tbuckley/cabot-search huggingface dataset:
Noninvasive Ventilation in Acute Cardiogenic Pulmonary Edema
Authors: Alasdair Gray, Steve Goodacre, David E. Newby, Moyra Masson, Fiona Sampson, Jon Nicholl
Journal: New England Journal of Medicine (2008)

Noninvasive ventilation (continuous positive airway pressure [CPAP] or noninvasive intermittent positive-pressure ventilation [NIPPV]) appears to be of benefit in the immediate treatment of patients with acute cardiogenic pulmonary edema and may reduce mortality. We conducted a study to determine whether noninvasive ventilation reduces mortality and whether there are important differences in outcome associated with the method of treatment (CPAP or NIPPV).In a multicenter, open, prospective, randomized, controlled trial, patients were assigned to standard oxygen therapy, CPAP (5 to 15 cm of water), or NIPPV (inspiratory pressure, 8 to 20 cm of water; expiratory pressure, 4 to 10 cm of water). The primary end point for the comparison between noninvasive ventilation and standard oxygen therapy was death within 7 days after the initiation of treatment, and the primary end point for the comparison between NIPPV and CPAP was death or intubation within 7 days.A total of 1069 patients (mean [+/-SD] age, 77.7+/-9.7 years; female sex, 56.9%) were assigned to standard oxygen therapy (367 patients), CPAP (346 patients), or NIPPV (356 patients). There was no significant difference in 7-day mortality between patients receiving standard oxygen therapy (9.8%) and those undergoing noninvasive ventilation (9.5%, P=0.87). There was no significant difference in the combined end point of death or intubation within 7 days between the two groups of patients undergoing noninvasive ventilation (11.7% for CPAP and 11.1% for NIPPV, P=0.81). As compared with standard oxygen therapy, noninvasive ventilation was associated with greater mean improvements at 1 hour after the beginning of treatment in patient-reported dyspnea (treatment difference, 0.7 on a visual-analogue scale ranging from 1 to 10; 95% confidence interval [CI], 0.2 to 1.3; P=0.008), heart rate (treatment difference, 4 beats per minute; 95% CI, 1 to 6; P=0.004), acidosis (treatment difference, pH 0.03; 95% CI, 0.02 to 0.04; P<0.001), and hypercapnia (treatment difference, 0.7 kPa [5.2 mm Hg]; 95% CI, 0.4 to 0.9; P<0.001). There were no treatment-related adverse events.In patients with acute cardiogenic pulmonary edema, noninvasive ventilation induces a more rapid improvement in respiratory distress and metabolic disturbance than does standard oxygen therapy but has no effect on short-term mortality. (Current Controlled Trials number, ISRCTN07448447.)
No-Fault and Enterprise Liability: The View From Utah
Authors: S. Keith Petersen
Journal: Annals of Internal Medicine (1995)

Editorials15 March 1995No-Fault and Enterprise Liability: The View From UtahS. Keith Petersen, MDS. Keith Petersen, MDUtah Medical Association, Salt Lake City, UT 84102-2784Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-122-6-199503150-00010 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail In the position paper in this issue [1], the American College of Physicians endorses demonstration projects for testing no-fault and enterprise liability systems. In Utah, we are about to embark on a project that incorporates elements of both concepts. As President of the Utah Medical Association, I am pleased to see the College's endorsement of such projects. As the position paper explains, the existing medical liability system is fundamentally flawed. It does not provide timely and adequate compensation to persons who sustain an injury, nor does it deter negligence. Rather, it promotes fear and mistrust, and it does not provide ...References1. American College of Physicians. Beyond MICRA: new ideas for liability reform. Ann Intern Med. 1995; 122:466-73. Google Scholar2. Brennan TA, Leape LL, Laird NM, Hebert L, Localio AR, Lawthers AG, et al. Incidence of adverse events and negligence in hospitalized patients. N Engl J Med. 1991; 324:370-6. Google Scholar3. Leape LL, Brennan TA, Laird NM, Lawthers AG, Localio AR, Barnes BA, et al. The nature of adverse events in hospitalized patients. N Engl J Med. 1991; 324:377-84. Google Scholar4. Localio AR, Lawthers AG, Brennan TA, Laird NM, Hebert LE, Peterson LM, et al. Relation between malpractice claims and adverse events due to negligence. N Engl J Med. 1991; 325:245-51. Google Scholar Author, Article, and Disclosure InformationAuthors: S. Keith Petersen, MDAffiliations: Utah Medical Association, Salt Lake City, UT 84102-2784Corresponding Author: S. Keith Petersen, MD, Utah Medical Association, 540 East Fifth South Street, Salt Lake City, UT 84102-2784. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoBeyond MICRA: New Ideas for Liability Reform Metrics Cited byNo-Fault Compensation Schemes for Medical Injury: A ReviewIs it effective to file medical malpractice litigations and the names of hospitals and physicians involved on the Internet or not?Relation between Negligent Adverse Events and the Outcomes of Medical-Malpractice LitigationMedical Malpractice and No-Fault SystemsDoes Clinical Risk Management Improve the Quality of Health Care? 15 March 1995Volume 122, Issue 6Page: 462-463KeywordsContinuous quality improvementDecision makingEmotionsEpidemiologyFearHealth careHealth care providersHealth economicsMotivationPatients ePublished: 15 August 2000 Issue Published: 15 March 1995 Copyright & PermissionsCopyright © 1995 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Effects of program of physical activity enhancement using pedometers in COPD patients
Authors: Laura Mendoza, Miguel Aguilera, Jose Espinoza, Nicolás Balmaceda, Paula Horta, Ariel Castro, Ely Jover, Paula Barcos, Orlando Díaz, Karen Czischke, Patricia Schonffeldt, Vivianne Agar, Nicholas S. Hopkinson
Journal: European Respiratory Journal (2013)

