tbuckley/cabot-search huggingface dataset:
Integrin Activation in the Heart
Authors: Maria L. Valencik, Dongfang Zhang, Bonnie Punske, Ping Hu, John A. McDonald, Sheldon E. Litwin
Journal: Circulation Research (2006)

Integrins mechanically link the cytoskeleton to the extracellular matrix in cardiac myocytes and are thereby involved in mechanotransduction. Integrins appear to be necessary for cardiac myocyte hypertrophy. To determine the effect of increased integrin ligation and signaling on adult cardiac function, a heart-specific truncated α 5 integrin (gain of function) was conditionally expressed in mice. Four days later, we observed an 80% reduction in amplitude of the QRS complex, profound systolic dysfunction, decreased connexin43, loss of gap junctions, and abnormal intercalated discs. Surprisingly, isolated left ventricular myocytes contracted normally and exhibited normal Ca 2+ transients. This suggested that cell/cell electrical and/or mechanical coupling was disrupted. To distinguish electrical from mechanical coupling deficits, we compared the papillary muscle force generated by electrically stimulated versus rapid cooling contractions in which intracellular Ca 2+ is released without electrical depolarization. Both were decreased in the transgenic muscle. However, electrically stimulated contractions were more significantly reduced than rapid cooling contractures. This suggests a component of cell/cell electrical uncoupling. Optical mapping revealed a loss of the normal elliptical isochronal activation pattern implying a loss of preferential conduction through gap junctions. For the first time, we have shown that integrins can regulate both mechanical and electrical coupling in the adult heart, even in the absence of primary hemodynamic alterations. Furthermore, we demonstrated that unregulated integrin activation leads to both contractile dysfunction and arrhythmias.
Asymptomatic, low risk adults should not be screened for coronary heart disease, says US guidance
Authors: M. McCarthy
Journal: BMJ (2015)

Adults without symptoms and who are at low risk of developing coronary artery disease should not be screened for heart disease with resting or stress electrocardiography, stress echocardiography, or stress myocardial perfusion imaging, says new guidance from the American College of Physicians.1

“Cardiac screening in adults at low risk for coronary heart disease is low value care because it does not improve patient outcomes and it can lead to potential harms,” David Fleming, the college’s president, said in a statement released with the guidelines. “Physicians should instead focus on strategies for improving cardiovascular health by treating modifiable risk factors such as smoking, diabetes, hypertension, high cholesterol, and obesity and encouraging healthy levels of …
Cardiac Exercise Program-Reply
Authors: Gerald F. Fletcher
Journal: JAMA (1978)

In Reply.—  Only one patient of our group (patient 5) continued to smoke cigarettes despite our repeated urging to stop. After reversible ventricular fibrillation, he had coronary arteriography and had noticeable lesions that were deemed operable. He refused surgery, however, and we thought that he should not exercise.  With regard to types of anaerobic activities, we do use short bursts of such in our session. The patient's program is gradually increased from a walking program to a jogging program, always setting the target heart rate at 75% to 85% of the maximum tolerated heart rate on his treadmill testing.  With regard to graduation of patients, we do think that some patients can leave a supervised exercised program. Many exercise programs now have an initial therapeutic phase of exercise that is medically supervised and usually entails the first 12 weeks after the cardiac event. After this, certain patients can be graduated
HOOKWORM DISEASE IN THE PARAGUAYAN CHACO
Authors: Alvin W. Gaede
Journal: JAMA (1952)

<h3>To the Editor:—</h3> During my medical work in the Paraguayan Gran Chaco from 1946 to 1948, human hookworm infection was the major debilitating disease. While hookworm was found in the native Paraguayan Indians in 1926, their superstitions and nescient habits prevented me from investigating this group. Considering their habitude, one would surmise that all should be infected. Surprisingly, however, on examination of a few of these Indians, a small percentage were found free of this infection. My work was concerned with Swiss-Dutch emigrees who, in the 1920's and 1930's, settled in the Chaco about 150 miles west of Puerto Casada, on the Paraguay River. The area involved is about 30 miles north of the Tropic of Capricorn and 150 miles west of the Paraguay River. This region receives an average annual rainfall of 28 inches. The temperature varies from 30 F in the winter to 110 F in the summer.
Rapid Intravenous Administration of Corticotropin as a Test of Adrenocortical Insufficiency
Authors: Byron U. Musa
Journal: JAMA (1967)

