tbuckley/cabot-search huggingface dataset:
Digitalis Pharmacology and Therapeutics: Recent Advances
Authors: DEAN T. MASON
Journal: Annals of Internal Medicine (1974)

The fundamental therapeutic action of digitalis is stimulation of ventricular contractile state. The expression of this increased contractility is dependent on the integrity of cardiocirculatory status when the glycoside is administered. Thus, by interplay between direct and indirect cardiac and vascular effects, variable and even opposite changes in cardiac output, peripheral circulatory dynamics, and myocardial oxygen consumption can occur. Apparently, the fundamental positive inotropic property of digitalis now rests on an influx of calcium intracellulary, produced by the drug's action on the cardiac cell membrane. In contrast, transmembrane fluxes of sodium and potassium underlie the electrical properties of the glycosides. Future research should clarify the nature of the digitalis receptor and further define the subcellular contractile and toxic mechanisms of the agent.
Prevention and Control of Nosocomial Infections
Authors: Jerry D. Smilack
Journal: JAMA (1994)

Here is a sampling of recent telephone calls I have received: "How long should my patient with methicillin-resistant<i>Staphylococcus aureus</i>pneumonia be isolated?" "Is it safe to replace an infected subclavian catheter over a guide wire?" "How do I interpret this report of a coagulase-negative staph in a blood culture?" Questions about<i>Candida</i>in a urinary tract culture, communicability of herpes zoster, and what antibiotics should be prescribed for surgical wound infection "prophylaxis" are almost daily occurrences and highlight the importance of nosocomial, or hospital-acquired, infections. This revised edition of<i>Prevention and Control of Nosocomial Infections</i>is now available to guide the reader through a broad field of knowledge that is enlarging at breakneck speed. The key word for this work is practicality. It is apparent that editor Wenzel has admonished the expert contributors to build upon a nucleus of key information dealing with nearly all aspects of infectious diseases
Cardiac neural crest orchestrates remodeling and functional maturation of mouse semilunar valves
Authors: Rajan Jain, Kurt A. Engleka, Stacey L. Rentschler, Lauren J. Manderfield, Li Li, Lijun Yuan, Jonathan A. Epstein
Journal: Journal of Clinical Investigation (2010)

Congenital anomalies of the aortic valve are common and are associated with progressive valvular insufficiency and/or stenosis. In addition, aneurysm, coarctation, and dissection of the ascending aorta and aortic arch are often associated conditions that complicate patient management and increase morbidity and mortality. These associated aortopathies are commonly attributed to turbulent hemodynamic flow through the malformed valve leading to focal defects in the vessel wall. However, numerous surgical and pathological studies have identified widespread cystic medial necrosis and smooth muscle apoptosis throughout the aortic arch in affected patients. Here, we provide experimental evidence for an alternative model to explain the association of aortic vessel and valvular disease. Using mice with primary and secondary cardiac neural crest deficiencies, we have shown that neural crest contribution to the outflow endocardial cushions (the precursors of the semilunar valves) is required for late gestation valvular remodeling, mesenchymal apoptosis, and proper valve architecture. Neural crest was also shown to contribute to the smooth muscle layer of the wall of the ascending aorta and aortic arch. Hence, defects of cardiac neural crest can result in functionally abnormal semilunar valves and concomitant aortic arch artery abnormalities.
China's psychiatric hospitals collude with officials to stifle dissent, say civil rights' groups
Authors: J. Parry, W. Cui
Journal: BMJ (2010)

In 2003, Xu Lindong, a farmer from Yancheng county, Henan province, China, decided to file a petition in Beijing to help his neighbour protest about maltreatment at the hands of local officials in a land dispute. Xu never filed his petition. On the outskirts of Beijing he was intercepted by a Daliu township government official and a policeman, taken home, and subsequently incarcerated in Zhumadian Psychiatric Hospital, Henan, at the request of township and county government officials.

Six and a half years later in April 2010, Xu was released from Luohe Psychiatric Hospital, also in Henan province, where he had spent the last five months of his ordeal, after being transferred there from Zhumadian Hospital. When he met the media he described barbaric treatment while in hospital, including being given electric shocks 54 times and being forced to take chlorprothixene and chlordiazepoxide, drugs which made him feel faint and dizzy. 

