tbuckley/cabot-search huggingface dataset:
Physiotherapy compared with advice for low back pain: Study supports concept of self management of pain…
Authors: Dan Doherty
Journal: BMJ (2004)

Physiotherapy compared with advice for low back painTargeting "physical factors" alone is not evidence based practice Editor-Frost et al's conclusion that "routine physiotherapy" based on physical factors was no more effective than one session of assessment and advice from a physiotherapist in the management of low back pain is not surprising. 1 But the defensive nature of the responses to this research is. 2 3 This defensiveness arises partly from the perceived rivalry between healthcare professions managing low back pain and the attention grabbing headlines used.In recent years the evidence base has highlighted that low back pain is a multifaceted phenomenon incorporating physical impairment, psychological distress, and social interruption.Thus the effective biopsychosocial management of low back pain should reflect its multifaceted nature and not just focus on the "physical factors," as was done by Frost et al.Being an evidence based practitioner should entail identifying and managing patients' risk factors because risk factors are clinical predictors of outcome and efforts to manage them may reduce the burden of low back pain for those who consult physiotherapists.Because of the recurrent nature of low back pain, talk of a "cure" is unrealistic.Thus the Physiotherapy Pain Association emphasises that patients should be taught skills to self manage their low back problem so that in the long term they are less likely to experience pain related disability and depression, thus improving their quality of life.Receiving passive treatments focusing on physical factors, which show only slight short term benefits, is not in the personal or economic interest of patients with low back pain.As is highlighted by the responses to the study by Frost et al, 3 beliefs about treatment preferences for low back pain vary across professions and can be traced to beliefs about the cause of the problem.
Adjuvant Docetaxel for High-Risk, Node-Negative Breast Cancer
Authors: Miguel Martín, Miguel A Seguí, Antonio Antón, Amparo Ruiz, Manuel Ramos, Encarna Adrover, Ignacio Aranda, Alvaro Rodríguez-Lescure, Regina Grosse, Lourdes Calvo, Agustí Barnadas, Dolores Isla, Purificación Martinez del Prado, Manuel Ruiz Borrego, Jerzy Zaluski, Angels Arcusa, Montserrat Muñoz, José M López Vega, José R Mel, Blanca Munarriz, Cristina Llorca, Carlos Jara, Emilio Alba, Jesús Florián, Junfang Li, José A López García-Asenjo, Amparo Sáez, María José Rios, Sergio Almenar, Gloria Peiró, Ana Lluch
Journal: New England Journal of Medicine (2010)

A regimen of docetaxel, doxorubicin, and cyclophosphamide (TAC) is superior to a regimen of fluorouracil, doxorubicin, and cyclophosphamide (FAC) when used as adjuvant therapy in women with node-positive breast cancer. The value of taxanes in the treatment of node-negative disease has not been determined.We randomly assigned 1060 women with axillary-node-negative breast cancer and at least one high-risk factor for recurrence (according to the 1998 St. Gallen criteria) to treatment with TAC or FAC every 3 weeks for six cycles after surgery. The primary end point was disease-free survival after at least 5 years of follow-up. Secondary end points included overall survival and toxicity.At a median follow-up of 77 months, the proportion of patients alive and disease-free was higher among the 539 women in the TAC group (87.8%) than among the 521 women in the FAC group (81.8%), representing a 32% reduction in the risk of recurrence with TAC (hazard ratio, 0.68; 95% confidence interval [CI], 0.49 to 0.93; P=0.01 by the log-rank test). This benefit was consistent, regardless of hormone-receptor status, menopausal status, or number of high-risk factors. The difference in survival rates (TAC, 95.2%; FAC, 93.5%) was not significant (hazard ratio, 0.76; 95% CI, 0.45 to 1.26); however, the number of events was small (TAC, 26; FAC, 34). Rates of grade 3 or 4 adverse events were 28.2% with TAC and 17.0% with FAC (P<0.001). Toxicity associated with TAC was diminished when primary prophylaxis with granulocyte colony-stimulating factor was provided.As compared with adjuvant FAC, adjuvant TAC improved the rate of disease-free survival among women with high-risk, node-negative breast cancer. (Funded by GEICAM and Sanofi-Aventis; ClinicalTrials.gov number, NCT00121992.).
Abstract 2962: Histone H3.3 mutations drive paediatric glioblastoma through upregulation of MYCN.
Authors: Lynn Bjerke, Alan Mackay, Meera Nandhabalan, Anna Burford, Alexa Jury, Sergey Popov, Dorine Bax, Diana Carvalho, Katy Taylor, Mara Vinci, Illirjana Bajrami, Imelda McGonnell, Chris Lord, Rui Reis, Darren Hargrave, Alan Ashworth, Paul Workman, Chris Jones
Journal: Cancer Research (2013)

