tbuckley/cabot-search huggingface dataset:
Collaborative quality improvement to promote evidence based surfactant for preterm infants: a cluster randomised trial
Authors: Jeffrey D Horbar, Joseph H Carpenter, Jeffrey Buzas, Roger F Soll, Gautham Suresh, Michael B Bracken, Laura C Leviton, Paul E Plsek, John C Sinclair
Journal: BMJ (2004)

<h3>Abstract</h3> <b>Objective</b> To test a multifaceted collaborative quality improvement intervention designed to promote evidence based surfactant treatment for preterm infants of 23-29 weeks9 gestation. <b>Design</b> Cluster randomised controlled trial <b>Setting and participants</b> 114 neonatal intensive care units (which treated 6039 infants of 23-29 weeks gestation born in 2001). <b>Main outcome measures</b> Process of care measures: proportion of infants receiving first surfactant in the delivery room, proportion receiving first surfactant more than two hours after birth, and median time from birth to first dose of surfactant. Clinical outcomes: death before discharge home, and pneumothorax. <b>Intervention</b> Multifaceted collaborative quality improvement advice including audit and feedback, evidence reviews, an interactive training workshop, and ongoing faculty support via conference calls and email. <b>Results</b> Compared with those in control hospitals, infants in intervention hospitals were more likely to receive surfactant in the delivery room (adjusted odds ratio 5.38 (95% confidence interval 2.84 to 10.20)), were less likely to receive the first dose more than two hours after birth (adjusted odds ratio 0.35 (0.24 to 0.53)), and received the first dose of surfactant sooner after birth (median of 21 minutes <i>v</i> 78 minutes, P &lt; 0.001). The intervention effect on timing of surfactant was larger for infants born in the participating hospitals than for infants transferred to a participating hospital after birth. There were no significant differences in mortality or pneumothorax. <b>Conclusion</b> A multifaceted intervention including audit and feedback, evidence reviews, quality improvement training, and follow up support changed the behaviour of health professionals and promoted evidence based practice.
Mortality and technique failure in patients starting chronic peritoneal dialysis: Results of the Netherlands Cooperative Study on the Adequacy of Dialysis
Authors: Kitty J. Jager, Maruschka P. Merkus, Friedo W. Dekker, Els W. Boeschoten, Jan G.P. Tijssen, Paul Stevens, Willem Jan W. Bos, Raymond T. Krediet, None for the Necosad Study Group
Journal: Kidney International (1999)
Phase II Trial of Consolidation Docetaxel and Samarium-153 in Patients With Bone Metastases From Castration-Resistant Prostate Cancer
Authors: Karim Fizazi, Philippe Beuzeboc, Jean Lumbroso, Vincent Haddad, Christophe Massard, Marine Gross-Goupil, Mario Di Palma, Bernard Escudier, Christine Theodore, Yohann Loriot, Elodie Tournay, Jeannine Bouzy, Agnes Laplanche
Journal: Journal of Clinical Oncology (2009)

