tbuckley/cabot-search huggingface dataset:
Opposing Effects of β <sub>1</sub> - and β <sub>2</sub> -Adrenergic Receptors on Cardiac Myocyte Apoptosis
Authors: Catherine Communal, Krishna Singh, Douglas B. Sawyer, Wilson S. Colucci
Journal: Circulation (1999)

Background —β-Adrenergic receptor (β-AR) stimulation increases apoptosis in adult rat cardiac (ventricular) myocytes (ARVMs) via activation of adenylyl cyclase. β 2 -ARs may couple to a G i -mediated signaling pathway that can oppose the actions of adenylyl cyclase. Methods and Results —In ARVMs, β-AR stimulation for 24 hours increased the number of apoptotic cells as measured by flow cytometry. β-AR–stimulated apoptosis was abolished by the β 1 -AR–selective antagonist CGP 20712A ( P &lt;0.05 versus β-AR stimulation alone) but was potentiated by the β 2 -AR–selective antagonist ICI 118,551 ( P &lt;0.05 versus β-AR stimulation alone). The muscarinic agonist carbachol also prevented β-AR–stimulated apoptosis ( P &lt;0.05 versus β-AR stimulation alone), whereas pertussis toxin potentiated the apoptotic action of β-AR stimulation ( P &lt;0.05 versus β-AR stimulation alone) and prevented the antiapoptotic action of carbachol. Conclusions —In ARVMs, stimulation of β 1 -ARs increases apoptosis via a cAMP-dependent mechanism, whereas stimulation of β 2 -ARs inhibits apoptosis via a G i -coupled pathway. These findings have implications for the pathophysiology and treatment of myocardial failure.
The old man's friend
Authors: Trisha Greenhalgh
Journal: BMJ (2006)

My father is dead. Given his physical, cognitive, and emotional status over the preceding few weeks, that is no bad thing. He received excellent NHS care, was not mismanaged in any way, and I was involved in all key decisions.

He lived in a residential home. After a series of small strokes he developed pneumonia and was sent into hospital. Not unreasonably, and with my full consent, the pneumonia was treated. After 32 days of impeccable nursing care, another stroke, and …
Patterns of Dermatomyositis and Polymyositis and Their Responses to Treatment.
Authors: C. M. Pearson
Journal: Annals of Internal Medicine (1963)

s1 April 1963Patterns of Dermatomyositis and Polymyositis and Their Responses to Treatment.C. M. Pearson, M.D., F.A.C.P.C. M. Pearson, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-58-4-728_4 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptSeveral clinical and pathological patterns of inflammatory nonsuppurative myositis have been discerned from an analysis of 45 cases and a review of those reported in the literature. All of the cases have muscular weakness as their principal clinical feature. They can be divided into the following categories:Type I. Polymyositis. This occurs more commonly in the female, especially in the third through fifth decades. It usually has an insidious onset and takes a chronic course; an infrequent and atypical skin rash occurs and, occasionally, an associated Raynaud phenomenon, arthritis, and related features which are also often found in other connective... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: C. M. Pearson, M.D., F.A.C.P.Affiliations: Los Angeles, Calif. (CS) PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 April 1963Volume 58, Issue 4Page: 728-729KeywordsArthritisDermatomyositisMuscular weaknessMyositisPolymyositisRashes ePublished: 1 December 2008 Issue Published: 1 April 1963 PDF downloadLoading ...
Weight Gain in Breast Cancer Patients: A Problem?
Authors: K. Smigel
Journal: JNCI Journal of the National Cancer Institute (1990)

Journal Article Weight Gain in Breast Cancer Patients: A Problem? Get access Kara Smigel Kara Smigel Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 82, Issue 5, 7 March 1990, Pages 348–350, https://doi.org/10.1093/jnci/82.5.348 Published: 07 March 1990
Role of sodium-hydrogen exchange in the proliferation of immortalised lymphoblasts from patients with essential hypertension and normotensive subjects
Authors: D. Rosskopf, K.-J. Schroder, W. Siffert
Journal: Cardiovascular Research (1995)

