DOCSLIB.ORG

WHO Drug Information Vol

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
WHO Drug Information Vol WHO Drug Information Vol. 25, No. 4, 2011 WHO Drug Information Contents Regulatory Focus Regulatory Action and News Seven years of EU pharmaceutical Recommended composition of regulation in Malta 343 influenza vaccines: 2012 southern hemisphere 369 International Harmonization Aprotinin: resumed marketing 369 Integration and application of equi- First ever PUMA for buccal valent regulatory assessments midazolam 369 from other countries 354 Fidaxomicin approved for Clostridium difficile infection 370 Safety and Efficacy Issues Dronedarone: restricted use 370 Asenapine maleate: serious Voclosporin: withdrawal of market- allergic reactions 358 ing authorization application 370 Lenalidomide: positive benefit-risk Lacosamide syrup: change in balance 358 formulation 371 Citalopram: dose-related cardiac New database of European risk 358 experts 371 Terpenic derivatives: new contra- indications 359 Recent Publications, Gonadotropin-releasing hormone: Information and Events cardiovascular risk 359 Marketing authorization of Uromitexan: infant fatal gasping pharmaceutical products 372 syndrome 359 Guidelines for medicine donations 372 Dasatinib: pulmonary arterial Quality control methods for herbal hypertension 360 materials 372 Drospirenone: increased risk of European Union and Andean blood clots 360 Community trade agreements 373 Ondansetron: QT prolongation 361 Pharmaceutical reform: improving TNFα blockers: Legionella and performance and equity 373 Listeria 362 Neonates exposed to antipsychotic Consultation Documents drugs: withdrawal symptoms 363 The International Pharmacopoeia Strontium ranelate: cardiovascular Bulk density and tapped density and cutaneous toxicity 364 of powders 374 Bevacizumab: ovarian failure 364 Tablet friability 378 Gadolinium: nephrogenic systemic Test for bacterial endotoxins 380 fibrosis 365 Test for sterility 391 Orlistat-containing medicines Chewable albendazole tablets 400 under review 365 Artenimol 403 Romiplostim: acute myelogenous Medroxyprogesterone injection 406 leukaemia 366 Ritonavir tablets 409 International Pharmaceutical Federation: pharmacovigilance International Nonproprietary Names seminar in India 366 Proposed List No. 106 413 341 WHO Drug Information Vol. 25, No. 4, 2011 WHO Drug Information & digital library are available online at: http://www.who.int/druginformation 342 WHO Drug Information Vol. 25, No. 4, 2011 Regulatory Focus Seven years of EU pharmaceutical regulation in Malta* In an era of globalization, governments are expected to provide safety and welfare for citizens while ensuring a level playing field and boosting competitiveness for businesses. Public authorities regulate in the public interest to protect health, en- sure patient access to safe medicines, stimulate innovation, encourage a competi- tive market, and preserve the environment (1). Malta is an island in the south of Europe with a population of 417 608 (2010). The country became a Member State of the European Union (EU) on 1 May 2004, when a total of 10 European countries joined the EU. During the process of Malta’s preparation for accession to the EU, the country transposed European pharmaceutical legislation into national legislation, leading to publication of the Medicines Act and subsidiary legislation. This established the Licensing Authority — a function which is vested in the Superintendent of Public Health — and the Medicines Authority (2). The mission of the Medicines Authority is the protection of public health in Malta through the regulation of medicinal products and pharmaceutical activities. The Authority is committed to being an effective and supportive regulator with loyalty towards its core values: protection of public health as the purpose of regulation; public trust through an impartial, consistent, disciplined and transparent approach; excellence through competent personnel with integrity, which is based on cus- tomer focused, robust, resilient and secure processes and infrastructure. Pharmaceutical regulatory patients make informed decisions on framework the choice and use of medicines. • Supporting innovation and competitive- The main objectives of medicines regula- ness through effective, efficient, pro- tion can be defined as: portionate and consistent regulation • Ensuring that