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https://www.readbyqxmd.com/read/29791923/inhaled-treprostinil-prodrug-lipid-nanoparticle-formulations-provide-long-acting-pulmonary-vasodilation
#1
Franziska G Leifer, Donna M Konicek, Kuan-Ju Chen, Adam J Plaunt, Dany Salvail, Charles E Laurent, Michel R Corboz, Zhili Li, Richard W Chapman, Walter R Perkins, Vladimir S Malinin
Treprostinil (TRE), a prostanoid analogue approved in the USA for the treatment of pulmonary arterial hypertension, requires continuous infusion or multiple dosing sessions per day for inhaled and oral routes of administration due to its short half-life. The inhaled drug is known to induce adverse systemic and local effects including headache, nausea, cough, and throat irritation which may be due at least in part to transiently high drug concentrations in the lungs and plasma immediately following administration [1]...
May 23, 2018: Drug Research
https://www.readbyqxmd.com/read/29789495/apolipoprotein-e-and-atherosclerosis-from-lipoprotein-metabolism-to-microrna-control-of-inflammation
#2
REVIEW
Laura Bouchareychas, Robert L Raffai
Apolipoprotein (apo) E stands out among plasma apolipoproteins through its unprecedented ability to protect against atherosclerosis. Although best recognized for its ability to mediate plasma lipoprotein clearance in the liver and protect against macrophage foam cell formation, our recent understanding of the influence that apoE can exert to control atherosclerosis has significantly widened. Among apoE's newfound athero-protective properties include an ability to control exaggerated hematopoiesis, blood monocyte activation and aortic stiffening in mice with hyperlipidemia...
May 23, 2018: Journal of Cardiovascular Development and Disease
https://www.readbyqxmd.com/read/29778482/randomized-noninferiority-field-trial-evaluating-cephapirin-sodium-for-treatment-of-nonsevere-clinical-mastitis
#3
T Tomazi, T A F Lopes, V Masson, J M Swinkels, M V Santos
The general objective of this study was to evaluate whether cephapirin sodium is noninferior compared with a positive control broad-spectrum product formulated with a combination of antimicrobials for intramammary treatment of nonsevere clinical mastitis. In addition, we compared the efficacy of treatments on the cure risks of pathogen groups (gram-positive, gram-negative, and cultures with no growth) based on culture results. A total of 346 cows distributed in 31 commercial dairy herds were selected to participate in the study, although only 236 met the criteria for evaluation of microbiological cure...
May 16, 2018: Journal of Dairy Science
https://www.readbyqxmd.com/read/29768710/improving-the-safety-of-high-dose-methotrexate-for-children-with-hematologic-cancers-in-settings-without-access-to-mtx-levels-using-extended-hydration-and-additional-leucovorin
#4
Kalthi Vaishnavi, Deepak Bansal, Amita Trehan, Richa Jain, Savita Verma Attri
BACKGROUND: A lack of access to methotrexate levels is common in low- and middle-income countries (LMIC), relevant for 80% of children with cancer worldwide. We evaluated whether high-dose methotrexate (HD-MTX) can be administered safely with extended hydration and leucovorin rescue, with monitoring of serum creatinine and urine pH. METHODS: The prospective study was conducted at a single centre in Chandigarh, India in 2015. Patients with B-cell acute lymphoblastic leukemia (ALL) or with T-cell ALL or non-Hodgkin lymphoma (T-NHL) were administered 3 and 5 gm/m2 of MTX (24 hr infusion), respectively...
May 16, 2018: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/29762905/pharmacokinetics-and-the-transition-to-extended-half-life-factor-concentrates-communication-from-the-ssc-of-the-isth
#5
Margaret V Ragni, Stacy E Croteau, Massimo Morfini, Marjon H Cnossen, Alfonso Iorio
Extended half-life proteins (EHL) are increasingly used in clinical practice, but there is no standardized approach to sampling, interpretation, and implementation of pharmacokinetics (PK) data to maximize treatment benefit. The goal of EHL treatment is to attain a trough level sufficient to protect against spontaneous bleeds and reduce infusion frequency and limitations on individual activity and lifestyle. Performing classical PK assessments requires multiple blood samples which is burdensome for patients and providers...
