tbuckley/cabot-search huggingface dataset:
Survival in COPD patients after regular use of fluticasone propionate and salmeterol
Authors: E. Marchand
Journal: European Respiratory Journal (2003)

Finally, we feel confident that the positive result of the Maugeri Foundation Respiratory Failure item set (MRF-28) questionnaire [3] assessment in the treated subjects, also showed a positive impact of one of the most important endpoints of the long-term ventilatory strategy in these patients, which is the health-related quality of life (HRQoL).Although, it is still not clear whether survival can be positively influenced by NPPV in addition to standard long-term oxygen therapy (LTOT), the result obtained on specific HRQoL (together with the positive, although not significant, trend towards the reduction in the follow-up admissions in the critical care area) seems to justify the prescripton of NPPV, at least when a poor condition of the patient (i.e.severe disability, frequent exacerbations and hospitalisations, low effect and clinical control by LTOT) can be proven.Obviously, any conclusion should be made with caution at present.However, although the prescription of noninvasive positive pressure ventilation cannot be recommended as a generalised option in the chronic obstructive pulmonary disease patients, an effort should be made to look for the best candidates on the basis of their history and the pathophysiological background available.
Glomerular type 1 angiotensin receptors augment kidney injury and inflammation in murine autoimmune nephritis
Authors: Steven D. Crowley, Matthew P. Vasievich, Phillip Ruiz, Samantha K. Gould, Kelly K. Parsons, A. Kathy Pazmino, Carie Facemire, Benny J. Chen, Hyung-Suk Kim, Trinh T. Tran, David S. Pisetsky, Laura Barisoni, Minolfa C. Prieto-Carrasquero, Marie Jeansson, Mary H. Foster, Thomas M. Coffman
Journal: Journal of Clinical Investigation (2009)

Studies in humans and animal models indicate a key contribution of angiotensin II to the pathogenesis of glomerular diseases. To examine the role of type 1 angiotensin (AT1) receptors in glomerular inflammation associated with autoimmune disease, we generated MRL-Faslpr/lpr (lpr) mice lacking the major murine type 1 angiotensin receptor (AT1A); lpr mice develop a generalized autoimmune disease with glomerulonephritis that resembles SLE. Surprisingly, AT1A deficiency was not protective against disease but instead substantially accelerated mortality, proteinuria, and kidney pathology. Increased disease severity was not a direct effect of immune cells, since transplantation of AT1A-deficient bone marrow did not affect survival. Moreover, autoimmune injury in extrarenal tissues, including skin, heart, and joints, was unaffected by AT1A deficiency. In murine systems, there is a second type 1 angiotensin receptor isoform, AT1B, and its expression is especially prominent in the renal glomerulus within podocytes. Further, expression of renin was enhanced in kidneys of AT1A-deficient lpr mice, and they showed evidence of exaggerated AT1B receptor activation, including substantially increased podocyte injury and expression of inflammatory mediators. Administration of losartan, which blocks all type 1 angiotensin receptors, reduced markers of kidney disease, including proteinuria, glomerular pathology, and cytokine mRNA expression. Since AT1A-deficient lpr mice had low blood pressure, these findings suggest that activation of type 1 angiotensin receptors in the glomerulus is sufficient to accelerate renal injury and inflammation in the absence of hypertension.
Neutrophils Promote the Malignant Glioma Phenotype through S100A4
Authors: Ji Liang, Yuji Piao, Lindsay Holmes, Gregory N. Fuller, Verlene Henry, Ningyi Tiao, John F. de Groot
Journal: Clinical Cancer Research (2013)