Abstract Glioblastomas of children and young adults (pGBM) have a median survival of only 12-15 months and are clinically and biologically distinct from histologically similar cancers in older adults. They are defined by highly specific mutations in the gene encoding the histone H3.3 variant H3F3A, occurring either at or close to key residues marked by methylation for regulation of transcription - K27 and G34. The G34 mutation is specific to tumours of the cerebral hemispheres and is associated with a distinct age of incidence (16 yrs) and gene expression signature compared to K27 and wild-type tumours. ChIP-Seq for the activating K36 trimethylation mark (H3K36me3) mark of G34V mutant KNS42 pGBM cells identified 156 genes differentially bound and expressed compared to wild-type pGBM control. The transcriptional program induced recapitulates that of the developing forebrain, and involves numerous markers of stem cell maintenance, cell fate decisions and self-renewal. Critically, H3F3A G34 mutations cause profound upregulation of MYCN, a potent oncogene which is causative of glioblastomas when expressed in the correct developmental context. A synthetic lethality siRNA screen revealed this driving aberration to be selectively targetable in this patient population by inhibiting kinases responsible for stabilisation of the protein such as AURKA and CHK1. We thus provide the mechanistic explanation for how the first histone gene mutation in human disease biology acts to deliver MYCN, a potent tumorigenic initiator, into a stem cell compartment of the developing forebrain, selectively giving rise to incurable cerebral hemispheric glioblastoma. Employing synthetic lethal approaches to these mutant tumour cells provides a rational way to develop novel and highly selective treatment strategies. Citation Format: Lynn Bjerke, Alan Mackay, Meera Nandhabalan, Anna Burford, Alexa Jury, Sergey Popov, Dorine Bax, Diana Carvalho, Katy Taylor, Mara Vinci, Illirjana Bajrami, Imelda McGonnell, Chris Lord, Rui Reis, Darren Hargrave, Alan Ashworth, Paul Workman, Chris Jones. Histone H3.3 mutations drive paediatric glioblastoma through upregulation of MYCN. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2962. doi:10.1158/1538-7445.AM2013-2962 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
Where have Peptic Lesions Gone?
Authors: A. Sonnenberg, H.J. Wedershoven
Journal: Endoscopy (1983)

The endoscopic diagnoses of the GI unit of a hospital department and of the private practice of a gastroenterologist were compared in a prospective study. Peptic lesions were found twice as often during endoscopy of GI outpatients than of GI inpatients. The results suggest that nowadays diagnosis and treatment of peptic lesions are largely a domain of private practice.
Autoantibodies against glucose-6-phosphate isomerase are not a diagnostic marker for juvenile idiopathic arthritis
Authors: A Schmitt
Journal: Annals of the Rheumatic Diseases (2004)

Rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA) are chronic inflammatory diseases that primarily affect the joints. The triggers that activate autoreactive T and B lymphocytes in arthritic patients are still unknown.1 It has been widely assumed, however, that the autoantigens recognised by arthritogenic lymphocytes are joint-specific. This assumption has been challenged by findings from a murine model of …
Hypoxia-inducible factor–dependent breast cancer–mesenchymal stem cell bidirectional signaling promotes metastasis
Authors: Pallavi Chaturvedi, Daniele M. Gilkes, Carmen Chak Lui Wong, None Kshitiz, Weibo Luo, Huafeng Zhang, Hong Wei, Naoharu Takano, Luana Schito, Andre Levchenko, Gregg L. Semenza
Journal: Journal of Clinical Investigation (2012)

