tbuckley/cabot-search huggingface dataset:
Diagnosis and Management of Stable Chronic Obstructive Pulmonary Disease: A Clinical Practice Guideline from the American College of Physicians
Authors: Amir Qaseem, Vincenza Snow, Paul Shekelle, Katherine Sherif, Timothy J. Wilt, Steven Weinberger, Douglas K. Owens
Journal: Annals of Internal Medicine (2007)

Recommendation 1: In patients with respiratory symptoms, particularly dyspnea, spirometry should be performed to diagnose airflow obstruction. Spirometry should not be used to screen for airflow obstruction in asymptomatic individuals. (Grade: strong recommendation, moderate-quality evidence.) Recommendation 2: Treatment for stable chronic obstructive pulmonary disease (COPD) should be reserved for patients who have respiratory symptoms and FEV1 less than 60% predicted, as documented by spirometry. (Grade: strong recommendation, moderate-quality evidence.) Recommendation 3: Clinicians should prescribe 1 of the following maintenance monotherapies for symptomatic patients with COPD and FEV1 less than 60% predicted: long-acting inhaled β-agonists, long-acting inhaled anticholinergics, or inhaled corticosteroids. (Grade: strong recommendation, high-quality evidence.) Recommendation 4: Clinicians may consider combination inhaled therapies for symptomatic patients with COPD and FEV1 less than 60% predicted. (Grade: weak recommendation, moderate-quality evidence.) Recommendation 5: Clinicians should prescribe oxygen therapy in patients with COPD and resting hypoxemia (Pao2 ≤55 mm Hg). (Grade: strong recommendation, moderate-quality evidence.) Recommendation 6: Clinicians should consider prescribing pulmonary rehabilitation in symptomatic individuals with COPD who have an FEV1 less than 50% predicted. (Grade: weak recommendation, moderate-quality evidence.) *This paper, written by Amir Qaseem, MD, PhD, MHA; Vincenza Snow, MD; Paul Shekelle, MD, PhD; Katherine Sherif, MD; Timothy J. Wilt, MD, MPH; Steven Weinberger, MD; and Douglas K. Owens, MD, MS, was developed for the Clinical Efficacy Assessment Subcommittee of the American College of Physicians (ACP): Douglas K. Owens, MD, MS (Chair); Donald E. Casey Jr., MD, MPH, MBA; J. Thomas Cross Jr., MD, MPH; Paul Dallas, MD; Nancy C. Dolan, MD; Mary Ann Forciea, MD; Lakshmi Halasyamani, MD; Robert H. Hopkins Jr., MD; and Paul Shekelle, MD, PhD. Approved by the ACP Board of Regents on 14 July 2007.
Generation of cytotoxic effector cells by immunocompetent thymus cell subpopulations.
Authors: J W Dyminski, R T Smith
Journal: The Journal of Experimental Medicine (1977)

Immunocompetent mouse thymus cell subsets (TH-2) cultured with allogeneic TH-2 cells, required a peripheral lymphoid cell in order to generate specifically cytotoxic T cells (CTL) in vitro. The helper cell is identified as a B cell, and can be supplied either in the mixture of target or responding peripheral cells, or in optimal ratios of 10:1 to 20:1 as nonproliferating cells syngeneic to the responder, when both responder and target are TH-2. Allogeneic helper cells are much less effective. Kinetic studies indicate that helper cell activity involves initial interaction with stimulator cell and is then required throughout the period of generation of cytotoxic lymphocytes. Addition of critical levels of certain IgG preparations, particularly IgG2A appears to support generation of CTL in TH-2/TH-2 cultures but is considerably less effective than intact B cells. Cytotoxicity generated under these conditions has the same genetic requirements for I-region histoincompatibility between stimulator and responder, and for K or D identity of stimulator and target cell, as has been reported for peripheral cell CTL.
Improved outcome in high-risk childhood acute lymphoblastic leukemia defined by prednisone-poor response treated with double Berlin-Frankfurt-Muenster protocol II
Authors: Maurizio Aricò, Maria Grazia Valsecchi, Valentino Conter, Carmelo Rizzari, Andrea Pession, Chiara Messina, Elena Barisone, Vincenzo Poggi, Giulio De Rossi, Franco Locatelli, Maria Concetta Micalizzi, Giuseppe Basso, Giuseppe Masera
Journal: Blood (2002)
Cell-Based Therapy for Myocardial Ischemia and Infarction: Pathophysiological Mechanisms
Authors: Michael A. Laflamme, Stephan Zbinden, Stephen E. Epstein, Charles E. Murry
Journal: Annual Review of Pathology Mechanisms of Disease (2007)

