tbuckley/cabot-search huggingface dataset:
Increased Bleeding Tendency and Decreased Susceptibility to Thromboembolism in Mice Lacking the Prostaglandin E Receptor Subtype EP <sub>3</sub>
Authors: Hong Ma, Akiyoshi Hara, Chun- Yang Xiao, Yuji Okada, Osamu Takahata, Kazuhiro Nakaya, Yukihiko Sugimoto, Atsushi Ichikawa, Shuh Narumiya, Fumitaka Ushikubi
Journal: Circulation (2001)

Among the prostanoids, thromboxane (TX) A(2) is a potent stimulator of platelets, whereas prostaglandin (PG) I(2) inhibits their activation. The roles of PGE(2) in the regulation of platelet function have not been established, however, and the contribution of PGE(2) in hemostasis and thromboembolism is poorly understood. The present study was intended to clarify these roles of PGE(2) by using mice lacking the PGE(2) receptor subtype 3 (EP(3)(-/-) mice).Expression of mRNAs for EP(3) in murine platelets was confirmed by quantitative reverse transcription-polymerase chain reaction. PGE(2) and AE-248, a selective EP(3) agonist, showed concentration-dependent potentiation of platelet aggregation induced by U46619, a TXA(2) receptor agonist, although PGE(2) alone could not induce aggregation. PGE(2) and AE-248 increased cytosolic calcium ion concentration ([Ca(2+)](i)), and AE-248 inhibited the forskolin-induced increase in cytosolic cAMP concentration ([cAMP](i)), suggesting G(i) coupling of EP(3). The potentiating effects of PGE(2) and AE-248 on platelet aggregation along with their effects on [Ca(2+)](i) and [cAMP](i) were absent in EP(3)(-/-) mice. In vivo, the bleeding time was significantly prolonged in EP(3)(-/-) mice. Moreover, when mice were challenged intravenously with arachidonic acid, mortality and thrombus formation in the lung were significantly reduced in EP(3)(-/-) mice.- PGE(2) potentiated platelet aggregation induced by U46619 via EP(3) by increasing [Ca(2+)](i), decreasing [cAMP](i), or both. This potentiating action of PGE(2) via EP(3) is essential in mediating both physiological and pathological effects of PGE(2) in vivo.
Prediction of defibrillation success from a single defibrillation threshold measurement with sequential pulses and two current pathways in humans.
Authors: D L Jones, G J Klein, G M Guiraudon, A D Sharma, R Yee, M J Kallok
Journal: Circulation (1988)

The ultimate aim of defibrillation testing is to predict consistent defibrillation. This study tested the hypothesis that defibrillation success could be predicted from a single measurement of defibrillation threshold. We measured defibrillation threshold by using three patch electrodes and a standard protocol intraoperatively in 49 patients undergoing arrhythmia surgery. Each patient was then assigned to one of five energy subgroups (0.5, 1.0, 1.5, 2.0, or 2.5 times defibrillation threshold) for a single shock (followed by a rescue shock if necessary) for a subsequent ventricular fibrillation episode. A curve relating percent success to energy was then constructed for the group. Defibrillation threshold averaged 4.7 +/- 2.98 J for the group (mean +/- SD). There was a curvilinear relation between the energy of the defibrillation threshold ratio test shock and percent success: 33.3%, 58.3%, 81.8%, 91.7%, and 100% at mean defibrillation threshold ratios of 0.56 +/- 0.14, 1.02 +/- 0.07, 1.53 +/- 0.14, 1.88 +/- 0.09, and 2.60 +/- 0.14, respectively. We conclude that consistent defibrillation is predictable from a single measurement of defibrillation threshold. Furthermore, for an individual patient, a safety margin of 2.6 times defibrillation threshold should approximate 100% successful defibrillation for a single test shock.
Cost-Benefit Analysis and Heart Transplantation
Authors: Brandon S. Centerwall
Journal: New England Journal of Medicine (1981)

Amid a flurry of controversy, the trustees of the Massachusetts General Hospital have disallowed heart transplantation by the cardiac surgical service.1 Meanwhile, the Mayo Clinic is establishing a new heart-transplantation program.2 Moribund in the 1970s, the procedure is reviving as a potentially viable clinical option, now that five-year survival rates are exceeding 50 per cent.2 The question, "Can it be done?" has changed to "Should it be done?" with major medical institutions splitting both ways.Cash is the bottom line. In 1972, when Medicare coverage was extended to patients with renal failure, it was "only a question of money." 3 Since . . .
Sodium Diatrizoate for Intravenous Pyelography
Authors: Howard A. Hoffman, Stanley J. Koczera, Nelson L. Portnoy, Emery O. Lewis, Edward C. Vogt, Wilson Simas
Journal: New England Journal of Medicine (1955)

