tbuckley/cabot-search huggingface dataset:
Influence of implantable cardioverter-defibrillators on the long-term prognosis of survivors of out-of-hospital cardiac arrest.
Authors: A C Powell, T Fuchs, D M Finkelstein, H Garan, D S Cannom, B A McGovern, E Kelly, G J Vlahakes, D F Torchiana, J N Ruskin
Journal: Circulation (1993)

Survivors of out-of-hospital cardiac arrest not associated with acute myocardial infarction are at high risk for recurrent cardiac arrest and sudden cardiac death. The impact of the implantable cardioverter-defibrillator on long-term prognosis in these patients is uncertain.Three hundred thirty-one survivors of out-of-hospital cardiac arrest (age, 56 +/- 13.7 years) underwent electrophysiologically guided therapy. Implantable defibrillators were placed in 150 patients (45.3%), and 181 patients (54.7%) received pharmacological and/or surgical therapy alone. Left ventricular ejection fraction was 35.2 +/- 16.6% in defibrillator recipients and 45.3 +/- 18.2% in nondefibrillator patients. Median patient follow-up was 24 months in the defibrillator group and 46 months in the nondefibrillator group. In a proportional hazards model, the independent predictors of total cardiac mortality were left ventricular ejection fraction of less than 0.40 (relative risk, 4.55; 95% confidence interval, 2.44 to 8.33; P = .0001), absence of an implantable defibrillator (relative risk, 2.70; confidence interval, 1.41 to 5.00; P = .017), and persistence of inducible sustained ventricular tachycardia (relative risk, 1.84; 95% confidence interval, 0.97 to 3.49; P = .045). The 1- and 5-year probabilities of survival free of cardiac mortality in patients with left ventricular ejection fraction of less than 0.40 were 94.3% and 69.6% with a defibrillator and 82.1% and 45.3% without a defibrillator, respectively. For patients with left ventricular ejection fraction of 0.40 or more, the 1- and 5-year probabilities of survival free of cardiac mortality were 97.7% and 94.6% with a defibrillator and 95.4% and 86.9% without a defibrillator, respectively.In survivors of out-of-hospital cardiac arrest, the implantable defibrillator is associated with a reduction in cardiac mortality, particularly in patients with impaired left ventricular function.
Management training for senior registrars
Authors: A M Cooper, N J Davies, D M Thomas
Journal: BMJ (1992)

Proportion of general practitioners indicating their wish for information in discharge letters conceming various aspects of their patients' attendance at accident and emergency departments No (%) of practitioners requiring information on aspect Aspect of attendance (n= 213) Mode of referral 194 (91) General practitioner diagnosis (prior to referral) 134 (63) Clinical findings in accident and emergency*: All positive findings 115 (54) All negative findings 57 (27) Only relevant findings 109 (51) Results of investigations in accident and emergency: Haematology 187 (88) Biochemistry 183 (86) x Ray 191 (90) Diagnosis in accident and emergency 208 (98) Treatment in accident and emergency 202 (95) Outcome (admit or discharge) 203 (95) Treatment suggested for general practitioner 192 (90) Follow up arrangements 200 (94) Information given to patient 175 (82) Information to general practitioner**: On all patients 160 (75) Only those sent home 53 (25)*Actual question: Would you like to know all positive findings?all negative findings?only "relevant" findings?other (please specify)?Some respondents replied to more than one category.
Abstract 2492: Microtubule-interacting agents increase Class I HLA and HLA-A2 molecules surface expression in ovarian cancer cells
Authors: Ilenia Pellicciotta, Gary L. Goldberg, Shohreh Shahabi
Journal: Cancer Research (2010)

