tbuckley/cabot-search huggingface dataset:
Medicine information leaflets fail concordance test
Authors: D K T. Raynor
Journal: BMJ (2001)

Medicine information leaflets fail concordance testEditor-Two initiatives about the use of medicines reflect the growing movement towards involving patients in their health care.The first is concordance, which promotes a model of prescribing based on negotiated agreements that respect the patient's perspective. 1 The second is a European directive requiring mandatory patient leaflets with all medicines. 2Manufacturers must produce these comprehensive leaflets, including all datasheet information, in a form understandable to patients.Unfortunately, concordance and such mandatory leaflets seem to be mutually incompatible.Concordance requires that patients be fully informed about their medicines in the widest sense.Perversely, the mandatory leaflets are in most senses narrow and undermine concordance.Firstly, patients only receive the information when they open their medicines.Any information throwing doubt on the appropriateness of the drug therefore comes too late.Secondly, patients need to know the various options for treatment.Currently leaflets include only information about the drug in question.Thirdly, patients need balanced information, but the leaflets present mainly negative information, such as side effects.Other problems exist.Recent research found that nearly a fifth of patients failed to notice the package leaflet.Of those who recalled receiving a leaflet, only two fifths read some of it and two tenths all of it. 3Unlike computer generated pharmacy leaflets (which are used in the United States and Australasia), the leaflets cannot be individualised. 3 Computer generation allows pharmacists to use leaflets as aides mémoire and go through them with patients.The electronic form also gives options for providing access to partially sighted people. 4 Surgery computers are already able to print condition-specific leaflets at doctors' desks. 5 They could be adapted as decision making aids for patients and hence facilitate concordance.The doctor makes a diagnosis and supplies a leaflet, which includes all treatment options.Having read and digested this information, the patient returns to make a decision jointly with the prescriber.This may reduce misunderstandings but might increase the number of consultations.But common conditions such as hypertension already necessitate multiple consultations before long term treatment options are decided.The introduction of comprehensive medicine leaflets is an important development in the provision of information, but the opportunity has been lost to support concordance in medicine taking, which is now endorsed by the NHS Plan.The inadequacies of such leaflets mean that they may become a legal backstop, with patients accessing more relevant, individualised, and wideranging information generated electronically.European law needs amending to reflect this.
Role of IL-17 and regulatory T lymphocytes in a systemic autoimmune disease
Authors: Jens Lohr, Birgit Knoechel, Jing Jing Wang, Alejandro V. Villarino, Abul K. Abbas
Journal: The Journal of Experimental Medicine (2006)

To explore the interactions between regulatory T cells and pathogenic effector cytokines, we have developed a model of a T cell–mediated systemic autoimmune disorder resembling graft-versus-host disease. The cytokine responsible for tissue inflammation in this disorder is interleukin (IL)-17, whereas interferon (IFN)-γ produced by Th1 cells has a protective effect in this setting. Because of the interest in potential therapeutic approaches utilizing transfer of regulatory T cells and inhibition of the IL-2 pathway, we have explored the roles of these in the systemic disease. We demonstrate that the production of IL-17 and tissue infiltration by IL-17–producing cells occur and are even enhanced in the absence of IL-2. Regulatory T cells favor IL-17 production but prevent the disease when administered early in the course by suppressing expansion of T cells. Thus, the pathogenic or protective effects of cytokines and the therapeutic capacity of regulatory T cells are crucially dependent on the timing and the nature of the disease.
Respiratory mechanics studied by forced oscillations during artificial ventilation
Authors: R Peslin, J Felicio da Silva, C Duvivier, F Chabot
Journal: European Respiratory Journal (1993)