Cell-based cardiac repair has emerged as an attractive approach to preventing or reversing heart failure resulting from myocyte dysfunction—e.g., due to infarction—and to enhancing the development of collaterals in patients with symptoms of myocardial ischemia. These two problems involve both overlapping and differing mechanisms, and these differences must be considered in cell-based therapies. In terms of myocardial dysfunction due to infarction, only committed cardiomyocytes have been shown to form new myocardium that is electrically coupled with the host heart. Despite this, multiple cell populations appear to improve function of the infarcted heart, including many that are clearly nonmyogenic. In terms of myocardial ischemia, although cell-based strategies improve ischemia in animal models, clinical trials to date have not shown robustly beneficial results. We review the evidence for potential mechanisms underlying the benefits of cell transplantation in the heart and discuss the clinical contexts in which they may be relevant.
Deja vu in the theories of atrial fibrillation dynamics
Authors: J. Jalife
Journal: Cardiovascular Research (2010)

This brief review looks back to the major theoretical, experimental, and clinical work on the dynamics and mechanisms of atrial fibrillation (AF).Its goal is to highlight the most important issues, controversies, and advances that have driven the field of investigation into AF mechanisms at any given time during the last 100 years.It emphasizes that while the history of AF research has been full of controversies from the start, such controversies have led to new information, and individual scientists have learned from those that have preceded them.However, in the face of the most common sustained cardiac arrhythmia seen in clinical practice, we are yet to fully understand its fundamental mechanisms and learn how to treat it effectively.Future research into AF dynamics and mechanisms should focus on the development and validation of new numerical and animal models.Such models should be relevant to and accurately reproduce the important substrates associated with ageing and with diseases such as hypertension, heart failure, and ischaemic heart disease which cause AF in the vast majority of patients.Knowledge derived from such models may help to greatly advance the field and hopefully lead to more effective prevention and therapy.
Landmark perspective. Sulfonamides and meningitis
Authors: W. M. Scheld
Journal: JAMA (1984)

The article reprinted in this issue ofThe Journal<sup>1</sup>was recognized as a landmark study even at the time of its publication in 1937. Schwentker and colleagues reported their preliminary observations on the treatment of 11 patients with invasive meningococcal disease with a new compound, sulfanilamide. The results achieved (ten of 11 survived; 91% survival) were far superior to those obtained with the then-conventional antimeningococcal antisera therapy (survival, 15% to 70%, dependent on age). In addition, there were fewer adverse side effects with sulfanilamide; horse serum injections could be avoided. As a result, sulfonamides became the mainstay of therapy for serious meningococcal disease for more than three decades. <h3>Presulfonamide Treatment of Meningococcal Meningitis</h3> "Epidemic cerebrospinal fever" (meningococcal meningitis) was described in detail by Gaspard Vieusseux after an outbreak in Geneva in the spring of 1805. The etiologic agent was first isolated from purulent CSF by Weichselbaum in 1887. At
Care of Children and Adolescents With Type 1 Diabetes
Authors: Janet Silverstein, Georgeanna Klingensmith, Kenneth Copeland, Leslie Plotnick, Francine Kaufman, Lori Laffel, Larry Deeb, Margaret Grey, Barbara Anderson, Lea Ann Holzmeister, Nathaniel Clark
Journal: Diabetes Care (2005)

During recent years, the American Diabetes Association (ADA) has published detailed guidelines and recommendations for the management of diabetes in the form of technical reviews, position statements, and consensus statements. Recommendations regarding children and adolescents have generally been included as only a minor portion of these documents. For example, the most recent ADA position statement on “Standards of Medical Care for Patients With Diabetes Mellitus” (last revised October 2003) included “special considerations” for children and adolescents (1). Other position statements included age-specific recommendations for screening for nephropathy (2) and retinopathy (3) in children with diabetes. In addition, the ADA has published guidelines pertaining to certain aspects of diabetes that apply exclusively to children and adolescents, including care of children with diabetes at school (4) and camp (5) and a consensus statement on type 2 diabetes in children and adolescents (6).