May 15, 2018: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/29757876/a-randomized-trial-of-prophylactic-extended-carboplatin-infusion-to-reduce-hypersensitivity-reactions-in-recurrent-ovarian-cancer
#6
Katherine LaVigne, David M Hyman, Qin C Zhou, Alexia Iasonos, William P Tew, Carol Aghajanian, Vicky Makker, Martee L Hensley, Jason Konner, Rachel N Grisham, Nicholas Cangemi, Krysten Soldan, David R Spriggs, Paul J Sabbatini, Roisin E OʼCearbhaill
OBJECTIVE: Hypersensitivity with repeated exposure to platinum agents is common and can preclude continued treatment, even in patients with disease that remains platinum sensitive. We sought to compare the effects of prophylactic, extended carboplatin infusion versus standard infusion on the rate of carboplatin hypersensitivity reactions (HSRs) in women with recurrent ovarian cancer. METHODS: This was a single-institution, randomized, nonblinded trial comparing a graded, 3-hour extended infusion of carboplatin with a standard 30-minute infusion in patients with recurrent ovarian cancer who were enrolled from January 2011 to April 2015...
May 4, 2018: International Journal of Gynecological Cancer
https://www.readbyqxmd.com/read/29753817/arch-augmentation-via-median-sternotomy-for-coarctation-of-aorta-with-proximal-arch-hypoplasia
#7
W Hampton Gray, Winfield J Wells, Vaughn A Starnes, S Ram Kumar
BACKGROUND: Coarctation of the aorta can be associated with hypoplasia of the proximal transverse aortic arch. One approach to manage this condition is via left thoracotomy and extended end-to-end anastomosis with the expectation that the proximal arch will grow over time. Our preferred approach is to augment the aorta via midline sternotomy. We hypothesized that this approach is safe, durable and allows reliable growth of the aorta. METHODS: We identified the records of patients with biventricular anatomy who had coarctation of the aorta, hypoplasia of the proximal transverse arch, and no other cardiac lesion that would mandate cardiopulmonary bypass use and midline sternotomy...
May 10, 2018: Annals of Thoracic Surgery
https://www.readbyqxmd.com/read/29735085/evaluating-the-effects-of-the-adulterants-in-milk-using-direct-infusion-high-resolution-mass-spectrometry
#8
Tatiane Melina Guerreiro, Diogo Noin de Oliveira, Carlos Fernando Odir Rodrigues Melo, Estela de Oliveira Lima, Marta da Silva Ribeiro, Rodrigo Ramos Catharino
Milk is an extremely complex food, capable of providing essential nutrients as well as being an important source of energy, and high-quality proteins and fats. Due to advances in technology, and to meet the increasing demand, production costs have increased, turning milk into a target of adulterations. Routine methods usually applied to certify the quality of the milk are restricted to microbiological tests, and assays that attest the nutritional composition within the expected values. However, potentially harmful byproducts generated by adulterating substances in general are not detected through these methodologies...
June 2018: Food Research International
https://www.readbyqxmd.com/read/29732708/pharmacokinetic-modelling-and-validation-of-the-half-life-extension-needed-to-reduce-the-burden-of-infusions-compared-with-standard-factor-viii
#9
C Hermans, J Mahlangu, J Booth, H Schütz, E Santagostino, G Young, H-Y Lee, K N Steinitz-Trost, V Blanchette, E Berntorp
INTRODUCTION: Currently, no universally accepted definition of extended half-life (EHL) recombinant FVIII (rFVIII) exists. Identifying the minimum half-life extension ratio required for a reduction in dosing frequency compared with standard rFVIII could enable a more practical approach to decisions around prophylaxis with EHL rFVIII. AIM: To identify the half-life extension ratio required to decrease rFVIII dosing frequency by at least 1 day while maintaining the proportion of patients with plasma rFVIII levels above 1 IU/dL and without increasing the total weekly dose...
