tbuckley/cabot-search huggingface dataset:
Bronchoscopic evaluation of peripheral lung tumours.
Authors: R J Shiner, J Rosenman, I Katz, N Reichart, E Hershko, A Yellin
Journal: Thorax (1988)

The results obtained from fibreoptic bronchoscopy preformed under fluoroscopic guidance were evaluated in a prospective study of 71 consecutive patients with a peripheral lung lesion more than 2 cm in diameter on the chest radiograph. A peripheral lung lesion was defined as a lesion that was not seen within the bronchial tree at fibreoptic bronchoscopy. Small volume washings, bronchoalveolar lavage, transbronchial biopsy, and bronchial brushings were carried out and fluid or tissue was sent for cytological or histological examination as appropriate. Of the 71 patients, 51 were subsequently shown to have malignant disease. In 38 of the patients the diagnosis of malignancy was made by bronchoscopy, from histological specimens alone or in conjunction with cytological specimens in 33, from brushings alone in two, and from bronchoalveolar lavage fluid alone in three patients. There were no important complications. Thus fibreoptic bronchoscopy in conjunction with fluoroscopic screening appears to be an effective and safe method for the initial investigation of a peripheral lung lesion more than 2 cm in diameter.
Evaluation of wireless telemonitoring of CPAP therapy in obstructive sleep apnea - TELEPAP study
Authors: Tiago Abreu, Ana Marta Silva, Cristina Canhão, Pinto Paula, Bárbara Cristina
Journal: European Respiratory Journal (2013)

Background : In Obstructive sleep apnea (OSA) compliance rates with CPAP therapy are disappointingly low and since long-term adherence can be predicted by early CPAP use, effective interventions are needed to improve CPAP compliance among patients newly diagnosed with OSA.   Aim:  To determine outcomes of telemonitoring CPAP compliance and efficacy data, compared with standard clinical care and active phone call care.   Material and Methods:  We performed a randomized controlled clinical study, in which 51 patients (42 males; mean age: 54 years old; mean Apnea/hypopnea index (AIH): 36.8/h) newly diagnosed with OSA were consecutively randomized to either standard clinical care (SC) (n=21), active weekly phone call care (PC) (n=18) or telemonitored clinical care (TC) (n=12) with the use of Restraxx™. All patients were submitted to a comprehensive educational program during APAP adaptation. Patients were followed for their first 4 weeks of treatment with APAP (AutoSetSpirit S8; Resmed™) and data regarding compliance and efficacy was analyzed.   Results:  Patients randomized to TC used APAP an average of 5.0 ± 1.8 hours per night (hpn), SC patients averaged 5.1 ± 2.5 hpn and PC patients averaged 3.9 ± 2.6 hpn. Residual AIH was 5.3 ± 3.0 in TC, 5.0 ± 2.5 in SC and 5.6 ± 3.8 in PC. No statistically significant differences were found between the groups regarding CPAP compliance or efficacy (p=0.296 and p=0.825, respectively).   Conclusions:  In the presence of a comprehensive educational program during APAP adaptation, telemonitoring OSA patients didn’t show benefits concerning compliance or efficacy. Standard clinical care, given its lower cost, should be privileged.
Daschle nomination as US health tsar failed because of income tax problems and industry ties
Authors: J. Hopkins Tanne
Journal: BMJ (2009)

The former Democratic Senator Tom Daschle withdrew his nomination as secretary of health and human services and as director of the new White House Office of Health Reform on 4 February after criticism of his late payment of income taxes and his industry ties.

The federal Department of Health and Human Services is a huge agency that accounts for about one quarter of federal spending. It oversees the National Institutes of Health, the Food and Drug Administration, the Centers for Disease Control and Prevention, the Centers for Medicare and Medicaid Services, the US Public Health Service Commissioned Corp of more than 6000 health professionals, and several other agencies.

President Barack Obama has promised to overhaul US health care and had planned a White House office to oversee it, but his plans are now likely to be delayed. 