The one-hour response of plasma-fluorescent corticoid concentrations to 25 units of corticotropin has allowed complete separation of a group of seven patients with adrenal insufficiency from another group of 31 patients with findings suggestive of adrenal insufficiency but having, in fact, normal adrenal function. From the standpoint of time required for the analytical procedure, availability of reagents, and apparatus requiring no modification, the laboratory techniques described are suitable for a small clinical laboratory.
1343 HIGH DOSE ATORVASTATIN ASSOCIATED WITH INCREASED RISK OF SIGNIFICANT HEPATOTOXICITY IN COMPARISON TO SIMVASTATIN: A RETROSPECTIVE COHORT STUDY USING THE UK GENERAL PRACTICE RESEARCH DATABASE
Authors: A.T. Clarke, P.C.D. Johnson, G.C. Hall, I. Ford, P.R. Mills
Journal: Journal of Hepatology (2012)
Locating the stem cell niche and tracing hepatocyte lineages in human liver
Authors: Tariq G. Fellous, Shahriar Islam, Paul J. Tadrous, George Elia, Hemant M. Kocher, Satyajit Bhattacharya, Lisa Mears, Douglas M. Turnbull, Robert W. Taylor, Laura C. Greaves, Patrick F. Chinnery, Geoffery Taylor, Stuart A.C. McDonald, Nicholas A. Wright, Malcolm R. Alison
Journal: Hepatology (2008)

Abstract We have used immunohistochemical and histochemical techniques to identify patches of hepatocytes deficient in the enzyme cytochrome c oxidase, a component of the electron transport chain and encoded by mitochondrial DNA (mtDNA). These patches invariably abutted the portal tracts and expanded laterally as they spread toward the hepatic veins. Here we investigate, using mtDNA mutations as a marker of clonal expansion, the clonality of these patches. Negative hepatocytes were laser-capture microdissected and mutations identified by polymerase chain reaction sequencing of the entire mtDNA genome. Patches of cytochrome c oxidase–deficient hepatocytes were clonal, suggesting an origin from a long-lived cell, presumably a stem cell. Immunohistochemical analysis of function and proliferation suggested that these mutations in cytochrome c oxidase-deficient hepatocytes were nonpathogenic. Conclusion : these data show, for the first time, that clonal proliferative units exist in the human liver, an origin from a periportal niche is most likely, and that the trajectory of the units is compatible with a migration of cells from the periportal regions to the hepatic veins. (Hepatology 2009.)
Removing industrial trans fat from foods
Authors: D. Mozaffarian, M. J. Stampfer
Journal: BMJ (2010)

A simple policy that will save lives

As part of a 12 step manifesto to better public health, the UK Faculty of Public Health and Royal Society for Public Health proposed that consumption of trans fatty acids (TFAs) should be virtually eliminated in the United Kingdom by next year.1 They noted that, “it has been proven that industrially-produced TFA can damage health,” “there is no known safe level of consumption,” and “banning TFA from foods is a relatively easy way to help protect the public.”1 Are these arguments sound?

TFAs are created when vegetable oils are partially hydrogenated to convert large numbers (typically 30-60%) of naturally occurring cis unsaturated double bonds into trans unsaturated double bonds. A high TFA content provides physical and chemical properties that are attractive to food manufacturers, including the creation of relatively inexpensive (compared with animal derived fats) solid or semi-solid fat. The process also destroys labile omega-3 acids (α-linolenic acid), and this reduces the propensity for fats to become rancid, increases shelf life, and optimises deep frying applications. Use of partially hydrogenated vegetable oils has increased since the 1950s because of these commercial advantages and since the 1960s because of public health recommendations to replace saturated fats (such as butter and lard) with alternatives.

