21 research outputs found
The exosomeâbinding factors Rrp6 and Rrp47 form a composite surface for recruiting the Mtr4 helicase
Safety and Usage of C1-Inhibitor in Hereditary Angioedema: Berinert Registry Data
BackgroundThe plasma-derived, highly purified, nanofiltered C1-inhibitor concentrate (Berinert; âpnfC1-INHâ) is approved in the United States for treating hereditary angioedema (HAE) attacks and in many European countries for attack treatment and short-term prophylaxis.ObjectiveThe objective of this study was to describe safety and usage patterns of pnfC1-INH.MethodsA multicenter, observational, registry was conducted between 2010 and 2014 at 30 United States and 7 European sites to obtain both prospective (occurring after enrollment) and retrospective (occurring before enrollment) safety and usage data on subjects receiving pnfC1-INH for any reason.ResultsOf 343 enrolled patients, 318 received 1 or more doses of pnfC1-INH for HAE attacks (11,848 infusions) or for prophylaxis (3142 infusions), comprising the safety population. Median dosages per infusion were 10.8 IU/kg (attack treatment) and 16.6 IU/kg (prophylaxis). Approximately 95% of infusions were administered outside of a health care setting. No adverse events (AEs) were reported in retrospective data. Among prospective data (n = 296 subjects; 9148 infusions), 252 AEs were reported in 85 (28.7%) subjects (rate of 0.03 events/infusion); 9 events were considered related to pnfC1-INH. Two thromboembolic events were reported in subjects with thrombotic risk factors. No patient was noted to have undergone viral testing for suspected blood-borne infection during registry participation.ConclusionsThe findings from this large, international patient registry documented widespread implementation of pnfC1-INH self-administration outside of a health care setting consistent with current HAE guidelines. These real-world data revealed pnfC1-INH usage for a variety of reasons in patients with HAE and showed a high level of safety regardless of administration setting or reason for use
Clamp loader ATPases and the evolution of DNA replication machinery
Clamp loaders are pentameric ATPases of the AAA+ family that operate to ensure processive DNA replication. They do so by loading onto DNA the ring-shaped sliding clamps that tether the polymerase to the DNA. Structural and biochemical analysis of clamp loaders has shown how, despite differences in composition across different branches of life, all clamp loaders undergo the same concerted conformational transformations, which generate a binding surface for the open clamp and an internal spiral chamber into which the DNA at the replication fork can slide, triggering ATP hydrolysis, release of the clamp loader, and closure of the clamp round the DNA. We review here the current understanding of the clamp loader mechanism and discuss the implications of the differences between clamp loaders from the different branches of life
Poverty, markets and democracy
Lecture delivered in London (GB), 25 Mar 1995SIGLEAvailable from British Library Document Supply Centre-DSC:6076.6085(1995) / BLDSC - British Library Document Supply CentreGBUnited Kingdo
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Ultrasound curriculum taught by first-year medical students: A four-year experience in Tanzania.