Objective: The aim was to investigate the effect of ethylisopropylamiloride (EIPA), an inhibitor of Na+/H+ exchange, and of extracellular pH on the proliferation of immortalised lymphoblasts derived from patients with essential hypertension and normotensive controls. Methods: Na+/H+ exchange activity was determined in cells loaded with the fluorescent pH indicator BCECF. Cell proliferation was determined by FACS analysis, by cell counting, and from the incorporation of [3H]-thymidine. Results: EIPA inhibited the Na+/H+ exchanger with an average K1 value of 14 nM in all cell lines. Cell growth and DNA synthesis were only inhibited at EIPA concentrations >10 μM suggesting a non-specific effect independent of Na+/H+ exchanger blockade. When extracellular pH was varied from 7.1 to 7.7 by changing the HCO3− concentration at constant Pco2, cell proliferation was optimal at pH 7.4, but reduced at acidic and alkaline pH in cells from normotensive and hypertensive subjects. The increased proliferation of lymphoblasts from hypertensive subjects persisted over the whole pH range. Comparable results were obtained when pH was altered by varying the Pco2 at constant HCO3−. Preincubation of cells with pertussis toxin inhibited serum stimulated DNA synthesis by 14.5% and 23.5% (P = 0.02) in cell lines from normotensive and hypertensive subjects. Conclusions: The enhanced Na+/H+ exchanger activity in lymphoblasts from patients with essential hypertension is obviously not the major determinant of the enhanced proliferation of these cells. The increased sensitivity of the growth of "hypersensitive" cell lines to pertussis toxin suggests a cellular alteration which resides upstream of Na+/H+ exchange activity and proliferation control.
Conservatism: In Defense of Freedom
Authors: Russell B. Roth
Journal: JAMA (1972)

Some publications, professional and other, devote much space to criticisms of the American Medical Association, as though the Association were an enemy of the profession or of the people. In the professional arena, conservative voices especially denounce AMA's sponsorship of the Medicredit proposal. Yet of all legislative proposals of this kind, Medicredit would be most supportive to private practice— the very thing conservative physicians hold most dear. It is understandable that some physicians would dislike the prospect of even so much federal intervention as would inevitably be caused by Medicredit. Nevertheless, among many purposes served, merely having this proposal before the Congress has given the AMA a ticket of admission to the whole three-ring circus of legislative shenanigans. When the AMA had no solid base on which to stand, as was the case in Medicare days, the Association, after the Johnson landslide of 1964, received scant hearings and almost no
Targeted disruption of the Kvlqt1 gene causes deafness and gastric hyperplasia in mice
Authors: Maxwell P. Lee, Jason D. Ravenel, Ren-Ju Hu, Lawrence R. Lustig, Gordon Tomaselli, Ronald D. Berger, Sheri A. Brandenburg, Tracy J. Litzi, Tracie E. Bunton, Charles Limb, Howard Francis, Melissa Gorelikow, Hua Gu, Kay Washington, Pedram Argani, James R. Goldenring, Robert J. Coffey, Andrew P. Feinberg
Journal: Journal of Clinical Investigation (2000)

The KvLQT1 gene encodes a voltage-gated potassium channel. Mutations in KvLQT1 underlie the dominantly transmitted Ward-Romano long QT syndrome, which causes cardiac arrhythmia, and the recessively transmitted Jervell and Lange-Nielsen syndrome, which causes both cardiac arrhythmia and congenital deafness. KvLQT1 is also disrupted by balanced germline chromosomal rearrangements in patients with Beckwith-Wiedemann syndrome (BWS), which causes prenatal overgrowth and cancer. Because of the diverse human disorders and organ systems affected by this gene, we developed an animal model by inactivating the murine Kvlqt1. No electrocardiographic abnormalities were observed. However, homozygous mice exhibited complete deafness, as well as circular movement and repetitive falling, suggesting imbalance. Histochemical study revealed severe anatomic disruption of the cochlear and vestibular end organs, suggesting that Kvlqt1 is essential for normal development of the inner ear. Surprisingly, homozygous mice also displayed threefold enlargement by weight of the stomach resulting from mucous neck cell hyperplasia. Finally, there were no features of BWS, suggesting that Kvlqt1 is not responsible for BWS.
Jacques Joseph: Surgical Sculptor
Authors: Bradford Cannon
Journal: JAMA (1983)