To assess docetaxel combined with samarium-153-ethylene diamine tetramethylene phosphonic acid (EDTMP), a radiopharmaceutical with a high affinity for bone, in patients with castration-resistant prostate cancer (CRPC).Patients with bone metastases from CRPC who achieved a response or stabilization after four cycles of docetaxel and estramustine were given consolidation docetaxel 20 mg/m(2)/wk for 6 weeks and samarium-153-EDTMP (37 MBq/kg) during week 1. Prostate-specific antigen (PSA) response was assessed by using consensus criteria, and pain was assessed by using a visual analog scale (VAS). This study used a Simon two-step design with PSA-progression-free survival (PFS) as the primary end point.Forty-three patients were included in the trial. A PSA response was obtained in 77% (95% CI, 61% to 82%). The pain response rate was 69% (95% CI, 49% to 85%). At least five of the six planned weekly injections of docetaxel were administered to 34 patients (81%). The consolidation docetaxel-samarium-153-EDTMP regimen was well tolerated; there was no febrile neutropenia, and only two episodes (5%) of rapidly reversible grade 3 thrombocytopenia occurred. Although a serum PSA relapse eventually occurred in all patient cases, this regimen resulted in pain control in the long-term. The median PSA-PFS was 6.4 months (95% CI, 6 to 7 months). The median survival was 29 months (95% CI, 22 to 31); the 1-year survival rate was 77% (62% to 87%); and the 2-year survival rate was 56% (41% to 70%).Combining docetaxel and samarium-153-EDTMP in patients with bone metastases from CRPC is well tolerated, and it yields major pain relief that persists long after treatment. Overall survival compares favorably with that expected in this population of patients, most of whom exhibit symptoms.
P261 Questionnaire to assess acceptability of venous thromboembolism risk assessment tool by admitting doctors and nurses in the medical assessment unit of a district general hospital
Authors: E. K. Nuttall, F. Zaman
Journal: Thorax (2010)

<h3>Introduction</h3> The House of Commons Health Committee estimated 25 000 people in the UK die from preventable hospital acquired venous thromboembolism (VTE) every year. The Department of Health now state all adult patients must have documented VTE risk assessment and have given guidance on thrombosis and bleeding risk factors based on guidance from the National Institute of Clinical Excellence (NICE). Our hospital trust has raised awareness of appropriate prescribing of thromboprophylaxis by alerts on the local intranet, posters in clinical areas, at staff inductions and the development of a VTE risk assessment tool that will be included in the new generic assessment document. The tool was audited with thromboprophylaxis prescribing and found that none of the tools were filled in correctly and 20 out of 50 patients (40%) were not prescribed thromboprophlaxis appropriately. We wanted to find out why these results occurred. <h3>Method</h3> A questionnaire was given to 34 members of staff who are exposed to the new risk assessment forms; 16 doctors and 18 nurses. <h3>Results</h3> All doctors were happy assessing VTE risk, whereas 61% of the nurses were not happy assessing all the risks included. The mean time to fill in the form was 4 min for doctors and nurses. 63% of doctors felt it should be a nursing job to fill in the risk assessment form whereas 77% of nurses felt it was a doctors job to complete the VTE risk assessment. 50% of doctors stated they used the risk assessment form when prescribing thromboprophylaxis and 62% of doctors felt they didn′t need a form to assess risk of VTE. <h3>Conclusion</h3> The trust has used numerous ways to raise awareness of thromboprophylaxis prescribing, including the risk assessment tool. However, 40% of patients audited were not correctly prescribed thromboprophylaxis despite these measures. The majority of nurses felt it was a doctors job to fill in the tool as not all nurses were happy to assess all the risk factors. Only half the doctors stated they used the risk assessment tool and over half the doctors felt they didn9t need a form to assess VTE risk.
Radioimmunotherapy with α-Particle–Emitting 213Bi-C-Functionalized <i>trans</i>-Cyclohexyl-Diethylenetriaminepentaacetic Acid-Humanized 3S193 Is Enhanced by Combination with Paclitaxel Chemotherapy
Authors: Marcus P. Kelly, Fook T. Lee, Kiki Tahtis, Fiona E. Smyth, Martin W. Brechbiel, Andrew M. Scott
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Previous experience in solid tumor radioimmunotherapy studies has indicated that greatest therapeutic efficacy is achieved in the treatment of small-volume disease. α-Particle–emitting radioisotopes possess several physical characteristics ideally suited to the treatment of minimal residual disease. Therefore, we have investigated the efficacy of the α-particle–emitting bismuth-213 (213Bi) radioimmunotherapy using the humanized anti-Lewis Y (Ley) monoclonal antibody humanized 3S193 (hu3S193). Experimental Design: The intracellular localization of hu3S193 in Ley-positive MCF-7 breast carcinoma cells was assessed by confocal microscopy. Cytotoxicity of 213Bi-hu3S193 and apoptosis was assessed using [3H]thymidine incorporation assay and ELISA, respectively. Immunoblotting for γ-H2AX assessed DNA strand breaks. In vivo efficacy of 213Bi-hu3S193 was assessed using a minimal residual disease model in BALB/c nude mice, with radioconjugate [15, 30, and 60 μCi (9.2 μg)] injected 2 days after s.c. implantation of MCF-7 cells. Radioimmunotherapy was also combined with a single injection of 300 μg paclitaxel to explore improved efficacy. Further, mice with established tumors received 30, 60, or 120 μCi (14.5 μg) of 213Bi-hu3S193 to assess the effect of tumor volume on treatment efficacy. Results: hu3S193 is internalized via an endosomal and lysosomal trafficking pathway. Treatment with 213Bi-hu3S193 results in &amp;gt;90% cytotoxicity in vitro and induces apoptosis and increased γ-H2AX expression. 213Bi-hu3S193 causes specific and significant retardation of tumor growth even in established tumors, and efficacy was enhanced by paclitaxel to produce defined complete responses. Conclusions: These studies show the potency of α-particle radioimmunotherapy and warrant its further exploration in the treatment of micrometastatic disease in Ley-positive malignancies.
von Willebrand factor mutation promotes thrombocytopathy by inhibiting integrin αIIbβ3
Authors: Caterina Casari, Eliane Berrou, Marilyne Lebret, Frédéric Adam, Alexandre Kauskot, Régis Bobe, Céline Desconclois, Edith Fressinaud, Olivier D. Christophe, Peter J. Lenting, Jean-Philippe Rosa, Cécile V. Denis, Marijke Bryckaert
Journal: Journal of Clinical Investigation (2013)