Metastasis involves critical interactions between cancer and stromal cells. Intratumoral hypoxia promotes metastasis through activation of hypoxia-inducible factors (HIFs). We demonstrate that HIFs mediate paracrine signaling between breast cancer cells (BCCs) and mesenchymal stem cells (MSCs) to promote metastasis. In a mouse orthotopic implantation model, MSCs were recruited to primary breast tumors and promoted BCC metastasis to LNs and lungs in a HIF-dependent manner. Coculture of MSCs with BCCs augmented HIF activity in BCCs. Additionally, coculture induced expression of the chemokine CXCL10 in MSCs and the cognate receptor CXCR3 in BCCs, which was augmented by hypoxia. CXCR3 expression was blocked in cocultures treated with neutralizing antibody against CXCL10. Conversely, CXCL10 expression was blocked in MSCs cocultured with BCCs that did not express CXCR3 or HIFs. MSC coculture did not enhance the metastasis of HIF-deficient BCCs. BCCs and MSCs expressed placental growth factor (PGF) and its cognate receptor VEGFR1, respectively, in a HIF-dependent manner, and CXCL10 expression by MSCs was dependent on PGF expression by BCCs. PGF promoted metastasis of BCCs and also facilitated homing of MSCs to tumors. Thus, HIFs mediate complex and bidirectional paracrine signaling between BCCs and MSCs that stimulates breast cancer metastasis.
Insulin-like growth factor system abnormalities in hepatitis C-associated osteosclerosis. Potential insights into increasing bone mass in adults.
Authors: S Khosla, A A Hassoun, B K Baker, F Liu, N N Zein, M P Whyte, C A Reasner, T B Nippoldt, R D Tiegs, R L Hintz, C A Conover
Journal: Journal of Clinical Investigation (1998)

Hepatitis C-associated osteosclerosis (HCAO) is a rare disorder characterized by a marked increase in bone mass during adult life. Despite the rarity of HCAO, understanding the mediator(s) of the skeletal disease is of great interest. The IGFs-I and -II have potent anabolic effects on bone, and alterations in the IGFs and/or IGF-binding proteins (IGFBPs) could be responsible for the increase in bone formation in this disorder. Thus, we assayed sera from seven cases of HCAO for IGF-I, IGF-II, IGF-IIE (an IGF-II precursor), and IGFBPs. The distribution of the serum IGFs and IGFBPs between their ternary ( approximately 150 kD) and binary (approximately 50 kD) complexes was also determined to assess IGF bioavailability. HCAO patients had normal serum levels of IGF-I and -II, but had markedly elevated levels of IGF-IIE. Of the IGFBPs, an increase in IGFBP-2 was unique to these patients and was not found in control hepatitis C or hepatitis B patients. IGF-I and -II in sera from patients with HCAO were carried, as in the case of sera from control subjects, bound to IGFBP-3 in the approximately 150-kD complex, which is retained in the circulation. However, IGF-IIE was predominantly in the approximately 50-kD complex in association with IGFBP-2; this complex can cross the capillary barrier and access target tissues. In vitro, we found that IGF-II enhanced by over threefold IGFBP-2 binding to extracellular matrix produced by human osteoblasts and that in an extracellular matrix-rich environment, the IGF-II/IGFBP-2 complex was as effective as IGF-II alone in stimulating human osteoblast proliferation. Thus, IGFBP-2 may facilitate the targeting of IGFs, and in particular IGF-IIE, to skeletal tissue in HCAO patients, with a subsequent stimulation by IGFs of osteoblast function. Our findings in HCAO suggest a possible means to increase bone mass in patients with osteoporosis.
The Gamma Globulins
Authors: Ezio Merler, Fred S. Rosen
Journal: New England Journal of Medicine (1966)

SINCE the last review of the gamma globulins appeared in the Journal eight years ago,1 2 3 4 a great deal of new knowledge on the structure and function of the immunoglobulins has accumulated. Much of this basic information has come from a study of the myelomatous diseases and the antibody-deficiency syndromes, as well as from the experimental laboratory. It is the purpose of the present review to survey these recent advances and their significance for clinical medicine. This discussion will mainly be restricted to the human gamma globulins, and will be divided into four parts. The first will deal with the structure . . .
NICE decision on dementia drugs was based on "common sense" not evidence, expert says
Authors: Z. Kmietowicz
Journal: BMJ (2010)

The claim by the National Institute for Health and Clinical Excellence that its decision to recommend three acetylcholinesterase inhibitors for people with mild Alzheimer’s disease is based on new evidence of the drugs’ effectiveness is a “red herring,” an expert has said.

Clive Ballard, from King’s College London and director of research at the Alzheimer’s Society, said that the change in the guidance was more a result of a “constructive dialogue” with interested parties and a new interpretation of existing evidence than novel data becoming available.