Abstract Objective: Ovarian cancer is the leading cause of death from gynecologic cancers in the United States. Standard first line therapy for ovarian cancer includes paclitaxel and platinum based agents. Epothilone B, Taxol and Vinblastin belong to a family of anti-neoplastic agents that interfere with microtubules and arrest cells in the G2/M phase of the cell cycle. Little is known about the effect of these drugs on the immune response to tumors. There is compelling evidence that cancer cells use multiple strategies to evade immune recognition. One of these mechanisms is the down-regulation of human leukocyte antigen (HLA) Class I molecule expression on the tumor cell surface, allowing the cancer cell to escape immune recognition and destruction. Data will be presented to illustrate the effect of microtubule affecting agents on HLA class I molecule expression in ovarian cancer cells. The effect on the expression of HLA-A2, the most common class I allele in the Caucasian population, has been evaluated as well. We also investigated the relationship between surface HLA expression and transcriptional modification of HLA induced by the drugs. Methods: IC50 was determined for each compound based on a 72 h cytotoxicity assay, using ovarian cancer cell line Hey. Cells were treated with different concentrations ranging from 1-fold IC50 to 100-fold IC50, and incubated at 37°C for 24 h, 48 h and 72 h. Cell surface expression of HLA class I molecules and HLA-A2 was examined by flow cytometry, using anti-HLA-A,B,C antibody (G46-2.6 clone) and HLA-A2 (BB7.2 clone). RT-PCR and real time PCR were used to amplify HLA genes, using Platinum Taq DNA Polymerase and Power SYBR Green master mix respectively. Results: Low dose Epothilone B, Taxol and Vinblastin (10-fold IC50) increased cell surface expression of HLA Class I up to four-fold in Hey ovarian cancer cells. HLA-A2 molecules were increased up to 2-fold. The increase of HLA Class I molecule expression was dose- and time-dependent. Conclusions: Nanomolar concentrations of microtubule-interacting agents increase the expression of HLA class I molecules in Hey ovarian cancer cells. Our data suggest that low doses of microtubule-interacting agents can mediate modulation of surface HLA expression and may enhance immune recognition of tumor cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2492.
Smoking and the brain
Authors: C. Brayne
Journal: BMJ (2000)

Papers p 1097 

Smoking prevents dementia? Smoking causes dementia? Over the past decade a succession of research findings has produced apparently conflicting evidence on this question. In the early 1990s results from case-control and family studies suggested a protective effect.1 2 The findings were widely reported,3 including in the mass media, and some scientists stated publicly that they would consider taking up smoking if they had a family history of dementia.

Tobacco companies began to sponsor conferences on dementia, perhaps because it seemed to offer them a lifeline in an otherwise relentless sequence of findings about the deleterious effects of smoking. If smoking reduced life expectancy and also reduced the likelihood of survivors developing dementia then, from a policy perspective, there might be a role for the habit in later life.

The potential protective effects have some biological plausibility. Alzheimer's disease affects neurotransmitter systems, particularly the cholinergic system. Nicotine is a cholinergic agonist. The effect of nicotine on cognition, attention, …
The Rough and the Smooth — Some Reflections on Diet Therapy
Authors: Howard M. Spiro
Journal: New England Journal of Medicine (1975)

GIVING diets often brings out the priest in an otherwise phlegmatic physician. Food habits, after all, have been one of the ways in which groups have separated themselves from other peoples. One religion chews what another culture eschews, to add sacramental virtues to the nutritional qualities of food. "You are what you eat" meant the most to primitive tribes whose new leader had to eat part of the old one. "You were what you eat" could be the current motto as the melting pot of America cools down, to our loss; the congealing of ethnicity brings interest in immigrant foods . . .
Endothelial dysfunction in conduit arteries and in microcirculation. Novel therapeutic approaches
Authors: Dimitris Tousoulis, Chryssa Simopoulou, Nikos Papageorgiou, Evangelos Oikonomou, George Hatzis, Gerasimos Siasos, Eleftherios Tsiamis, Christodoulos Stefanadis
Journal: Pharmacology & Therapeutics (2014)
Escort aptamers: a delivery service for diagnosis and therapy
Authors: Brian J. Hicke, Andrew W. Stephens
Journal: Journal of Clinical Investigation (2000)

In 1990, the discovery of aptamers by Tuerk and Gold (1) and subsequently by Ellington and Szostak (2) spawned significant interest within academia and industry.Aptamers have quickly become valuable research tools (3-5).More than that, a therapeutic aptamer (6) has entered clinical evaluation just eight years after the inception of the technology.While aptamers have built inroads into therapeutic applications, they may also become important in vitro diagnostic tools (7).Here, we discuss a new development: the use of "escort aptamers" as targeting agents for in vivo diagnosis and therapy.Instead of directly interrupting a disease process, as would a function-blocking aptamer, escort aptamers are designed to deliver radionuclides, toxins, or cytotoxic agents to diseased tissue.Specifically, we focus on the delivery of benign radionuclides for in vivo diagnosis of disease.For discussion of function-blocking aptamers, see White et al., this Perspective series (8). Aptamers and antibodiesThe advent of monoclonal antibodies in 1974 brought to mind Paul Ehrlich's turn-of-the-century insight that molecules could serve as "magic bullets" that home to pathological organisms with precision (http://nobel.sdsc.edu/medicine/laureates/1908/ehrlich-bio.html).Indeed, the high affinity and specificity of antibodies provide some of the key properties in Ehrlich's concept.Despite some successes in tissue targeting, antibodies are saddled with a fundamental disadvantage: their large size (∼155 kDa) results in slow tissue penetration and long blood residence.For example, in clinical settings where an antibody is coupled to a cellkilling radionuclide, this long circulation half-life leads to bone marrow toxicity that limits the permissible dose (9).To decrease blood half-life while maintaining target specificity, a second generation of smaller antibody fragments has been designed (10,11).Antibody pretargeting strategies also show promise (12-14), and small peptides can have excellent pharmacokinetic profiles (15).However, many approaches are limited by complexity of clinical protocols, paucity of available targeting molecules, low-
Profoundly Reduced Neovascularization Capacity of Bone Marrow Mononuclear Cells Derived From Patients With Chronic Ischemic Heart Disease
Authors: Christopher Heeschen, Ralf Lehmann, Jörg Honold, Birgit Assmus, Alexandra Aicher, Dirk H. Walter, Hans Martin, Andreas M. Zeiher, Stefanie Dimmeler
Journal: Circulation (2004)

