tbuckley/cabot-search huggingface dataset:
Percutaneous transluminal coronary angioplasty improves survival in acute myocardial infarction complicated by cardiogenic shock.
Authors: L Lee, E R Bates, B Pitt, J A Walton, N Laufer, W W O'Neill
Journal: Circulation (1988)

Modest survival benefits have been reported in patients with acute myocardial infarction complicated by cardiogenic shock who were treated with early surgical revascularization or thrombolytic therapy. To determine whether coronary angioplasty improves survival, 87 patients with cardiogenic shock complicating acute myocardial infarction at the University of Michigan, Ann Arbor, Michigan, from 1975 to 1985 were retrospectively analyzed. Patients in group 1 (n = 59) were treated with conventional therapy; patients in group 2 (n = 24) were treated with conventional therapy and angioplasty. Extent of coronary artery disease, infarct location, and incidence of multivessel disease were similar between groups. Hemodynamic variables including cardiac index, mean arterial pressure, and pulmonary capillary wedge pressure were also similar. The 30-day survival was significantly improved for group 2 patients (50% vs. 17%, p = 0.006). Survival in group 2 patients with successful angioplasty was 77% (10 of 13 patients) versus 18% (two of 11 patients) in patients with unsuccessful angioplasty, (p = 0.006). The findings suggest that angioplasty improves survival in cardiogenic shock compared with conventional therapy with survival contingent upon successful reperfusion of the infarct-related artery.
Remodelling of gap junctions and connexin expression in diseased myocardium
Authors: N. J. Severs, A. F. Bruce, E. Dupont, S. Rothery
Journal: Cardiovascular Research (2008)

Gap junctions form the cell-to-cell pathways for propagation of the precisely orchestrated patterns of current flow that govern the regular rhythm of the healthy heart. As in most tissues and organs, multiple connexin types are expressed in the heart: connexin43 (Cx43), Cx40 and Cx45 are found in distinctive combinations and relative quantities in different, functionally-specialized subsets of cardiac myocyte. Mutations in genes that encode connexins have only rarely been identified as being a cause of human cardiac disease, but remodelling of connexin expression and gap junction organization are well documented in acquired adult heart disease, notably ischaemic heart disease and heart failure. Remodelling may take the form of alterations in (i) the distribution of gap junctions and (ii) the amount and type of connexins expressed. Heterogeneous reduction in Cx43 expression and disordering in gap junction distribution feature in human ventricular disease and correlate with electrophysiologically identified arrhythmic changes and contractile dysfunction in animal models. Disease-related alterations in Cx45 and Cx40 expression have also been reported, and some of the functional implications of these are beginning to emerge. Apart from ventricular disease, various features of gap junction organization and connexin expression have been implicated in the initiation and persistence of the most common form of atrial arrhythmia, atrial fibrillation, though the disparate findings in this area remain to be clarified. Other major tasks ahead focus on the Purkinje/working ventricular myocyte interface and its role in normal and abnormal impulse propagation, connexin-interacting proteins and their regulatory functions, and on defining the precise functional properties conferred by the distinctive connexin co-expression patterns of different myocyte types in health and disease.
Erythrocyte peripheral type benzodiazepine receptor/voltage-dependent anion channels are upregulated by Plasmodium falciparum
Authors: Guillaume Bouyer, Anne Cueff, Stéphane Egée, Justyna Kmiecik, Yelena Maksimova, Edyta Glogowska, Patrick G. Gallagher, Serge L. Y. Thomas
Journal: Blood (2011)
Improved exercise capacity and differing arterial and venous tolerance during chronic isosorbide dinitrate therapy for congestive heart failure.
Authors: C V Leier, P Huss, R D Magorien, D V Unverferth
Journal: Circulation (1983)

