tbuckley/cabot-search huggingface dataset:
Take dietary truths with a pinch of salt
Authors: Nigel Hawkes
Journal: BMJ (2011)

The more dominant that guidelines become, the more dangerous they are



As a child of the 1950s I grew up knowing that margarine, though nearly as nasty as cod liver oil, was good for you. Doctors had been pushing it for decades, or so the advertisements told us. As early as 1915 Sainsbury’s advertised its “Nuts and Milk Double Weight” margarine under the slogan “Doctors recommend it,” although no doctors were named. As late as the 1990s hard margarines containing trans fats were sold as a healthy alternative to butter, their claims backed by a medical consensus.

Two weeks ago the BMJ published a study by Pelham Barton and colleagues on the effectiveness of cardiovascular disease prevention programmes.1 It concluded that eliminating trans fats from the diet would, over 10 years, prevent 27 000 deaths, gain 570 000 life years, and return a cash benefit of £2bn (€2.3bn; $3.3bn) in England and Wales alone. Its effects far outweighed a 5% reduction in cholesterol concentrations or in systolic blood pressure or a reduction in salt intake of 3 g a day.

Far from being “heart smart” (as one product claimed), hard margarines were heart stupid. Equally stupid—it now appears—was the 1990s mantra that the route …
Development of autoimmune hepatitis in patients with typical primary biliary cirrhosis
Authors: Raoul Poupon, Olivier Chazouilleres, Christophe Corpechot, Yves Chrétien
Journal: Hepatology (2006)

Primary biliary cirrhosis (PBC)–autoimmune hepatitis (AIH) overlap syndrome is a clinical entity characterized by the occurence of both conditions at the same time in the same patient. In addition to PBC-AIH overlap syndrome, transitions from one autoimmune disease to another have been reported, but no systematic series have been published. We report a series of 12 patients with consecutive occurrence of PBC and AIH ( i.e. , PBC followed by AIH). Among 282 PBC patients, 39 were identified who fulfilled criteria for probable or definitive AIH. AIH developed in 12 patients (4.3%). The baseline characteristics of the patients were similar to those of patients with classical PBC. Time elapsed between the diagnosis of PBC and the diagnosis of AIH varied from 6 months to 13 years. Patients with multiple flares of hepatitis at the time of diagnosis of AIH had cirrhosis on liver biopsy. Ten patients were given prednisone ± azathioprine; short-term as well as sustained remissions were obtained in 8 of these, while two had multiple relapses and eventually died 8 and 7 years after diagnosis of AIH. In conclusion , the development of superimposed AIH could not be predicted from baseline characteristics and initial response to UDCA therapy. If not detected early, superimposed AIH can result in rapid progression toward cirrhosis and liver failure in PBC patients.
Nephrin mutations cause childhood- and adult-onset focal segmental glomerulosclerosis
Authors: Sheila Santín, Rafael García-Maset, Patricia Ruíz, Isabel Giménez, Isabel Zamora, Antonia Peña, Álvaro Madrid, Juan A. Camacho, Gloria Fraga, Ana Sánchez-Moreno, Maria Ángeles Cobo, Carmen Bernis, Alberto Ortiz, Augusto Luque de Pablos, Guillem Pintos, Maria Luisa Justa, Emilia Hidalgo-Barquero, Patricia Fernández-Llama, José Ballarín, Elisabet Ars, Roser Torra, None on behalf of the FSGS Spanish Study Group
Journal: Kidney International (2009)
P173Vascular endothelial fibrosis induced by endotoxin: characteristics, mechanism and therapeutic perspectives
Authors: F Simon, C Echeverria, I Montorfano, A Becerra, D Varela, T Hermosilla, C Cabello-Verrugio, R Armisen
Journal: Cardiovascular Research (2014)

