tbuckley/cabot-search huggingface dataset:
S70 Implementing a COPD discharge bundle on a large scale
Authors: L Sewell, M Cheung, C Mitchell-Issitt, K Barley, C Chebbout, S Msimanga, S Boyce, MC Steiner, SJ Singh
Journal: Thorax (2013)

<h3>Introduction</h3> There is emerging interest in the delivery of discharge care bundles to manage patients admitted with an an exacerbation of a chronic disease. This approach has been tested on a limited number of patients and the importance of care bundles has been acknowledged by the BTS. However, it is unclear how COPD discharge bundles could be implemented on a larger number of patients without additonal resources. <h3>Objective</h3> We wanted to audit the effect of implementing a COPD discharge bundle to all patients discharged with a primary diagnosis of COPD upon smoking cessation and pulmonary rehabilitation (PR) referral rates and to establish the effect upon length of stay (LoS). <h3>Methods</h3> We redeployeda Respiratory Early Discharge Service (REDS) in order to deliver the University Hospitals of Leicester COPD discharge bundle. This is comprised of evidence-based interventions including:referral to smoking cessation and PR services, implementation of a self management plan, assessment of inhaler technique, follow up phone calls at 2 working days and 15 days post discharge. The discharge bundle was delivered by the REDS team from April 2012 to March 2013. The total number of patients discharged with a primary diagnosis of COPD (diagnosis code J41–44) from Glenfield Hospital was collected along with referral rates to smoking cessation and PR services. Mean LoS for those patients receiving the care bundle was also recorded. <h3>Results</h3> From April 2012 to March 2013 a total of 1742 patients were discharged with a primary diagnosis of COPD. 1160 of these patients received the COPD discharge bundle. Smoking cessation referrals rose from 23.7% in quarter 1 to 48.3% in quarter 4. Pulmonary rehabilitation referals rose from 39.7% in quarter 1 to 55.9% in quarter 4. Mean LoS for patients who received the discharge care bundle was 6.17 days compared to 7.22 days for 2011–2012. The mean LoS for patients who did not receive the care bundle was 7.08 days. <h3>Conclusions</h3> A COPD discharge care bundle can be implemented on a large scale with increased referral rates to smoking cessation and PR services. No increase in LoS was noted dispite redeploying an early discharge service.
Lung transplantation for pulmonary silicosis: The Israeli scene
Authors: Anat Amital, David Shitrit, Yael Raviv, Benjamin Medalion, Ilana Bakal, Mordechai Kramer
Journal: European Respiratory Journal (2011)

Background:  Silicosis is a rare indication for lung transplantion (LT). The number of patients with silicosis in Israel is increasing due to improper processing of a new quarts stone Caesarstone.   Methods and materials:  We retrospectively reviewed the files of patients that were transplanted in Rabin Medical center (RMC) and compared the data to that of the ISHLT.   Results:  According to the ISHLT registry out of 24,090 transplants 50 patients were transplanted for Silicosis between 1994-may 2009.  Out of 336 lung transplantations in RMC between 1997- may 2010 8 patients underwent LT for silicosis. There were more patients transplanted for silicosis in RMC compared to the ISHLT (p  All of our patients were men, their average age being 50.5. Four underwent left LT 3 right LT and 1 bilateral sequential LT. Before transplant their average FEV1 and DLCO were 298.9 and 28.58, one patient was treated with ECMO. In all the patients the native lung extraction was difficult because of severe pleural adhesions.  Three patients died, due to technical failure, recurrent pneumothorax, and recurrent infections. Three patients had intra-operative bleeding, one of them needed a second operative procedure.  Post operative complications also included severe infections in 3 patients, severe primary graft dysfunction in 2 patients, injury to the phrenic nerve and diaphragm paralysis in 2 patients. According to the ISHLT 6 of 36 patients needed additional surgical procedure, and 20 out of 39 were treated for infection.   Conclusions:  Compared to the ISHLT registry, in Israel there are more transplantations for silicosis. LT in patients with silicosis is technically difficult with higher morbidity and mortality.
Approximate Likelihood Calculation on a Phylogeny for Bayesian Estimation of Divergence Times
Authors: M. d. Reis, Z. Yang
Journal: Molecular Biology and Evolution (2011)

