tbuckley/cabot-search huggingface dataset:
The National Heart, Lung, and Blood Institute Pediatric Circulatory Support Program
Authors: J. Timothy Baldwin, Harvey S. Borovetz, Brian W. Duncan, Mark J. Gartner, Robert K. Jarvik, William J. Weiss, Tracey R. Hoke
Journal: Circulation (2006)

Options for the circulatory support of pediatric patients under the age of 5 years are currently limited to short-term extracorporeal devices, the use of which is often complicated by infection, bleeding, and thromboembolism. Recognizing this void, the National Heart, Lung, and Blood Institute solicited proposals for the development of novel circulatory support systems for infants and children from 2 to 25 kg with congenital or acquired cardiovascular disease. Five contracts were awarded to develop a family of devices that includes (1) an implantable mixed-flow ventricular assist device designed specifically for patients up to 2 years of age, (2) another mixed-flow ventricular assist device that can be implanted intravascularly or extravascularly depending on patient size, (3) compact integrated pediatric cardiopulmonary assist systems, (4) apically implanted axial-flow ventricular assist devices, and (5) pulsatile-flow ventricular assist devices. The common objective for these devices is to reliably provide circulatory support for infants and children while minimizing risks related to infection, bleeding, and thromboembolism. The devices are expected to be ready for clinical studies at the conclusion of the awards in 2009.
Clinical and Angiographic Factors Associated With Asymptomatic Restenosis After Percutaneous Coronary Intervention
Authors: Peter N. Ruygrok, Mark W.I. Webster, Vincent de Valk, Gerrit-Anne van Es, John A. Ormiston, Marie-Angèle M. Morel, Patrick W. Serruys
Journal: Circulation (2001)

Background Angiographic restenosis after percutaneous coronary interventional procedures is more common than recurrent angina. Clinical and angiographic factors associated with asymptomatic versus symptomatic restenosis after percutaneous coronary intervention were compared. Methods and Results All patients with angiographic restenosis from the BENESTENT I, BENESTENT II pilot, BENESTENT II, MUSIC, WEST 1, DUET, FINESS 2, FLARE, SOPHOS, and ROSE studies were analyzed. Multivariate analysis evaluated 46 clinical and angiographic variables, comparing those with and without angina. The 10 studies recruited 2690 patients who underwent percutaneous revascularization and 6-month follow-up angiography (86% of those eligible). Restenosis (≥50% diameter stenosis) occurred in 607 patients and was clinically silent in 335 (55%). Male sex ( P =0.008), absence of antianginal therapy with nitrates ( P =0.0002) and calcium channel blockers ( P =0.02) at 6 months, greater reference diameter after the procedure ( P =0.04), greater reference diameter at follow-up ( P =0.004), and lesser lesion severity (percent stenosis) at 6 months ( P =0.0004) were univariate predictors of asymptomatic restenosis. By multivariate analysis, only male sex ( P =0.04), greater reference diameter at follow-up ( P =0.002), and lesser lesion severity at 6 months ( P =0.0001) were associated with restenosis without angina. Conclusions Approximately half of patients with angiographic restenosis have no symptoms. The only multivariate predictors of silent restenosis at 6 months were male sex, greater reference diameter at follow-up, and lesser lesion severity on follow-up angiography.
Minicircle DNA is Superior to Plasmid DNA in Eliciting Antigen-specific CD8+ T-cell Responses
Authors: Wynette M Dietz, Nicole E B Skinner, Sara E Hamilton, Michelle D Jund, Suzanne M Heitfeld, Adam J Litterman, Patrick Hwu, Zhi-Ying Chen, Andres M Salazar, John R Ohlfest, Bruce R Blazar, Christopher A Pennell, Mark J Osborn
Journal: Molecular Therapy (2013)