Potential advantages of the forced oscillation technique over other methods for monitoring total respiratory mechanics during artificial ventilation are that it does not require patient relaxation, and that additional information may be derived from the frequency dependence of the real (Re) and imaginary (Im) parts of respiratory impedance. We wanted to assess feasibility and usefulness of the forced oscillation technique in this setting and therefore used the approach in 17 intubated patients, mechanically ventilated for acute respiratory failure. Sinusoidal pressure oscillations at 5, 10 and 20 Hz were applied at the airway opening, using a specially devised loudspeaker-type generator placed in parallel with the ventilator. Real and imaginary parts were corrected for the flow-dependent impedance of the endotracheal tube; they usually exhibited large variations during the respiratory cycle, and were computed separately for the inspiratory and expiratory phases. In many instances the real part was larger during inspiration, probably due to the larger respiratory flow, and decreased with increasing frequency. The imaginary part of respiratory impedance usually increased with increasing frequency during expiration, as expected for a predominately elastic system, but often varied little, or even decreased, with increasing frequency during inspiration. In most patients, the data were inconsistent with the usual resistance-inertance-compliance model. A much better fit was obtained with a model featuring central airways and a peripheral pathway in parallel with bronchial compliance. The results obtained with the latter model suggest that dynamic airway compression occurred during passive expiration in a number of patients. We conclude that the use of forced oscillation is relatively easy to implement during mechanical ventilation, that it allows the study of respiratory mechanics at various points in the respiratory cycle, and may help in detecting expiratory flow limitation.
111Indium autologous granulocytes in the detection of inflammatory bowel disease.
Authors: S H Saverymuttu, A M Peters, M E Crofton, H Rees, J P Lavender, H J Hodgson, V S Chadwick
Journal: Gut (1985)

Indium leucocyte scanning and measurement of faecal Indium leucocyte excretion are techniques which have recently been introduced for assessing patients with inflammatory bowel disease. The methodology has recently been made more specific for acute inflammation by labelling pure granulocytes rather than the mixed leucocyte preparation. To determine the accuracy of this modified technique in detecting inflammatory bowel disease, we have prospectively compared Indium granulocyte scanning and faecal In granulocyte excretion with rectal histology and contrast bowel radiology as screening procedures in 100 patients with suspected inflammatory bowel disease. Thirty three patients were shown to have inflammatory bowel disease - 24 with Crohn's disease and nine with ulcerative colitis or indeterminate colitis. Overall the respective sensitivities for detecting inflammatory bowel disease were 97% for faecal Indium granulocyte excretion, 94% for Indium granulocyte scanning, 79% for radiology and 70% for rectal histology. The superiority of In granulocytes over radiology and rectal histology in detecting inflammatory bowel disease was, in the main, due to the difficulty in diagnosing Crohn's with conventional techniques. Although three of the patients with ulcerative colitis and indeterminate colitis had normal sigmoidoscopic appearances - all had abnormal rectal histology. No patient with a non-inflammatory bowel disorder had a positive In granulocyte scan or a raised faecal excretion. These results show that investigations using In granulocytes are accurate in identifying inflammatory bowel disease and offer important advantages over conventional procedures for detecting Crohn's disease.
Poly(ADP‐ribose) Polymerase 1 (PARP1) in Atherosclerosis: From Molecular Mechanisms to Therapeutic Implications
Authors: Suowen Xu, Peter Bai, Peter J. Little, Peiqing Liu
Journal: Medicinal Research Reviews (2013)

Abstract Poly(ADP‐ribosyl)ation reactions, carried out by poly(ADP‐ribose) polymerases (PARPs/ARTDs), are reversible posttranslational modifications impacting on numerous cellular processes (e.g., DNA repair, transcription, metabolism, or immune functions). PARP1 (EC 2.4.2.30), the founding member of PARPs, is particularly important for drug development for its role in DNA repair, cell death, and transcription of proinflammatory genes. Recent studies have established a novel concept that PARP1 is critically involved in the formation and destabilization of atherosclerotic plaques in experimental animal models and in humans. Reduction of PARP1 activity by pharmacological or molecular approaches attenuates atherosclerotic plaque development and enhances plaque stability as well as promotes the regression of pre‐established atherosclerotic plaques. Mechanistically, PARP1 inhibition significantly reduces monocyte differentiation, macrophage recruitment, Sirtuin 1 (SIRT1) inactivation, endothelial dysfunction, neointima formation, foam cell death, and inflammatory responses within plaques, all of which are central to the pathogenesis of atherosclerosis. This article presents an overview of the multiple roles and underlying mechanisms of PARP1 activation (poly(ADP‐ribose) accumulation) in atherosclerosis and emphasizes the therapeutic potential of PARP1 inhibition in preventing or reversing atherosclerosis and its cardiovascular clinical sequalae.
The learning curve for detection of non-polypoid (flat and depressed) colorectal neoplasms
Authors: Sarah K McGill, Tonya Kaltenbach, Shai Friedland, Roy Soetikno
Journal: Gut (2013)