Purpose: Pathogenesis of vascular inflammatory diseases is characterized by endothelial dysfunction, including the endotoxemia-derived systemic inflammatory syndrome. Although interactions between the endotoxin and endothelial cells (ECs) evoke EC death, a significant portion of ECs are resistant to endotoxin challenge by means of the conversion of ECs into activated fibroblasts. However, the underlying mechanism that promotes the endotoxin-induced vascular endothelial fibrosis (EVEF) and its implications are not known. The activation of fibroblasts are dependent on intracellular Ca2+ concentration increases through the participation of calcium channels. However, the molecular identity of the calcium channel that mediates the Ca2+ influx during EVEF is unknown. Transient receptor potential melastatin 7 (TRPM7) is a calcium channel expressed in ECs. TRPM7 promotes fibroblasts activation inducing their characteristics. However, the role of TRPM7 in EVEF is unknown. Thus, our aim was to investigate the features of EVEF and study the role of TRPM7 as a new pharmacological target to avoid EVEF.

Methods: Primary cultures of ECs and whole blood vessels were isolated from umbilical cords from normal pregnancies, after patient′s informed consent conforms with the principles outlined in the Declaration of Helsinki.

Results: Endotoxin-challenged ECs showed an upregulation of both, fibroblast-specific proteins expression and extracellular matrix (ECM) proteins secretion, as well as a downregulation of endothelial markers, through a mechanism dependent on: ALK5/Smad2/3 and TLR4/NF-κB/NOX intracellular pathways. Furthermore, TRPM7 suppression protected ECs from the endotoxin-induced fibrogenesis. TRPM7 downregulation prevented the endotoxin-induced endothelial markers decrease and fibrotic genes increase. In addition, TRPM7 suppression abolished the endotoxin-induced increase in ECM proteins. Furthermore, the intracellular Ca2+ levels were greatly increased upon endotoxin challenge in a mechanism dependent on TRPM7 expression.

Conclusions: Endotoxin exposition is a crucial factor for inducing vascular endothelial fibrosis which perpetuates endothelial dysfunction as a maladaptive process rather than a survival mechanism for protection against LPS. Noteworthy, TRPM7 appears as a key protein involved in the mechanism underlying EVEF, emerging as a novel target for pharmacological design useful in improving current treatment against endotoxemia-derived systemic inflammation and other vascular inflammatory diseases.
An Anesthesiologist's Plea
Authors: Richard G. Laurens
Journal: JAMA (1982)

<h3>To the Editor.—</h3> "An Anesthesiologist's Plea" by T. Cameron MacCaughelty, MD (1981;246:2692), illustrates the unfortunate growing controversy among anesthesiologists, internal medicine subspecialists, surgeons, and general internists as to who is most qualified to provide primary care in the rapidly developing field of critical care medicine. As Dr MacCaughelty states, the anesthesiologist is unquestionably the most qualified physician to care for the surgical patient during surgery and the immediate postoperative period. However, expertise in this area does not necessarily extend to the general care of the critically ill patient, as Dr MacCaughelty implies. While programs may vary from institution to institution, no anesthesiology residency can provide adequate training in (1) evaluation and treatment of acute renal failure; (2) treatment of acute gastrointestinal (GI) tract bleeding; (3) use of antibiotics in a broad spectrum of respiratory tract, GI tract, and urogenital infection; (4) interpretation and treatment of complex ECG changes and arrhythmias;
Severe atherosclerosis of the aorta and development of peripheral T-cell lymphoma in an adolescent with angiolymphoid hyperplasia with eosinophilia
Authors: J. Andreae, C. Galle, K. Magdorf, D. Staab, L. Meyer, M. Goldman, U. Querfeld
Journal: British Journal of Dermatology (2005)