The purpose of this document is to provide a single resource on current standards of care pertaining specifically to children and adolescents with type 1 diabetes. It is not meant to be an exhaustive compendium on all aspects of the management of pediatric diabetes. However, relevant references are provided and current works in progress are indicated as such. The information provided is based on evidence from published studies whenever possible and, when not, supported by expert opinion or consensus (7). Several excellent detailed guidelines and chapters on type 1 diabetes in pediatric endocrinology texts exist, including those by the International Society of Pediatric and Adolescent Diabetes (ISPAD) (8), by the Australian Pediatric Endocrine Group (www.chw.edu/au/prof/services/endocrinology/apeg), in Lifshitz’s Pediatric Endocrinology (9–11), and by Plotnick and colleagues (12,13).

Children have characteristics and needs that dictate different standards of care. The management of diabetes in children must take the major differences between children of various ages and …
Searching for a Balance of Responsibilities: OECD Countries' Changing Elderly Assistance Policies
Authors: Katherine Swartz
Journal: Annual Review of Public Health (2013)

The rapid aging of OECD country populations and the now five-year-long financial crisis in Europe are causing many OECD countries to reconfigure their assistance programs for the elderly, particularly their long-term care (LTC) policies. Debates about intergenerational responsibilities are evident in recently published research papers that examine how countries are revising programs for the elderly. Building financial sustainability into program reforms has suddenly become a priority. Until just recently, reform efforts focused on creating efficiencies and better quality of services. What emerges from the recent literature is a strong sense that the OECD countries are responding to the financial crisis and the rapid aging of populations in very similar ways. Given the countries' different histories of how they provide assistance to their elderly citizens, the convergence of policy responses is not something we might have foreseen. The United States could learn much from the OECD countries' choices.
Long term outcomes from the IMPACT randomised trial for depressed elderly patients in primary care
Authors: Enid M Hunkeler, Wayne Katon, Lingqi Tang, John W Williams, Kurt Kroenke, Elizabeth H B Lin, Linda H Harpole, Patricia Arean, Stuart Levine, Lydia M Grypma, William A Hargreaves, Jürgen Unützer
Journal: BMJ (2006)

To determine the long term effectiveness of collaborative care management for depression in late life.Two arm, randomised, clinical trial; intervention one year and follow-up two years.18 primary care clinics in eight US healthcare organisations. Patients 1801 primary care patients aged 60 and older with major depression, dysthymia, or both.Patients were randomly assigned to a 12 month collaborative care intervention (IMPACT) or usual care for depression. Teams including a depression care manager, primary care doctor, and psychiatrist offered education, behavioural activation, antidepressants, a brief, behaviour based psychotherapy (problem solving treatment), and relapse prevention geared to each patient's needs and preferences.Interviewers, blinded to treatment assignment, conducted interviews in person at baseline and by telephone at each subsequent follow up. They measured depression (SCL-20), overall functional impairment and quality of life (SF-12), physical functioning (PCS-12), depression treatment, and satisfaction with care.IMPACT patients fared significantly (P < 0.05) better than controls regarding continuation of antidepressant treatment, depressive symptoms, remission of depression, physical functioning, quality of life, self efficacy, and satisfaction with care at 18 and 24 months. One year after IMPACT resources were withdrawn, a significant difference in SCL-20 scores (0.23, P < 0.0001) favouring IMPACT patients remained.Tailored collaborative care actively engages older adults in treatment for depression and delivers substantial and persistent long term benefits. Benefits include less depression, better physical functioning, and an enhanced quality of life. The IMPACT model may show the way to less depression and healthier lives for older adults.
Increased risk of cancer among 3663 patients with cutaneous lupus erythematosus: a Swedish nationwide cohort study
Authors: C.M. Grönhagen, C.M. Fored, F. Granath, F. Nyberg
Journal: British Journal of Dermatology (2011)