We read with interest the two excellent studies on interval colorectal cancers (CRC) following colonoscopy and wish to present important data relevant to the prevention of interval CRC. In a pooled multicohort analysis, Robertson and coauthors found that invasive cancer was diagnosed in 0.6% of patients after clearing colonoscopy among eight large North American trials, and concluded that half of these were likely missed lesions.1 In a population-based study, le Clercq and coauthors reported that CRC found following colonoscopy were more likely to have non-polypoid morphology than prevalent cancers.2

We previously described that non-polypoid colorectal neoplasms (NP-CRN) harbour more advanced pathology than polypoid neoplasms.3 Indeed, due to their subtle appearance, NP-CRN may be a key contributor to interval CRC. The learning curve in their detection is largely unknown.

Using available data, we summarised the learning curve (see figure 1) for the detection …
Evidence for Joint Genetic Control of Insulin Sensitivity and Systolic Blood Pressure in Hispanic Families With a Hypertensive Proband
Authors: Anny H. Xiang, Stanley P. Azen, Leslie J. Raffel, Sylvia Tan, Li Shu-Chuan Cheng, Justo Diaz, Edgar Toscano, Paula C. Henderson, Howard N. Hodis, Willa A. Hsueh, Jerome I. Rotter, Thomas A. Buchanan
Journal: Circulation (2001)

Background —The clustering of hypertension, insulin resistance, and obesity remains unexplained. We tested for genetic and nongenetic influences on the association among these traits in Hispanic families with hypertension. Methods and Results —Blood pressure and body mass index (BMI) were measured in 331 members of 73 Hispanic families in which an index case (proband) had hypertension. Insulin sensitivity (S I ) was measured by euglycemic clamp in 287 probands and their spouses (parents’ generation) or their adult offspring. Correlation analysis examined relationships among traits within and between generations. Path analysis estimated genetic and nongenetic contributions to variability in systolic blood pressure (SBP), S I , and the correlation between them. In the offspring, there was a significant correlation between individuals for each trait, as well as significant correlations within and between individuals for all possible pairs of traits. Between generations, SBP, S I , and BMI in parents correlated with the same traits in their offspring; BMI in parents correlated with S I and SBP in offspring; and S I in parents correlated with SBP in offspring. Path analysis estimated that among offspring, genetic effects unrelated to BMI accounted for 60.8% of the variation in SBP, 36.8% of the variation in S I , and 31.5% of the correlation between SBP and S I after adjustment for age and sex. Heritable effects related to BMI accounted for an additional 14.0% of variation in SBP, 26.8% of variation in S I , and 56.3% of variation in their correlation. Conclusions —Clustering of hypertension and insulin resistance in Hispanic Americans is accounted for in part by heritable factors both associated with and independent of BMI.
Embryo Ethics — The Moral Logic of Stem-Cell Research
Authors: Michael J Sandel
Journal: New England Journal of Medicine (2004)

The Stem-Cell DebateAt first glance, the case for federal funding of embryonic stem-cell research seems too obvious to need defending. Why should the government refuse to support research that holds promise for the treatment and cure of devastating conditions such as Parkinson's disease, Alzheimer's disease, diabetes, and spinal cord injury? Critics of stem-cell research offer two main objections: some hold that despite its worthy ends, stem-cell research is wrong because it involves the destruction of human embryos; others worry that even if research on embryos is not wrong in itself, it will open the way to a slippery slope . . .
Raised serum APRIL levels in patients with systemic lupus erythematosus
Authors: T Koyama
Journal: Annals of the Rheumatic Diseases (2004)

To determine whether serum levels of a proliferation-inducing ligand (APRIL) are raised in patients with systemic lupus erythematosus (SLE) and correlate with autoantibody titres or disease activity, or both.Serum samples from 48 patients with SLE, 41 normal healthy subjects, and 21 patients with rheumatoid arthritis (RA) were assayed for APRIL by enzyme linked immunosorbent assay. Medical charts were retrospectively reviewed for autoantibody titres and immunoglobulin levels. Disease activity was assessed using the British Isles Lupus Assessment Group (BILAG) index.The APRIL levels in the serum samples from patients with SLE were significantly higher than in those from healthy controls and those from patients with RA. Serum APRIL levels did not correlate with serum IgG and IgM levels, but had a tendency to correlate with anti-double stranded DNA antibody titres. Moreover, serum APRIL levels correlated significantly with musculoskeletal manifestations among patients with SLE when assessed by the BILAG index.APRIL may be an important factor in raised autoantibody titres and musculoskeletal disease in patients with SLE. Patients with raised serum APRIL levels may be ideal candidates for therapeutic targeting of APRIL.
Selective adenosine A3 receptor stimulation reduces ischemic myocardial injury in the rabbit heart
Authors: W Tracey
Journal: Cardiovascular Research (1997)