Mr Daschle was widely considered to be highly qualified for the two posts, and his withdrawal left President Obama and his team without a substitute …
Update in Hematology
Authors: Edward D. Ball
Journal: Annals of Internal Medicine (2003)

Updates from the Annual Session2 December 2003Update in HematologyEdward D. Ball, MDEdward D. Ball, MDFrom the University of California, San Diego, San Diego, California.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-139-11-200312020-00010 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail This year's Update in Hematology focuses on 3 exciting topics in the field: nonablative hematopoietic stem-cell transplantation, targeted therapy, and stem-cell plasticity. Groundbreaking research in the first 2 areas is changing standards of hematology care. The third area, hematopoietic stem-cell plasticity, is showing some early potential for future therapy.Nonmyeloablative Hematopoietic Stem-Cell TransplantationEvery year, thousands of patientstypically patients with acute leukemia, chronic leukemia, non-Hodgkin lymphoma, and multiple myelomareceive a blood or bone marrow transplant to support high-dose chemotherapy. The procedure can be difficult and risky, and the mortality rate after stem-cell transplantation is approximately 12% in the first 100 ...Reference1. Forrester JS, Price MJ, Makkar RR. Stem cell repair of infarcted myocardium: an overview for clinicians. Circulation. 2003;108:1139-45. [PMID: 12952828] CrossrefMedlineGoogle Scholar Author, Article, and Disclosure InformationAuthors: Edward D. Ball, MDAffiliations: From the University of California, San Diego, San Diego, California.Contributing Editor: Jennifer Fisher Wilson.Disclosures: None disclosed.Corresponding Author: Edward D. Ball, MD, Division of Blood and Bone Marrow Transplantation, University of California San Diego, 9310 Campus Point Drive, La Jolla, CA 92093-0960; e-mail, tball@ucsd.edu. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byRegeneration and Repair 2 December 2003Volume 139, Issue 11 Page: 916-922 Keywords Blood cells Bone marrow Cells Chronic myelocytic leukemia Hematopoietic stem cells Lymphoma Multiple myeloma Proteins Stem cells Transplantation ePublished: 2 December 2003 Issue Published: 2 December 2003 Copyright & PermissionsCopyright © 2003 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Prion Diseases and Neurodegeneration
Authors: S B Prusiner, S J DeArmond
Journal: Annual Review of Neuroscience (1994)

Prion diseases are neurodegenerative disorders of humans and animals. In humans, the three forms of the prion disease are manifest as infectious, sporadic, and inherited disorders (Table I) (Prusiner 199 1) . Prions cause six transmissible neurodegenerative diseases of animals (Table 2) and four of humans. Prions are composed largely, if not entirely, of an abnormal isoform of the prion protein (PrP) designated Prpsc. Genetic linkage studies of people suffering from prion diseases as well as investigations with transgenic (Tg) mice expressing mutant PrP genes indicate that mutations in human PrP genes cause neurodegeneration. Studies of Tg mice expressing Syrian hamster (SHa) PrP or chimeric SHalmouse (Mo) PrP suggest that an interaction between Prpsc and homolo­ gous Prpc is important in the replication of prions (Prusiner 199 1) . By using these Tg mice, researchers have found the pattern of Prpsc accumulation in brain to be specific for a particular prion isolate. The existence of distinct isolates or strains of prions poses a conundrum, since a wealth of experimental data indicates that prions are devoid of nucleic acid, yet distinct isolates each possess a unique set of properties characterized by the length of the incubation time, distribution of neuropathologic lesions, and pattern of PrpSc accumulation (Dickinson et al 1968, Fraser & Dickinson 1973, Hecker et al 1992, DeArmond et al 1993) . The unique patterns of Prpsc deposition suggest that each prion isolate E a cell-specific trophism that in tum leads to the conversion of PrP into Prpsc within a restricted population of cells. The synthesis of Prpsc is a post-translational process (Borchelt et al
Transient and Prolonged Increase in Endothelial Permeability Induced by Histamine and Thrombin
Authors: Geerten P. van Nieuw Amerongen, Richard Draijer, Mario A. Vermeer, Victor W. M. van Hinsbergh
Journal: Circulation Research (1998)