Clinical trials reveal that plasmid DNA (pDNA)–based gene delivery must be improved to realize its potential to treat human disease. Current pDNA platforms suffer from brief transgene expression, primarily due to the spread of transcriptionally repressive chromatin initially deposited on plasmid bacterial backbone sequences. Minicircle (MC) DNA lacks plasmid backbone sequences and correspondingly confers higher levels of sustained transgene expression upon delivery, accounting for its success in preclinical gene therapy models. In this study, we show for the first time that MC DNA also functions as a vaccine platform. We used a luciferase reporter transgene to demonstrate that intradermal delivery of MC DNA, relative to pDNA, resulted in significantly higher and persistent levels of luciferase expression in mouse skin. Next, we immunized mice intradermally with DNA encoding a peptide that, when presented by the appropriate major histocompatibility complex class I molecule, was recognized by endogenous CD8+ T cells. Finally, immunization with peptide-encoding MC DNA, but not the corresponding full-length (FL) pDNA, conferred significant protection in mice challenged with Listeria monocytogenes expressing the model peptide. Together, our results suggest intradermal delivery of MC DNA may prove more efficacious for prophylaxis than traditional pDNA vaccines. Clinical trials reveal that plasmid DNA (pDNA)–based gene delivery must be improved to realize its potential to treat human disease. Current pDNA platforms suffer from brief transgene expression, primarily due to the spread of transcriptionally repressive chromatin initially deposited on plasmid bacterial backbone sequences. Minicircle (MC) DNA lacks plasmid backbone sequences and correspondingly confers higher levels of sustained transgene expression upon delivery, accounting for its success in preclinical gene therapy models. In this study, we show for the first time that MC DNA also functions as a vaccine platform. We used a luciferase reporter transgene to demonstrate that intradermal delivery of MC DNA, relative to pDNA, resulted in significantly higher and persistent levels of luciferase expression in mouse skin. Next, we immunized mice intradermally with DNA encoding a peptide that, when presented by the appropriate major histocompatibility complex class I molecule, was recognized by endogenous CD8+ T cells. Finally, immunization with peptide-encoding MC DNA, but not the corresponding full-length (FL) pDNA, conferred significant protection in mice challenged with Listeria monocytogenes expressing the model peptide. Together, our results suggest intradermal delivery of MC DNA may prove more efficacious for prophylaxis than traditional pDNA vaccines.
Seasonal intermittent preventive treatment with artesunate and sulfadoxine-pyrimethamine for prevention of malaria in Senegalese children: a randomised, placebo-controlled, double-blind trial
Authors: Badara Cissé, Cheikh Sokhna, Denis Boulanger, Jacqueline Milet, El Hadj Bâ, Keshena Richardson, Rachel Hallett, Colin Sutherland, Kirsten Simondon, François Simondon, Neal Alexander, Oumar Gaye, Geoffrey Targett, Jo Lines, Brian Greenwood, Jean-François Trape
Journal: The Lancet (2006)
Placental growth factor mediates mesenchymal cell development, cartilage turnover, and bone remodeling during fracture repair
Authors: C. Maes
Journal: Journal of Clinical Investigation (2006)

Current therapies for delayed- or nonunion bone fractures are still largely ineffective. Previous studies indicated that the VEGF homolog placental growth factor (PlGF) has a more significant role in disease than in health. Therefore we investigated the role of PlGF in a model of semi-stabilized bone fracture healing. Fracture repair in mice lacking PlGF was impaired and characterized by a massive accumulation of cartilage in the callus, reminiscent of delayed- or nonunion fractures. PlGF was required for the early recruitment of inflammatory cells and the vascularization of the fracture wound. Interestingly, however, PlGF also played a role in the subsequent stages of the repair process. Indeed in vivo and in vitro findings indicated that PlGF induced the proliferation and osteogenic differentiation of mesenchymal progenitors and stimulated cartilage turnover by particular MMPs. Later in the process, PlGF was required for the remodeling of the newly formed bone by stimulating osteoclast differentiation. As PlGF expression was increased throughout the process of bone repair and all the important cell types involved expressed its receptor VEGFR-1, the present data suggest that PlGF is required for mediating and coordinating the key aspects of fracture repair. Therefore PlGF may potentially offer therapeutic advantages for fracture repair.
Handling the hijacker.
Authors: W J McArthur, P J Dean, J R Carroll, T Holliday, R E Stokes
Journal: BMJ (1973)

