tbuckley/cabot-search huggingface dataset:
Effects of Thyroid Hormone on Left Ventricular Performance and Regulation of Contractile and Ca <sup>2+</sup> -Cycling Proteins in the Baboon
Authors: Saeb F. Khoury, Brian D. Hoit, Vrushank Dave, Corinn M. Pawloski-Dahm, Yanfu Shao, Marjorie Gabel, Muthu Periasamy, Richard A. Walsh
Journal: Circulation Research (1996)

The transcriptional, posttranscriptional, and related functional effects of thyroid hormone on primate myocardium are poorly understood. Therefore, we studied the effects of thyroid hormone on sarcoplasmic reticulum (SR) Ca 2+ -cycling proteins and myosin heavy chain (MHC) composition at the steady state mRNA and protein level and associated alterations of left ventricular (LV) performance in 8 chronically instrumented baboons. The force-frequency and relaxation-frequency relations were assessed as the response of LV isovolumic contraction (dP/dt max ) and relaxation (Tau), respectively, to incremental atrial pacing. Both the heart rate at which dP/dt max was maximal and Tau was minimal (critical heart rates) in response to pacing were increased significantly after thyroid hormone. Postmortem LV tissue from 5 thyroid-treated and 4 additional control baboons was assayed for steady state mRNA levels with cDNA probes to MHC isoforms and SR Ca 2+ -cycling proteins. Steady state SR Ca 2+ -ATPase and phospholamban mRNA increased in the hyperthyroid state, and α-MHC mRNA appeared de novo, whereas β-MHC mRNA decreased. Western analysis (4 thyroid-treated and 4 control baboons) showed directionally similar changes in MHC isoforms and a slight increase in SR Ca 2+ -ATPase. In contrast, there was a statistically nonsignificant decrease in phospholamban protein, which resulted in a significant 40% decrease in the ratio of phospholamban to SR Ca 2+ -ATPase. Thus, thyroid hormone increases the transcription of Ca 2+ -cycling proteins and shifts MHC isoform expression in the primate LV. Our data suggest that both transcriptional and posttranslational mechanisms determine the levels of these proteins in the hyperthyroid primate heart and mediate, in part, the observed enhanced basal and frequency-dependent LV performance.
Calculation of left ventricular wall stress.
Authors: D M Regen
Journal: Circulation Research (1990)

Chamber-stress equations relate wall stresses to pressure and wall dimensions. Such equations play a central role in the analysis and understanding of heart-chamber function. Over the past three decades, several stress equations giving radically different results have been derived, used, and/or espoused. They can be classified into two categories, according to the definition of stress underlying the equation. The stresses in one class of equations are total forces per unit normal area, excluding ambient pressure but including pressure in the wall exerted by more external elements of the wall. The stresses in the other class of equations are fiber-pulling forces per unit normal area, that is, total forces per unit normal area excluding all pressure. The validity of stress equations can be tested at least three ways: 1) Do they predict that the pressure inside a small chamber nested in a larger chamber would be the sum of transmural pressures of the two chambers? 2) Do they satisfy the expectation from Laplace's law that a sphere with a given circular stress and thickness/radius ratio would exert twice the pressure of a cylinder with the same circular stress and thickness/radius ratio? 3) Do they predict that the ratio of principle stresses depends on chamber shape but not on wall/cavity ratio, with the circular/longitudinal stress ratio of a cylinder being 2 and that of a prolate spheroid being between 1 and 2? Stress equations of the first class fail all of these tests by large margins, whereas those of the second class pass all of these tests exactly.(ABSTRACT TRUNCATED AT 250 WORDS)
QUINIDINE: ARTERIAL, VENOUS, CORONARY SINUS AND MYOCARDIAL CONCENTRATIONS*
Authors: Leonard Scherlis, Luis F. Gonzalez, Samuel P. Bessman
Journal: Journal of Clinical Investigation (1961)