only medicines of good and provision of excellent scientific and quality and favourable benefit/risk pro- regulatory advice. file are authorized and available. Pharmaceutical regulation supports • Optimizing timely, equitable and afford- the various components of a national able access to essential medicines. pharmaceutical policy, mainly research and development, authorization, produc- • Enhancing the safe and rational use of tion, distribution and use of medicinal medicines through independent infor- products. The tangible public health mation which helps prescribers and outcomes of these processes result in *Article by Patricia Vella Bonanno, CEO, Medicines Authority, and Gavril Flores, Operations and Regulatory Affairs Manager, Medicines Authority, Malta 343 Regulatory Focus WHO Drug Information Vol. 25, No. 4, 2011 Figure 1. Model of the pharmaceutical framework (3) Resources Activities Outputs Stakehoders Outcomes of the process Access Avilability Affordability & efficacy safety Quality, Rational use Structural & Legislation Human Marketing EU/national R&D, registration, √ √ √ √ √ authorization safety Patients holders Regulatory EU/national Registration, authorities safety, √ √ √ √ √ enforcement Public health Consumers Pricing EU/national Setting of price √ authorities & profit Reimbursement EU/national Establishment of Free movement Healthcare √ √ authorities reimbursement list of goods professionals Manufacturers EU/national Manufacturing/ √ √ √ & importers distribution Wholesale EU/national Distribution Open Pharmacies √ √ √ dealers competition Pharmacies National Distribution Wholesale √ √ √ dealers Healthcare EU/national Prescribing/ A true Manufacturers & √ √ professionals dispensing/ single importers administration market Patient/ EU/national Administration √ √ consumer access, availability and affordability of empowerment of healthcare professionals medicinal products which are of good and consumers (4). quality, and safe and efficacious when used rationally (Figure 1). The rational use of medicines ensures that patients receive medicines appro- Medicinal products are not always avai- priate to their clinical needs in doses that lable on the market. Affordable prices meet their individual requirements for an are an important prerequisite to ensuring adequate period of time at an affordable access to essential medicines in the cost. Continuous education of healthcare public and private sectors. Affordability is providers, patients and consumers, and influenced through promotion of compe- independent and unbiased medicines tition, through policies that encourage information empower and support deci- the use of generic medicinal products, sion making to enhance health outcomes. alternative and therapeutic substitution, Regulatory and managerial strategies good procurement practices and regula- should help to optimize safe and rational tion/control and information on prices and use of medicines and to minimize any 344 WHO Drug Information Vol. 25, No. 4, 2011 Regulatory Focus interventions which negatively impact on Within the EU regulatory framework, a rational medicines use (4). medicinal product is authorized following evaluation to ensure that it has a positive Medicines regulation within EU benefit to risk balance: that is, the product The principles of medicines regulation in should be of good quality, efficacious and the EU support public health, the free mo- safe. In these evaluations, the products vement of goods and people, compliance are assessed to ensure that the recom- with legal requirements and the concepts mended indications and any user safety of harmfulness and therapeutic efficacy. restrictions are evidence based, that The essential aim of any rules governing generic products are bio-equivalent to these areas is to additionally safeguard the reference product, that labels, patient public health through a framework which information leaflets and packaging are does not stifle the deveopment of the appropriate and patient-friendly and that pharmaceutical industry, innovation, information for health care professionals investment or trade in medicinal products (the summary of product characteristics) within the community (5). reflects authorized information. During this process, products are also assessed EU legislation is implemented on a natio- for aspects related to quality, expiry date nal level