AS urologists and radiologists we are interested in devising safer and better methods of urologic examination. The opportunity was presented to us a short time ago to use sodium diatrizoate†† as a new radiopaque contrast medium for intravenous pyelography. The substance had previously been used by Moore and Mayer1 with good results, and it was considered for trial in this hospital. Martineau, Forsythe and Soderberg2 had likewise reported 100 cases, with significantly better films.Accordingly, we collected 100 cases, which are presented in this paper. Our results are considered to show a significant improvement in film contrast with a minimum . . .
Effect of beta-blockers on arrhythmias.
Authors: M Husaini
Journal: BMJ (1979)

of myocardial infarction,"' 12 together with the relationship between the incidence of PVF and early admission in the hospital series,7 suggests electrophysiological dis- turbance within the heart leading to ventricular fibrillation but clearing within 24 hours.Thus, although it is true that the heart at 17-18 hours after the onset of symptoms may not be especially vulnerable to serious arrhythmias and that they do not at this stage constitute an independent risk factor, the same conclusion cannot be drawn when these serious arrythmias occur within the first two hours.
Osteopontin is induced by hedgehog pathway activation and promotes fibrosis progression in nonalcoholic steatohepatitis
Authors: Wing-Kin Syn, Steve S. Choi, Evaggelia Liaskou, Gamze F. Karaca, Kolade M. Agboola, Ye Htun Oo, Zhiyong Mi, Thiago A. Pereira, Marzena Zdanowicz, Padmini Malladi, Yuping Chen, Cynthia Moylan, Youngmi Jung, Syamal D. Bhattacharya, Vanessa Teaberry, Alessia Omenetti, Manal F. Abdelmalek, Cynthia D. Guy, David H. Adams, Paul C. Kuo, Gregory A. Michelotti, Peter F. Whitington, Anna Mae Diehl
Journal: Hepatology (2010)

Nonalcoholic steatohepatitis (NASH) is a leading cause of cirrhosis. Recently, we showed that NASH-related cirrhosis is associated with Hedgehog (Hh) pathway activation. The gene encoding osteopontin (OPN), a profibrogenic extracellular matrix protein and cytokine, is a direct transcriptional target of the Hh pathway. Thus, we hypothesize that Hh signaling induces OPN to promote liver fibrosis in NASH. Hepatic OPN expression and liver fibrosis were analyzed in wild-type (WT) mice, Patched-deficient (Ptc+/−) (overly active Hh signaling) mice, and OPN-deficient mice before and after feeding methionine and choline–deficient (MCD) diets to induce NASH-related fibrosis. Hepatic OPN was also quantified in human NASH and nondiseased livers. Hh signaling was manipulated in cultured liver cells to assess direct effects on OPN expression, and hepatic stellate cells (HSCs) were cultured in medium with different OPN activities to determine effects on HSC phenotype. When fed MCD diets, Ptc+/− mice expressed more OPN and developed worse liver fibrosis ( P &lt; 0.05) than WT mice, whereas OPN-deficient mice exhibited reduced fibrosis ( P &lt; 0.05). In NASH patients, OPN was significantly up-regulated and correlated with Hh pathway activity and fibrosis stage. During NASH, ductular cells strongly expressed OPN. In cultured HSCs, SAG (an Hh agonist) up-regulated, whereas cyclopamine (an Hh antagonist) repressed OPN expression ( P &lt; 0.005). Cholangiocyte-derived OPN and recombinant OPN promoted fibrogenic responses in HSCs ( P &lt; 0.05); neutralizing OPN with RNA aptamers attenuated this ( P &lt; 0.05). Conclusion: OPN is Hh-regulated and directly promotes profibrogenic responses. OPN induction correlates with Hh pathway activity and fibrosis stage. Therefore, OPN inhibition may be beneficial in NASH (Hepatology 2011)
Action of sotalol on potential reentrant pathways and ventricular tachyarrhythmias in conscious dogs in the late postmyocardial infarction phase.
Authors: S M Cobbe, E Hoffman, A Ritzenhoff, J Brachmann, W Kübler, J Senges
Journal: Circulation (1983)