Because mammals and most edible plants synthesise only cis double bonds, TFAs are rare in the natural …
The GM-CSF Analogue E21R Induces Apoptosis of Normal and Activated Eosinophils
Authors: PER O. IVERSEN, DOUGLAS ROBINSON, SUN YING, QIU MENG, A. BARRY KAY, IAN CLARK-LEWIS, ANGEL F. LOPEZ
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

There is evidence that eosinophils have an important role in the pathogenesis of allergy and asthma. These cells are regulated by two classes of polypeptides, the colony-stimulating factors, such as granulocyte-macrophage colony-stimulating factor (GM-CSF), and the chemokines, such as RANTES and eotaxin. GM-CSF is involved in the production, survival, and functional activation of eosinophils. RANTES and eotaxin regulate the migration of eosinophils to inflammatory sites, but any effect of these chemokines on eosinophil survival is not known. In this study we demonstrate that although GM-CSF promoted eosinophil survival, the specific GM-CSF analogue E21R induced apoptosis of eosinophils. Apoptosis was observed with unstimulated as well as with chemokine (RANTES and eotaxin)- activated eosinophils. Neither RANTES nor eotaxin supported eosinophil survival, and a RANTES antagonist did not affect either cell survival or apoptosis. E21R also induced apoptosis of eosinophils from asthmatic patients. These findings suggest that the GM-CSF receptor may actively control the death as well as the survival of eosinophils, and thus precisely regulate their numbers and activities. Our data also indicate that chemokines are not involved in regulating the lifespan of eosinophils. The introduction of the GM-CSF analogue E21R may offer a novel therapy in inflammatory diseases associated with eosinophil infiltration of different etiologies.
Effect of the Distal-Balloon Protection System on Microembolization During Carotid Stenting
Authors: Nadim Al-Mubarak, Gary S. Roubin, Jiri J. Vitek, Sriram S. Iyer, Gishel New, Martin B. Leon
Journal: Circulation (2001)

Background The distal-balloon protection system is being evaluated for its efficacy in preventing embolic neurological events during carotid stenting (CAS). We sought to determine the effect of this system on the frequency of Doppler-detected microembolic signals (MES) during CAS. Methods and Results Using transcranial Doppler, we compared the frequency of MES during CAS in 2 groups: 39 patients without distal protection and 37 who used the distal-balloon protection system (GuardWire). There were no significant differences in the clinical or angiographic characteristics between the 2 groups. Three phases with increased MES counts were identified during unprotected CAS; these were stent deployment, predilation, and postdilation (75±57, 32±36, and 27±25 METS, respectively). The distal-balloon protection significantly reduced the frequency of MES during CAS (MES counts: 164±108 in the control versus 68±83 in the protection group; P =0.002), particularly during these 3 phases. MES in the protection group were detected predominantly during sheath placement, guidewire manipulation, and distal-balloon deflation. Conclusion Three phases with increased MES counts were identified during unprotected CAS (eg, stent deployment, predilation, and postdilation). The distal-balloon protection system significantly reduced the frequency of MES during CAS, particularly during these 3 phases.
Segmental Heterogeneity of Vasa Vasorum Neovascularization in Human Coronary Atherosclerosis
Authors: Mario Gössl, Daniele Versari, Heike A. Hildebrandt, Thomas Bajanowski, Giuseppe Sangiorgi, Raimund Erbel, Erik L. Ritman, Lilach O. Lerman, Amir Lerman
Journal: JACC. Cardiovascular imaging (2010)
Vitamin K and the Newborn
Authors: Margaret W. Hilgartner
Journal: New England Journal of Medicine (1993)

Once again the most appropriate method of administering vitamin K to newborns is under discussion. This fat-soluble naphthoquinone is essential for the gamma-carboxylation of the prothrombin-complex proteins into their active forms, which bind calcium in the coagulation process, as well as proteins C and S. Low plasma levels of these compounds are associated with potentially lethal hemorrhagic disease of the newborn at two to five days of age, when the levels fall to their lowest point1. Vitamin K given orally or intramuscularly at birth prevents this decrease. Hepatic dysfunction, caused by the immaturity of the liver or by disease . . .
UK parliament creates all party group for tuberculosis
Authors: Peter Moszynski
Journal: BMJ (2006)

The urgency of reversing the spread of tuberculosis worldwide, particularly new resistant strains, was stressed at last week's inaugural meeting of the All Party Parliamentary Group on Global Tuberculosis. Support was strong for new resources “to prevent two million people each year dying unnecessarily from a disease that is entirely treatable and preventable.”

The meeting was co-chaired by the Liberal Democrat MP Andrew George, the Labour MP Julie Morgan, and the Conservative MP Nick Herbert. Mario Raviglione, director of the World Health Organization's stop tuberculosis department; junior development minister Gareth Thomas MP; and Winston Zulu, an HIV …
Dorothy Jane Oluman ffoulkes-Crabbe
Authors: R. Desalu
Journal: BMJ (2009)

The Department of Anaesthesia, College of Medicine University of Lagos and the Lagos University Teaching Hospital, as well as the entire membership of the Nigerian Society of Anaesthetists, announce the death of Professor Dorothy Jane Oluman ffoulkes-Crabbe, popularly known as “Mama Anaesthesia,” on the 24 December 2008 at her home in Accra, Ghana.

