tbuckley/cabot-search huggingface dataset:
Intramuscular administration of human tissue-type plasminogen activator in rabbits and dogs and its implications for coronary thrombolysis.
Authors: B E Sobel, J E Saffitz, L E Fields, D W Myears, S J Sarnoff, A K Robison, D A Owensby, K A Fox
Journal: Circulation (1987)

To determine whether sustained plasma concentration of human tissue-type plasminogen activator (t-PA) can be induced promptly after intramuscular injection with enhancers of absorption devoid of deleterious local and systemic effects, we studied 250 rabbits and 13 dogs. In rabbits with t-PA injected directly into exposed muscle followed by local electrical stimulation at the site, early absorption was increased markedly by addition of 0.63M methylamine plus 0.079M hydroxylamine to the excipient. Elevations peaked within 5 min and increased with dose of t-PA, concentration of methylamine, and volume of injection medium. The enhancers were effective with percutaneous injections in the absence of local electrical stimulation as well. They did not elicit any obviously deleterious local or systemic effects. In separate experiments in rats, intramuscular injections of 0.63M methylamine plus 0.079M hydroxylamine induced local egress of intravascular radiolabeled albumin within the injection site and endothelial gaps in venules detected with colloidal carbon--changes consistent with direct effects on vascular permeability. In dogs, percutaneous intramuscular injection of t-PA in excipient without enhancers did not lead to early elevations of human t-PA in plasma, although late elevations were seen. When the enhancers were used, early elevations occurred as well, with functional activity documented by fibrin plate assays of serially obtained plasma samples and by sequential coronary angiography delineating thrombolysis after experimentally induced coronary thrombosis. The results indicate that intramuscular administration of t-PA with selected enhancers of absorption is a feasible approach for rapid induction of fibrinolysis.
Public backs the idea of an independently run NHS
Authors: Zosia Kmietowicz
Journal: BMJ (2007)

More than eight in 10 respondents to a survey on the NHS said that they would like to see doctors taking a lead role in deciding what is best for their patients and how money should be spent locally.

The survey, conducted by the BMA on the eve of its annual conference of representatives, also found that support among the public for an independent board of governors to run the NHS was widespread. 

Sixty per cent of the 1000 respondents to the survey endorsed loosening the government's control of the NHS, one of the …
Bronchial hyperreactivity in systemic sclerosis patients: influence of associated Sjogren's syndrome.
Authors: R La Corte, G Bajocchi, A Potena, M Govoni, F Trotta
Journal: Annals of the Rheumatic Diseases (1995)

OBJECTIVE--To determine the frequency and relative risk of bronchial hyperreactivity to methacholine in systemic sclerosis patients with or without associated Sjögren9s syndrome. METHODS--A prospective study of 56 patients with systemic sclerosis (42 with the diffuse and 14 with the limited variant; 24 with associated Sjögren9s syndrome), 57 with primary Sjögren9s syndrome, and 61 healthy controls. RESULTS--Bronchial hyperreactivity (BH) was present in 6.5% of the healthy controls, 25% of the systemic sclerosis patients without associated Sjögren9s syndrome, 42.2% of those with primary Sjögren9s syndrome, and in 50% of those with systemic sclerosis with associated Sjögren9s syndrome. The presence of BH did not correlate with age, disease duration, chest radiograph abnormalities, respiratory, and immunological data. The subgroup of subjects with the limited variant of systemic sclerosis more frequently had associated BH than did those with the diffuse variant of the disease; coexisting Sjögren9s syndrome further increased this frequency. CONCLUSIONS--In agreement with previous studies, we have confirmed the high prevalence of bronchial hyperreactivity in primary Sjögren9s syndrome; systemic sclerosis likewise appears to be associated with an increased frequency of bronchial hyperreactivity compared with healthy control subjects. There is evidence also that the coexistence of Sjögren9s syndrome and systemic sclerosis further increases the frequency and the calculated relative risk of developing bronchial hyperreactivity.
Apparent progression of lentigo maligna to invasive melanoma during treatment with topical azelaic acid
Authors: D.I. MCLEAN, K.K. PETER
Journal: British Journal of Dermatology (1986)