Abstract : The primary objective in controlling hijackers must be to prevent them from getting aboard an aircraft and techniques to achieve this objective are being developed. However, for the foreseeable future some hijackers will be able to escape detection and gain entry to aircraft. It is consequently desirable that flight deck crews, cabin attendants and air crew management have practical guidelines to assist them in coping with the in-cabin hijacker when the aircraft is airborne or on the ground. The paper is based on information gained from studies of hijackings which have occurred in the United States and Canada. (Author Modified Abstract)
Refined severity assessment of asthmatic children using molecular allergy diagnostics
Authors: Jon Konradsen, Björn Nordlund, Magnus Borres, Annica Onell, Hans Grönlund, Gunilla Hedlin
Journal: European Respiratory Journal (2013)

Introduction: Allergy to furry animals is a risk factor for asthma and is associated with asthma severity. A major step forward in the diagnostic work-up is the introduction of molecular allergology. We compared sensitization to individual allergen components from furry animals in children with severe and controlled asthma.  Methods: Children with a positive ImmunoCAP towards any furry animal (cat, dog or horse) were recruited from a Nationwide Swedish study on severe childhood asthma. Severe (n=37, age 12.9 years) and controlled (n=28, age 13.9 years) asthmatics underwent assessment of allergic sensitization by ImmunoCap and Immunosolid-phase allergen chip (ISAC). In addition, Asthma control test, spirometry and a methacholine challenge were performed.  Results: Children with severe asthma had lower asthma control (p  800ug budesonide). Using ImmunoCAP, severe asthmatics had increased levels of IgE antibodies towards cat (p=0.03), dog (p=0.01) and horse (p=0.01). Results from ISAC are presented in Table 1. IgE levels towards Equ c 1 correlated with Asthma control (r=-0.41, p=0.04). Multisensitization towards ≥3 lipocalin allergens (Fel d 4, Can f 1, Can f 3, Equ c 1) was more common in severe asthma (30% vs. 4%, p=0.007).  Conclusion: Higher sIgE levels and a more complex molecular spreading of allergen components were observed for children with severe allergic asthma.
Activity of Oxaliplatin in Patients With Relapsed or Cisplatin-Refractory Germ Cell Cancer: A Study of the German Testicular Cancer Study Group
Authors: C. Kollmannsberger, O. Rick, H.-G. Derigs, N. Schleucher, P. Schöffski, J. Beyer, R. Schoch, H.G. Sayer, A. Gerl, M. Kuczyk, C. Spott, L. Kanz, C. Bokemeyer
Journal: Journal of Clinical Oncology (2002)