Abstract —In the present study, we differentiated between short- and long-term effects of vasoactive compounds on human endothelial permeability in an in vitro model. Histamine induced a rapid and transient (&lt;3 minutes) decrease in barrier function, as evidenced by a decreased transendothelial electrical resistance and an increased passage of 22 Na ions. This increase in permeability was inhibited completely by chelation of intracellular calcium ions by BAPTA-AM and inhibition of calmodulin activity and myosin light chain (MLC) phosphorylation. The presence of serum factors prolonged the barrier dysfunction induced by histamine. Thrombin by itself induced a prolonged barrier dysfunction (&gt;30 minutes) as evidenced by an increased passage of peroxidase and 40 kDa dextran. It was dependent only partially on calcium ions and calmodulin. The protein tyrosine kinase inhibitors genistein and herbimycin A, but not the inactive analogue daidzein, inhibited to a large extent the increase in permeability induced by thrombin. Genistein and BAPTA-AM inhibited the thrombin-induced permeability in an additive way, causing together an almost complete prevention of the thrombin-induced increase in permeability. Inhibition of protein tyrosine kinase was accompanied by a decrease in MLC phosphorylation and a reduction in the extent of F-actin fiber and focal attachment formation. Inhibition of Rho A by C3 transferase toxin reduced both the thrombin-induced barrier dysfunction and MLC phosphorylation. Genistein and C3 transferase toxin did not elevate the cellular cAMP levels. No evidence was found for a significant role of protein kinase C in the thrombin-induced increase in permeability or in the accompanying MLC phosphorylation. These data indicate that in endothelial cell monolayers that respond to histamine in a physiological way, thrombin induces a prolonged increase in permeability by “calcium sensitization,” which involves protein tyrosine phosphorylation and Rho A activation.
Time-Dependent Associations between Iron and Mortality in Hemodialysis Patients
Authors: Kamyar Kalantar-Zadeh, Deborah L. Regidor, Charles J. McAllister, Beckie Michael, David G. Warnock
Journal: Journal of the American Society of Nephrology (2005)

The independent association between the indices of iron stores or administered intravenous iron, both of which vary over time, and survival in patients who are on maintenance hemodialysis (MHD) is not clear. It was hypothesized that the observed associations between moderately high levels of three iron markers (serum ferritin, iron, and iron saturation ratio) or administered intravenous iron and all-cause and cardiovascular death is due to the time-varying confounding effect of malnutrition-inflammation-cachexia syndrome (MICS). Time-dependent Cox regression models were examined using prospectively collected data of the 2-yr (July 2001 to June 2003) historical cohort of 58,058 MHD patients from virtually all DaVita dialysis clinics in the United States. After time-dependent and multivariate adjustment for case mix, administered intravenous iron and erythropoietin doses, and available surrogates of MICS, serum ferritin levels between 200 and 1200 ng/ml (reference 100 to 199 ng/ml), serum iron levels between 60 and 120 μg/ml (reference 50 to 59 μg/ml), and iron saturation ratio between 30 and 50% (reference 45 to 50%) were associated with the lowest all-cause and cardiovascular death risks. Compared with those who did not receive intravenous iron, administered intravenous iron up to 400 mg/mo was associated with improved survival, whereas doses &gt;400 mg/mo tended to be associated with higher death rates. The association between serum ferritin levels &gt;800 ng/ml and mortality in MHD patients seems to be due mostly to the confounding effects of MICS. For ascertaining whether the observed associations between moderate doses of administered intravenous iron and improved survival are causal or due to selection bias by indication, clinical trials are warranted.
The JAK inhibitor tofacitinib suppresses synovial JAK1-STAT signalling in rheumatoid arthritis
Authors: D L Boyle, K Soma, J Hodge, A Kavanaugh, D Mandel, P Mease, R Shurmur, A K Singhal, N Wei, S Rosengren, I Kaplan, S Krishnaswami, Z Luo, J Bradley, G S Firestein
Journal: Annals of the Rheumatic Diseases (2014)

