tbuckley/cabot-search huggingface dataset:
Randomised trial of octreotide for long term management of cirrhosis after variceal haemorrhage
Authors: S. A Jenkins, J. N Baxter, M. Critchley, A. N Kingsnorth, C. A Makin, S. Ellenbogen, J S. Grime, J. G Love, R. Sutton
Journal: BMJ (1997)

<h3>Abstract</h3> <b>Objective:</b> To assess the efficacy of long term octreotide as adjuvant treatment to programmed endoscopic sclerotherapy after acute variceal haemorrhage in cirrhotic portal hypertension. <b>Design:</b> Randomised clinical trial. <b>Setting:</b> University hospital. <b>Subjects:</b> 32 patients with cirrhotic portal hypertension. <b>Interventions:</b> Programmed injection sclerotherapy with subcutaneous octreotide 50 μg twice daily for 6 months, or programmed injection sclerotherapy alone. <b>Main outcome measures:</b> Episodes of recurrent variceal bleeding and survival. <b>Results:</b> Significantly fewer patients receiving combined octreotide and sclerotherapy had episodes of recurrent variceal bleeding compared with patients given sclerotherapy alone (1/16 <i>v</i> 7/16; P=0.037, Fisher9s exact test), and their survival was significantly improved (P&lt;0.02, log rank test); this improvement was maintained for 12 months after the end of the study. Combined treatment also resulted in a sustained decrease in portal pressure (median decrease −6.0 mm Hg, interquartile range −10 to −4.75 mm Hg, P=0.0002) compared with sclerotherapy alone (median increase 1.5 mm Hg, interquartile range 0.25 to 3.25 mm Hg), as well as a significant improvement in liver function as assessed by plasma concentrations of bilirubin, albumin, and alanine aminotransferase and by hepatocyte metabolism of aminopyrine labelled with carbon-14. <b>Conclusion:</b> Long term octreotide may be a valuable adjuvant to endoscopic sclerotherapy for acute variceal haemorrhage in cirrhotic portal hypertension. <h3>Key messages</h3> The long term use of vasoactive drugs as adjuvant treatment after endoscopic sclerotherapy or ligation for acute variceal haemorrhage has been suggested to reduce the risk of variceal rebleeding This randomised trial found that the addition of long term octreotide to endoscopic treatment reduced the rate of recurrent variceal haemorrhage in patients with cirrhotic portal hypertension Octreotide also improved survival after acute variceal haemorrhage in such patients Long term administration of somatostatin analogues offers a promising treatment to prevent recurrent variceal haemorrhage
Abstract 4913: Systematic analysis of LY30-induced sensitization of cancer cells to TRAIL
Authors: Yuan Shi, Lisa Tucker-Kellogg, Jakob White, Shazib Pervaiz
Journal: Cancer Research (2011)

Abstract TRAIL (Tumor necrosis factor-Related Apoptosis Inducing Ligand) can selectively induce apoptosis in cancer cells expressing the TRAIL receptors. However, the problem of TRAIL resistance poses a significant therapeutic challenge. We recently demonstrated that the small molecule compound, LY30, sensitizes human cancer cells to TRAIL induced apoptosis via mechanisms that involve upregulation and/or oligomerization of the death receptors. However, the underlying biology of this phenomenon remains less well defined. Here we describe a mathematical modeling approach to tease out the molecular circuitry in the synergistic response of human cervical cancer cells (HeLa) to LY30 and TRAIL mediated apoptosis. We made use of ODE (Ordinary Differential Equation) to build two distinct pathway models for Hela cells to represent TRAIL-induced apoptosis (TRAIL Model) or LY30-induced cellular modification (LY30 Model) using the existing models and previous data sets. Moreover, in accordance with the experimental settings we integrated the LY30 Model and TRAIL Model as the CTM (Combination Treatment Model). The CTM showed that the level of simulated death correlated well with experimental observations, including the synergistic level of death from the combination treatment. However, simulation and experimental data exhibited numerous mismatches for some molecules in the pathway, such as differences in the slope and onset of the synergistic activation of caspase-8 and caspase-3. Such mismatch implies some flaw in the model and thus led us to additional measurement on the early dynamics of the species involved upstream of the apoptotic pathway. In specific, assessment of cFLIP, an inhibitor of caspase-8 activation, showed slight up-regulation very early after LY30 treatment (1 hour), followed by a significant down-regulation over prolonged exposure. By including such biological phenomenon into the CTM, we are able to improve the agreement between data and simulation while maintaining the consistency in synergistic cell death. Further model analysis revealed the fluctuation of FLIP is regulated by LY30 through a complicated ratio change between two main ROS (Reactive Oxygen Species), superoxide and hydrogen peroxide. These data provide a novel means for assessment of mechanisms for small molecule-induced sensitization of human cancer cells to TRAIL mediated apoptosis, with broader clinical implications. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4913. doi:10.1158/1538-7445.AM2011-4913
Intracellular Signal Transduction Pathway Proteins As Targets for Cancer Therapy
Authors: Alex A. Adjei, Manuel Hidalgo
Journal: Journal of Clinical Oncology (2005)