PURPOSE: To investigate the efficacy and toxicity of oxaliplatin, a diaminocyclohaxane platinum derivative with incomplete cross-resistance to cisplatin in patients with relapsed or cisplatin-refractory germ cell cancer. PATIENTS AND METHODS: Thirty-two patients with nonseminomatous cisplatin-refractory germ cell cancer or relapsed disease after high-dose chemotherapy (HDCT) plus autologous stem-cell support were treated with single-agent oxaliplatin 60 mg/m 2 on days 1, 8, and 15 repeated every 4 weeks (group 1; n = 16) or oxaliplatin 130 mg/m 2 given on days 1 and 15 of a 4-week cycle (group 2; n = 16). Patients were pretreated with a median of seven (range, three to 13) cisplatin-containing treatment cycles; 78% had received carboplatin/etoposide-based HDCT before oxaliplatin therapy. Twenty-seven patients (84%) were considered refractory (n = 20; 63%) or absolutely refractory (n = 7; 22%) to cisplatin therapy. RESULTS: Overall, four patients achieved a partial remission (13%; 95% confidence interval, 1% to 24%). Two additional patients achieved disease stabilization. All responses were observed in cisplatin-refractory patients, including three who had not responded to previous HDCT. Patients received a median two cycles of oxaliplatin with a median cumulative dose of 350 mg/m 2 . Hematologic toxicity was generally mild, with five patients developing grade 3/4 thrombocytopenia. Nonhematologic side effects consisted mainly of nausea/vomiting. One patient developed grade 3 neurotoxicity. CONCLUSION: Considering the particularly unfavorable prognostic characteristics of this patient population compared with patients from previous trials for new drugs in germ cell cancer, eg, paclitaxel and gemcitabine, a 13% overall response rate and a 19% response rate in the group treated with oxaliplatin 130 mg/m 2 seems to be of interest. Oxaliplatin may be a palliative treatment option for this patient population, and evaluation in combination regimens is warranted.
Exploratory Clinical Trial of (4<i>S</i>)-4-(3-[18F]fluoropropyl)-<scp>l</scp>-glutamate for Imaging xC− Transporter Using Positron Emission Tomography in Patients with Non–Small Cell Lung or Breast Cancer
Authors: Sora Baek, Chang-Min Choi, Sei Hyun Ahn, Jong Won Lee, Gyungyub Gong, Jin-Sook Ryu, Seung Jun Oh, Claudia Bacher-Stier, Lüder Fels, Norman Koglin, Christina Hultsch, Christoph A. Schatz, Ludger M. Dinkelborg, Erik S. Mittra, Sanjiv S. Gambhir, Dae Hyuk Moon
Journal: Clinical Cancer Research (2012)

(4S)-4-(3-[(18)F]fluoropropyl)-l-glutamate (BAY 94-9392, alias [(18)F]FSPG) is a new tracer to image x(C)(-) transporter activity with positron emission tomography (PET). We aimed to explore the tumor detection rate of [(18)F]FSPG in patients relative to 2-[(18)F]fluoro-2-deoxyglucose ([(18)F]FDG). The correlation of [(18)F]FSPG uptake with immunohistochemical expression of x(C)(-) transporter and CD44, which stabilizes the xCT subunit of system x(C)(-), was also analyzed.Patients with non-small cell lung cancer (NSCLC, n = 10) or breast cancer (n = 5) who had a positive [(18)F]FDG uptake were included in this exploratory study. PET images were acquired following injection of approximately 300 MBq [(18)F]FSPG. Immunohistochemistry was done using xCT- and CD44-specific antibody.[(18)F]FSPG PET showed high uptake in the kidney and pancreas with rapid blood clearance. [(18)F]FSPG identified all 10 NSCLC and three of the five breast cancer lesions that were confirmed by pathology. [(18)F]FSPG detected 59 of 67 (88%) [(18)F]FDG lesions in NSCLC, and 30 of 73 (41%) in breast cancer. Seven lesions were additionally detected only on [(18)F]FSPG in NSCLC. The tumor-to-blood pool standardized uptake value (SUV) ratio was not significantly different from that of [(18)F]FDG in NSCLC; however, in breast cancer, it was significantly lower (P < 0.05). The maximum SUV of [(18)F]FSPG correlated significantly with the intensity of immunohistochemical staining of x(C)(-) transporter and CD44 (P < 0.01).[(18)F]FSPG seems to be a promising tracer with a relatively high cancer detection rate in patients with NSCLC. [(18)F]FSPG PET may assess x(C)(-) transporter activity in patients with cancer.
Sleep HERMES: a European training project for respiratory sleep medicine
Authors: W. De Backer, A.K. Simonds, V. Horn, S. Andreas, M. Bonsignore, P. Calverley, V. Donic, P. Lévy, S. Mitchell, W.T. McNicholas, M. Morrell, W. Randerath, R.L. Riha, H. Trang, J. Verbraecken, P. Palange
Journal: European Respiratory Journal (2011)

