tbuckley/cabot-search huggingface dataset:
Divergent Tumor Necrosis Factor Receptor–Related Remodeling Responses in Heart Failure
Authors: Tariq Hamid, Yan Gu, Roger V. Ortines, Chhandashri Bhattacharya, Guangwu Wang, Yu-Ting Xuan, Sumanth D. Prabhu
Journal: Circulation (2009)

Although preclinical data suggested that tumor necrosis factor-alpha (TNF) neutralization in heart failure (HF) would be beneficial, clinical trials of TNF antagonists were paradoxically negative. We hypothesized that TNF induces opposing inflammatory and remodeling responses in HF that are TNF-receptor (TNFR) specific.HF was induced in wild-type (WT), TNFR1(-/-), and TNFR2(-/-) mice via coronary ligation. Compared with WT HF, 4-week postinfarction survival was significantly improved in both TNFR1(-/-) and TNFR2(-/-) HF. Compared with sham, WT HF hearts exhibited significant remodeling with robust activation of nuclear factor (NF)-kappaB, p38 mitogen-activated protein kinase, and JNK2 and upregulation of TNF, interleukin (IL)-1beta, IL-6, and IL-10. Compared with WT HF, TNFR1(-/-) HF exhibited (1) improved remodeling, hypertrophy, and contractile function; (2) less apoptosis; and (3) diminished NF-kappaB, p38 mitogen-activated protein kinase, and JNK2 activation and cytokine expression. In contrast, TNFR2(-/-) HF showed exaggerated remodeling and hypertrophy, increased border zone fibrosis, augmented NF-kappaB and p38 mitogen-activated protein kinase activation, higher IL-1beta and IL-6 gene expression, greater activated macrophages, and greater apoptosis. Oxidative stress and diastolic function were improved in both TNFR1(-/-)and TNFR2(-/-) HF. In H9c2 cardiomyocytes, sustained NF-kappaB activation was proapoptotic, an effect dependent on TNFR1 signaling, whereas TNFR2 overexpression attenuated TNF-induced NF-kappaB activation.TNFR1 and TNFR2 have disparate and opposing effects on remodeling, hypertrophy, NF-kappaB, inflammation, and apoptosis in HF: TNFR1 exacerbates, whereas TNFR2 ameliorates, these events. However, signaling through both receptors is required to induce diastolic dysfunction and oxidative stress. TNFR-specific effects in HF should be considered when therapeutic anti-TNF strategies are developed.
Trypsin activates pancreatic duct epithelial cell ion channels through proteinase-activated receptor-2
Authors: Toan D. Nguyen, Mark W. Moody, Martin Steinhoff, Charles Okolo, Duk-Su Koh, Nigel W. Bunnett
Journal: Journal of Clinical Investigation (1999)

Proteinase-activated receptor-2 (PAR-2) is a G protein-coupled receptor that is cleaved by trypsin within the NH2-terminus, exposing a tethered ligand that binds and activates the receptor. We examined the secretory effects of trypsin, mediated through PAR-2, on well-differentiated nontransformed dog pancreatic duct epithelial cells (PDEC). Trypsin and activating peptide (AP or SLIGRL-NH2, corresponding to the PAR-2 tethered ligand) stimulated both an 125I- efflux inhibited by Ca2+-activated Cl- channel inhibitors and a 86Rb+ efflux inhibited by a Ca2+-activated K+ channel inhibitor. The reverse peptide (LRGILS-NH2) and inhibited trypsin were inactive. Thrombin had no effect, suggesting absence of PAR-1, PAR-3, or PAR-4. In Ussing chambers, trypsin and AP stimulated a short-circuit current from the basolateral, but not apical, surface of PDEC monolayers. In monolayers permeabilized basolaterally or apically with nystatin, AP activated apical Cl- and basolateral K+ conductances. PAR-2 agonists increased [Ca2+]i in PDEC, and the calcium chelator BAPTA inhibited the secretory effects of AP. PAR-2 expression on dog pancreatic ducts and PDEC was verified by immunofluorescence. Thus, trypsin interacts with basolateral PAR-2 to increase [Ca2+]i and activate ion channels in PDEC. In pancreatitis, when trypsinogen is prematurely activated, PAR-2-mediated ductal secretion may promote clearance of toxins and debris.
Per Os, not "Orem."
Authors: Ephraim Cutter
Journal: JAMA (1898)