Circulating cytokines, hormones, and growth factors control all aspects of cell proliferation, differentiation, angiogenesis, apoptosis, and senescence. These chemical signals are propagated from the cell surface to intracellular processes via sequential kinase signaling, arranged in modules that exhibit redundancy and cross talk. This signal transduction system comprising growth factors, transmembrane receptor proteins, and cytoplasmic secondary messengers is often exploited to optimize tumor growth and metastasis in malignancies. Thus, it represents an attractive target for cancer therapy. This review will summarize current knowledge of selected intracellular signaling networks and their role in cancer therapy. The focus will be on pathways for which inhibitory agents are currently undergoing clinical testing. Original data for inclusion in this review were identified through a MEDLINE search of the literature. All papers from 1966 through March 2005 were identified by the following search terms: "signal transduction," "intracellular signaling," "kinases," "proliferation," "growth factors," and "cancer therapy." All original research and review papers related to the role of intracellular signaling in oncogenesis and therapeutic interventions relating to abnormal cell signaling were identified. This search was supplemented by a manual search of the Proceedings of the Annual Meetings of the American Association for Cancer Research, American Society of Clinical Oncology, and the American Association for Cancer Research (AARC)--European Organisation for Research and Treatment of Cancer (EORTC)--National Cancer Institute (NCI) Symposium on New Anticancer Drugs.
Effects of potassium deficiency on renal function in the dog
Authors: Peter H. Abbrecht
Journal: Journal of Clinical Investigation (1969)

Serial determinations of the renal clearance for inulin and para-aminohippuric acid (PAH), maximum renal tubular reabsorptive rate for glucose, maximum urinary concentrating ability, total exchangeable potassium, extracellular volume, and plasma sodium and potassium concentrations were done in seven dogs before and after dietary potassium depletion. The same measurements were also made in two of the dogs during potassium repletion. Inulin and PAH clearances and transport maxima for glucose decreased progressively during depletion. These changes correlated well with both the duration of depletion and the extent of depletion as measured by total exchangeable potassium. Decreases in inulin and PAH clearance closely paralleled each other, suggesting that there might be a renal hemodynamic basis for both effects. The decreases in transport maxima for glucose were greater than those for inulin or PAH clearance, indicating the presence of a defect in the cellular transport mechanism for glucose. In the dogs that were repleted, renal function gradually returned to the predepletion state. No significant changes were found in extracellular volume or plasma sodium concentration during depletion. Renal concentrating ability decreased only moderately during depletion, with the decrease correlating better with plasma potassium concentration than with total exchangeable potassium. This finding contrasts with the marked decrease in concentrating ability and the severe polydipsia and polyuria found in animals depleted of potassium with the aid of corticosteroids. The results of the present study emphasize the importance of considering species differences and the method of producing depletion in interpreting studies of the effects of hypokalemia on renal function.
Mexiletine-quinidine in isolated hearts: an interaction involving the sodium channel
Authors: H J DUFF, N J CANNON, R S SHELDON
Journal: Cardiovascular Research (1989)

