tbuckley/cabot-search huggingface dataset:
WHO budget set to reflect new priorities
Authors: P. Brown
Journal: BMJ (1999)

The director general of the World Health Organisation, Gro Harlem Brundtland, will next week ask the organisation's governing body to approve radically overhauled spending plans reflecting her programme of reforms.

The WHO's executive board, which meets from 25January in Geneva, will be presented with budget proposals for the years 2000-1that require an increase of nearly one fifth in voluntary contributions by …
Fibulin-4 Deficiency Results in Ascending Aortic Aneurysms
Authors: Jianbin Huang, Elaine C. Davis, Shelby L. Chapman, Madhusudhan Budatha, Lihua Y. Marmorstein, R. Ann Word, Hiromi Yanagisawa
Journal: Circulation Research (2009)

Rationale : Loss of fibulin-4 during embryogenesis results in perinatal lethality because of aneurysm rupture, and defective elastic fiber assembly has been proposed as an underlying cause for the aneurysm phenotype. However, aneurysms are never seen in mice deficient for elastin, or for fibulin-5, which absence also leads to compromised elastic fibers. Objective : We sought to determine the mechanism of aneurysm development in the absence of fibulin-4 and establish the role of fibulin-4 in aortic development. Methods and Results : We generated germline and smooth muscle cell (SMC)-specific deletion of the fibulin-4 gene in mice ( Fbln4 GKO and Fbln4 SMKO , respectively). Fbln4 GKO and Fbln4 SMKO aortic walls fail to fully differentiate, exhibiting reduced expression of SM-specific contractile genes and focal proliferation of SMCs accompanied by degenerative changes of the medial wall. Marked upregulation of extracellular signal-regulated kinase 1/2 signaling pathway was observed in the aneurysmal wall of Fbln4 GKO and Fbln4 SMKO mice and both mutants developed aneurysm predominantly in the ascending thoracic aorta. In vitro, Fbln4 GKO SMCs exhibit an immature SMC phenotype with a marked reduction of SM-myosin heavy chain and increased proliferative capacity. Conclusions : The vascular phenotype in Fbln4 mutant mice is remarkably similar to a subset of human thoracic aortic aneurysms caused by mutations in SMC contractile genes. Our study provides a potential link between the intrinsic properties of SMCs and aneurysm progression in vivo and supports the dual role of fibulin-4 in the formation of elastic fibers as well as terminal differentiation and maturation of SMCs in the aortic wall.
New recreational drugs and the primary care approach to patients who use them
Authors: A. R. Winstock, L. Mitcheson
Journal: BMJ (2012)

#### Summary points

In recent years, hundreds of new drugs have appeared on the recreational drugs market in Europe.1 Some of these substances, such as ketamine and γ-hydroxybutyrate (GHB), have legitimate medical purposes. These compounds have been joined by many novel psychoactive substances that, combined with their online marketing, pose a challenge for policy makers and health providers.2

The origins of these new drugs vary from synthetic compounds (such as 4-methylmethcathinone, or mephedrone) to traditional herbal products (such as salvia divinorum and kratom). The synthetic compounds are often designed and promoted to avoid contravening drug, medicine, and consumer protection laws. Although mephedrone, other cathinones, and various other synthetic compounds (including several cannabinoids) were classified in the United Kingdom as class B drugs in April 2010, many other new substances with psychoactive potential remain legally available. Rapid changes in legislation, combined with diverse branding and poor quality control, have led to a marked variation in the composition of these products, making it difficult for users and clinicians to identify exactly what is being consumed.

