tbuckley/cabot-search huggingface dataset:
Tissue factor expression in neutrophil extracellular traps and neutrophil derived microparticles in antineutrophil cytoplasmic antibody associated vasculitis may promote thromboinflammation and the thrombophilic state associated with the disease
Authors: Konstantinos Kambas, Akrivi Chrysanthopoulou, Dimitrios Vassilopoulos, Eirini Apostolidou, Panagiotis Skendros, Andreas Girod, Stella Arelaki, Marios Froudarakis, Lydia Nakopoulou, Alexandra Giatromanolaki, Prodromos Sidiropoulos, Maria Koffa, Dimitrios T Boumpas, Konstantinos Ritis, Ioannis Mitroulis
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> Antineutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV) is characterised by neutrophil activation. An elevated prevalence of venous thromboembolic events has been reported in AAV. Because of the critical role of neutrophils in inflammation associated thrombosis, we asked whether neutrophil tissue factor (TF) may be implicated in the thrombotic diathesis in AAV. <h3>Methods</h3> Neutrophils from four patients and sera from 17 patients with ANCA associated vasculitis with active disease and remission were studied. TF expression was assessed by immunoblotting and confocal microscopy. Circulating DNA levels were evaluated. TF expressing microparticles (MPs) were measured by flow cytometry and thrombin–antithrombin complex levels by ELISA. <h3>Results</h3> Peripheral blood neutrophils from four patients with active disease expressed elevated TF levels and released TF expressing neutrophil extracellular traps (NETs) and MPs. TF positive NETs were released by neutrophils isolated from the bronchoalveolar lavage and were detected in nasal and renal biopsy specimens. Elevated levels of circulating DNA and TF expressing neutrophil derived MPs were further observed in sera from patients with active disease. Induction of remission attenuated the aforementioned effects. Control neutrophils treated with sera from patients with active disease released TF bearing NETs and MPs which were abolished after IgG depletion. Treatment of control neutrophils with isolated IgG from sera from patients with active disease also resulted in the release of TF bearing NETs. TF implication in MP dependent thrombin generation was demonstrated by antibody neutralisation studies. <h3>Conclusions</h3> Expression of TF in NETs and neutrophil derived MPs proposes a novel mechanism for the induction of thrombosis and inflammation in active AAV.
NHS regulator plans to make it easier for doctors to raise concerns and break "mafia" code of silence
Authors: A. O'Dowd
Journal: BMJ (2013)

The main regulator of the NHS wants to help doctors come forward to raise safety concerns at work and break through a “mafia” code of silence that still exists in the health service, MPs have been told.

The leaders of the Care Quality Commission told MPs during a parliamentary health select committee evidence session on 21 October of their intention to make whistleblowing easier for all health professionals.

During the committee’s annual accountability hearing about the commission, MPs asked about whistleblowing in the NHS.

David Prior, the CQC’s chairman, giving evidence, said, “One of the things I’ve learnt over the past six months is to be a whistleblower you’ve got to be very, very brave. …
The fate of human Langerhans cells in hematopoietic stem cell transplantation
Authors: Matthew P. Collin, Derek N.J. Hart, Graham H. Jackson, Gordon Cook, James Cavet, Stephen Mackinnon, Peter G. Middleton, Anne M. Dickinson
Journal: The Journal of Experimental Medicine (2006)

Langerhans cells (LC) and other antigen-presenting cells are believed to be critical in initiating graft versus host responses that influence the outcome of allogeneic hematopoietic stem cell transplantation. However, their fate in humans is poorly understood. We have sought to define the effect of conditioning regimes and graft versus host disease (GVHD) on the survival of recipient LC and reconstitution of donor cells after transplant. Confocal microscopy of epidermal sheets shows that full intensity transplant (FIT) depletes LC more rapidly than reduced intensity transplant (RIT) at day 0, although the nadir is similar in both at 14–21 d. Recovery occurs rapidly within 40 d in the absence of acute GVHD, but is delayed beyond 100 d when GVHD is active. LC chimerism was determined in sex-mismatched transplants using a two-step Giemsa/fluorescence in situ hybridization assay on isolated cells. Acquisition of donor chimerism at 40 d is more rapid after FIT (97%) than RIT (36.5%), irrespective of blood myeloid engraftment. At 100 d, all transplants achieve at least 90% LC donor chimerism and over half achieve 100%. Complete donor chimerism is associated with prior acute cutaneous GVHD, suggesting a role for allogeneic T cells in promoting LC engraftment.
The challenge of quality and patient safety
Authors: Liam Donaldson
Journal: Journal of the Royal Society of Medicine (2008)