Cell therapy with bone marrow-derived stem/progenitor cells is a novel option for improving neovascularization and cardiac function in ischemic heart disease. Circulating endothelial progenitor cells in patients with coronary heart disease are impaired with respect to number and functional activity. However, whether this impairment also extends to bone marrow-derived mononuclear cells (BM-MNCs) in patients with chronic ischemic cardiomyopathy (ICMP) is unclear.BM-MNCs were isolated from bone marrow aspirates in 18 patients with ICMP (ejection fraction, 38+/-11%) and 8 healthy control subjects (controls). The number of hematopoietic stem/progenitor cells (CD34+/CD133+), CD49d(+) (VLA-4) cells, and CXCR4+ cells did not differ between the 2 groups. However, the colony-forming capacity of BM-MNCs from patients with ICMP was significantly lower compared with BM-MNCs from healthy controls (37.3+/-25.0 versus 113.8+/-70.4 granulocyte-macrophage colony-forming units; P=0.009). Likewise, the migratory response to stromal cell-derived factor 1 (SDF-1) and vascular endothelial growth factor (VEGF) was significantly reduced in BM-MNCs derived from patients with ICMP compared with BM-MNCs from healthy controls (SDF-1, 46.3+/-26.2 versus 108.6+/-40.4 cells/microscopic field, P<0.001; VEGF, 34+/-24.2 versus 54.8+/-29.3 cells/microscopic field, P=0.027). To assess the in vivo relevance of these findings, we tested the functional activity of BM-MNCs to improve neovascularization in a hindlimb animal model using nude mice. Two weeks after ligation of the femoral artery and intravenous injection of 5x10(5) BM-MNCs, laser Doppler-derived relative limb blood flow in mice treated with BM-MNCs from patients with ICMP was significantly lower compared with mice treated with BM-MNCs from healthy controls (0.45+/-0.14 versus 0.68+/-0.15; P<0.001). The in vivo neovascularization capacity of BM-MNCs closely correlated with the in vitro assessment of SDF-1-induced migration (r=0.78; P<0.001) and colony-forming capacity (r=0.74; P<0.001).BM-MNCs isolated from patients with ICMP have a significantly reduced migratory and colony-forming activity in vitro and a reduced neovascularization capacity in vivo despite similar content of hematopoietic stem cells. This functional impairment of BM-MNCs from patients with ICMP may limit their therapeutic potential for clinical cell therapy.
Kallmann’s Syndrome — Beyond “Migration”
Authors: Verne S. Caviness
Journal: New England Journal of Medicine (1992)

THE analysis by Bick et al. in this issue of the Journal1 closes the circle on a rapidly evolving set of discoveries that have implicated the function of a defined protein in neuronal migration. Specifically, these investigators have identified, as the common genetic mutation associated with Kallmann's syndrome in two brothers, a 3.3-kb deletion confined to the KALIG-1 locus on the short arm of the X chromosome. The deletion was also carried on one X chromosome of their unaffected mother.The defining clinical characteristics of Kallmann's syndrome are anosmia and hypogonadism. A series of stunning discoveries has revealed a rational . . .
Abstract 1423: SatB2, targeted by miR31, is a modulator in cancer microenvironment
Authors: Xiang Yu, Olga Aprelikova, John Palla, Simone John, Ming Yi, Robert Stephens, John I. Risinger, Amir Jazaeri, John Niederhuber
Journal: Cancer Research (2010)

