76 FR 49649 - Oral Dosage Form New Animal Drugs; Change of Sponsor; Chlortetracycline; Sulfamethazine

Science.gov (United States)

2011-08-11

... of Pfizer, Inc., to Boehringer Ingelheim Vetmedica, Inc. DATES: This rule is effective August 11...-018, 055-039, 065-071, and 065-440) to Boehringer Ingelheim Vetmedica, Inc., 2621 North Belt Highway...

75 FR 69462 - Importer of Controlled Substances; Notice of Registration

Science.gov (United States)

2010-11-12

... 36683), Boehringer Ingelheim Chemicals, Inc., 2820 N. Normandy Drive, Petersburg, Virginia 23805, made... registration of Boehringer Ingelheim Chemicals, Inc. to import the basic class of controlled substance is..., conventions, or protocols in effect on [[Page 69463

Induction therapy with the selective interleukin-23 inhibitor risankizumab in patients with moderate-to-severe Crohn's disease: a randomised, double-blind, placebo-controlled phase 2 study

NARCIS (Netherlands)

Feagan, Brian G.; Sandborn, William J.; D'Haens, Geert; Panés, Julián; Kaser, Arthur; Ferrante, Marc; Louis, Edouard; Franchimont, Denis; Dewit, Olivier; Seidler, Ursula; Kim, Kyung-Jo; Neurath, Markus F.; Schreiber, Stefan; Scholl, Paul; Pamulapati, Chandrasena; Lalovic, Bojan; Visvanathan, Sudha; Padula, Steven J.; Herichova, Ivona; Soaita, Adina; Hall, David B.; Böcher, Wulf O.

2017-01-01

Background The interleukin-23 pathway is implicated genetically and biologically in the pathogenesis of Crohn's disease. We aimed to assess the efficacy and safety of risankizumab (BI 655066, Boehringer Ingelheim, Ingelheim, Germany), a humanised monoclonal antibody targeting the p19 subunit of

Pharmacokinetics and safety of olodaterol administered with the Respimat Soft Mist inhaler in subjects with impaired hepatic or renal function

Directory of Open Access Journals (Sweden)

Kunz C

2016-03-01

Full Text Available Christina Kunz,1 Doreen Luedtke,1 Anna Unseld,2 Alan Hamilton,3 Atef Halabi,4 Martina Wein,5 Stephan Formella6 1Translational Medicine and Clinical Pharmacology, 2Global Biometrics and Clinical Applications, Boehringer Ingelheim Pharma GmbH and Co KG, Biberach, Germany; 3Boehringer Ingelheim, Burlington, ON, Canada; 4CRS Clinical Research Services Kiel GmbH, Kiel, 5Drug Metabolism and Pharmacokinetics, Boehringer Ingelheim Pharma GmbH and Co KG, Biberach, 6Medicine Coordination, Boehringer Ingelheim Pharma GmbH and Co KG, Ingelheim, Germany Purpose: In two trials, the influences of hepatic and renal impairment on the pharmacokinetics of olodaterol, a novel long-acting inhaled β2-agonist for treatment of COPD, were investigated.Subjects and methods: The first trial included eight subjects with mild hepatic function impairment (Child–Pugh A, eight subjects with moderate impairment (Child–Pugh B, and 16 matched healthy subjects with normal hepatic function. The second trial included eight subjects with severe renal impairment (creatinine clearance <30 mL·min-1 and 14 matched healthy subjects with normal renal function. Subjects received single doses of 20 or 30 µg olodaterol administered with the Respimat Soft Mist inhaler.Results: Olodaterol was well tolerated in all subjects. The geometric mean ratios and 90% confidence intervals of dose-normalized area under the plasma concentration-time curve from time zero to 4 hours (AUC0–4 for subjects with mild and moderate hepatic impairment compared to healthy subjects were 97% (75%–125% and 105% (79%–140%, respectively. Corresponding values for dose-normalized maximum concentration (Cmax were 112% (84%–151% (mild impairment and 99% (73%–135% (moderate impairment. The geometric mean ratio (90% confidence interval of AUC0–4 for subjects with severe renal impairment compared to healthy subjects was 135% (94%–195%, and for Cmax was 137% (84%–222%. There was no significant relationship

Verslag symposium : "M€€r welzijn zonder pijn"

NARCIS (Netherlands)

Driesse, M.; Kluivers-Poodt, M.

2010-01-01

Op 27 april 2010 hield men in Lelystad het symposium 'Meer welzijn zonder pijn' over het thema welzijn bij landbouwhuisdieren, georganiseerd door Wageningen UR Livestock Research in samenwerking met Boehringer Ingelheim. Hoewel het symposium primair bedoeld was voor rundvee- en varkensdierenartsen,

Stroke and recurrent haemorrhage associated with antithrombotic treatment after gastrointestinal bleeding in patients with atrial fibrillation

DEFF Research Database (Denmark)

Staerk, Laila; Lip, Gregory Y H; Olesen, Jonas B

2015-01-01

with better outcomes for all cause mortality and thromboembolism compared with patients who did not resume treatment. This was despite an increased longitudinal associated risk of bleeding. FUNDING, COMPETING INTERESTS, DATA SHARING: This study was supported by a grant from Boehringer-Ingelheim. Competing...

Availability, affordability, and consumption of fruits and vegetables in 18 countries across income levels: findings from the Prospective Urban Rural Epidemiology (PURE study

Directory of Open Access Journals (Sweden)

Victoria Miller, BSc

2016-10-01

Funding: Population Health Research Institute, the Canadian Institutes of Health Research, Heart and Stroke Foundation of Ontario, AstraZeneca (Canada, Sanofi-Aventis (France and Canada, Boehringer Ingelheim (Germany and Canada, Servier, GlaxoSmithKline, Novartis, King Pharma, and national or local organisations in participating countries.

76 FR 36577 - Manufacturer of Controlled Substances; Notice of Application

Science.gov (United States)

2011-06-22

... DEPARTMENT OF JUSTICE Drug Enforcement Administration Manufacturer of Controlled Substances; Notice of Application Pursuant to Sec. 1301.33(a), Title 21 of the Code of Federal Regulations (CFR), this is notice that on May 4, 2011, Boehringer Ingelheim Chemicals Inc., 2820 N. Normandy Drive...

75 FR 32506 - Manufacturer of Controlled Substances; Notice of Application

Science.gov (United States)

2010-06-08

... DEPARTMENT OF JUSTICE Drug Enforcement Administration Manufacturer of Controlled Substances; Notice of Application Pursuant to Sec. 1301.33(a) of Title 21 of the Code of Federal Regulations (CFR), this is notice that on April 12, 2010, Boehringer Ingelheim Chemicals Inc., 2820 N. Normandy Drive...

Diffusion-weighted magnetic resonance imaging in ileocolonic Crohn's disease

DEFF Research Database (Denmark)

Juel, Mie A; Rafaelsen, Søren Rafael; Nathan, Torben

protocol contained coronal e-thrive and SShT2 with free-breathing and a factor b fixed at 800 s/mm2. Patients were examined in the prone position before and after intravenous administration of 20 mg Hyoscin Butylbromide (Buscopan®, Boehringer Ingelheim, Basel, Switzerland). Ileocolonoscopy with Simple...

Ipratropium bromide delivered by metered-dose aerosol to infant ...

African Journals Online (AJOL)

Two methods of administration of ipratropium bromide (Atrovent; Boehringer Ingelheim) to wheezing children'< 25 months of age were compared: (i) the conventional nebulisation (15 children); and (ii) a metered-dose aerosol plus spacer and mask (MDA group, 17 children). The drug induced a significant and similar fall in ...

Ettevõttel lasub ühiskondlik vastutus / Karen Schmidt

Index Scriptorium Estoniae

Schmidt, Karen

2011-01-01

Terve Eesti SA algatusel Eesti ettevõtete poolt moodustatud koalitsioonist "Ettevõtted HIV vastu", kuhu kuuluvad Hill & Knowlton, Nordecon, Swedbank, TNS Emor, Coca-Cola, Johnson & Johnson, Rimi Eesti Food, DHL Estonia, Boehringer Ingelheim, Radisson BLU Hotell Tallinn ja TBWA/Guvatrak. Koalitsiooni töös osales kolm aastat ka Statoil

Ipratropium bromide delivered by metered-dose aerosol to infant ...

African Journals Online (AJOL)

1990-08-21

Aug 21, 1990 ... Two methods of administration of ipratropium bromide. (Atrovent; Boehringer Ingelheim) to wheezing children'< 25 months of age were compared: (I) the conventional nebulisa- tion (15 children); and (iI) a metered-dose aerosol plus spacer and mask (MDA group, 17 children). The drug induced a significant ...

"Partners in Science": A Model Cooperative Program Introducing High School Teachers and Students to Leading-Edge Pharmaceutical Science

Science.gov (United States)

Woska, Joseph R., Jr.; Collins, Danielle M.; Canney, Brian J.; Arcario, Erin L.; Reilly, Patricia L.

2005-01-01

"Partners in Science" is a cooperative program between Boehringer Ingelheim Pharmaceuticals, Inc. and area high schools in the community surrounding our Connecticut campus. It is a two-phase program that introduces high school students and teachers to the world of drug discovery and leading-edge pharmaceutical research. Phase 1 involves…

Similar Efficacy and Safety of Basaglar® and Lantus® in Patients with Type 2 Diabetes in Age Groups (< 65 Years, ≥ 65 Years): A Post Hoc Analysis from the ELEMENT-2 Study.

Science.gov (United States)

Pollom, Robyn K; Costigan, Timothy; Lacaya, Lyndon B; Ilag, Liza L; Hollander, Priscilla A

2018-04-01

To compare efficacy and safety of Basaglar ® [insulin glargine 100 units/mL; LY insulin glargine (LY IGlar)] to Lantus ® [insulin glargine 100 units/mL; SA insulin glargine (SA IGlar)] in older (≥ 65 years) or younger (Eli Lilly and Company and Boehringer-Ingelheim.

Idiopathic pulmonary fibrosis: current treatment options and critical appraisal of nintedanib

Directory of Open Access Journals (Sweden)

Bonella F

2015-12-01

Full Text Available Francesco Bonella,1 Susanne Stowasser,2 Lutz Wollin3 1Interstitial and Rare Lung Disease Unit, Ruhrlandklinik, University Hospital, University of Duisburg-Essen, Essen, 2Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim am Rhein, 3Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an der Riss, Germany Abstract: Idiopathic pulmonary fibrosis (IPF is the most common type of idiopathic interstitial pneumonia and is characterized by a poor prognosis, with an estimated 5-year survival of approximately 20%. Progressive and irreversible lung functional impairment leads to chronic respiratory insufficiency with a severely impaired quality of life. In the last 2 decades, novel treatments for IPF have been developed as a consequence of an increasing understanding of disease pathogenesis and pathobiology. In IPF, injured dysfunctional alveolar epithelial cells promote fibroblast recruitment and proliferation, resulting in scarring of the lung tissue. Recently, pirfenidone and nintedanib have been approved for the treatment of IPF, having shown efficacy to slow functional decline and disease progression. This article focuses on the pharmacologic characteristics and clinical evidence supporting the use of nintedanib, a potent small-molecule tyrosine kinase inhibitor, as therapy for IPF. After introducing the mechanism of action and pharmacokinetics, an overview of the safety and efficacy results from the most recent clinical trials of nintedanib in IPF is presented. Keywords: tyrosine kinase, disease progression, treatment outcome, usual interstitial pneumonia, therapeutics

Once-daily long-acting beta-agonists for chronic obstructive pulmonary disease: an indirect comparison of olodaterol and indacaterol

Directory of Open Access Journals (Sweden)

Roskell NS

2014-07-01

Full Text Available Neil S Roskell,1 Antonio Anzueto,2 Alan Hamilton,3 Bernd Disse,4 Karin Becker5 1Statistics, Bresmed Health Solutions Ltd, Sheffield, UK; 2School of Medicine, University of Texas Health Science Center, San Antonio, TX, USA; 3Medical Department, Boehringer Ingelheim (Canada Ltd, Burlington, ON, Canada; 4Medical Department, Boehringer Ingelheim GmbH, Ingelheim am Rhein, Germany; 5Global Health Economics and Outcomes Research, Boehringer Ingelheim GmbH, Ingelheim am Rhein, Germany Purpose: In the absence of head-to-head clinical trials comparing the once-daily, long-acting beta2-agonists olodaterol and indacaterol for the treatment of chronic obstructive pulmonary disease (COPD, an indirect treatment comparison by systematic review and synthesis of the available clinical evidence was conducted. Methods: A systematic literature review of randomized, controlled clinical trials in patients with COPD was performed to evaluate the efficacy and safety of olodaterol and indacaterol. Network meta-analysis and adjusted indirect comparison methods were employed to evaluate treatment efficacy, using outcomes based on trough forced expiratory volume in 1 second (FEV1, Transition Dyspnea Index, St George’s Respiratory Questionnaire total score and response, rescue medication use, and proportion of patients with exacerbations. Results: Eighteen trials were identified for meta-analysis (eight, olodaterol; ten, indacaterol. Olodaterol trials included patients of all severities, whilst indacaterol trials excluded patients with very severe COPD. Concomitant maintenance bronchodilator use was allowed in most olodaterol trials, but not in indacaterol trials. When similarly designed trials/data were analyzed for change from baseline in trough FEV1 (liters, the following mean differences (95% confidence interval were observed: trials excluding concomitant bronchodilator: indacaterol 75 mcg versus olodaterol 5 mcg, –0.005 (–0.077 to 0.067, and indacaterol 150 mcg

Lipids as organizers of cell membranes.

Science.gov (United States)

Kornmann, Benoît; Roux, Aurélien

2012-08-01

The 105th Boehringer Ingelheim Fonds International Titisee Conference 'Lipids as Organizers of Cell Membranes' took place in March 2012, in Germany. Kai Simons and Gisou Van der Goot gathered cell biologists and biophysicists to discuss the interplay between lipids and proteins in biological membranes, with an emphasis on how technological advances could help fill the gap in our understanding of the lipid part of the membrane.

Determination of the Role of Estrogen Receptors and Estrogen Regulated Genes in B cell Autoreactivity. Addendum

Science.gov (United States)

2012-07-01

Weidler C, Harle P, Schedel J, Schmidt M, Scholmerich J, Straub RH. (2004) Patients with rheumatoid arthritis and systemic lupus erythe- matosus have...Bronx, New York, United States of America; and 3current affiliation: Boehringer Ingelheim Pharmaceuticals , Ridgefield, Connecticut, United States of...Institutional Animal Care and Use Committee. WT BALB/c mice, ERα- deficient (β-sufficient) and ERβ-deficient (α-sufficient) C57Bl/6 mice were obtained from

Conception through build of an automated liquids processing system for compound management in a low-humidity environment.

Science.gov (United States)

Belval, Richard; Alamir, Ab; Corte, Christopher; DiValentino, Justin; Fernandes, James; Frerking, Stuart; Jenkins, Derek; Rogers, George; Sanville-Ross, Mary; Sledziona, Cindy; Taylor, Paul

2012-12-01

Boehringer Ingelheim's Automated Liquids Processing System (ALPS) in Ridgefield, Connecticut, was built to accommodate all compound solution-based operations following dissolution in neat DMSO. Process analysis resulted in the design of two nearly identical conveyor-based subsystems, each capable of executing 1400 × 384-well plate or punch tube replicates per batch. Two parallel-positioned subsystems are capable of independent execution or alternatively executed as a unified system for more complex or higher throughput processes. Primary ALPS functions include creation of high-throughput screening plates, concentration-response plates, and reformatted master stock plates (e.g., 384-well plates from 96-well plates). Integrated operations included centrifugation, unsealing/piercing, broadcast diluent addition, barcode print/application, compound transfer/mix via disposable pipette tips, and plate sealing. ALPS key features included instrument pooling for increased capacity or fail-over situations, programming constructs to associate one source plate to an array of replicate plates, and stacked collation of completed plates. Due to the hygroscopic nature of DMSO, ALPS was designed to operate within a 10% relativity humidity environment. The activities described are the collaborative efforts that contributed to the specification, build, delivery, and acceptance testing between Boehringer Ingelheim Pharmaceuticals, Inc. and the automation integration vendor, Thermo Scientific Laboratory Automation (Burlington, ON, Canada).