Journal Article Mexiletine-quinidine in isolated hearts: an interaction involving the sodium channel Get access H J DUFF, H J DUFF From the Department of Medicine, Division of Cardiology, University of Calgary, Faculty of Medicine, Calgary, Alberta, Canada Address for correspondence and reprints: Dr Henry J Duff, MD, FRCP(C), Department of Medicine, University of Calgary, Health Science Centre, 3330 Hospital Drive NW, Calgary, Alberta T2N 4N1, Canada. Search for other works by this author on: Oxford Academic PubMed Google Scholar N J CANNON, N J CANNON From the Department of Medicine, Division of Cardiology, University of Calgary, Faculty of Medicine, Calgary, Alberta, Canada Search for other works by this author on: Oxford Academic PubMed Google Scholar R S SHELDON R S SHELDON From the Department of Medicine, Division of Cardiology, University of Calgary, Faculty of Medicine, Calgary, Alberta, Canada Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 23, Issue 7, July 1989, Pages 584–592, https://doi.org/10.1093/cvr/23.7.584 Published: 01 July 1989 Article history Accepted: 22 February 1989 Published: 01 July 1989
Comparison of the HDL Subclasses, APO A, APO B, CETP Mass and Activity Levels Between the Patients with Coronary Atherosclerosis and Healthy Subjects Although Having Higher HDL-C Levels
Authors: Tolga Kunak, Ayşegül Ülgen, Erhan Yazıcı, Emrullah Kızıltunç, Hilal Olgun Küçük, Burak Sezenöz, Serkan Ünlü, Adnan Abacı
Journal: Journal of the American College of Cardiology (2013)
Severe reaction on SPT
Authors: E.s. Netti, G. Napoli, E. Damiani, A. Ferrannini, T. Alfredo
Journal: Allergy (2002)

Since their introduction skin prick tests (SPTs) have been fundamental to the diagnosis of allergic diseases. More than a hundred reagents are available now (1). SPTs are considered safe and systemic reactions during their execution are extremely rare (1,2). Here we describe the case of a very severe systemic reaction during SPT to cypress extract. The patient is a 35-year-old nurse who came to our Allergy Department because of itching and diffused erythema, cough, asthma, palpebral–labial edema, and rhinoconjunctivitis. This reaction began after using latex gloves. The patient also referred dyspnoea, conjunctivitis and rhinitis every time she entered the coronary unit in which she worked. Because of a positive history suggesting a latex allergy, a blood sample was collected for latex radioallergosorbant assay (CAP RAST FEIA Pharmacia, Uppsala, Sweden) which was positive, showing a high concentration of specific IgE for latex (90.2 KU/l). Furthermore, the patient referred three months of oculorhinitis and asthma between December and February. For this reason, she received SPTs to common inhalants including cypress at 1/100 w/v (Bayropharm, DHS, Milan, Italy), using a 1-mm tip disposable lancette (Bayer). Wheals less than + + by comparison with histamine 10 mg/ml were considered negative (3). The patient showed a + + + + cypress SPT 3 min after prick test execution, and showed diffused urticaria, dysphonia, dyspnoea and itching hands. The reaction completely faded within 1 h of therapy with intravenous chlorphenamine, intravenous bethamethasone and subcutaneous epinephrine. This is the first case in the literature of a reaction after SPT to cypress. In our clinic we have performed 15 000 cutaneous tests for this allergen without any adverse reactions. Such a systemic reaction after a cutaneous test for cypress might arise from cross-reactivity between latex and cypress antigens. In fact there are common carbohydrate antigens in the extract of Cupressus arizonica and Ficus benjamina latex, to which IgE of patients presenting with cypress allergy would react (4,5). Previous studies have shown that latex SPT is a safe test, not causing any adverse reactions if correctly executed (6,7). In contrast, more recent studies have shown reactions to cutaneous tests for latex, which suggests that tests should be performed in vitro before being performed cutaneously on patients with a history of latex allergy with systemic symptoms (2,8,9). Therefore we propose that patients with severe allergic latex reactions in which allergy to cypress is suspected should undergo specific IgE evaluation for cypress before cutaneous tests in order to avoid systemic reactions. Accepted for publication 13 December 2001
Enhanced catabolic rate and a structural anomaly in the serum IgG of RA patients.
Authors: J Watkins, A J Swannell
Journal: Annals of the Rheumatic Diseases (1972)