Mama joined the staff of the College of Medicine University of Lagos and the Lagos University Teaching Hospital as a lecturer/consultant in 1968 and became a professor of anaesthesia in 1978. She retired in 1999.

During this time, …
Ultrasonic Evaluation of Prosthetic Valve Motion
Authors: MICHAEL L. JOHNSON, BRUCE C. PATON, JOSEPH H. HOLMES
Journal: Circulation (1970)

1. Ultrasound echo tracing is a simple, atraumatic method for examining prosthetic valve function. 2. In vitro experiments have elucidated the meaning of traces obtained from various types of caged balls. 3. By the use of this method ball diameter, poppet excursion, and opening and closing velocities can be measured in patients. 4. Both in vitro and in vivo experience has demonstrated that the measurements obtained are accurate and reproducible.
Pneumococcus-induced serotonin release from human platelets. Identification of the participating plasma/serum factor as immunoglobulin.
Authors: T S Zimmerman, H L Spiegelberg
Journal: Journal of Clinical Investigation (1975)

Pneumococcus-induced serotonin release from human platelets is greatly facilitated by a factor present in normal human plasma and serum. We have identified this factor as immunoglobulin by: (a) removing if from plasma and serum with solid phase antiFab antibody; (b) demonstrating its absence from the serum of an individual with severe immunoglobulin deficiency; and, (c) showing its presence in IgG preparations isolated from normal individuals. Evidence suggesting that the release reaction is triggered by pneumococcal antigen-antibody complexes rather than by nonimmune interaction of immunoglobulin with pneumococcus includes: (a) the failure of isolated IgG myeloma proteins to support release; (b) a lack of correlation between IgG concentration and "releasing factor activity" in normal human sera; (c) the identification of a normal serum that supports release by types II and III pneumococci but not type VII; and, (d) the ability of most normal sera to support release by pneumococca serotypes II and VII, though these types have not shown nonimmune reactivity with the Fc portion of the IgG molecule. The ability of antibodies present in normal serum to support pneumococcus-induced serotonin release suggests that the thrombocytopenia seen in pneumococcal infection may at least in part be caused by pneumococcal antigen-antibody complexes.
The effect of vitamin A acid on experimentally induced comedones: an electron microscope study
Authors: P.C. WOO-SAM
Journal: British Journal of Dermatology (1979)

Various concentrations of vitamin A acid were applied to experimentally induced comedones. All concentrations produced non-cohesive hyperkeratinization, which loosened the cohesive horny mass induced by oleic acid and expelled it from the follicle within 7 days. The highest concentration (0.1%) produced the greatest degree of non-cohesive desquamation in the shortest time. In follicles treated with the acid, the cell membrane of horny cells was thin and ruptured easily to produce a non-cohesive debris. Desmosomes were scarce and desmosomal bodies (fusiform electron-dense bodies) and tight junctions between horny cells were not seen in follicles treated with the acid. The acid also produced hyperplasia of the epithelial wall and an apparently increased mitotic rate. A 0.025% concentration of the acid increased the number of membrane coating granules by about 70% in all regions of the follicle.
Cost Implications of Reduced Work Hours and Workloads for Resident Physicians
Authors: Teryl K. Nuckols, Jay Bhattacharya, Dianne Miller Wolman, Cheryl Ulmer, José J. Escarce
Journal: New England Journal of Medicine (2009)

Although the Accreditation Council for Graduate Medical Education (ACGME) limits the work hours of residents, concerns about fatigue persist. A new Institute of Medicine (IOM) report recommends, among other changes, improved adherence to the 2003 ACGME limits, naps during extended shifts, a 16-hour limit for shifts without naps, and reduced workloads.
Reducing the Burden of Diabetes: The National Diabetes Education Program
Authors: Charles M. Clark
Journal: Diabetes Care (1998)