Afatinib versus methotrexate as second-line treatment in patients with recurrent or metastatic squamous-cell carcinoma of the head and neck progressing on or after platinum-based therapy (LUX-Head & Neck 1)

DEFF Research Database (Denmark)

Machiels, Jean-Pascal H; Haddad, Robert I; Fayette, Jérôme

2015-01-01

BACKGROUND: Patients with recurrent or metastatic squamous-cell carcinoma of the head and neck (HNSCC) progressing after first-line platinum regimens have a poor prognosis and few treatment options. Afatinib, an irreversible ERBB family blocker, has shown efficacy in a phase 2 study in this setting......%]), and neutropenia (1 [... provide important new insights into the treatment of this patient population and support further investigations with irreversible ERBB family blockers in HNSCC. FUNDING: Boehringer Ingelheim....

The efficacy and safety of combined tiotropium and olodaterol via the Respimat® inhaler in patients with COPD: results from the Japanese sub-population of the Tonado® studies

Directory of Open Access Journals (Sweden)

Ichinose M

2016-08-01

Full Text Available Masakazu Ichinose,1 Hiroyuki Taniguchi,2 Ayako Takizawa,3 Lars Grönke,4 Lazaro Loaiza,4 Florian Voß,4 Yihua Zhao,5 Yoshinosuke Fukuchi61Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan; 2Department of Respiratory Medicine and Allergy, Tosei General Hospital, Aichi, Japan; 3Nippon Boehringer Ingelheim Co. Ltd, Tokyo, Japan; 4Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany; 5Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut, USA; 6Juntendo University School of Medicine, Tokyo, JapanBackground: The efficacy and safety of once-daily tiotropium + olodaterol (T+O maintenance treatment was demonstrated in the large, multinational, replicate, randomized, Phase III, Tonad® 1 (NCT01431274 and 2 (NCT01431287 studies in patients with moderate to very severe COPD. However, there may be racial differences in the effects of T+O on lung function in patients with COPD.Methods: In this Tondao® subgroup analysis, we assessed efficacy and safety of T+O in Japanese participants.Results: Versus the overall population, the 413 Japanese patients randomized and treated were slightly older, with more men, lower body mass index, lower baseline St George’s Respiratory Questionnaire (SGRQ scores, fewer current smokers, but with higher pack-year smoking history. A lower proportion of Japanese patients used inhaled corticosteroids, short-acting muscarinic antagonists, or short- or long-acting β-adrenergic agonists at baseline, but use of long-acting muscarinic antagonists was higher. At Week 24, mean improvements with T+O 5/5 µg in forced expiratory volume in 1 second area under the curve from 0–3 hours response were 151 mL versus olodaterol and 134 mL versus tiotropium 5 µg; mean improvements with T+O 2.5/5 µg were 87 mL versus olodaterol and 70 mL versus tiotropium 2.5 µg. Mean improvements with T+O 5/5 µg in trough forced expiratory volume in 1 second were 131 mL versus

Availability and affordability of blood pressure-lowering medicines and the effect on blood pressure control in high-income, middle-income, and low-income countries: an analysis of the PURE study data

Directory of Open Access Journals (Sweden)

Marjan W Attaei, MA

2017-09-01

Funding: Population Health Research Institute, the Canadian Institutes of Health Research, Heart and Stroke Foundation of Ontario, Canadian Institutes of Health Research Strategy for Patient Oriented Research through the Ontario SPOR Support Unit, the Ontario Ministry of Health and Long-Term Care, pharmaceutical companies (with major contributions from AstraZeneca [Canada], Sanofi Aventis [France and Canada], Boehringer Ingelheim [Germany amd Canada], Servier, and GlaxoSmithKline, Novartis and King Pharma, and national or local organisations in participating countries.

Boehringer immunoinhibition procedure for creatine kinase-MB evaluated and compared with column ion-exchange chromatography

NARCIS (Netherlands)

ter Welle, H. F.; Baartscheer, T.; Fiolet, J. W.

1983-01-01

In determination of creatine kinase isoenzyme MB (CK-MB), the Boehringer immunoinhibition method gives a high and variable blank activity as compared with column-chromatography. Thus a correction must be applied. Furthermore, a second correction of 1% of total creatine kinase activity is necessary

Higher lung deposition with Respimat® Soft Mist™ Inhaler than HFA-MDI in COPD patients with poor technique

Directory of Open Access Journals (Sweden)

Peter Brand

2008-08-01

Full Text Available Peter Brand1, Bettina Hederer2, George Austen3, Helen Dewberry3, Thomas Meyer41RWTH, Aachen, Germany; 2Boehringer Ingelheim, Ingelheim, Germany; 3Boehringer Ingelheim, Bracknell, UK; 4Inamed Research, Gauting, GermanyAbstract: Aerosols delivered by Respimat® Soft Mist™ Inhaler (SMI are slower-moving and longer-lasting than those from pressurized metered-dose inhalers (pMDIs, improving the efficiency of pulmonary drug delivery to patients. In this four-way cross-over study, adults with chronic obstructive pulmonary disease (COPD and with poor pMDI technique received radiolabelled Berodual® (fenoterol hydrobromide 50 µg/ipratropium bromide 20 µg via Respimat® SMI or hydrofluoroalkane (HFA-MDI (randomized order on test days 1 and 2, with no inhaler technique training. The procedure was repeated on test days 3 and 4 after training. Deposition was measured by gamma scintigraphy. All 13 patients entered (9 males, mean age 62 years; FEV1 46% of predicted inhaled too fast at screening (peak inspiratory flow rate [IF]: 69–161 L/min. Whole lung deposition was higher with Respimat® SMI than with pMDI for untrained (37% of delivered dose vs 21% of metered dose and trained patients (53% of delivered vs 21% of metered dose (pSign-Test = 0.15; pANOVA< 0.05. Training also improved inhalation profiles (slower average and peak IF as well as longer breath-hold time. Drug delivery to the lungs with Respimat® SMI is more efficient than with pMDI, even with poor inhaler technique. Teaching patients to hold their breath as well as to inhale slowly and deeply increased further lung deposition using Respimat® SMI.Keywords: chronic obstructive pulmonary disease, drug delivery, inhalation, metered-dose inhaler, poor inhalation technique, training

THE ROLE OF SPASMOLYTIC THERAPY IN THERAPY OF CHRONIC CONSTIPATIONS AMONG CHILDREN

Directory of Open Access Journals (Sweden)

A.S. Potapov

2007-01-01

Full Text Available The article grounds the application of the spasmolytic therapy in complex treatment of chronic constipations among children by the example of hyoscine butylbromide (buscopan, boehringer ingelheim pharma, germany. favourable impact of the medication on the motoraevacuation function of the large intestine has been proved both clinically and by means of functional and ultrasonic methods of the large intestine examination. Good tolerance of the medication allows for its application in pediatric practice.Key words: children, chronic constipation, diagnostics, treatment, hyoscine butylbromide.

Development of Respimat® Soft Mist™ Inhaler and its clinical utility in respiratory disorders

Directory of Open Access Journals (Sweden)

Dalby RN

2011-09-01

Full Text Available Richard N Dalby1, Joachim Eicher2, Bernd Zierenberg21Department of Pharmaceutical Sciences, University of Maryland, Baltimore, MD, USA; 2Boehringer Ingelheim, Ingelheim, GermanyAbstract: The Respimat® Soft Mist™ Inhaler (SMI (Boehringer Ingelheim International GmbH, Ingelheim, Germany was developed in response to the need for a pocket-sized device that can generate a single-breath, inhalable aerosol from a drug solution using a patient-independent, reproducible, and environmentally friendly energy supply. This paper describes the design and evolution of this innovative device from a laboratory concept model and the challenges that were overcome during its development and scaleup to mass production. A key technical breakthrough was the uniblock, a component combining filters and nozzles and made of silicon and glass, through which drug solution is forced using mechanical power. This allows two converging jets of solution to collide at a controlled angle, generating a fine aerosol of inhalable droplets. The mechanical energy comes from a spring which is tensioned by twisting the base of the device before use. Additional features of the Respimat® SMI include a dose indicator and a lockout mechanism to avoid the problems of tailing-off of dose size seen with pressurized metered dose inhalers. The Respimat® SMI aerosol cloud has a unique range of technical properties. The high fine particle fraction allied with the low velocity and long generation time of the aerosol translate into a higher fraction of the emitted dose being deposited in the lungs compared with aerosols from pressurized metered dose inhalers and dry powder inhalers. These advantages are realized in clinical trials in adults and children with obstructive lung diseases, which have shown that the efficacy and safety of a pressurized metered dose inhaler formulation of a combination bronchodilator can be matched by a Respimat® SMI formulation containing only one half or one quarter

Efficacy and safety of the long-acting β2-agonist olodaterol over 4 weeks in Japanese patients with chronic obstructive pulmonary disease

Directory of Open Access Journals (Sweden)

Ichinose M

2015-08-01

Full Text Available Masakazu Ichinose,1 Ayako Takizawa,2 Toshiyasu Izumoto,2 Yusuke Tadayasu,2 Alan L Hamilton,3 Christina Kunz,4 Yoshinosuke Fukuchi51Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan; 2Nippon Boehringer Ingelheim Co. Ltd, Tokyo, Japan; 3Boehringer Ingelheim, Burlington, Ontario, Canada; 4Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an der Riß, Germany; 5Juntendo University School of Medicine, Tokyo, JapanBackground: Olodaterol is a novel long-acting β2-agonist with proven ≥24-hour duration of action in preclinical and clinical studies.Objective: This randomized, double-blind, placebo-controlled, parallel-group study evaluated the dose response of once-daily (QD olodaterol based on bronchodilator efficacy, safety, and pharmacokinetics over 4 weeks in Japanese patients with chronic obstructive pulmonary disease (COPD.Methods: All eligible patients were randomized to receive 2 µg, 5 µg, or 10 µg of olodaterol or placebo for 4 weeks via the Respimat® Soft Mist™ inhaler. The primary end point was the change from baseline in trough forced expiratory volume in 1 second (FEV1 after 4 weeks of olodaterol treatment. Secondary end points included trough FEV1 after 1 week and 2 weeks of treatment, FEV1 area under the curve from 0 hour to 3 hours (AUC0–3, peak FEV1 from 0 hour to 3 hours (peak FEV1, and corresponding forced vital capacity (FVC responses. Rescue medication use, COPD symptoms, physician global evaluation, pharmacokinetics, and safety were also assessed.Results: A total of 328 patients with COPD were randomized to receive treatment. All olodaterol doses assessed in the study showed statistically significant increases in trough FEV1 compared to placebo at Day 29 (P<0.0001. Mean increases in peak FEV1 and FEV1 AUC0–3 compared to placebo were also significant (P<0.0001. A clear dose–response relationship was observed across all treatment groups. FVC responses (trough

Blood eosinophil count and exacerbations in severe chronic obstructive pulmonary disease after withdrawal of inhaled corticosteroids

DEFF Research Database (Denmark)

Watz, Henrik; Tetzlaff, Kay; Wouters, Emiel F M

2016-01-01

were seen with eosinophil cutoffs of 300 cells per μL and 400 cells per μL, and mutually exclusive subgroups. INTERPRETATION: Blood eosinophil counts at screening were related to the exacerbation rate after complete ICS withdrawal in patients with severe to very severe COPD and a history...... of exacerbations. Our data suggest that counts of 4% or greater or 300 cells per μL or more might identify a deleterious effect of ICS withdrawal, an effect not seen in most patients with eosinophil counts below these thresholds. FUNDING: Boehringer Ingelheim....

Silent Revolution in the Library: Electronic Media Replace Printed Products. Official Pharmacopoeias: An Example from the Boehringer Mannheim Central Library.

Science.gov (United States)

Gretz, Marianne; And Others

1996-01-01

The Boehringer Mannheim Library (Germany) switched its loose-leaf pharmacopoeias from printed versions to electronic media. Discusses the decision-making and implementation process, and considers costs, technical requirements, availability of databases, user acceptance, installation, maintenance, and skills needed. Found that electronic media…

"The molecular basis of aging": the Boehringer Ingelheim Fonds 95th International Titisee Conference.

Science.gov (United States)

Garinis, George A; Patil, Christopher K; Schumacher, Björn

2007-01-01

Nearly 20 years ago, researchers discovered that lifespan can be extended by single-gene mutations in the nematode worm Caenorhabditis elegans. Further studies revealed that the mechanisms governing aging in the smallest organisms have been evolutionarily conserved and may operate in human beings. Since then, the field of biogerontology has expanded considerably, learning from - and contributing to - such disparate fields as cell signaling, metabolism, endocrinology, and a wide range of human diseases including cancer. To date, newly discovered connections and novel interdisciplinary approaches gradually unify what once seemed unrelated observations between seemingly disparate research areas. While this unification is far from complete, several overlapping themes have clearly emerged. At the 95th International Titisee Conference, devoted to "The Molecular Basis of Aging," 60 of the world's pre-eminent biogerontologists shared their most recent findings in the biology of aging, and discussed interdisciplinary connections between diverse fields.

The impact of data integrity on decision making in early lead discovery

Science.gov (United States)

Beck, Bernd; Seeliger, Daniel; Kriegl, Jan M.

2015-09-01

Data driven decision making is a key element of today's pharmaceutical research, including early drug discovery. It comprises questions like which target to pursue, which chemical series to pursue, which compound to make next, or which compound to select for advanced profiling and promotion to pre-clinical development. In the following paper we will exemplify how data integrity, i.e. the context data is generated in and auxiliary information that is provided for individual result records, can influence decision making in early lead discovery programs. In addition we will describe some approaches which we pursue at Boehringer Ingelheim to reduce the risk for getting misguided.

