numbers of cells positive for cathepsin L, were significantly higher upstream as compared with downstream regions of the atherosclerotic lesions (58±7 upstream vs 33.1±5 downstream; p&lt;0.001). Similarly, the expression of chymase was markedly increased in the upstream region of the plaque (34.3±5 upstream vs 17.1±4 downstream, p&lt;0.001, n=70). The key enzyme in leukotriene production, 5-lipoxygenase, was abundantly expressed in majority of the analyzed plaques, however, no significant differences were observed in its expression between the two plaque shoulders. Pro-apoptotic protein Bax was detected more frequently at the upstream plaque shoulder, and localized mainly to smooth muscle cells and macrophages. The immunoreactivity of CTGF and VEGF showed a very high degree of variability between different plaques, but the overall statistical analyses demonstrated a significant increase in both CTGF and VEGF expression at the upstream shoulder in majority of the analysed plaques. Conclusions: Local hemodynamic forces affect plaque stability. Rupture at the upstream region of atherosclerotic lesion is related to activation of proteolytic and pro-apototic mechanisms, as well as enhanced neovascularization and intraplaque hemorrhage.
Abstract 1352: Gender Differences In Cardiac Repolarization In Transgenic Long QT Syndrome 2 (LQT2) Rabbits
Authors: Katja E Odening, Mohammad Hajjiri, Michael Brunner, Peem Lorvidhaya, Lorraine Schofield, Xuwen Peng, Manfred Zehender, Malcolm Kirk, Gideon Koren
Journal: Circulation (2007)

Introduction: Adult women with LQT2 are at higher risk for clinical events and sudden cardiac death (SCD) than men. We have created transgenic rabbits over-expressing pore mutants of the human KvLQT1 (LQT1) and HERG (LQT2) selectively in the heart. We report the gender differences in cardiac repolarization, incidence of polymorphic VT and SCD in these cohorts. Methods: Adult female and male LQT1, LQT2, and littermate controls (ages 5 to 33 mo were similar in f/m, LQT2 were younger due to higher mortality) underwent telemetric ECG monitoring, surface ECG and in vivo electrophysiological studies under general anaesthesia with isoflurane (2–5%). Results: Monitoring data showed a steeper QT/RR slope in female (0.745 ± 0.05, n=4) than in male (0.513 ± 0.06, n=9; p&lt;0.05) LQT2 rabbits. No significant gender differences were observed in QT/RR slopes in either LQT1 or WT rabbits. QT-, QTpeak-index and Tp-e were significantly longer in female than in male LQT2 rabbits (females, n=6: QT: 129.2% ± 3.9; QTp: 105.9% ± 2.1; Tp-e: 42.9ms ± 4.1 vs. males, n=8: QT: 117.5% ± 4.3; p&lt;0.05; QTp: 93.5% ± 5.6, p&lt;0.05; Tp-e: 29.5ms ± 2.9, p&lt;0.02). EP studies revealed significantly longer atrial (AERP) and ventricular (VERP) refractory periods in LQT2 females compared to males (females, n=4: AERP: 143.3 ± 5.8 ms; VERP: 212.5 ± 22.2 ms vs. males, n=8: AERP: 102.5 ± 7.7 ms, p&lt;0.01; VERP: 178.1 ± 7.8 ms, p&lt;0.05). AERP and VERP were significantly longer in LQT2 females than in LQT1 females (LQT1 females, n=7: AERP: 101.4 ± 7.7 ms, p&lt;0.01, VERP: 156.9 ± 6.2, p&lt;0.001), whereas in male LQT rabbits this genotype difference was only found in VERP but not in AERP. Survival was significantly shorter in female LQT2 rabbits compared to LQT1 or WT controls, with 4 sudden deaths among 10 LQT2, 1 among 19 WT and no SCD in 13 LQT1 females (p&lt;0.02). No gender difference was observed in mortality. All cases of SCD occurred after sexual maturation and two LQT2 females died during lactation. Monitoring revealed the cause of SCD was polymorphic VT. Conclusions: Monitoring of LQT rabbits reveal gender differences in LQT2 rabbits. QT/RR slope is steeper in female than in male adult LQT2 rabbits. AERP and VERP are longer in LQT2 females than in males. Finally, in LQT2 females, SCD was associated with lactation, but not pregnancy.
O109 : Treatment of severe HCV-recurrence after liver transplantation using sofosbuvir-based regimens: The ANRS CO23 CUPILT study
Authors: J. Dumortier, D. Botta-Fridlund, A. Coilly, V. Leroy, C. Fougerou-Leurent, H. Danjou, S. Radenne, F. Durand, N. Kamar, V. di Martino, V. de Ledinghen, P. Houssel-Debry, L d’Alteroche, C. Duvoux, F. Conti, V. Canva, A. Diallo, A. Rohel, J.-C. Duclos-Vallée, G.-P. Pageaux
Journal: Journal of Hepatology (2015)
Isolated pulse oximetry readings are unreliable
Authors: I. Waite, R. W M Walker, A. Sharples, O. Dearlove
Journal: BMJ (1995)