through Directives which are and recommendations for storage condi- transposed into national legislation, while tions, etc. Medicinal products are classi- Regulations are implemented in full. fied either as prescription-only medicines (POM) or over-the-counter (OTC). Figure 2. Framework for medicines regulation within EU (6) Pharmacists Policy makers Wholesale dealers Healthcare professionals National Stakeholders Importers Patient & patient organizations Manufacturers Consumers Public Health Competition National EU Pharmaceutical Legislation Legislation Rational Medicines medicine use regulation National Supply medicines policy systems Essential Medicines Research medicines Policy Human Medicines resources financing Legislation Marketing and Affordability evaluation 345 Regulatory Focus WHO Drug Information Vol. 25, No. 4, 2011 A medicinal product can only be placed Pharmaceutical regulation
Load more

Recommended publications
  • Cross-Linking of Alpha 2-Plasmin Inhibitor to Fibrin by Fibrin- Stabilizing Factor
    Cross-linking of alpha 2-plasmin inhibitor to fibrin by fibrin- stabilizing factor. Y Sakata, N Aoki J Clin Invest. 1980;65(2):290-297. https://doi.org/10.1172/JCI109671. Research Article The concentration of alpha 2-plasmin inhibitor in blood plasma is higher than that in serum obtained from the blood clotted in the presence of calcium ions, but is the same as that in serum obtained in the absence of calcium ions. Radiolabeled alpha2-plasmin inhibitor was covalently bound to fibrin only when calcium ions were present at the time of clotting of plasma or fibrinogen. Whereas, when batroxobin, a snake venom enzyme that lacks the ability to activate fibrin- stabilizing factor, was used for clotting fibrinogen, the binding was not observed. When fibrin-stablizing, factor-deficient plasma was clotted, the specific binding of alpha 2-plasmin inhibitor to fibrin did not occur even in the presence of calcium ions and the concentration of alpha 2-plasmin inhibitor in serum was the same as that in plasma. Monodansyl cadaverine, a fluorescent substrate of the fibrin-stablizing factor, was incorporated into alpha 2-plasmin inhibitor by activated fibrin-stablizing factor. All these findings indicate that alpha 2-plasmin inhibitor is cross-linked to fibrin by activated fibrin-stabilizing factor when blood is clotted. Analysis of alpha 2-plasmin inhibitor-incorporated fibrin by sodium dodecyl sulfate gel electrophoresis showed that the inhibitor was mainly cross-linked to polymerized alpha-chains of cross-linked fibrin. Cross-linking of alpha 2-plasmin inhibitor to fibrin renders fibrin clot less susceptible to fibrinolysis by plasmin.
    [Show full text]
  • United States Patent (19) 11 Patent Number: 6,019,993 Bal (45) Date of Patent: Feb
    USOO6O19993A United States Patent (19) 11 Patent Number: 6,019,993 Bal (45) Date of Patent: Feb. 1, 2000 54) VIRUS-INACTIVATED 2-COMPONENT 56) References Cited FIBRIN GLUE FOREIGN PATENT DOCUMENTS 75 Inventor: Frederic Bal, Vienna, Austria O 116 263 1/1986 European Pat. Off.. O 339 607 4/1989 European Pat. Off.. 73 Assignee: Omrix Biopharmaceuticals S.A., O 534 178 3/1993 European Pat. Off.. Brussels, Belgium 2 201993 1/1972 Germany. 2 102 811 2/1983 United Kingdom. 21 Appl. No.: 08/530,167 PCTUS85O1695 9/1985 WIPO. PCTCH920.0036 2/1992 WIPO. 22 PCT Filed: Mar. 27, 1994 PCT/SE92/ 00441 6/1992 WIPO. 86 PCT No.: PCT/EP94/00966 PCTEP9301797 7/1993 WIPO. S371 Date: Nov.30, 1995 Primary Examiner-Carlos Azpuru Attorney, Agent, or Firm-Jacobson, Price, Holman, & S 102(e) Date: Nov.30, 1995 Stern, PLLC 87 PCT Pub. No.: WO94/22503 57 ABSTRACT PCT Pub. Date: Oct. 13, 1994 A two-component fibrin glue for human application includes 30 Foreign Application Priority Data a) a component A containing i) a virus-inactivated and concentrated cryoprecipitate that contains fibrinogen, and ii) Mar. 30, 1993 EP European Pat. Off. .............. 93105298 traneXamic acid or a pharmaceutically acceptable Salt, 51 Int. Cl." A61F 2/06; A61K 35/14 thereof, and b) component B containing a proteolytic 52 U s C - - - - - - - - - - - - - - - - - - - - - - - - - - -424/426. 530,380, 530/381: enzyme that, upon combination with component A, cleaves, O X O -- O - - - s 530(383. 530ass Specifically, fibrinogen present in the cryoprecipitate of 58) Field of Search 424/426,530,380 component A, thereby, effecting a fibrin polymer.