Assessing patient report of function: content validity of the Functional Performance Inventory-Short Form (FPI-SF in patients with chronic obstructive pulmonary disease (COPD

Directory of Open Access Journals (Sweden)

Leidy NK

2012-08-01

Full Text Available Nancy Kline Leidy,1 Alan Hamilton,2 Karin Becker31Outcomes Research, United BioSource Corporation, Bethesda, MD, USA; 2Medical Department, Boehringer Ingelheim (Canada Ltd, Burlington, ON, Canada; 3Global Health Economics and Outcomes Research, Boehringer Ingelheim GmbH, Ingelheim am Rhein, GermanyPurpose: The performance of daily activities is a major challenge for people with chronic obstructive pulmonary disease (COPD. The Functional Performance Inventory (FPI was developed based on an analytical framework of functional status and qualitative interviews with COPD patients describing these difficulties. The 65-item FPI was reduced to a 32-item short form (SF through a systematic process of qualitative and quantitative item reduction and formatted for greater clarity and ease of use. This study examined the content validity of the reduced, reformatted form of the instrument, the FPI-SF.Patients and methods: Qualitative cognitive interviews were conducted with COPD patients recruited from three geographically diverse pulmonary clinics in the United States. Interviews were designed to assess respondent interpretation of the instrument, evaluate clarity and ease of completion, and identify any new activities participants found important and difficult to perform that were not represented by the existing items.Results: Twenty subjects comprised the sample; 12 (60% were male, 14 (70% were Caucasian, the mean age was 63.0 ± 11.3 years, 12 (60% were retired, the mean forced expiratory volume in 1 second (FEV1 was 1.5 ± 0.5 L, and the mean percent predicted FEV1 was 48.4% ± 13.1%. Participants understood the FPI-SF as intended, including instructions, items, and response options. Two minor formatting changes were suggested to improve clarity of presentation. Participants found the content of the FPI-SF to be comprehensive, with items covering activities they felt were important and often difficult to perform.Conclusion: These results, together with

Nicoboxil/nonivamide cream effectively and safely reduces acute nonspecific low back pain – a randomized, placebo-controlled trial

Directory of Open Access Journals (Sweden)

Blahova Z

2016-12-01

Full Text Available Zuzana Blahova,1 Janina Claudia Holm,1 Thomas Weiser,2 Erika Richter,2 Matthias Trampisch,2 Elena Akarachkova3 1Boehringer Ingelheim RCV GmbH & Co KG, Vienna, Austria; 2Boehringer Ingelheim Pharma GmbH & Co KG, Ingelheim am Rhein, Germany; 3I.M. Sechenov First Moscow State Medical University, Moscow, Russian Federation Background/objective: Low back pain affects many patients and has a high socioeconomic impact. Topical capsaicinoids have been used for decades to treat musculoskeletal pain. This study investigated the effects of the fixed dose combination (FDC of nonivamide (a capsaicinoid and nicoboxil (a nicotinic acid ester cream in the treatment of acute nonspecific low back pain.Materials and methods: This phase III randomized, double-blind, placebo-controlled, multinational, multi-center trial investigated efficacy, safety, and tolerability of topical nicoboxil 1.08%/nonivamide 0.17% (Finalgon® cream in treatment of acute nonspecific low back pain with the endpoints: pain intensity (PI difference between pre-dose baseline and 8 hours after first application and the end of treatment, mobility score, and efficacy score.Results: Patients (n=138, 21–65 years of age, were treated for up to 4 days with FDC or placebo cream. Mean baseline PI was 6.8 on a 0–10 point numerical rating scale. After 8 hours, pain was more reduced with the FDC than with placebo (adjusted means: 2.824 vs. 0.975 points; p<0.0001. On the last treatment day, mean pain reduction by the FDC was stronger than with placebo (adjusted means: 5.132 vs. 2.174 points; p<0.0001. Mobility on Day 1 was in favor of the FDC when compared to placebo (odds ratio [95% confidence interval {CI}]: 7.200 [3.609, 14.363], p<0.0001. At the end of treatment, patients treated with the FDC rated efficacy significantly higher than placebo (odds ratio [95% CI]: 11.370 [5.342, 24.199], p<0.0001. Both treatments were tolerated well. No serious adverse events were reported.Conclusion: Nicoboxil

Afatinib versus erlotinib as second-line treatment of patients with advanced squamous cell carcinoma of the lung (LUX-Lung 8)

DEFF Research Database (Denmark)

Soria, Jean-Charles; Felip, Enriqueta; Cobo, Manuel

2015-01-01

BACKGROUND: There is a major unmet need for effective treatments in patients with squamous cell carcinoma of the lung. LUX-Lung 8 compared afatinib (an irreversible ErbB family blocker) with erlotinib (a reversible EGFR tyrosine kinase inhibitor), as second-line treatment for patients with advanced...... squamous cell carcinoma of the lung. METHODS: We did this open-label, phase 3 randomised controlled trial at 183 cancer centres in 23 countries worldwide. We enrolled adults with stage IIIB or IV squamous cell carcinoma of the lung who had progressed after at least four cycles of platinum...... be an additional option for the treatment of patients with squamous cell carcinoma of the lung. FUNDING: Boehringer Ingelheim....

A Systematic Review of the Role of Dysfunctional Wound Healing in the Pathogenesis and Treatment of Idiopathic Pulmonary Fibrosis

Directory of Open Access Journals (Sweden)

Alan Betensley

2016-12-01

Full Text Available Idiopathic pulmonary fibrosis (IPF is a chronic, progressive interstitial lung disorder showcasing an interaction between genetic predisposition and environmental risks. This usually involves the coaction of a mixture of cell types associated with abnormal wound healing, leading to structural distortion and loss of gas exchange function. IPF bears fatal prognosis due to respiratory failure, revealing a median survival of approximately 2 to 3 years. This review showcases the ongoing progress in understanding the complex pathophysiology of IPF and it highlights the latest potential clinical treatments. In IPF, various components of the immune system, particularly clotting cascade and shortened telomeres, are highly involved in disease pathobiology and progression. This review also illustrates two US Food and Drug Administration (FDA-approved drugs, nintedanib (OFEV, Boehringer Ingelheim, Ingelheim am Rhein, Germany and pirfenidone (Esbriet, Roche, Basel, Switzerland, that slow IPF progression, but unfortunately neither drug can reverse the course of the disease. Although the mechanisms underlying IPF remain poorly understood, this review unveils the past and current advances that encourage the detection of new IPF pathogenic pathways and the development of effective treatment methods for the near future.

Sandra Boehringer, L'Homosexualité féminine dans l'Antiquité grecque et romaine

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Rostom Mesli

2008-07-01

Full Text Available La publication de L’Homosexualité féminine dans l’Antiquité grecque et romaine de Sandra Boehringer est, à plusieurs titres, une excellente nouvelle.Sur le plan universitaire et éditorial, d’abord, ce livre vient confirmer qu’après de longues années de chape de plomb, les départements de lettres classiques et d’histoire ancienne sont en train de s’ouvrir aux recherches sur la sexualité. L’université française ne s’est mise – c’est le moins que l’on puisse dire – que très lentement aux recherc...

Daily home-based spirometry during withdrawal of inhaled corticosteroid in severe to very severe chronic obstructive pulmonary disease

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Rodriguez-Roisin R

2016-08-01

Full Text Available Roberto Rodriguez-Roisin,1 Kay Tetzlaff,2,3 Henrik Watz,4 Emiel FM Wouters,5 Bernd Disse,2 Helen Finnigan,6 Helgo Magnussen,4 Peter MA Calverley7 1Respiratory Institute, Servei de Pneumologia, Hospital Clínic IDIBAPS-CIBERES, Universitat de Barcelona, Barcelona, Spain; 2Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany; 3Department of Sports Medicine, University of Tübingen, Tübingen, Germany; 4Pulmonary Research Institute at Lung Clinic Grosshansdorf, Airway Research Center North, German Center for Lung Research, Grosshansdorf, Germany; 5Department of Respiratory Medicine, University Hospital Maastricht, Maastricht University, Maastricht, the Netherlands; 6Department of Biostatistics and Data Sciences, Boehringer Ingelheim, Bracknell, UK; 7Institute of Ageing and Chronic Disease, Aintree University Hospital, Liverpool, UK Abstract: The WISDOM study (NCT00975195 reported a change in lung function following withdrawal of fluticasone propionate in patients with severe to very severe COPD treated with tiotropium and salmeterol. However, little is known about the validity of home-based spirometry measurements of lung function in COPD. Therefore, as part of this study, following suitable training, patients recorded daily home-based spirometry measurements in addition to undergoing periodic in-clinic spirometric testing throughout the study duration. We subsequently determined the validity of home-based spirometry for detecting changes in lung function by comparing in-clinic and home-based forced expiratory volume in 1 second in patients who underwent stepwise fluticasone propionate withdrawal over 12 weeks versus patients remaining on fluticasone propionate for 52 weeks. Bland–Altman analysis of these data confirmed good agreement between in-clinic and home-based measurements, both across all visits and at the individual visits at study weeks 6, 12, 18, and 52. There was a measurable difference between the forced expiratory volume

Treatment of exacerbations as a predictor of subsequent outcomes in patients with COPD

Directory of Open Access Journals (Sweden)

Calverley PMA

2018-04-01

Full Text Available Peter MA Calverley,1 Antonio R Anzueto,2 Daniel Dusser,3 Achim Mueller,4 Norbert Metzdorf,5 Robert A Wise6 1Clinical Science Centre, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, UK; 2Pulmonary/Critical Care, University of Texas and South Texas Veterans Health Care System, San Antonio, TX, USA; 3Department of Pneumology, Hôpital Cochin, AP-HP, Université Paris Descartes, Sorbonne Paris Cité, Paris, France; 4Biostatistics and Data Sciences Europe, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an der Riss, Germany; 5Respiratory Medicine, Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim am Rhein, Germany; 6Division of Pulmonary and Critical Care Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA Rationale: Exacerbations of COPD are managed differently, but whether treatment of one exacerbation predicts the likelihood of subsequent events is unknown. Objective: We examined whether the treatment given for exacerbations predicted subsequent outcomes. Methods: This was a post-hoc analysis of 17,135 patients with COPD from TIOtropium Safety and Performance In Respimat® (TIOSPIR®. Patients treated with tiotropium with one or more moderate to severe exacerbations on study were analyzed using descriptive statistics, logistic and Cox regression analysis, and Kaplan–Meier plots. Results: Of 8,061 patients with moderate to severe exacerbation(s, demographics were similar across patients with exacerbations treated with antibiotics and/or steroids or hospitalization. Exacerbations treated with systemic corticosteroids alone or in combination with antibiotics had the highest risk of subsequent exacerbation (HR: 1.21, P=0.0004 and HR: 1.33, P<0.0001, respectively, and a greater risk of having a hospitalized (severe exacerbation (HR: 1.59 and 1.63, P<0.0001, respectively or death (HR: 1.50, P=0.0059 and HR: 1.47, P=0.0002, respectively compared with exacerbations treated

An industry update: the latest developments in Therapeutic delivery.

Science.gov (United States)

Steinbach, Oliver C

2018-05-01

The present industry update covers the period of 1 January-31 January 2018, with information sourced from company press releases, regulatory and patent agencies as well as scientific literature. Several public offerings (Gecko, Insmed), licensing (Foresee) and commercialization agreements (Alnylam, Collegium Pharmaceutical) as well as patent filings (Elute) continue to prove the sustained investments in the drug delivery market. In increasing numbers, more effective ways to deliver the active ingredient to the right location and the right dose through devices (Boehringer Ingelheim's Respimat, Medtronics' SynchroMedII) or improved compound properties through formulation (Aquestive Therapeutics' PharmFilm, Noven Pharmaceuticals' transdermal patch) are reaching the market. Furthering biologics and gene delivery (Avacta, Bracco) proves that novel drug delivery technologies are successfully addressing more challenging drug formats.

Challenge-based Learning: The Case of Sustainable Development Engineering at the Tecnologico de Monterrey, Mexico City Campus

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Jorge Membrillo-Hernández

2018-05-01

Full Text Available Recently, The Tecnologico de Monterrey (ITESM in Mexico has launched the Tec21 Educational Model. It is a flexible model in its curriculum that promotes student participation in challenging and interactive learning experiences. At the undergraduate level, one of the central scopes of this model is addressing challenges by the student, to develop disciplinary and cross-disciplinary skills. Two institutional strategies have been implemented to reach the ultimate goal of the ITESM, to work in all careers under the Challenge Based Learning (CBL system: the innovation week (i-week and the innovation semester (i-semester. Here we report on the results of four i-week and one i-semester models implemented in 2016. The i-semester was carried out in conjunction with a training partner, the worldwide leader Pharmaceutical Company Boehringer Ingelheim. Thirteen Sustainable Development Engineering career students were immersed for a 14 week period into the strategies to solve real-life challenges in order to develop the contents of four different courses. Six teachers of the academic institution and four engineers from the Boehringer plant served as mentors. Continuous evaluations were carried out throughout the abilities examination and partial and final examinations were performed by both experts, from the company and from the University.

Budget Impact Analysis of Afatinib for First-Line Treatment of Patients with Metastatic Non-Small Cell Lung Cancer with Epidermal Growth Factor Receptor Exon 19 Deletions or Exon 21 Substitution Mutations in a U.S. Health Plan.

Science.gov (United States)

Graham, Jonathan; Earnshaw, Stephanie; Burslem, Kate; Lim, Jonathan

2018-06-01

to be $1,606, $65,542, $140,564, $209,272, and $303,368, respectively. These budget increases translated to per-member-per-month increases ranging from $0.00 to $0.03 in years 1 to 5. The increase in afatinib use resulted in the proportion of the treated population (134 patients treated over 5 years) remaining in progression-free disease increasing from 23.7% to 26.2% at the end of year 5, versus if afatinib treatment share had stayed constant. Increasing the treatment share of afatinib in a health plan for the first-line treatment of NSCLC with EGFR del19 or L858R mutations was estimated to increase the proportion of treated patients remaining in progression-free disease, while having small budget impact to the health plan. Boehringer Ingelheim Pharmaceuticals funded this study research and was involved in all stages of study conduct, including the analysis of data, and also undertook all costs associated with the development and publication of this manuscript. Graham and Earnshaw are employees of RTI Health Solutions, an independent contract research organization that has received research funding for this and other studies from Boehringer Ingelheim Pharmaceuticals. Lim and Burslem are employees of Boehringer Ingelheim Pharmaceuticals, which developed and produces afatinib, along with other pharmaceutical products.

Primary Nonadherence to Oral Anticoagulants in Patients with Atrial Fibrillation: Real-World Data from a Population-Based Cohort.

Science.gov (United States)

Rodriguez-Bernal, Clara L; Peiró, Salvador; Hurtado, Isabel; García-Sempere, Aníbal; Sanfélix-Gimeno, Gabriel

2018-05-01

) from the Valencia Ministry of Health and Boehringer Ingelheim, a nonconditioned program to conduct independent research in chronic health care, pharmacoepidemiology, and medical practice variation. Rodriguez-Bernal was funded by the Instituto de Salud Carlos III, Spanish Ministry of Health, and cofinanced by the European Regional Development Fund (grant number RD12/0001/0005). The views presented here are those of the authors and not necessarily those of the FISABIO Foundation, the Valencia Ministry of Health, or the study sponsors. The funding sources had no access to study data and did not participate in any way in the design or conduct of the study, data analysis, decisions regarding the dissemination of findings, the development of the manuscript, or its publication. Peiró has received fees for participation in scientific meetings and courses sponsored by Novartis and Ferrer International. In 2014, Sanfélix-Gimeno participated in an advisory meeting of Boehringer Ingelheim. García-Sempere is a former employee of Boehringer Ingelheim. Rodriguez-Bernal and Hurtado have no relationships relevant to the contents of this article to disclose. This work was previously submitted as an abstract (podium presentation) at the 31st International Society of Pharmacoepidemiology (ISPE) Annual Conference; August 22-26, 2015; Boston, Massachusetts.