Nine patients with lentigo maligna were treated with topical azelaic acid. Clinical improvement was observed in four, with complete clearing in one. Two patients developed invasive lentigo maligna melanoma while on treatment. Caution should be exercised in the use of topical azelaic acid in the treatment of lentigo maligna.
Angiographic Changes in Aortocoronary Vein Grafts:
Authors: JACQUES LESPÉRANCE, MARTIAL G. BOURASSA, JACQUES SALTIEL, LUCIEN CAMPEAU, CLAUDE M. GRONDIN
Journal: Circulation (1973)

The angiographic aspect of aortocoronary vein grafts was reviewed three years after operation in 43 patients. These patients had been previously subjected to two selective angiographic studies: two weeks and one year after operation. The review of these angiographic studies suggests that the attrition rate of aortocoronary vein grafts levels off after the first year. Only three occlusions (5.4%) were found on the three-year study in the 55 grafts which were patent on the study conducted at one year. Two of the three occlusions occurred in grafts which had already displayed severe segmental reduction in size after one year. Moreover, the slight to moderate reduction in caliber noted in more than 70% of vein grafts between two weeks and one year after operation did not progress between one and three years. Thus, it appears that fibrous hyperplasia. which is believed responsible for these changes, is a time-limited process, and is not expected to progress after the first year.
Henoch-Schönlein Purpura
Authors: Ann R. Punnoose, Cassio Lynm, Robert M. Golub
Journal: JAMA (2012)

Typical symptoms and signs of Henoch-Schönlein purpuraFoot and ankle edema (swelling) Joint inflammation and painAbdominal pain, nausea, vomiting, bloody diarrhea Raised reddish-purple spots or bruised areas mainly on buttocks, legs, and feet.In some individuals, spots may appear on body trunk
M143 Progression Of Central Arterial Stiffness In Copd After 2 Years Of Observation
Authors: N. Gale, A. Albarrati, M. Munnery, I. Munnery, R. Tal-Singer, J. Cockcroft, D. Shale
Journal: Thorax (2014)

<h3>Background</h3> COPD is a systemic disease with associated comorbidities including cardiovascular disease which have significant impact on morbidity and mortality. The heterogeneity of COPD has led to the concept of phenotypes; one of which may describe patients at greater cardiovascular risk. Aortic pulse wave velocity (aPWV) is a validated measure of arterial stiffness and an independent predictor of cardiovascular outcomes, and has been shown to be elevated in patients with COPD.<sup>1</sup> We hypothesised that a subgroup of patients (progressors) would demonstrate increased aPWV over 2 years. <h3>Methods</h3> The ARCADE study is a longitudinal study of cardiovascular risk and other comorbidities. Assessments include spirometry, BMI, aPWV and blood pressure, (BP), mean arterial pressure (MAP), heart rate and 6 min walk distance (6MWT). Based on the change in PWV in hypertensive patients, progressors were defined as individuals with &gt;0.5 m/s PWV increase, over 2 years.<sup>2</sup> <h3>Results</h3> Thus far 200 patients with COPD have completed the 2 year follow-up assessment. At baseline the progressor and non-progressor were similar in age, gender, BMI, heart rate and 6 MWT. However the progressors had greater airways obstruction, and lower mean arterial pressure and aPWV (Table 1). After 2 years the mean [95% CI] PWV change in progressors was +1.7 [2.0–1.5]m/s while FEV<sub>1</sub> declined by 140 [76–206]ml (p &lt; 0.05). In contrast the non-progressors had no change in lung function, while there was a decrease in aPWV 0.7 [0.5–0.9] m/s and MAP 5 [3–7] mmHg (p &lt; 0.05). <h3>Conclusions</h3> Almost half of the ARCADE subjects with COPD had a significant increase of PWV, the clinical relevance requires investigation using longer-term outcome data. The identification of CV risk phenotypes in COPD and the underlying pathophysiology may help identify novel therapeutic targets and improve CV outcomes for patients. Thank you to all our volunteers and GlaxoSmithKline who funded ARCADE NCT01656421 <h3>References</h3> Sabit, R., <i>et al</i>., AJRCCM, 2007. 175(12): p. 1259-1265 Benetos, A., <i>et al</i>., Circulation, 2002. 105(10): p. 1202-1207
Quantitative Immunochemical Fecal Occult Blood Test for Diagnosing Colorectal Neoplasia
Authors: Paul Rozen, Zohar Levi, Yaron Niv
Journal: Annals of Internal Medicine (2007)