Sotalol is a beta-adrenergic blocker that also prolongs action potential duration and myocardial refractoriness over the short term (class III effect). Its short-term antiarrhythmic effects were compared with those of metoprolol, which has neither short-term class III nor membrane-stabilizing action, on reentrant ventricular arrhythmias produced by programmed stimulation in 17 conscious dogs 3 to 8 days after myocardial infarction. Ventricular arrhythmias were prevented or significantly slowed by sotalol in 11 of 19 studies (58%) compared with in one of 14 (7%) studies with metoprolol. Sotalol prolonged refractoriness in the infarct zone, measured from an implanted "composite" electrode, by 41 +/- 45% (mean +/- SD, p less than .01), which was significantly greater than the increases it produced in effective refractory period of the normal ventricle (14.0 +/- 5.5%) or QT interval (12.5 +/- 7.8%). Metoprolol had no effect on infarct-zone refractoriness. Sotalol differentially increases refractoriness in potential reentry circuits in ischemic myocardium. Its antiarrhythmic effect in this model is not due to beta-blockade, and is presumably related to prolongation of action potential duration.
Screening, isolation, and decolonisation strategies in the control of meticillin resistant Staphylococcus aureus in intensive care units: cost effectiveness evaluation
Authors: J. V. Robotham, N. Graves, B. D. Cookson, A. G. Barnett, J. A. Wilson, J. D. Edgeworth, R. Batra, B. H. Cuthbertson, B. S. Cooper
Journal: BMJ (2011)

<h3>Background</h3> Cervical cancer is the leading cause of cancer death for women in Uganda, despite the potential for prevention through organised screening. Community-based self-collected human papillomavirus (HPV) testing has been proposed to reduce barriers to screening. <h3>Objective</h3> Our objective was to evaluate the cost-effectiveness of the Advances in Screening and Prevention of Reproductive Cancers (ASPIRE) trial, conducted in Kisenyi, Uganda in April 2014 (n=500). The trial compared screening uptake and compliance with follow-up in two arms: (1) community-based (ie, home or workplace) self-collected HPV testing (facilitated by community health workers) with clinic-based visual inspection with acetic acid (VIA) triage of HPV-positive women (‘HPV-VIA’) and (2) clinic-based VIA (‘VIA’). In both arms, VIA was performed at the local health unit by midwives with VIA-positive women receiving immediate treatment with cryotherapy. <h3>Design</h3> We informed a Monte Carlo simulation model of HPV infection and cervical cancer with screening uptake, compliance and retrospective cost data from the ASPIRE trial; additional cost, test performance and treatment effectiveness data were drawn from observational studies. The model was used to assess the cost-effectiveness of each arm of ASPIRE, as well as an HPV screen-and-treat strategy (‘HPV-ST’) involving community-based self-collected HPV testing followed by treatment for all HPV-positive women at the clinic. <h3>Outcome measures</h3> The primary outcomes were reductions in cervical cancer risk and incremental cost-effectiveness ratios (ICERs), expressed in dollars per year of life saved (YLS). <h3>Results</h3> HPV-ST was the most effective and cost-effective screening strategy, reducing the lifetime absolute risk of cervical cancer from 4.2% (range: 3.8%–4.7%) to 3.5% (range: 3.2%–4%), 2.8% (range: 2.4%–3.1%) and 2.4% (range: 2.1%–2.7%) with ICERs of US$130 (US$110–US$150) per YLS, US$240 (US$210–US$280) per YLS, and US$470 (US$410–US$550) per YLS when performed one, three and five times per lifetime, respectively. Findings were robust across sensitivity analyses, unless HPV costs were more than quadrupled. <h3>Conclusions</h3> Community-based self-collected HPV testing followed by treatment for HPV-positive women has the potential to be an effective and cost-effective screening strategy.
Wave of paediatric eye injuries from liquid detergent capsules
Authors: R. G Mathew, K. Kennedy, M. C Corbett
Journal: BMJ (2010)

We highlight a new wave of paediatric ocular surface injuries.1

In 2001 the cleaning products industry produced liquid capsules for fabric detergents. Last year chemical injuries associated with these capsules accounted for 40% of ocular chemical injuries in children under the age of 5 at this hospital. Guy’s and St Thomas’ Poisons Unit received 192 enquires related …
Protease-Activated Receptor-2 Is Essential for Factor VIIa and Xa–Induced Signaling, Migration, and Invasion of Breast Cancer Cells
Authors: Dionne R. Morris, Yu Ding, Tiffany K. Ricks, Anuradha Gullapalli, Breann L. Wolfe, JoAnn Trejo
Journal: Cancer Research (2006)