A cross-sectional study to assess inhalation device handling and patient satisfaction in COPD

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Miravitlles M

2016-02-01

Full Text Available Marc Miravitlles,1 Jéssica Montero-Caballero,2 Frank Richard,2 Salud Santos,3 Juan Luis Garcia-Rivero,4 Francisco Ortega,5 Xavier Ribera61Pneumology Department, Hospital Universitari Vall d’Hebron, Ciber de Enfermedades Respiratorias (CIBERES, Barcelona, Spain; 2Boehringer Ingelheim Pharma GmbH & Co KG, Ingelheim, Germany; 3Pulmonology Department, Hospital Universitari de Bellvitge, IDIBELL, Universitat de Barcelona, Ciber de Enfermedades Respiratorias (CIBERES, Barcelona, Spain; 4Pneumology Department, Hospital de Laredo, Cantabria, Spain; 5Pneumology Department, Hospital Virgen del Rocío, Sevilla, Spain; 6Boehringer Ingelheim Pharma GmbH & Co KG, Barcelona, Spain Abstract: Delivery of inhaled medications via an inhaler device underpins the effectiveness of treatment for patients with chronic obstructive pulmonary disease (COPD. Correct inhaler technique among patients is also a predictor of achieving treatment compliance and adherence. Reporting of patient satisfaction with inhalers is therefore gaining increasing attention and is now recognized as an important patient-reported outcome in clinical trials involving patients with COPD or asthma. In this cross-sectional study, we use the validated Patient Satisfaction and Preference Questionnaire (PASAPQ to assess the handling and satisfaction for Respimat® Soft Mist™ Inhaler (SMI compared with the Breezhaler® dry powder inhaler (DPI among patients with COPD in Spain. Patients were already assigned to therapy with either SPIRIVA® (tiotropium Respimat® or with Hirobriz®/Onbrez®/Oslif® (indacaterol Breezhaler® for at least 3 but not more than 6 months before completing the PASAPQ at a single visit to the study site. The primary endpoint of the trial was the mean total PASAPQ score. Secondary endpoints were the performance score domain of the PASAPQ, the convenience score domain of the PASAPQ, and the overall satisfaction score of the PASAPQ. For the primary endpoint, the mean PASAPQ

Lung function and long-term safety of tiotropium/olodaterol in East Asian patients with chronic obstructive pulmonary disease

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Bai C

2017-11-01

Full Text Available Chunxue Bai,1 Masakazu Ichinose,2 Sang Haak Lee,3 Kwan Ho Lee,4 Olaf Jöns,5 Ulrich Bothner,6 Yihua Zhao,7 Roland Buhl8 1Department of Pulmonary Medicine, Shanghai Respiratory Research Institute, Zhongshan Hospital, Fudan University, Shanghai, China; 2Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan; 3Department of Internal Medicine, St Paul’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea; 4Department of Internal Medicine, Yeungnam University Medical Center, Daegu, South Korea; 5Department of Medicine TA Respiratory Diseases, 6Department of Pharmacovigilance, Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany; 7Department of Biostatistics and Data Sciences, Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, USA; 8Pulmonary Department, Mainz University Hospital, Mainz, Germany Background and purpose: While the efficacy and safety of combined tiotropium and olodaterol in patients with COPD was established in a large clinical trial program, it is important to assess whether clinical data can be applied to geographic patient groups, particularly for East Asian patients who may have a different phenotypic profile to the global trial population. This study aimed to compare the lung function and safety profiles of tiotropium/olodaterol and monocomponents in East Asian and global populations from the TONADO® trials.Materials and methods: In the replicate, double-blind, parallel-group, active-controlled, randomized, 52-week, Phase III TONADO studies, patients received tiotropium/olodaterol, tiotropium, or olodaterol. We assessed the forced expiratory volume in 1 second (FEV1 area under the curve from 0 to 3 hours (AUC0–3 response and trough FEV1 response at 24 weeks for the approved doses, tiotropium/olodaterol 5/5 µg, tiotropium 5 µg, and olodaterol 5 µg. Treatment-emergent adverse events were recorded throughout treatment and ≤21 days

Is exercise important in chronic obstructive pulmonary disease?

Science.gov (United States)

Make, Barry; Casaburi, Richard

2007-09-01

Chronic obstructive pulmonary disease impairs the ability of patients to perform maximal physical exercise, particularly in patients with severe lung disease. However, differing perceptions of the meaning and importance of exercise to patients and caregivers is likely to impair patient-physician communication about current medical status and outcomes of therapeutic interventions. Other outcomes of importance to patients including actual performance of functional activity during daily life and health-related quality of life may also be affected by impaired exercise capacity. However, the relationships between exercise, activity, and quality of life are inconsistent. Thus, measurement of physiologic and patient-centered outcomes may provide the best approach to assessing responses to therapeutic interventions. These concepts were explored in a conference sponsored by Boehringer Ingelheim Pharmaceuticals, Inc. and Pfizer Inc and reviewed in the articles generated from the symposium in this issue of COPD.

Comorbidities of patients in tiotropium clinical trials: comparison with observational studies of patients with chronic obstructive pulmonary disease

Directory of Open Access Journals (Sweden)

Miravitlles M

2015-03-01

Full Text Available Marc Miravitlles,1 David Price,2 Klaus F Rabe,3,7 Hendrik Schmidt,4 Norbert Metzdorf,5 Bartolome Celli6 1Pneumology Department, Hospital Universitari Vall d’Hebron, Ciber de Enfermedades Respiratorias (CIBERES, Barcelona, Spain; 2Academic Primary Care, Division of Applied Health Sciences, University of Aberdeen, Aberdeen, UK; 3Department of Medicine, Christian-Albrechts-Universität zu Kiel (CAU, Großhansdorf, Germany; 4Global Biometrics and Clinical Applications, Boehringer Ingelheim Pharma GmbH and Co KG, Ingelheim am Rhein, Germany; 5TA Respiratory Diseases, Boehringer Ingelheim Pharma GmbH and Co KG, Ingelheim am Rhein, Germany; 6Pulmonary Division, Brigham and Women’s Hospital, Boston, MA, USA; 7LungenClinic Grosshansdorf, Großhansdorf, Germany Background: There is an ongoing debate on whether patients with chronic obstructive pulmonary disease (COPD seen in real-life clinical settings are represented in randomized controlled trials (RCTs of COPD. It is thought that the stringent inclusion and exclusion criteria of RCTs may prevent the participation of patients with specific characteristics or risk factors.Methods: We surveyed a database of patients recruited into 35 placebo-controlled tiotropium RCTs and also conducted a systematic literature review of large-scale observational studies conducted in patients with a documented diagnosis of COPD between 1990 and 2013. Patient demographics and comorbidities with a high prevalence in patients with COPD were compared between the two patient populations at baseline. Using the Medical Dictionary for Regulatory Activities (MedDRA; v 14.0, patient comorbidities in the pooled tiotropium RCTs were classified according to system organ class, pharmacovigilance (PV endpoints, and Standardised MedDRA Queries to enable comparison with the observational studies.Results: We identified 24,555 patients in the pooled tiotropium RCTs and 61,361 patients among the 13 observational studies that met our

[Screening for colorectal cancer: a cost benefit analysis on a health prevention programme at the Boehringer Ingelheim Company].

Science.gov (United States)

Schneider, M; Häck, H-J

2011-05-01

In Germany, approximately 70.000 people are diagnosed with colorectal cancer every year. With early diagnosis the recovery rates are over 90 % and early intervention can significantly reduce the costs of medical treatment as well as the economic losses from worker productivity. We here present the organisational procedure for bowel cancer screening and have weighed the costs against benefits to employees, the company and the healthcare system. The screening costs are compared with economic benefits. The target group for the study consisted of all 11.536 employees at the company's site in Germany. Volunteers were given a standardized questionnaire about the risk factors for colorectal cancers and an immunological fecal occult blood test (IFOBT). If risk factors for development of colorectal cancer were present or if the test result was positive, a colonoscopy was recommended in accordance with DGVS guidelines (German Society of Digestive and Metabolic diseases). A total of 4.287 employees (37.2 %) indicated an interest in undergoing screening; at the end of the period 3.958 complete datasets (2.296 men and 1.662 women, mean age 51.2 years) were available for evaluation. A colonoscopy was performed on 114 persons. Six cases of overt cancer were detected with three in the 36 - 50 age group and three in the 51 - 65 age group. Five of the six cases were stage T1 or T2. Adenomatous polyps were found and removed in 29 persons. The calculated cost benefit ratio was 1:2 for the company and 1:35 for the public health system. Using the example of colorectal screening, this study represents a cost benefit analysis of this preventative health measure in a company environment. The results show that even while taking into account the financial and personal commitment required, the cost benefit ratio is positive both for the company and for the healthcare system. © Georg Thieme Verlag KG Stuttgart · New York.

Precautions to be taken by radiologists and radiographers when prescribing hyoscine-N-butylbromide

Energy Technology Data Exchange (ETDEWEB)

Dyde, R. [Department of Radiology, Leeds Teaching Hospitals NHS Trust, Leeds (United Kingdom); Chapman, A.H. [Department of Radiology, Leeds Teaching Hospitals NHS Trust, Leeds (United Kingdom)], E-mail: tony_chapman@ntlworld.com; Gale, R. [Department of Opthalmology, University of Leeds, Leeds (United Kingdom); Mackintosh, A. [Department of Cardiology, Leeds Teaching Hospitals NHS Trust, Leeds (United Kingdom); Tolan, D.J.M. [Department of Radiology, Leeds Teaching Hospitals NHS Trust, Leeds (United Kingdom)

2008-07-15

Hyoscine-N-butylbromide (Buscopan, Boehringer Ingelheim) is a widely used antispasmodic in radiological practice. There seems to be no consensus as to best practice within radiology regarding the precautions that need to be taken when prescribing Buscopan. We have performed a thorough review of the available literature and make the following recommendations to those administering Buscopan: (1) enquire whether there is an allergic history; (2) ensure patient literature warns that 'in the rare event that following the examination you develop painful, blurred vision in one or both eyes, you must attend hospital immediately for assessment'; (3) warn patients to expect blurred vision and not to drive until this has worn off; (4) remind clinicians that special consideration needs to be given as to the method of investigating patients with cardiac instability, such as those recently admitted with acute coronary syndrome, recurrent cardiac pain at rest, uncontrolled left ventricular failure and recent ventricular arrhythmias.

Precautions to be taken by radiologists and radiographers when prescribing hyoscine-N-butylbromide

International Nuclear Information System (INIS)

Dyde, R.; Chapman, A.H.; Gale, R.; Mackintosh, A.; Tolan, D.J.M.

2008-01-01

Hyoscine-N-butylbromide (Buscopan, Boehringer Ingelheim) is a widely used antispasmodic in radiological practice. There seems to be no consensus as to best practice within radiology regarding the precautions that need to be taken when prescribing Buscopan. We have performed a thorough review of the available literature and make the following recommendations to those administering Buscopan: (1) enquire whether there is an allergic history; (2) ensure patient literature warns that 'in the rare event that following the examination you develop painful, blurred vision in one or both eyes, you must attend hospital immediately for assessment'; (3) warn patients to expect blurred vision and not to drive until this has worn off; (4) remind clinicians that special consideration needs to be given as to the method of investigating patients with cardiac instability, such as those recently admitted with acute coronary syndrome, recurrent cardiac pain at rest, uncontrolled left ventricular failure and recent ventricular arrhythmias

Donated chemical probes for open science.

Science.gov (United States)

Müller, Susanne; Ackloo, Suzanne; Arrowsmith, Cheryl H; Bauser, Marcus; Baryza, Jeremy L; Blagg, Julian; Böttcher, Jark; Bountra, Chas; Brown, Peter J; Bunnage, Mark E; Carter, Adrian J; Damerell, David; Dötsch, Volker; Drewry, David H; Edwards, Aled M; Edwards, James; Elkins, Jon M; Fischer, Christian; Frye, Stephen V; Gollner, Andreas; Grimshaw, Charles E; IJzerman, Adriaan; Hanke, Thomas; Hartung, Ingo V; Hitchcock, Steve; Howe, Trevor; Hughes, Terry V; Laufer, Stefan; Li, Volkhart Mj; Liras, Spiros; Marsden, Brian D; Matsui, Hisanori; Mathias, John; O'Hagan, Ronan C; Owen, Dafydd R; Pande, Vineet; Rauh, Daniel; Rosenberg, Saul H; Roth, Bryan L; Schneider, Natalie S; Scholten, Cora; Singh Saikatendu, Kumar; Simeonov, Anton; Takizawa, Masayuki; Tse, Chris; Thompson, Paul R; Treiber, Daniel K; Viana, Amélia Yi; Wells, Carrow I; Willson, Timothy M; Zuercher, William J; Knapp, Stefan; Mueller-Fahrnow, Anke

2018-04-20

Potent, selective and broadly characterized small molecule modulators of protein function (chemical probes) are powerful research reagents. The pharmaceutical industry has generated many high-quality chemical probes and several of these have been made available to academia. However, probe-associated data and control compounds, such as inactive structurally related molecules and their associated data, are generally not accessible. The lack of data and guidance makes it difficult for researchers to decide which chemical tools to choose. Several pharmaceutical companies (AbbVie, Bayer, Boehringer Ingelheim, Janssen, MSD, Pfizer, and Takeda) have therefore entered into a pre-competitive collaboration to make available a large number of innovative high-quality probes, including all probe-associated data, control compounds and recommendations on use (https://openscienceprobes.sgc-frankfurt.de">https://openscienceprobes.sgc-frankfurt.dehttps://openscienceprobes.sgc-frankfurt.de/">/). Here we describe the chemical tools and target-related knowledge that have been made available, and encourage others to join the project. © 2018, Müller et al.

Lung function efficacy and symptomatic benefit of olodaterol once daily delivered via Respimat® versus placebo and formoterol twice daily in patients with GOLD 2–4 COPD: results from two replicate 48-week studies

Directory of Open Access Journals (Sweden)

Koch A

2014-07-01

Full Text Available Andrea Koch,1 Emilio Pizzichini,2 Alan Hamilton,3 Lorna Hart,3 Lawrence Korducki,4 Maria Cristina De Salvo,5 Pierluigi Paggiaro6 1Medical Clinic III for Pneumology, Allergology, Sleep and Respiratory Medicine, University Hospital Bochum-Bergmannsheil, Bochum, Germany; 2NUPAIVA (Asthma Research Center, Universidade Federal de Santa Catarina, Santa Catarina, Brazil; 3Boehringer Ingelheim, Burlington, Ontario, Canada; 4Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, CT, USA; 5Centro Médico Dra. De Salvo, Fundación Respirar, Buenos Aires, Argentina; 6Cardio-Thoracic and Vascular Department, University of Pisa, Pisa, Italy Abstract: Two replicate, multicenter, randomized, double-blind, placebo-controlled, parallel-group, Phase III studies investigated the long-term efficacy and safety of once-daily olodaterol via Respimat® versus placebo and formoterol over 48 weeks in patients with moderate to very severe chronic obstructive pulmonary disease receiving usual-care background therapy. Patients received once-daily olodaterol 5 or 10 µg, twice-daily formoterol 12 µg, or placebo. Co-primary end points were forced expiratory volume in 1 second (FEV1 area under the curve from 0–3 hours response, FEV1 trough response, and Mahler transition dyspnea index total score after 24 weeks; secondary end points included St George's Respiratory Questionnaire. Overall, 904 (Study 1222.13 and 934 (Study 1222.14 patients received treatment. Olodaterol significantly improved FEV1 area under the curve from 0–3 hours versus placebo in both studies (with olodaterol 5 µg, 0.151 L and 0.129 L; with olodaterol 10 µg, 0.165 L and 0.154 L; for all comparisons P<0.0001 and FEV1 trough responses versus placebo (0.053–0.085 L; P<0.01, as did formoterol. Primary analysis revealed no significant difference in transition dyspnea index focal score for any active treatment versus placebo. Post hoc analysis using pattern mixture modeling (accounting for

HCVerso1 and 2: faldaprevir with deleobuvir (BI 207127 and ribavirin for treatment-naïve patients with chronic hepatitis C virus genotype-1b infection

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Sarrazin C

2016-11-01

Full Text Available Christoph Sarrazin,1 Francesco Castelli,2 Pietro Andreone,3 Maria Buti,4 Massimo Colombo,5 Stanislas Pol,6 Filipe Calinas,7 Massimo Puoti,8 Antonio Olveira,9 Mitchell Shiffman,10 Jerry O Stern,11 George Kukolj,12 Michael Roehrle,13 Stella Aslanyan,11 Qiqi Deng,11 Richard Vinisko,11 Federico J Mensa,11 David R Nelson,14 on behalf of the HCVerso1 and 2 study groups 1Department of Internal Medicine 1, JW Goethe University Hospital, Frankfurt, Germany; 2Department of Infectious and Tropical Diseases, University of Brescia, Brescia, 3Department of Medical and Surgical Sciences, Università di Bologna and Azienda Ospedaliero-Universitaria, Policlinico Sant‘Orsola-Malpighi, Bologna, Italy; 4Department of Internal Medicine, Hospital Universitari Vall d’Hebron and CIBERehd del Instituto Carlos III, Barcelona, Spain; 5Division of Gastroenterology and Hepatology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy; 6University Paris Descartes, Department of Hepatology, Hospital Cochin, APHP and INSERM UMS-20, Institut Pasteur, Paris, France; 7Department of Gastroenterology, Centro Hospitalar de Lisboa Central, Lisbon, Portugal; 8Department of Infectious Diseases, AO Ospedale Niguarda Cà Granda, Milan, Italy; 9Liver Unit, Hospital Universitario La Paz, CIBERehd, Madrid, Spain; 10Liver Institute of Virginia, Bon Secours Health System, Richmond, VA, USA; 11Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, USA; 12Boehringer Ingelheim Ltd/Ltée, Burlington, ON, Canada; 13Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany; 14Clinical and Translational Science Institute, University of Florida, Gainesville, FL, USA Abstract: The interferon-free combination of once-daily faldaprevir 120 mg, twice-daily deleobuvir 600 mg, and weight-based ribavirin was evaluated in two Phase III studies (HCVerso1, HCVerso2 in hepatitis C virus genotype-1b-infected, treatment-naïve patients, including

Cardiac safety strategies. 25-26 October 2005, the Radisson SAS Hotel, Nice, France.