Abstract Cancer growth and metastasis involve an active interaction between primary tumor cells and the tumor's microenvironment, which consists of fibroblasts, vascular cells and inflammatory cells. Such interactions between the cancer and the cells within the microenvironment induce differential expression of genes that act to foster the growth, invasion and spread of tumor cells. This study utilizes pair-wise primary cultures of fibroblasts from normal and cancerous human endometrial tissues of the same patients to investigate the potential factors in the tumor microenvironment and their role in carcinogenesis. Both microRNA and mRNA profiling were performed on paired normal and cancer fibroblasts. SatB2 emerged as a promising candidate when its expression was shown to be significantly increased in fibroblasts surrounding the tumor tissues in all but one patients tested (n=8). Further investigation documented that SatB2 is a target for miR31, via 2 binding sites located within the SATB2 3’ UTR region. In concordance, miR31 is down-regulated in tumor fibroblasts, which further implicates the potential role of SatB2 in promoting a favorable environment for tumors. Ectopic expression of SATB2 in normal fibroblasts does not affect the growth rate of an endometrial cancer cell line (EC-1) in co-culture experiments; however, it did increase the motility of EC-1 cells towards these fibroblasts by multiple folds in both in vitro migration and invasion assays. A reduction of SATB2 expression in cancer activated fibroblasts (CAFs) by shRNA attenuated the migratory ability of EC-1 cells, further supporting the role of SatB2 in tumor aggression. Our observations also indicated that the conditioned media from CAFs were sufficient to induce the motility changes in the EC-1 cells. We believe the elucidation of SatB2 pathway(s) will assist in uncovering the intricate connections between tumors and their microenvironments, leading to new targets for treating tumor progression. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1423.
Rediscovering dignity at the bedside
Authors: Irene J Higginson, S Hall
Journal: BMJ (2007)

当Gerasim先生坐在他旁边甚至有时坐上一整夜的时候，对于他来说真的是一种安慰。Gerasim是惟一一个从不说谎的人。从他的所作所为可以看出他是惟一一个清楚情况而且对此不加掩饰的人。因此这种关系对于他来说是个安慰。

——列夫·托尔斯泰《伊凡·伊里奇之死》
CD11c+ dendritic cells and plasmacytoid DCs are activated by human cytomegalovirus and retain efficient T cell-stimulatory capability upon infection
Authors: Espen Ø. Kvale, Jakob Dalgaard, Fridtjof Lund-Johansen, Halvor Rollag, Lorant Farkas, Karsten Midtvedt, Frode L. Jahnsen, Jan E. Brinchmann, Johanna Olweus
Journal: Blood (2005)
Chronic tissue response to carboxymethyl cellulose based dissolvable insertion needle for ultra-small neural probes
Authors: Takashi D.Y. Kozai, Zhannetta Gugel, Xia Li, Peter J. Gilgunn, Rakesh Khilwani, O. Burak Ozdoganlar, Gary K. Fedder, Douglas J. Weber, X. Tracy Cui
Journal: Biomaterials (2014)
Abnormal Hepatic Energy Homeostasis in Type 2 Diabetes†
Authors: Julia Szendroedi, Marek Chmelik, Albrecht Ingo Schmid, Peter Nowotny, Attila Brehm, Martin Krssak, Ewald Moser, Michael Roden
Journal: Hepatology (2009)