Most of the current knowledge of relationships between blood levels of quinidine and therapeutic or toxic effects were ascertained by determining peripheral venous levels following oral administration. After single oral administration of quinidine sulfate to patients with atrial fibrillation, Wegria and Boyle (1) observed that the intensity of the cardiac effect of the drug and its plasma concentration were grossly parallel but not parallel in a strictly quantitative manner. Discrepancies were found between the intensity of cardiac effect and quinidine plasma concentration, the plasma level of the drug decreasing faster than the intensity of its cardiac effect. Some investigators utilize quinidine concentration of venous blood as a guide in determining optimal therapy (2-6). Wegria and Boyle (1) reported no significant difference between the arterial and venous concentration of quinidine a few hours after oral administration. Higher levels were found in the myocardium than in the peripheral venous blood. A recent publication (7) contains a review of the pertinent literature on the subject. In spite of the clinical practice of administering quinidine intravenously to patients with certain life-threatening arrhythmias for immediate therapeutic effects, there is a paucity of data relative to blood levels
Recombinant human tumor necrosis factor induces acute reductions in food intake and body weight in mice.
Authors: S H Socher, A Friedman, D Martinez
Journal: The Journal of Experimental Medicine (1988)

We examined the effects of treatment with rHuTNF on food consumption and body weight in C3H/HeJ mice. rHuTNF was administered intraperitoneally either by injections of 3, 12, or 24 micrograms twice a day or by implantation of osmotic pumps that released 0.75, 3, or 12 micrograms per day. Dose-dependent reductions in both food intake and weight were induced by rHuTNF. However, in spite of continued exposure to rHuTNF, the mice developed a resistance to rHuTNF and resumed their pretreatment food intake and weight. Non-immunological factors may play a role in the development of this tolerance, since it developed rapidly and faded within 2 wk of cessation of exposure to rHuTNF.
Surface microscopy of naevi and melanomas—clues to melanoma
Authors: M. NILLES, R-H. BOEDEKER, W-B. SCHILL
Journal: British Journal of Dermatology (1994)

In this present study, 260 histologically confirmed melanocytic skin tumours (188 benign naevi and 72 malignant melanomas; from 1989 to 1990) were investigated with regard to valid surface microscopical criteria of malignancy. The tumours were analysed using a system which assessed eight components. Most melanomas were characterized by the following pattern: asymmetrical pigment distribution, more than three colours, black pigment, peripheral stripes, and asymmetrical depigmentation. The results were evaluated statistically by contingency tables and logistic regression procedures. On the basis of the classification derived, the sensitivity and specificity were determined for lesions from 1991, and were 0.9 and 0.85, respectively. Many melanocytic naevi were not identified by the above criteria, or were found only occasionally. Pigment network was often absent in naevi and melanomas, and was not decisive for the diagnosis. The present investigation demonstrates that in vivo diagnosis of pigmented melanocytic lesions can be improved by surface microscopy.
Talking With Patients, vol 1: The Theory of Doctor-Patient Communications; vol 2: Clinical Technique
Authors: Paul J. Schwab
Journal: JAMA (1985)

"... the spoken language is our most important diagnostic and therapeutic tool, and we must be as precise in its use as a surgeon with a scalpel." The author states that the dialogue between the physician and patient is the source from which all diagnostic and treatment efforts flow. He believes that insufficient attention has been given to teaching medical students and clinicians communication skills. His basic goal is to teach the clinician to listen and to speak with discipline, attention, and precision. He defines basic principles of linguistics and illustrates their clinical applications with excerpts from over 1,000 hours of tape-recorded interactions between physicians and about 800 consenting patients. A research team reviewed all of these transcriptions made in 1974 and 1975 and selected segments to demonstrate each section. Rich, detailed, and unexpurgated, the dialogue illustrates how to and how not to listen and speak with patients. The spoken word
Late Congestive Heart Failure After Hematopoietic Cell Transplantation
Authors: Saro H. Armenian, Can-Lan Sun, Liton Francisco, Julia Steinberger, Seira Kurian, F. Lennie Wong, Jon Sharp, Richard Sposto, Stephen J. Forman, Smita Bhatia
Journal: Journal of Clinical Oncology (2008)