    [Show full text]
  • Safety and Efficacy of Prothrombin Complex Concentrate As First-Line
    Cappabianca et al. Critical Care (2016) 20:5 DOI 10.1186/s13054-015-1172-6 RESEARCH Open Access Safety and efficacy of prothrombin complex concentrate as first-line treatment in bleeding after cardiac surgery Giangiuseppe Cappabianca1†, Giovanni Mariscalco2*† , Fausto Biancari3, Daniele Maselli4, Francesca Papesso1, Marzia Cottini1, Sandro Crosta5, Simona Banescu5, Aamer B. Ahmed6 and Cesare Beghi1 Abstract Background: Bleeding after cardiac surgery requiring surgical reexploration and blood component transfusion is associated with increased morbidity and mortality. Although prothrombin complex concentrate (PCC) has been used satisfactorily in bleeding disorders, studies on its efficacy and safety after cardiopulmonary bypass are limited. Methods: Between January 2005 and December 2013, 3454 consecutive cardiac surgery patients were included in an observational study aimed at investigating the efficacy and safety of PCC as first-line coagulopathy treatment as a replacement for fresh frozen plasma (FFP). Starting in January 2012, PCC was introduced as solely first-line treatment for bleeding following cardiac surgery. Results: After one-to-one propensity score–matched analysis, 225 pairs of patients receiving PCC (median dose 1500 IU) and FFP (median dose 2 U) were included. The use of PCC was associated with significantly decreased 24-h post-operative blood loss (836 ± 1226 vs. 935 ± 583 ml, p < 0.0001). Propensity score–adjusted multivariate analysis showed that PCC was associated with significantly lower risk of red blood cell (RBC) transfusions (odds ratio [OR] 0.50; 95 % confidence interval [CI] 0.31–0.80), decreased amount of RBC units (β unstandardised coefficient −1.42, 95 % CI −2.06 to −0.77) and decreased risk of transfusion of more than 2 RBC units (OR 0.53, 95 % CI 0.38–0.73).
    [Show full text]
  • A Study on Ulinastatin in Preventing Post ERCP Pancreatitis
    International Journal of Advances in Medicine Vedamanickam R et al. Int J Adv Med. 2017 Dec;4(6):1528-1531 http://www.ijmedicine.com pISSN 2349-3925 | eISSN 2349-3933 DOI: http://dx.doi.org/10.18203/2349-3933.ijam20175083 Original Research Article A study on ulinastatin in preventing post ERCP pancreatitis R. Vedamanickam1, Vinoth Kumar2*, Hariprasad2 1Department of Medicine, 2Department of Gasto and Hepatology , SREE Balaji Medical College and Hospital, Chrompet, Chennai, Tamil Nadu, India Received: 19 September 2017 Accepted: 25 October 2017 *Correspondence: Dr. Vinothkumar, E-mail: [email protected] Copyright: © the author(s), publisher and licensee Medip Academy. This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. ABSTRACT Background: Pancreatitis remains the major complication of endoscopic retrograde cholangiopancreatography (ERCP), and hyperenzymemia after ERCP is common. Ulinastatin, a protease inhibitor, has proved effective in the treatment of acute pancreatitis. The aim of this study was to assess the efficacy of ulinastatin, compare to placebo study to assess the incidence of complication due to ERCPP procedure. Methods: In this study a randomized placebo controlled trial, patients undergoing the first ERCP was randomizing to receive ulinastatin one lakh units (or) placebo by intravenous infusion one hour before ERCP for ten minutes duration. Clinical evaluation, serum amylase, ware analysed before the procedure 4 hours and 24 hours after the procedure. Results: Total of 46 patients were enrolled (23 in ulinastatin and 23 in placebo group).
    [Show full text]
  • Antiproteases in Preventing Post-ERCP Acute Pancreatitis
    JOP. J Pancreas (Online) 2007; 8(4 Suppl.):509-517. ROUND TABLE Antiproteases in Preventing Post-ERCP Acute Pancreatitis Takeshi Tsujino, Takao Kawabe, Masao Omata Department of Gastroenterology, Faculty of Medicine, University of Tokyo. Tokyo, Japan Summary there is no other randomized, placebo- controlled trial on ulinastatin under way. Pancreatitis remains the most common and Large scale randomized controlled trials potentially fatal complication following revealed that both the long-term infusion of ERCP. Various pharmacological agents have gabexate and the short-term administration of been used in an attempt to prevent post-ERCP ulinastatin may reduce pancreatic injury, but pancreatitis, but most randomized controlled these studies involve patients at average risk trials have failed to demonstrate their of developing post-ERCP pancreatitis. efficacy. Antiproteases, which have been Additional research is needed to confirm the clinically used to manage acute pancreatitis, preventive efficacy of these antiproteases in would theoretically reduce pancreatic injury patients at a high risk of developing post- after ERCP because activation of proteolytic ERCP pancreatitis. enzymes is considered to play an important role in the pathogenesis of post-ERCP pancreatitis. Gabexate and ulinastatin have Introduction recently been evaluated regarding their efficacy in preventing post-ERCP ERCP is widely performed for the diagnosis pancreatitis. Long-term (12 hours) infusion of and management of various pancreaticobiliary gabexate significantly decreased the incidence diseases. Early complications after ERCP of post-ERCP pancreatitis; however, no include acute pancreatitis, bleeding, prophylactic effect was observed for short- perforation, and infection (cholangitis and term infusion (2.5 and 6.5 hours). These cholecystitis) [1, 2]. Of these ERCP-related results may be due to the short-life of complications, pancreatitis remains the most gabexate (55 seconds).