The National Diabetes Education Program (NDEP) is a joint initiative sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health and the Division of Diabetes Translation of the Centers for Disease Control and Prevention. The program will develop a partnership of public and private organizations and implement educational activities to help reduce the morbidity and mortality associated with diabetes and its complications. Participating public and private organizations include the Indian Health Service, the Department of Veterans Affairs, the American Diabetes Association, the American College of Physicians, the American Dietetic Association, and the American Association of Diabetes Educators. Key program activities will include (1) ongoing public awareness and education (2) and identification and dissemination of existing educational tools and resources for patients and their families, health care providers, and payers and purchasers of health care. The NDEP will also sponsor the development and dissemination of new educational tools and resources, including science-based guidelines, efforts to improve quality and access to diabetes care, and program evaluation.
Evaluation of polyethylene glycol modification of first-generation and helper-dependent adenoviral vectors to reduce innate immune responses
Authors: Hoyin Mok, Donna J. Palmer, Philip Ng, Michael A. Barry
Journal: Molecular Therapy (2004)

Adenoviruses are robust gene delivery vectors in vivo, but are limited by their propensity to provoke strong innate and adaptive responses. Previous work has demonstrated that polyethylene glycol (PEG) modification of adenovirus can protect the vectors from preexisting and adaptive immune responses by reducing protein–protein interactions. To test whether PEGylation can reduce innate immune responses to adenovirus by reducing their interactions with immune cells, first-generation (FG-Ad) and helper-dependent (HD-Ad) Ad5 vectors were PEGylated with SPA-PEG and tested in vitro and in vivo. We demonstrate that increasing PEGylation ablated in vitro transduction, but surprisingly had no negative effect on the level or distribution of in vivo gene delivery. This poor in vitro transduction could be rescued in part by physically forcing the PEGylated vectors onto cells, suggesting that physiological forces in vivo may enable transduction via heparin sulfate proteoglycan and integrin interactions. While transduction remained the same as for unmodified vectors, the PEGylated vectors reduced innate IL-6 responses by 70 and 50% in vivo for FG-Ad and HD-Ad. These reduced innate responses paralleled similar reductions in vector uptake by macrophages in vitro and Kupffer cells in vivo. These data suggest that PEGylation of Ad vectors can reduce innate immune responses without reducing transduction in vivo. These data also suggest that nonspecific vector uptake by macrophages and Kupffer cells may be critically involved in the initial activation of innate immune responses.
Esterified Estrogens and Conjugated Equine Estrogens and the Risk of Venous Thrombosis
Authors: Nicholas L. Smith, Susan R. Heckbert, Rozenn N. Lemaitre, Alex P. Reiner, Thomas Lumley, Noel S. Weiss, Eric B. Larson, Frits R. Rosendaal, Bruce M. Psaty
Journal: JAMA (2004)

Clinical trial evidence indicates that estrogen therapy with or without progestins increases venous thrombotic risk. The findings from these trials, which used oral conjugated equine estrogens, may not be generalizable to other estrogen compounds.To compare risk of venous thrombosis among esterified estrogen users, conjugated equine estrogen users, and nonusers.This population-based, case-control study was conducted at a large health maintenance organization in Washington State. Cases were perimenopausal and postmenopausal women aged 30 to 89 years who sustained a first venous thrombosis between January 1995 and December 2001 and controls were matched on age, hypertension status, and calendar year.Risk of first venous thrombosis in relation to current use of esterified or conjugated equine estrogens, with or without concomitant progestin. Current use was defined as use at thrombotic event for cases and a comparable reference date for controls.Five hundred eighty-six incident venous thrombosis cases and 2268 controls were identified. Compared with women not currently using hormones, current users of esterified estrogen had no increase in venous thrombotic risk (odds ratio [OR], 0.92; 95% confidence interval [CI], 0.69-1.22). In contrast, women currently taking conjugated equine estrogen had an elevated risk (OR, 1.65; 95% CI, 1.24-2.19). When analyses were restricted to estrogen users, current users of conjugated equine estrogen had a higher risk than current users of esterified estrogen (OR, 1.78; 95% CI, 1.11-2.84). Among conjugated equine estrogen users, increasing daily dose was associated with increased risk (trend P value = .02). Among all estrogen users, concomitant progestin use was associated with increased risk compared with use of estrogen alone (OR, 1.60; 95% CI, 1.13-2.26).Our finding that conjugated equine estrogen but not esterified estrogen was associated with venous thrombotic risk needs to be replicated and may have implications for the choice of hormones in perimenopausal and postmenopausal women.