The molecular clock provides a powerful way to estimate species divergence times. If information on some species divergence times is available from the fossil or geological record, it can be used to calibrate a phylogeny and estimate divergence times for all nodes in the tree. The Bayesian method provides a natural framework to incorporate different sources of information concerning divergence times, such as information in the fossil and molecular data. Current models of sequence evolution are intractable in a Bayesian setting, and Markov chain Monte Carlo (MCMC) is used to generate the posterior distribution of divergence times and evolutionary rates. This method is computationally expensive, as it involves the repeated calculation of the likelihood function. Here, we explore the use of Taylor expansion to approximate the likelihood during MCMC iteration. The approximation is much faster than conventional likelihood calculation. However, the approximation is expected to be poor when the proposed parameters are far from the likelihood peak. We explore the use of parameter transforms (square root, logarithm, and arcsine) to improve the approximation to the likelihood curve. We found that the new methods, particularly the arcsine-based transform, provided very good approximations under relaxed clock models and also under the global clock model when the global clock is not seriously violated. The approximation is poorer for analysis under the global clock when the global clock is seriously wrong and should thus not be used. The results suggest that the approximate method may be useful for Bayesian dating analysis using large data sets.
Ionizing Radiation Activates Late Herpes Simplex Virus 1 Promoters via the p38 Pathway in Tumors Treated with Oncolytic Viruses
Authors: James J. Mezhir, Sunil J. Advani, Kerrington D. Smith, Thomas E. Darga, Alice P.W. Poon, Hank Schmidt, Mitchell C. Posner, Bernard Roizman, Ralph R. Weichselbaum
Journal: Cancer Research (2005)

Abstract Ionizing radiation potentiates the oncolytic activity of attenuated herpes simplex viruses in tumors exposed to irradiation at specific time intervals by inducing higher virus yields. Cell culture studies have shown that an attenuated virus lacking the viral γ134.5 genes underproduces late proteins whose synthesis depends on sustained synthesis of viral DNA. Here we report that ionizing radiation enhances gene expression from late viral promoters in transduced cells in the absence of other viral gene products. Consistent with this result, we show that in tumors infected with the attenuated virus, ionizing radiation increases 13.6-fold above baseline the gene expression from a late viral promoter as early as 2 hours after virus infection, an interval too short to account for viral DNA synthesis. The radiation-dependent up-regulation of late viral genes is mediated by the p38 pathway, inasmuch as the enhancement is abolished by p38 inhibitors or a p38 dominant-negative construct. The p38 pathway is not essential for wild-type virus gene expression. The results suggest that ionizing radiation up-regulates late promoters active in the course of viral DNA synthesis and provide a rationale for use of radiation to up-regulate cytotoxic genes introduced into tumor cells by viral vectors for cytoreductive therapy.
A Descriptive and Comparative Study of the Prevalence of Depressive and Anxiety Disorders in Low-Income Adults With Type 2 Diabetes and Other Chronic Illnesses
Authors: Janet Thomas, Glenn Jones, Isabel Scarinci, Phillip Brantley
Journal: Diabetes Care (2003)

OBJECTIVE—To determine whether type 2 diabetes contributes to the presence of depressive and anxiety disorder diagnoses in low-income adults with hypertension, asthma, and/or arthritis. RESEARCH DESIGN AND METHODS—Using a cross-sectional design, this study administered a structured diagnostic interview to low-income primary care patients diagnosed with type 2 diabetes, hypertension, arthritis, and asthma, as well as to those with no chronic illness (n = 326), to determine the 12-month prevalence of depressive and anxiety disorders. A logistic regression (LR) model was used to assess whether a diagnosis of depression and/or anxiety was associated with type 2 diabetes after adjusting for known risk factors. RESULTS—A high prevalence rate of depressive and/or anxiety disorders was found in the total sample (29%) and in all three illness groups: type 2 diabetes (36%), other chronic illnesses (24%), and no chronic illness (31%). Using LR, a main effect was detected for illness group when age and education were controlled (χ2 = 22.66, df 4, P = 0.000). Specifically, the odds of occurrence of a depressive and/or anxiety disorder in those with comorbid type 2 diabetes were twice that in the nondiabetic, chronically ill comparison group (odds ratio 2.26, 95% CI 1.28–4.01, P = 0.005). CONCLUSIONS—These results suggest a positive contribution of type 2 diabetes to increased rates of depressive and/or anxiety disorders in patients with hypertension, asthma, and/or arthritis and support prior research that type 2 diabetes may serve as an indicator of depression and anxiety in low-income adults treated in primary care clinics.
Modified Dendritic Cells Coexpressing Self and Allogeneic Major Histocompatability Complex Molecules
Authors: Vincenzo Mirenda, Ivan Berton, Joseph Read, Terence Cook, Jennifer Smith, Anthony Dorling, Robert Ian Lechler
Journal: Journal of the American Society of Nephrology (2004)