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Hanton, Gilles; Tilbury, Lorraine

2006-03-01

This meeting was organised by IIR Life Sciences. It was chaired by Brian Guth, (head of General Pharmacology at Boehringer Ingelheim Pharma) and brought together scientists and clinicians from the pharmaceutical industry, university and regulatory agencies. The meeting presented emerging trends in cardiac safety, including its regulatory context pertaining to ICH S7A, S7B and E14. ICH S7A and S7B highlight the importance of the hERG test and telemetric studies in non-rodents. ICH E14 describes the clinical 'thorough QT study' that is required by the FDA for any new drug. Marked physiological variability in QT interval over time can be observed, partly as a result of fluctuation in autonomic tone. Beat-to-beat QT variability and T-wave morphology should be considered as a part of an integrated estimate of proarrhythmic risk. A case study illustrated the predictivity of preclinical data for proarrhythmic risk in humans, showing the importance of evaluating QT effects in patients to establish a safety margin.

Partners in Science: A Model Cooperative Program Introducing High School Teachers and Students to Leading-Edge Pharmaceutical Science

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Woska, Joseph R., Jr.; Collins, Danielle M.; Canney, Brian J.; Arcario, Erin L.; Reilly, Patricia L.

2005-12-01

Partners in Science is a cooperative program between Boehringer Ingelheim Pharmaceuticals, Inc. and area high schools in the community surrounding our Connecticut campus. It is a two-phase program that introduces high school students and teachers to the world of drug discovery and leading-edge pharmaceutical research. Phase 1 involves a series of lectures, tours, and demonstrations given by scientists within our research and development division (R&D). Phase 2 involves the selection of a small group of participants to intern for the summer in a research laboratory, working side by side with a scientist within R&D. In this manuscript, the specific aims, goals, and development of the Partners in Science program are described, as well as the syllabus/agenda, the logistics surrounding the operation of the program, and our shared personal experiences with students and teachers who have participated. Some of the pitfalls/problems associated with the program will be presented, and finally, the future direction of the program including areas of improvement and expansion are described.

Impact and prevention of severe exacerbations of COPD: a review of the evidence

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Halpin DMG

2017-10-01

Full Text Available David MG Halpin,1 Marc Miravitlles,2 Norbert Metzdorf,3 Bartolomé Celli4 1Department of Respiratory Medicine, Royal Devon and Exeter Hospital, Exeter, UK; 2Pneumology Department, Hospital Universitari Vall d’Hebron, CIBER de Enfermedades Respiratorias (CIBERES, Barcelona, Spain; 3Respiratory Medicine, Boehringer Ingelheim Pharma GmBH & Co KG, Ingelheim am Rhein, Germany; 4Pulmonary Division, Brigham and Women’s Hospital, Boston, MA, USA Abstract: Severe exacerbations of COPD, ie, those leading to hospitalization, have profound clinical implications for patients and significant economic consequences for society. The prevalence and burden of severe COPD exacerbations remain high, despite recognition of the importance of exacerbation prevention and the availability of new treatment options. Severe COPD exacerbations are associated with high mortality, have negative impact on quality of life, are linked to cardiovascular complications, and are a significant burden on the health-care system. This review identified risk factors that contribute to the development of severe exacerbations, treatment options (bronchodilators, antibiotics, corticosteroids [CSs], oxygen therapy, and ventilator support to manage severe exacerbations, and strategies to prevent readmission to hospital. Risk factors that are amenable to change have been highlighted. A number of bronchodilators have demonstrated successful reduction in risk of severe exacerbations, including long-acting muscarinic antagonist or long-acting β2-agonist mono- or combination therapies, in addition to vaccination, mucolytic and antibiotic therapy, and nonpharmacological interventions, such as pulmonary rehabilitation. Recognition of the importance of severe exacerbations is an essential step in improving outcomes for patients with COPD. Evidence-based approaches to prevent and manage severe exacerbations should be implemented as part of targeted strategies for disease management. Keywords

COPD depicted – patients drawing their lungs

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Kaptein AA

2017-11-01

Full Text Available Ad A Kaptein,1 Jitske Tiemensma,2 Elizabeth Broadbent,3 Guus M Asijee,4,5 Maarten Voorhaar4,5 1Medical Psychology, Leiden University Medical Centre (LUMC, Leiden, the Netherlands; 2Psychological Sciences, University of California, Merced, CA, USA; 3Psychology Department, Auckland University Medical School, Auckland, New Zealand; 4CAPHRI School for Public Health and Primary Care, Maastricht University, Maastricht, the Netherlands; 5Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim am Rhein, Germany Background: Given the increasing importance of patient-reported outcomes (PRO in quality medical care, we examined the value and feasibility of an innovative method for assessing patients’ illness perceptions, represented in drawings made by patients with COPD of their lungs. Aim: The aim of our study was: to study patients’ representation of COPD as reflected in their drawings of their lungs; and to examine scores on a validated measure that assesses illness perceptions (ie, Brief Illness Perception Questionnaire [B-IPQ]. Patients and methods: One hundred outpatients with COPD, mean age 70 years, selected from a pharmacy database, participated and 98 filled out the B-IPQ. Eighty-seven patients completed the drawing task. Results: The illness perceptions as reflected in the responses to the B-IPQ scales represented a quite optimistic view of COPD and its consequences. The drawings of the lungs reflected a considerable discordance between patients’ representations and medically accepted representations of lungs of a person with COPD. Conclusion: Assessing illness perceptions in clinical care and research about COPD offers opportunities to identify goals for patient education and self-management. Inviting patients to draw their illness is an innovative and promising approach to assessing PRO. Keywords: COPD, drawings, illness perceptions, PRO, quality of life, self-management

A Comparative Pharmacokinetics Study of the Anti-Parkinsonian Drug Pramipexole

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Ratih S. I. Putri

2016-11-01

Full Text Available The present study aimed to compare pharmacokinetic parameters of two pramipexole 0.25 mg formulations in order to show bioequivalence. The study was conducted in a randomized, open-label, two-period, two-sequence, and crossover design, involving 23 healthy volunteers. One of the 0.25 mg formulations of pramipexole evaluated in the study was manufactured by PT Dexa Medica, Palembang, Indonesia, the other, used as the reference, by Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim am Rhein, Germany. All eligible subjects were required to fast before each drug administration period, which was separated by a one-week washout period. Pramipexole concentrations in plasma were assayed using a validated ultra performance liquid chromatography with mass spectrometry (UPLC-MS/MS detector. The evaluated pharmacokinetic parameters included the area under the plasma concentration curve from time zero to the last observed measurable concentration (AUC0-t, the area under the plasma concentration curve extrapolated to infinite time (AUC0-∞, the maximum plasma concentration (Cmax, the time to reach Cmax (tmax, and the plasma concentration half-life (t1/2. To evaluate the bioequivalence of those two pramipexole formulations, 90% confidence intervals (CIs for geometric mean ratios of both formulations were calculated for AUC and Cmax parameters, while tmax and t1/2 differences were analyzed on the non-transformed data using Wilcoxon matched-pairs and a Student’s paired t-test, respectively. The 90% CIs for the geometric mean ratios of the two pramipexole formulations were 95.89% (90.73%–101.34%, 95.53% (89.75%–101.68%, and 92.11% (84.35%–100.58% for AUC0-t, AUC0-∞, and Cmax, respectively. There were no statistically significant differences for tmax and t1/2 between the two pramipexole formulations. It is concluded that two pramipexole formulations in this study were bioequivalent.

A Comparative Pharmacokinetics Study of the Anti-Parkinsonian Drug Pramipexole.

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Putri, Ratih S I; Setiawati, Effi; Aziswan, Syifa A; Ong, Fenny; Tjandrawinata, Raymond R; Susanto, Liana W

2016-11-18

The present study aimed to compare pharmacokinetic parameters of two pramipexole 0.25 mg formulations in order to show bioequivalence. The study was conducted in a randomized, open-label, two-period, two-sequence, and crossover design, involving 23 healthy volunteers. One of the 0.25 mg formulations of pramipexole evaluated in the study was manufactured by PT Dexa Medica, Palembang, Indonesia, the other, used as the reference, by Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim am Rhein, Germany. All eligible subjects were required to fast before each drug administration period, which was separated by a one-week washout period. Pramipexole concentrations in plasma were assayed using a validated ultra performance liquid chromatography with mass spectrometry (UPLC-MS/MS) detector. The evaluated pharmacokinetic parameters included the area under the plasma concentration curve from time zero to the last observed measurable concentration (AUC 0-t ), the area under the plasma concentration curve extrapolated to infinite time (AUC 0-∞ ), the maximum plasma concentration (C max ), the time to reach C max (t max ), and the plasma concentration half-life (t 1/2 ). To evaluate the bioequivalence of those two pramipexole formulations, 90% confidence intervals (CIs) for geometric mean ratios of both formulations were calculated for AUC and C max parameters, while t max and t 1/2 differences were analyzed on the non-transformed data using Wilcoxon matched-pairs and a Student's paired t -test, respectively. The 90% CIs for the geometric mean ratios of the two pramipexole formulations were 95.89% (90.73%-101.34%), 95.53% (89.75%-101.68%), and 92.11% (84.35%-100.58%) for AUC 0-t , AUC 0-∞ , and C max , respectively. There were no statistically significant differences for t max and t 1/2 between the two pramipexole formulations. It is concluded that two pramipexole formulations in this study were bioequivalent.

Epidemiology of chronic obstructive pulmonary disease: a literature review

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Rycroft CE

2012-07-01

Full Text Available Catherine E Rycroft,1 Anne Heyes,1 Lee Lanza,2 Karin Becker31Market Access and Outcomes Strategy, RTI Health Solutions, Manchester, United Kingdom; 2Epidemiology, RTI Health Solutions, Waltham, MA, USA; 3Global Health Economics and Outcomes Research, Boehringer Ingelheim GmbH, Ingelheim, GermanyAbstract: The aim of this study is to quantify the burden of chronic obstructive pulmonary disease (COPD – incidence, prevalence, and mortality – and identify trends in Australia, Canada, France, Germany, Italy, Japan, The Netherlands, Spain, Sweden, the United Kingdom, and the United States of America. A structured literature search was performed (January 2000 to September 2010 of PubMed and EMBASE, identifying English-language articles reporting COPD prevalence, incidence, or mortality. Of 2838 articles identified, 299 full-text articles were reviewed, and data were extracted from 133 publications. Prevalence data were extracted from 80 articles, incidence data from 15 articles, and mortality data from 58 articles. Prevalence ranged from 0.2%–37%, but varied widely across countries and populations, and by COPD diagnosis and classification methods. Prevalence and incidence were greatest in men and those aged 75 years and older. Mortality ranged from 3–111 deaths per 100,000 population. Mortality increased in the last 30–40 years; more recently, mortality decreased in men in several countries, while increasing or stabilizing in women. Although COPD mortality increased over time, rates declined more recently, likely indicating improvements in COPD management. In many countries, COPD mortality has increased in women but decreased in men. This may be explained by differences in smoking patterns and a greater vulnerability in women to the adverse effects of smoking.Keywords: COPD, incidence, literature review, mortality, prevalence

Differences in All-Cause Health Care Utilization and Costs in a Type 2 Diabetes Mellitus Population with and Without a History of Cardiovascular Disease.

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Mehta, Sandhya; Ghosh, Sabyasachi; Sander, Stephen; Kuti, Effie; Mountford, William K

2018-03-01

% longer mean inpatient length of stay (RR = 1.15, 95% CI = 1.06-1.25); and 11% more outpatient visits (RR = 1.11, 95% CI = 1.09-1.13) compared with T2DM adults without a history of CVD. Furthermore, the difference in total PPPM health care cost was found to be 16% ($200) higher in adults with a history of CVD (RR = 1.16, 95% CI = 1.13-1.19). PPPM costs associated with outpatient and ER visits were approximately 21% and 19% higher among adults with a history of CVD, respectively (P costs for inpatient visits were similar between the 2 groups. In addition, a subgroup analysis revealed that adjusted differences in PPPM total cost was larger in the younger age group (56% higher cost in those aged costs remains significantly higher in T2DM patients with a history of CVD compared with patients without a history of CVD even after controlling for significant patient comorbid and demographic characteristics. Also, younger age groups had higher differences in outcomes compared with older age groups. This study underscores the importance of cost-effective interventions that may reduce economic burden in this T2DM population with a history of CVD. This study was funded by Boehringer Ingelheim. At the time of this study, Mehta and Mountford were employed by IQVIA, which received funding from Boehringer Ingelheim to conduct this study. Mountford is employed by Allergan, which has no connection with this study. Ghosh, Sander, and Kuti are employed by Boehringer Ingelheim. Study concept and design were contributed by Mountford, Mehta, and Ghosh, along with Sander and Kuti. Mountford and Mehta collected the data, and data interpretation was performed by all the authors. The manuscript was written by Sander and Kuti, along with the other authors, and revised by Mehta and Gosh, along with the other authors.

Kill rate of mastitis pathogens by a combination of cefalexin and kanamycin.

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Maneke, E; Pridmore, A; Goby, L; Lang, I

2011-01-01

To assess the bacterial killing rate produced by a combination of cefalexin and kanamycin at two different concentration ratios. Time-kill kinetics of cefalexin and kanamycin, individually and in combination, were determined against one strain each of Escherichia coli, Staphylococcus aureus, Streptococcus agalactiae, Streptococcus dysgalactiae and Streptococcus uberis. The combination was tested using two fixed ratios (cefalexin : kanamycin ratios of 1·25 : 1 and 1 : 2·3) and two concentrations of each ratio. Time-kill curves produced with either ratio were quite similar. Against most bacterial species, higher concentrations produced faster kill. In all cases, the combination of cefalexin and kanamycin showed faster and greater kill at lower antibiotic concentrations than those observed with either drug alone. The combination of cefalexin and kanamycin results in a fast initial killing of major mastitis pathogens at both concentration ratios. The combination of cefalexin and kanamycin achieved rapid bacterial kill at concentrations and ratios that can be achieved in vivo following intramammary infusion of a mastitis treatment. © 2010 Boehringer Ingelheim Vetmedica GmbH. Journal of Applied Microbiology © 2010 The Society for Applied Microbiology.