In 1948, the health service in the UK stood on the brink of resolving a major quality problem that dogs many countries even today: making access to healthcare free, based on need. The children of the post-war National Health Service (NHS) have never had to live with the fear of financial burden or ruin as a consequence of serious illness. This was sometimes forgotten in the subsequent years as criticisms of the new NHS gradually emerged.

The NHS towards the end of the first decade of the 21st century, in the year of its 60th birthday, is very different from the one that started as a cornerstone of a new welfare state in the years after the Second World War.

Its infrastructure of buildings, equipment and staff has expanded and modernized. The range of technologies and drugs available to diagnose and treat illness has burgeoned, offering life and hope where it was impossible midway through the 20th century. The range of diseases and the consequent demand for care has increased exponentially as the so-called epidemics of modern living (e.g. cancer, heart disease, diabetes) and an ageing population have generated pools of need on a much larger scale than when the NHS began. On top of all this, in common with other developed countries, the proportion of the country's budget devoted to healthcare has expanded dramatically.
Conditional ablation of Stat3 or Socs3 discloses a dual role for reactive astrocytes after spinal cord injury
Authors: Seiji Okada, Masaya Nakamura, Hiroyuki Katoh, Tamaki Miyao, Takuya Shimazaki, Ken Ishii, Junichi Yamane, Akihiko Yoshimura, Yukihide Iwamoto, Yoshiaki Toyama, Hideyuki Okano
Journal: Nature Medicine (2006)
Toll-Like Receptors
Authors: Kiyoshi Takeda, Tsuneyasu Kaisho, Shizuo Akira
Journal: Annual Review of Immunology (2003)

The innate immune system in drosophila and mammals senses the invasion of microorganisms using the family of Toll receptors, stimulation of which initiates a range of host defense mechanisms. In drosophila antimicrobial responses rely on two signaling pathways: the Toll pathway and the IMD pathway. In mammals there are at least 10 members of the Toll-like receptor (TLR) family that recognize specific components conserved among microorganisms. Activation of the TLRs leads not only to the induction of inflammatory responses but also to the development of antigen-specific adaptive immunity. The TLR-induced inflammatory response is dependent on a common signaling pathway that is mediated by the adaptor molecule MyD88. However, there is evidence for additional pathways that mediate TLR ligand-specific biological responses.
Problems In Phasing Out a Large Public Psychiatric Hospital
Authors: ALEX STEWART, H. G. LAFAVE, F. GRUNBERG, M. HERJANIC
Journal: American Journal of Psychiatry (1968)

The four community mental health centers now providing comprehensive services in southern Saskatchewan have contributed to a dramatic decline in the patient population of the state hospital at Weyburn, and there are strong indications that the hospital will be phased out in coming years. Results from two follow-up studies indicate that many former long-term patients are being managed adequately in the community. Community concern about the economic consequences of the hospital's decline has been partially alleviated by the conversion of vacated hospital facilities into a vocational training school serving former patients as well as the local population.
Besides adhesion: new perspectives of integrin functions in angiogenesis
Authors: G. Serini, L. Napione, M. Arese, F. Bussolino
Journal: Cardiovascular Research (2008)

During angiogenic remodelling in embryo and adult life, endothelial cells lining blood vessel walls dynamically modify their integrin-mediated adhesive contacts with the surrounding extracellular matrix. However, besides regulating cell adhesion and migration, integrins dynamically participate in a network with soluble molecules and their receptors. Angiogenesis is characterized by opposing autocrine and paracrine loops of growth factors and semaphorins that regulate the activation of integrins on the endothelial surface through tyrosine kinase receptors (TKR) and the neuropilin/plexin system. Moreover, pro- and anti-angiogenic factors can directly bind integrins and regulate endothelial cell behaviour. This review summarizes the recent progress in understanding the reciprocal interactions between integrins, TKR, and semaphorin receptors.
Modeling the Cost Effectiveness of Secondary Febrile Neutropenia Prophylaxis During Standard-Dose Chemotherapy
Authors: Johanna N.H. Timmer-Bonte, Eddy M.M. Adang, Evelien Termeer, Johan L. Severens, Vivianne C.G. Tjan-Heijnen
Journal: Journal of Clinical Oncology (2008)