May 6, 2018: Haemophilia: the Official Journal of the World Federation of Hemophilia
https://www.readbyqxmd.com/read/29716492/extended-duration-regional-analgesia-for-total-knee-arthroplasty-a-randomised-controlled-trial-comparing-five-days-to-three-days-of-continuous-adductor-canal-ropivacaine-infusion
#10
S C Sargant, M J Lennon, R J Khan, D Fick, H Robertson, S Haebich
There is a growing body of evidence in favour of continuous adductor canal block (CACB) for total knee arthroplasty. However, there are no studies describing the optimal duration of the infusion. At our institution the usual practice was to stop the infusion on day three. Our hypothesis was that extending the infusion to five days would improve analgesia and quality of recovery. A prospective, non-blinded, randomised trial was undertaken. Patients received a continuous infusion of 0.2% ropivacaine via an adductor canal catheter for either three or five days...
May 2018: Anaesthesia and Intensive Care
https://www.readbyqxmd.com/read/29701544/safe-and-stable-noninvasive-focal-gene-delivery-to-the-mammalian-brain-following-focused-ultrasound
#11
Mihaela A Stavarache, Nicholas Petersen, Eric M Jurgens, Elizabeth R Milstein, Zachary B Rosenfeld, Douglas J Ballon, Michael G Kaplitt
OBJECTIVE Surgical infusion of gene therapy vectors has provided opportunities for biological manipulation of specific brain circuits in both animal models and human patients. Transient focal opening of the blood-brain barrier (BBB) by MR-guided focused ultrasound (MRgFUS) raises the possibility of noninvasive CNS gene therapy to target precise brain regions. However, variable efficiency and short follow-up of studies to date, along with recent suggestions of the potential for immune reactions following MRgFUS BBB disruption, all raise questions regarding the viability of this approach for clinical translation...
April 27, 2018: Journal of Neurosurgery
https://www.readbyqxmd.com/read/29694815/tenecteplase-versus-alteplase-before-thrombectomy-for-ischemic-stroke
#12
RANDOMIZED CONTROLLED TRIAL
Bruce C V Campbell, Peter J Mitchell, Leonid Churilov, Nawaf Yassi, Timothy J Kleinig, Richard J Dowling, Bernard Yan, Steven J Bush, Helen M Dewey, Vincent Thijs, Rebecca Scroop, Marion Simpson, Mark Brooks, Hamed Asadi, Teddy Y Wu, Darshan G Shah, Tissa Wijeratne, Timothy Ang, Ferdinand Miteff, Christopher R Levi, Edrich Rodrigues, Henry Zhao, Patrick Salvaris, Carlos Garcia-Esperon, Peter Bailey, Henry Rice, Laetitia de Villiers, Helen Brown, Kendal Redmond, David Leggett, John N Fink, Wayne Collecutt, Andrew A Wong, Claire Muller, Alan Coulthard, Ken Mitchell, John Clouston, Kate Mahady, Deborah Field, Henry Ma, Thanh G Phan, Winston Chong, Ronil V Chandra, Lee-Anne Slater, Martin Krause, Timothy J Harrington, Kenneth C Faulder, Brendan S Steinfort, Christopher F Bladin, Gagan Sharma, Patricia M Desmond, Mark W Parsons, Geoffrey A Donnan, Stephen M Davis
BACKGROUND: Intravenous infusion of alteplase is used for thrombolysis before endovascular thrombectomy for ischemic stroke. Tenecteplase, which is more fibrin-specific and has longer activity than alteplase, is given as a bolus and may increase the incidence of vascular reperfusion. METHODS: We randomly assigned patients with ischemic stroke who had occlusion of the internal carotid, basilar, or middle cerebral artery and who were eligible to undergo thrombectomy to receive tenecteplase (at a dose of 0...