Abstract Purpose: Antiangiogenic therapy is effective in blocking vascular permeability, inhibiting vascular proliferation, and slowing tumor growth, but studies in multiple cancer types have shown that tumors eventually acquire resistance to blockade of blood vessel growth. Currently, the mechanisms by which this resistance occurs are not well understood. Experimental Design: In this study, we evaluated the effects of neutrophils on glioma biology both in vitro and in vivo and determined target genes by which neutrophils promote the malignant glioma phenotype during anti-VEGF therapy. Results: We found that an increase in neutrophil infiltration into tumors is significantly correlated with glioma grade and in glioblastoma with acquired resistance to anti-VEGF therapy. Our data demonstrate that neutrophils and their condition media increased the proliferation rate of glioblastoma-initiating cells (GIC). In addition, neutrophils significantly increased GICs Transwell migration compared with controls. Consistent with this behavior, coculture with neutrophils promoted GICs to adopt morphologic and gene expression changes consistent with a mesenchymal signature. Neutrophil-promoting tumor progression could be blocked by S100A4 downregulation in vitro and in vivo. Furthermore, S100A4 depletion increased the effectiveness of anti-VEGF therapy in glioma. Conclusions: Collectively, these data suggest that increased recruitment of neutrophils during anti-VEGF therapy promotes glioma progression and may promote treatment resistance. Tumor progression with mesenchymal characteristics is partly mediated by S100A4, the expression of which is increased by neutrophil infiltration. Targeting granulocytes and S100A4 may be effective approaches to inhibit the glioma malignant phenotype and diminish antiangiogenic therapy resistance. Clin Cancer Res; 20(1); 187–98. ©2013 AACR.
High-Dose Therapy and Autologous Peripheral-Blood Stem-Cell Transplantation As Salvage Treatment for HIV-Associated Lymphoma in Patients Receiving Highly Active Antiretroviral Therapy
Authors: Alessandro Re, Chiara Cattaneo, Mariagrazia Michieli, Salvatore Casari, Michele Spina, Maurizio Rupolo, Bernardino Allione, Annamaria Nosari, Clara Schiantarelli, Mariagrazia Viganò, Immacolata Izzi, Piero Ferremi, Arnalda Lanfranchi, Maurizio Mazzuccato, Gianpiero Carosi, Umberto Tirelli, Giuseppe Rossi
Journal: Journal of Clinical Oncology (2003)

High-dose therapy (HDT) and peripheral-blood stem-cell transplantation (PBSCT) in HIV-associated lymphoma (HIV-Ly) has been recently reported in selected patients. We describe the results of a multi-institutional program of HDT and PBSCT as salvage therapy in HIV-Ly responsive to highly active antiretroviral therapy (HAART) in unselected patients.Patients with resistant or relapsed HIV-Ly after first-line chemotherapy (CT) underwent PBSC collection after a course of second-line CT or cyclophosphamide and granulocyte colony-stimulating factor. Patients with chemotherapy-sensitive disease received carmustine, etoposide, cytarabine, and melphalan (BEAM regimen) and PBSC reinfusion. Effective HAART was maintained during the entire program.Sixteen consecutive patients entered the program. Adequate collection of PBSC was obtained in 80% of patients (median CD34+ cells 6.8 x 106/kg). Three patients had early progression. Ten patients (62%) received PBSCT with prompt engraftment in all patients (neutrophils and platelet engraftment after a median of 10 days [range, 8 to 10 days] and 13 days [range, 8 to 18 days], respectively). No patients died as a result of opportunistic or other infections or treatment-related complications. Eight of nine assessable patients achieved complete remission (one patient after radiotherapy for residual disease) and one patient achieved partial remission. Two patients experienced relapse and died at +10 and +14 months. Six patients are alive and disease free at a median of 8 months after transplantation.Our data confirm that HDT plus PBSCT is feasible and active as salvage therapy in HIV-Ly on a multi-institutional basis and in unselected HAART-responding patients. HIV infection should no longer preclude the opportunity of HDT in patients with lymphoma.
Lymphatic Imaging: Focus on Imaging Probes
Authors: Gang Niu, Xiaoyuan Chen
Journal: Theranostics (2015)

In view of the importance of sentinel lymph nodes (SLNs) in tumor staging and patient management, sensitive and accurate imaging of SLNs has been intensively explored.Along with the advance of the imaging technology, various contrast agents have been developed for lymphatic imaging.In this review, the lymph node imaging agents were summarized into three groups: tumor targeting agents, lymphatic targeting agents and lymphatic mapping agents.Tumor targeting agents are used to detect metastatic tumor tissue within LNs, lymphatic targeting agents aim to visualize lymphatic vessels and lymphangionesis, while lymphatic mapping agents are mainly for SLN detection during surgery after local administration.Coupled with various signal emitters, these imaging agents work with single or multiple imaging modalities to provide a valuable way to evaluate the location and metastatic status of SLNs.
Surgery for Aortic Regurgitation in Women
Authors: Elizabeth Klodas, Maurice Enriquez-Sarano, A. Jamil Tajik, Charles J. Mullany, Kent R. Bailey, James B. Seward
Journal: Circulation (1996)