New York City, Dec. 25, 1897. <h3>To the Editor:</h3> —Thanks to "F" (page 1284, column 2, lines 46 to 51,Journal, Dec. 18, 1897), because I had rather be right than wrong; because Daniel Webster said that he "would not give a cent for a man who never made a mistake"; because Ambassador Phelps said, "a man who never made a mistake never made anything," and because our beloved, great and honored Dr. Lewis A. Sayre said that he was "thankful for any true criticism, no matter how sharp, keen or cutting." Respectfully yours,
Telmisartan did not prevent recurrent stroke or major cardiovascular events
Authors: Michael A. Sloan
Journal: Annals of Internal Medicine (2009)

ACP Journal Club17 February 2009Telmisartan did not prevent recurrent stroke or major cardiovascular eventsMichael A. Sloan, MD, MSMichael A. Sloan, MD, MSUniversity of South Florida, Tampa, Florida, USA (M.A.S.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-150-4-200902170-02009 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationYusuf S, Diener HC, Sacco RL, et al. Telmisartan to prevent recurrent stroke and cardiovascular events. N Engl J Med. 2008;359:1225-37. https://pubmed.ncbi.nlm.nih.gov/18753639Clinical Impact RatingsGIM/FP/GP: Cardiology: Endocrinology: Neurology: References1 Sacco RL, Adams R, Albers G, et al. Guidelines for prevention of stroke in patients with ischemic stroke or transient ischemic attack: a statement for healthcare professionals from the American Heart Association/American Stroke Association Council on Stroke: co-sponsored by the Council on Cardiovascular Radiology and Intervention: the American Academy of Neurology affirms the value of this guideline. Stroke. 2006;37:577-617. [PMID: 16432246] Google Scholar2 Thijs V, Lemmens R, Fieuws S. Network meta-analysis: simultaneous meta-analysis of common antiplatelet regimens after transient ischaemic attack or stroke. Eur Heart J. 2008;29:1086-92. [PMID: 18349026] Google Scholar3 Diener HC, Bogousslavsky J, Brass LM, et al. Aspirin and clopidogrel compared with clopidogrel alone after recent ischaemic stroke or transient ischaemic attack in high-risk patients (MATCH): randomised, double-blind, placebo-controlled trial. Lancet. 2004;364:331-7. [PMID: 15276392] Google Scholar4 PROGRESS Collaborative Group. Randomised trial of a perindopril-based blood-pressure-lowering regimen among 6, 105 individuals with previous stroke or transient ischaemic attack. Lancet. 2001;358:1033-41. [PMID: 11589932] Google Scholar Author, Article, and Disclosure InformationAffiliations: University of South Florida, Tampa, Florida, USA (M.A.S.)This article was published at Annals.org on 3 February 2009. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoAspirin plus extended-release dipyridamole and clopidogrel were similarly effective for preventing recurrent stroke Michael A. Sloan Metrics 17 February 2009Volume 150, Issue 4Page: JC2-9KeywordsAspirinBlood pressureHeart failureHemorrhageIschemic strokeMyocardial infarctionRelative riskSafetyStrokeSystolic pressure ePublished: 17 February 2009 Issue Published: 17 February 2009 Copyright & PermissionsCopyright © 2009 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Effect of Severe Burn Injury on Substrate Cycling by Glucose and Fatty Acids
Authors: Robert R. Wolfe, David N. Herndon, Farook Jahoor, Hiroshi Miyoshi, Marta Wolfe
Journal: New England Journal of Medicine (1987)

Increases in metabolic rate and core temperature are common responses to severe injury. We have investigated the hypothesis that these responses are due to increases in substrate cycling. A substrate cycle exists when opposing, nonequilibrium reactions catalyzed by different enzymes are operating simultaneously. At least one of the reactions must involve the hydrolysis of ATP. Thus, a substrate cycle both liberates heat and increases energy expenditure, yet there is not net conversion of substrate to product. In studies in volunteers (n = 18) and in patients with severe burns who were in a hypermetabolic state (n = 18), we used stable-isotope tracers to quantify substrate cycling in the pathways of glycolysis and gluconeogenesis and a cycle involving the simultaneous breakdown and synthesis of stored triglyceride (triglyceride-fatty acid cycle). The total rates of triglyceride-fatty acid and glycolytic-gluconeogenic cycling were elevated in the patients by 450 and 250 percent, respectively (P less than 0.01). An infusion of propranolol in the patients greatly reduced triglyceride-fatty acid cycling but did not affect gluconeogenic-glycolytic cycling. We conclude that increased substrate cycling contributes to the increased thermogenesis and energy expenditure following severe burns and that the increased triglyceride-fatty acid cycling is due to beta-adrenergic stimulation.
Lupus pernio: a clinico-radiological study of thirty-five cases
Authors: M.A. SPITERI, F. MATTHEY, T. GORDON, L.S. CARSTAIRS, D.GERAINT JAMES
Journal: British Journal of Dermatology (1985)