Xu’s family did not know what had happened to him until July 2007. “Someone from his home town visited other patients in the same hospital as Xu and he managed to ask the visitor to get a message to his family,” says Xu’s lawyer Chang Boyang. The family tried to secure his release but it was only when journalists brought the case to the attention of the lawyer Chang that …
Epidermal Growth Factor Receptor Biology in Head and Neck Cancer
Authors: Shailaja Kalyankrishna, Jennifer R. Grandis
Journal: Journal of Clinical Oncology (2006)

Epidermal growth factor receptor (EGFR) is overexpressed in several epithelial malignancies, including head and neck squamous cell carcinoma (HNSCC), which exhibits EGFR overexpression in up to 90% of tumors. EGFR ligands such as transforming growth factor alpha are also overexpressed in HNSCC. EGFR plays a critical role in HNSCC growth, invasion, metastasis and angiogenesis. However, EGFR inhibitors as monotherapy have yielded only modest clinical outcomes. Potential mechanisms for lack of response to EGFR inhibition in HNSCC include constitutive activation of signaling pathways independent of EGFR, as well as genetic aberrations causing dysregulation of the cell cycle. EGFR-directed therapy may be optimized by identifying and selecting those HNSCC patients most likely to benefit from EGFR inhibition. Resistance to EGFR inhibition may be circumvented by combination therapy employing EGFR inhibitors together with other treatment modalities.
Danger of skin burns from thiomersal.
Authors: H T Jones
Journal: BMJ (1972)

that the elective migration to the liver is probably not due to a cytotoxic effect of antilymphocyte globulin occurring in vivo after introduction of the lymphocytes coated with A.L.G., but rather to an opsonizing effect involving different mechanisms and the action on the first four components of complement (Gigli and Nelson, 1968).We thank Dr. J. Dormont for his valuable advice about the choice of A.L.
POISONING FROM AUTOINTOXICATION.
Authors: T. D. CROTHERS
Journal: JAMA (1901)

In Hufeland's "Art of Prolonging Life," written in 1790, and one of the few books of that century still published and read, there is a distinct recognition of autointoxication states generated in the intestinal canal by the fermentation and changes of foods and drinks. Several of the proprietary medicines owe their success to the recognition of this condition and the application of antiseptic and eliminative measures. One such remedy, widely advertised and supported by volumes of testimonials as having cured obscure disorders and averted serious diseases, contains sulphate of magnesia and soda concealed by some flavoring substances. The value of this remedy is in its power to overcome these autointoxicative states which are largely unknown. A book written by an unknown man, claiming to be the science of a new life, nothing more than a promulgation of the theory of two meals a day, points out the same range of
The relationship between p38 mitogen-activated protein kinase and AMP-activated protein kinase during myocardial ischemia
Authors: S JACQUET, E ZARRINPASHNEH, A CHAVEY, A GINION, I LECLERC, B VIOLLET, G RUTTER, L BERTRAND, M MARBER
Journal: Cardiovascular Research (2007)

Objective p38 mitogen-activated protein kinase (p38 MAPK) and AMP-activated protein kinase (AMPK) are activated by, and influence sensitivity to, myocardial ischemia. Recently a number of studies have suggested that AMPK may participate in the activation of p38 MAPK. We therefore examined whether AMPK may be the principal "ischemia sensor" responsible for p38 MAPK activation during myocardial ischemia. Methods We used a variety of approaches to alter AMPK activity during ischemia and studied the repercussions on p38 MAPK activation. Results The activities of AMPK and p38 MAPK were temporally related in adult rat ventricular myocytes (ARVM) subjected to simulated ischemia and in isolated mouse hearts subjected to no-flow ischemia. However p38 MAPK activation was unaltered in mouse hearts lacking the predominant or minor myocardial isoforms, AMPKα2 or AMPKα1 respectively. Likewise, in ARVM, adenoviral-driven expression of the minor myocardial isoform AMPKα1, in a constitutively active or dominant negative form reducing AMPK activity, did not alter p38 MAPK activation under basal conditions or during simulated ischemia. Finally, pharmacological inhibition of AMPK during ischemia with compound C did not attenuate the coincident activation of p38 MAPK. Conclusions Although AMPK and p38 MAPK are both activated during myocardial ischemia, the activation of p38 MAPK occurs independently of AMPK.
Specification in the global array
Authors: Thomas A. Stoffregen, Benoît G. Bardy
Journal: Behavioral and Brain Sciences (2001)