Background Indications for surgical correction of aortic regurgitation have been established mostly in men and have not been validated in women. The outcome of this surgical correction in women is unknown. Methods and Results Baseline characteristics and postoperative outcomes were compared between 51 women and 198 men undergoing surgery for isolated aortic regurgitation between 1980 and 1989. Compared with men, women had surgery rarely for severe left ventricular enlargement (systolic diameter ≥55 mm in 11% versus 27%, P =.031; diastolic diameter ≥80 mm in 0% versus 16%, P &lt;.0001) and more often for class III to IV symptoms (59% versus 32%, P &lt;.0001). Operative mortalities were similar in women and men (3.9% and 4.5%, respectively). Among operative survivors, 10-year survival was worse for women than for men (39±9% versus 72±4%, P =.0002) and, in contrast with men, was worse than expected for women ( P &lt;.0001). Independent predictors of late survival were different for men (age and ejection fraction) and women (age and concomitant coronary bypass grafting). By multivariate analysis, female sex was an independent predictor of worse late survival (adjusted relative risk, 1.80; 95% CI, 1.04 to 3.11). Conclusions The generalization to women of the unadjusted left ventricular diameter surgical criteria established in men results in irrelevant criteria almost never reached in women, who often undergo surgery after developing severe symptoms. After surgery, women exhibit an excess late mortality, suggesting that surgical correction of aortic regurgitation should be considered at an earlier stage in women.
Invasive and Noninvasive Strategies for Management of Suspected Ventilator-Associated Pneumonia
Authors: Jean-Yves Fagon, Jean Chastre, Michel Wolff, Claude Gervais, Sylvie Parer-Aubas, François Stéphan, Thomas Similowski, Alain Mercat, Jean-Luc Diehl, Jean-Pierre Sollet, Alain Tenaillon
Journal: Annals of Internal Medicine (2000)

Background: Optimal management of patients who are clinically suspected of having ventilator-associated pneumonia remains open to debate. Objective: To evaluate the effect on clinical outcome and antibiotic use of two strategies to diagnose ventilator-associated pneumonia and select initial treatment for this condition. Design: Multicenter, randomized, uncontrolled trial. Setting: 31 intensive care units in France. Patients: 413 patients suspected of having ventilator-associated pneumonia. Intervention: The invasive management strategy was based on direct examination of bronchoscopic protected specimen brush samples or bronchoalveolar lavage samples and their quantitative cultures. The noninvasive ("clinical") management strategy was based on clinical criteria, isolation of microorganisms by nonquantitative analysis of endotracheal aspirates, and clinical practice guidelines. Measurements: Death from any cause, quantification of organ failure, and antibiotic use at 14 and 28 days. Results: Compared with patients who received clinical management, patients who received invasive management had reduced mortality at day 14 (16.2% and 25.8%; difference, −9.6 percentage points [95% CI, −17.4 to −1.8 percentage points]; P = 0.022), decreased mean Sepsis-related Organ Failure Assessment scores at day 3 (6.1 ± 4.0 and 7.0 ± 4.3; P = 0.033) and day 7 (4.9 ± 4.0 and 5.8 ± 4.4; P = 0.043), and decreased antibiotic use (mean number of antibiotic-free days, 5.0 ± 5.1 and 2.2 ± 3.5; P < 0.001). At 28 days, the invasive management group had significantly more antibiotic-free days (11.5 ± 9.0 compared with 7.5 ± 7.6; P < 0.001), and only multivariate analysis showed a significant difference in mortality (hazard ratio, 1.54 [CI, 1.10 to 2.16]; P = 0.01). Conclusions: Compared with a noninvasive management strategy, an invasive management strategy was significantly associated with fewer deaths at 14 days, earlier attenuation of organ dysfunction, and less antibiotic use in patients suspected of having ventilator-associated pneumonia. *For members of the VAP Trial Group, see the Appendix.
Thromboprophylaxis Is Associated With Reduced Post-hospitalization Venous Thromboembolic Events in Patients With Inflammatory Bowel Diseases
Authors: Ashwin N. Ananthakrishnan, Andrew Cagan, Vivian S. Gainer, Su-Chun Cheng, Tianxi Cai, Elizabeth Scoville, Gauree G. Konijeti, Peter Szolovits, Stanley Y. Shaw, Susanne Churchill, Elizabeth W. Karlson, Shawn N. Murphy, Isaac Kohane, Katherine P. Liao
Journal: Clinical Gastroenterology and Hepatology (2014)
Treg-mediated immunosuppression involves activation of the Notch-HES1 axis by membrane-bound TGF- 
Authors: M. Ostroukhova
Journal: Journal of Clinical Investigation (2006)