Thirty-five patients with lupus pernio were observed in a series of 818 patients with clinical and histological evidence of sarcoidosis. This analysis provides the natural history of lupus pernio and its associated clinico-radiographic features. There was intrathoracic involvement in 74% of patients, upper respiratory tract disease in 54%, reticulo-endothelial involvement in 54%, bone cysts in 43% and ocular lesions in 37%. It predominated in West Indies-born women. Histological confirmation was easily obtained by nasal mucosal biopsy and this could be repeated serially to evaluate the response to various treatments. Nasal bone radiographs showed destruction of the nasal bones, porosis and alteration in bone texture. Peripheral bone cysts were evident in 50% of patients who were radiographed, and in about 50% of these patients, the cysts were found in both hands and feet.
Relationship Between Central Sympathetic Drive and Magnetic Resonance Imaging–Determined Left Ventricular Mass in Essential Hypertension
Authors: Joanna Burns, Mohan U. Sivananthan, Stephen G. Ball, Alan F. Mackintosh, David A.S.G. Mary, John P. Greenwood
Journal: Circulation (2007)

Sympathetic activation has been implicated in the development of left ventricular hypertrophy (LVH). However, the relationship between sympathetic activation and LV mass (LVM) has not been clearly defined across a range of arterial pressure measurements. The present study was planned to determine that relationship, using cardiac magnetic resonance imaging to accurately quantify LVM, in hypertensive patients with and without LVH and in normal subjects.Twenty-four patients with uncomplicated and untreated essential hypertension (LVH[-]) were compared with 25 patients with essential hypertension and left ventricular hypertrophy (LVH[+]) and 24 normal control subjects. Resting muscle sympathetic nerve activity was quantified as multiunit bursts and single units. Cardiac magnetic resonance imaging-determined LVM was indexed to body surface area (LVM index); in the LVH[-] group, LVM index was 67+/-2.1 g/m2, a value between those of the LVH[+] (91+/-3.4 g/m2) and normal control (57+/-2.2 g/m2) groups, respectively. The sympathetic activity in the LVH[-] group (53+/-1.3 bursts per 100 cardiac beats and 63+/-1.6 impulses per 100 cardiac beats) was between (at least P<0.001) those of the LVH[+] (66+/-1.7 bursts per 100 cardiac beats and 77+/-2.2 impulses per 100 cardiac beats) and normal control (39+/-3.0 bursts per 100 cardiac beats and 45+/-3.4 impulses per 100 cardiac beats) groups. Significant positive correlation existed between sympathetic activity and LVM index in the LVH[-] and LVH[+] groups (at least r=0.76, P<0.0001) but not in the normal control group. However, no consistent relationship existed between arterial blood pressure and sympathetic activity or LVM index.These findings further support the hypothesis that central sympathetic activation is associated with the development of LVH in human hypertension.
Implementing Formative Health Planning under PL 93–641
Authors: Stanley H. Werlin, Alexandra Walcott, Michael Joroff
Journal: New England Journal of Medicine (1976)

The National Health Planning and Resources Development Act of 1974 (PL 93-641) melds the Hill-Burton program, Regional Medical Program and Comprehensive Health Planning into a new network for health planning and resources development. Health-systems agencies will possess broader powers than predecessor agencies, particularly in the areas of regulation, control of federal funds, resources development and implementation. PL 93-641 thus offers the possibility of transforming the basic concept of health planning from reactive to "proactive." Successful legislative implementaion will require each health-systems agency to build local legitimacy, ensure constructive consumer/provider dialogue, and respond to state and national managerial requirements. Many questions about planning implementation, the role of subarea councils, agency co-ordination and local governance remain unresolved. The new health-planning network has the potential to assume the function of active system transformation, but will be critically dependent on adequate program budgeting to fulfill this promise. (N Engl J Med 295:698-703, 1976).
Primarily nasal origin of exhaled nitric oxide and absence in Kartagener's syndrome
Authors: JO Lundberg, E Weitzberg, SL Nordvall, R Kuylenstierna, JM Lundberg, K Alving
Journal: European Respiratory Journal (1994)