We review some common examples of these new drugs, and provide a framework for conducting an interview in the primary care setting with people who may have problems with their use. Since evidence relating to these substances is …
A Potent Indole-3-Carbinol–Derived Antitumor Agent with Pleiotropic Effects on Multiple Signaling Pathways in Prostate Cancer Cells
Authors: Jing-Ru Weng, Chen-Hsun Tsai, Samuel K. Kulp, Dasheng Wang, Chia-Hui Lin, Hsiao-Ching Yang, Yihui Ma, Aaron Sargeant, Chang-Fang Chiu, Ming-Hsui Tsai, Ching-Shih Chen
Journal: Cancer Research (2007)

Abstract Indole-3-carbinol has emerged as a promising chemopreventive agent due to its in vivo efficacy in various animal models. However, indole-3-carbinol exhibits weak antiproliferative potency and is unstable in acidic milieu. Thus, this study was aimed at exploiting indole-3-carbinol to develop potent antitumor agents with improved chemical stability. This effort culminated in OSU-A9 {[1-(4-chloro-3-nitrobenzenesulfonyl)-1H-indol-3-yl]-methanol}, which is resistant to acid-catalyzed condensation, and exhibits 100-fold higher apoptosis-inducing activity than the parent compound. Relative to indole-3-carbinol, OSU-A9 displays a striking qualitative similarity in its effects on the phosphorylation or expression of multiple signaling targets, including Akt, mitogen-activated protein kinases, Bcl-2 family members, survivin, nuclear factor-κB, cyclin D1, p21, and p27. The ability of OSU-A9 to concurrently modulate this broad range of signaling targets underscores its in vitro and in vivo efficacy in prostate cancer cells. Nevertheless, despite this complex mode of mechanism, normal prostate epithelial cells were less susceptible to the antiproliferative effect of OSU-A9 than PC-3 and LNCaP prostate cancer cells. Treatment of athymic nude mice bearing established s.c. PC-3 xenograft tumors with OSU-A9 at 10 and 25 mg/kg i.p. for 42 days resulted in a 65% and 85%, respectively, suppression of tumor growth. Western blot analysis of representative biomarkers in tumor lysates revealed significant reductions in the intratumoral levels of phosphorylated (p-) Akt, Bcl-xL, and RelA, accompanied by robust increases in p-p38 levels. In conclusion, the ability of OSU-A9 to target multiple aspects of cancer cell survival with high potency suggests its clinical value in prostate cancer therapy. [Cancer Res 2007;67(16):7815–24]
Mechanisms mediating the heart rate response to hypoxemia.
Authors: H Kato, A S Menon, A S Slutsky
Journal: Circulation (1988)