Letters2 October 2007Quantitative Immunochemical Fecal Occult Blood Test for Diagnosing Colorectal NeoplasiaPaul Rozen, MBBS, Zohar Levi, MD, and Yaron Niv, MDPaul Rozen, MBBSFrom Rabin Medical Center, Beilinson Hospital, and Tel Aviv University, Petach Tikva and Tel Aviv, Israel.Search for more papers by this author, Zohar Levi, MDFrom Rabin Medical Center, Beilinson Hospital, and Tel Aviv University, Petach Tikva and Tel Aviv, Israel.Search for more papers by this author, and Yaron Niv, MDFrom Rabin Medical Center, Beilinson Hospital, and Tel Aviv University, Petach Tikva and Tel Aviv, Israel.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-147-7-200710020-00021 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:We thank Drs. Shastri and Stein for their comments and their very relevant questions, which provide us with an opportunity to address several important clinical issues. First, our comment on “systematic evaluation” refers to the automated developed and quantitative immunochemical FOBT. As Drs. Shastri and Stein point out, they, we, and others have evaluated the office-developed immunochemical FOBT (1, 2). However, the test uses a fixed threshold set by the manufacturer, and the hand development is not conducive for large-scale population screening. Evaluating the immunochemical FOBT as a laboratory test, with a quantified result, allows the treating physician ...References1. Hoepffner N, Shastri YM, Hanisch E, Rösch W, Mössner J, Caspary WF, et al. Comparative evaluation of a new bedside faecal occult blood test in a prospective multicentre study. Aliment Pharmacol Ther. 2006;23:145-54. [PMID: 16393292] CrossrefMedlineGoogle Scholar2. Rozen P, Knaani J, Samuel Z. Comparative screening with a sensitive guaiac and specific immunochemical occult blood test in an endoscopic study. Cancer. 2000;89:46-52. [PMID: 10896999] CrossrefMedlineGoogle Scholar Author, Article, and Disclosure InformationAffiliations: From Rabin Medical Center, Beilinson Hospital, and Tel Aviv University, Petach Tikva and Tel Aviv, Israel. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoA Quantitative Immunochemical Fecal Occult Blood Test for Colorectal Neoplasia Zohar Levi , Paul Rozen , Rachel Hazazi , Alex Vilkin , Amal Waked , Eran Maoz , Shlomo Birkenfeld , Moshe Leshno , and Yaron Niv Quantitative Immunochemical Fecal Occult Blood Test for Diagnosing Colorectal Neoplasia Yogesh M. Shastri and Jürgen Stein Metrics 2 October 2007Volume 147, Issue 7Page: 523KeywordsConflicts of interestHematologic testsLaboratory tests ePublished: 2 October 2007 Issue Published: 2 October 2007 Copyright & PermissionsCopyright © 2007 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Co-Administration of Nitric Oxide-Aspirin (NCX-4016) and Aspirin Prevents Platelet and Monocyte Activation and Protects Against Gastric Damage Induced by Aspirin in Humans
Authors: Stefano Fiorucci, Andrea Mencarelli, Alessandra Meneguzzi, Alessandro Lechi, Barbara Renga, Piero del Soldato, Antonio Morelli, Pietro Minuz
Journal: Journal of the American College of Cardiology (2004)
Radiofrequency thermal angioplasty maintains arterial duct patency. An experimental study.
Authors: S E Abrams, K P Walsh, M J Diamond, M J Clarkson, P Sibbons
Journal: Circulation (1994)