The clinical characterisation and description of the obstructive sleep apnoea/hypopnoea syndrome (OSAHS) and related syndromes have been revealed by several epidemiological studies conducted in the late 20th and 21st centuries. These highly prevalent syndromes affect about 9% of middle-aged males and 4% of females. These syndromes have serious medical and social consequences, such as cardiovascular or metabolic diseases and even premature death. Consequently, respiratory sleep medicine has evolved and progressed rapidly within the sleep medicine field over the last decades. New diagnostic and therapeutic techniques appeared in response to an increasing number of patients and clinical interventions. The research progressed to focus not only on the clinical and pathophysiological, but also on the genetic and molecular aspects of these syndromes [1–4]. Nevertheless, the literature in the field does not provide any clear consensus on diagnostic classification and assessment. No harmonised standards of training exist across Europe for respiratory sleep medicine. The European Respiratory Society (ERS) conducted a survey in 2010 to enquire about the structure and organisation of training in different countries within Europe. National experts in the field of respiratory sleep medicine from 21 different countries were consulted. They were first asked about the duration of training in respiratory disorders during sleep. A huge diversity in training organisations and durations was revealed. Across 18 collected responses, it was observed that nine countries do not have any specific training for the specialty. Those countries are Luxembourg, Belgium, Denmark, Greece, Sweden, Poland, Cyprus, Ireland and the UK. On the contrary, training is organised in the Czech Republic, Germany, Romania, Spain, Lithuania, Finland, Austria, the Slovak Republic and Lithuania but could last from 1 week to 12 yrs. Moreover, except for the UK and the …
Effect of acute hyperoxia on the bronchodilator response to salbutamol in stable asthmatic patients.
Authors: K. D. Dagg, L. J. Thomson, S. G. Ramsay, N. C. Thomson
Journal: Thorax (1996)

Recent animal studies have suggested that changes in oxygen tension may alter airway responses to bronchoconstrictor and bronchodilator stimuli. These effects may have relevance to the management of acute exacerbations of asthma but have not been well studied in man. This study was designed therefore to examine the effect of acute hyperoxia (Fio2 1.0) on the bronchodilator response to salbutamol in stable asthmatic patients.Twelve stable adult asthmatic patients (three women) were studied using a randomised double blind placebo controlled crossover design. On two study days following baseline measurements patients breathed either air (Fio2 0.21) or oxygen (Fio2 1.0) for 10 minutes alone and then in combination with three incremental doses of nebulised salbutamol administered at 15 minute intervals. The same protocol was employed on two further study days using nebulised saline instead of salbutamol.The mean absolute change in forced expiratory volume in one second (FEV1) from baseline after salbutamol was similar on the normoxic and hyperoxic study days but significantly greater than the study days on which nebulised saline was administered.Acute hyperoxi does not potentiate the immediate bronchodilator response to salbutamol in stable asthmatic patients.
Preradiation high-dose intravenous methotrexate with leucovorin rescue for untreated primary childhood brain tumors.
Authors: J C Allen, R Walker, G Rosen
Journal: Journal of Clinical Oncology (1988)