ABSTRACT. A feature of the tolerance that has been described in experimental models is that it can be transferred by CD4+ T cells to a naive recipient. Described is a novel approach to induce indirect pathway regulatory T cells in a rat model that exploits the natural processing and presentation of major histocompatability complex (MHC) molecules as peptide by the MHC class II molecules of the same cell. Dendritic cells (DC) coexpressing donor (AUG) and recipient (LEW) MHC molecules were rendered tolerogenic by treatment with dexamethasone. After injection into LEW animals followed by a single low dose of CTLA4-Ig, T cells were rendered unresponsive to indirectly presented AUG alloantigens, but retained direct pathway responsiveness to fully allogeneic AUG cells. The T cells from the DC-injected rats were unresponsive to (LEW × AUG)F1 stimulator cells, suggesting the presence of indirect pathway regulatory cells whose activity depended on the presence of LEW MHC molecules. Depletion of CD25+ cells from the responder population led to a marked increase in proliferation, and the T cells from the DC-injected rats inhibited the response of naive LEW T cells to (LEW × AUG)F1, but not to AUG, stimulator cells, further indicating indirect pathway-mediated regulation. Most importantly, pretreatment of LEW rats with the dexamethasone-treated DC led to the indefinite survival of AUG kidney grafts after a short course of cyclosporin to inhibit the early direct pathway response. Similarly treated AUG DC had no effect, confirming the privileged status of F1 cells in the induction of indirect pathway regulation.
Identification of Highly Responsive Kidney Transplant Recipients Using Pretransplant Soluble CD30
Authors: Caner Süsal, Steffen Pelzl, Bernd Döhler, Gerhard Opelz
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. The identification of high immunologic responders is desirable for the selection of appropriate immunosuppressive regimens. With the collaboration of 29 transplant centers in 15 countries, we investigated whether the pretransplant serum content of soluble CD30 (sCD30), a marker for the activation state of Th2-type cytokine producing T cells, is a useful predictor of kidney graft outcome. Pretransplant sera of 3899 cadaver kidney recipients were tested for serum sCD30 concentration using a commercially available enzyme-linked immunosorbent assay kit. Subsequent kidney graft survival was analyzed. The 5-yr graft survival rate in 901 recipients with a high pretransplant serum sCD30 (≥100 U/ml) was 64 ± 2%, significantly lower than the 75 ± 1% rate in 2998 recipients with low sCD30 (<100 U/ml) (P < 0.0001). High sCD30 was associated primarily with graft loss and not with patient death. The sCD30 effect on graft survival was evident in first transplants as well as in retransplants, in presensitized patients with lymphocytotoxic antibodies as well as in nonsensitized patients, and in patients who received HLA well-matched kidneys as well as in patients who received poorly matched grafts. Recipients with a high pretransplant sCD30 needed significantly more rejection treatment after the first posttransplant year and continued to lose grafts at a higher rate during the 5-yr follow-up period, indicating that pretransplant sCD30 predicts not only the risk of acute rejection but also of chronic allograft nephropathy.
Agents with vasodilator properties in acute heart failure: how to design successful trials
Authors: Alexandre Mebazaa, Dan Longrois, Marco Metra, Christian Mueller, Arthur Mark Richards, Lothar Roessig, Marie France Seronde, Naoki Sato, Norman L. Stockbridge, Wendy Gattis Stough, Angeles Alonso, Robert J. Cody, Nancy Cook Bruns, Mihai Gheorghiade, Johannes Holzmeister, Said Laribi, Faiez Zannad
Journal: European Journal of Heart Failure (2015)
HLA Class II Expression by Hodgkin Reed-Sternberg Cells Is an Independent Prognostic Factor in Classical Hodgkin's Lymphoma
Authors: Arjan Diepstra, Gustaaf W. van Imhoff, Henrike E. Karim-Kos, Anke van den Berg, Gerard J. te Meerman, Marijke Niens, Ilja M. Nolte, Esther Bastiaannet, Michael Schaapveld, Edo Vellenga, Sibrand Poppema
Journal: Journal of Clinical Oncology (2007)