Paul Natvig's scholarly biography of Jacques Joseph is a moving account of the life of a leading European pioneer in plastic surgery. It is a model of biographical writing, portraying an absorbing story carefully and accurately. The voluminous index, filling half the pages, has 15 specifically designated sections that include all the source material (bibliography, original documents, correspondence, etc) from which the story is based. What a pity that Natvig did not live to receive the well-deserved accolades for his achievement! (He died Nov 13, 1982.) Joseph's life spanned the last 3 1/2 decades of the 19th century and the first 3 1/2 decades of the 20th. He was the son of a rabbi, and throughout the book there are hints of the undercurrent of German antisemitism, a prejudice that seemed to be decreasing with the emergence of German science during his lifetime. Joseph was spared any threats during the
The Need for Oblique or Lateral Ventilation Images in the Diagnosis of Pulmonary Embolism
Authors: PETER W. BLUE, EDWIN J. FORTENBERY
Journal: Clinical Nuclear Medicine (1990)

Numerous recent textbooks in nuclear medicine suggest that, for the evaluation of pulmonary embolism, a single posterior initial-breath xenon-133 view followed by equilibrium and washout images is sufficient to evaluate ventilation. One recent text suggests that lateral initial breath views should be included. Two cases in which the additional views were essential for correct interpretation are presented in support of this latter position. Because anterior abnormalities are not well represented on low photon-energy xenon-133 posterior images, it is recommended that, in all ventilation-perfusion studies for pulmonary embolism, at least both oblique or both lateral initial breath views must be obtained. Other views, such as anterior or anterior oblique views, may be needed and can be obtained before or following perfusion imaging.
Bioactive glass as a drug delivery system of tetracycline and tetracycline associated with β-cyclodextrin
Authors: Z.R. Domingues, M.E. Cortés, T.A. Gomes, H.F. Diniz, C.S. Freitas, J.B. Gomes, A.M.C. Faria, R.D Sinisterra
Journal: Biomaterials (2003)
419. Rescue of Cone Photoreceptors after Lentiviral Gene Transfer of Rpe65 cDNA in Knockout Mouse Models of Leber Congenital Amaurosis
Authors: Alexis-Pierre Bemelmans, Corinne Kostic, Dana Hornfeld, Meriem Tekaya, Sylvain V. Crippa, William W. Hauswirth, Janis Lem, Mathias Seeliger, Andreas Wenzel, Yvan Arsenijevic
Journal: Molecular Therapy (2006)

Gene transfer is a promising approach for single gene defects occurring in several retinal degenerations, such as Leber congenital amaurosis (LCA), a group of severe retinal dystrophies affecting children. About 10% of LCA cases are due to a mutation in RPE65, a key enzyme for the metabolism of Vitamin A during the visual cycle. The consequence of RPE65 deficiency is a lack of the 11-cis- retinal chromophore at the photoreceptor level and an associated retinal degeneration. Gene therapy in dogs lacking RPE65 protein restores visual function on the long term (Acland et al., Nat Genet 28: 92; Narfstrom et al., Invest Ophthalmol Vis Sci 44: 1663). However no confirmed indications on cone rescue and cone function restoration, necessary for day vision and high visual acuity, have been reported in the different animal models used in gene therapy studies. To evaluate the efficiency of Rpe65 replacement by gene transfer in rodent models of LCA, we have constructed a lentiviral vector expressing the Rpe65 mouse cDNA under the control of a promoter fragment from the human RPE65 gene. We studied the therapeutic efficiency of this vector in the Rpe65 knockout mouse as well as in the Rpe65/Gnat1a double knockout mouse, to reveal the effect of Rpe65 gene transfer on the cone photoreceptors. Gnat1a-/- mice do not have any rod function. Thus, any photoreceptor activity occurring in the Rpe65/Gnat1a double knockout background after Rpe65 gene replacement should arise from cone photoreceptors.
Cardiovascular Outcomes after a Change in Prescription Policy for Clopidogrel
Authors: Cynthia A. Jackevicius, Jack V. Tu, Virginie Demers, Magda Melo, Jafna Cox, Stephane Rinfret, Dimitri Kalavrouziotis, Helen Johansen, Hassan Behlouli, Alice Newman, Louise Pilote
Journal: New England Journal of Medicine (2008)