The exact origin of nitric oxide (NO) in exhaled air is not known. We wanted to further investigate at what site exhaled NO is produced and to determine whether children with Kartagener's syndrome exhibited altered levels of exhaled NO. NO was measured by chemiluminescence technique in air sampled directly from the nose and in normally exhaled air of four children (2.5-13 years old) with Kartagener's syndrome, 20 healthy children, four healthy adults, and four conscious tracheostomized adults. NO was almost absent (98% reduced) in air sampled directly from the nose in four children with Kartagener's syndrome (4 +/- 1 parts per billion (ppb)), compared to age-matched controls (221 +/- 14 (ppb)). Tracheostomized adult subjects had considerably higher NO values in nasally (22 +/- 3 ppb) and orally (14 +/- 2 ppb) exhaled air, compared to levels in air exhaled through the tracheostomy (2 +/- 0 ppb). Treatment with intranasal corticosteroids for 14 days, or with antibiotics for 1 week, did not affect exhaled NO. These results clearly show that, basically, all NO in exhaled air of healthy subjects originates from the upper respiratory tract, with only a minor contribution from the lower airways. Furthermore, the absence of nasal NO in children with Kartagener's syndrome could be of use as a simple noninvasive diagnostic test.
Radiotherapy for lentigo maligna: a literature review and recommendations for treatment
Authors: G.B. Fogarty, A. Hong, R.A. Scolyer, E. Lin, L. Haydu, P. Guitera, J. Thompson
Journal: British Journal of Dermatology (2013)

Lentigo maligna (LM) incidence is increasing. LM frequently involves the face near critical anatomical structures and as a consequence clinical management is challenging. Nonsurgical therapies, including radiotherapy (RT), are increasingly used. Evidenced-based treatment guidelines are lacking. We conducted a review of previously published data analysing RT treatment of LM. A search of PubMed, Embase and Medline databases to June 2012 identified nine clinical studies that examined the use of RT for LM treatment in at least five patients. Nine studies described 537 patients with LM treated with definitive primary RT, between 1941 and 2009, with a median reported follow-up time of 3 years. Eight articles could be reviewed for oncological outcome data. There were 18 recurrences documented in a total of 349 assessable patients (5%). Salvage was successful in the majority of recurrent LM cases by using further RT, surgery or other therapies. Progression to LM melanoma (LMM) occurred in five patients (five out of 349, 1.4%) who all had poor outcomes. There were five marginal recurrences documented out of 123 assessable patients (4%). There were eight in-field recurrences documented with either LM (five) or LMM (three) out of 171 assessable patients (5%). A series of recommendations were then developed for RT parameters for treatment of LM. These parameters include treatment volume, dose, dose per fraction and outcome measures. These may be of use in prospective data collection.
Roles for Endothelin Receptor B and BCL2A1 in Spontaneous CNS Metastasis of Melanoma
Authors: William Cruz-Muñoz, Maria L. Jaramillo, Shan Man, Ping Xu, Myriam Banville, Catherine Collins, Andre Nantel, Giulio Francia, Sherif S. Morgan, Lee D. Cranmer, Maureen D. O'Connor-McCourt, Robert S. Kerbel
Journal: Cancer Research (2012)

Abstract Metastatic spread of melanoma to the central nervous system (CNS) is a common and devastating manifestation of disease progression, which, despite its clinical importance, remains poorly understood with respect to underlying molecular mechanisms. Using a recently developed preclinical model of spontaneous melanoma CNS metastasis, we have identified alterations in expression of endothelin receptor B (EDNRB) as a potential factor that influences brain metastatic potential. Induced overexpression of this gene mediated enhanced overall metastatic disease, and resulted in an increased incidence of spontaneous CNS metastases. In contrast, the overexpression of other highlighted genes, such as BCL2A1, did not affect the incidence of CNS metastases but nevertheless appears to facilitate intracranial tumor growth. The prometastatic effect in the CNS associated with EDNRB appears to be mediated by the interaction with its ligands resulting in enhanced tumor cell proliferation and thus intracranial melanoma growth. That EDNRB contributes to melanoma metastasis is underscored by the fact that its therapeutic inhibition by the EDNRB-specific inhibitor A192621 translated into improved outcomes when treating mice with either visceral metastases or intracranial tumors. The identification of an influential role of EDNRB in CNS melanoma spontaneous metastasis may provide both a target for therapeutic intervention as well as a potential prognostic marker for patients having an increased predisposition for incidence of CNS melanoma metastases. Cancer Res; 72(19); 4909–19. ©2012 AACR.
Predictors of one-year death in men and women: GUSTO-IV acute coronary syndrome
Authors: Cynthia M. Westerhout, Jan-Paul Otterbanger, Paul W. Armstrong, Judith S. Hochman, Stefan James, Lars Wallentin, Elliot S. Barnathan, E. Magnus Ohman, Maarten L. Simoons, Eric Boersma
Journal: Journal of the American College of Cardiology (2003)
E. W. Thornton "Exercise and Aging: an unproven relationship"
Authors: H. Selcon
Journal: British Journal of Sports Medicine (1984)