We studied the effect of phasic pulmonary afferent information on heart rate (HR) during a progressive reduction in oxygen saturation (SaO2). The Hering-Breuer reflex was evaluated with the use of the ratio of apnea duration after lung inflation to the preceding expiratory time (dT). Phasic afferent activity was stopped in anesthetized, paralyzed dogs by constant-flow ventilation (CFV), a technique that removes cyclic changes in lung volume. During normocapnic (PaCO2 = 36.4 +/- 1.1 mm Hg) spontaneous breathing, there was a wide variability in HR response, with a mean delta HR/delta SaO2 (+/- SE) of 0.62 +/- 0.27 beats/min/% (values greater than 0 indicate a tachycardiac response). There was a good correlation between delta HR/delta SaO2 and dT (r = .79). Mean delta HR/delta SaO2 for the combined normocapnic and hypercapnic studies during CFV was lower (-1.32 +/- 0.19 bpm/%) than that during spontaneous breathing (0.23 +/- 0.19, p less than .0001). We suggest that the HR response to hypoxemia is strongly related to the strength of the Hering-Breuer reflex, which may explain the large interdog variability in HR responses.
P760 HIGH-THROUGHPUT AND ULTRASENSITIVE NEXT-GENERATION PCR ASSAY FOR THE QUANTIFICATION OF THE HEPATITIS C VIRUS MUTATION AT CORE AMINO ACID 70
Authors: M. Mukaide, M. Sugiyama, M. Korenaga, K. Murata, T. Kanto, N. Masaki, M. Mizokami
Journal: Journal of Hepatology (2014)
Multifocal Ectopic Purkinje-Related Premature Contractions
Authors: Gabriel Laurent, Samuel Saal, Mohamed Yassine Amarouch, Delphine M. Béziau, Roos F.J. Marsman, Laurence Faivre, Julien Barc, Christian Dina, Geraldine Bertaux, Olivier Barthez, Christel Thauvin-Robinet, Philippe Charron, Véronique Fressart, Alice Maltret, Elisabeth Villain, Estelle Baron, Jean Mérot, Rodolphe Turpault, Yves Coudière, Flavien Charpentier, Jean-Jacques Schott, Gildas Loussouarn, Arthur A.M. Wilde, Jean-Eric Wolf, Isabelle Baró, Florence Kyndt, Vincent Probst
Journal: Journal of the American College of Cardiology (2012)
989 PREDISPOSING FACTORS FOR POOR CLINICAL OUTCOME OF HEPATITIS B VIRUS ASSOCIATED HEPATOCELLULAR CARCINOMA FOLLOWING CURATIVE RESECTION: FOCUSED ON THE GENOMIC CHANGES IN HEPATITIS B VIRUS
Authors: P. Mathews, Y.-H. Chung, J.A. Kim, D. Lee, J.-H. Lee, H. Lyu, Y.-J. Jin, W. Park, E. Jaffee, L. Zheng, E. Yu, Y.J. Lee
Journal: Journal of Hepatology (2011)
Simultaneous Red Cell and Plasma Protein Indicator-Dilution Curves Across the Peripheral Circulation During Open-Heart Surgery
Authors: STANLEY GIANNELLI, STEPHEN M. AYRES, WILLIAM I. WOLFF, META BUEHLER, E. FOSTER CONKLIN
Journal: Circulation (1966)

Data have been presented showing the applicability of indicator-dilution technique to the entire human peripheral circulation during open-heart surgery. Initial results from simultaneous tagged red cell and plasma protein indicator-dilution curves demonstrate a consistently greater volume of distribution for plasma proteins than for red cells.
Terbinafine (LamisilR) treatment of toenail onychomycosis in patients with insulin-dependent and non-insulin-dependent diabetes mellitus: a multicentre trial
Authors: B. Farkas, C. Paul, A. Dobozy, J. Hunyadi, A. Horvath, G. Fekete
Journal: British Journal of Dermatology (2002)

Journal Article Terbinafine (Lamisil®) treatment of toenail onychomycosis in patients with insulin‐dependent and non‐insulin‐dependent diabetes mellitus: a multicentre trial Get access B. Farkas, B. Farkas Department of Dermatology, Pécs University Medical Centre, Kodály u. 20, H‐7624 Pécs, Hungary Prof. Dr Beatrix Farkas. E‐mail: farkasb@derma.pote.hu Search for other works by this author on: Oxford Academic Google Scholar C. Paul, C. Paul Clinical Research and Development, Novartis Pharma AG, Basel, Switzerland Search for other works by this author on: Oxford Academic Google Scholar A. Dobozy, A. Dobozy Department of Dermatology, Albert Szent‐Györgyi University Medical Centre, Szeged, Hungary Search for other works by this author on: Oxford Academic Google Scholar J. Hunyadi, J. Hunyadi Department of Dermatology, Debrecen University Medical Centre, Debrecen, Hungary Search for other works by this author on: Oxford Academic Google Scholar A. Horváth, A. Horváth Department of Dermatology, Semmelweis University, Budapest, Hungary Search for other works by this author on: Oxford Academic Google Scholar G. Fekete G. Fekete Department of Dermatology, Petz Aladár Hospital, Györ, Hungary Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 146, Issue 2, 1 February 2002, Pages 254–260, https://doi.org/10.1046/j.1365-2133.2002.04606.x Published: 01 February 2002 Article history Accepted: 01 October 2001 Published: 01 February 2002
Investigation of Arrhythmia Markers and KCNJ8-S422L Gene Mutation in a Population with Early Repolarization Pattern on ECG
Authors: Emrah Ermiş, Selami Demirelli, Emrah İpek, Çavlan Çiftçi, Veysel Sabri Hançer, Esra Poyraz
Journal: Journal of the American College of Cardiology (2013)
What is (and what is not) a COPD exacerbation: thoughts from the new GOLD guidelines
Authors: J R Hurst, J A Wedzicha
Journal: Thorax (2007)