    [Show full text]
  • Alternatives and Adjuncts to Blood Transfusion
    Joint United Kingdom (UK) Blood Transfusion and Tissue PDF Generated JPAC Transplantation Services Professional Advisory Committee 02/10/2021 03:05 Transfusion Handbook Update 6: Alternatives and adjuncts to blood transfusion http://www.transfusionguidelines.org/transfusion-handbook-update/6-alternatives-and-adjuncts-to-blood-transfusion 6: Alternatives and adjuncts to blood transfusion Essentials Transfusion alternatives were mostly developed to reduce blood use in surgery but have much wider application. They are most effective when used in combination and as part of a comprehensive patient blood management programme. Predeposit autologous blood donation before surgery is of uncertain benefit and now has very restricted indications in the UK. Intraoperative cell salvage (ICS) is effective (and may be life-saving) in elective or emergency high blood loss surgery and management of major haemorrhage. Postoperative cell salvage (PCS) and reinfusion can reduce blood use in joint replacement and scoliosis surgery. ICS and PCS are usually acceptable to Jehovah’s Witnesses. Tranexamic acid (antifibrinolytic) is inexpensive, safe and reduces mortality in traumatic haemorrhage. It reduces bleeding and transfusion in many surgical procedures and may be effective in obstetric and gastrointestinal haemorrhage. Off-label use of recombinant activated Factor VII (rFVIIa) for haemorrhage does not reduce mortality and can cause serious thromboembolic complications. Erythropoiesis stimulating agents (ESAs), such as erythropoietin, are standard therapy in renal anaemia and can support blood conservation in some cancer chemotherapy patients and autologous blood donation programmes. They may also be effective in selected patients with myelodysplasia. ESAs may cause hypertension and thromboembolic problems. Careful monitoring is required to keep the haematocrit below 35%.
    [Show full text]
  • Prothrombin Complex Concentrates: a Brief Review
    European Journal of Anaesthesiology 2008; 25: 784–789 r 2008 Copyright European Society of Anaesthesiology doi:10.1017/S0265021508004675 Review Prothrombin complex concentrates: a brief review C. M. Samama Hotel-Dieu University Hospital, Department of Anaesthesiology and Intensive Care, Paris Cedex, France Summary Prothrombin complex concentrates are haemostatic blood products containing four vitamin K-dependent clotting factors (II, VII, IX and X). They are a useful, reliable and fast alternative to fresh frozen plasma for the reversal of the effects of oral anticoagulant treatments (vitamin K antagonists). They are sometimes used for factor II or factor X replacement in patients with congenital or acquired deficiencies. They are widely prescribed in Europe. Several retrospective and prospective studies have demonstrated their efficacy in nor- malizing coagulation and in helping to control life-threatening bleeding. Few side-effects, mainly throm- boembolic events, have been reported. The link between these events and prothrombin complex concentrate infusion has, however, often been brought into question. The use of prothrombin complex concentrates in new promising indications such as the management of massive bleeding requires prospective studies providing a high level of evidence in a high-risk setting. Keywords: PROTHROMBIN COMPLEX CONTENTRATES; VITAMIN K; HAEMORRHAGE; DISSEMINATED INTRAVASCULAR COAGULATION; BLEEDING; THROMBOSIS; FACTOR IX. Introduction and side-effects, and on suggested extensions to their current authorized indications. It will not address Prothrombin complex concentrates (PCCs) are highly activated PCCs for the treatment of patients having purified concentrates with haemostatic activity pre- clotting factor inhibitors. pared from pooled plasma. They contain four vitamin K-dependent clotting factors (F) (II (prothrombin), VII, IX and X).