Journal Article Severe atherosclerosis of the aorta and development of peripheral T‐cell lymphoma in an adolescent with angiolymphoid hyperplasia with eosinophilia Get access J. Andreae, J. Andreae Departments of Paediatric Nephrology, Paediatric Pneumology and Immunology Search for other works by this author on: Oxford Academic Google Scholar C. Galle, C. Galle Department of Immunology‐Haematology‐Transfusion, Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium Search for other works by this author on: Oxford Academic Google Scholar K. Magdorf, K. Magdorf Departments of Paediatric Nephrology, Paediatric Pneumology and Immunology Search for other works by this author on: Oxford Academic Google Scholar D. Staab, D. Staab Departments of Paediatric Nephrology, Paediatric Pneumology and Immunology Search for other works by this author on: Oxford Academic Google Scholar L. Meyer, L. Meyer Haematology and Oncology, Charité Children's Hospital, Augustenburger Platz 1, 13353 Berlin, Germany Search for other works by this author on: Oxford Academic Google Scholar M. Goldman, M. Goldman Department of Immunology‐Haematology‐Transfusion, Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium Search for other works by this author on: Oxford Academic Google Scholar U. Querfeld U. Querfeld Departments of Paediatric Nephrology, Paediatric Pneumology and Immunology Uwe Querfeld. E‐mail: uwe.querfeld@charite.de Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 152, Issue 5, 1 May 2005, Pages 1033–1038, https://doi.org/10.1111/j.1365-2133.2005.06421.x Published: 01 May 2005 Article history Accepted: 29 July 2004 Published: 01 May 2005
Book: Serious Shopping: Essays in Psychotherapy and Consumerism
Authors: P. Shaw
Journal: BMJ (2001)

Ed Adrienne Baker Free Association Books, £15.95, pp 220 ISBN 1 85343 483 3 Rating ![Graphic][1]</img>![Graphic][2]</img> I have often wondered whether the BMJ should have a fashion column for doctors, giving tips on where to buy the latest in hospital chic. I was therefore thrilled to review Serious Shopping . Sadly, it is anything but a clarion call to Claridges. Instead, it attempts to establish shopping addiction as a major mental health problem and to describe its psychotherapeutic treatment. Shoppers can thus join the long list of addicts—gymaholics, dot.comaholics, sexaholics—initially identified by a media apparently addicted to identifying addictions. … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif
The Medical Outcomes Study
Authors: Don Riesenberg
Journal: JAMA (1989)

In an eloquent exposition of the structure of clinical medicine, Pellegrino<sup>1</sup>has said that health "depends as much on the patient's assessment as the physician's. If full restoration is not possible, then amelioration of suffering, adaptation, or coping with chronic or fatal illness become the ends of the healing relationship." The Medical Outcomes Study (MOS), baseline data from which appear in this issue ofThe Journal,<sup>2-4</sup>examines the means and ends of medical care in the spirit of Pellegrino's blueprint. The MOS involves prospective monitoring of clinical interactions between hundreds of physicians and thousands of patients over a 2-year period. The investigators selected "tracer" conditions, eg, hypertension, coronary heart disease, diabetes mellitus, and depression, and repeatedly assessed the status of patients with these conditions during the 2-year study. Reports on the longitudinal phase will correlate the structures (eg, organization, payment), processes (eg, hospitalization rate, physician's interpersonal style), and
Ondansetron and irritable bowel syndrome
Authors: Pavit Luthra, Alexander C Ford
Journal: Gut (2014)

