tbuckley/cabot-search huggingface dataset:
Primary care groups: Improving the quality of care through clinical governance
Authors: S. Campbell
Journal: BMJ (2001)

This is the third in a series of five articles 

The UK government has set a challenging agenda for monitoring and improving the quality of health care. It is based on a series of national standards and guidelines, a strategy for quality improvement termed “clinical governance,” and a framework for monitoring the quality of care in and performance of NHS organisations (box). Clinical governance is “a framework through which NHS organisations are accountable for continually improving the quality of their services, safeguarding high standards by creating an environment in which excellence in clinical care will flourish.”1 To be successful this strategy requires effective leadership by clinicians who have responsibility for improving quality; it must engage the doctors and nurses who provide care on a daily basis; and it must have commitment and support from managers within the NHS.

#### Summary points

Primary care groups and trusts are responsible for implementing clinical governance, including monitoring and improving the quality of care

In their first two years they have concentrated on educating and supporting health professionals and encouraging shared learning

Information about the quality of care provided in general practice is being shared between practices and with the public, often in a form that permits practices to be identified

Many groups and trusts are offering incentives to practices to promote improvements in the quality of care

Sanctions and disciplinary action are rarely used when dealing with poor performance

Limited resources and the pace of change are potential obstacles to future success in improving the quality of care

#### Goals of quality improvement strategies in the NHS

National service frameworks, National Institute for Clinical Excellence —set standards, develop guidelines

Clinical governance —deliver care, improve quality

National performance framework, annual appraisal of doctors, Commission for Health Improvement, national surveys of patients —monitor quality and performance

Primary care groups and trusts are responsible for implementing clinical …
STRESS AND HIPPOCAMPAL PLASTICITY
Authors: Bruce S. McEwen
Journal: Annual Review of Neuroscience (1999)

▪ Abstract The hippocampus is a target of stress hormones, and it is an especially plastic and vulnerable region of the brain. It also responds to gonadal, thyroid, and adrenal hormones, which modulate changes in synapse formation and dendritic structure and regulate dentate gyrus volume during development and in adult life. Two forms of structural plasticity are affected by stress: Repeated stress causes atrophy of dendrites in the CA3 region, and both acute and chronic stress suppresses neurogenesis of dentate gyrus granule neurons. Besides glucocorticoids, excitatory amino acids and N-methyl-d-aspartate (NMDA) receptors are involved in these two forms of plasticity as well as in neuronal death that is caused in pyramidal neurons by seizures and by ischemia. The two forms of hippocampal structural plasticity are relevant to the human hippocampus, which undergoes a selective atrophy in a number of disorders, accompanied by deficits in declarative, episodic, spatial, and contextual memory performance. It is important, from a therapeutic standpoint, to distinguish between a permanent loss of cells and a reversible atrophy.
Obstructive jaundice from hepatic amyloidosis in a patient with multiple myeloma
Authors: James A. Calomeni, J. Robert Smith
Journal: American Journal of Hematology (1985)

Abstract A patient with multiple myeloma is described who developed severe intrahepatic cholestasis secondary to hepatic deposition of amyloid. This is the first reported case of this complication's developing in a patient with multiple myeloma.
Selective phosphodiesterase inhibitors modulate the activity of alveolar macrophages from sensitized guinea-pigs
Authors: N Germain, B Bertin, A Legendre, B Martin, V Lagente, A Payne, E Boichot
Journal: European Respiratory Journal (1998)