    [Show full text]
  • Pharmacological Interventions for Acute Pancreatitis (Review)
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by UCL Discovery Cochrane Database of Systematic Reviews Pharmacological interventions for acute pancreatitis (Review) Moggia E, Koti R, Belgaumkar AP, Fazio F, Pereira SP, Davidson BR, Gurusamy KS Moggia E, Koti R, Belgaumkar AP, Fazio F, Pereira SP, Davidson BR, Gurusamy KS. Pharmacological interventions for acute pancreatitis. Cochrane Database of Systematic Reviews 2017, Issue 4. Art. No.: CD011384. DOI: 10.1002/14651858.CD011384.pub2. www.cochranelibrary.com Pharmacological interventions for acute pancreatitis (Review) Copyright © 2017 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. TABLE OF CONTENTS HEADER....................................... 1 ABSTRACT ...................................... 1 PLAINLANGUAGESUMMARY . 2 SUMMARY OF FINDINGS FOR THE MAIN COMPARISON . ..... 4 BACKGROUND .................................... 8 OBJECTIVES ..................................... 9 METHODS ...................................... 9 Figure1. ..................................... 12 RESULTS....................................... 15 Figure2. ..................................... 16 Figure3. ..................................... 17 Figure4. ..................................... 22 Figure5. ..................................... 23 Figure6. ..................................... 24 Figure7. ..................................... 25 Figure8. ..................................... 26 ADDITIONALSUMMARYOFFINDINGS . 26 DISCUSSION ....................................
    [Show full text]
  • Clinical Review: Prothrombin Complex Concentrates - Evaluation of Safety and Thrombogenicity
    Sørensen et al. Critical Care 2011, 15:201 http://ccforum.com/content/15/1/201 REVIEW Clinical review: Prothrombin complex concentrates - evaluation of safety and thrombogenicity Benny Sørensen1*, Donat R Spahn2, Petra Innerhofer3, Michael Spannagl4 and Rolf Rossaint5 patients with inhibitors [1]. Th ese concen trates have Abstract largely been superseded in this setting by high-purity, Prothrombin complex concentrates (PCCs) are used plasma-derived factor IX and, more recently, recom- mainly for emergency reversal of vitamin K antagonist binant factor IX and bypassing agents such as activated therapy. Historically, the major drawback with PCCs PCC and recombinant activated factor VII. has been the risk of thrombotic complications. The Today, PCCs are mainly used for the emergency aims of the present review are to examine thrombotic reversal of oral vitamin K antagonist (VKA) therapy [2,3], complications reported with PCCs, and to compare the although in the USA they are only approved for haemo- safety of PCCs with human fresh frozen plasma. The philia. Bleeding is the most frequent complication of oral risk of thrombotic complications may be increased by anticoagulation, causing considerable morbidity and underlying disease, high or frequent PCC dosing, and mortality [4]. Emergency reversal of anticoagulation is poorly balanced PCC constituents. The causes of PCC most commonly needed to control bleeding as quickly as thrombogenicity remain uncertain but accumulating possible. Th e use of PCCs has also been proposed in evidence indicates the importance of factor II severe liver disease and in perioperative and trauma- (prothrombin). With the inclusion of coagulation related bleeding [5-8], although fewer studies have been inhibitors and other manufacturing improvements, performed in these settings than for anticoagulation today’s PCCs may be considered safer than earlier reversal.