We studied 30 patients with moderate-to-severe congestive heart failure in a double-blind, randomized, placebo-controlled trial to determine the acute and long-term effects of isosorbide dinitrate on clinical status and on resting and exercise hemodynamics. Seventeen patients received placebo and 13 isosorbide dinitrate. First-dose isosorbide dinitrate (40 mg orally) decreased resting and exercise pulmonary capillary wedge pressure, pulmonic and systemic arterial pressures and pulmonic and systemic vascular resistances without augmenting exercise capacity. Compared with placebo, chronic therapy with isosorbide dinitrate (40 mg orally every 6 hours for 12 weeks) significantly improved clinical status and exercise capacity. Resting and exercise systemic blood pressure and systemic vascular resistance returned to baseline values during chronic isosorbide dinitrate therapy, but pulmonary capillary wedge pressure, pulmonary artery pressure and pulmonary vascular resistance remained improved. In patients with congestive heart failure, 12 weeks of oral isosorbide dinitrate therapy improves resting and exercise hemodynamics, exercise capacity, and clinical status; tolerance develops to the systemic arterial vascular effects without attenuation of the venous and pulmonary vascular effects.
Surgical Treatment of Esophageal Hypermotility Disturbances
Authors: F. Henry Ellis, Arthur M. Olsen, Jerry F. Schlegel, Charles F. Code
Journal: JAMA (1964)

Forty-six patients with diffuse spasm of the esophagus, hypertensive gastroesophageal sphincter, or localized esophageal spasm occurring either singly or in combination, have undergone long esophagomyotomy at the Mayo Clinic as of July, 1963, without mortality or significant complication. Of the patients under study, 78% were symptomatically improved by the operation. Late postoperative esophageal motility studies on 23 patients operated on prior to 1962 showed that the reduction in pressure seen in the incised region soon after operation was maintained during the follow-up period in all but one patient. Manometric evidence suggestive of a hiatal hernia was present in eight patients, but was without roentgenographic confirmation.
Noninvasive assessment of left and right ventricular filling in myocardial infarction with a two-dimensional Doppler echocardiography method
Authors: Junichi Fujii, Yoshizumi Yazaki, Hitoshi Sawada, Tadanori Aizawa, Hiroshi Watanabe, Kazuzo Kato
Journal: Journal of the American College of Cardiology (1985)
AMPUTATIONS AT THE SHOULDER AND AT THE HIP
Authors: H. Littlewood
Journal: BMJ (1922)

Conclusion.The consideration of the evidence suggests that an error in the metabolism of lecitlhin, probably in the liver, may be a causal factor in the failure of bone formation in rickets, and that this faulty metabolism may in some cases be accom- panied by an increased conversion of cliolin into guanidin compounds, thus explain-ing the association of tetany with rickets.Tihe theory is put forward tentatively in the lhope that it may indicate lines for further work upon the nature of the disturbance in rickets.
Anorexia Nervosa Clue
Authors: Joan Stephenson
Journal: JAMA (2007)

Anorexia nervosa and the appetite-suppressing “club drug” ecstasy (3,4-methylenedioxymethamphetamine) activate some of the same brain pathways, according to research in mice by French scientists (Jean A. Proc Natl Acad Sci U S A. 2007;104[41]:16335-16340).
"Paid for by the NHS"
Authors: K. Patel
Journal: BMJ (2009)

“There are four ways in which you can spend money. You can spend your own money on yourself. When you do that, then you really watch out what you’re doing, and you try to get the most for your money.

“Then you can spend your own money on somebody else. For example, I buy a birthday present for someone. Well, then I’m not so careful about the content of the present, but I’m very careful about the cost.

“Then, I can spend somebody else’s money on myself. And …
Ezrin, a membrane cytoskeletal cross-linker, is essential for the regulation of phosphate and calcium homeostasis
Authors: Ryo Hatano, Eiko Fujii, Hiroko Segawa, Kenichi Mukaisho, Mitsunobu Matsubara, Ken-ichi Miyamoto, Takanori Hattori, Hiroyuki Sugihara, Shinji Asano
Journal: Kidney International (2012)
B7-1/B7-2 Costimulation Regulates Plaque Antigen–Specific T-Cell Responses and Atherogenesis in Low-Density Lipoprotein Receptor–Deficient Mice
Authors: Chiara Buono, Hong Pang, Yasushi Uchida, Peter Libby, Arlene H. Sharpe, Andrew H. Lichtman
Journal: Circulation (2004)