Other autoimmune diseases have been associated with higher risks for cancer, and numerous case reports of cutaneous lupus erythematosus (CLE) and different cancer types are available.To estimate the overall and specific cancer risks in a nationwide cohort study of patients diagnosed with CLE in Sweden and compare that risk with that in a control cohort without CLE.A cohort of 3663 individuals with CLE and a matched control cohort from the general population (three controls to each CLE case) without a diagnosis of CLE were derived from the Swedish National Patient Register, 1997-2007, and were electronically linked to the Swedish Cancer Register and the Swedish Cause of Death Register. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated to compare the observed vs. the expected numbers of cancers.A total of 183 incident cancers occurred within the observation interval, yielding a HR of 1·8 (95% CI 1·5-2·2) for cancer overall. Median follow-up was 4·1 years. About a fourfold risk increase was seen for buccal cancer, lymphomas, respiratory cancer and nonmelanoma skin cancer.Patients with CLE appear to have an elevated risk for certain cancer types, an increase that remains when excluding patients also diagnosed with systemic lupus erythematosus. Our findings point to the importance of counselling about not smoking and sun avoidance, and underscore the need for specialized monitoring of this patient group along with bench-to-bedside research efforts to clarify pathogenesis.
Renal Progenitor Cells Contribute to Hyperplastic Lesions of Podocytopathies and Crescentic Glomerulonephritis
Authors: Bart Smeets, Maria Lucia Angelotti, Paola Rizzo, Henry Dijkman, Elena Lazzeri, Fieke Mooren, Lara Ballerini, Eliana Parente, Costanza Sagrinati, Benedetta Mazzinghi, Elisa Ronconi, Francesca Becherucci, Ariela Benigni, Eric Steenbergen, Laura Lasagni, Giuseppe Remuzzi, Jack Wetzels, Paola Romagnani
Journal: Journal of the American Society of Nephrology (2009)

Glomerular injury can involve excessive proliferation of glomerular epithelial cells, resulting in crescent formation and obliteration of Bowman's space. The origin of these hyperplastic epithelial cells in different glomerular disorders is controversial. Renal progenitors localized to the inner surface of Bowman's capsule can regenerate podocytes, but whether dysregulated proliferation of these progenitors contributes to crescent formation is unknown. In this study, we used confocal microscopy, laser capture microdissection, and real-time quantitative reverse transcriptase–PCR to demonstrate that hypercellular lesions of different podocytopathies and crescentic glomerulonephritis consist of three distinct populations: CD133+CD24+podocalyxin (PDX)−nestin− renal progenitors, CD133+CD24+PDX+nestin+ transitional cells, and CD133−CD24−PDX+nestin+ differentiated podocytes. In addition, TGF-β induced CD133+CD24+ progenitors to produce extracellular matrix, and these were the only cells to express the proliferation marker Ki67. Taken together, these results suggest that glomerular hyperplastic lesions derive from the proliferation of renal progenitors at different stages of their differentiation toward mature podocytes, providing an explanation for the pathogenesis of hyperplastic lesions in podocytopathies and crescentic glomerulonephritis.
Phase I Study of Sequence-Selective Minor Groove DNA Binding Agent SJG-136 in Patients with Advanced Solid Tumors
Authors: Daniel Hochhauser, Timothy Meyer, Victoria J. Spanswick, Jenny Wu, Peter H. Clingen, Paul Loadman, Margaret Cobb, Lindsey Gumbrell, Richard H. Begent, John A. Hartley, Duncan Jodrell
Journal: Clinical Cancer Research (2009)

This phase I dose-escalation study was undertaken to establish the maximum tolerated dose of the sequence-selective minor groove DNA binding agent SJG-136 in patients with advanced solid tumors. The study also investigated antitumor activity and provided pharmacokinetic and pharmacodynamic data.Sixteen patients were assigned sequentially to escalating doses of SJG-136 (15-240 microg/m(2)) given as a 10-minute i.v. infusion every 21 days. The dose was subsequently reduced in incremental steps to 45 microg/m(2) due to unexpected toxicity.The maximum tolerated dose of SJG-136 was 45 microg/m(2). The main drug-related adverse event was vascular leak syndrome (VLS) characterized by hypoalbuminemia, pleural effusions, ascites, and peripheral edema. Other unexpected adverse events included elevated liver function tests and fatigue. The VLS and liver toxicity had delayed onset and increased in severity with subsequent cycles. Disease stabilization was achieved for >6 weeks in 10 patients; in 2 patients this was maintained for >12 weeks. There was no evidence of DNA interstrand cross-linking in human blood lymphocytes with the use of the comet assay. Evidence of DNA interaction in lymphocytes and tumor cells was shown through a sensitive gamma-H2AX assay. SJG-136 had linear pharmacokinetics across the dose range tested.SJG-136 was associated with dose-limiting VLS and hepatotoxicity when administered by short injection every 21 days. DNA damage was noted, at all dose levels studied, in circulating lymphocytes. The etiology of the observed toxicities is unclear and is the subject of further preclinical research. Alternative clinical dosing strategies are being evaluated.
Effects of Smoking on Benzo(a)pyrene Metabolism by Human Placental Microsomes
Authors: J. B. Vaught, H. L. Gurtoo, N. B. Parker, R. LeBoeuf, G. Doctor
Journal: Cancer Research (1979)