The neoplastic Hodgkin Reed-Sternberg (HRS) cells in classical Hodgkin's lymphoma (cHL) are derived from B cells. The frequency of HLA class II downregulation and its effect on prognosis are unknown.Immunohistochemistry results for HLA class II were evaluated in 292 primary cHL patients in a population-based approach. Patients were diagnosed between 1989 and 2000 in the northern part of the Netherlands. Median age at diagnosis was 38 years (range, 8 to 88 years); 63% had Ann Arbor stage I or II, 24% stage III, and 13% stage IV disease. Median follow-up was 7.1 years. For 168 patients, HLA genotype data were available.Lack of HLA class II cell-surface expression on HRS cells was observed in 41.4% and was more common in patients with extranodal disease, patients with Epstein-Barr virus-negative disease, and patients with HLA class I-negative HRS cells. Alleles of three microsatellite markers in the HLA class II region were associated with presence or absence of protein expression. In univariate analyses, lack of HLA class II expression coincided with adverse outcome (5-years failure free survival [FFS], 67% v 85%; P = .001; 5-years age and sex matched relative survival (RS), 80% v 90%; P = .027). This effect remained in multivariate analyses for FFS with a hazard ratio of 2.40 (95% CI, 1.45 to 3.98) and RS with a relative excess risk of death of 2.55 (95% CI, 1.22 to 5.31).Lack of membranous HLA class II expression by HRS cells in diagnostic lymph node specimens is an independent adverse prognostic factor in cHL.
Fatal hepatitis associated with diclofenac.
Authors: E G Breen, J McNicholl, E Cosgrove, J McCabe, F M Stevens
Journal: Gut (1986)

Non-steroidal anti-inflammatory agents (NSAIDS) are a well recognised cause of hepatotoxicity. Diclofenac, a relatively new NSAID, was first introduced into the UK in 1979. Five cases of hepatitis have recently been reported, principally in the French literature. We report the first fulminant case of hepatitis in the English literature in a patient taking diclofenac and indomethacin.
Neuronal Chemorepellent Slit2 Inhibits Vascular Smooth Muscle Cell Migration by Suppressing Small GTPase Rac1 Activation
Authors: Dong Liu, Jie Hou, Xing Hu, Xuerong Wang, Yan Xiao, Yongshan Mou, Hector De Leon
Journal: Circulation Research (2006)

The Slits are secreted proteins with roles in axonal guidance and leukocyte migration. On binding to Robo receptors, Slit2 repels developing axons and inhibits leukocyte chemotaxis. Slit2 is cleaved into Slit2-N, a protein tightly binding to cell membranes, and Slit2-C, a diffusible fragment. In the present study, we characterized the functional role of Slit2-N in vascular smooth muscle cells (VSMCs) and the cell association properties of 2 truncated versions of Slit2-N. Here, we document for the first time that Slit2-N is a chemorepellent of VSMCs. Intact blood vessels expressed Slit2 and Robo receptors as demonstrated by immunohistochemistry and quantitative real time PCR. Recombinant Slit2-N prevented the platelet-derived growth factor (PDGF)-stimulated migration of VSMCs. Slit2-N also abrogated PDGF-mediated activation of small guanosine triphosphatase (GTPase) Rac1, a member of the Rho GTPase superfamily of proteins involved in regulating the actin cytoskeleton. Furthermore, Slit2-N inhibited the PDGF-induced formation of lamellipodia, a crucial cytoskeletal reorganization event for cell motility. Slit2-N had no effect on the PDGF-mediated increase in DNA synthesis determined by [3H]thymidine uptake, suggesting that VSMC growth is unaffected by Slit2. Analysis of 2 engineered Slit2-N fragments (Slit2-N/1118 and Slit2-N/1121) indicated that 3 amino acids upstream of the putative cleavage site (Arg1121, Thr1122) are involved in the association of Slit2-N to the cell membrane. Our data assign a novel functional role to Slit2 in vascular function and show that cell guidance mechanisms that operate in the developing central nervous system are conserved in VSMCs.
Clofarabine and cytarabine combination as induction therapy for acute myeloid leukemia (AML) in patients 50 years of age or older
Authors: Stefan Faderl, Srdan Verstovsek, Jorge Cortes, Farhad Ravandi, Miloslav Beran, Guillermo Garcia-Manero, Alessandra Ferrajoli, Zeev Estrov, Susan O'Brien, Charles Koller, Francis J. Giles, William Wierda, Monica Kwari, Hagop M. Kantarjian
Journal: Blood (2006)
PHENOMENON OF LOCAL SKIN REACTIVITY TO BACTERIAL FILTRATES: PASSIVE IMMUNITY TO REACTING FACTORS
Authors: Gregory Shwartzman
Journal: The Journal of Experimental Medicine (1931)