Abstract Protease-activated receptors (PAR) are G protein–coupled receptors that function as cell-surface sensors for coagulant proteases, as well as other proteases associated with the tumor microenvironment. PAR1 is activated by thrombin whereas the upstream coagulant protease VIIa bound to tissue factor and Xa can activate both PAR1 and PAR2. PAR1 has been implicated in tumor cell growth, migration, and invasion whereas the function of PAR2 in these processes is largely unknown. Towards defining the functional importance of PAR2 in cancer cells, we used small interfering RNAs to deplete highly invasive breast cancer cells of endogenous PAR proteins. Our findings strongly suggest that PAR2 is critical for MDA-MB-231 and BT549 breast cancer cell migration and invasion towards NIH 3T3 fibroblast conditioned medium. To define the relative importance of PAR1 versus PAR2 in mediating factor VIIa and Xa responses, we assessed signaling in cancer cells lacking either endogenous PAR1 or PAR2 proteins. Strikingly, in MDA-MB-231 cells depleted of PAR2, we observed a marked inhibition of VIIa and Xa signaling to phosphoinositide hydrolysis and extracellular signal–regulated kinase 1/2 activation whereas signaling by VIIa and Xa remained intact in PAR1-deficient cells. Factor VIIa and Xa–induced cellular migration was also impaired in MDA-MB-231 cells deficient in PAR2 but not in cells lacking PAR1. Together, these studies reveal the novel findings that PAR2, a second protease-activated G protein–coupled receptor, has a critical role in breast cancer cell migration and invasion and functions as the endogenous receptor for coagulant proteases VIIa and Xa in these cells. (Cancer Res 2006; 66(1): 307-14)
Human exposure to carcinogenic heterocyclic amines and their mutational fingerprints in experimental animals.
Authors: M Nagao, K Wakabayashi, T Ushijima, M Toyota, Y Totsuka, T Sugimura
Journal: Environmental Health Perspectives (1996)

Heterocyclic amines (HCAs) are mutagens/carcinogens to which humans are exposed on almost a daily basis. 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhlP) is the most abundant of the various carcinogenic HCAs (present at a level of 0.56 to 69.2 ng/g of cooked meat or fish), with 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MelQx) following it at 0.64 to 6.44 ng/g. HCAs have been found in the urine of healthy people who consume ordinary diets, while patients receiving parenteral alimentation lack, for example, PhlP and MelQx in their urine. Based on the concentrations of PhlP and MelQx in urine samples from 10 healthy volunteers, daily intake of MelQx in Japanese was calculated to be 0.3 to 3.9 micrograms/person, while that of PhlP was 0.005 to 0 micrograms. The Japanese consume more MelQx than Americans, whereas Japanese intake of PhlP was about one-third that of Americans. MelQx-DNA adducts have also detected in Japanese Kidney, colon, and rectum samples using the 32P-postlabeling method followed by identification using high-performance liquid chromatography (HPLC) analysis; the levels were 0.18, 1.8, and 1.4 per 10(9) nucleotides, respectively. In addition, we elucidated the mutational fingerprints of Phlp by analyzing Apc mutations in rat colon cancers induced by this carcinogen. Four of eight tumors had a total of five mutations in the Apc gene, four of which featured a guanine deletion from 5'-GTGGGAT-3' sequences. This specific mutation spectrum may be used as a fingerprint of PhlP in evaluating its risk potential for human colon carcinogenesis. Mutations were not found in similar 2-amino-3-methylimidazo[4,5-f]quinoline-induced colon lesions. Microsatellite instability was detected in both colon and mammary tumors induced by PhlP. The mechanisms involved in this development of microsatellite instability in PhlP. The mechanisms involved in this development of microsatellite instability in PhlP-induced cancers remain to be elucidated.
Private sector run hospital made 2.3m loss in first quarter
Authors: I. Torjesen
Journal: BMJ (2012)

The first financially challenged NHS hospital to have its management franchised out to the private sector has recorded a loss of £2.3m (€2.9m; $3.6m) in the first quarter of this financial year.

In February this year Circle took over the management of Hinchingbrooke Healthcare NHS Trust in Cambridgeshire, which had debts of around £40m. At the time, Circle said it was confident it could turn the trust’s fortunes around and drew up a 16 point transformational plan to make cost improvements of £9.9m this …
Treating psoriasis with calcipotriol.
Authors: P. C. Newbold
Journal: BMJ (1992)

studies are analysed not only by patients' ages but also according to their functional state and the presence of co- existent disease.At present, age is too frequently used as a convenient but inaccurate proxy for other, less easily measured indices of likely benefit and possible risk.Clear reasons exist for treating elderly patients with thrombolytic agents: lives can be saved and myocardial function improved.We should ensure that the reasons for withholding treatment are equally clear.Age alone is not sufficient.
Cushing's Syndrome in Childhood
Authors: W. P. U. Jackson, B. Zilberg, B. Lewis, D. McKenzie
Journal: BMJ (1958)