Studies in humans and mice show an important role for Tregs in the control of immunological disorders. The mechanisms underlying the immunosuppressive functions of Tregs are not well understood. Here, we show that CD4+ T cells expressing Foxp3 and membrane-bound TGF-beta (TGF-beta(m+)Foxp3+), previously shown to be immunosuppressive in both allergic and autoimmune diseases, activate the Notch1-hairy and enhancer of split 1 (Notch1-HES1) axis in target cells. Soluble TGF-beta and cells secreting similar levels of soluble TGF-beta were unable to trigger Notch1 activation. Inhibition of Notch1 activation in vivo reversed the immunosuppressive functions of TGF-beta(m+)Foxp3+ cells, resulting in severe allergic airway inflammation. Integration of the TGF-beta and Notch1 pathways may be an important mechanism for the maintenance of immune homeostasis in the periphery.
Quality of Private and Public Ambulatory Health Care in Low and Middle Income Countries: Systematic Review of Comparative Studies
Authors: Sima Berendes, Peter Heywood, Sandy Oliver, Paul Garner
Journal: PLoS Medicine (2011)

In developing countries, the private sector provides a substantial proportion of primary health care to low income groups for communicable and non-communicable diseases. These providers are therefore central to improving health outcomes. We need to know how their services compare to those of the public sector to inform policy options.We summarised reliable research comparing the quality of formal private versus public ambulatory health care in low and middle income countries. We selected studies against inclusion criteria following a comprehensive search, yielding 80 studies. We compared quality under standard categories, converted values to a linear 100% scale, calculated differences between providers within studies, and summarised median values of the differences across studies. As the results for for-profit and not-for-profit providers were similar, we combined them. Overall, median values indicated that many services, irrespective of whether public or private, scored low on infrastructure, clinical competence, and practice. Overall, the private sector performed better in relation to drug supply, responsiveness, and effort. No difference between provider groups was detected for patient satisfaction or competence. Synthesis of qualitative components indicates the private sector is more client centred.Although data are limited, quality in both provider groups seems poor, with the private sector performing better in drug availability and aspects of delivery of care, including responsiveness and effort, and possibly being more client orientated. Strategies seeking to influence quality in both groups are needed to improve care delivery and outcomes for the poor, including managing the increasing burden of non-communicable diseases.
A role for leptin in rheumatic diseases?
Authors: G Palmer
Journal: Annals of the Rheumatic Diseases (2003)

<h3>AIMS</h3> To compare the rate of recurrence and complication after surgery for primary pterygium performed by one surgeon using either intraoperative mitomycin C or β irradiation. <h3>METHODS</h3> A retrospective study was performed of 164 eyes in 164 patients who had undergone primary pterygium surgery. After the pterygium was excised, the bare sclera was covered by sliding adjacent superior conjunctiva. 103 eyes received intraoperative mitomycin C (0.04%, 150 seconds) and 61 eyes β irradiation (total dose 21.6 Gy). The mean follow up period was 20.2 (SD 17.9) months (range 1–66 months). Recurrence was defined as the postoperative regrowth of fibrovascular tissue crossing the corneoscleral limbus. <h3>RESULTS</h3> The recurrence rate after mitomycin C and β irradiation was 8.74% and 23.0% of eyes, respectively, after mean follow up of 17.9 and 31.2 months, respectively. The Kaplan–Meier survival analysis revealed a significantly better outcome for those who had intraoperative mitomycin C (Mantel–Cox log rank analysis, p=0.031). The mean interval to recurrence was not significantly different between the two groups. During the follow up, none of the patients showed side effects or reactions related to mitomycin C or β irradiation. <h3>CONCLUSIONS</h3> The intraoperative administration of 0.04% mitomycin C is more effective than β irradiation as an adjunctive treatment for pterygium surgery in the patient population examined in this study.
Food Group Consumption and Glycemic Control in People With and Without Type 2 Diabetes
Authors: Emilia Papakonstantinou, Demosthenes B. Panagiotakos, Christos Pitsavos, Christina Chrysohoou, Antonis Zampelas, Yannis Skoumas, Christodoulos Stefanadis
Journal: Diabetes Care (2005)

Results from population-based studies on the effects of food groups on glycemic control seem conflicting (1–10). In this report, we sought to evaluate the association of various food groups with indexes of glycemic control in adults with or without type 2 diabetes without any evidence of cardiovascular disease and randomly selected from the general population.