We read the paper by Garsed et al, 1 which revives interest in 5-hydroxytryptamine (5-HT) receptor antagonists as treatment for diarrhoea-predominant irritable bowel syndrome (IBS-D). As a highly prevalent functional gastrointestinal (GI) disorder,2 without a known organic pathology to target, IBS continues to be challenging to treat. Interest in agents acting on 5-HT receptors selectively is not novel, with alosetron, the most well-studied 5-HT3 antagonist, demonstrating efficacy in treating IBS-D.3 However, cases of severe constipation and ischaemic colitis led to the withdrawal of the drug. Ondansetron first demonstrated effects on GI transit over …
Relapse-specific mutations in NT5C2 in childhood acute lymphoblastic leukemia
Authors: Julia A Meyer, Jinhua Wang, Laura E. Hogan, Jun J Yang, Smita Dandekar, Jay P Patel, Zuojian Tang, Paul Zumbo, Sheng-Bo Li, Jiri Zavadil, Ross L. Levine, Timothy Cardozo, Stephen P. Hunger, Elizabeth A. Raetz, William E Evans, Debra J Morrison, Christopher E Mason, William L. Carroll
Journal: Nature Genetics (2013)
Renal effects of environmental and occupational lead exposure.
Authors: M Loghman-Adham
Journal: Environmental Health Perspectives (1997)

Environmental and industrial lead exposures continue to pose major public health problems in children and in adults. Acute exposure to high concentrations of lead can result in proximal tubular damage with characteristic histologic features and manifested by glycosuria and aminoaciduria. Chronic occupational exposure to lead, or consumption of illicit alcohol adulterated with lead, has also been linked to a high incidence of renal dysfunction, which is characterized by glomerular and tubulointerstitial changes resulting in chronic renal failure, hypertension, hyperuricemia, and gout. A high incidence of nephropathy was reported during the early part of this century from Queensland, Australia, in persons with a history of childhood lead poisoning. No such sequela has been found in studies of three cohorts of lead-poisoned children from the United States. Studies in individuals with low-level lead exposure have shown a correlation between blood lead levels and serum creatinine or creatinine clearance. Chronic low-level exposure to lead is also associated with increased urinary excretion of low molecular weight proteins and lysosomal enzymes. The relationship between renal dysfunction detected by these sensitive tests and the future development of chronic renal disease remains uncertain. Epidemiologic studies have shown an association between blood lead levels and blood pressure, and hypertension is a cardinal feature of lead nephropathy. Evidence for increased body lead burden is a prerequisite for the diagnosis of lead nephropathy. Blood lead levels are a poor indicator of body lead burden and reflect recent exposure. The EDTA lead mobilization test has been used extensively in the past to assess body lead burden. It is now replaced by the less invasive in vivo X-ray fluorescence for determination of bone lead content.
Ras-mediated modulation of pyruvate dehydrogenase activity regulates mitochondrial reserve capacity and contributes to glioblastoma tumorigenesis
Authors: Antony Prabhu, Bhaswati Sarcar, C. Ryan Miller, Sung-Hak Kim, Ichiro Nakano, Peter Forsyth, Prakash Chinnaiyan
Journal: Neuro-Oncology (2015)

Even though altered metabolism representing a hallmark of cancer was proposed nearly a century ago, recent technological advances have allowed investigators to continue uncovering a previously unrecognized complexity of metabolic programs that drive tumorigenesis beyond that of aerobic glycolysis.
Cost of road traffic accidents to an orthopaedic department.
Authors: J V Tilsed
Journal: BMJ (1991)

Pain perception of5SI patients injecting inszulin subcutaneously Volume injected 0-025ml 0 10ml 010ml 0-20ml 0 25ml OSOml Median(95%CI) pain score* 0 (OtoO) 0 (Oto 1-3) 0 (OtoO) 0 (Oto I 0) 0 (Oto0) 0 (OtoO) % (95% CI) Patients scoring < 10% of worst pain 92 (85 to 100) 80 (70 to 91) 77 (65 to 88) 77 (65 to 88) 77 (65 to 88) 75 (63 to 86)*0=No pain at all, 21 =worst pain, on visual analogue scale.volume.Insertion of sharp 27 gauge or 28 gauge needles was essentially painless, with a median pain score of 0 (95% confidence interval 0 to 3d1) for the NovoPen, 3 05 (0 to 9 8) for the Plastipak, and 5 0 (2-0 to 12-8) for the Omnikan.Blunted needles increased the median pain score to 11 9 (1-8 to 20 5) for the NovoPen, 19-45 (3 5 to 20 5) for the Plastipak, and 20-15 (6 5 to 20 5) for the Omnikan.
Integrin α4β1 Promotes Monocyte Trafficking and Angiogenesis in Tumors
Authors: Hui Jin, Jingmei Su, Barbara Garmy-Susini, Jeanine Kleeman, Judy Varner
Journal: Cancer Research (2006)