To examine the independent roles of pre-hematopoietic cell transplantation (HCT) therapeutic exposures, transplantation-related conditioning, and comorbidities (pre- and post-HCT) in the development of late congestive heart failure (CHF) after HCT.This was a nested case-control design. Individuals with late CHF (diagnosed >or= 1 year after HCT) were identified from a cohort of 2,938 1+ year survivors who underwent transplantation at City of Hope National Medical Center, Duarte, CA. This cohort formed the sampling frame for selecting controls (without CHF) matched for age and year of HCT, donor source (allogeneic v autologous), and length of follow-up.Sixty patients with late CHF were identified; median age at HCT was 45.3 years (range, 16.6 to 68.6 years); median time to CHF was 3.0 years (range, 1.03 to 18.9 years); 68% received autologous HCT. Median ejection fraction was 36.9% (range, 15% to 53%). Compared with matched controls (n = 166), patients with late CHF received more cycles of pre-HCT chemotherapy (8.6 v 4.9 cycles; P < .01), had greater body mass index at HCT (28.4 v 26.2 kg/m(2); P = .01), greater lifetime anthracycline exposure (285.3 v 175.6 mg/m(2); P < .01), and were more likely to have multiple chronic comorbidities (30.0% v 13.9%; P < .01). Multivariable analysis revealed number of pre-HCT chemotherapy cycles (odds ratio [OR] = 1.2; P < .01), anthracycline dose >/= 250 mg/m(2) (OR = 3.2; P = .05), and two or more chronic comorbidities (OR = 4.3; P = .01) to be independently associated with late CHF.Pre-HCT exposure to anthracyclines and presence of comorbidities are primarily responsible for the risk associated with late CHF after HCT. Conditioning-related therapeutic exposure does not contribute significantly to the risk. These results form the basis for identifying high-risk individuals for targeted surveillance, as well as developing preventive strategies in the form of aggressive management of comorbidities.
EU warns four countries over tobacco advertising
Authors: Rory Watson
Journal: BMJ (2006)

The European Commission has stepped up its campaign against tobacco advertising by threatening to take four EU countries to court for not fully respecting the Europe-wide ban, which came into force last summer. Italy, Spain, Hungary, and the Czech Republic were sent formal warnings this week and told to comply with the new restrictions.

Announcing the legal action, Markos Kyprianou, the European Union's health commissioner, said, “Stopping the glamorisation of tobacco through advertising and sponsorship is a key aspect in reducing the number of people who smoke or start to smoke.”

The four countries now have two months to …
The Clinical Value of Scintigraphic Brain Scanning Experience at the Hillbrow Hospital, Johannesburg, South Africa
Authors: R WINTERTON, M TOBIAS, J LEVIN, J ESSER, B I SAVITCH, E SPRINGOLO, D VELLET
Journal: Clinical Nuclear Medicine (1985)

Patients were referred to the Department of Nuclear Medicine for brain scintigraphy to be screened for possible intracranial pathology. These referrals were made in order to reduce the heavy load on the transmission computerized tomography (TCT) facilities. Great clinical importance, therefore, has been attached to scintigraphic findings; this emphasizes the need for an accurate assessment of the predictive value of this procedure.
CONTEMPORARY ANGIOGRAPHIC AND CLINICAL OUTCOMES OF ACUTE ST-SEGMENT ELEVATION MYOCARDIAL INFARCTION TREATED WITH PRIMARY PERCUTANEOUS CORONARY INTERVENTION IN PATIENTS WITH PRIOR CORONARY ARTERY BYPASS GRAFTS
Authors: M. Fuad Jan, Naoyo Mori, Anjan Gupta, Tanvir Bajwa, Suhail Allaqaband
Journal: Journal of the American College of Cardiology (2011)
Good news about a bad subject: scientific evidence to help defeat multidrug/extensively drug-resistant tuberculosis
Authors: Giovanni Sotgiu, Mark Woodhead
Journal: European Respiratory Journal (2014)

The good news about tuberculosis (TB) is that in the 29 reporting European Union/European Economic Area countries the number of incident TB cases is falling, with an average annual decline of 6% since 2011 [1].The bad news is that, however you look at it, multidrug-resistant TB (MDR-TB) and extensively drugresistant TB (XDR-TB) remain a major clinical and public health problem worldwide, particularly in former Soviet Union countries and Central Asia [2][3][4].Less than a quarter of the total estimated MDR-TB cases were actually diagnosed in 2012 [2], with dramatic consequences from an individual and a community perspective (i.e.increased morbidity, mortality and drug-resistant Mycobacterium tuberculosis transmission).It was estimated that 450 000 incident patients developed MDR-TB and 170 000 died from MDR-TB.More than half of such cases die, fail or stop taking treatment and only one in three cases in reporting countries completes the long treatment course (.20 months).The treatment success in the 2010 MDR-TB cohort was 48%, only 34 (31.8%)out of 107 countries reached a therapeutic success rate of at least 75%.About 9.6% of the MDR-TB cohort was XDR-TB.The direct and indirect costs are significant from a healthcare and a societal perspective [5,6].While the cost per case for drug-susceptible TB is estimated to be ,J10 000, that for MDR-TB and for XDR-TB is estimated to be ,J50 000 and J170 000, respectively [5].The reasons for this increased cost are fairly obvious since successful management often requires a prolonged inpatient stay, exposure to a cocktail of multiple, expensive, usually less effective medications with frequent serious and unpleasant toxicities, to be taken under close medical and/or social supervision for many months (so-called directly observed therapy).That a significant proportion of initially drugsusceptible TB can become MDR during treatment, following poor patient adherence mainly caused by drug toxicity and long treatment duration, is also a concern [7][8][9].Case management is not helped by the geographical distribution of TB patients across countries.For instance, of the 54 World Health Organization (WHO) European Region countries reporting 33 371 cases of MDR-TB in 2012, five reported more than 1 000 individuals with TB annually (Belarus, Kazakhstan, Russia, Ukraine and Uzbekistan), while 20 countries reported less than 10 individuals annually.Clinical experience in MDR-TB management is thus concentrated in few, sometimes poorly resourced countries, whereas cases are thinly spread across other better resourced countries.Guidance on MDR-TB management is, therefore, welcome to most healthcare workers involved in TB patient care and the consensus statement produced by the Tuberculosis Network European Trials Group (TBNET) group in this issue of the European Respiratory Journal delivers exactly what is needed [10].
What does the white paper mean for hospital consultants?
Authors: H. Mascie-Taylor
Journal: BMJ (2010)