Objective Tofacitinib is an oral Janus kinase (JAK) inhibitor for the treatment of rheumatoid arthritis (RA). The pathways affected by tofacitinib and the effects on gene expression in situ are unknown. Therefore, tofacitinib effects on synovial pathobiology were investigated. Methods A randomised, double-blind, phase II serial synovial biopsy study (A3921073; NCT00976599 ) in patients with RA with an inadequate methotrexate response. Patients on background methotrexate received tofacitinib 10 mg twice daily or placebo for 28 days. Synovial biopsies were performed on Days -7 and 28 and analysed by immunoassay or quantitative PCR. Clinical response was determined by disease activity score and European League Against Rheumatism (EULAR) response on Day 28 in A3921073, and at Month 3 in a long-term extension study (A3921024; NCT00413699 ). Results Tofacitinib exposure led to EULAR moderate to good responses (11/14 patients), while placebo was ineffective (1/14 patients) on Day 28. Tofacitinib treatment significantly reduced synovial mRNA expression of matrix metalloproteinase (MMP)-1 and MMP-3 (p&lt;0.05) and chemokines CCL2, CXCL10 and CXCL13 (p&lt;0.05). No overall changes were observed in synovial inflammation score or the presence of T cells, B cells or macrophages. Changes in synovial phosphorylation of signal transducer and activator of transcription 1 (STAT1) and STAT3 strongly correlated with 4-month clinical responses (p&lt;0.002). Tofacitinib significantly decreased plasma CXCL10 (p&lt;0.005) at Day 28 compared with placebo. Conclusions Tofacitinib reduces metalloproteinase and interferon-regulated gene expression in rheumatoid synovium, and clinical improvement correlates with reductions in STAT1 and STAT3 phosphorylation. JAK1-mediated interferon and interleukin-6 signalling likely play a key role in the synovial response. Trial registration number NCT00976599.
Biomarkers and low risk in heart failure. Data from <scp>COACH</scp> and <scp>TRIUMPH</scp>
Authors: Wouter C. Meijers, Rudolf A. de Boer, Dirk J. van Veldhuisen, Tiny Jaarsma, Hans L. Hillege, Alan S. Maisel, Salvatore Di Somma, Adriaan A. Voors, W. Frank Peacock
Journal: European Journal of Heart Failure (2015)
A Direct Comparison of Insulin Aspart and Insulin Lispro in Patients With Type 1 Diabetes
Authors: Johannes Plank, Andrea Wutte, Gernot Brunner, Andrea Siebenhofer, Barbara Semlitsch, Romana Sommer, Sabine Hirschberger, Thomas R. Pieber
Journal: Diabetes Care (2002)

OBJECTIVE—Both rapid-acting insulin analogs, insulin aspart and lispro, attenuate prandial glucose excursion compared with human soluble insulin. This trial was performed to study the pharmacokinetic and pharmacodynamic profiles of insulin aspart and insulin lispro in type 1 diabetic patients in a direct comparison and to investigate whether the administration of one analog results in favorable effects on prandial blood glucose control. RESEARCH DESIGN AND METHODS—A total of 24 type 1 diabetic patients (age 36 ± 8 years, 16 men and 8 women, BMI 24.3 ± 2.6 kg/m2, diabetes duration 17 ± 11 years, HbA1c 7.9 ± 0.8%) on intensified insulin therapy were recruited into a single-center, randomized, double-blind, two-period, cross-over, glucose clamp trial. The subjects were given an individual need-derived dose of prandial insulin lispro or aspart immediately before a standard mixed meal. RESULTS—With respect to blood glucose excursions from time 0 to 6 h (Excglu(0–6 h)) and from time 0 to 4 h (Excglu(0–4 h)), the pharmacodynamic effect of insulin aspart and insulin lispro can be declared equivalent. This was supported by comparison with maximum postprandial blood glucose excursions (Cmax(glu)) (estimated ratio aspart/lispro ANOVA [90% CI]: 0.95 [0.80–1.13], 0.97 [0.82–1.17], and 1.01 [0.95–1.07] for Excglu(0–6 h), Excglu(0–4 h), and Cmax(glu), respectively). For pharmacokinetic end points (maximum postprandial insulin excursions and area under the curve for insulin from time 0 to 6 h and from time 0 to 4 h), equivalence was indicated. No difference concerning absorption or elimination for time to maximal insulin concentration, time to half-maximum insulin concentration, and time to decrease to 50% of maximum insulin concentration was observed. CONCLUSIONS—These data suggest that in type 1 diabetic patients, both insulin analogs are equally effective for control of postprandial blood glucose excursions.
Structural basis for complement factor H–linked age-related macular degeneration
Authors: Beverly E. Prosser, Steven Johnson, Pietro Roversi, Andrew P. Herbert, Bärbel S. Blaum, Jess Tyrrell, Thomas A. Jowitt, Simon J. Clark, Edward Tarelli, Dušan Uhrín, Paul N. Barlow, Robert B. Sim, Anthony J. Day, Susan M. Lea
Journal: The Journal of Experimental Medicine (2007)