Objective: The aim of this study was to determine whether selective activation of the adenosine A3 receptor reduces infarct size in a Langendorff model of myocardial ischemia-reperfusion injury. Methods: Buffer-perfused rabbit hearts were exposed to 30 min regional ischemia and 120 min of reperfusion. Infarct size was measured by tetrazolium staining and normalized for area-at-risk (IA/AAR). Results: Preconditioning by 5 min global ischemia and 10 min reperfusion reduced infarct size (IA/AAR) to 19±4% (controls: 67±5%). Replacing global ischemia with 5 min perfusion of the rabbit A3-selective agonist, IB-MECA (A3Ki: 2 nM; A1Ki: 30 nM) elicited a concentration-dependent reduction in infarct size; 50 nM IB-MECA reduced IA/AAR to 24±4%. The A1-selective agonist, R-PIA (25 nM) reduced IA/AAR to a similar extent (21±6%). However, while the cardioprotective effect of R-PIA was significantly inhibited (54±7% IA/AAR) by the rabbit A1-selective antagonist, BWA1433 (50 nM), the IB-MECA-dependent cardioprotection was unaffected (28±6% IA/AAR). A non-selective (A1 vs. A3) concentration of BWA1433 (5 μM) significantly attenuated the IB-MECA-dependent cardioprotection (61±7% IA/AAR). Conclusions: These data clearly demonstrate that selective A3 receptor activation provides cardioprotection from ischemia-reperfusion injury in the rabbit heart. Furthermore, the degree of A3-dependent cardioprotection is similar to that provided by A1 receptor stimulation or ischemic preconditioning.
Cost-Utility of Three Approaches to the Diagnosis of Sleep Apnea: Polysomnography, Home Testing, and Empirical Therapy
Authors: Ronald D. Chervin
Journal: Annals of Internal Medicine (1999)

Background: Obstructive sleep apnea syndrome (OSAS) is usually diagnosed with overnight polysomnography in a sleep laboratory. Home sleep studies can be performed at lower cost, but results are somewhat less reliable. Bedside diagnosis of OSAS without any testing has also been discussed. Objective: To model the costs and utility of laboratory polysomnography, home study, and no testing during the 5 years after initial evaluation for OSAS. Design: Cost-utility analysis. Data Sources: Published data. Target Population: Hypothetical cohort of persons suspected of having OSAS. Time Horizon: The 5 years after initial evaluation for OSAS. Perspective: Societal. Intervention: Nasal continuous positive airway pressure when OSAS was diagnosed. Measurements: Quality of life, survival and charges (as proxies for costs) for each diagnostic method. Results of Base-Case Analysis: Under almost all modeled conditions, polysomnography provided maximal quality-adjusted life-years in the 5 years after the initial diagnostic evaluation. The incremental charges for polysomnography over home study or no testing were about $13 400 and $9200, respectively, per quality-adjusted life-year gained during this period. Results of Sensitivity Analysis: Results were sensitive to the utility of treatment in the absence of OSAS. Conclusions: The cost–utility of polysomnography instead of home study or no testing in the diagnosis of OSAS compares favorably with that of other procedures for which society judges the added utility per dollar spent to be worthwhile. More precise determination of certain key variables in this model should be a goal of future research.
RhoB Determines Tumor Aggressiveness in a Murine EGFRL858R-Induced Adenocarcinoma Model and Is a Potential Prognostic Biomarker for Lepidic Lung Cancer
Authors: Olivier Calvayrac, Anne Pradines, Isabelle Raymond-Letron, Isabelle Rouquette, Emilie Bousquet, Valérie Lauwers-Cances, Thomas Filleron, Jacques Cadranel, Michèle Beau-Faller, Anne Casanova, Julie Milia, Gilles Favre, Julien Mazières
Journal: Clinical Cancer Research (2014)