BACKGROUND Long-term maintenance of arterial duct patency by a catheter technique would be a valuable nonsurgical method of palliation for duct-dependent circulations. We used a new method: percutaneous radiofrequency thermal balloon angioplasty of neonatal lamb arterial ducts. METHODS AND RESULTS Radiofrequency balloons 5 or 6 mm in diameter were introduced via the femoral vein of 32 neonatal lambs and inflated to 4 atm. In 28, a radiofrequency generator was used to heat the saline/contrast mixture in the balloon to 65 degrees C (n = 2), 75 degrees C (n = 2), 85 degrees C (n = 10), 100 degrees C (n = 8), and 120 degrees C (n = 6). In 4 lambs, angioplasty alone was performed. Lambs were recatheterized to assess patency at intervals up to 78 weeks. Immediate results showed the arterial duct to be patent in all cases, with a mean rise in systolic pulmonary artery pressure of 13 +/- 8 mm Hg and a mean rise in pulmonary artery oxygen saturation of 12 +/- 15%. With a mean follow-up of 45.7 +/- 28 weeks, 3 of the 4 (75%) angioplasty alone ducts closed, but only 5 of the 28 (18%) radiofrequency-treated ducts (P &lt; .05). The mean rise in oxygen saturation between the superior vena cava and the pulmonary artery was 7.6 +/- 7% at last follow-up. Follow-up angiography of the arterial ducts showed the development of stenoses in all patent ducts. CONCLUSIONS Radiofrequency thermal balloon angioplasty leads to long-term arterial duct patency in lambs in &gt; 80% of the treated group and is significantly more effective than balloon angioplasty alone.
Preoperative Intravitreal Bevacizumab Use as an Adjuvant to Diabetic Vitrectomy: Histopathologic Findings and Clinical Implications
Authors: Hazem A. El-Sabagh, Walid Abdelghaffar, Ahmad M. Labib, Carlos Mateo, Tarek M. Hashem, Dalal M. Al-Tamimi, Abdulhafez A. Selim
Journal: Ophthalmology (2010)
Plerixafor is superior to conventional chemotherapy for first-line stem cell mobilisation, and is effective even in heavily pretreated patients
Authors: R E Clark, J Bell, J O Clark, B Braithwaite, U Vithanarachchi, N McGinnity, T Callaghan, S Francis, R Salim
Journal: Blood Cancer Journal (2014)

This study (PHANTASTIC) compares first-line plerixafor with granulocyte colony-stimulating factor (G-CSF) in 98 myeloma and lymphoma patients with 151 historic controls mobilised by conventional chemotherapy+G-CSF. Eleven patients developed mild transient symptoms possibly related to plerixafor. No serious adverse events were seen. Seventy (71%) plerixafor-mobilised patients achieved both ⩾4 × 106 CD34+ cells/kg in ⩽2 aphereses and no neutropenia (<1.0 × 109/l). This is significantly >48 (32%) of 151 historical chemotherapy+G-CSF-mobilised control patients achieving this end point (P<0.001). Ninety-six (98%) plerixafor-mobilised patients achieved ⩾2 × 106 CD34+ cells/kg within one harvest round compared with 114 (75%) of controls (P=0.001). Engraftment times and 12-month outcome were comparable in both groups. Prior treatment was summarised by two scoring systems. Controls mobilising either >2.0 or >4.0 × 106 CD34+ cells/kg have significantly lower scores than mobilisation failures (P=0.002), but this relationship was not seen for plerixafor-mobilised patients. Plerixafor is a more effective and less toxic mobilising agent than conventional chemotherapy (especially in heavily pretreated patients), with comparable subsequent outcome, and merits consideration as the first-line standard of care for stem cell mobilisation.
Abstract 66: Inhibition of glioma cell proliferation and tumor development by Sox21
Authors: Demet Caglayan, Marianne Kastemar, Bengt Westermark, Maria Ferletta
Journal: Cancer Research (2012)