von Willebrand disease type 2B (vWD-type 2B) is characterized by gain-of-function mutations in von Willebrand factor (vWF) that enhance its binding to the glycoprotein Ib-IX-V complex on platelets. Patients with vWD-type 2B have a bleeding tendency that is linked to loss of vWF multimers and/or thrombocytopenia. In this study, we uncovered evidence that platelet dysfunction is a third possible mechanism for bleeding tendency. We found that platelet aggregation, secretion, and spreading were diminished due to inhibition of integrin αIIbβ3 in platelets from mice expressing a vWD-type 2B-associated vWF (vWF/p.V1316M), platelets from a patient with the same mutation, and control platelets pretreated with recombinant vWF/p.V1316M. Impaired platelet function coincided with reduced thrombus growth. Further, αIIbβ3 activation and activation of the small GTPase Rap1 were impaired by vWF/p.V1316M following exposure to platelet agonists (thrombin, ADP, or convulxin). Conversely, thrombin- or ADP-induced Ca2+ store release, which is required for αIIbβ3 activation, was normal, indicating that vWF/p.V1316M acts downstream of Ca2+ release and upstream of Rap1. We found normal Syk phosphorylation and PLCγ2 activation following collagen receptor signaling, further implying that vWF/p.V1316M acts directly on or downstream of Ca2+ release. These data indicate that the vWD-type 2B mutation p.V1316M is associated with severe thrombocytopathy, which likely contributes to the bleeding tendency in vWD-type 2B.
Use of an inert marker (phenol red) to improve accuracy in gastric secretion studies
Authors: M. Hobsley, W. Silen
Journal: Gut (1969)