Placentas were collected at term from a series of 21 women. Thirteen were smokers, and eight were nonsmokers. Microsomes were prepared and used in the following studies of benzo( a )pyrene metabolism: aryl hydrocarbon hydroxylase, epoxide hydrase, high-pressure liquid chromatographic analysis of benzo( a )pyrene metabolites, and DNA binding. DNA-binding adducts were further characterized by Sephadex LH-20 chromatography. Aryl hydrocarbon hydroxylase activity was much higher in smokers than in nonsmokers. Epoxide hydrase activity with styrene oxide as the substrate showed no difference between smokers and nonsmokers. High-pressure liquid chromatographic analysis showed much greater formation of dihydrodiols, quinones, and phenols by microsomes from smokers. The amount of benzo( a )pyrene-7,8-dihydrodiol was almost equal to the amount of phenols produced by the microsomes of the smokers. Sephadex LH-20 analysis of DNA binding resulted in only one major benzo( a )pyrene-DNA adduct when microsomes from smokers were used; this peak corresponds to benzo( a )pyrene 7,8-diol-9,10-oxide bound to DNA nucleoside(s).
High glucose and hyperinsulinemia stimulate connective tissue growth factor expression: A potential mechanism involved in progression to fibrosis in nonalcoholic steatohepatitis
Authors: Valerie Paradis, Gabriel Perlemuter, Franck Bonvoust, Delphine Dargere, Beatrice Parfait, Michel Vidaud, Marc Conti, Stephane Huet, Nathalie Ba, Catherine Buffet, Pierre Bedossa
Journal: Hepatology (2001)

Nonalcoholic steatohepatitis (NASH) may progress to liver fibrosis and cirrhosis. Mechanisms directly involved in the development of fibrosis have been poorly investigated. Because connective tissue growth factor (CTGF) is an intermediate key molecule involved in the pathogenesis of fibrosing chronic liver diseases and is potentially induced by hyperglycemia, the aims of this study were to (1) study the expression of CTGF in vivo both in human liver biopsy specimens of patients with NASH and in an experimental model of obesity and type II diabetes (Zucker rats); and (2) analyze the effects of hyperglycemia and insulin in vitro on hepatic stellate cells. In vivo , CTGF overexpression was observed in the liver tissue of all of the 16 patients with NASH. CTGF immunostaining was mild in 7 cases (44%) and moderate or strong in 9 cases (56%). Staining was mainly detected in the liver extracellular matrix in parallel with the amount of liver fibrosis. Liver from fa/fa rats also showed CTGF overexpression by comparison with Fa/fa rats both at the messenger RNA (mRNA) level (3-fold increase) and protein level. In vitro , both CTGF mRNA and protein were significantly increased when hepatic stellate cells were incubated with either glucose or insulin. A slight increase in type I procollagen mRNA level was also observed in hepatic stellate cells incubated with glucose. In conclusion, this study suggests that hyperglycemia and insulin are key-factors in the progression of fibrosis in patients with NASH through the up-regulation of CTGF.
8-Year Follow-Up of Patients Treated for Borderline Personality Disorder: Mentalization-Based Treatment Versus Treatment as Usual
Authors: Anthony Bateman, Peter Fonagy
Journal: American Journal of Psychiatry (2008)

This study evaluated the effect of mentalization-based treatment by partial hospitalization compared to treatment as usual for borderline personality disorder 8 years after entry into a randomized, controlled trial and 5 years after all mentalization-based treatment was complete.Interviewing was by research psychologists blind to original group allocation and structured review of medical notes of 41 patients from the original trial. Multivariate analysis of variance, chi-square, univariate analysis of variance, and nonparametric Mann-Whitney statistics were used to contrast the two groups depending on the distribution of the data.Five years after discharge from mentalization-based treatment, the mentalization-based treatment by partial hospitalization group continued to show clinical and statistical superiority to treatment as usual on suicidality (23% versus 74%), diagnostic status (13% versus 87%), service use (2 years versus 3.5 years of psychiatric outpatient treatment), use of medication (0.02 versus 1.90 years taking three or more medications), global function above 60 (45% versus 10%), and vocational status (employed or in education 3.2 years versus 1.2 years).Patients with 18 months of mentalization-based treatment by partial hospitalization followed by 18 months of maintenance mentalizing group therapy remain better than those receiving treatment as usual, but their general social function remains impaired.