April 26, 2018: New England Journal of Medicine
https://www.readbyqxmd.com/read/29694674/local-anaesthetics-and-regional-anaesthesia-versus-conventional-analgesia-for-preventing-persistent-postoperative-pain-in-adults-and-children
#13
REVIEW
Erica J Weinstein, Jacob L Levene, Marc S Cohen, Doerthe A Andreae, Jerry Y Chao, Matthew Johnson, Charles B Hall, Michael H Andreae
BACKGROUND: Regional anaesthesia may reduce the rate of persistent postoperative pain (PPP), a frequent and debilitating condition. This review was originally published in 2012 and updated in 2017. OBJECTIVES: To compare local anaesthetics and regional anaesthesia versus conventional analgesia for the prevention of PPP beyond three months in adults and children undergoing elective surgery. SEARCH METHODS: We searched CENTRAL, MEDLINE, and Embase to December 2016 without any language restriction...
April 25, 2018: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/29691064/novel-ace2-fc-chimeric-fusion-provides-long-lasting-hypertension-control-and-organ-protection-in-mouse-models-of-systemic-renin-angiotensin-system-activation
#14
Pan Liu, Jan Wysocki, Tomokazu Souma, Minghao Ye, Veronica Ramirez, Bisheng Zhou, Lisa D Wilsbacher, Susan E Quaggin, Daniel Batlle, Jing Jin
Angiotensin-converting enzyme 2 (ACE2) is a carboxypeptidase that potently degrades angiotensin II to angiotensin 1-7. Previous studies showed that injection of the enzymatic ectodomain of recombinant ACE2 (rACE2) markedly increases circulatory levels of ACE2 activity, and effectively lowered blood pressure in angiotensin II-induced hypertension. However, due to the short plasma half-life of rACE2, its therapeutic potential for chronic use is limited. To circumvent this, we generated a chimeric fusion of rACE2 and the Ig fragment Fc segment to increase its plasma stability...
April 21, 2018: Kidney International
https://www.readbyqxmd.com/read/29668579/gallbladder-cancer-with-tumor-thrombus-in-the-portal-vein-a-case-report
#15
Xiao-Zhen Zhang, Jian-Jun Tu, Wei Chen, Tao Ma, Xue-Li Bai, Ting-Bo Liang
RATIONALE: Gallbladder cancer (GBC) is a highly fatal malignancy. Due to its invasiveness and delayed diagnosis, many GBC patients are diagnosed with synchronous liver and hepatoduodenal ligament involvement. In our case, we report a gallbladder cancer with portal vein thrombus. PATIENT CONCERNS: A 60-year-old woman presented with persistent upper abdominal dull pain for 2 months. DIAGNOSES: Ultrasound examination showed gallbladder carcinoma invading liver segment IV, and a tumor thrombus in the left and right main portal trunk...
April 2018: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29662199/a-single-injection-of-crystallizable-fragment-domain-modified-antibodies-elicits-durable-protection-from-shiv-infection
#16
Rajeev Gautam, Yoshiaki Nishimura, Natalie Gaughan, Anna Gazumyan, Till Schoofs, Alicia Buckler-White, Michael S Seaman, Bruce J Swihart, Dean A Follmann, Michel C Nussenzweig, Malcolm A Martin
In the absence of an effective and safe vaccine against HIV-1, the administration of broadly neutralizing antibodies (bNAbs) represents a logical alternative approach to prevent virus transmission. Here, we introduced two mutations encoding amino acid substitutions (M428L and N434S, collectively referred to as 'LS') into the genes encoding the crystallizable fragment domains of the highly potent HIV-specific 3BNC117 and 10-1074 bNAbs to increase their half-lives and evaluated their efficacy in blocking infection following repeated low-dose mucosal challenges of rhesus macaques (Macaca mulatta) with the tier 2 SHIVAD8-EO ...