We discuss issues raised by the commentators, such as specification in single-energy arrays, task-specific pickup of information, general principles of the ecological approach to perception and action, and how specification may be constrained by the facts of physical relativity. While the commentaries raise many important issues we conclude that they do not undermine our argument that specification exists solely in the global array.
A Processable Shape Memory Polymer System for Biomedical Applications
Authors: Keith Hearon, Mark A. Wierzbicki, Landon D. Nash, Todd L. Landsman, Christine Laramy, Alexander T. Lonnecker, Michael C. Gibbons, Sarah Ur, Kristen O. Cardinal, Thomas S. Wilson, Karen L. Wooley, Duncan J. Maitland
Journal: Advanced Healthcare Materials (2015)

Polyurethane shape memory polymers (SMPs) with tunable thermomechanical properties and advanced processing capabilities are synthesized, characterized, and implemented in the design of a microactuator medical device prototype. The ability to manipulate glass transition temperature ( T g ) and crosslink density in low‐molecular weight aliphatic thermoplastic polyurethane SMPs is demonstrated using a synthetic approach that employs UV catalyzed thiol‐ene “click” reactions to achieve postpolymerization crosslinking. Polyurethanes containing varying C=C functionalization are synthesized, solution blended with polythiol crosslinking agents and photoinitiator and subjected to UV irradiation, and the effects of number of synthetic parameters on crosslink density are reported. Thermomechanical properties are highly tunable, including glass transitions tailorable between 30 and 105 °C and rubbery moduli tailorable between 0.4 and 20 MPa. This new SMP system exhibits high toughness for many formulations, especially in the case of low crosslink density materials, for which toughness exceeds 90 MJ m −3 at select straining temperatures. To demonstrate the advanced processing capability and synthetic versatility of this new SMP system, a laser‐actuated SMP microgripper device for minimally invasive delivery of endovascular devices is fabricated, shown to exhibit an average gripping force of 1.43 ± 0.37 N and successfully deployed in an in vitro experimental setup under simulated physiological conditions.
Risk of cardiovascular serious adverse events associated with varenicline use for tobacco cessation: systematic review and meta-analysis
Authors: J. J. Prochaska, J. F. Hilton
Journal: BMJ (2012)

<b>Objective</b> To examine the risk of treatment emergent, cardiovascular serious adverse events associated with varenicline use for tobacco cessation. <b>Design</b> Meta-analysis comparing study effects using four summary estimates. <b>Data sources</b> Medline, Cochrane Library, online clinical trials registries, and reference lists of identified articles. <b>Review methods</b> We included randomised controlled trials of current tobacco users of adult age comparing use of varenicline with an inactive control and reporting adverse events. We defined treatment emergent, cardiovascular serious adverse events as occurring during drug treatment or within 30 days of discontinuation, and included any ischaemic or arrhythmic adverse cardiovascular event (myocardial infarction, unstable angina, coronary revascularisation, coronary artery disease, arrhythmias, transient ischaemic attacks, stroke, sudden death or cardiovascular related death, or congestive heart failure). <b>Results</b> We identified 22 trials; all were double blinded and placebo controlled; two included participants with active cardiovascular disease and 11 enrolled participants with a history of cardiovascular disease. Rates of treatment emergent, cardiovascular serious adverse events were 0.63% (34/5431) in the varenicline groups and 0.47% (18/3801) in the placebo groups. The summary estimate for the risk difference, 0.27% (95% confidence interval −0.10 to 0.63; P=0.15), based on all 22 trials, was neither clinically nor statistically significant. For comparison, the relative risk (1.40, 0.82 to 2.39; P=0.22), Mantel-Haenszel odds ratio (1.41, 0.82 to 2.42; P=0.22), and Peto odds ratio (1.58, 0.90 to 2.76; P=0.11), all based on 14 trials with at least one event, also indicated a non-significant difference between varenicline and placebo groups. <b>Conclusions</b> This meta-analysis—which included all trials published to date, focused on events occurring during drug exposure, and analysed findings using four summary estimates—found no significant increase in cardiovascular serious adverse events associated with varenicline use. For rare outcomes, summary estimates based on absolute effects are recommended and estimates based on the Peto odds ratio should be avoided.
Reliance on direct payment for health care in Asia is higher in poorer than in richer countries, new study shows
Authors: Roger Dobson
Journal: BMJ (2008)

The proportion of the cost of health care that is paid directly by patients themselves varies widely in Asia, with the Japanese paying the least out of their own pockets and the Nepalese paying the most, new research shows ( Journal of Health Economics 2008;27:460-75).