Background— Several lines of evidence indicate that T-cell responses influence the progression of atherosclerotic disease. Interferon-γ (IFN-γ)–producing T cells specific for lesional antigens, including oxidized LDLs and heat shock protein 60 (HSP60), may promote lesion development as well as plaque instability. B7-1 and B7-2 are closely related molecules expressed on antigen-presenting cells that provide costimulatory signals for T-cell activation. This study tested the hypothesis that the ability of T cells to influence atherosclerosis depends on B7-1/B7-2 costimulation. Methods and Results— B7-1/B7-2/LDL receptor (LDLR)–deficient mice and LDLR-deficient control mice were fed a 1.25% cholesterol or control diet for 8 and 20 weeks. Total serum cholesterol levels and extent and phenotype of atherosclerosis were analyzed. Splenic and lymph node CD4 + T cells from the animals were cultured with mouse recombinant HSP60 or media and antigen-presenting cells and analyzed for IFN-γ and interleukin-4 production. The absence of B7-1 and B7-2 significantly reduced early cholesterol diet–induced atherosclerotic lesion development in LDLR-deficient mice compared with B7-1/B7-2–expressing control mice. Furthermore, CD4 + T cells from the cholesterol-fed B7-deficient mice secreted a significantly lower amount of IFN-γ in response to mouse HSP60 in vitro than did T cells from B7-expressing control mice. Conclusions— The data show that B7-1 and B7-2 regulated the development of atherosclerotic lesions and the priming of lesional antigen–specific T cells. This study highlights the B7-CD28 pathway as a potentially important target for immunomodulation of atherosclerosis.
Xeroderma pigmentosum, Cockayne syndrome and trichothiodystrophy: do the genes explain the diseases?
Authors: Gilbert Chu, Lynn Mayne
Journal: Trends in Genetics (1996)

Xeroderma pigmentosum, Cockayne syndrome and trichothiodystrophy are three distinct human syndromes associated with sensitivity to ultraviolet radiation. We review evidence that these syndromes overlap with each other and arise from mutations in genes involved in nucleotide-excision repair and RNA transcription. Attempts have been made to explain the syndromes in terms of defects in repair and transcription. These two biochemical pathways do not easily account for all the features of the syndromes. Therefore, we propose a third pathway, in which the syndromes are due, in part, to defects in a demethylation mechanism involving the excision of methylated cytosine. Perturbation of demethylation could affect the developmentally regulated expression of some genes.
Gastro-oesophageal disorders in adults with severe mental impairment
Authors: A Hauck, R A Collacott
Journal: BMJ (1989)

BCG immunisationSIR,-The Department of Health, in circular EL(89)P/93, asked health authorities to postpone their regular BCG programme for schoolchildren this autumn because the British supplier of the vaccine is in the throes of moving to a new site.I wonder if others share my view that this request is unacceptable.As district vaccination coordinator I hear much stout talk "from on high" about targets and accountability, and I feel that the department must now be seen to meet the standards it lays down for others.No target date for resumption of supply has been offered-is the problem for a week, a month, a year?Or is the hope that the programme will quietly wither away?The department should be held to account for this avoidable disruption to the immunisation programme.I also do not understand why, in a health service increasingly exposed to market forces, the market cannot be allowed to provide a solution.There is more than one reput- able manufacturer of BCG vaccine.We are already threatened with a resurgence of tuberculosis thanks to HIV, increasing poverty, and the possibility of a wave of refugees from Hong Kong and Indo-China.The last thing we need is departmental own goals.
Ethical debate: Vaccination against mumps, measles, and rubella: is there a case for deepening the debate? How safe is MMR vaccine? Validity of the evidence Dealing with uncertainty GP's response
Authors: T. Heller, D. Heller, S. Pattison, T. Heller
Journal: BMJ (2001)

Primary careEthical debate Vaccination against mumps, measles, and rubella: is there a case for deepening the debate?Complex issues relating to ethics, values, and the nature of evidence lie behind the decision whether to give the MMR (mumps, measles, and rubella) vaccine.Tom Heller, a general practitioner, is uncomfortable with the evidence that the vaccine is safe.Together with Dick Heller, an epidemiologist, and Stephen Pattison, an ethicist, he explores some of the processes involved in doctors' decisions about whether to vaccinate. How safe is MMR vaccine? Tom HellerMy duties as a general practitioner include immunising babies and small children against a range of common diseases.Recently, I have been increasingly uncomfortable when giving the combined mumps, measles, and rubella (MMR) vaccine.I find myself wondering if I would submit my own children for this immunisation if they were currently at that age.I find it difficult to be certain that the vaccine is as safe as the authorities say that it is.Somehow, the more strident the experts become, the less believable I seem to find them.The Department of Health website (http://193.32.28.83/mmrvac.htm)gives many references and internet links to the published studies that support its views, but it gives only one reference that raises the issue of a link between MMR vaccine and potential adverse reactions.The partial use of evidence that is apparent within official pronouncements is echoed by other experts.For example, Elliman and Bedford focus on possible problems with the research methods of people concerned about possible adverse effects of the MMR vaccine. 1 They do not mention potential problems with the research that concludes that the vaccines are safe.In addition, what are we to make of these and other researchers 2 who declare funding from drug manufacturers involved in manufacturing vaccines?Whether to vaccinate children can be a difficult decision
Antiplatelet Polypharmacy in Primary Percutaneous Coronary Intervention
Authors: Ahmed Abdel-Latif, David J. Moliterno
Journal: Circulation (2009)