Definition of what is (and what is not) a COPD exacerbation

During November 2006 an updated version of the World Health Organisation/US National Heart Lung and Blood Institute global initiative for chronic obstructive lung disease (GOLD) guideline was made available online.1 We applaud those involved in creating a living document which has done much to raise the profile of this devastating disease. For many years chronic obstructive pulmonary disease (COPD) was a neglected condition, but research output is now considerable and there have been many developments in the 5 years since the first GOLD report of 2001.2 It is widely appreciated that these include an increased understanding of the pathobiology of COPD and the availability of new agents in our evidence-based therapeutic armamentarium. So what else is new in the 2006 GOLD update? 

First, and perhaps most importantly, the definition of COPD and the staging classification have been revised. COPD is now defined as a “preventable and treatable disease with some significant extrapulmonary effects that may contribute to the severity in individual patients. Its pulmonary component is characterised by airflow limitation that is not fully reversible. The airflow limitation is usually progressive and associated with an abnormal inflammatory response of the lung to noxious particles or gases”.1 Although somewhat lengthy, this change of emphasis reflects an admirable attempt to dispel therapeutic nihilism with the …
ALTERATIONS IN THE BLOOD COAGULATION SYSTEM INDUCED BY BACTERIAL ENDOTOXINS
Authors: Donald G. McKay, Sandor S. Shapiro, Jacob N. Shanberge
Journal: The Journal of Experimental Medicine (1958)

Bacterial endotoxins in vitro are capable of shortening the coagulation time of normal whole blood, native platelet-rich and platelet-poor plasma, and the blood of a hemophilic patient in silicone but not in glass. The point in the coagulation system at which the endotoxins act has not been found but the search has been narrowed by the demonstration that these materials act independently of leukocytes and red blood cells, and do not act as preformed thromboplastin or thrombin. The shortening of the coagulation time in vivo 4 hours after endotoxin injection is probably through a different mechanism than in vitro.
An Address on Some of the Applications of the Spectroscope to Medicine
Authors: C. A. MacMunn
Journal: BMJ (1891)

TIlB B-RITISH MEDICAL JOU-RNAL.3 alkali albumen, and the bacilli themselves afterwards sepa- rated by filtration through porcelain, the filtrate contains a mixture of proto-and deutero-albumose, and a trace of pep- tone formed by the action of the bacilli on the albumen.The albumoses produce, like those of snake poison, much local cedema, sluggishness, coma, and death.Like the venomalbumose, its activity is lessened, but not destroyed, by boil- ing.But, in addition to these substances, he has obtained aIn alkaloid whichl has tlhe same actioin as the albumose, but much more powerful, and this alkaloid, he thinks, is present in a nascent condition in the albumose, and is separated from it by the tissues of the living animal into which it has been introduced.Wlhether something .of the same sort exists in serpent venom or not one cannot say, but the analogies between it and the products of disease germs are becoming every day more apparent, and it seems highly probable that wlhile studies of serpent venom may throw light on the pro- ducts of disease, a "study of the latter may lead to the dis- covery of an efficient antidote to the former.
Plasma cholesterol is hyperresponsive to statin in ABCG5/ABCG8 transgenic mice
Authors: Weiqing Tang, Yinyan Ma, Liqing Yu
Journal: Hepatology (2006)