The researchers looked at healthcare financing in 13 countries and territories in central, southern, and eastern Asia, accounting for 55% of the total population of Asia and 33% of the world population. Direct payments by patients accounted for …
Building a better micro-foundation for institutional analysis
Authors: Elinor Ostrom
Journal: Behavioral and Brain Sciences (2005)

The target article summarizes important research demonstrating that the canonical model of selfish, economic man is not empirically supported outside competitive settings, and that experimental research conducted in university settings should not be discounted because undergraduates were the subjects. Assuming that individuals are capable of reciprocity and trust provides a firmer foundation for the study of institutions, incentives, and outcomes.
Mutations in LMF1 cause combined lipase deficiency and severe hypertriglyceridemia
Authors: Miklós Péterfy, Osnat Ben-Zeev, Hui Z Mao, Daphna Weissglas-Volkov, Bradley E Aouizerat, Clive R Pullinger, Philip H Frost, John P Kane, Mary J Malloy, Karen Reue, Päivi Pajukanta, Mark H Doolittle
Journal: Nature Genetics (2007)
B cell tolerance in mice transgenic for anti-CD8 immunoglobulin mu chain.
Authors: F Brombacher, G Köhler, H Eibel
Journal: The Journal of Experimental Medicine (1991)

To analyze in vivo the induction of B cell tolerance against a T cell surface antigen, we generated transgenic mice expressing an anti-CD8.2 mu heavy chain gene. We show that self-specific B cells are efficiently tolerized if they express the membrane-bound form of the transgenic mu chain on their surface but that they can escape tolerization if they express only the secreted form. In the latter, we find an enhanced expression of anti-CD8.2 antibodies after polyclonal B cell activation. As a result, transgenic anti-CD8.2 antibodies bind to the CD8+ T cells but they did not induce their elimination. Furthermore, we observed the preferential expression of a limited subset of endogenous light chains with the transgenic mu chain. This suggests a positive or negative selection for particular heavy and light chain combinations in B lymphocytes.
Report of the Committee on Medical Education Appointed by the Illinois State Medical Society.Presented at the meeting held at Decatur, Ill. May 15, 16, 17, 1894.
Authors: SANGER BROWN
Journal: JAMA (1894)

It will be quite readily conceded by any one who examines into the subject that there is a conspicuous lack of uniformity in the quality of the medical diplomas of this country. That this lack of uniformity has been recognized by other countries is well known, and evidence of the fact is furnished when it is stated that no American degree entitles its possessor to legally practice his profession in the countries of Europe, while nearly all their degrees are recognized here, as entitling their holders to practice under the protection of the law. It does not follow that the present very unsatisfactory and uncertain status of the American diploma implies either a want of ability, perception or honesty on the part of the American doctor; it came about naturally in the course of rapid national development, and indeed, in view of all the facts I think we should rather feel proud than apologetic of our medical schools. But many of the causes which in the past furnished sufficient excuse or perhaps created a necessity for the medical schools throughout the land to pursue the course and adopt the methods
Consumers' Association voices concern at over the counter statins
Authors: Owen Dyer
Journal: BMJ (2004)

As statins went on sale without prescription in British pharmacies last week, the Consumers' Association argued that the public is being used as guinea pigs.

Simvastatin, one of the earliest and most used statins, is the first to be approved and will be sold in a low dose (10 mg) formulation under the brand name Zocor Heart-Pro, by Johnson & Johnson MSD.