BACKGROUND:Diagnostic imaging is an integral aspect of care that is often insufficient, if not altogether absent, in rural and remote regions of low to middle income countries (LMICs) such as Tanzania. The introduction of ultrasound can significantly impact treatment in these countries due to its portability, low cost, safety, and usefulness in various medical assessments. This study reviews the implementation of a four-week ultrasound course administered annually from 2013-2016 in a healthcare professional school in Mwanza, Tanzania by first-year allopathic US medical students. METHODS:Participants (n=582, over 4 years) were recruited from the Tandabui Institute of Health Sciences and Technology to take the ultrasound course. Subjects were predominantly clinical officer students, but other participants included other healthcare professional students, practicing healthcare professionals, and school employees. Data collected includes pre-course examination scores, post-course examination scores, course quiz scores, demographic surveys, and post-course feedback surveys. Data was analyzed using two-tailed t-tests and the single factor analysis of variance (ANOVA). RESULTS:For all participants who completed both the pre- and post-course examinations (n=229, 39.1% of the total recruited), there was a significant mean improvement in their ultrasound knowledge of 42.5%, P<0.01. CONCLUSION:Our data suggests that trained first-year medical students can effectively teach a point of care ultrasound course to healthcare professional students within four weeks in Tanzania. Future investigation into the level of long-term knowledge retention, impact of ultrasound training on knowledge of human anatomy and diagnostic capabilities, and how expansion of an ultrasound curriculum has impacted access to care in rural Tanzania is warranted
Transcatheter therapy in partially abnormal pulmonary venous return with additional drainage to the left atrium
Background A persistent anastomosis between the pulmonary veins that connect with the left atrium and the systemic vein that drains into the right atrium has occasionally been reported. We report characteristics and transcatheter therapy in partially abnormal pulmonary venous return with additional drainage to the left atrium. Methods We retrospectively studied such patients in 5 institutions. Results Ten patients (6 girls) presented at a median age of 8 (0.1 to 54) years with 2 anatomic types: 8 vertical vein types with drainage of the left upper lobe to the innominate vein via a large vertical vein (left superior cardinal vein) and to the left atrium via the left upper pulmonary vein; and 2 scimitar vein (SV) types with drainage of the right middle and lower pulmonary veins into the inferior vena cava and to the left atrium via an anomalous connecting vein. Associated malformations were aortic coarctation (n = 2) and secundum atrial septal defects (n = 3). Two patients of the vertical vein type were operated. Transcatheter occlusion of the abnormal pulmonary venous return was performed in 7 cases, associated with occlusion of systemic arterial supply (n = 2), secundum atrial septal closure (n = 2), left upper pulmonary vein stenosis stenting (n = 1), and coarctation stenting (n = 1). Including previously published cases, 18 patients (13 vertical veins and 5 scimitar veins) underwent transcatheter repair. Patients over 40 years of age tend to be symptomatic at presentation (p = 0.056). Conclusion In partially abnormal pulmonary venous return with dual drainage, transcatheter therapy can be offered in the majority of patients. © 2013 Elsevier Ireland Ltd
Efficacy and Safety of an Intravenous C1-Inhibitor Concentrate for Long-Term Prophylaxis in Hereditary angioedema
Background The plasma-derived, pasteurized, nanofiltered C1-inhibitor concentrate (pnfC1-INH) is approved in the United States as an intravenous (IV) on-demand treatment for hereditary angioedema (HAE) attacks, and, in Europe, as on demand and short-term prophylaxis. Objective This analysis evaluated Berinert Patient Registry data regarding IV pnfC1-INH used as long-term prophylaxis (LTP). Methods The international registry (2010â2014) collected prospective and retrospective usage, dosing, and safety data on individuals who used pnfC1-INH for any reason. Results The registry included data on 47 subjects (80.9% female subjects; mean age, 44.8 years), which reflected 4082 infusions categorized as LTP and a total of 430.2 months of LTP administration. The median absolute dose of pnfC1-INH given for LTP was 1000 IU (range, 500â3000 IU), with a median time interval between infusion and a subsequent pnfC1-INHâtreated attack of 72.0 hours (range, 0.0â166.4 hours). Fifteen subjects (31.9%) had no pnfC1-INHâtreated HAE attacks within 7 days after pnfC1-INH infusion for LTP; 32 subjects (68.1%) experienced 246 attacks, with rates of 0.06 attacks per infusion and 0.57 attacks per month. A total of 81 adverse events were reported in 16 subjects (34.0%) (0.02 events per infusion; 0.19 events per month); only 3 adverse events were considered related to pnfC1-INH (noncardiac chest pain, postinfusion headache, deep vein thrombosis in a subject with an IV port). Conclusion In this international registry, IV pnf-C1-INH given as LTP for HAE was safe and efficacious, with a low rate of attacks that required pnfC1-INH treatment, particularly within the first several days after LTP administration