Gastric secretion from 24 subjects was collected by continuous nasogastric aspiration during the plateau of secretion evoked by intravenous histamine diphosphate, 0.01 mg/kg/hr. Simultaneously, phenol red was instilled at a constant rate into the proximal part of the stomach. Concentrations of phenol red in 15-minute aspirates were measured, and used to deduce pyloric losses and the reasons for random variation in the volumes aspirated. The average coefficient of variation in the volume was 26%, irrespective of the nature of the nasogastric tube. Correction by phenol red reduced this value to 21%. The coefficient of variation of volume diminished as secretion rate increased. Pyloric losses amounted to 7 ml/15 min, and were independent of the secretion rate. The quantitative effect of these errors upon the assessment of gastric secretion was minimal at high secretion rates but important at low rates.
Trends in Compulsory Licensing of Pharmaceuticals Since the Doha Declaration: A Database Analysis
Authors: Reed Beall, Randall Kuhn
Journal: PLoS Medicine (2012)

It is now a decade since the World Trade Organization (WTO) adopted the "Declaration on the TRIPS Agreement and Public Health" at its 4th Ministerial Conference in Doha. Many anticipated that these actions would lead nations to claim compulsory licenses (CLs) for pharmaceutical products with greater regularity. A CL is the use of a patented innovation that has been licensed by a state without the permission of the patent title holder. Skeptics doubted that many CLs would occur, given political pressure against CL activity and continued health system weakness in poor countries. The subsequent decade has seen little systematic assessment of the Doha Declaration's impact.We assembled a database of all episodes in which a CL was publically entertained or announced by a WTO member state since 1995. Broad searches of CL activity were conducted using media, academic, and legal databases, yielding 34 potential CL episodes in 26 countries. Country- and product-specific searches were used to verify government participation, resulting in a final database of 24 verified CLs in 17 nations. We coded CL episodes in terms of outcome, national income, and disease group over three distinct periods of CL activity. Most CL episodes occurred between 2003 and 2005, involved drugs for HIV/AIDS, and occurred in upper-middle-income countries (UMICs). Aside from HIV/AIDS, few CL episodes involved communicable disease, and none occurred in least-developed or low-income countries.Given skepticism about the Doha Declaration's likely impact, we note the relatively high occurrence of CLs, yet CL activity has diminished markedly since 2006. While UMICs have high CL activity and strong incentives to use CLs compared to other countries, we note considerable countervailing pressures against CL use even in UMICs. We conclude that there is a low probability of continued CL activity. We highlight the need for further systematic evaluation of global health governance actions. Please see later in the article for the Editors' Summary.
Essential role for proteinase-activated receptor-2 in arthritis
Authors: William R. Ferrell, John C. Lockhart, Elizabeth B. Kelso, Lynette Dunning, Robin Plevin, Stephen E. Meek, Andrew J.H. Smith, Gary D. Hunter, John S. McLean, Frances McGarry, Robert Ramage, Lu Jiang, Toru Kanke, Junichi Kawagoe
Journal: Journal of Clinical Investigation (2003)

Using physiological, pharmacological, and gene disruption approaches, we demonstrate that proteinase-activated receptor-2 (PAR-2) plays a pivotal role in mediating chronic inflammation. Using an adjuvant monoarthritis model of chronic inflammation, joint swelling was substantially inhibited in PAR-2–deficient mice, being reduced by more than fourfold compared with wild-type mice, with virtually no histological evidence of joint damage. Mice heterozygous for PAR-2 gene disruption showed an intermediate phenotype. PAR-2 expression, normally limited to endothelial cells in small arterioles, was substantially upregulated 2 weeks after induction of inflammation, both in synovium and in other periarticular tissues. PAR-2 agonists showed potent proinflammatory effects as intra-articular injection of ASKH95, a novel synthetic PAR-2 agonist, induced prolonged joint swelling and synovial hyperemia. Given the absence of the chronic inflammatory response in the PAR-2–deficient mice, our findings demonstrate a key role for PAR-2 in mediating chronic inflammation, thereby identifying a novel and important therapeutic target for the management of chronic inflammatory diseases such as rheumatoid arthritis.
Genetic polymorphism of the third component of human complement (C′3)
Authors: Chester A. Alper, Richard P. Propp
Journal: Journal of Clinical Investigation (1968)