Development and Evaluation of a Rapid Antigen Detection and Serotyping Lateral Flow Antigen Detection System for Foot-and-Mouth Disease Virus.

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Kazuki Morioka

Full Text Available We developed a lateral flow strip using monoclonal antibodies (MAbs which allows for rapid antigen detection and serotyping of foot-and-mouth disease virus (FMDV. This FMDV serotyping strip was able to detect all 7 serotypes and distinguish serotypes O, A, C and Asia1. Its sensitivities ranged from 10(3 to 10(4 of a 50% tissue culture infectious dose of each FMDV stain; this is equal to those of the commercial product Svanodip (Boehringer Ingelheim Svanova, Uppsala, Sweden, which can detect all seven serotypes of FMDV, but does not distinguish them. Our evaluation of the FMDV serotyping strip using a total of 118 clinical samples (vesicular fluids, vesicular epithelial emulsions and oral and/or nasal swabs showed highly sensitive antigen detection and accuracy in serotyping in accordance with ELISA or RT-PCR. To the best of our knowledge, this is the first report on any FMDV serotyping strip that provides both rapid antigen detection and serotyping of FMDV at the same time on one strip without extra devices. This method will be useful in both FMD-free countries and FMD-infected countries, especially where laboratory diagnosis cannot be carried out.

Evaluation of a fixed-dose combination of benazepril and pimobendan in dogs with congestive heart failure: a randomized non-inferiority clinical trial.

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King, Jonathan N; Hirakawa, Atsushi; Sonobe, Junko; Otaki, Hiroshi; Sakakibara, Nobuhiro; Seewald, Wolfgang; Forster, Sophie

2018-01-31

A fixed-dose combination tablet of benazepril and pimobendan (Fortekor Plus; Elanco Animal Health) was tested in dogs with congestive heart failure (CHF) caused by myxomatous mitral valve disease (MMVD) in a three-arm, masked, randomized, non-inferiority clinical trial in Japan. The test group (n = 34) received Fortekor Plus twice daily. Two control groups received registered formulations of benazepril (Fortekor; Elanco Animal Health) and pimobendan (Vetmedin; Boehringer Ingelheim Vetmedica) with administration of Vetmedin twice daily and Fortekor twice (Control I, n = 14) or once (Control II, n = 19) daily. Diuretics were used in 22 dogs (32.8%). Global clinical scores decreased significantly from baseline in all groups; there were no significant differences between groups, and non-inferiority of Fortekor Plus compared to Control I, Control II, and combined Control I + II groups was demonstrated. There were no significant differences between groups for relevant clinical chemistry and hematology variables or frequency of all adverse events. Frequency of emesis was significantly ( p = 0.0042) lower in the Fortekor Plus (8.8%) group than in the Control I + II (39.4%) group. In conclusion, Fortekor Plus had non-inferior efficacy and was associated with significantly less emesis compared to Fortekor and Vetmedin in dogs with CHF caused by MMVD.

Optimization of the Büchi B-90 spray drying process using central composite design for preparation of solid dispersions.

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Gu, Bing; Linehan, Brian; Tseng, Yin-Chao

2015-08-01

A central composite design approach was applied to study the effect of polymer concentration, inlet temperature and air flow rate on the spray drying process of the Büchi B-90 nano spray dryer (B-90). Hypromellose acetate succinate-LF was used for the Design of Experiment (DoE) study. Statistically significant models to predict the yield, spray rate, and drying efficiency were generated from the study. The spray drying conditions were optimized according to the models to maximize the yield and efficiency of the process. The models were further validated using a poorly water-soluble investigational compound (BI064) from Boehringer Ingelheim Pharmaceuticals. The polymer/drug ratio ranged from 1/1 to 3/1w/w. The spray dried formulations were amorphous determined by differential scanning calorimetry and X-ray powder diffraction. The particle size of the spray dried formulations was 2-10 μm under polarized light microscopy. All the formulations were physically stable for at least 3h when suspended in an aqueous vehicle composed of 1% methyl cellulose. This study demonstrates that DoE is a useful tool to optimize the spray drying process, and the B-90 can be used to efficiently produce amorphous solid dispersions with a limited quantity of drug substance available during drug discovery stages. Copyright © 2015 Elsevier B.V. All rights reserved.

Efficacy and safety of eco-friendly inhalers: focus on combination ipratropium bromide and albuterol in chronic obstructive pulmonary disease

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Panos RJ

2013-04-01

Full Text Available Ralph J Panos1,2 1Pulmonary, Critical Care, and Sleep Medicine Division, Cincinnati Veterans Affairs Medical Center, 2Pulmonary, Critical Care, and Sleep Medicine Division, University of Cincinnati College of Medicine, Cincinnati, OH, USA Background: Chronic obstructive pulmonary disease (COPD is a major cause of morbidity and mortality and its treatment is critical to improve quality of life, reduce symptoms, and diminish the frequency of COPD exacerbations. Due to the harmful environmental effects of pressurized metered-dose inhalers (pMDIs containing chlorofluorocarbons (CFCs, newer systems for delivering respiratory medications have been developed. Methods: A search of the literature in the PubMed database was undertaken using the keywords “COPD,” “albuterol,” “ipratropium bromide,” and “Respimat® Soft Mist Inhaler™”; pertinent references within the identified citations were included. The environmental effect of CFC-pMDIs, the invention of the Respimat® Soft Mist Inhaler™ (SMI (Boehringer Ingelheim, Ingelheim, Germany, and its use to deliver the combination of albuterol and ipratropium bromide for the treatment of COPD were reviewed. Results: The adverse environmental effects of CFC-pMDIs stimulated the invention of novel delivery systems including the Respimat SMI. This review presents its development, internal mechanism, and use to deliver the combination of albuterol and ipratropium bromide. Conclusion: CFC-pMDIs contributed to the depletion of the ozone layer and the surge in disorders caused by harmful ultraviolet B radiation. The banning of CFCs spurred the development of novel delivery systems for respiratory medications. The Respimat SMI is an innovative device that produces a vapor of inhalable droplets with reduced velocity and prolonged aerosol duration that enhance deposition within the lower airway and is associated with improved patient satisfaction. Clinical trials have demonstrated that the Respimat SMI

In vitro dose comparison of Respimat® inhaler with dry powder inhalers for COPD maintenance therapy

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Ciciliani A

2017-05-01

Full Text Available Anna-Maria Ciciliani,1,2 Peter Langguth,1 Herbert Wachtel2 1Institute of Pharmacy and Biochemistry, Faculty 09 (Chemistry, Pharmaceutics and Geosciences, Johannes Gutenberg University, Mainz, 2Analytical Development Department, Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany Background: Combining in vitro mouth–throat deposition measurements, cascade impactor data and computational fluid dynamics (CFD simulations, four different inhalers were compared which are indicated for chronic obstructive pulmonary disease (COPD treatment.Methods: The Respimat inhaler, the Breezhaler, the Genuair, and the Ellipta were coupled to the idealized Alberta throat model. The modeled dose to the lung (mDTL was collected downstream of the Alberta throat model using either a filter or a next generation impactor (NGI. Idealized breathing patterns from COPD patient groups – moderate and very severe COPD – were applied. Theoretical lung deposition patterns were assessed by an individual path model.Results and conclusion: For the Respimat the mDTL was found to be 59% (SD 5% for the moderate COPD breathing pattern and 67% (SD 5% for very severe COPD breathing pattern. The percentages refer to nominal dose (ND in vitro. This is in the range of 44%–63% in vivo in COPD patients who display large individual variability. Breezhaler showed a mDTL of 43% (SD 2% for moderate disease simulation and 51% (SD 2% for very severe simulation. The corresponding results for Genuair are mDTL of 32% (SD 2% for moderate and 42% (SD 1% for very severe disease. Ellipta vilanterol particles showed a mDTL of 49% (SD 3% for moderate and 55% (SD 2% for very severe disease simulation, and Ellipta fluticasone particles showed a mDTL of 33% (SD 3% and 41% (SD 2%, respectively for the two breathing patterns. Based on the throat output and average flows of the different inhalers, CFD simulations were performed. Laminar and turbulent steady flow calculations indicated that

The inherent dangers of using computable general equilibrium models as a single integrated modelling framework for sustainability impact assessment. A critical note on Boehringer and Loeschel (2006)

International Nuclear Information System (INIS)

Scrieciu, S. Serban

2007-01-01

The search for methods of assessment that best evaluate and integrate the trade-offs and interactions between the economic, environmental and social components of development has been receiving a new impetus due to the requirement that sustainability concerns be incorporated into the policy formulation process. A paper forthcoming in Ecological Economics (Boehringer, C., Loeschel, A., in press. Computable general equilibrium models for sustainability impact assessment: status quo and prospects, Ecological Economics.) claims that Computable General Equilibrium (CGE) models may potentially represent the much needed 'back-bone' tool to carry out reliable integrated quantitative Sustainability Impact Assessments (SIAs). While acknowledging the usefulness of CGE models for some dimensions of SIA, this commentary questions the legitimacy of employing this particular economic modelling tool as a single integrating modelling framework for a comprehensive evaluation of the multi-dimensional, dynamic and complex interactions between policy and sustainability. It discusses several inherent dangers associated with the advocated prospects for the CGE modelling approach to contribute to comprehensive and reliable sustainability impact assessments. The paper warns that this reductionist viewpoint may seriously infringe upon the basic values underpinning the SIA process, namely a transparent, heterogeneous, balanced, inter-disciplinary, consultative and participatory take to policy evaluation and building of the evidence-base. (author)

SOSPES: SPIRIVA® observational study measuring SGRQ score in routine medical practice in Central and Eastern Europe

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Fležar M

2013-10-01

Full Text Available Matjaž Fležar,1 Karina Jahnz-Rózyk,2 Gloria Enache,3 Tatiana Martynenko,4 Peter Kristufek,5 Sanda Škrinjaric-Cincar,6 Pavla Kadlecová,7 Goran Martinovic81University Clinic of Respiratory and Allergic Diseases Golnik, Golnik, Slovenia; 2Military Institute of Medicine, Department of Immunology and Allergology, Warsaw, Poland; 3Saint John Clinical Emergency Hospital, Bucharest, Romania; 4Municipal Medical Institution City Hospital, Barnaul, Russian Federation; 5SACCME, Slovak Medical University, Bratislava, Slovakia; 6Clinical Hospital Center, Osijek, Croatia; 7ADDS Sro, Jana Uhra, Brno, Czech Republic; 8Boehringer Ingelheim RCV GmbH and Co KG, Ingelheim, Vienna, AustriaPurpose: The long-acting inhaled anticholinergic agent, tiotropium, is recommended as first-line maintenance therapy for moderate to very severe Chronic Obstructive Pulmonary Disease (COPD to improve symptoms, exercise tolerance, health status, and to reduce exacerbations. Few studies have evaluated the therapeutic efficacy of tiotropium in patients in routine clinical conditions. The current study was designed to investigate the therapeutic efficacy of tiotropium delivered via the HandiHaler® device on the health status of patients with COPD with Global initiative for chronic Obstructive Lung Disease (GOLD disease classification 2–4 in six central and eastern European countries in a real-life clinical setting.Methods: The study was an open-label, prospective, uncontrolled, and single-arm surveillance study with three clinic visits during a 6-month observation period (baseline, and months 3 and 6. Health status was measured using the disease-specific St George's Respiratory Questionnaire (SGRQ. The primary efficacy endpoint was the mean change from baseline in SGRQ total score at the end of the 6-month observational period.Results: Patients treated with tiotropium 18 µg once daily showed statistically significant and clinically meaningful reduction (improvement of 21

Guideline-based survey of outpatient COPD management by pulmonary specialists in Germany

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Buhl R

2012-02-01

Full Text Available Thomas Glaab1,2, Claus Vogelmeier3, Andreas Hellmann4, Roland Buhl11Department of Respiratory Diseases III, Medical Center of the Johannes Gutenberg-University, Mainz, 2Medical Affairs Germany, Respiratory Medicine, Boehringer Ingelheim Pharma GmbH and Co, KG, Ingelheim, 3Department of Respiratory Diseases, University Hospitals of Giessen and Marburg, Marburg, 4Federal Association of Pneumologists, Augsburg, GermanyBackground: Little is known about the role of guidelines for the practical management of chronic obstructive pulmonary disease (COPD by office-based pulmonary specialists. The aim of this study was to assess their outpatient management in relation to current guideline recommendations for COPD.Methods: A nationwide prospective cross-sectional COPD questionnaire survey in the form of a multiple-choice questionnaire was sent to 1000 office-based respiratory specialists in Germany. The product-neutral questions focused on routine COPD management and were based on current national and international COPD guideline recommendations being consistent in severity classification and treatment recommendations.Results: A total of 590 pulmonary specialists (59% participated in the survey. Body plethysmography was considered the standard for diagnosis (65.9%, followed by spirometry (32%. Most respondents were able to cite the correct spirometric criteria for classifying moderate (87% to very severe COPD (77%. A quarter of the respondents equated the World Health Organization (WHO definition of chronic bronchitis with COPD. Notably, most participants preferred the updated national COPD guidelines (51.4% to the Global Initiative for Chronic Obstructive Lung Disease (GOLD guidelines (40.2%. Improvement of functional exercise capacity and quality of life were considered the two most relevant treatment goals; whereas impact on mortality was secondary. Treatment of COPD largely complied with the guidelines. However, a significant percentage of the

A global RNA-seq-driven analysis of CHO host and production cell lines reveals distinct differential expression patterns of genes contributing to recombinant antibody glycosylation.

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Könitzer, Jennifer D; Müller, Markus M; Leparc, Germán; Pauers, Martin; Bechmann, Jan; Schulz, Patrick; Schaub, Jochen; Enenkel, Barbara; Hildebrandt, Tobias; Hampel, Martin; Tolstrup, Anne B

2015-09-01

Boehringer Ingelheim uses two CHO-DG44 lines for manufacturing biotherapeutics, BI-HEX-1 and BI-HEX-2, which produce distinct cell type-specific antibody glycosylation patterns. A recently established CHO-K1 descended host, BI-HEX-K1, generates antibodies with glycosylation profiles differing from CHO-DG44. Manufacturing process development is significantly influenced by these unique profiles. To investigate the underlying glycosylation related gene expression, we leveraged our CHO host and production cell RNA-seqtranscriptomics and product quality database together with the CHO-K1 genome. We observed that each BI-HEX host and antibody producing cell line has a unique gene expression fingerprint. CHO-DG44 cells only transcribe Fut10, Gfpt2 and ST8Sia6 when expressing antibodies. BI-HEX-K1 cells express ST8Sia6 at host cell level. We detected a link between BI-HEX-1/BI-HEX-2 antibody galactosylation and mannosylation and the gene expression of the B4galt gene family and genes controlling mannose processing. Furthermore, we found major differences between the CHO-DG44 and CHO-K1 lineages in the expression of sialyl transferases and enzymes synthesizing sialic acid precursors, providing a rationale for the lack of immunogenic NeuGc/NGNA synthesis in CHO. Our study highlights the value of systems biotechnology to understand glycoprotein synthesis and product glycoprofiles. Such data improve future production clone selection and process development strategies for better steering of biotherapeutic product quality. Copyright © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Colon cleansing protocol in children: research conditions vs. clinical practice.