Increased hepatocellular lipids relate to insulin resistance and are typical for individuals with type 2 diabetes mellitus (T2DM). Steatosis and T2DM have been further associated with impaired muscular adenosine triphosphate (ATP) turnover indicating reduced mitochondrial fitness. Thus, we tested the hypothesis that hepatic energy metabolism could be impaired even in metabolically well-controlled T2DM. We measured hepatic lipid volume fraction (HLVF) and absolute concentrations of gammaATP, inorganic phosphate (Pi), phosphomonoesters and phosphodiesters using noninvasive (1)H/ (31)P magnetic resonance spectroscopy in individuals with T2DM (58 +/- 6 years, 27 +/- 3 kg/m (2)), and age-matched and body mass index-matched (mCON; 61 +/- 4 years, 26 +/- 4 kg/m (2)) and young lean humans (yCON; 25 +/- 3 years, 22 +/- 2 kg/m (2), P < 0.005, P < 0.05 versus T2DM and mCON). Insulin-mediated whole-body glucose disposal (M) and endogenous glucose production (iEGP) were assessed during euglycemic-hyperinsulinemic clamps. Individuals with T2DM had 26% and 23% lower gammaATP (1.68 +/- 0.11; 2.26 +/- 0.20; 2.20 +/- 0.09 mmol/L; P < 0.05) than mCON and yCON individuals, respectively. Further, they had 28% and 31% lower Pi than did individuals from the mCON and yCON groups (0.96 +/- 0.06; 1.33 +/- 0.13; 1.41 +/- 0.07 mmol/L; P < 0.05). Phosphomonoesters, phosphodiesters, and liver aminotransferases did not differ between groups. HLVF was not different between those from the T2DM and mCON groups, but higher (P = 0.002) than in those from the yCON group. T2DM had 13-fold higher iEGP than mCON (P < 0.05). Even after adjustment for HLVF, hepatic ATP and Pi related negatively to hepatic insulin sensitivity (iEGP) (r =-0.665, P = 0.010, r =-0.680, P = 0.007) but not to whole-body insulin sensitivity.These data suggest that impaired hepatic energy metabolism and insulin resistance could precede the development of steatosis in individuals with T2DM.
Sorafenib inhibits transforming growth factor β1-Mediated Epithelial-Mesenchymal Transition and apoptosis in mouse hepatocytes
Authors: Yue-Lei Chen, Jing Lv, Xiao-Lei Ye, Ming-Yu Sun, Qin Xu, Cheng-Hai Liu, Li-Hua Min, Hui-Ping Li, Ping Liu, Xiaoyan Ding
Journal: Hepatology (2011)

Epithelial-mesenchymal transition (EMT) is a physiological process that has been recognized to occur during the progression of an increasingly large number of human diseases, including liver fibrosis, cirrhosis, and hepatocellular carcinoma. The activation of transforming growth factor β (TGF-β) signaling is considered a critical event during EMT, and efforts have been made to screen small molecules that interfere with the TGF-β signaling pathway during EMT. Here we report the identification of sorafenib, a clinical agent that inhibits TGF-β signaling. When applied to AML12 cells and primary hepatocytes, sorafenib strikingly suppressed TGF-β1-induced EMT and apoptosis. Additionally, sorafenib inhibited TGF-β1-induced signal transducer and activator of transcription 3 phosphorylation. We further present in vitro evidence that sorafenib ameliorates the proapoptotic and profibrotic effects of TGF-β1 in mouse primary hepatocytes, suggesting that this drug exerts a protective effect on hepatocytes and has therapeutic potential for the treatment of liver fibrosis. (HEPATOLOGY 2011;)
TCT-324 New Simulation System for Percutaneous Coronary Intervention Training Improves Resident Performance
Authors: Makoto Hyodo, Masashi Iwabuchi, Katsuhiro Kondo, Kenji Ando, Shinichi Shirai, Koyu Sakai, Hiroyoshi Yokoi, Masakiyo Nobuyoshi
Journal: Journal of the American College of Cardiology (2012)
Plague: Its Symptomatology, Pathology, Treatment and Prophylaxis
Authors: W. J. Simpson
Journal: BMJ (1899)

Two features are specially characteristic of plague.They are, first, the slow, irregular, and gradual manner in which the disease acquires a hold over a locality into which it is imported, andwhich may later on become the scene of an epidemic; and secondly, the obscurity which often surrounds the earlier cases.
Synergistic Silencing: Combinations of Lipid-like Materials for Efficacious siRNA Delivery
Authors: Kathryn A Whitehead, Gaurav Sahay, George Z Li, Kevin T Love, Christopher A Alabi, Minglin Ma, Christopher Zurenko, William Querbes, Robert S Langer, Daniel G Anderson
Journal: Molecular Therapy (2011)

Despite the promise of RNA interference (RNAi) therapeutics, progress toward the clinic has been slowed by the difficulty of delivering short interfering RNA (siRNA) into cellular targets within the body. Nearly all siRNA delivery vehicles developed to date employ a single cationic or ionizable material. In order to increase the material space available for development of siRNA delivery therapeutics, this study examined the possibility of using binary combinations of ionizable lipid-like materials to synergistically achieve gene silencing. Interestingly, it was found that ineffective single lipid-like materials could be formulated together in a single delivery vehicle to induce near-complete knockdown of firefly luciferase and factor VII in HeLa cells and in mice, respectively. Microscopy experiments suggested that synergistic action resulted when combining materials that respectively mediated cellular uptake and endosomal escape, two important steps in the delivery process. Together, the data indicate that formulating lipid-like materials in combination can significantly improve siRNA delivery outcomes while increasing the material space available for therapeutic development. It is anticipated that this binary formulation strategy could be applicable to any siRNA delivery material in any target cell population that utilizes the two-step endosomal delivery pathway.