Introduction: Physical activity is reduced in COPD with negative effects on morbidity and mortality. Advice alone is not sufficient to reverse the sedentary condition. Pedometers can be used but their effects on behaviour in COPD are not well understood.  Aim: To determine the effects of a program of physical activity enhancement using pedometers in COPD.  Method: COPD patients were recruited for a 3 month individual program promoting daily physical activity enhancement and randomly assigned to a pedometer-based program (Experimental Group, EG) or to a standard one (Control Group, CG). At the beginning and the end of the intervention period the average daily steps over one week, six-minute walking test (6MWT), the mMRC scale, the Saint George’s Respiratory Questionnaire (SGRQ) and the COPD assessment Test (CAT) were assessed.  Results: 94 patients were recruited, 88 completed the follow-up (46 EG, 42 CG), 60.6% men, age = 68.2 ± 8.4 y. (mean ± SD), FEV1/FVC%= 55.3 ± 9, 4, FEV1= 66.3 ± 19.1%, PY= 40.6 ± 19.9. EG and CG had comparable basal characteristics. The changes in steps/day (3028.9 ± 526.6 vs. 76.2 ± 1881.7 EG vs. CG, p  Conclusion: A program of physical activity enhancement using pedometers can significantly improve physical activity level and quality of life in COPD patients. Funded by FONIS, project SA10i20022.
Occupational asthma due to styrene.
Authors: J P Hayes, L Lambourn, J A Hopkirk, S R Durham, A J Taylor
Journal: Thorax (1991)

In a patient with asthma who was exposed to styrene serial self recorded measurements of peak expiratory flow showed the asthma to be work related, and inhalation tests with styrene reproducibly provoked a dual asthmatic response and increased responsiveness to inhaled histamine.
Activation of Lectin-Like Oxidized Low-Density Lipoprotein Receptor-1 Induces Apoptosis in Cultured Neonatal Rat Cardiac Myocytes
Authors: Eri Iwai-Kanai, Koji Hasegawa, Tatsuya Sawamura, Masatoshi Fujita, Tetsuhiko Yanazume, Shinya Toyokuni, Souichi Adachi, Yasuki Kihara, Shigetake Sasayama
Journal: Circulation (2001)