T imely and sustained reperfusion in the ST-elevation myocardial infarction setting improves mortality, and primary percutaneous coronary intervention (PCI) is the guideline-favored revascularization strategy. 1Primary PCI requires pharmacological support with antiplatelet and antithrombin therapy, and many drugs and combinations are established for this purpose.Likewise, patients with STelevation myocardial infarction are at risk for subsequent ischemic events in the weeks to months after their index event, and long-term antiplatelet therapy is needed.Aspirin alone provides an inadequate effect on a substantial number of patients with atherosclerotic plaque rupture, whether the vascular disruption occurs as part of an acute coronary syndrome (ACS) or a PCI procedure.Indeed, patients with concomitant spontaneous plaque rupture (ie, troponinpositive ACS) and subsequent disruption from PCI have a particularly high rate of ischemic events with aspirin therapy alone and a notably large risk reduction with antiplatelet adjuncts, such as thienopyridines and glycoprotein IIb/IIIa inhibitors.
Treatment of Type 1 Myotonic Dystrophy by Engineering Site-specific RNA Endonucleases that Target (CUG)n Repeats
Authors: Wenjing Zhang, Yang Wang, Shuyun Dong, Rajarshi Choudhury, Yongfeng Jin, Zefeng Wang
Journal: Molecular Therapy (2013)

Myotonic dystrophy type 1 (DM1) is caused by the expansion of (CTG)n in the 3′ untranslated region of the dystrophia myotonica-protein kinase (DMPK) gene, which is transcribed as (CUG)n repeats that accumulate in the nucleus. The RNA repeats specifically sequester or change the expression levels of several RNA-binding proteins, leading to aberrant splicing of many target genes. In this study, we developed artificial site-specific RNA endonucleases (ASREs) that specifically bind and cleave (CUG)n repeats RNA. We have generated one ASRE that can target the expanded RNA repeats in DM1 patient cells and specifically degrade the pathogenic DMPK messenger RNAs with minimal effect on wild-type alleles. Such ASRE treatment significantly decreased the number of nuclear foci in DM1 patient cells and can reverse the missplicing of many genes affected in DM1 patients. Taken together, the application of ASRE provides a new route of gene therapy for DM1 treatment. Myotonic dystrophy type 1 (DM1) is caused by the expansion of (CTG)n in the 3′ untranslated region of the dystrophia myotonica-protein kinase (DMPK) gene, which is transcribed as (CUG)n repeats that accumulate in the nucleus. The RNA repeats specifically sequester or change the expression levels of several RNA-binding proteins, leading to aberrant splicing of many target genes. In this study, we developed artificial site-specific RNA endonucleases (ASREs) that specifically bind and cleave (CUG)n repeats RNA. We have generated one ASRE that can target the expanded RNA repeats in DM1 patient cells and specifically degrade the pathogenic DMPK messenger RNAs with minimal effect on wild-type alleles. Such ASRE treatment significantly decreased the number of nuclear foci in DM1 patient cells and can reverse the missplicing of many genes affected in DM1 patients. Taken together, the application of ASRE provides a new route of gene therapy for DM1 treatment.
Freedom from pain goes a long way to a "good death"
Authors: J. Riley
Journal: BMJ (2003)

My sister in law died of metastatic malignant melanoma five years ago, leaving behind a six year old boy, a four year old boy, and a pair of 10 month old twins. My recollection of her last weeks is pain, pain, and more pain.

A year after her death the family attended a bereavement weekend at Winston's Wish—a charity that supports bereaved children and young adults—in Gloucestershire. Winston's Wish offers young people support and information to help them understand what has happened, slowly allowing them to learn to live with their loss. The charity has worked with over 2000 young people since 1992.