NICE announced on 6 October that it was recommending that the three drugs—donepezil (marketed as Aricept), galantamine (Reminyl), and rivastigmine (Exelon)—be prescribed for people with mild forms of the disease in updated draft guidance on the treatment of Alzheimer’s disease …
Analysis of transmural trend of myocardial integrated ultrasound backscatter for differentiation of hypertrophic cardiomyopathy and ventricular hypertrophy due to hypertension
Authors: Johji Naito, Tohru Masuyama, Jun Tanouchi, Toshiaki Mano, Hiroya Kondo, Kazuhiro Yamamoto, Reiko Nagano, Masatsugu Hori, Michitoshi Inoue, Takenobu Kamada
Journal: Journal of the American College of Cardiology (1994)
THE IMMUNOLOGICAL SPECIFICITY OF STAPHYLOCOCCI
Authors: L. A. Julianelle, C. W. Wieghard
Journal: The Journal of Experimental Medicine (1935)

1. The carbohydrates derived from Staphylococcus are type specific. 2. The specific carbohydrates fail to induce formation of antibodies in rabbits. 3. Acetylation or adsorption of the carbohydrates on collodion particles does not render them antigenic. 4. The specific carbohydrates may be employed to elicit immediate, type specific, skin reactions in patients with Staphylococcus infection. 5. The protein of Staphylococcus is species specific. 6. The protein is antigenic and stimulates in rabbits species specific antibodies. 7. The protein causes in hypersensitive individuals a species specific, delayed, inflammatory skin reaction.
Noninvasive assessment of cardiac function and ventricular dyssynergy by precordial Q wave mapping in anterior myocardial infarction.
Authors: N A Awan, R R Miller, Z Vera, D A Janzen, E A Amsterdam, D T Mason
Journal: Circulation (1977)

To determine whether multiple lead precordial electrocardiographic recordings offer an improved index for noninvasive estimation of left ventricular hemodynamic function and segmental dyssynergy, precordial mapping was performed in patients with anterior myocardial infarction, and the number of pathologic Q waves (greater than or equal to 0.04 sec) was counted (Q-Index). Left ventricular function was determined by cardiac catheterization and angiography and correlated with the Q-Index. The Q-Index correlated well with dyssynergy extent (r = 0.84) and inversely with ejection fraction (r= -0.87), stroke work index (r = -0.79) and cardiac index (r = =0.66). Three patient groups were defined by Q-Index; group I, 0.04 sec Q complexes less than 15; group II, 15-25; group III, 26-35. Q-Index related closely to functional classification and survival (mean follow-up 12.2 months): group I, 91%; group II, 81%; group III, 40%. Thus 35-lead precordial Q wave mapping with determination of total number of pathologic Q waves permits practical, atraumatic assessment of hemodynamic and functional status and allows prediction of survival in acute and chronic anterior myocardial infarction.
Anti-tumor antibody profile analysis to harness the potentials of B cells in melanomas and the natural humoral immune response
Authors: Beatrix Kotlan, Gabriella Liszkay, Miri Blank, Judit Olasz, Orsolya Csuka, Timea Balatoni, Kinga Borbola, Laszlo Toth, Gyorgy Naszados, Francesco M Marincola, Maria Godeny, Miklos Kasler, Yehuda Shoenfeld
Journal: Journal for ImmunoTherapy of Cancer (2013)

Meeting abstracts Natural humoral immune response and autoimmune mechanisms have great importance in keeping the balance of tumorimmunity, although it has not yet been fully understood. We aimed to reveal potential anti-tumor immune response by immunoglobulin (Ig) profile analysis of patients with
Reducing Blood Cholesterol Levels in Children
Authors: Russell V. Luepker
Journal: JAMA (1995)

The main findings of the multicenter Dietary Intervention Study in Children (DISC) are presented in this issue ofThe Journal.<sup>1</sup>This national project sought to evaluate the safety and efficacy of lowering dietary total fat, saturated fat, and cholesterol in reducing low-density lipoprotein cholesterol (LDL-C) in healthy hypercholesterolemic children. The results have important implications for clinicians who provide care for children, public health officials, and future research in cardiovascular disease prevention. DISC represents an intense effort to modify food intake in healthy free-living children by dietary education of students and their parents. The intervention was well designed and used current behavioral modification techniques to change eating patterns. The results of DISC deserve serious consideration given the study size and quality of the design. The first finding relates to the safety of a low-fat diet, which some have suggested is deleterious to the growth and development of children.<sup>2</sup>DISC
The Health of Adults in the Developing World
Authors: Jane E. Hodgson
Journal: JAMA (1993)