It has proved possible to elicit passive immunity to B. typhosus reacting factors by means of normal and immune homologous neutralizing antibodies. The in vivo serum protection against these factors followed the law of multiple proportions. There was observed a considerable loss of antibodies from the blood stream. Passive immunity was best obtained when the immune serum was injected intravenously (1/2) hour before the intravenous injection of the reacting factors. It was possible to prevent the occurrence of the local skin reaction by an intravenous injection of serum after the intravenous injection of the reacting factors, provided the serum dose was very large and provided the serum injection was made immediately after the filtrate injection. A number of experiments clearly demonstrated the interesting fact that the greater the amount of antiserum injected intravenously, the more efficient was the in vivo neutralization, in a ratio distinctly greater than the quantitative increase of serum. It is suggested that there may be a practical value of the observation in relation to serum therapy. The results also demonstrated passive serum protection against the lethal effect of B. typhosus "agar washings" filtrates, in a ratio which seemed to suggest the law of multiple proportions.
Evidence-Based Nutrition Guidelines for Critically Ill Adults
Authors: Marcus J. Schultz
Journal: JAMA (2009)

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KIAA1549:BRAF FUSION GENE IN PEDIATRIC BRAIN TUMORS OF DIFFERENT HISTOGENESIS
Authors: F. Giangaspero, M. Antonelli, M. Badiali, F. R. Buttarelli, L. Moi, M. Sanson
Journal: Neuro-Oncology (2014)

BACKGROUND: The KIAA1549:BRAF fusion (K-B fusion) gene has been considered a driver genetic events and a useful diagnostic marker in pilocytic astrocytomas (PA). However B-K gene fusion has been reported at low frequency in adult diffuse gliomas in association with IDH mutations. To further evaluate the possible occurrence of the B-K gene in non-PA tumors, we investigated the presence of the fusion gene in a series of 69 pediatric brain neoplasms of different histogenesis and grading. METHODS: Reverse-transcription polymerase chain reaction (RT-PCR) and subsequent sequencing. To further validate our findings we performed DNA-based methods as CNV and FISH. For CNV analysis, we used BRAF and KIAA specific primers for quantitative PCR in order to demonstrate the specific gain of the two genes, and for FISH analysis we used a commercially available probe. RESULTS: We detected B-K fusion gene in 5 out 34 (14,7%) non-PA primary tumors, i.e, 1 glioblastomas, 1 anaplastic astrocytoma, 1 anaplastic PXA, 1 ependymoma and 1 ATRT. Moreover, the fusion gene was present in 21 of 35 (63.6%) PAs, and out 3 (33%) WHO grade I gangliogliomas, a percentage overlapping previous studies on pediatric low grade gliomas. Both methods confirmed the presence of the B-K fusion gene but also indicate that the cells harboring the alteration in non-PAs neoplasms were less numerous compared to PAs. Screening for IDH, BRAFv600, and H3F3A mutations showed only one case with K27M-H3.3 mutation, which was not associated with B-K gene. CONCLUSIONS: Our study indicates that: 1) K-B fusion gene can be occasionally detected at low frequency in non-PA tumor of different histogenesis; 2) its occurrence in these neoplasms, probably, represents a random alteration related to genomic instability more than a driver molecular event, 3) its role as diagnostic marker outside the histological spectrum of pediatric low grade gliomas needs to be cautious. SECONDARY CATEGORY: Pediatrics.