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Elitsur, Yoram; Balfaqih, Yaslam; Preston, Deborah

2018-04-01

 Colon preparation rates are the limiting factor for a successful diagnostic colonoscopy in children. Different colon cleansing protocols have been published for use in children. Unfortunately, the applicability of those published research protocols has not been formally evaluated in routine clinical practice. We investigated the success rate of our previously published colon cleansing protocol as utilized in our clinical practice.  This was a retrospective study. In the clinical practice, the colon cleansing protocol included PEG-3350 at a dose of 2 g/kg/day plus Dulcolax (Bisacodyl, Boehringer Ingelheim, TX USA) 5 mg/day for 2 days. Adequate colon preparation was graded between 1 - 5, as previously described, and grade ≥ 4.0 was considered an adequate preparation. Patients were instructed to complete a questionnaire that included PEG-3350 dose, number of stools per day, consistency of each stool, and side effects (vomiting, abdominal pain). Clinical and endoscopic results were compared between the protocol under research conditions and routine practice.  The success rate of the colon preparation in our clinical practice was similar to the results observed under our research protocol (75 % vs. 73.6 %). Moreover, the total number of stools, stool consistency, and the intubation rate of the terminal ileum were also similar. We concluded, that in our experience, the colon cleansing protocol used under research conditions was effective and appropriate for use in routine clinical practice.  We recommend testing each new protocol under the routine conditions of clinical practice to confirm its applicability for general practitioners.

Efficacy and tolerability of a single-pill combination of telmisartan 80 mg and hydrochlorothiazide 25 mg according to age, gender, race, hypertension severity, and previous antihypertensive use: planned analyses of a randomized trial

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Zhu D

2013-04-01

Full Text Available Dingliang Zhu,1 Harold Bays,2 Pingjin Gao,1 Michaela Mattheus,3 Birgit Voelker,3 Luis M Ruilope4 1Shanghai Ruijin Hospital, Shanghai, People’s Republic of China; 2Louisville Metabolic and Atherosclerosis Research Center Inc, Louisville, KY, USA; 3Boehringer Ingelheim International GmbH, Ingelheim, Germany; 4Hospital 12 de Octubre, Madrid, Spain Background: The purpose of this work was to describe the efficacy and safety of a telmisartan 80 mg + hydrochlorothiazide 25 mg (T80/H25 single-pill combination therapy in patients with moderate-severe hypertension (mean seated trough cuff systolic blood pressure [BP] ≥ 160 mmHg and diastolic BP ≥ 100 mmHg in specific patient subpopulations. Methods: This was a planned analysis of a double-blind, multicenter, parallel-group trial that demonstrated the superiority of a single-pill combination of T80/H25 versus T80 monotherapy in terms of systolic BP change from baseline to week 7. Subpopulations included older (aged ≥ 65 years versus younger, gender, race, hypertension severity, and prior antihypertensive therapy. Endpoints were change from baseline in mean seated trough cuff systolic and diastolic BP, proportion of patients achieving their BP goal (systolic/diastolic BP 30 mmHg and >40 mmHg. Results: Across all subgroups, the T80/H25 single-pill combination provided consistently greater systolic and diastolic BP reductions than T80 and more patients had systolic BP reductions of >30 mmHg. In the T80 and T80/H25 groups, BP control was achieved in 34.1% and 48.8% of men, 35.5% and 62.7% of women, 34.5% and 56.6% of Asians, 22.6% and 38.6% of blacks, 36.7% and 57.8% of whites, 36.9% and 57.5% of patients < 65 years, 29.3% and 49.3% ≥65 years, 44.2% and 66.2% of those with grade 2 hypertension, 20.4% and 39.4% of those with grade 3 hypertension, 38.9% and 53.2% of previously untreated patients, 38.1% and 62.5% of patients previously treated with one antihypertensive, and 29.7% and 48.9% of patients

Tiotropium HandiHaler® and Respimat® in COPD: a pooled safety analysis

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Halpin DMG

2015-02-01

Full Text Available David MG Halpin,1 Ronald Dahl,2 Christoph Hallmann,3 Achim Mueller,3 Donald Tashkin4 1NHS SW, Royal Devon and Exeter Hospital, Exeter, Devon, England, UK; 2Allergy Centre, Odense University Hospital, Odense, Denmark; 3Boehringer Ingelheim Pharma GmbH & Co KG, Ingelheim am Rhein, Germany; 4Department of Medicine, David Geffen School of Medicine UCLA, Los Angeles, CA, USAIntroduction: Tiotropium is prescribed for the treatment of chronic obstructive pulmonary disease (COPD and delivered via HandiHaler® (18 µg once daily or Respimat® Soft Mist™ inhaler (5 µg once daily. The recent TIOtropium Safety and Performance In Respimat® (TIOSPIR™ study demonstrated that both exhibit similar safety profiles. This analysis provides an updated comprehensive safety evaluation of tiotropium® using data from placebo-controlled HandiHaler® and Respimat® trials.Methods: Pooled analysis of adverse event (AE data from tiotropium HandiHaler® 18 µg and Respimat® 5 µg randomized, double-blind, parallel-group, placebo-controlled, clinical trials in patients with COPD (treatment duration ≥4 weeks. Incidence rates, rate ratios (RRs, and 95% confidence intervals (CIs were determined for HandiHaler® and Respimat® trials, both together and separately.Results: In the 28 HandiHaler® and 7 Respimat® trials included in this analysis, 11,626 patients were treated with placebo and 12,929 with tiotropium, totaling 14,909 (12,469 with HandiHaler®; 2,440 with Respimat® patient-years of tiotropium exposure. Mean age was 65 years, and mean prebronchodilator forced expiratory volume in 1 second (FEV1 was 1.16 L (41% predicted. The risk (RR [95% CI] of AEs (0.90 [0.87, 0.93] and of serious AEs (SAEs (0.94 [0.89, 0.99] was significantly lower in the tiotropium than in the placebo group (HandiHaler® and Respimat® pooled results, and there was a numerically lower risk of fatal AEs (FAEs (0.90 [0.79, 1.01]. The risk of cardiac AEs (0.93 [0.85, 1.02] was numerically

Fisiopatologia da Dispneia em doentes cardíacos com Congestão Pulmonar** Trabalbo vencedor ex-aqueo do Prémio Thomé Villar/Boehringer Ingelheim, 1995

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Miguel Mota Carmo

1997-03-01

Full Text Available SUMÁRIO: O objectivo deste estudo foi avaliar a importância da comparticipação das alterações do controlo da ventilaçõe da força dos músculos respiratórios na génese da dispneia em doentes cardíacos com estase pulmonar. Para isso comparámos 48 doentes (GI, com uma idade média de 61 anos e uma pressão capilar pulmonar (PCP de 19,9 mmHg, com um grupo de 35 controlos (GII, com uma idade média de 62 anos. Foram efectuadas as seguintes avaliações: volumes e capacidades pulmonares pelo método de diluição do hétio e por pneumotacografia, pressão de oclusão e resposta ventilatória em hipercánia, bem como a quantificação simultânea da dispneia utilizando uma escala visual analógica. Foram também medidas as pressões máximas dos músculos respiratórios, ao nível da boca, em repouso. Os doentes cardíacos foram submetidos a cateterismo cardíaco direito com determinação do débito cardíaco por termodilui determinação. Nestes doentes encontrou-se um aumento da pressão de oclusão basal em comparação com o grupo controlo (P0,1 GI-1,7 cmH20 / GII -1,35 cmH20; p<0,001, provavelmente devido ao padrão espirométrico restritivo que apresentavam. Não se detectaram alterações na variação da P0,1 durante a prova de hiperclápnia pelo que admitimos que o controlo central da ventilação se encontrava integro. Durante esta prova e para um mesmo aumento da ventilação, os doentes cardiacos apresentaram um maior grau de dispneia. A redução das pressões máximas respiratórias, bem como o aumento da “drive” respiratória em repouso, poderão estar implicadas na génese da dispneia oeste grupo de doentes. ABSTRACT: The purpose of this study was to evaluate whether pulmonary congestion (PC in cardiac patients may induce changes in the control of breathing or in the respiratory muscles strength, that could be implicated in the genesis of dyspnea in this group of patients. We have compared 48 patients (GI, with a mean age of 61 years and a mean pulmonary capillary (wedge pressure of 19.9 mmHg, with a group of 35 controls (GII with a mean age of 62 years. We have performed the following measurements: pulmonary volumes and capacities using the helium dilution method, airway flows by pneumotachography. We also determined the occlusion pressure and the ventilatory response to C02, with simultaneous quantification of dyspnea using a visual analogue scale. Measurements of maximal inspiratory and expiratory pressures were also performed. PC patients underwent right heart catheterization and assessment of cardiac output by thermodilution technic. Cardiac patients had an increase in the central output to breathing (P0.1 GI-1.7 cmH20/GII - l.35 cmH20; < 0.001, probably due to the respiratory restrictive pattern. Because we found no changes in the P0.1, during C02 stimulation, we admit that the central command is not altered. During the C02 stimulation, and for a similar increase in ventilation, the cardiac patients showed a higher degree of dyspnea. The reduction of maximal respiratory pressures and the increased basal respiratory drive can be important factors in the generation of dyspnea presented by these patients. Palavras-chave: dispneia, congestão pulmonar, insuficiência ventricular esquerda, : Key- words, dyspnea, pulmonary congestion, left ventricular failure

Lack of paradoxical bronchoconstriction after administration of tiotropium via Respimat® Soft Mist™ Inhaler in COPD

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Hodder R

2011-04-01

Full Text Available Rick Hodder1, Demetri Pavia2, Angela Lee2, Eric Bateman31Divisions of Pulmonary and Critical Care, University of Ottawa, Ottawa, ON, Canada; 2Boehringer Ingelheim Limited, Bracknell, England, UK; 3Division of Pulmonology, Department of Medicine, University of Cape Town, Cape Town, South AfricaAbstract: Bronchoconstriction has been reported in asthma and chronic obstructive pulmonary disease (COPD patients after administration of some aqueous inhalation solutions. We investigated the incidence of this event during long-term clinical trials of tiotropium delivered via Respimat® Soft Mist™ Inhaler (SMI. We retrospectively analyzed pooled data from two identical Phase III clinical trials, in which 1990 patients with COPD received 48 weeks' treatment with once-daily tiotropium (5 or 10 µg or placebo inhaled via Respimat® SMI. We recorded the incidence of bronchospasm and of a range of respiratory events that could suggest bronchoconstriction during the first 30 minutes after inhalation of study treatment on each of the eight test days. No patients reported bronchospasm. Six patients (0.3% reported a combination of at least two events suggestive of bronchoconstriction, and 21 (1.1% reported either rescue medication use or a respiratory adverse event. Asymptomatic falls in forced expiratory volume in one second (FEV1 of ≥15% were recorded on all test days, with no change in incidence over time, and affected 8.2% of those in the tiotropium groups and 14.5% of those on placebo. In COPD patients receiving long-term treatment with tiotropium 5 or 10 µg via Respimat® SMI, no bronchospasm was recorded, and the number of events possibly indicative of paradoxical bronchoconstriction was very low.Keywords: inhalation device, bronchoconstriction, COPD, tiotropium

Following the results of the EMPA-REG OUTCOME trial with empagliflozin, is it possible to speak of a class effect?

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Ampudia-Blasco FJ

2017-01-01

Full Text Available Francisco Javier Ampudia‑Blasco,1 Irene Romera,2 Bernat Ariño,3 Ramón Gomis4 1Endocrinology and Nutrition Department, Clinic University Hospital Valencia, Valencia, Spain; 2Eli Lilly and Company España, Madrid, Spain; 3Boehringer Ingelheim España, Barcelona, Spain; 4Endocrinology Department, Hospital Clinic Barcelona, Barcelona, Spain Background: The recently published cardiovascular outcomes data for the first sodium–glucose cotransporter 2 (SGLT2 inhibitor, empagliflozin, have shown cardiovascular safety and additional benefits in patients with type 2 diabetes and established cardiovascular disease. Empagliflozin showed lower rates of death from cardiovascular causes or from any causes and lower hospitalization rates from heart failure compared with placebo, both in addition to standard care. This commentary discusses the existence of a possible class effect considering the available evidence described for other SGLT2 inhibitors. Main text: Empagliflozin, dapagliflozin and canagliflozin share the same mechanism of action, and it is a plausible hypothesis that some of the benefits of empagliflozin treatment could also be expected from other SGLT2 inhibitors. However, the rapid and persistent occurrence of cardiovascular benefits observed with empagliflozin and the different results shown by the three inhibitors in meta-analyses of some of their respective Phase II and III trials might suggest another possible mechanism of action, perhaps related to the different selectivity to inhibit SGLT-2 and other SGLT family members that these compounds present. Conclusion: There is still lack of evidence to answer whether the cardiovascular benefits observed with empagliflozin in the EMPA-REG OUTCOME study could be seen as a “class effect”, which is also attributable to dapagliflozin and canagliflozin. Keywords: cardiovascular, outcome studies, SGLT2 inhibitors, empagliflozin, dapagliflozin, canagliflozin

Time to Angiographic Reperfusion and Clinical Outcome after Acute Ischemic Stroke in the Interventional Management of Stroke Phase III (IMS III) Trial: A Validation Study

Science.gov (United States)

Khatri, Pooja; Yeatts, Sharon D.; Mazighi, Mikael; Broderick, Joseph P.; Liebeskind, David S.; Demchuk, Andrew M.; Amarenco, Pierre; Carrozzella, Janice; Spilker, Judith; Foster, Lydia D.; Goyal, Mayank; Hill, Michael D.; Palesch, Yuko Y.; Jauch, Edward C.; Haley, E. Clarke; Vagal, Achala; Tomsick, Thomas A.

2014-01-01

BACKGROUND The IMS III Trial did not demonstrate clinical benefit of the endovascular approach compared to IV rt-PA alone for moderate or severe ischemic strokes (NIHSS≥8) enrolled within three hours of stroke onset. Late reperfusion of tissue that is no longer salvageable may be one explanation, as suggested by prior exploratory studies showing an association between time to reperfusion and good clinical outcome. We sought to validate this relationship in the large-scale IMS III trial, and consider its implications for future endovascular trials. METHODS The analysis consisted of the endovascular cohort with proximal arterial occlusions in the anterior circulation that achieved angiographic reperfusion (TICI 2–3) during the endovascular procedure (within 7 hours from the onset of symptoms). Logistic regression was used to model good clinical outcome (90-day modified Rankin 0–2) as a function of the time to reperfusion, and prespecified variables were considered for adjustment. FINDINGS Among 240 proximal vessel occlusions, angiographic reperfusion (TICI 2–3) was achieved in 182 (76%). Mean time to reperfusion was 325 minutes (range 180–418 minutes). Longer time for reperfusion was associated with a decreased likelihood of good clinical outcome (RR [95% CI] for every 30 minute delay: unadjusted 0·85 [0·77–0·94]; adjusted 0·88 [0·80–0·98]). INTERPRETATION We confirm that delay in time to angiographic reperfusion leads to a decreased likelihood of good clinical outcome. Achieving rapid reperfusion may be critical for the successes of future acute endovascular trials. FUNDING: NIH/NINDS (study sponsor), Genentech Inc. (study drug - intra-arterial t-PA), EKOS Corp. (device), Concentric Inc. (device), Cordis Neurovascular, Inc. (device), and Boehringer Ingelheim (European Investigator Meeting support). PMID:24784550

Tiotropium and Salmeterol in COPD Patients at Risk of Exacerbations: A Post Hoc Analysis from POET-COPD(®).