During 2001–2002, we randomly enrolled 1,514 men (18–87 years old) and 1,528 women (18–89 years old) from the Attica region of Greece (of them, 5% of men and 3% of women were excluded because of history of cardiovascular diseases). Diabetes was defined according to the established criteria of the American Diabetes Association (11). Only subjects with type 2 diabetes were included in the analysis due to the small sample size of people with type 1 diabetes. Details about the aims and methods of the ATTICA study have been presented elsewhere (12).

### Anthropometrical, clinical, and biochemical characteristics

Standing height and weight were recorded, and BMI was calculated (weight [in kilograms] divided by the square of height [in meters]).

Arterial blood pressure and lipids were measured as previously described (11). Blood glucose levels were measured immediately with a Beckman Glucose Analyzer (Beckman Instruments, Fullerton, …
Fungal Viability Is Essential in Modulating of Adaptive Immune Responses in Mice
Authors: Brett J. Green, Ajay P. Nayak, Tara L. Croston, Angela R. Lemons, Nikki B. Marshall, W.Travis Goldsmith, Michael Kashon, Brandon F. Law, Lauren M. Wagner, Carrie M. Long, Dori M. Germolec, Donald H. Beezhold
Journal: Journal of Allergy and Clinical Immunology (2015)
Pulmonary exacerbations as indicators of progression of lung disease in young children with CF
Authors: Don B Sanders, Christopher Hooper Goss
Journal: Thorax (2013)

The approval of ivacaftor by the European Medicines Agency (EMA) and the US Food and Drug Administration (US FDA) and the ongoing development of other drugs that target the underlying defect that causes cystic fibrosis (CF) have generated a great deal of excitement and hope for patients with CF.1 ,2 To truly maximise the potential benefits of these drugs, they will need to be administered before irreversible lung disease (eg, bronchiectasis) develops. Most patients with CF who have taken part in therapeutic drug trials have been at least 6 years of age, when most patients begin to be able to perform spirometry, the most commonly used endpoint in CF therapeutic trials. However, an observational study in Australian Respiratory Early Surveillance Team for Cystic Fibrosis (AREST CF) demonstrated that structural lung disease, including bronchiectasis, may be present even in infancy.3 Thus, to minimise the progression of lung disease, we must initiate treatment as early as safely possible for those patients who are at risk for developing lung disease. The challenge in obtaining EMA or FDA approval for new therapeutic interventions to be administered in early life, where the progression of lung disease occurs in a ‘black box’, is demonstrating safety and efficacy in children too young to perform traditional spirometry. Given that pulmonary exacerbations occur frequently even in young children, they offer an inviting clinical endpoint for future studies in this age group. The FDA defines clinical endpoints as direct measures of how a patient feels, functions or survives.4 Pulmonary exacerbations are …
What Can We Learn from Rodents about Prolactin in Humans?
Authors: Nira Ben-Jonathan, Christopher R. LaPensee, Elizabeth W. LaPensee
Journal: Endocrine Reviews (2007)

Prolactin (PRL) is a 23-kDa protein hormone that binds to a single-span membrane receptor, a member of the cytokine receptor superfamily, and exerts its action via several interacting signaling pathways. PRL is a multifunctional hormone that affects multiple reproductive and metabolic functions and is also involved in tumorigenicity. In addition to being a classical pituitary hormone, PRL in humans is produced by many tissues throughout the body where it acts as a cytokine. The objective of this review is to compare and contrast multiple aspects of PRL, from structure to regulation, and from physiology to pathology in rats, mice, and humans. At each juncture, questions are raised whether, or to what extent, data from rodents are relevant to PRL homeostasis in humans. Most current knowledge on PRL has been obtained from studies with rats and, more recently, from the use of transgenic mice. Although this information is indispensable for understanding PRL in human health and disease, there is sufficient disparity in the control of the production, distribution, and physiological functions of PRL among these species to warrant careful and judicial extrapolation to humans.