Although high-dose intravenous (IV) methotrexate (MTX) with leucovorin rescue (HDMTX) is effective for certain recurrent primary brain tumors, concern for inducing leukoencephalopathy has restrained its use as adjuvant therapy following therapeutic brain irradiation (RT). We have conducted a phase I to II clinical trial using four biweekly courses of HDMTX (8 g/m2) in a neoadjuvant setting in ten patients with newly diagnosed high-risk pediatric primary brain tumors. Four patients experienced an objective response after two to four courses of HDMTX alone (medulloblastoma, one; pineoblastoma, one; malignant cerebral astrocytoma, two). All ten patients subsequently received a course of therapeutic RT, and in seven cases, adjuvant chemotherapy with other agents. One patient acquired an acute transient encephalopathy before RT that completely resolved, and another developed a seizure disorder following RT associated with white matter abnormalities on a magnetic resonance imaging (MRI) scan. Five patients have survived a minimum of 33+ months, and four remain in continuous remission. The acute and delayed neurotoxicity of neoadjuvant HDMTX is acceptable, and we favor further use of this neoadjuvant approach in the context of a phase III trial.
Cost Efficiency of Treatments for the Schizophrenic Patient
Authors: PHILIP R.A. MAY
Journal: American Journal of Psychiatry (1971)

The findings of a controlled experimental study in which five treatment methods were compared by both clinical and cost criteria indicate that, for most schizophrenic patient, milieu care alone is both expensive and relatively ineffective. In terms of cost per patient released and cost per case treated, it is far less expensive to provide the most effective available treatment than to merely provide a good level of milieu care without special additional treatment.
New challenges in viral hepatitis
Authors: David Thomas, Fabien Zoulim
Journal: Gut (2012)

Over the past few decades there has been remarkable progress in viral hepatitis. Beginning with discovery of the viral agents, we now have reliable methods to diagnose and monitor all hepatitis virus infections, as well significant advances in treatment and prevention. Nonetheless, important challenges remain. This supplement to Gut looks forward to the next generation of challenges in the field of viral hepatitis, and this introductory article highlights several key issues.
Antifibrotic effect of adrenomedullin on coronary adventitia in angiotensin II-induced hypertensive rats
Authors: T TSURUDA, J KATO, K HATAKEYAMA, H MASUYAMA, Y CAO, T IMAMURA, K KITAMURA, Y ASADA, T ETO
Journal: Cardiovascular Research (2004)

The extracellular matrix (ECM) determines the structural integrity of the heart and vasculature, participating in cardiovascular remodeling. We previously reported that adrenomedullin (AM) inhibited cellular proliferation and protein synthesis of cardiac fibroblasts; however, the precise mechanisms of AM actions as an antifibrotic factor remain unknown. The purpose of this study was to examine the biological actions of AM against the profibrotic factor angiotensin II (Ang II) in coronary adventitia.Rats with hypertension induced by Ang II infusion were administered 0.06 mug/kg/min recombinant human AM subcutaneously for 14 days. The AM infusion significantly (p<0.05) reduced the Ang II-induced increase of coronary adventitial fibroblasts expressing Ki-67 and alpha-smooth muscle actin (alpha-SMA) in the left ventricle, by 65%, and 62%, respectively, without affecting systolic blood pressure, left ventricle/body weight, or cross-sectional area of myocardial fibers. Collagen deposition of coronary arteries was reduced by the AM infusion (-24%, p<0.01), and these effects of AM were accompanied by significant reductions in gene expression of type 1 collagen (-49%, p<0.05) and transforming growth factor-beta1 (TGF-beta1) (-55%, p<0.01). In cultured cardiac fibroblasts, 10(-7) mol/L AM exerted an inhibitory effect on TGF-beta1-induced alpha-SMA expression (p<0.01) that was mimicked by 8-bromo-cAMP and attenuated by the protein kinase A inhibitor H-89.AM decreased Ang II-induced collagen deposition surrounding the coronary arteries, inhibiting myofibroblast differentiation and expressions of ECM-related genes in rats. The present findings further support the biological action of AM as an antifibrotic factor in vascular remodeling.
Retinal choroidal anastomoses and occult choroidal neovascularization in age-related macular degeneration
Authors: Jason S Slakter, Lawrence A Yannuzzi, Ulrike Schneider, John A Sorenson, Antonio Ciardella, David R Guyer, Richard F Spaide, K.Bailey Freund, Dennis A Orlock
Journal: Ophthalmology (2000)