Purpose Current guidelines (ie, by the American Society of Clinical Oncology and the European Organisation for Research and Treatment of Cancer) do not recommend secondary infection prophylaxis, whereas, in contrast, caregivers prefer secondary prophylaxis to chemotherapy dose reduction after an episode of febrile neutropenia (FN). Because granulocyte colony-stimulating factor (G-CSF) is expensive, this study investigates the economic consequences of secondary prophylactic use of different prophylactic strategies (antibiotics, antibiotics plus G-CSF, and a combined sequential approach) in a population at risk of FN, using a Markov model. Methods The input for the model is mainly based on the clinical outcome and patient-based cost data set (adopting the health care payer's perspective for the Netherlands) derived from a randomized study on primary prophylaxis in small-cell lung cancer (SCLC) patients; establishing mean cost of an episode FN of €3,290 and prophylaxis of €79 (antibiotics) ± €1,616 (G-CSF) per cycle. The economic analysis was analyzed probabilistically using first- and second-order Monte Carlo simulation. The incremental cost-effectiveness ratio (ICER) was defined as cost per FN-free cycle. Results Secondary prophylaxis with antibiotics was the least expensive strategy (mean, €4,496/patient). The strategy antibiotics plus G-CSF was most expensive (mean, € 8,998/patient). Comparison of these two strategies resulted in an unacceptably high ICER (€343,110 per FN-free cycle) in the Dutch context. In scenarios using higher FN-related costs (as found in the United States), the strategies are less distinct in their monetary effects, but still favor antibiotics. Conclusion This model-based economic analysis demonstrates that in the Netherlands and most likely also in the United States, if secondary prophylaxis is preferred, the strategy with antibiotics is recommended.
Weekly Epoetin Alfa Maintains Hemoglobin, Improves Quality of Life, and Reduces Transfusion in Breast Cancer Patients Receiving Chemotherapy
Authors: Jose Chang, Felix Couture, Scott Young, Kara-Lee McWatters, Catherine Y. Lau
Journal: Journal of Clinical Oncology (2004)

Epoetin alfa administered at 40,000 U once weekly (qw) to anemic cancer patients receiving chemotherapy increases hemoglobin levels, improves quality of life (QOL), and reduces transfusions. The benefit of epoetin alfa in maintaining hemoglobin levels in cancer patients with hemoglobin less than 12 g/dL has not been evaluated.Breast cancer patients (N = 354) receiving chemotherapy were randomly assigned in 1:1 ratio to epoetin alfa (40,000 U qw) or standard of care (SOC). QOL was assessed at baseline and week 12. Hemoglobin responses, transfusion requirements, and prognostic factors for responses were measured.At week 12, Functional Assessment of Cancer Therapy-Anemia (FACT-An; mean, 2.16 +/- 12.84 for epoetin alfa v -4.43 +/- 13.42 for SOC) and FACT-An fatigue (mean, 1.85 +/- 10.52 for epoetin alfa v -3.55 +/- 11.14 for SOC) change scores were significantly higher in the epoetin alfa group (P < .0001). Hemoglobin responses defined as mean hemoglobin > or = 12 g/dL or a > or = 2 g/dL increase compared with baseline were significantly higher in the epoetin alfa group versus SOC: 52.0% v 5.1% and 65.7% v 6.3%, respectively (P < .0001 for both comparisons). Percentage transfused was significantly lower in the epoetin alfa group compared with SOC (8.6% v 22.9%). More than 90% of patients did not require a dose increase and 28.7% had a dose reduction.Epoetin alfa administered at 40,000 U qw is effective in improving QOL, maintaining hemoglobin level, and reducing transfusion requirements in breast cancer patients. The high effectiveness observed could be attributed in part to early treatment with epoetin alfa.
Future Forum was truly independent and not influenced by government, claims chairman
Authors: A. O'Dowd
Journal: BMJ (2011)

The panel of experts that led a listening exercise to review the government’s planned health reforms was not influenced by the government, MPs have been told.