Abstract Monocytes and macrophages extensively colonize solid tumors, where they are thought to promote tumor angiogenesis. Here, we show that integrin α4β1 (VLA4) promotes the invasion of tumors by myeloid cells and subsequent neovascularization. Antagonists of integrin α4β1, but not of other integrins, blocked the adhesion of monocytes to endothelium in vitro and in vivo as well as their extravasation into tumor tissue. These antagonists prevented monocyte stimulation of angiogenesis in vivo, macrophage colonization of tumors, and tumor angiogenesis. These studies indicate the usefulness of antagonists of integrin α4β1 in suppressing macrophage colonization of tumors and subsequent tumor angiogenesis. These studies further indicate that suppression of myeloid cell homing to tumors could be a useful supplementary approach to suppress tumor angiogenesis and growth. (Cancer Res 2006; 66(4):2146-52)
Long-Term Care for the Elderly and Disabled
Authors: Anne R. Somers
Journal: New England Journal of Medicine (1982)

OF all the difficult health-care issues facing the nation today, none is more complex or urgent than the formulation of a viable policy of long-term care for the elderly and the chronically ill and disabled. The tragic irony of the existing neglect is clearly evident in the plight of millions of frail and dependent elders, rejected by both Medicare and Medicaid as well as by most private carriers of health insurance, even as the costs of these programs soar.Although many of the current remedial proposals recognize the importance of long-term care, they appear to be prepared to settle for . . .
Role of IFN-g in induction of Foxp3 and conversion of CD4+CD25- T cells to CD4+ Tregs
Authors: Z. Wang
Journal: Journal of Clinical Investigation (2006)

IFN-γ is an important Th1 proinflammatory cytokine and has a paradoxical effect on EAE in which disease susceptibility is unexpectedly heightened in IFN-γ–deficient mice. In this study, we provide what we believe is new evidence indicating that IFN-γ is critically required for the conversion of CD4+CD25– T cells to CD4+ Tregs during EAE. In our study, the added severity of EAE in IFN-γ knockout mice was directly associated with altered encephalitogenic T cell responses, which correlated with reduced frequency and function of CD4+CD25+Foxp3+ Tregs when compared with those of WT mice. It was demonstrated in both human and mouse systems that in vitro IFN-γ treatment of CD4+CD25– T cells led to conversion of CD4+ Tregs as characterized by increased expression of Foxp3 and enhanced regulatory function. Mouse CD4+CD25– T cells, when treated in vitro with IFN-γ, acquired marked regulatory properties as evidenced by suppression of EAE by adoptive transfer. These findings have important implications for the understanding of the complex role of IFN-γ in both induction and self regulation of inflammatory processes.
PROTEIN BINDING OF CORTICOIDS STUDIED BY GEL FILTRATION*
Authors: P. De Moor. K. Heirwegh, J. F. Heremans, M. Declerck-Raskin
Journal: Journal of Clinical Investigation (1962)