HAEMORRHAGIC THROMBOCYTHAEMIA routine tests of haemostatic function are invariably nor- mal; No deficiency of platelet factor as evidenced by the normal thromboplastin generation tests was detected in either of the above patients.In both patients the platelet count returned to normal and bleeding ceased after treatment with radioactive phosphorus.
Needs of black and ethnic minorities.
Authors: R. Bhopal
Journal: BMJ (1992)

Prophylaxis against venous thromboembolismEDITOR,-We are disappointed that the review article on the risk of and prophylaxis against venous thromboembolism in hospital patients does not mention the advantageous effects of afferent blockade for patients undergoing surgical procedures.'The stress response to surgery increases angiotensin and catecholamine concentrations, which increase platelet aggregation." Hepatic synthesis of fibrinogen is increased, while synthesis of antithrombin III is reduced.5Attenuated stress responses can be shown with epidural and spinal analgesia for lower abdominal and more distal surgery9 and with paravertebral analgesia for thoracic surgery J Richardson et al, unpublished data).Proved benefits of afferent blockade include increased fibrinolytic activity-and improved thromboelastography.5 In addition, lower limb blood flows are raised with epidural analgesia.9These pathophysiological advantages are supported by an improvement in outcome after major surgery in patients managed with regional anal- gesia as well as, or instead of, general anaesthesia.Not only are venous thromboembolic events significantly (p < 0 05) reduced "' but other events related to coagulation are also favourably affected, including perioperative myocardial infarction9,, and vascular graft patency.9We do not take issue with the value of the mechanical and pharmacological methods described in the review, but the additional benefits offered by regional analgesia for surgical patients deserve emphasis.
TCT-376 SIMPLIPHieDE Study - Single center IMPella LVAD supported Pci in High Risk group of patients – Detroit Medical Center Experience – Clinical Outcomes
Authors: Haroon Faraz, Tamam Mohamad, Rohit Amin, Hassan Ismail, Obrad Kokanovic, Antwon Robinson, Sabeeh Siddiqui, Muhammad Shahzad, Theodore Schreiber
Journal: Journal of the American College of Cardiology (2012)
Diagnostic and therapeutic implications of transesophageal echocardiography in medical ICU patients with unexplained shock, hypoxemia, or suspected endocarditis
Authors: M. A. Slama, A. Novara, P. Van De Putte, B. Diebold, A. Safavian, M. Safar, M. Ossart, J. Y. Fagon
Journal: Intensive Care Medicine (1996)
Birth Defects Compendium
Authors: Allen L. Horwitz
Journal: JAMA (1980)

This is a valuable book that should be of use to all branches of medicine and will be the desk "bible" for medical geneticists and many pediatricians. Although there are several books available summarizing major malformation syndromes or genetic defects, none is as extensive or inclusive as this compendium. Birth defects are defined for this volume as any anatomic or functional variant from the normal that is inherited, or caused by new mutations, chromosomal abnormalities, or insult to embryo or fetus. There are listed more than 1,000 syndromes, patterns of malformation, and most of the metabolic disorders of a hereditary nature. The format is standardized for each condition so as to make easily available most of the information necessary for diagnosis and counseling, as well as a summary of therapeutic approaches. Most of the authors of each section are well established in the fields under discussion. The references supplied for
Integration of Horizontally Transferred Genes into Regulatory Interaction Networks Takes Many Million Years
Authors: M. J. Lercher, C. Pal
Journal: Molecular Biology and Evolution (2007)

Adaptation of bacteria to new or changing environments is often associated with the uptake of foreign genes through horizontal gene transfer. However, it has remained unclear how (and how fast) new genes are integrated into their host's cellular networks. Combining the regulatory and protein interaction networks of Escherichia coli with comparative genomics tools, we provide the first systematic analysis of this issue. Genes transferred recently have fewer interaction partners compared to nontransferred genes in both regulatory and protein interaction networks. Thus, horizontally transferred genes involved in complex regulatory and protein-protein interactions are rarely favored by selection. Only few protein-protein interactions are gained after the initial integration of genes following the transfer event. In contrast, transferred genes are gradually integrated into the regulatory network of their host over evolutionary time. During adaptation to the host cellular environment, horizontally transferred genes recruit existing transcription factors of the host, reflected in the fast evolutionary rates of the cis-regulatory regions of transferred genes. Further, genes resulting from increasingly ancient transfer events show increasing numbers of transcriptional regulators as well as improved coregulation with interacting proteins. Fine-tuned integration of horizontally transferred genes into the regulatory network spans more than 8-22 million years and encompasses accelerated evolution of regulatory regions, stabilization of protein-protein interactions, and changes in codon usage.