A crucial event in lung adenocarcinoma progression is the switch from an aerogenous spread toward an infiltrating tumor. Loss of RhoB expression has been suggested to be critical for lung cancer invasion. Here, we tested RhoB expression as a prognostic biomarker in non-small cell lung cancer (NSCLC) with a special focus on lepidic pattern.We analyzed RhoB expression using both IHC and RT-qPCR in two series of operated patients (n = 100 and 48, respectively) and in a series of advanced lepidic adenocarcinoma (n = 31) from different hospitals. Next, we examined the role of RhoB in lung cancer progression in transgenic mice that express inducible EGFR(L858R) crossed with Rhob null mice.We identified that loss of RhoB expression was strongly associated with worse survival (P = 0.0001) and progression-free survival (P < 0.001) in the first series. We then confirmed these results after multivariate analyses of the second series. In the series of adenocarcinoma with lepidic features issued from a clinical trial (IFCT-0401), we showed that loss of RhoB expression was associated with higher aggressiveness of stage IV. Finally, we showed that EGFR(L858R)/Rhob(+/+) mice developed mainly diffuse lung tumors with a lepidic pattern, whereas EGFR(L858R)/Rhob(+/-) and EGFR(L858R)/Rhob(-/-) developed a greater number of tumors, and aggressive adenocarcinomas with invasive properties.We showed that RhoB is not only a strong prognostic factor in NSCLC but it is also critical for the acquisition of an aggressive phenotype of adenocarcinoma.
Effects of a Multimodal Management Strategy for Acute Mesenteric Ischemia on Survival and Intestinal Failure
Authors: Olivier Corcos, Yves Castier, Annie Sibert, Sebastien Gaujoux, Maxime Ronot, Francisca Joly, Catherine Paugam, Frederic Bretagnol, Mohamed Abdel–Rehim, Fadi Francis, Vanessa Bondjemah, Marianne Ferron, Magaly Zappa, Aurelien Amiot, Carmen Stefanescu, Guy Leseche, Jean–Pierre Marmuse, Jacques Belghiti, Philippe Ruszniewski, Valerie Vilgrain, Yves Panis, Jean Mantz, Yoram Bouhnik
Journal: Clinical Gastroenterology and Hepatology (2012)
The 41st David A. Karnofsky Memorial Award Lecture: Academic Research Worldwide—Quo Vadis?
Authors: Martine J. Piccart-Gebhart
Journal: Journal of Clinical Oncology (2013)

Academiaplaysavitalrole inrandomizedclinical trials; by counterbalancing commercial interests, it can act as a guardian to protect patients’ needs. Moreover, the relationship between investigators and patients enrolling onto clinical trials can be viewed as one based on an implicit ethical contract. Its premise is that the primary objective of randomized clinical trials is to improve patient outcome, free from bias, whether commercial or academic. Indeed, more than 50 years of sustained commitment to randomized clinical trials in early breastcancerhavecontributedtothedecliningmortality from the disease in the Western world and would not have been possible without this understanding. The Breast International Group (BIG), created in 1996, is an umbrella organization harnessing the efforts and supporting the activities of its almost 50 national and international cooperative group members worldwide. It has become a major actor in the conduct of early breast cancer trials, particularly those run in partnership with the pharmaceutical industry for the global registration of new anticancer drugs in the adjuvant setting. The HERA (Herceptin Adjuvant) trial (NCT00045032) is one such example, contributing to the registration of adjuvant trastuzumab in 39 countries in fewer than 4 years. BIG also supports clinical trials sponsored by its academic member groups and facilitates collaboration between international researchers and US cooperative groups. The International Breast Cancer Study Group (IBCSG) –led SOFT (Suppression of Ovarian Function Trial) and TEXT (Tamoxifen and Exemestane Trial) trials (NCT00066690 and NCT00963417, respectively) evaluating endocrine therapies for 5,738 premenopausal women are cases in point. BIG is therefore uniquely positioned to examine how academic research in oncology has evolved over the last two decades, to alert the oncology community about the dangerous shift toward commercially oriented research, and to propose some new routes for empowering academics at a critical time when the remarkable progress in elucidating cancer complexity, stemming from The Cancer Genome Atlas (TCGA) project, needs to be translated into new and effective clinical applications.
Detection of trisomy 12 in CD34+ progenitor cells in a patient with B-cell chronic lymphocytic leukemia by florescence in situ hybridization
Authors: B. Gahn, C. Schäfer, J. Neef, C. Troff, M. Feuring-Buske, W. Hiddemann, B. Wörmann
Journal: Annals of Oncology (1997)