Background — Lectin-like oxidized LDL receptor-1 (LOX-1) was originally identified as a receptor expressed predominantly in endothelial cells. LOX-1 can also be expressed in other cell types, and the activation of the LOX-1 pathway has been implicated in apoptosis. There have been no reports, however, about LOX-1 expression in cardiac myocytes or regulation of myocardial cell apoptosis by LOX-1. Methods and Results — In primary cardiac myocytes from neonatal rats, immunohistochemical analyses using a specific monoclonal antibody against LOX-1 demonstrated that LOX-1 expression was markedly induced by stimulation with norepinephrine and endothelin-1. LOX-1 expression was upregulated in cardiac myocytes as well as in vessel walls of failing rat hearts in vivo. In the presence of a low concentration of oxidized LDL that did not induce apoptosis by itself, artificial overexpression of LOX-1 in cardiac myocytes in culture resulted in apoptosis. LOX-1 overexpression induced activation of p38 mitogen-activated protein kinase (MAPK) and oxidative stress in cardiac myocytes, as demonstrated by an increase in positive immunostaining for 8-hydroxy-2′-deoxyguanosine. Inhibition of p38 MAPK by cotransfection of a dominant-negative form of MKK6 as well as by administration of a specific inhibitor, SB203580 or FR167653, almost completely blocked the induction of apoptosis by LOX-1 activation. Antioxidant catalase also blocked LOX-1-induced apoptosis as well as activation of p38 MAPK. Conclusions — These findings demonstrate that LOX-1 expression in cardiac myocytes is induced by neurohormonal factors activated in heart failure and that LOX-1-dependent apoptosis in these cells requires p38 MAPK, a component of oxidant stress-sensitive signaling pathways.
Activation of the <i>RAS</i> Pathway Is Predictive for a Chemosensitive Phenotype of Acute Myelogenous Leukemia Blasts
Authors: Thomas Illmer, Christian Thiede, Anke Fredersdorf, Sylvia Stadler, Andreas Neubauer, Gerhard Ehninger, Markus Schaich
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Activation of the RAS pathway plays a major role in cancer cells. In acute myeloid leukemia (AML), mutations of the RAS genes cause an intrinsic activation of this pathway. Until now, clinical studies could not find clear association of RAS mutations with the clinical outcome after AML therapy. This could be due to alternative initiating events for activation of the RAS pathway like constitutive tyrosine kinase activation or mutations in Ras-regulating genes. Experimental Design: In total, 191 AML patients (126 as training population and 65 as test population) were studied for Ras activity with a glutathione S-transferase pull-down assay using Raf binding of activated Ras. Results: AML samples showed a wide range of Ras activity values, which was in contrast to normal bone marrow donors who showed no or very limited Ras activity. Using a Ras binding score based on semiquantitative Western blotting, we defined patients with strong Ras activity and compared Ras activity with RAS mutation. Surprisingly, only a minority of RAS mutated AML samples (22.2%) showed strong Ras activity, whereas 25 patients presented strong Ras activity in the absence of RAS mutations. Clinical outcome did not show differences according to RAS mutations. In contrast, Ras activity predicted for a high response rate (P &amp;lt; 0.05) and proved to be an independent factor for overall survival rate (P &amp;lt; 0.05) in younger AML patients receiving high-dose 1-β-d-arabinofuranosylcytosine as induction therapy. Conclusion: The data highlight the role for alternative pathways of Ras activation without RAS mutations. Intrinsically activated Ras seems to increase sensitivity of the AML blast to high-dose 1-β-d-arabinofuranosylcytosine therapy.
Anti-phenyltrimethylamino immunity in mice. II. L-Tyrosine-p-azophenyltrimethylammonium-induced suppressor T cells selectively inhibit the expression of B-cell clones bearing a cross-reactive idiotype.
Authors: Y G Alevy, C J Bellone
Journal: The Journal of Experimental Medicine (1980)