Studies of IgG catabolism in patients with RA and SLE have indicated that they may possess enhanced immunological mechanisms for the removal of this protein.This communication reports a preliminary study of IgG catabolism in RA and in health and a parallel study of the catabolism of human IgG proteins in mice.Six patients with seropositive rheumatoid arthritis who were not receiving gold or corticosteroids, were studied.Immunologically pure IgG was isolated from their serum by column chromatography on DEAE-cellulose.Each immunoglobulin preparation was labelled with radioiodine and injected back intravenously into the patient.Some preparations were also injected intraperitoneally in a batch ofmice (20 male; 20 female).The elimination of the isotope was followed by scintillation counting of serum samples (in man) and by whole radiation measurements (in mice).Biological half-lives were measured over 32 days in man and 14 days in the mouse.Individual half-life values in man are shown in Table I.TABLE I Individual half-life values Subjects Age Duration State of Terminal'biological (yrs) of disease disease half-life (days) RA Patients M. N. (F) 42 5 yrs 'Inactive' 20-0 H. T. (M) 32 1 yr 'Inactive' 22-4 I. R. (F) 50 11 yrs Flare 120 R. W.
Pulsed electromagnetic (short-wave) energy therapy.
Authors: G C Goats
Journal: British Journal of Sports Medicine (1989)

Therapy using pulsed electromagnetic energy is now used widely in the UK and many claims are made regarding its clinical effectiveness.The technique de- veloped about 40 years ago from that of continuous short-wave diathermy, to which it is similar in many respects.There are, however, certain important differences between these therapies that influence significantly their clinical application.Continuous short-wave diathermy (SWD) is de- scribed fully elsewhere' ' and relies principally for its therapeutic effect upon the pattern of heating generated deep within the tissues of the patient by a strong oscillating electromagnetic field.Heat is generated by the movement of ions and distortion of molecules and crystal lattices within the field, and by eddy currents induced within the tissues.The electromagnetic field oscillates at a frequency of 27.12 MHz.More energy enters the tissue than is transported away in the circu- lation and tissue easily achieves temperatures within the therapeutic range of 40-450C3.This technique is thus accurately described as diathermy.Pulsed electromagnetic energy therapy (PEMET) cannot correctly be called a diathermy because little or no heating of the tissue occurs.The apparatus oper- ates at the same frequency as continuous SWD but the output is delivered as a train of pulses5.The intense electromagnetic field is thus established only briefly, and during the subsequent period of nil output, any heat produced is dissipated by the circulation6.This technique allows the use of a very high peak power output without the risk of an undesirable in- crease in tissue temperature.Peak power output ap- pears to be more significant biologically than mean output .The therapeutic effects of PEMET appear to depend more upon subtle interactions between the electric and magnetic field and biological tissue than upon heating.These processes are as yet poorly un- derstood, although investigations are continuing.This paper will attempt to describe the apparatus, biophysics and physiological and therapeutic effects of PEMET with reference to the types of condition encountered frequently in sports medicine. ApparatusMany short-wave diathermy units are capable of deliv- ering either a pulsed or continuous output, although some are manufactured to fulfil only one role.The
Regional Alterations in Protein Expression in the Dyssynchronous Failing Heart
Authors: David D. Spragg, Christophe Leclercq, Morteza Loghmani, Owen P. Faris, Richard S. Tunin, Deborah DiSilvestre, Elliot R. McVeigh, Gordon F. Tomaselli, David A. Kass
Journal: Circulation (2003)

Left ventricular (LV) mechanical dyssynchrony induces regional heterogeneity of mechanical load and is an independent predictor of mortality and sudden death in heart failure (HF) patients. We tested whether dyssynchrony also induces localized disparities in the expression of proteins involved with mechanical stress, function, and arrhythmia susceptibility.Eleven dogs underwent tachycardia-induced HF pacing, either from the right atrium or high right ventricular free wall. Whereas global LV dysfunction was similar between groups, LV contractile coordination assessed by tagged MRI was markedly dyssynchronous with right ventricular pacing but synchronous with right atrial pacing. In dyssynchronous failing hearts, the lateral LV endocardium displayed a 2-fold increase in phosphorylated erk mitogen-activated protein kinase expression (with no change in phospho-p38 or phospho-jnk), a 30% decline in sarcoplasmic reticulum Ca2+-ATPase, an 80% reduction in phospholamban, and a 60% reduction in the gap junction protein connexin43, relative to neighboring myocardial segments. In contrast, hearts from both right atrial-paced HF dogs and an additional 4 noninstrumented control animals showed minimal regional variability in protein expression.LV dyssynchrony in failing hearts generates myocardial protein dysregulation concentrated in the late-activated, high-stress lateral endocardium. Such molecular polarization within the LV creates transmural and transchamber expression gradients of calcium handling and gap junction proteins that may worsen chamber function and arrhythmia susceptibility.
Plasma Vitamin B <sub>6</sub> and Risk of Myocardial Infarction in Women
Authors: John H. Page, Jing Ma, Stephanie E. Chiuve, Meir J. Stampfer, Jacob Selhub, JoAnn E. Manson, Eric B. Rimm
Journal: Circulation (2009)