BronchioliisHome observation is inadvisable EDIrOR,-David Isaacs's editorial on bronchiolitis contains guidelines that should cause some concern.Bronchiolitis does not always fit into the static categories of mild, moderate, or severe but
HAZARDOUS JOURNEYS. CAR COLOUR AND RISK OF CAR CRASH INJURY: POPULATION BASED CASE CONTROL STUDY
Authors: S Furness, J Connor, E Robinson, R Norton, S Ameratunga, R Jackson
Journal: BMJ (2003)

Worldwide, highway traffic crashes kill about 3,000 people/day. Identification of modifiable risk factors is an important step in reducing this burden. Prior research suggests that white or light colored cars are less likely to be involved in a crash than are cars of other colors. In this work, the authors investigated the effect of car color on the risk of a serious injury from a crash, using a population-based case control study designed to identify and quantify modifiable risk factors.
BMA annual meeting: BMA issues warning over dangerous working patterns
Authors: J. Wise
Journal: BMJ (2015)

Seven in 10 doctors never have rest time after a busy night on call, a survey by the BMA has found. The organisation has warned that these working patterns compromise patient safety and put doctors at risk of chronic fatigue and burnout.

The survey of 847 consultants in England and Northern Ireland found that 88% reported being on an on-call rota and that just under half were called to attend hospital during the week, on one to six occasions. This figure was even higher at weekends, when almost two thirds of consultants on …
Substance P enhances photosensitizer uptake in MAT-LyLu prostate tumors.
Authors: Xiaodong R. Zhou, Brian W. Pogue, P. Jack Hoopes, Tayyaba Hasan
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

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The aim of this study is to characterize the transvascular transport of photosensitizer conjugates in MAT-LyLu subcutaneous tumors and to investigate the effects of inflammatory mediator on the photosensitizer uptake. We have examined the tumor vasculature morphology, pore cutoff size, vascular permeability, and photosensitizer uptake temporal and spatial dynamics and in response to intratumor injection of a neuropeptide, substance P. Average diameter of tumor vessels were increased significantly in response to SP administration. Vessel wall pore cutoff size evaluated by intravital fluorescence microscopy showed SP increased vessel pore cutoff size. This result has been confirmed with electron microscopy illustrated the opening intercellular gaps after injection of SP. Vascular permeability to LDL (22 nm in diameter), BSA (6 nm in diameter), fluorescence dextrans (3, 10, 70, 500, 2,000KDa) and fluorescence beads (40, 200, 1,000 nm in diameter) were determined by intravital fluorescence microscopy. Permeability was found temporally and spatially heterogeneous. Vascular permeability to LDL and BSA were found increased significantly and more homogeneous after SP administration. These changes were further confirmed by Evans Blue albumin extravasation assay showing significant increase of albumin extravasation in SP injected tumors. Photosensitizer uptake was evaluated by fluorescence microscopy and fluorometer at 3 hours post photosensitizer administration. SP injected tumors showed a significant higher cellular uptake and a more homogeneous distribution than the control tumors. Our study suggested that intratumor administration of substance P can induce transient opening of intercellular gaps, enhance the photosensitizer extravasation and achieve a homogeneous photosensitizer cellular uptake.
THE PROBLEM OF THE INTERNIST IN THE NAVY
Authors: Ross T. Mcintire
Journal: Annals of Internal Medicine (1941)

Article1 June 1941THE PROBLEM OF THE INTERNIST IN THE NAVYROSS T. MCINTIRE, F.A.C.P.ROSS T. MCINTIRE, F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-14-12-2179 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe subject of this paper which I am presenting this afternoon, "The Problem of the Internist in the Navy," may seem a bit commonplace among such a distinguished group of internists as are the Fellows of this College. However, in view of the marked increase in the personnel of the Army and Navy, it occurred to me that it might be well for me to review something of the peculiarities of the duties that face the internists in the Navy, when to you who are in civil practice like situations would be very routine matters. Because many of you may... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Medical Corps U. S. N. The Surgeon General of the Navy*Prepared for the Annual Session of the American College of Physicians, Symposium on Military Medicine, Boston, April 24, 1941. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 June 1941Volume 14, Issue 12Page: 2179-2183KeywordsMilitary medicine ePublished: 1 December 2008 Issue Published: 1 June 1941 PDF downloadLoading ...