Steve Field, chairman of the NHS Future Forum, appearing before the parliamentary health select committee on 16 June, denied that the forum had been somehow pressured and controlled by the Department of Health for England.

The forum, which published its Summary Report on Proposed Changes to the NHS on 13 June, recommended significant changes to the Health and Social Care Bill, almost all of which have been accepted by the government ( BMJ 2011;342:d3777, doi:10.1136/bmj.d3777).

Professor Field, giving evidence to the committee as part of its inquiry into the forum’s report, was asked how …
Potential paracrine role of the pericardium in the regulation of cardiac function
Authors: Alexandre Mebazaa, Randall C. Wetzel, Jeffrey M. Dodd-o, Eileen M. Redmond, Ajay M. Shah, Kaori Maeda, Geneviève Maistre, Edward G. Lakatta, James L. Robotham
Journal: Cardiovascular Research (1998)

Objective: Both coronary and endocardial endothelium regulate cardiac contractile function via paracrine pathways. We investigated whether pericardial fluid (PF) and pericardial mesothelial cells (PMC) could exert a similar paracrine action. Methods: Both PF and PMC were extracted from sheep pericardial space. Endothelin-1, prostaglandins and atrial natriuretic factor were measured in PF in vivo. In the other hand, PMC were grown on T-75 flasks and microcarrier beads to investigate endothelin-1, nitric oxide and prostaglandin pathways in vitro. In addition, effects of PF and PMC effluent were tested on adult rat cardiac myocyte contraction in vitro. Results: In vitro, cultured PMC expressed endothelin-1 mRNA but not the endothelial nitric oxide synthase III, and released endothelin-1 and prostaglandins. Both PF and cultured PMC superfusate induced a potent, rapidly reversible decrease in the shortening of isolated rat cardiac myocytes. This effect was not associated with changes in intracellular calcium. In vivo, prostaglandins, atrial natriuretic factor and endothelin were present in PF. A greater concentration of atrial natriuretic factor was present in PF than in serum, suggesting molecular diffusion from the myocardium to PF. Preliminary results show that the instillation of vasoactive agents into the pericardial space of dogs rapidly alter coronary and systemic vascular tone, consistent with a molecular diffusion of these substances from PF into the myocardium and circulation. Conclusions: In addition to its mechanical role, the pericardium may contribute to the integration and the regulation of cardiovascular function via a paracrine mechanism.
Intravenous iron: From anathema to standard of care
Authors: Michael Auerbach, Dan Coyne, Harold Ballard
Journal: American Journal of Hematology (2008)

Abstract A growing body of literature supports the use of intravenous iron as a compliment to erythropoiesis stimulatory therapy and in a significant number of disease states where iron is necessary and oral iron is ineffective or not tolerated. The differences in efficacy, safety, and clinical nature of serious adverse events that occur with the various iron preparations are poorly understood. Misinterpretation of adverse events leads to underutilization of this important treatment modality. Understanding the history of the development and use of intravenous iron is crucial to appreciate its importance in the management of anemias of dialysis, cancer, and cancer chemotherapy and properly assess side effects and toxicity. The benefits seen with intravenous iron therapy are independent of the pretreatment levels of serum ferritin, iron, total iron binding capacity, and percent transferrin saturation. Intravenous iron has been shown to overcome hepcidin induced iron restricted erythropoiesis in iron‐replete patients. Available clinical and experimental data suggest that increased utilization of intravenous iron should be considered. Am. J. Hematol., 2008. © 2008 Wiley‐Liss, Inc.
Effects of Deep Femoral Thrombophlebitis on the Circulation of the Lower Extremities
Authors: J. ALEX HALLER
Journal: Circulation (1963)

Studies of the patterns of venous collateral circulation in patients with acute iliofemoral venous thrombosis and in patients with chronic postphlebitic limbs secondary to iliofemoral venous thrombosis show a close similarity to the collateral circulation which develops in experimental iliofemoral venous thrombosis. Serial phlebograms indicate that the collateral circulation will disappear only if the originally thrombosed deep system is returned to functional patency. This reconstitution of function to the venous valves is accomplisbed by early thrombectomy. Thrombectomy may, therefore, be the best protection against the development of a chronic postphlebitic limb.
Reduced cortical responses to noxious heat in patients with rheumatoid arthritis
Authors: A K P Jones, S W G Derbyshire
Journal: Annals of the Rheumatic Diseases (1997)