Interindividual variation exists in response to statin therapy. It has been hypothesized that subjects with higher baseline cholesterol synthesis rates are more sensitive to statins. To directly test this hypothesis, mice overexpressing the heterodimeric ATP-binding cassette (ABC) transporter G5/G8 (G5G8(Tg) mice) were treated with lovastatin because they have a compensatory increase in cholesterol biosynthesis as a result of increased cholesterol excretion into bile and feces. As expected, lovastatin treatment did not alter plasma and hepatic cholesterol levels in wild-type mice. Interestingly, this treatment significantly reduced plasma concentration and hepatic content of cholesterol by 42% and 17.3%, respectively, in the statin-treated versus untreated G5G8(Tg) mice despite a greater feedback upregulation of genes in the pathway of cholesterol biosynthesis in the lovastatin-treated G5G8(Tg) mice. The reduced plasma cholesterol concentration is unlikely to be attributed to LDL and HDL receptors because the protein levels of both receptors remained unchanged. Surprisingly, statin treatment resulted in an increase in biliary cholesterol concentration, which was associated with an upregulation in hepatic mRNA and protein levels of ABCG5 and ABCG8, and in hepatic mRNA levels of Niemann-Pick C1-Like 1 (NPC1L1), a gene that is required for intestinal cholesterol absorption. In conclusion, mice with higher endogenous cholesterol synthesis rates are more sensitive to statin. A synergistic hypocholesterolemic effect could be potentially achieved in humans by simultaneously inhibiting cholesterol biosynthesis and promoting ABCG5/ABCG8-mediated cholesterol excretion.
Common sequence variants on 2p15 and Xp11.22 confer susceptibility to prostate cancer
Authors: Julius Gudmundsson, Patrick Sulem, Thorunn Rafnar, Jon T Bergthorsson, Andrei Manolescu, Daniel Gudbjartsson, Bjarni A Agnarsson, Asgeir Sigurdsson, Kristrun R Benediktsdottir, Thorarinn Blondal, Margret Jakobsdottir, Simon N Stacey, Jelena Kostic, Kari T Kristinsson, Birgitta Birgisdottir, Shyamali Ghosh, Droplaug N Magnusdottir, Steinunn Thorlacius, Gudmar Thorleifsson, S Lilly Zheng, Jielin Sun, Bao-Li Chang, J Bradford Elmore, Joan P Breyer, Kate M McReynolds, Kevin M Bradley, Brian L Yaspan, Fredrik Wiklund, Par Stattin, Sara Lindström, Hans-Olov Adami, Shannon K McDonnell, Daniel J Schaid, Julie M Cunningham, Liang Wang, James R Cerhan, Jennifer L St Sauver, Sara D Isaacs, Kathleen E Wiley, Alan W Partin, Patrick C Walsh, Sonia Polo, Manuel Ruiz-Echarri, Sebastian Navarrete, Fernando Fuertes, Berta Saez, Javier Godino, Philip C Weijerman, Dorine W Swinkels, Katja K Aben, J Alfred Witjes, Brian K Suarez, Brian T Helfand, Michael L Frigge, Kristleifur Kristjansson, Carole Ober, Eirikur Jonsson, Gudmundur V Einarsson, Jianfeng Xu, Henrik Gronberg, Jeffrey R Smith, Stephen N Thibodeau, William B Isaacs, William J Catalona, Jose I Mayordomo, Lambertus A Kiemeney, Rosa B Barkardottir, Jeffrey R Gulcher, Unnur Thorsteinsdottir, Augustine Kong, Kari Stefansson
Journal: Nature Genetics (2008)
Do structural changes (eg, collagen/matrix) explain the response to therapeutic exercises in tendinopathy: a systematic review
Authors: Benjamin T Drew, Toby O Smith, Chris Littlewood, Ben Sturrock
Journal: British Journal of Sports Medicine (2012)