Drug-reimbursement policies may have an adverse effect on patient outcomes if they interfere with timely access to efficacious medications for acute medical conditions. Clopidogrel in combination with aspirin is the recommended standard of care for patients receiving coronary stents to prevent thrombosis. We examined the population-level effect of a change by a Canadian provincial government in a pharmacy-benefits program from a prior-authorization policy to a less restrictive, limited-use policy on access to clopidogrel among patients undergoing percutaneous coronary intervention (PCI) with stenting after acute myocardial infarction.We conducted a population-based, retrospective, time-series analysis from April 1, 2000, to March 31, 2005, of all patients 65 years of age or older with acute myocardial infarction who underwent PCI with stenting in Ontario, Canada. The primary outcome was the composite rate of death, recurrent acute myocardial infarction, PCI, and coronary-artery bypass grafting at 1 year, with adjustment for sex and age. The secondary outcome was major bleeding.The rate of clopidogrel use within 30 days after hospital discharge following myocardial infarction increased from 35% in the prior-authorization period to 88% in the limited-use period. The median time to the first dispensing of a clopidogrel prescription decreased from 9 days in the first period to 0 days in the second period. The 1-year composite cardiovascular outcome significantly decreased from 15% in the prior-authorization group to 11% in the limited-use group (P=0.02). Rates of bleeding in the two groups did not change.The removal of a prior-authorization program led to improvement in timely access to clopidogrel for coronary stenting and improved cardiovascular outcomes.
Non-coding RNAs as regulators of gene expression and epigenetics
Authors: M. U. Kaikkonen, M. T. Y. Lam, C. K. Glass
Journal: Cardiovascular Research (2011)

Genome-wide studies have revealed that mammalian genomes are pervasively transcribed. This has led to the identification and isolation of novel classes of non-coding RNAs (ncRNAs) that influence gene expression by a variety of mechanisms. Here we review the characteristics and functions of regulatory ncRNAs in chromatin remodelling and at multiple levels of transcriptional and post-transcriptional regulation. We also describe the potential roles of ncRNAs in vascular biology and in mediating epigenetic modifications that might play roles in cardiovascular disease susceptibility. The emerging recognition of the diverse functions of ncRNAs in regulation of gene expression suggests that they may represent new targets for therapeutic intervention.
Multiple recurring gastric erosions/aphthous ulcers).
Authors: A G Morgan, W A McAdam, R D Pyrah, E G Tinsley
Journal: Gut (1976)

Five patients are described who had repeated endoscopy because of continuing dyspeptic symptoms associated with a negative barium meal. They were found to have multiple recurring gastric erosions (aphthous ulcers). No common aetiological factor could be found, although four of these patients did have a mild or moderatley active superficial chronic gastritis. Conventional peptic ulcer therapy failed to control either symptoms or ulceration. Two patients finally came to gastric surgery (highly selective vagotomy), which resulted in the relief of symptoms and healing of the gastric aphthous ulceration.
The Identification of Right-to-Left Shunts in the Central Circulation by the Injection of Ether
Authors: ROBERT S. FRASER, RICHARD E. ROSSALL, JOSEPH DVORKIN, CESAR VALLE-CAVERO
Journal: Circulation (1961)

A method is described for localizing central right-to-left shunts by means of anesthetic ether injected through a cardiac catheter at various sites during cardiac catheterization. The presence and location of right-to-left shunts were correctly demonstrated in 42 of 43 patients in whom the diagnosis was later confirmed at operation or autopsy. The instance in which the site was interpreted incorrectly is explained. Three false-negative results were obtained from the test and reasons for these are also given. In our view the test is simple, safe, gives accurate results, allows immediate interpretation, and requires no special equipment. It has proved to be a most useful test for preliminary localization of shunts prior to selective angiocardiography.
Monitoring of upper oesophageal sphincter pressure in children.
Authors: G P Davidson, J Dent, J Willing
Journal: Gut (1991)