Existing NHS guidelines say that statins should be prescribed only to patients who face a 30% risk of a heart attack over 10 years, but over the counter sales will be …
Haploinsufficiency of the <i>Maspin</i> Tumor Suppressor Gene Leads to Hyperplastic Lesions in Prostate
Authors: Long-jiang Shao, Heidi Y. Shi, Gustavo Ayala, David Rowley, Ming Zhang
Journal: Cancer Research (2008)

Abstract Maspin is a key tumor suppressor gene in prostate and breast cancers with diverse biological functions. However, how maspin regulates prostate tumor progression is not fully understood. In this study, we have used maspin heterozygous knockout mice to determine the effect of maspin haploinsufficiency on prostate development and tumor progression. We report that loss of one copy of maspin gene in Mp+/− heterozygous knockout mice leads to the development of prostate hyperplastic lesions, and this effect was mediated through decreased level of cyclin-dependent kinase inhibitors p21 and p27. Prostate hyperplastic lesions in Mp+/− mice also induced stromal reaction, which occurred in both aged prostate tissues and in neonatal prostates during early ductal morphogenesis. We showed that maspin was also expressed in prostate smooth muscle cells (PSMC), and recombinant maspin increased PSMC cell adhesion but inhibited cell proliferation. We also observed a defective interaction between epithelial cells and basement membrane in the prostate of Mp+/− mice, which was accompanied with a changed pattern of matrix deposition and a loss of epithelial cell polarity. Therefore, we have identified a novel property of maspin, which involves the control of the proliferation in prostate epithelial and smooth muscle cells. This is the first report that a partial loss of maspin caused an early developmental defect of the prostate and prostate hyperplastic lesions in mouse. [Cancer Res 2008;68(13):5143–51]
Protective effect of vitamin E (DL-alpha-tocopherol) against intraventricular haemorrhage in premature babies.
Authors: M L Chiswick, M Johnson, C Woodhall, M Gowland, J Davies, N Toner, D G Sims
Journal: BMJ (1983)

Forty four babies, of less than 32 weeks' gestation, were either randomly given 25 mg/kg vitamin E (DL-alpha-tocopherol acetate) intramuscularly after birth (day 0) and on days 1, 2, and 3 or served as controls. Frequent real time ultrasound examinations of the brain were made in each baby during the first week and less frequently thereafter. In babies under 32 weeks' gestation the incidence of intraventricular haemorrhage was lower in supplemented babies (18.8%) compared with the controls (56.3%). On days 0, 1, 2, and 3 median plasma vitamin E concentrations in babies without haemorrhage and in those with subependymal haemorrhage only were similar. Babies with intraventricular haemorrhage had lower median concentrations on day 1 (p less than 0.002) and day 2 (p less than 0.05) compared with those with subependymal haemorrhage and lower concentrations on day 0 (p less than 0.02) and day 1 (p less than 0.05) compared with those without haemorrhage. These findings suggest that in premature babies vitamin E, an antioxidant, protects endothelial cell membranes from oxidative damage and disruption and limits the magnitude of haemorrhage and its spread from the subependyma into the ventricles.
Emerging Tick-borne Diseases Expand Range Along With Rebounding Deer Populations
Authors: Bridget M. Kuehn
Journal: JAMA (2013)

Babesiosis, a tick-borne disease, is becoming a growing concern in the Northeast and upper Midwest as burgeoning deer populations help spread the malaria-like condition, according to data presented at the American Society of Tropical Medicine and Hygiene (ASTMH) meeting in November.
Association between duodenal bulb ulceration and reduced exocrine pancreatic function.
Authors: S Schulze, N Thorsgaard Pedersen, M J Jorgensen, K M Mollmann, S J Rune
Journal: Gut (1983)

Seventy two patients admitted to a medical department with dyspepsia but without a previous diagnosis of peptic ulcer disease or chronic pancreatitis were studied consecutively. A pancreatic function test (Lundh meal test) and an upper endoscopy was made in all patients. There was no difference in age, sex ratio, occurrence of upper abdominal pain or chronic alcoholism between the groups of patients with reduced pancreatic function (20) and the group with normal function (52). Seven duodenal ulcers were found, two in patients with normal pancreatic function (2/52 = 3.8%; 95% conf lim: 0.5-13.2) and five in patients with reduced pancreatic function (5/20 = 25%; 95% conf lim: 8.7-49.1). This difference was statistically significant (p less than 0.01). Duodenitis occurred with equal frequency in the two groups.