The aim of this study was to investigate the effects of selective phosphodiesterase (PDE)3 and PDE4 inhibitors on arachidonate release by alveolar macrophages from sensitized and challenged guinea-pigs. Guinea-pigs were sensitized and challenged with ovalbumin administered by aerosol. Bronchoalveolar lavage was performed 48 h later and the PDE and cyclic adenosine monophosphate (cAMP) contents of or the arachidonate release from alveolar macrophages, stimulated in vitro with N-formyl-Met-Leu-Phe (fMLP), were evaluated. PDE3 and PDE4 activities were detected in preparations of macrophage lysate from sensitized challenged and sensitized control animals. Oral pretreatment, prior to antigen challenge in sensitized guinea-pigs, with rolipram or Ro 20-1724 (PDE4 inhibitors) but not milrinone (PDE3 inhibitor) significantly reduced the arachidonate release from alveolar macrophages. In vitro incubation of alveolar macrophages from challenged guinea-pigs with Ro 20-1724 or the cAMP analogue dibutyryl cAMP (db-cAMP) but not milrinone or the cyclic guanosine monophosphate (cGMP) analogue 8-bromo-cGMP (8-br-cGMP) significantly reduced arachidonate release. Incubation of the cells with a combination of milrinone plus rolipram or Ro 20-1724 elicited a marked and significant reduction in arachidonate release by alveolar macrophages stimulated with fMLP. In conclusion, these data show that phosphodiesterase-4 isoenzyme may regulate the release of inflammatory mediators such as arachidonate from macrophages through an increase in intracellular cyclic adenosine monophosphate. This suggests that phosphodiesterase-4 inhibitors have potential in the treatment of inflammatory disorders of the lung.
Inhibition of in Vitro Paroxysmal Nocturnal Hemoglobinuria Lysis by Tryptophan Metabolites.
Authors: Kenneth S. Graff
Journal: Annals of Internal Medicine (1968)

s1 May 1968Inhibition of in Vitro Paroxysmal Nocturnal Hemoglobinuria Lysis by Tryptophan Metabolites.Kenneth S. Graff, Charles E. Mengel, M.D., F.A.C.P., Stanley P. Balcerzak, M.D.Kenneth S. GraffSearch for more papers by this author, Charles E. Mengel, M.D., F.A.C.P.Search for more papers by this author, Stanley P. Balcerzak, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-68-5-1168_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptIn vitro lysis of paroxysmal nocturnal hemoglobinuria (PNH) erythrocytes presumably results from the unique interaction between these cells and the third component (C′3) of complement without the requirement for antibody and early phase reactants (C′1, C′4, C′2). Since various aromatic amino acid derivatives had been shown to inhibit C′3 in other systems, we examined the effects of some tryptophan metabolites on the HAM acid-serum lysis and the sucrose lysis tests of natural PNH and glutathione (GSH)-treated erythrocytes. Our previous studies had shown GSH-treated red cells to be indistinguishable from those of PNH patients. A range of 0 to 99% inhibition... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Columbus, Ohio PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1968Volume 68, Issue 5Page: 1168-1168KeywordsAmino acidsCellsGlutathioneHemoglobinMetabolitesSucroseTryptophan Issue Published: 1 May 1968 PDF DownloadLoading ...
Intrastriatal transplantation of microcarrier-bound human retinal pigment epithelial cells versus sham surgery in patients with advanced Parkinson's disease: a double-blind, randomised, controlled trial
Authors: Robert E Gross, Raymond L Watts, Robert A Hauser, Roy AE Bakay, Heinz Reichmann, Rüdiger von Kummer, William G Ondo, Elke Reissig, Wilhelm Eisner, Heike Steiner-Schulze, Harald Siedentop, Klaus Fichte, Walter Hong, Michael Cornfeldt, Katherine Beebe, Rupert Sandbrink
Journal: The Lancet Neurology (2011)
B cell stimulatory factor 1 (interleukin 4) is a potent costimulant for normal resting T lymphocytes.
Authors: J Hu-Li, E M Shevach, J Mizuguchi, J Ohara, T Mosmann, W E Paul
Journal: The Journal of Experimental Medicine (1987)

Resting T cells proliferate in response to B cell stimulatory factor 1 (BSF-1; interleukin 4) plus phorbol myristate acetate (PMA). This response is obtained with highly purified T cells and is density independent, suggesting that accessory cells are not required. Both L3T4+ and Lyt-2+ T cells respond to BSF-1 plus PMA. Although BSF-1 alone does not cause T cell proliferation, it maintains the viability of small, dense T cells, indicating that it acts on resting T cells. Furthermore, BSF-1 is required early in the proliferative response of resting T cells to BSF-1 plus PMA, further supporting the concept that it acts on G0 or early G1 cells. However, BSF-1 is also needed late in the first round of division of T cells stimulated with BSF-1 plus PMA. Removing BSF-1 at 24 h of stimulation prevents entry into S phase. These results indicate that BSF-1 is involved in both the induction of competence and in the progression phases of T cell division.
Transcutaneous carbon dioxide profile during sleep reveals metabolic risk factors in post-menopausal females
Authors: J. Aittokallio, T. Saaresranta, A. Virkki, N. Karppinen, O. J. Heinonen, T. Aittokallio, O. Polo
Journal: European Respiratory Journal (2009)