Background— We prospectively evaluated the relationships between fasting plasma levels of vitamin B 6 , as pyridoxal phosphate, and subsequent myocardial infarction risk in women. Methods and Results— Among 32 826 women who provided blood samples between 1989 and 1990 (27% of the original 1976 cohort), 239 were diagnosed with incident myocardial infarction (fatal and nonfatal) after blood collection but before July 1998. Of these women, 144 had provided a sample after fasting &gt;10 hours. Cases were matched 1:2 by age, cigarette smoking status, and month of and fasting status at the time of blood collection with controls from the same cohort. Conditional logistic regression was used to adjust for potential confounders, including traditional coronary risk factors, anthropometric factors, dietary intake, and selected biomarkers. Median age at blood collection was 63 years. Plasma levels of pyridoxal phosphate were inversely associated with risk of myocardial infarction; the multivariable-adjusted rate ratio for the highest compared with the lowest quartiles (&gt;70 versus &lt;27.9 pmol/mL) was 0.22 (95% confidence interval, 0.09 to 0.55; P for trend=0.05). The association varied by age: among women who were &lt;60 years of age at blood sampling, the rate ratio comparing the highest and lowest quartiles was 0.05 (95% confidence interval, 0.004 to 0.61), whereas among older women, the corresponding rate ratio was 0.36 (95% confidence interval, 0.13 to 1.02). Conclusions— Fasting plasma concentration of pyridoxal phosphate was inversely associated with myocardial infarction risk, an effect that was in part independent of dietary B 6 intake. In addition to dietary vitamin B 6 intake, there are other determinants of plasma vitamin B 6 status, and these factors warrant further research.
Effect of Physical Exercise on Alimentary Lipaemia
Authors: H. Cohen, C. Goldberg
Journal: BMJ (1960)

PETHIDINE AND IPRONLAZIDBso 509After initial enthusiasm, two adverse reports on the efficacy of iproniazid in angina pectoris have appeared (Dewar et al., 1959; Snow and Anderson, 1959).Both papers were based on controlled " double-blind " clinical trials.It seems unlikely that the drug will benefit many patients with angina pectoris.Angina patients are particularly liable to develop cardiac infarction and to be admitted to hospital under the care of physicians not fully acquainted with their previous medical histories, and may be given pethidine for the relief of their pain.It is suggested, in the light of the two cases reported here and that reported by Papp -and Benaim, that iproniazid be reserved for the most intractable cases of angina, and be given only where all other measures have failed.If a patient on iproniazid has to be admitted to hospital for any reason, his introductory letter should state, " No pethidine, please." Sum ayTwo cases are described in which patients receiving iproniazid for angina pectoris were precipitated into rapid and deep coma by the injection of pethidine.In each case intravenous prednisolone appeared to cause immediate and specific reversal of the reaction.
The Book Review
Authors: Lester S. King
Journal: JAMA (1968)

A book review serves two major functions— descriptive and evaluative. It first of all can indicate to the reading public some general idea of the contents and it can offer a critique, an evaluation of merit. The two functions are rather distinct and yet they belong together. The description or indication of contents requires only reporting skill. With technical books (as contrasted with, say, novels) a competent writer can do a fairly good job of telling what the book is about without reading it. Careful study of the table of contents and the preface, as well as the jacket blurb, will enable the experienced reviewer to write a passable notice without glancing at the text. Recently a publishing house brought out a special journal to indicate the contents of new books. It provided facsimile reproductions of the title page of each new book, along with the preface, table of contents,