The ability of porous bodies to distinguish between molecules of different sizes has been re- peatedly observed.If these porous bodies are devoid of charged groups, solutes placed on top of a column filled with such a material will be parti- tioned chiefly by molecular sieve effect (1).Mole- cules with a size above a limiting value will leave the column immediately after the displacement volume.Smaller particles will enter the gel grains and will be retarded and eventually separated into groups of different molecular weight.Such columns, on the other hand, may perform an exhaustive dialysis.The use of dextran gels for these purposes was introduced by Porath and Flodin (2); as suggested by Tiselius the method was named gel filtration.Nonmetabolized corticoids may be found in hu- man plasma in three different forms: a very small fraction of unbound steroids, a fraction weakly bound to albumin, and a fraction strongly but reversibly bound (3) to a specific protein called transcortin (4).Under basal conditions the latter fraction represents 95 to 98 per cent of total plasma cortisol.1
H-2Dd exploits a four residue peptide binding motif.
Authors: M Corr, L F Boyd, E A Padlan, D H Margulies
Journal: The Journal of Experimental Medicine (1993)

We have characterized the amino acid sequences of over 20 endogenous peptides bound by a soluble analog of H-2Dd, H-2Dds. Synthetic analogs corresponding to self, viral, tumor, or motif peptides were then tested for their ability to bind to H-2Dd by serologic epitope induction assays using both purified soluble protein and cell surface H-2Dd. The dominant primary sequence motif included glycine at position 2, proline at position 3, and a hydrophobic COOH terminus: leucine, isoleucine, or phenylalanine at position 9 or 10. Ancillary support for high affinity binding was contributed by a positively charged residue at position 5. Three-dimensional computer models of H-2Dds/peptide complexes, based on the crystallographic structure of the human HLA-B27/peptide complex, showed that the basic residue at position 5 was in position to form a salt bridge with aspartic acid at position 156, a polymorphic residue of the H-2Dd heavy (H) chain. Analysis of 28 such models, including 17 based on nonamer self-peptides, revealed considerable variation in the structure of the major histocompatibility complex (MHC) surrounding peptide residue 1, depending on the size and charge of the side chain. Interactions between the side chains of peptide residues 5 and 7, and 6 and 8 commonly occurred. Those peptide positions with limited sequence variability and least solvent accessibility may satisfy structural requirements for high affinity binding of the peptide to the MHC class I H chain, whereas the highly variable positions of the peptide (such as positions 4, 6, and 8) may contribute more to the T cell epitopes.
Myocardial Contrast Echocardiography for Distinguishing Ischemic From Nonischemic First-Onset Acute Heart Failure
Authors: Roxy Senior, Raj Janardhanan, Paramjit Jeetley, Leah Burden
Journal: Circulation (2005)

Distinguishing ischemic from nonischemic origin in patients presenting with acute heart failure (AHF) not resulting from acute myocardial infarction has both therapeutic and prognostic implications. The aim of the study was to assess whether myocardial contrast echocardiography (MCE) can identify underlying coronary artery disease (CAD) as the cause of AHF.Fifty-two consecutive patients with AHF with no prior clinical history of CAD and no clinical evidence of acute myocardial infarction underwent resting echocardiography and MCE both at rest and after dipyridamole stress at a mean of 9+/-2 days after admission. All patients underwent coronary arteriography before discharge. Of the 52 patients, 22 demonstrated flow-limiting CAD (>50% luminal diameter narrowing). Sensitivity, specificity, and positive and negative predictive values of MCE for the detection of CAD were 82%, 97%, 95%, and 88%, respectively. Among clinical, ECG, biochemical, resting echocardiographic, and MCE markers of CAD, MCE was the only independent predictor of CAD (P<0.0001). Quantitative MCE demonstrated significantly (P<0.0001) lower myocardial blood flow velocity reserve in vascular territories subtended by >50% CAD (0.59+/-0.46) compared with patients with normal coronary arteries (1.99+/-1.00). However, myocardial blood flow velocity reserve in patients with no significant CAD was significantly (P=0.03) lower compared with control (2.91+/-0.41). Myocardial blood flow velocity reserve correlated significantly (P<0.0001) with increasing severity of CAD.MCE, which is a bedside technique, may be used to detect CAD in patients presenting with AHF without a prior history of CAD or evidence of acute myocardial infarction. Quantitative MCE may further risk-stratify patients with AHF but no CAD.