Abstract Sox2 and Sox21 are two transcription factors important for the developing, as well as the adult, CNS, and they are often co-expressed. Sox2 is an embryonic stem cell marker, whereas ectopic forced expression of Sox21 has been shown to induce differentiation in embryonic stem cells. Further, Sox2 is important for maintenance of neural stem cells whereas Sox21 is important for neurogenesis. These two transcriptionfactors are thus in opposite relation to each other and it is believed that a proper balance between them is needed to regulate target genes. Sox2 is highly expressed in brain tumors and up to 97% of GBM samples express Sox2. While the expression of Sox2 has been shown in GBM, in primary glioma cells and established glioma cell lines, less is known about Sox21 in glioma. We have previously shown that Sox2 and Sox21 are co-expressed in adult and childhood brain tumors and are in a functional relationship in glioma cells. Sox2 keeps glioma cells in a proliferative state whereas over expression of Sox21 reduces Sox2 expression and decreases cell proliferation with an increased tendency of apoptosis and differentiation of the glioma cells. We have now further elucidated this effect in vivo by injecting established inducible-Sox21 glioma cell lines subcutaneously into the flank and orthotopically into the brain of SCID mice. Regardless of the injection site, increased Sox21 expression in these tumors reduces tumor growth. The tumors from treated mice were significantly smaller in size and there is a significant increase in survival time. This effect was dependent on the time of Sox21 induction, where an earlier turn on gives even smaller tumors. Total depletion of Sox2 was not achieved despite forced Sox21 expression. Further we show that Sox2 deficiency leads to an inability to form tumors. With its dual effect, the ability to decrease Sox2 expression and the ability to aberrantly differentiate tumor cells, Sox21 becomes a very important factor for future research around therapeutic possibilities in GBM. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 66. doi:1538-7445.AM2012-66
ASCOT: a tale of two treatment regimens
Authors: David G Phizackerley
Journal: BMJ (2005)

EDITOR—McDougall et al reviewed the evidence from ASCOT (the Anglo Scandinavian cardiac outcomes trial).1 For patients with hypertension and for the clinicians helping to manage their blood pressure this must be the best of times and the worst of times. The best of times—currently we have a wealth of clinical trials on the management of blood pressure, giving us a mass of data, statistics and information to absorb. The worst of times—whenever a new trial is published, the …
Fluticasone propionate 750 g/day versus beclomethasone dipropionate 1500 g/day: comparison of efficacy and adrenal function in paediatric asthma
Authors: D. Fitzgerald, P. Van Asperen, C. Mellis, M. Honner, L. Smith, G. Ambler
Journal: Thorax (1998)