Greater influence and greater accountability

Since the general election the movement towards reform and reorganisation in the health service has been rapid. The recently published white paper and the subsequent Transparency in Outcomes—A Framework for the NHS could completely recast the way the NHS is managed, governed, and held to account.1 2 Many commentators consider that a series of radical and far reaching changes to the NHS is under way.3 4 5 Consultants and their patients are understandably concerned about what these changes mean for them. A consideration of the four broad themes that run through the white paper and its supporting documents is crucial to tackling these concerns.

The first of these, and perhaps the most important, is the principle that patient empowerment, facilitated by information and choice of health providers, is paramount. Second is the substantial strengthening and clarification at all levels of the purchaser-provider split. This will be supported by the third ambition, to free the provider market and promote greater choice. Finally, increasingly robust regulation will be directed towards internationally comparable quality outcomes and …
Inhibition of Matrix Metalloproteinase Activity Inhibits Smooth Muscle Cell Migration but Not Neointimal Thickening After Arterial Injury
Authors: Michelle P. Bendeck, Colleen Irvin, Michael A. Reidy
Journal: Circulation Research (1996)

Abstract Smooth muscle cell (SMC) migration and replication are important for neointimal formation after arterial injury. Migration of SMCs requires degradation of basement membrane and extracellular matrix surrounding the cell, and our previous work has shown a correlation between expression of two matrix-degrading metalloproteinases (MMPs), MMP-2 and MMP-9, and smooth muscle migration into the intima in the balloon catheter–injured rat carotid artery. In the present study, an MMP inhibitor, GM 6001, was administered to rats for various times after balloon injury of the carotid artery. Inhibition of MMP activity resulted in a 97% decrease in the number of SMCs that migrated into the intima by 4 days after injury, and lesion growth was retarded by continuous treatment with GM 6001 for up to 10 days after injury. At 10 days, intimal area in GM 6001–treated rats was 0.035±0.008 mm 2 compared with 0.095±0.01 mm 2 in the control group. Neither intimal nor medial SMC replication rates were decreased by GM 6001 treatment, supporting our hypothesis that the decrease in lesion size was due to inhibition of MMP-mediated migration and not inhibition of replication. By 14 days after injury, however, intimal area and SMC number were the same in control and inhibitor-treated rats. An increased rate of SMC replication in the GM 6001 rats (replication rates at 10 days were 56.7±10.0% in the GM 6001 group and 16.97±1.73% in the control group) contributed to “catch-up” growth of the neointima. Thus, it appears that inhibiting SMC migration with MMP inhibitors is not sufficient to inhibit lesion growth, and lesion size eventually catches up to control via increased SMC replication.
Immediate and short-term benefit of multilesion coronary angioplasty: Influence of degree of revascularization
Authors: Michel G. Vandormael, Bernard R. Chaitmanz, Thomas Ischinger, Umit T. Aker, Michael Harper, Jorge Hernandez, Ubeydullah Deligonul, Harold L. Kennedy
Journal: Journal of the American College of Cardiology (1985)
SHISTOSOMIASIS-ASSOCIATED PULMONARY ARTERIAL HYPERTENSION SURVIVAL IN ENDEMIC AREA IN BRAZIL
Authors: Carlos Piscoya Roncal, Adriano A. Mendes, Maria TC Muniz, Sheilla A. Oliveira, Leonidas M. Valle Neto, Dario C. Sobral Filho, Mardi Gomberg-Maitland
Journal: Journal of the American College of Cardiology (2014)
Glucokinase gene transfer to skeletal muscle of diabetic Zucker fatty rats improves insulin-sensitive glucose uptake
Authors: Josep C. Jim[eacute]nez-Chillar[oacute]n, Sabine Telemaque-Potts, Al[iacute]cia G. G[oacute]mez-Valad[eacute]s, Paul Anderson, Christopher B. Newgard, Anna M. G[oacute]mez-Foix
Journal: Metabolism (2002)
Manpower planning and accurate information.
Authors: R S Viner
Journal: BMJ (1980)