The risks of metabolic syndrome and sleep-disordered breathing increase around the time of the menopause. We have previously shown that features of the nocturnal transcutaneous carbon dioxide (TcCO 2 ) profile are associated with metabolic variables such as cholesterol, glycosylated haemoglobin A1C (GHbA1C) and blood pressure in patients with sleep apnoea. In the present study, we investigated whether these metabolic variables can be predicted using noninvasive TcCO 2 measurements during sleep in generally healthy post-menopausal females. 22 post-menopausal females underwent an overnight polygraphic sleep study that involved the continuous monitoring of arterial oxygen saturation ( S a,O 2 ) and TcCO 2 . Body composition, GHbA1C, plasma cholesterol and blood pressure were measured prior to the sleep study. Nocturnal TcCO 2 features were the most important predictors of lipoprotein cholesterols, triglycerides and blood pressure levels. A longer sleep period and higher TcCO 2 levels were linked with lower GHbA1C, and fragmented sleep with lower high-density lipoprotein cholesterol. Neither nocturnal S a,O 2 indices nor the apnoea/hypopnoea index had a predictive power. The results suggest that nocturnal TcCO 2 events revealed metabolic risk factors already present in healthy post-menopausal females.
Effectiveness of hip protectors: It's more the effectiveness of compliance strategies
Authors: Peter D O'Halloran
Journal: BMJ (2006)

Ramifications of screening for breast cancerSee Research p 689 in 4 cancers detected by mammography are pseudocancersEditor-In this issue Zackrisson et al report on follow-up data from the Malmö mammographic screening trial and conclude that the rate of overdiagnosis of breast cancer was 10%. 1 They do not, however, calculate the risk we believe is most relevant to women considering mammography: What is the chance that a screen detected cancer represents overdiagnosis?After 15 years of follow-up, there were 1320 diagnosed in the screened group and 1205 in the control group (table 1).The excess detection of 115 cancers associated with screening led to their conclusion of an overdiagnosis rate of 10% (115/1205).However, because the intervention had stopped 15 years earlier and yet breast cancer cases continue to accumulate in both groups, the approach understates the risk of overdiagnosis.A more relevant denominator is the number of cancers found in the screened group at the end of the trial-741 (table 2).This addresses the question: Were I found to have cancer after being randomised to screening, how likely is it to represent overdiagnosis?As shown in the figure, using this denominator the risk of overdiagnosis is 15% (115/741).However, many of the cancers detected in the screened group are not detected by screening.They are instead clinically detected (either during the interval between screening examinations or among nonattenders).The most relevant denominator is the number of screen detected cancers found at the end of the trial.This addresses the question: Were I found to have cancer by a mammogram, how likely is it to represent overdiagnosis?Although this denominator is not reported by Zackrisson et al, the original BMJ article describing Malmö reported that 64% of the cancers detected in the screened group were detected by screening mammography. 2Thus one can deduce that the number of screen detected cancers at the end of the trial was about 475.As shown in the figure, using this denominator the risk of overdiagnosis is 24% (115/475).
Breast Cancer Stem Cells: We've Got Them Surrounded
Authors: Hasan Korkaya, Max S. Wicha
Journal: Clinical Cancer Research (2012)

Breast cancer stem cells are regulated by cell intrinsic pathways as well as by elements in the tumor microenvironment. New evidence suggests that an important interaction between the interleukin (IL)-8 receptor CXCR1/2 and HER2 is involved in this regulation. Simultaneous targeting of these pathways provides a novel therapeutic approach.
Down-regulation of PLCγ2–β-catenin pathway promotes activation and expansion of myeloid-derived suppressor cells in cancer
Authors: Aude-Hélène Capietto, Seokho Kim, Dominic E. Sanford, David C. Linehan, Masaki Hikida, Tomohiro Kumosaki, Deborah V. Novack, Roberta Faccio
Journal: The Journal of Experimental Medicine (2013)