The anti-phenyltrimethylamino (TMA) response in A/J mice is characterized by a cross-reactive idiotype(s) (CRI) that appears linked to the Ig-Ie allotype. These findings made it attractive to look for a CRI on T cells reactive to the same TMA determinant. Thus a suppressor T-cell (Ts) assay specific for L-tyrosine-p-azophenyltrimethylammonium [tyr(TMA)] was developed. A/J mice were primed with either tyr(TMA) in complete Freund's adjuvant (CFA), L-tyrosine-azobenzenearsonate [tyr(ABA)] in CFA, or with CFA alone. 6 wk later all mice were inoculated with TMA-bovine serum albumin (BSA) in CFA, boosted with soluble TMA-BSA 3 wk later, and plaqued 7 d after the soluble boost. Priming with tyr(TMA) in CFA resulted in 66% suppression of anti-TMA plaque-forming cells (PFC) as compared with control groups primed with tyr(ABA) in CFA or CFA alone. The suppression was shown to be mediated by Ts, as only T cells but not B cells from suppressed animals transfer the suppression in adoptive cell transfer experiments into lethally irradiated recipients. The profile of the anti-TMA PFC in the suppressed and nonsuppressed animals was examined via incorporation of anti-idiotypic sera (specific for CRI-TMA) into the plaquing medium. The results of these experiments indicate that the suppression of the major CRI+-TMA PFC was virtually complete, whereas the CRI--TMA PFC are left intact. When A/J mice were primed with idiotypic antisera (anti-Id) or normal rabbit serum (NRS) rather than with the antigen on CFA alone, and the same protocol was followed thereafter, the anti-Id-inoculated mice were suppressed by 63% when compared with the NRS-primed controls. Again the suppression could be accounted for by the exclusive elimination of CRI+ anti-TMA PFC. The possibility that the antigen-induced idiotype suppression may result from idiotypic restrictions between interacting CRI+-Ts and CRT+-B cells will be discussed.
Human immunodeficiency virus infection of the human thymus and disruption of the thymic microenvironment in the SCID-hu mouse.
Authors: S K Stanley, J M McCune, H Kaneshima, J S Justement, M Sullivan, E Boone, M Baseler, J Adelsberger, M Bonyhadi, J Orenstein
Journal: The Journal of Experimental Medicine (1993)

Infection with the human immunodeficiency virus (HIV) results in immunosuppression and depletion of circulating CD4+ T cells. Since the thymus is the primary organ in which T cells mature it is of interest to examine the effects of HIV infection in this tissue. HIV infection has been demonstrated in the thymuses of infected individuals and thymocytes have been previously demonstrated to be susceptible to HIV infection both in vivo, using the SCID-hu mouse, and in vitro. The present study sought to determine which subsets of thymocytes were infected in the SCID-hu mouse model and to evaluate HIV-related alterations in the thymic microenvironment. Using two different primary HIV isolates, infection was found in CD4+/CD8+ double positive thymocytes as well as in both the CD4+ and CD8+ single positive subsets of thymocytes. The kinetics of infection and resulting viral burden differed among the three thymocyte subsets and depended on which HIV isolate was used for infection. Thymic epithelial (TE) cells were also shown to endocytose virus and to often contain copious amounts of viral RNA in the cytoplasm by in situ hybridization, although productive infection of these cells could not be definitively shown. Furthermore, degenerating TE cells were observed even without detection of HIV in the degenerating cells. Two striking morphologic patterns of infection were seen, involving either predominantly thymocyte infection and depletion, or TE cell involvement with detectable cytoplasmic viral RNA and/or TE cell toxicity. Thus, a variety of cells in the human thymus is susceptible to HIV infection, and infection with HIV results in a marked disruption of the thymic microenvironment leading to depletion of thymocytes and degeneration of TE cells.
Abdominal swelling in a patient with cirrhosis
Authors: I.-T. Lin, M.-J. Bair, H.-L. Chen, C.-H. Lee
Journal: Gut (2010)

The acetylation of histone proteins in the core of DNA regulates gene expression, including those affecting mitochondria. Both histone acetylation and mitochondrial deficit have been implicated in neuronal damage associated with drinking problems. Many alcoholics repeat unsuccessful attempts at abstaining, developing a pattern of repeated withdrawal from ethanol exposure. Here, we investigated whether aberrant histone acetylation contributes to mitochondrial and cellular damage induced by repeated ethanol withdrawal (EW). We also investigated whether this effect of histone acetylation involves a small non-coding RNA (microRNA) let-7f. Male rats receive two cycles of ethanol diet (7.5%, four weeks) and withdrawal. Prefrontal cortex was collected to measure mitochondrial respiration and histone acetylation using XF real-time respirometry and gold immunostaining, respectively. Separately, HT22 (mouse hippocampal) cells received two cycles of ethanol exposure (100 mM, 20 hours) and withdrawal. Histone acetylation promoter (Trichostatin A, TSA) and let-7f antagomir were applied during withdrawal. Mitochondrial respiration, let-7f level, and cell viability were assessed using XF respirometry, qPCR, TaqMan let-7f primers, and Calcein-AM assay, respectively. Repeated ethanol withdrawn rats show more than a twofold increase in histone acetylation, accompanied by mitochondrial respiratory suppression. EW-induced mitochondrial respiratory suppression is exacerbated by TSA treatment in a manner that is attenuated by let-7f antagomir cotreatment. TSA treatment does not alter the increasing effect of EW on let-7f level but dramatically exacerbates cell death induced by EW. These data suggest that the multiple episodes of withdrawal from chronic ethanol impede mitochondrial and cellular integrity through upregulating histone acetylation, independently or additively with let-7f.
Sensitive and Specific New Enzyme-Linked Immunosorbent Assay for N-ERC/Mesothelin Increases its Potential as a Useful Serum Tumor Marker for Mesothelioma
Authors: Kazu Shiomi, Yoshiaki Hagiwara, Kouji Sonoue, Tatsuya Segawa, Kazuya Miyashita, Masahiro Maeda, Hiroshi Izumi, Kimihiko Masuda, Masataka Hirabayashi, Takao Moroboshi, Takashi Yoshiyama, Atsuko Ishida, Yuji Natori, Akira Inoue, Masashi Kobayashi, Yukinori Sakao, Hideaki Miyamoto, Kazuhisa Takahashi, Okio Hino
Journal: Clinical Cancer Research (2008)