Polymorphism of human C'3 has been defined by prolonged agarose electrophoresis of fresh serum. At least four, and probably five, alleles have been identified by the electrophoretic mobilities of gene products. Inheritance of three alleles, F(1) F, and S, is consistent with the autosomal condominant type. The inheritance of S(1) is probably codominant and that of F(0.8) is not known. Of the 15 phenotypes predicted by these alleles, eight have been observed. The allotypes appear to differ in net surface charge at pH 8.6, but show no obvious differences in complement activity, in molecular size, or in binding of Ca(++). The concentrations of the two gene products in serum from all known heterozygotes are approximately equal. The S gene is most common in the three major races of man. The F gene is relatively common in Caucasians, less common in American Negroes, and relatively uncommon in Orientals.
Spontaneous hemodynamic improvement or stabilization and associated biopsy findings in patients with congestive cardiomyopathy.
Authors: H R Figulla, G Rahlf, M Nieger, H Luig, H Kreuzer
Journal: Circulation (1985)

The hemodynamic courses of 56 patients with congestive cardiomyopathy (CCM) were investigated. Fourteen patients died within 24 months after diagnosis. The hemodynamic courses of the remaining 42 patients were investigated in subsequent examinations by determination of left ventricular ejection fraction (LVEF), mean pulmonary arterial pressure at maximal workload, and peak systolic pressure/end-systolic volume index. During the study interval of 32.2 +/- 20.0 months the conditions of 20 patients (48%) deteriorated, according to their hemodynamic status, and at least five of these died of terminal heart failure. Surprisingly, the conditions of 22 patients (52%) improved or stabilized. One of these died of leukemia. Seven patients in the latter group with initial LVEFs of 0.30 or less experienced an average increase from 0.22 to 0.51. Retrospectively consideration of age, alcohol intake, exercise capacity, and hemodynamic status were not helpful in predicting the course of the disease. In 38 patients endomyocardial biopsy samples could be obtained at the time of diagnosis. Reduced myofibril volume fraction (less than 60%) had prognostic significance for both hemodynamic deterioration and death (sensitivity 23/24 = 96%), while 14 of 15 patients whose conditions improved or stabilized had a myofibril volume fraction of 60% or more (specificity 14/15 or 93%, p less than .002). A relationship between hemodynamic status and the myofibril volume fraction could not be found. Individual patients with CCM differ significantly with respect to course of the disease. A distinct separation of the patients by means of morphologic criteria is possible. This makes it more likely that the pathogenesis of the disease is not unique.
A Novel Unstable Mutation in Mitochondrial DNA Responsible for Maternally Inherited Diabetes and Deafness
Authors: Sylvie Bannwarth, Meriame Abbassi, René Valéro, Konstantina Fragaki, Noémie Dubois, Bernard Vialettes, Véronique Paquis-Flucklinger
Journal: Diabetes Care (2011)

OBJECTIVE The m.3243A&amp;gt;G mutation in mitochondrial DNA (mtDNA) is responsible for maternally inherited diabetes and deafness (MIDD). Other mtDNA mutations are extremely rare. RESEARCH DESIGN AND METHODS We studied a patient presenting with diabetes and deafness who does not carry the m.3243A&amp;gt;G mutation. RESULTS We identified a deficiency of respiratory chain complex I in the patient’s fibroblasts. mtDNA sequencing revealed a novel mutation that corresponds to an insertion of one or two cytosine residues in the coding region of the MT-ND6 gene (m.14535_14536insC or CC), leading to premature stop codons. This heteroplasmic mutation is unstable in the patient’s somatic tissues. CONCLUSIONS We describe for the first time an unstable mutation in a mitochondrial gene coding for a complex I subunit, which is responsible for the MIDD phenotype. This mutation is likely favored by the m.14530T&amp;gt;C polymorphism, which is homoplasmic and leads to the formation of an 8-bp polyC tract responsible for genetic instability.
Genetic Cre-loxP Assessment of Epicardial Cell Fate Using Wt1-Driven Cre Alleles
Authors: Bin Zhou, William T. Pu
Journal: Circulation Research (2012)