In children technical limitations of upper oesophageal sphincter manometry have restricted investigation to the pull through technique under sedation. In this study we have used an adapted sleeve manometric technique for upper oesophageal sphincter monitoring in unsedated children and determined the influence of the state of arousal on upper oesophageal sphincter pressure. Twenty six children aged 3 to 42 months (median 17.5 months), who were referred for evaluation of oesophageal motor function, were studied with dual sleeve manometric assemblies which monitored upper and lower oesophageal sphincter pressures simultaneously. Pharyngeal, oesophageal body, and gastric pressures were also monitored with seven perfused side holes. Recordings were made for four hours after a meal and were technically successful in 24 children. The child9s state of arousal was scored every 12th minute as follows: (A) resting, eyes closed, (B) resting, eyes open, (C) moving but comfortable, (D) restless and uncomfortable, (E) crying. In 67% of the 12 minute samples the children showed good adaptation to the procedure (arousal states A to C). There was a highly significant difference in upper oesophageal sphincter pressure between each of the arousal states (p less than 0.0001), being lowest in category A at (mean (SD) 18.1 (10.3) mmHg and highest in category D 55.7 (13.2) mm Hg. Abrupt changes in the state of arousal were associated with equally abrupt changes in upper oesophageal sphincter pressure. The state of arousal of unsedated children has an important influence on upper oesophageal sphincter pressure. It is essential that this factor is controlled for in any studies of upper oesophageal sphincter tone in children. The sleeve technique is capable of monitoring upper oesophageal sphincter motility for prolonged periods in unsedated children.
Controlled HIV viral replication, not liver disease severity associated with low bone mineral density in HIV/HCV co-infection
Authors: Diala El-Maouche, Shruti H. Mehta, Catherine Sutcliffe, Yvonne Higgins, Michael S. Torbenson, Richard D. Moore, David L. Thomas, Mark S. Sulkowski, Todd T. Brown
Journal: Journal of Hepatology (2011)
Hyaluronic acid-chitosan nanoparticles for co-delivery of MiR-34a and doxorubicin in therapy against triple negative breast cancer
Authors: Xiongwei Deng, Minjun Cao, Jiakun Zhang, Kelei Hu, Zhaoxia Yin, Zhixiang Zhou, Xiangqian Xiao, Yishu Yang, Wang Sheng, Yan Wu, Yi Zeng
Journal: Biomaterials (2014)
The teaching nursing home
Authors: R. N. Butler
Journal: JAMA (1981)

EXPERIENCING a rapid growth of its elderly population, the United States finds itself short of professionals trained in geriatric medicine, nursing, social work, and allied disciplines. Knowledge about aging, diseases of the elderly, and their effective diagnosis and treatment is being developed at a snail's pace. A corrosive pessimism about later life and prejudice against the elderly still persist in many areas of our society, including the health care field. Many elderly persons and their families find scant comfort in the ministrations of health care organizations. Physicians refer but tend not to follow up their patients in the nursing home. The image of the nursing home is scarred by scandal, abuse, ignorance, and fear—an image similar to that of the ancient hospital untouched by science. It appears that the mainstream of US medicine points away from its most prominent clientele. The nation's 25 million persons aged 65 years and older
Trans fatty acids and coronary heart disease
Authors: Robert Clarke, Sarah Lewington
Journal: BMJ (2006)

This perspective article proposes a conceptual model for the pain experience for individuals diagnosed with knee osteoarthritis (OA). Pain in knee OA is likely a heterogeneous, multifactorial phenomenon that involves not only the OA disease process but also elements specific to patient psychology and pain neurophysiology. The relevant contributions to the pain experience for any individual patient remain difficult, if not impossible, to definitively determine, and the rationale for many clinical treatment decisions arises primarily from a mechanistic understanding of OA pathophysiology. The Osteoarthritis Research Society International (OARSI) recently identified “phenotyping” of OA pain as a research priority to “better target pain therapies to individual patients.” This perspective article proposes that contributions from 3 domains—knee pathology, psychological distress, and pain neurophysiology—should be considered equally important in future efforts to understand pain phenotypes in knee OA. Ultimately, characterization of pain phenotypes may aid in the understanding of the pain experience and the development of interventions specific to pain for individual patients.
Guanylin and uroguanylin induce natriuresis in mice lacking guanylyl cyclase-C receptor
Authors: Stephen L. Carrithers, Cobern E. Ott, Michael J. Hill, Brett R. Johnson, Weiyan Cai, Jason J. Chang, Rajesh G. Shah, Congmei Sun, Elizabeth A. Mann, Manasses C. Fonteles, Leonard R. Forte, Brian A. Jackson, Ralph A. Giannella, Richard N. Greenberg
Journal: Kidney International (2003)
Military medical services are at crisis point
Authors: J. Warden
Journal: BMJ (1997)

The House of Commons Defence Select Committee last week expressed fears for the future of Britain's military medical services.

Its report states that the medical services are not capable of supporting Britain's global military commitment: “A choice would have to be made between sending troops without proper medical support-or only sending the limited number of troops who could be supported.”

The prime minister, John Major, responded by maintaining …