MARCH 1980 it is a pity that the design was not better.The treatment group received specific and non- specific therapy (exercise therapy and regular supervision from a nurse, with occasional medical review), while the controlled group received neither on leaving hospital.As the non-specific factors were uncontrolled, the conclusion that simple exercise rehabilitation is of benefit is invalid.
Alpha fetoprotein directly induces a unique pro-inflammatory, IL-2 hyperresponsive phenotype in human natural killer cells
Authors: Lazar Vujanovic, Elizabeth Stahl, Lisa H Butterfield
Journal: Journal for ImmunoTherapy of Cancer (2014)

Meeting abstracts Alpha fetoprotein (AFP) is an oncofetal antigen commonly produced by hepatocellular carcinomas (HCC). Previous studies have shown that tumor-derived AFP (tAFP) has an immunosuppressive role on natural killer (NK), T, B, and dendritic (DC) cells which may play a role in HCC
Abstract 1501: Optimizing small RNAseq of archived serum samples from the Janus Serum Bank - a search for cancer biomarkers
Authors: Trine B. Rounge, Robert Lyle, Marianne Lauritzen, Kristina Kjaerheim, Tom Grotmol, Tom K. Grimsrud, Randi E. Gislefoss, Steinar Tretli, Giske Ursin, Hilde Langseth
Journal: Cancer Research (2014)

Abstract Introduction miRNAs are a distinct class of small non-coding RNA molecules that regulate the expression of protein coding genes. They are present and stable in the cell-free body fluids such as plasma, serum and urine. The Janus Serum Bank contains 317 000 serum samples and more than 61 000 incident cancer cases diagnosed during follow-up. It is well-suited for studies of miRNAs as early cancer biomarkers since samples are collected pre-diagnostically. Aim To establish a high-throughput sequencing approach for obtaining high quality miRNA expression profiles from archived Janus serum samples stored for up to 41 years. Further aims were to assess the quantity and quality of small RNAs in the samples, and establish guidelines for the optimal sequencing depth. Methods Total RNA was extracted from eight pilot samples using Trizol and miRNeasy (Qiagen) columns. Sequencing libraries were made using ScriptMiner (EpiCentre) and the samples were sequenced on one HiSeq (Illumina) lane. After adaptor removal the sequences were aligned unguided to the genome. Reads mapping to mirBASE and Ensembl smallRNA features were counted and sequencing saturation curves were calculated. DESeq was used for differential expression analyses. Results High-throughput sequencing results from the Janus samples, with storage times ranging from 13 to 39 years, show that miRNAs are preserved in the samples. High quality miRNA expression profiles, including on average 641 miRNAs per sample, were obtained from our pilot samples. Most of the uniquely mapped reads, on average 84%, are miRNA. We can also identify protein coding RNAs and other groups of small RNA, on average respectively 9% and 6% of the uniquely mapped reads. The preliminary results from sequencing saturation curves, tracking miRNA discovery in each sample as a measure of input reads, have identified a guideline for optimal sequencing depth. Conclusion and future perspectives Here we have shown that the stability, quantity and quantity of long-term stored sera from the Janus Serum Bank are sufficient for obtaining high-quality miRNA expression profiles. High-throughput sequencing approach will be used in the search for miRNA expression profiles as early cancer biomarkers for early diagnosis, improved therapy and surveillance of cancer. Citation Format: Trine B. Rounge, Robert Lyle, Marianne Lauritzen, Kristina Kjaerheim, Tom Grotmol, Tom K. Grimsrud, Randi E. Gislefoss, Steinar Tretli, Giske Ursin, Hilde Langseth. Optimizing small RNAseq of archived serum samples from the Janus Serum Bank - a search for cancer biomarkers. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1501. doi:10.1158/1538-7445.AM2014-1501