Background Previous reviews have highlighted the benefit of loaded therapeutic exercise in the treatment of tendinopathy. Changes in observable structural outcomes have been suggested as a possible explanation for this response to therapeutic exercise. However, the mechanism for the efficacy of therapeutic exercise remains unclear. Objective To systematically review the relationship between the observable structural change and clinical outcomes following therapeutic exercise. Data sources An electronic search of AMED, CiNAHL, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, PEDro and SPORTDiscus was undertaken from their inception to June 2012. Study eligibility criteria Any study design that incorporated observable structural outcomes and clinical outcomes when assessing the effect of therapeutic exercise on participants with tendinopathy. Study appraisal and synthesis methods Included studies were appraised for risk of bias using the tool developed by the Cochrane Back Review Group. Due to heterogeneity of studies, a qualitative synthesis was undertaken. Results Twenty articles describing 625 patients were included. Overall, there is a strong evidence to refute any observable structural change as an explanation for the response to therapeutic exercise when treated by eccentric exercise training. Moderate evidence does exist to support the response of heavy-slow resistance training (HSR). Conclusions and implications of key findings The available literature does not support observable structural change as an explanation for the response of therapeutic exercise except for some support from HSR. Future research should focus on indentifying other explanations including neural, biochemical and myogenic changes. Registration Number Registered with PROSPERO, registration number CRD42011001638.
ANTI-INFLAMMATORY EFFECT OF OLMESARTAN ON CORONARY PLAQUE PROGRESSION, FINDING FROM THE IMPACT OF OLMESARTAN ON PROGRESSION OF CORONARY ATHEROSCLEROSIS: EVALUATION BY INTRAVASCULAR ULTRASOUND (OLIVUS) TRIAL
Authors: Toru Miyoshi, Atsushi Hirohata, Shozo Kusachi, Satoshi Hirohata, Kazufumi Nakamura, Hiroshi Morita, Kengo Kusano, Hiroshi Ito
Journal: Journal of the American College of Cardiology (2011)
Alexithymia, Hemisphericity, and Conjugate Lateral Eye Movements
Authors: Gordon Cole, Paul Bakan
Journal: Psychotherapy and Psychosomatics (1985)

The conjugate lateral eye movements (CLEMs) of 102 university students were measured in conjunction with the administration of the Schalling-Sifneos Personality Scale, a self-report measure of alexithymia. There was a significant positive correlation between CLEM scores and alexithymia scores for all subjects, suggesting the existence of a relationship between right hemisphere activation and alexithymic characteristics. These results are discussed in terms of some theoretical models of alexithymia.
Interpreting measurements of physical function in clinical trials
Authors: M. M Ward
Journal: Annals of the Rheumatic Diseases (2007)

Improving physical functioning is one of the major goals of anti-rheumatic treatment. However, functional limitations can have several different causes, which may differ in their capacity to respond to a given treatment. Functional limitations due to pain or other acute symptoms or signs may be readily reversible with efficacious treatment, while those due to chronic structural changes may be relatively irreversible in the short term. Because measures of physical function characterise the degree of limitation without regard to cause, patients with the same apparent degree of functional limitation may differ greatly in their ability to demonstrate response to treatment. Structural damage accumulates over the course of disease, so measures of functional limitations tend to be less responsive among patients with more longstanding disease. This decreased responsiveness leads to a decreased ability to discriminate between treatments in patients with more longstanding arthritis. In addition, the criteria for minimal clinically important improvement may be underestimated when patients with irreversible functional limitations are included as test subjects, because judgments of improvement may be associated with smaller measured changes in physical functioning. The interpretation of measurements of physical function in clinical trials should consider the composition of the study sample, with attention to the stage of disease and the heterogeneity in disease duration or structural damage among subjects.
COMPARATIVE OUTCOMES OF CATHETER-DIRECTED THROMBOLYSIS PLUS ANTICOAGULATION VERSUS ANTICOAGULATION ALONE IN THE TREATMENT OF PROXIMAL DEEP VEIN THROMBOSIS IN PATIENTS WITH CHRONIC KIDNEY DISEASE
Authors: Yevgeniy Brailovsky, Chad Zack, Huaqing Zhao, Riyaz Bashir
Journal: Journal of the American College of Cardiology (2014)