April 16, 2018: Nature Medicine
https://www.readbyqxmd.com/read/29655373/the-risk-of-adverse-events-related-to-extended-dwell-peripheral-intravenous-access
#17
Sara Campagna, Silvia Gonella, Pietro Antonio Zerla, Gianvito Corona, Tiziana Correggia, Baudolino Mussa, Paola Berchialla, Valerio Dimonte
Midline catheters (MCs) may be useful to avoid repeated venipuncture in patients requiring prolonged intravenous infusions with limited adverse events (AEs). We analyzed 2 Italian hospital databases to ascertain the safety of MCs. Among 1,538 adult patients, 154 MC-related AEs (10%; 2.49 AEs per 1,000 MC days) were reported.Infect Control Hosp Epidemiol 2018;1-3.
April 15, 2018: Infection Control and Hospital Epidemiology
https://www.readbyqxmd.com/read/29623216/feasibility-of-mesenchymal-stem-cell-culture-expansion-for-a-phase-i-clinical-trial-in-multiple-sclerosis
#18
Sarah M Planchon, Karen T Lingas, Jane Reese Koç, Brittney M Hooper, Basabi Maitra, Robert M Fox, Peter B Imrey, Kylie M Drake, Micheala A Aldred, Hillard M Lazarus, Jeffrey A Cohen
Background: Multiple sclerosis is an inflammatory, neurodegenerative disease of the central nervous system for which therapeutic mesenchymal stem cell transplantation is under study. Published experience of culture-expanding multiple sclerosis patients' mesenchymal stem cells for clinical trials is limited. Objective: To determine the feasibility of culture-expanding multiple sclerosis patients' mesenchymal stem cells for clinical use. Methods: In a phase I trial, autologous, bone marrow-derived mesenchymal stem cells were isolated from 25 trial participants with multiple sclerosis and eight matched controls, and culture-expanded to a target single dose of 1-2 × 106 cells/kg...
January 2018: Multiple Sclerosis Journal—Experimental, Translational and Clinical
https://www.readbyqxmd.com/read/29619607/pharmacokinetic-pharmacodynamic-considerations-of-beta-lactam-antibiotics-in-adult-critically-ill-patients
#19
REVIEW
Anne M Masich, Mojdeh S Heavner, Jeffrey P Gonzales, Kimberly C Claeys
PURPOSE OF REVIEW: Beta-lactam antibiotics are commonly prescribed in critically ill patients for a variety of infectious conditions. Our understanding of how critical illness alters beta-lactam pharmacokinetics/pharmacodynamics (PK/PD) is rapidly evolving. RECENT FINDINGS: There is a growing body of literature in adult patients demonstrating that physiological alterations occurring in critically ill patients may limit our ability to optimally dose beta-lactam antibiotics to reach these PK/PD targets...
April 4, 2018: Current Infectious Disease Reports
https://www.readbyqxmd.com/read/29611182/factor-f-viii-viia-enhances-global-haemostatic-function-in-the-co-presence-of-bypassing-agents-and-fviii-among-patients-with-haemophilia-a-with-inhibitor
#20
Keiji Nogami, Tomoko Matsumoto, Koji Yada, Kenichi Ogiwara, Shoko Furukawa, Yasuaki Shida, Masahiro Takeyama, Midori Shima
Bypassing therapy is essential for the haemostatic management of patients with haemophilia A with inhibitor (PWHA-inh), but the therapeutic effects are inconsistent. We previously reported that activated prothrombin complex concentrates (aPCC) activated factor (F)VIIIin vitro, and was mediated mainly by the activated FVII (FVIIa) contained in aPCC. We have extended those studies to assess global coagulation in whole blood from 18 PWHA-inh in the co-presence of aPCC and FVIII using Ca2+ -triggered rotational thromboelastometry...
April 2, 2018: British Journal of Haematology
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