    [Show full text]
  • Stability of an Autologous Platelet Clot in the Pericardial Sac: an Experimental and Clinical Study
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE General Thoracic Surgery providedRademakers by Elsevier - Publisher et al Connector Stability of an autologous platelet clot in the pericardial sac: An experimental and clinical study Leonard M. Rademakers, MD,a Paul F. Gru¨ndeman, MD, PhD,b Robert W. Bolderman, MD,a Frederik H. van der Veen, PhD,a and Jos G. Maessen, MD, PhDa Objective: Autologous platelet clots serve as slow-release delivery systems for platelet-derived growth factors and cytokines. Their application to the pericardial sac might facilitate salvage and repair of ischemically injured myocardium. However, little is known about platelet clot stability in the pericardial sac. We investigated the sta- bility of platelet clots in vitro and after administration to the pericardial sac in pigs and patients. Methods: In 5 Yorkshire-Landrace pigs and 10 patients, in vitro manufactured autologous platelet gel (Medtronic Magellan Platelet Separator) and platelet-rich fibrin (Vivolution Vivostat System) were administered to the peri- cardial sac for 30 minutes. Two antifibrinolytics (tranexamic acid and aprotinin) were tested for their capacity to stabilize autologous platelet gel. In vitro clots, incubated at 37C for 48 hours, served as controls. Clot weight was measured before and after administration. Results: In vitro, autologous platelet gel clots of either formula liquefied almost entirely within 60 minutes whereas platelet-rich fibrin clots remained intact. In the pig, platelet clot weight decreased to 16.7% Æ 7.8% (P<.05) and 66.4% Æ 3.2% (P<.05) of initial clot weight for autologous platelet gel and platelet-rich fibrin, respectively.
    [Show full text]
  • Prospectus Brochure of the Bond Bayer
    http://www.oblible.com Prospectus Dated April 1, 2015 BAYER AKTIENGESELLSCHAFT (incorporated in the Federal Republic of Germany) as Issuer EUR 1,300,000,000 Subordinated Resettable Fixed Rate Notes due 2075 Bayer Aktiengesellschaft (the "Issuer " or " Bayer AG " and together with its consolidated subsidiaries, the " Bayer Group ", " Group " or " Bayer ") will issue EUR 1,300,000,000 in aggregate principal amount of subordinated notes subject to interest rate reset with a first call date on October 2, 2022 (the " Notes ") in a denomination of EUR 1,000 on April 2, 2015 (the " Issue Date ") at an issue price of 99.499 % of their principal amount (the " Offering "). The Notes will bear interest on their principal amount (i) from and including April 2, 2015 (the "Interest Commencement Date ") to but excluding October 2, 2022 (the " First Call Date ") at a rate of 2.375 % per annum (first short coupon); (ii) from and including the First Call Date to but excluding October 2, 2027 (the "First Step-up Date ") at the relevant 5-year swap rate for the relevant reset period plus a margin of 200.7 basis points per annum; (iii) from and including the First Step-up Date to but excluding October 2, 2042 (the " Second Step-up Date ") at the relevant 5-year swap rate for the relevant reset period plus a margin of 225.7 basis points per annum; and (iv) from and including the Second Step-up Date to but excluding April 2, 2075 (the "Maturity Date ") at the relevant 5-year swap rate for the relevant reset period plus a margin of 300.7 basis points per annum (last short coupon).
    [Show full text]
  • Antifibrinolytic Therapy in Cardiac Surgery
    Antifibrinolysis and Blood-Saving Antifibrinolytic Therapy Techniques in Cardiac Surgery Ray H. Chen, MD Bleeding remains an important complication after repeat and complicated cardiac sur- O.H. Frazier, MD gery. Although aprotinin has recently been approved by the Food and Drug Administra- Denton A. Cooley, MD tion for use as an antifibrinolytic agent, many surgeons continue to have concerns about its added cost and potential side effects. We review here the current state of anti- fibrinolytic therapy for excessive bleeding in cardiothoracic surgery and suggest the use of a single intravenous dose of 10 g of e-aminocaproic acid immediately before cardio- pulmonary bypass as a safe, inexpensive, and effective alternative to aprotinin. Further clinical and laboratory studies are needed to confirm or modify this protocol. (Tex Heart Inst J 1995;22:211-5) B leeding continues to be a significant complication after cardiac surgery, even in the current, state-of-the-art, surgical practice. Public apprehension of transfusion-related communicable diseases, particularly acquired im- munodeficiency syndrome, has refocused the attention of cardiac surgeons on the importance of hemostasis to minimize the need for, and therefore the risks of, blood transfusion.'"3 Recent approval by the Food and Drug Administration of aprotinin as an agent for reducing blood loss during surgery has generated enthusiasm among cardiac surgeons. However, the use of aprotinin in routine practice has not been widely accepted because of the added cost, the risk of anaphylactic reaction, and the potential for increased incidence of postoperative myocardial infarction and graft thrombosis.47 Because both laboratory and clinical data support fibrinolysis as the mecha- nism of postoperative bleeding in open-heart surgery,"'2 the use of an antifibrino- lytic agent seems appropriate.
    [Show full text]