Myeloid-derived suppressor cells (MDSCs) favor tumor promotion, mainly by suppressing antitumor T cell responses in many cancers. Although the mechanism of T cell inhibition is established, the pathways leading to MDSC accumulation in bone marrow and secondary lymphoid organs of tumor-bearing hosts remain unclear. We demonstrate that down-regulation of PLCγ2 signaling in MDSCs is responsible for their aberrant expansion during tumor progression. PLCγ2−/− MDSCs show stronger immune-suppressive activity against CD8+ T cells than WT MDSCs and potently promote tumor growth when adoptively transferred into WT mice. Mechanistically, PLCγ2−/− MDSCs display reduced β-catenin levels, and restoration of β-catenin expression decreases their expansion and tumor growth. Consistent with a negative role for β-catenin in MDSCs, its deletion in the myeloid population leads to MDSC accumulation and supports tumor progression, whereas expression of β-catenin constitutively active reduces MDSC numbers and protects from tumor growth. Further emphasizing the clinical relevance of these findings, MDSCs isolated from pancreatic cancer patients show reduced p-PLCγ2 and β-catenin levels compared with healthy controls, similar to tumor-bearing mice. Thus, for the first time, we demonstrate that down-regulation of PLCγ2–β-catenin pathway occurs in mice and humans and leads to MDSC-mediated tumor expansion, raising concerns about the efficacy of systemic β-catenin blockade as anti-cancer therapy.
CONSORT 2010 statement: Updated guidelines for reporting parallel group randomised trials
Authors: Kenneth F. Schulz, Douglas G. Altman, David Moher
Journal: International Journal of Surgery (2011)

The CONSORT statement is used worldwide to improve the reporting of randomised controlled trials. Kenneth Schulz and colleagues describe the latest version, CONSORT 2010, which updates the reporting guideline based on new methodological evidence and accumulating experience. To encourage dissemination of the CONSORT 2010 Statement, this article is freely accessible on bmj.com and will also be published in the Lancet, Obstetrics and Gynecology, PLoS Medicine, Annals of Internal Medicine, Open Medicine, Journal of Clinical Epidemiology, BMC Medicine, and Trials.
Comparative genomic analysis of three Leishmania species that cause diverse human disease
Authors: Christopher S Peacock, Kathy Seeger, David Harris, Lee Murphy, Jeronimo C Ruiz, Michael A Quail, Nick Peters, Ellen Adlem, Adrian Tivey, Martin Aslett, Arnaud Kerhornou, Alasdair Ivens, Audrey Fraser, Marie-Adele Rajandream, Tim Carver, Halina Norbertczak, Tracey Chillingworth, Zahra Hance, Kay Jagels, Sharon Moule, Doug Ormond, Simon Rutter, Rob Squares, Sally Whitehead, Ester Rabbinowitsch, Claire Arrowsmith, Brian White, Scott Thurston, Frédéric Bringaud, Sandra L Baldauf, Adam Faulconbridge, Daniel Jeffares, Daniel P Depledge, Samuel O Oyola, James D Hilley, Loislene O Brito, Luiz R O Tosi, Barclay Barrell, Angela K Cruz, Jeremy C Mottram, Deborah F Smith, Matthew Berriman
Journal: Nature Genetics (2007)
Extracellular DNA in Pancreatic Cancer Promotes Cell Invasion and Metastasis
Authors: Fushi Wen, Alex Shen, Andrew Choi, Eugene W. Gerner, Jiaqi Shi
Journal: Cancer Research (2013)

Abstract Aggressive metastasis is the chief cause of the high morbidity and mortality associated with pancreatic cancer, yet the basis for its aggressive behavior remains elusive. Extracellular DNA (exDNA) is a recently discovered component of inflammatory tissue states. Here, we report that exDNA is present on the surface of pancreatic cancer cells where it is critical for driving metastatic behavior. exDNA was abundant on the surface and vicinity of cultured pancreatic cancer cells but absent from normal pancreas cells. Strikingly, treatment of cancer cell cultures with DNase I to degrade DNA nonspecifically reduced metastatic characters associated with matrix attachment, migration, and invasion. We further assessed the role of exDNA in pancreatic cancer metastasis in vivo using an orthotopic xenograft model established by implantation of pancreatic cancer cells expressing firefly luciferase. Noninvasive bioluminescent imaging confirmed that DNase I treatment was sufficient to suppress tumor metastasis. Mechanistic investigations suggested the existence of a positive feedback loop in which exDNA promotes expression of the inflammatory chemokine CXCL8, which leads to higher production of exDNA by pancreatic cancer cells, with a significant reduction in CXCL8 levels achieved by DNase I treatment. Taken together, our results strongly suggest that exDNA contributes to the highly invasive and metastatic character of pancreatic cancer. Cancer Res; 73(14); 4256–66. ©2013 AACR.
Palliative whole brain radiation therapy (WBRT) for brain metastases (BM) revisited: The patient population in the modern era is different from the original patient cohort of the RTOG WBRT clinical trials
Authors: S. RushM. Savetsky, A. Vinokur, N. Mehta
Journal: Journal of Clinical Oncology (2006)