Viral infections may adversely affect the ability of an individual to regulate his body temperature as well as having potentially dangerous effects on the myocardium.For these reasons, it is most unwise for any individual to take part in a marathon race, or other hard physical activity, while suffering from, or recovering from, such an illness.These precautions will not guarantee immunity from heat-related problems, nor will they compensate for lack of adequate training in the pre-competition period, but they may help to reduce the number of casualties on race day.
The Trauma of Terrorism. Sharing Knowledge and Shared Care: An International Handbook
Authors: Judith Issroff
Journal: BMJ (2005)

The recent London bombings demonstrated several inefficiencies in the services called on to respond to such a disaster. For example, it was not acceptable that 48 hours after the event bodies (and, for all anyone knew, even survivors) were trapped underground, and some of those bodies recovered were not yet identified. It was not acceptable that the emergency services could not provide adequately trained translators.

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Eds Yael Danieli, Danny Brom, Joe Sills

Haworth, $69.95, pp 932 ISBN 0 7890 2773 3 …

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EFFECT OF HIGH SENSITIVITY CRP LEVELS AND IMPAIRED RENAL FUNCTION ON THE TISSUE CHARACTERISTICS AND MORPHOLOGY OF CORONARY CULPRIT PLAQUES IN PATIENTS WITH STABLE ANGINA PECTORIS AND MILD-TO-MODERATE CHRONIC KIDNEY DISEASE: AN INTEGRATED BACKSCATTER INTRAVASCULAR ULTRASOUND AND OPTICAL COHERENCE TOMOGRAPHY STUDY
Authors: Kenichiro Saka, Kiyoshi Hibi, Nobuhiko Maejima, Naoki Nakayama, Hiroyuki Suzuki, Zenko Nagashima, Masayoshi Kiyokuni, Kouzou Okada, Yasushi Matsuzawa, Masaaki Konishi, Katsutaka Hashiba, Noriaki Iwahashi, Mitsuaki Endo, Kenigo Tsukahara, Yoshio Tahara, Masami Kosuge, Toshiaki Ebina, Satoshi Umemura, Kazuo Kimura
Journal: Journal of the American College of Cardiology (2011)
Michael Taylor Stather-Dunn
Authors: L. Stather-Dunn
Journal: BMJ (2003)

Former consultant psychiatrist St David's Hospital, Carmarthen, Dyfed, south Wales (b London 1923; q St Bartholomew's Hospital, London, 1953; DPM), died from chronic obstructive airways disease and cardiac failure on 27 October 2002.​2002.




Figure 1




Michael left his training as a quantity surveyor to join the Royal Air Force as a Spitfire pilot in the second world war. He saw action in the Far East, taking his matriculation exams in a tent in the jungle. He then took advantage of a scheme supporting former servicemen to train in needed disciplines and studied medicine. After qualification and training in psychiatry, he was appointed consultant psychiatrist in Carmarthen. In 1977 he retired early following a coronary artery bypass graft. He leaves a wife, Brenda; three daughters; and five grandchildren.
Early assessment of severity of acute pancreatitis using peritoneal lavage.
Authors: I R Pickford, R L Blackett, M J McMahon
Journal: BMJ (1977)

Diagnostic peritoneal lavage using one litre of isotonic saline was performed on 27 patients with acute pancreatitis as soon as possible after diagnosis. There were no complications. Severe attacks (defined retrosepctively according to the progress of the attack) were characterised by the presence of free peritoneal fluid and by dark-coloured and often opalescent return fluid. The concentrations of albumin, aspartate aminotransferase (SGOT) and total protein in the return fluid provided good discrimination between severe and mild attacks, and there were also significant differences in the concentrations of amylase, urea, calcium, potassium, bilirubin, alkaline phosphatase, and the white cell count. Lavage successfully predicted severe disease in five patients whose condtion had been clinically assessed as mild.
Therapeutic effects of ablative radiation on local tumor require CD8+ T cells: changing strategies for cancer treatment
Authors: Youjin Lee, Sogyong L. Auh, Yugang Wang, Byron Burnette, Yang Wang, Yuru Meng, Michael Beckett, Rohit Sharma, Robert Chin, Tony Tu, Ralph R. Weichselbaum, Yang-Xin Fu
Journal: Blood (2009)