Previous studies have suggested a 2:1 efficacy advantage of fluticasone propionate (FP) over beclomethasone dipropionate (BDP) in adults on high dose inhaled steroids and children on low dose inhaled steroids. The lower doses of FP required to provide equivalent efficacy to BDP also appear to have fewer systemic effects as measured by adrenal function.The efficacy and safety of FP 750 micrograms/day and BDP 1500 micrograms/day were compared in 30 children with persistent asthma (requiring 1000-2000 micrograms/day of inhaled corticosteroids) in a 12 week randomised double blind crossover study. Medication was delivered by a spacer device in two divided doses. Primary efficacy variables were peak expiratory flows (PEF). Adrenal function was assessed by 24 hour urinary free cortisol levels at eight and 12 weeks and ACTH and low dose synacthen tests (LDST) at 12 weeks. The results were adjusted for sequence and period differences.There was no difference in the primary efficacy variables over the two 12 week treatment periods (difference in adjusted means for morning PEF 1.3 l/min (95% CI -6.1 to 8.8), p = 0.112) and symptom scores (cough, tachypnoea, wheeze, shortness of breath; difference in adjusted means of night time scores: -0.06 (95% CI -0.14 to 0.03); p = 0.136). Similar degrees of mild adrenal dysfunction were found during BDP and FP treatment phases. Identical height gain velocities were shown during the corresponding periods.FP 750 micrograms/day is as effective as BDP 1500 micrograms/day in children with persistent asthma. At these very high doses we were unable to demonstrate a safety advantage of FP over BDP as assessed by adrenal function. However, measures of adrenal function may have been influenced by concurrent and previous systemic steroid usage, and possibly by effects of disease activity.
Abstract 5210: KPT-330, a selective small molecule inhibitor of nuclear export, is active in bone and soft tissue sarcoma.
Authors: Jayasree S. Nair, William Tap, Shyamprasad Deraje Vasudeva, Jason K. Sicklick, Michael Kauffman, Sharon Shacham, Gary K. Schwartz
Journal: Cancer Research (2013)

Abstract KPT-330 is a small molecule Selective Inhibitor of Nuclear Export (SINE) that irreversibly block the major nuclear export protein CRM1 (exportin 1, XPO1). The Chromosome Region Maintenance 1 (CRM1) protein is responsible for the nuclear export of snRNAs and of proteins bearing a leucine-rich nuclear export signal (NES). This class of drugs is expected to induce forced nuclear accumulation of tumor suppressor proteins (TSPs) and is believed to initiate a ‘genome survey’ leading to the death of cancer cells with normal cells undergoing transient, reversible cell cycle arrest. Our effort was to investigate the effects of KPT-330 in sarcomas and the mechanism by which it exerts the effect of tumor suppression. Our data clearly shows KPT-330 as active against a broad panel of human bone and soft tissue sarcoma cell lines at low nanomolar concentrations. The effect was mainly due to the induction of apoptosis. Target specificity of the drug was confirmed by the decrease in CRM1 protein level. An induction of p53 and p21 protein levels was observed. However, the effect of apoptosis or inhibition in proliferation seems to be independent of p53 status of the cell line. The effect of KPT-330 was further tested in xenograft models using malignant peripheral nerve sheath (MPNST) and de-differentiated liposarcoma (LS141) cell lines. Tumor suppression was observed in both the sarcoma models and its target specificity was confirmed in the xenografts. KPT-330 may represent a new drug for the treatment of bone and soft tissue sarcoma. Citation Format: Jayasree S. Nair, William Tap, Shyamprasad Deraje Vasudeva, Jason K. Sicklick, Michael Kauffman, Sharon Shacham, Gary K. Schwartz. KPT-330, a selective small molecule inhibitor of nuclear export, is active in bone and soft tissue sarcoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5210. doi:10.1158/1538-7445.AM2013-5210
Tissue response to poly(l-lactic acid)-based blend with phospholipid polymer for biodegradable cardiovascular stents
Authors: Hyung Il Kim, Kazuhiko Ishihara, Seungbok Lee, Ji-Hun Seo, Hye Young Kim, Dongwhan Suh, Min Uk Kim, Tomohiro Konno, Madoka Takai, Jeong-Sun Seo
Journal: Biomaterials (2010)
Evolving the future by learning from the future (as it emerges)? Toward an epistemology of change
Authors: Markus F. Peschl, Thomas Fundneider
Journal: Behavioral and Brain Sciences (2014)

Abstract At the core of Wilson et al.'s paper stands the question of intentional change. We propose to extend this notion by introducing concepts from the domains of innovation and knowledge creation. By going beyond their “acceptance and commitment therapy” approach we present a comprehensive framework for a theory of change culminating in the change strategy of “learning from the future as it emerges.”