Nearly 50 million people worldwide suffer from age-related macular degeneration (AMD), which causes severe loss of central vision. A single-nucleotide polymorphism in the gene for the complement regulator factor H (FH), which causes a Tyr-to-His substitution at position 402, is linked to ∼50% of attributable risks for AMD. We present the crystal structure of the region of FH containing the polymorphic amino acid His402 in complex with an analogue of the glycosaminoglycans (GAGs) that localize the complement regulator on the cell surface. The structure demonstrates direct coordination of ligand by the disease-associated polymorphic residue, providing a molecular explanation of the genetic observation. This glycan-binding site occupies the center of an extended interaction groove on the regulator's surface, implying multivalent binding of sulfated GAGs. This finding is confirmed by structure-based site-directed mutagenesis, nuclear magnetic resonance–monitored binding experiments performed for both H402 and Y402 variants with this and another model GAG, and analysis of an extended GAG–FH complex.
Costs of rituximab maintenance treatment in patients with refractory rheumatoid arthritis
Authors: A. Risselada, J. Tekstra, Y. K. Teng, P. M. J. Welsing, F. Breedveld, J. M. van Laar, J. W. J. Bijlsma
Journal: Annals of the Rheumatic Diseases (2010)

Rituximab, an anti-CD20 antibody targeting B cells, has been approved as treatment for patients with rheumatoid arthritis (RA) failing treatment with tumour necrosis factor α (TNFα) inhibitors.1 Reports from France, Sweden and the UK stated that rituximab as second line maintenance treatment has lower treatment costs with quality-adjusted life-year (QALY) gains compared to second line TNF inhibitors.2,–,4 Annual medical costs were estimated to be 31% lower for the rituximab strategy (ie, €11.444 and €16.555, respectively).2 However, these investigators used a modelling approach, since the medical and non-medical costs for patients treated with rituximab have not yet been measured.

In the present study, we analysed medical and non-medical costs of rituximab maintenance treatment for a period of 2 years. Patients were participants of a two-centre non-randomised open-label pilot study investigating the safety …
Functional genomics in gastroenterology
Authors: S SCHREIBER
Journal: Gut (2000)

Functional genomics in gastroenterologyIdentification of the DNA structure as a double stranded helix consisting of two nucleotide chain molecules was a milestone in modern molecular biology.This discovery has lead to a rapidly accumulating body of genomic information.The dramatic developments in genetic analysis during the past decade have placed genomics at the forefront of life science research.Large multinational projects (for example, the human genome project) have generated a host of sequence, mapping, and expression data.At the same time, new technologies for automated sequencing, data analysis, genotyping, expression, and protein analysis have been developed.An important result is identification of the genetic aetiology of many monogenic diseases and the enormous progress in the exploration of polygenic disorders.This article reviews the possible applications and future developments of genomic technologies in disorders of the gastrointestinal tract. Development of genomic technologyIn recent years, significant progress in the elucidation of the pathophysiology and aetiology of gastrointestinal disorders has been made.Novel experimental therapies which specifically target single steps in disease relevant regulatory pathways have been designed and are in diVerent stages of clinical development.][4] This process was made possible by technological advances in cell biology, biochemistry, and microbiology and their application to disorders of the gastrointestinal tract.While this methodological approach has produced substantial advances in our understanding of gastrointestinal pathophysiology and increased available treatment options, there are currently several new challenges that call for the development of novel research techniques.(i) The pursuit of hypothesis driven functional research limits the scope of discovery to known genes and pathways and may therefore hamper the elucidation of novel genes and regulatory mechanisms.(ii) Exploration of signalling cascades and their role in disease pathophysiology has reached an enormous degree of complexity.Therefore, distinction between primary and secondary events is impossible in most cases.Even the exact mechanisms of a successful therapeutic application of targeted immune therapies (for example, therapy of Crohn's disease with tumour necrosis factor binding monoclonal antibodies) are not completely clear. 5 6Application of exploratory techniques
How (and why) Darwinian selection restricts environmental feedback
Authors: Mohan Matthen
Journal: Behavioral and Brain Sciences (2001)

Selectionist models date back to Empedocles in Ancient Greece. The novelty of Darwinian selection is that it is able to produce adaptively valuable things without being sensitive to adaptive value. Darwin achieved this result by a restriction of environmental feedback to the replicative process. Immune system selection definitely does not respect this restriction, and it is doubtful whether operant learning does.