To test the hypothesis that patients with chronic inflammatory pain develop adaptive cortical responses to noxious stimulation characterised by reduced anterior cingulate responses.Positron emission tomography was used to measure changes in regional cerebral blood flow (rCBF) in response to an acute experimental pain stimulus in six patients with rheumatoid arthritis (RA) in comparison to six age and sex matched controls. A standardised and reproducible non-painful and painful phasic heat stimulus was delivered by a thermal probe to the back of the right hand during six two minute periods during which time rCBF measurements were made. The effects of non-painful heat were subtracted from those of painful heat to weight the analysis towards the non-discriminatory or 'suffering' components of pain processing. Significance maps of pain processing were generated and compared in each group and contrasted with results obtained in a group of patients with atypical facial pain (AFP) that have been previously published.The RA patients showed remarkably damped cortical and subcortical responses to pain compared with the control group. Significant differences between the two groups were observed in the prefrontal (BA 10) and anterior cingulate (BA 24) and cingulofrontal transition cortical (BA 32) areas. The reduced anterior cingulate responses to standardised heat pain were compared with the increased cingulate responses seen in patients with psychogenically maintained pain (AFP) who had both lower pain tolerance and mood than the RA group.Major cortical adaptive responses to standardised noxious heat can be measured and contrasted in patients with different types of chronic pain. The different pattern of cingulate and frontal cortical responses in the patients with inflammatory and non-nociceptive pain suggest that different mechanisms are operating, possibly at a thalamocortical level. Implications for treatment strategies for chronic pain are discussed.
Respiratory Sinus Arrhythmia
Authors: Robert A. Neff, Jijiang Wang, Sunit Baxi, Cory Evans, David Mendelowitz
Journal: Circulation Research (2003)

The heart rate increases during inspiration and decreases during expiration. This respiratory sinus arrhythmia (RSA) occurs by modulation of premotor cardioinhibitory parasympathetic neuron (CPN) activity. However, RSA has not been fully characterized in rats, and despite the critical role of CPNs in the generation of RSA, little is known about the mechanisms that mediate this cardiorespiratory interaction. This study demonstrates that RSA in conscious rats is similar to that in other species. The mechanism of RSA was then examined in vitro. Rhythmic inspiratory-related activity was recorded from the hypoglossal rootlet of 700- to 800-μm medullary sections. CPNs were identified by retrograde fluorescent labeling, and neurotransmission to CPNs was examined using patch-clamp electrophysiological techniques. During inspiratory bursts, the frequency of both spontaneous γ-aminobutyric acidergic (GABAergic) and spontaneous glycinergic synaptic events in CPNs was significantly increased. Focal application of the nicotinic antagonist dihydro-β-erythroidine in an α 4 β 2 -selective concentration (3 μmol/L) abolished the respiratory-evoked increase in GABAergic frequency. In contrast, the increase in glycinergic frequency during inspiration was not altered by nicotinic antagonists. Prenatal nicotine exposure exaggerated the increase in GABAergic frequency during inspiration and enhanced GABAergic synaptic amplitude both between and during inspiratory events. Glycinergic synaptic frequency and amplitude were unchanged by prenatal nicotine exposure. This study establishes a neurochemical link between neurons essential for respiration and CPNs, reveals a functional role for endogenous acetylcholine release and the activation of nicotinic receptors in the generation of RSA, and demonstrates that this cardiorespiratory interaction is exaggerated in rats prenatally exposed to nicotine.
The Application of Synthetic hANP in Diabetic Nephropathy With Nephrotic Syndrome
Authors: Yoko Kikumoto, Jun Wada, Hirofumi Makino
Journal: Diabetes Care (2006)

Although the optimal time to initiate hemodialysis is not well defined, it is necessary to start extracorporeal ultrafiltration methods (ECUM) earlier in uremic diabetic patients to avoid life-threatening events, such as anasarca, heart failure, and lung congestion. These patients frequently manifest the poor response to the administration of high dosage of loop diuretics. To investigate the effectiveness of concomitant usage of synthetic human atrial natriuretic peptide (hANP) with loop diuretics, we administered carperitide (hANP) in a case with diabetic nephropathy and nephrotic syndrome.

A 44-year-old woman with 10-year history of type 2 diabetes …