The charity workers' greatest skill is in encouraging children to communicate non-verbally. On their weekend …
Association of the 2011 ACGME Resident Duty Hour Reform With General Surgery Patient Outcomes and With Resident Examination Performance
Authors: Ravi Rajaram, Jeanette W. Chung, Andrew T. Jones, Mark E. Cohen, Allison R. Dahlke, Clifford Y. Ko, John L. Tarpley, Frank R. Lewis, David B. Hoyt, Karl Y. Bilimoria
Journal: JAMA (2014)

In 2011, the Accreditation Council for Graduate Medical Education (ACGME) restricted resident duty hour requirements beyond those established in 2003, leading to concerns about the effects on patient care and resident training.To determine if the 2011 ACGME duty hour reform was associated with a change in general surgery patient outcomes or in resident examination performance.Quasi-experimental study of general surgery patient outcomes 2 years before (academic years 2009-2010) and after (academic years 2012-2013) the 2011 duty hour reform. Teaching and nonteaching hospitals were compared using a difference-in-differences approach adjusted for procedural mix, patient comorbidities, and time trends. Teaching hospitals were defined based on the proportion of cases at which residents were present intraoperatively. Patients were those undergoing surgery at hospitals participating in the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP). General surgery resident performance on the annual in-training, written board, and oral board examinations was assessed for this same period.National implementation of revised resident duty hour requirements on July 1, 2011, in all ACGME accredited residency programs.Primary outcome was a composite of death or serious morbidity; secondary outcomes were other postoperative complications and resident examination performance.In the main analysis, 204,641 patients were identified from 23 teaching (n = 102,525) and 31 nonteaching (n = 102,116) hospitals. The unadjusted rate of death or serious morbidity improved during the study period in both teaching (11.6% [95% CI, 11.3%-12.0%] to 9.4% [95% CI, 9.1%-9.8%], P < .001) and nonteaching hospitals (8.7% [95% CI, 8.3%-9.0%] to 7.1% [95% CI, 6.8%-7.5%], P < .001). In adjusted analyses, the 2011 ACGME duty hour reform was not associated with a significant change in death or serious morbidity in either postreform year 1 (OR, 1.12; 95% CI, 0.98-1.28) or postreform year 2 (OR, 1.00; 95% CI, 0.86-1.17) or when both postreform years were combined (OR, 1.06; 95% CI, 0.93-1.20). There was no association between duty hour reform and any other postoperative adverse outcome. Mean (SD) in-training examination scores did not significantly change from 2010 to 2013 for first-year residents (499.7 [ 85.2] to 500.5 [84.2], P = .99), for residents from other postgraduate years, or for first-time examinees taking the written or oral board examinations during this period.Implementation of the 2011 ACGME duty hour reform was not associated with a change in general surgery patient outcomes or differences in resident examination performance. The implications of these findings should be considered when evaluating the merit of the 2011 ACGME duty hour reform and revising related policies in the future.
Multiple Domains Contribute to the Distinct Inactivation Properties of Human Heart and Skeletal Muscle Na <sup>+</sup> Channels
Authors: Naomasa Makita, Paul B. Bennett, Alfred L. George
Journal: Circulation Research (1996)

Voltage-gated Na+ channels are essential for the normal electrical excitability of neuronal and striated muscle membranes. Distinct isoforms of the Na+ channel alpha-subunit have been identified by molecular cloning, and their functional attributes have been defined by heterologous expression coupled with electrophysiological recording. Two closely related Na+ channel alpha-subunit isoforms, hH1 (human heart) and hSkM1 (human skeletal muscle), exhibit differences in their inactivation properties and in their response to the coexpressed beta 1-subunit. To localize regions that contribute to inactivation and to beta 1-subunit response, we have exploited these functional differences by studying chimeric channels composed of segments from both hH1 and hSkM1. Chimeras in which one or more of the cytoplasmic interdomain regions (ID1-2, ID2-3, and ID3-4) were exchanged between hH1 and hSkM1 exhibit inactivation properties identical with the background channel isoform, suggesting that these regions are not sufficient to cause gating differences. In contrast, inactivation properties of chimeras composed of approximately equal halves of the two channel isoforms were intermediate between hH1 and hSkM1. Furthermore, the response to the coexpressed beta 1-subunit was dependent on structures located in the carboxy-terminal half of the alpha-subunit, although domains D3, D4, and the carboxy terminal are not singularly responsible for this effect. These data indicate that inactivation differences between hH1 and hSkM1 are determined by multiple alpha-subunit domains.