This book concerns the nature and extent of adult ill health in the world with special attention to the developing countries. It represents more than two years of collaborative effort among the Population, Health, and Nutrition Division of the World Bank, the World Health Organization, and the US Centers for Disease Control and Prevention in Atlanta, Ga. The subject, the neglected health issues of adults and the things that kill them, is treated from an international perspective by a total of 14 contributors, representing Australia, Bangladesh, Brazil, New Zealand, the Philippines, the United Kingdom, and the United States. Aware of the vacuum of information and health policy surrounding the topic of adult health in the developing world, the authors seek to overcome this neglect by directing the attention of health policymakers and researchers to the major causes of adult ill health, namely, tuberculosis, cardiovascular disease, cancer, and injuries. At first
A protection against beriberi.
Authors: D Raman
Journal: BMJ (1980)

who continued treatment with tamoxifen alone did not have a response.We agree that tamoxifen-induced hyper- calcaemia probably is not uncommon, but as yet there is no firm evidence to support the suggestion that induced hypercalcaemia is indicative of a good response to tamoxifen or other additive hormones used in the treatment of breast cancer.
Intranasal Desmopressin in Mild Hemophilia A
Authors: VICENTE VICENTE
Journal: Annals of Internal Medicine (1985)

Letters and Corrections1 November 1985Intranasal Desmopressin in Mild Hemophilia AVICENTE VICENTE, M.D., IGNACIO ALBERCA, M.D., ROGELIO GONZALEZ, M.D., ADRIAN ALEGRE, M.D.VICENTE VICENTE, M.D.Search for more papers by this author, IGNACIO ALBERCA, M.D.Search for more papers by this author, ROGELIO GONZALEZ, M.D.Search for more papers by this author, ADRIAN ALEGRE, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-103-5-807 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: Recently, de la Fuente and coworkers (1) confirmed that intravenous administration of desmopressin to persons with mild or moderate hemophilia is useful in the management of hemorragic episodes. In a previous study (2) we have shown that a significant increase of procoagulant activity of factor VIII (FVIII:C) can be obtained after a single standard dose of intranasal desmopressin (260 µg) in persons with mild hemophilia and in healthy persons.In view of such findings, we have treated 11 patients with mild hemophilia (basal values of VIII:C, 5 to 25 U/dL) with a single dose (260 µg) of...References1. DE LA FUENTEKASPERRICKLESHOYER BCFL. Response of patients with mild and moderate hemophilia A and von Willebrand's disease to treatment with desmopressin. Ann Intern Med. 1985;103:6-14. LinkGoogle Scholar2. VICENTEALBERCALOPEZ BORRASCA VIA. Response of factor VIII/von Willebrand factor to intranasal DDAVP in healthy subjects and mild haemophiliacs (with observations in patients with combined deficiency of factors V and VIII). Thromb Haemost. 1982;48:91-3. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: University Hospital Salamanca 37007 Spain PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByClinical Experience in Disorders of Haemostasis 1 November 1985Volume 103, Issue 5Page: 807-808KeywordsHemophiliaHemophilia A Issue Published: 1 November 1985 PDF DownloadLoading ...
Simultaneous activation of the liver X receptors (LXR and LXR ) drives murine collagen-induced arthritis disease pathology
Authors: D. L. Asquith, A. M. Miller, J. Reilly, S. Kerr, P. Welsh, N. Sattar, I. B. McInnes
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Background</h3> It has previously been shown that dual activation of the Liver X Receptors (LXRα and LXRβ) by the agonist, GW3965, enhances pathology in a murine model of collagen-induced arthritis. <h3>Objective</h3> To determine whether LXRα or LXRβ have discrete roles in driving articular inflammation. <h3>Methods</h3> Arthritis was induced in male C57BL/6 wild-type (WT), <i>LXRα−/−</i>, <i>LXRβ−/−</i> and <i>LXRα/β</i> double KO mice by injection with type II collagen and treated with 30 mg/kg of the LXR agonist GW3965 or vehicle control. The mice were monitored for articular inflammation and cartilage degradation by scoring for clinical signs of arthritis and by histological examination of the joints. <h3>Results</h3> Administration of 30 mg/kg GW3965 significantly increases the severity of arthritis in WT but not <i>LXRα−/−</i>, <i>LXRβ−/−</i> or <i>LXRα/β KO</i> mice as assessed by an increase in the clinical score, paw thickness and articular histological analysis. <h3>Conclusion</h3> The proinflammatory effects associated with the administration of GW3965 are mediated specifically through LXRs. The absence of increased disease severity in the <i>LXRα−/−</i> and <i>LXRβ−/−</i> GW3965-treated groups shows for the first time that agonism of both LXRα and LXRβ is required to drive proinflammatory pathways in vivo.
Feasibility, symptoms, adverse effects and complications associated with noninvasive assessment of coronary flow velocity reserve during intravenous adenosine infusion: Experience in 1,222 patients
Authors: Roberta Montisci, Massimo Ruscazio, Carlo Calati, Norma Zedda, Rosa Manzi, Christian Cadeddu, Simone Pisanu, Sabino Illiceto, Luigi Meloni
Journal: Journal of the American College of Cardiology (2003)