Abstract Background: Because mesothelioma initially progresses on the surface of the pleura and peritoneum without forming masses, it has been difficult to diagnose at an early stage. It would be very useful to identify a tumor marker that could be used for screening to enable more diagnoses to be made at an early, treatable stage. Materials and Methods: We had previously identified N-ERC/mesothelin as a potential biomarker for mesothelioma. In the current work, we used a newly developed ELISA system to gain data on N-ERC/mesothelin levels in various clinical settings. A total of 102 healthy volunteers were recruited. In addition, 39 patients were diagnosed with mesothelioma, 53 patients were diagnosed with diseases that should be distinguished from mesothelioma, and 201 subjects were diagnosed with asbestos-related nonmalignant diseases (including simple exposure to asbestosis) who were treated at any of the cooperating hospitals were enrolled. Results: Serum N-ERC/mesothelin levels measured by a new ELISA system showed that the median values from patients with mesothelioma were extremely high compared with levels obtained from other patients. Analysis in terms of histologic type showed that serum levels of N-ERC/mesothelin were elevated in epithelioid type mesothelioma, especially. In four important models of clinical settings, the sensitivity and specificity of N-ERC/mesothelin were about 71% to 90% and 88% to 93%, respectively. Conclusion: N-ERC/mesothelin is a very promising tumor marker for mesothelioma, especially epithelioid mesothelioma.
Book Review: Get through the MRCP Part 2: 360 Best of Fives
Authors: Kieran Walsh
Journal: Journal of the Royal Society of Medicine (2004)

Who led the Scottish forces at the Battle of Ancrum Moor?



Robert the Bruce


Angus


William Wallace


Bonnie Prince Charlie


King James IV






This—in case you are wondering—is a best-of-five question. There is a stem with five options, only one of which is correct. The others are distractors which are wrong though plausible. The idea is that you have to have a reasonable grasp of Scottish history to answer the question correctly.

Get Through the MRCP Part 2 contains 360 such best-of-five questions. It has six mock papers with 60 questions in each—as in the actual exam. In ‘Membership books’ the introduction often contains dubious tips about how to answer multiple choice questions; for example, always choose the longest answer. Such tips are about as reliable as ones you hear at Cheltenham races. Aruna Dias steers well clear of them and instead lays out how the exam has changed in recent years; for example, negative marking is now a thing of the past. Thus, blind guessing will earn you 20%, but that is unlikely to be enough to get you a framed certificate on your wall. In fact all parts of the Membership have changed a lot in the past few years. The oral exam is long gone: examiners can no longer grill candidates about emergencies, evidence-based medicine and chronic disease management. Instead these topics must be tested in the written paper and Dr Dias has done a good job of including them.

And what about the questions and answers themselves? They are excellent. The text has been edited by Eric Beck, former chief examiner of the Royal College of Physicians, and this undoubtedly helped a lot. There are only a few clangers. The author occasionally asks trick questions such as ‘the drug that would not be used to treat this illness is’ and then asking the candidate to choose between five possible options. When you see a patient, you do not start thinking about what treatment you would not give them. So why test juniors’ knowledge in this way? But the bottom line is: will it help people pass the exam and should I recommend it to my juniors? The answer to these questions is yes and yes.

In case you are still wondering, the Scottish forces at the Battle of Ancrum Moor were led by Angus. Successfully.