1544 Background: RTOG trials in the 1970’s established WBRT (3000 cGy/10 fractions) as an effective palliative tool for symptomatic BM. This was in the era before CT/ MRI and effective systemic therapy. Inclusion criteria was based on clinical symptoms, and studies such as EEG and arteriography though not required. This study was undertaken to determine if pts. in the modern era are similar to those aforementioned, since it may not be appropriate to use accelerated WBRT (aWBRT) in these pts. based on the RTOG guidelines if the cohorts are different. (Other issues such as delayed cognitive dysfunction, alopecia and the impact of and integration with systemic therapy are pertinent to the application and prescription of aWBRT, but not the focus of this study). Methods: A retrospective chart review of 414 consecutive pts. with BM treated with radiation therapy in a single practice from 1990 through 2004 form the basis of this study. There were 256 females and 158 males. Lung cancer was the most common primary site (249/60%) and breast cancer next (75/18%). 121 pts (29%) had a single brain metastsis. 66 symptomatic patients underwent surgical resection of a brain metastasis prior to WBRT. The use of CT or MRI was determined. Results: Of the 414 pts, 105 were asymptomatic (25%). An additonal 66 pts. were rendered asymptomatic with surgical resection. Therefore, a total of 171 (40%) pts. were asymptomatic. All pts underwent imaging with CT (132) or MRI (282). Conclusions: Many pts. with BM seen in a modern radiation oncology practice are different from those in the RTOG series’ in which pts. were designated to receive aWBRT. 1. A notable proportion (40%) of a large number of pts. treated since 1990 for BM was asymptomatic vs. none of the pts. in the RTOG trials. 2. All pts. in this series underwent direct imaging vs. none in the RTOG series’. The systematic prescription of aWBRT for all pts. with BM as dictated by RTOG studies in the 1970’s may not be appropriate and alternative strategies and clinical trials are warranted. No significant financial relationships to disclose.
Macrophage stimulation by angiopoietins-1 and -2 promotes recruitment and retention of white blood cells at sites of inflammation
Authors: S. Krausz, M. E. Sanders, P. P. Tak, K. A. Reedquist
Journal: Annals of the Rheumatic Diseases (2010)

The authors have previously found that macrophages are predominant targets of the angiogenic factors angiopoietin (Ang)-1 and -2 in synovial tissue of patients with rheumatoid arthritis (RA). How macrophage Tie2 ligation by Ang might contribute to disease in RA is currently …
Pathogenesis of Chronic Chagas Heart Disease
Authors: Jose Antonio Marin-Neto, Edécio Cunha-Neto, Benedito C. Maciel, Marcus V. Simões
Journal: Circulation (2007)

Background— Chagas disease remains a significant public health issue and a major cause of morbidity and mortality in Latin America. Despite nearly 1 century of research, the pathogenesis of chronic Chagas cardiomyopathy is incompletely understood, the most intriguing challenge of which is the complex host-parasite interaction. Methods and Results— A systematic review of the literature found in MEDLINE, EMBASE, BIREME, LILACS, and SCIELO was performed to search for relevant references on pathogenesis and pathophysiology of Chagas disease. Evidence from studies in animal models and in anima nobile points to 4 main pathogenetic mechanisms to explain the development of chronic Chagas heart disease: autonomic nervous system derangements, microvascular disturbances, parasite-dependent myocardial aggression, and immune-mediated myocardial injury. Despite its prominent peculiarities, the role of autonomic derangements and microcirculatory disturbances is probably ancillary among causes of chronic myocardial damage. The pathogenesis of chronic Chagas heart disease is dependent on a low-grade but incessant systemic infection with documented immune-adverse reaction. Parasite persistence and immunological mechanisms are inextricably related in the myocardial aggression in the chronic phase of Chagas heart disease. Conclusions— Most clinical studies have been performed in very small number of patients. Future research should explore the clinical potential implications and therapeutic opportunities of these 2 fundamental underlying pathogenetic mechanisms.