Rationale: Wt1-Cre-based tools are important reagents for studying epicardial cell fate and gene function. Objective: To better describe the properties of Wt1-Cre-based tools to enhance their use in Cre-loxP-based experiments. Methods and Results: In contrast to recently reported results, we show that constitutive Wt1 GFPCre in combination with certain Cre-activated reporters can be used to trace (pro) epicardial cell fate. Wt1 CreERT2 can be efficiently induced by tamoxifen administration. We show substantial labeling of coronary endothelial cells when induction is performed at late but not early stages of heart development. Conclusions: Wt1-based Cre alleles are useful tools for genetic lineage tracing of epicardial cells and mesothelium of other organs. Using these tools with proper understanding of their properties and limitations enables genetic labeling of epicardial cells and their derivatives.
Histone Deacetylase Inhibitors Promote the Tumoricidal Effect of HAMLET
Authors: Patrick Brest, Mattias Gustafsson, Ann-Kristin Mossberg, Lotta Gustafsson, Caroline Duringer, Ali Hamiche, Catharina Svanborg
Journal: Cancer Research (2007)

Abstract Histone deacetylase inhibitors (HDIs) and HAMLET (human α-lactalbumin made lethal to tumor cells) interact with histones, modify the structure of chromatin, and trigger tumor cell death. This study investigated how the combination of HDIs and HAMLET influences cell viability, histone acetylation, and DNA integrity. The pretreatment of tumor cells with HDIs was shown to enhance the lethal effect of HAMLET and the histone hyperacetylation response to HDIs increased even further after HAMLET treatment. HDIs and HAMLET were shown to target different histone domains as HAMLET bound tailless core histones, whereas HDIs modify the acetylation of the histone tail. DNA damage in response to HAMLET was increased by HDIs. The DNA repair response (p21WAFI expression) was induced by both agonists but abolished when the two agonists were combined. The results suggest that the synergy of HDIs and HAMLET is based on different but converging death pathways, both involving chromatin alterations. We speculate that HAMLET and HDIs might be combined to promote tumor cell death in vivo. [Cancer Res 2007;67(23):11327–34]
Prostaglandin I2 Signaling Exacerbates Experimental Autoimmune Encephalomyelitis
Authors: D.R. Dowell, W. Zhou, M.M. Huckabee, D.C. Newcomb, K. Goleniewska, G.A. Fitzgerald, R.S. Peebles Jr.
Journal: Journal of Allergy and Clinical Immunology (2011)
POU1F1 is a novel fusion partner of NUP98 in acute myeloid leukemia with t(3;11)(p11;p15)
Authors: Susana Lisboa, Nuno Cerveira, Susana Bizarro, Cecília Correia, Joana Vieira, Lurdes Torres, José M Mariz, Manuel R Teixeira
Journal: Molecular Cancer (2013)

Abstract Background NUP98 gene rearrangements have been reported in acute myeloid leukemia, giving rise to fusion proteins that seem to function as aberrant transcription factors, and are thought to be associated with poor prognosis. Findings A patient with treatment-related acute myeloid leukemia presented a t(3;11)(p11;p15) as the only cytogenetic abnormality. FISH and molecular genetic analyses identified a class 1 homeobox gene, POU1F1 , located on chromosome 3p11, as the fusion partner of NUP98 . In addition, we have found that the patient harbored an FLT3-ITD mutation, which most likely collaborated with the NUP98-POU1F1 fusion gene in malignant transformation. Conclusions We have identified POU1F1 as the NUP98 fusion partner in therapy-related AML with a t(3;11)(p11;p15). This is the first POU family member identified as a fusion partner in human cancer.