Science.gov (United States)

Vogelmeier, Claus F; Asijee, Guus M; Kupas, Katrin; Beeh, Kai M

2015-06-01

Among patients with chronic obstructive pulmonary disease (COPD), the frequency and severity of past exacerbations potentiates future events. The impact of current therapies on exacerbation frequency and severity in patients with different exacerbation risks is not well known. A post hoc analysis of patients at low (≤1 exacerbation [oral steroids/antibiotics requirement] and no COPD-related hospitalization in the year preceding trial entry) or high (≥2 exacerbations [oral steroids/antibiotics requirement] or ≥1 COPD-related hospitalization[s] in the year preceding trial entry) exacerbation risk, from the Prevention of Exacerbations with Tiotropium in Chronic Obstructive Pulmonary Disease (POET-COPD(®)) database. Compared with salmeterol, tiotropium significantly increased time to first COPD exacerbation (hazard ratio 0.84; 95% confidence interval [CI] 0.76-0.92; p = 0.0002) and reduced the number of COPD exacerbations (rate ratio 0.90; 95% CI 0.81-0.99; p = 0.0383) in patients at high exacerbation risk. With treatment, the risk of remaining in the high-risk exacerbator subgroup was statistically lower with tiotropium versus salmeterol (risk ratio [RR] 0.89; 95% CI 0.80-1.00; p = 0.0478). For low-risk patients, time to first COPD exacerbation and number of COPD exacerbations were numerically lower with tiotropium versus salmeterol. With treatment, the risk of transitioning from a low to a high exacerbation risk was lower with tiotropium versus salmeterol (RR 0.87; 95% CI 0.71-1.07; p = 0.1968). This analysis confirms the higher efficacy of tiotropium versus salmeterol in prolonging time to first COPD exacerbation and reducing number of exacerbations in patients both at low and high exacerbation risk. Boehringer Ingelheim and Pfizer. ClinicalTrials.gov NCT00563381.

Combination of the sodium-glucose cotransporter-2 inhibitor empagliflozin with orlistat or sibutramine further improves the body-weight reduction and glucose homeostasis of obese rats fed a cafeteria diet

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Vickers SP

2014-07-01

Full Text Available Steven P Vickers,1 Sharon C Cheetham,1 Katie R Headland,1 Keith Dickinson,1 Rolf Grempler,2 Eric Mayoux,2 Michael Mark,2 Thomas Klein2 1RenaSci, BioCity Nottingham, Nottingham, UK; 2Boehringer Ingelheim Pharma, Biberach an der Riss, Germany Abstract: The present study assessed the potential of the sodium glucose-linked transporter (SGLT-2 inhibitor empagliflozin to decrease body weight when administered alone or in combination with the clinically effective weight-loss agents orlistat and sibutramine in obese rats fed a cafeteria diet. Female Wistar rats were exposed to a cafeteria diet to induce obesity. Empagliflozin was dosed once daily (10, 30, and 60 mg/kg for 28 days. Combination studies were subsequently performed using a submaximal empagliflozin dose (10 mg/kg with either sibutramine or orlistat. Body weight, food, and water intake were recorded daily. The effect of drug treatment on glucose tolerance, relevant plasma parameters, and carcass composition was determined. Empagliflozin dose-dependently reduced body weight, plasma leptin, and body fat though increased urinary glucose excretion. The combination of empagliflozin and orlistat significantly reduced body weight compared to animals treated with either drug alone, and significantly improved glucose tolerance, plasma insulin, and leptin compared to vehicle-treated controls. The effect of sibutramine to improve glycemic control in an oral glucose-tolerance test was also significantly increased, with empagliflozin and combination treatment leading to a reduction in carcass fat greater than that observed with either drug alone. These data demonstrate that empagliflozin reduces body weight in cafeteria-fed obese rats. In combination studies, empagliflozin further improved the body-weight or body-fat loss of animals in comparison to orlistat or sibutramine alone. Such studies may indicate improved strategies for the treatment of obese patients with prediabetes or type 2 diabetes. Keywords

Assessment of the insecticidal activity of afoxolaner against Aedes aegypti in dogs treated with NexGard®

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Liebenberg Julian

2017-01-01

Full Text Available Twelve healthy dogs were studied in this parallel group, blinded, randomised, and negative controlled efficacy study. On Day -1, the 12 dogs included were ranked within sex in descending order of individual pre-treatment (Day -5 fed mosquito counts and randomly allocated by blocks of two dogs to the untreated control group or the afoxolaner-treated group. NexGard® (Merial, now part of Boehringer Ingelheim Animal Health was administered orally on Day 0 in accordance with the European label instructions. On Days 1, 7, 14, 21 and 28, all dogs were exposed for a duration of 1 hour to 50 ± 5 unfed Aedes aegypti females. After each exposure, mosquitoes were collected after 1 hour and assessed for viability during collection and at 24 ± 2 hours. The arithmetic (and geometric mean values of live fed mosquito counts at 24 hours after the exposure periods for the negative control group ranged from 33.7 (32.3 to 49.8 (49.7, indicating that this was a vigorous mosquito strain. There was no significant difference between control and treated groups in the number of live and fed mosquitoes at each 1 hour post-exposure collection time. Based on arithmetic and geometric mean values at 24 hours after each exposure, significantly fewer live fed mosquitoes were recorded in the treated group, compared to the negative control group, throughout the study (p < 0.001. The afoxolaner insecticidal efficacy against A. aegypti varied from 98% (Day 2 to 75.3% (Day 29 based on arithmetic means, and 98.7% (Day 2 to 89.8% (Day 29 based on geometric means.

HIV Salvage Therapy Does Not Require Nucleoside Reverse Transcriptase Inhibitors: A Randomized, Controlled Trial.

Science.gov (United States)

Tashima, Karen T; Smeaton, Laura M; Fichtenbaum, Carl J; Andrade, Adriana; Eron, Joseph J; Gandhi, Rajesh T; Johnson, Victoria A; Klingman, Karin L; Ritz, Justin; Hodder, Sally; Santana, Jorge L; Wilkin, Timothy; Haubrich, Richard H

2015-12-15

Nucleoside reverse transcriptase inhibitors (NRTIs) are often included in antiretroviral regimens in treatment-experienced patients in the absence of data from randomized trials. To compare treatment success between participants who omit versus those who add NRTIs to an optimized antiretroviral regimen of 3 or more agents. Multicenter, randomized, controlled trial. (ClinicalTrials.gov: NCT00537394). Outpatient HIV clinics. Treatment-experienced patients with HIV infection and viral resistance. Open-label optimized regimens (not including NRTIs) were selected on the basis of treatment history and susceptibility testing. Participants were randomly assigned to omit or add NRTIs. The primary efficacy outcome was regimen failure through 48 weeks using a noninferiority margin of 15%. The primary safety outcome was time to initial episode of a severe sign, symptom, or laboratory abnormality before discontinuation of NRTI assignment. 360 participants were randomly assigned, and 93% completed a 48-week visit. The cumulative probability of regimen failure was 29.8% in the omit-NRTIs group versus 25.9% in the add-NRTIs group (difference, 3.2 percentage points [95% CI, -6.1 to 12.5 percentage points]). No significant between-group differences were found in the primary safety end points or the proportion of participants with HIV RNA level less than 50 copies/mL. No deaths occurred in the omit-NRTIs group compared with 7 deaths in the add-NRTIs group. Unblinded study design, and the study may not be applicable to resource-poor settings. Treatment-experienced patients with HIV infection starting a new optimized regimen can safely omit NRTIs without compromising virologic efficacy. Omitting NRTIs will reduce pill burden, cost, and toxicity in this patient population. National Institute of Allergy and Infectious Diseases, Boehringer Ingelheim, Janssen, Merck, ViiV Healthcare, Roche, and Monogram Biosciences (LabCorp).

A simple semipaced 3-minute chair rise test for routine exercise tolerance testing in COPD

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Aguilaniu B

2014-09-01

Full Text Available Bernard Aguilaniu,1,2 Hubert Roth,3 Jesus Gonzalez-Bermejo,4 Marie Jondot,5 Jocelyne Maitre,5 François Denis,6 Thomas Similowski4,7 1Medicine Faculty, Université Joseph Fourier, Grenoble, France; 2McGill University, Montreal, Canada; 3Centre de Recherche en Nutrition Humaine Rhône-Alpes, CHU Grenoble, France; 4Assistance Publique-Hôpitaux de Paris, Groupe Hospitalier Pitié-Salpêtrière, Respiratory and Intensive Care Medicine, Paris, France; 5Clinique Universitaire de Pneumologie, CHU Grenoble, France, Grenoble, France; 6Boehringer Ingelheim, 7Université Paris, Paris, France Abstract: The functional work capacity of chronic obstructive pulmonary disease (COPD patients is usually assessed with walk tests such as the 6-minute walk test (6MWT or the shuttle test. Because these exercise modalities require a controlled environment which limits their use by pulmonologists and severely restricts their use among general practitioners, different modalities of a short (1 minute or less sit-to-stand test were recently proposed. In this study, we evaluated a new modality of a semipaced 3-minute chair rise test (3CRT in 40 patients with COPD, and compared the reproducibility of physiological responses and symptoms during the 3CRT and their interchangeability with the 6MWT. The results demonstrate that physiological variables, heart rate, pulse oxygen saturation, work done, and symptoms (Borg dyspnea and fatigue scores, during the 3CRT were highly reproducible, and that the physiological responses and symptoms obtained during the 3CRT and the 6MWT were interchangeable for most patients. Moreover, these preliminary data suggest that patients able to perform more than 50 rises during 3 minutes had no significant disability. The simplicity and ease of execution of the 3CRT will facilitate the assessment of exercise symptoms and disability in COPD patients during routine consultations with pulmonologists and general practitioners, and will thus contribute

Design, rationale, and baseline demographics of SEARCH I: a prospective cluster-randomized study

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Albers F

2012-07-01

Full Text Available Frank Albers,1 Asif Shaikh,2 Ahmar Iqbal,31Medical Affairs Respiratory, 2Clinical Development and Medical Affairs, Field Based Medicine-Respiratory, Boehringer Ingelheim Pharmaceuticals, Inc, Ridgefield, CT, USA; 3Respiratory Medical Affairs, Pfizer Inc, New York, NY, USAAbstract: Questionnaires are available to identify patients at risk for several chronic diseases, including COPD, but are infrequently utilized in primary care. COPD is often underdiagnosed, while at the same time the US Preventive Services Task Force recommends against spirometric screening for COPD in asymptomatic adults. Use of a symptom-based questionnaire and subsequent handheld spirometric device depending on the answers to the questionnaire is a promising approach to identify patients at risk for COPD. Screening, Evaluating and Assessing Rate CHanges of diagnosing respiratory conditions in primary care 1 (SEARCH I was a prospective cluster-randomized study in 168 US primary care practices evaluating the effect of the COPD-Population Screener (COPD-PS™ questionnaire. The effect of this questionnaire alone or sequentially with the handheld copd-6TM device was evaluated on new diagnoses of COPD and on respiratory diagnostic practice patterns (including referrals for pulmonary function testing, referrals to pulmonologists, new diagnoses of COPD, and new respiratory medication prescriptions. Participating practices entered a total of 9704 consecutive consenting subjects aged ≥ 40 years attending primary care clinics. Study arm results were compared for new COPD diagnosis rates between usual care and (1 COPD-PS plus copd-6 and (2 COPD-PS alone. A cluster-randomization design allowed comparison of the intervention effects at the practice level instead of individuals being the subjects of the intervention. Regional principal investigators controlled the flow of study information to sub-investigators at participating practices to reduce observation bias (Hawthorne effect. The

New approaches to the modulation of inflammatory processes in airway disease models: ATS 2001, May 18-23, San Francisco

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Hele David J

2001-07-01

Full Text Available Abstract The 97th American Thoracic Society meeting proved to be an excellent meeting, providing a wealth of new information on inflammatory diseases of the airways. Once again there appeared to be an increased emphasis on chronic obstructive pulmonary disease (COPD with most of the major drug companies concentrating a large part of their efforts in this field. An assessment of the new British Thoracic Society guidelines, which are designed to promote better management of COPD, was also presented at the meeting. Potential new treatments for inflammatory diseases of the airways including COPD were described, ranging from phase III trial data with GlaxoSmithKline's PDE4 inhibitor, Cilomilast (Ariflo® to the development of AstraZeneca's novel dual dopamine D2-receptor/β2-adrenoreceptor agonist, Viozan™. Of particular interest was Byk Gulden's Ciclesonide, a new corticosteroid with equivalent efficacy to the market leaders but with an improved safety profile. The same company also presented data on their PDE4 inhibitor, Roflumilast, which is now in phase II/III. Bayer presented data on their PDE4 inhibitor, BAY 19-8004, in a smoking animal model and claimed greater anti-inflammatory efficacy than with a steroid. Asta Medica (now known as Elbion also described a new potent PDE4 inhibitor, AWD 12-281, with anti-inflammatory activity. In the bronchodilator field, an analysis of data from a one-year trial with Boehringer Ingelheim's Tiotropium revealed a possible improvement in lung function in COPD patients; this needs to be confirmed in a specifically designed study. Inhibitors of p38 (c-Jun NH2-terminal kinase and syk kinase were also discussed as anti-inflammatory agents with potential in the treatment of COPD and asthma. GlaxoSmithKline's p38 kinase inhibitor, SB 239063, appeared to be the most advanced of these with clinical data expected in two to three years. Lyn kinase was also discussed as a novel target for inflammatory airway diseases.

Comparison of a commercially available oral nutritional supplement and intravenous fluid therapy for dehydration in dairy calves.

Science.gov (United States)

Taylor, Jared D; Rodenburg, Merel; Snider, Timothy A

2017-06-01

Calf scours is a primary cause of morbidity and mortality in the dairy industry. Effective treatments are needed to minimize death, maximize welfare, and maintain growth and productivity. The objective of this trial was to compare the efficacy of a commercially available nutritional supplement (Diaque, Boehringer-Ingelheim Vetmedica Inc., St. Joseph, MO) and i.v. lactated Ringer's solution (LRS) in rehydrating, preventing acidemia, and correcting electrolyte imbalances in an experimental model for calf scours. Twenty-four colostrum-fed suckling dairy calves were used in a modified crossover design. An osmotic diarrhea was induced by orally feeding commercial milk replacer modified with high level of sucrose to create a hypertonic milk solution, and administering oral hydrochlorothiazide and spironolactone for 48 h. The intention was to create a challenge sufficient to result in moderately dehydrated, standing calves without producing severe depression or loss of suckle. The efficacy of i.v. fluid therapy and a commercial nutritional supplement were subsequently compared for reversing the effects of the diarrheal disease. Treatment A consisted of administering the nutritional supplement according to label directions (100 g in 1.9 L of warm water, 3 times a day), and treatment B consisted of i.v. LRS (2 L, once a day). Clinical signs and laboratory results were obtained once daily by a blinded observer. The induction method was effective in creating the desired effect, as demonstrated by weight loss and subjective health and hydration scores. Both treatment groups experienced increases in body weight, base excess, and bicarbonate, and decreases in total protein and packed cell volume following treatment. Both i.v. LRS and Diaque are effective methods to correct hypovolemia and control derangements in acid-base status in calves with diarrhea and dehydration. The Authors. Published by the Federation of Animal Science Societies and Elsevier Inc. on behalf of the

Pingevabalt / Priidu Beier

Index Scriptorium Estoniae

Beier, Priidu, 1957-

1995-01-01

Arvustus: Vee, Elo. Ingelheim. Tln.: Eesti Raamat, 1995. Vastukaja : Viiding, Elo. Kirjaniku nimest ja veest // Kultuurileht. - 1995. - 10.nov. - Lk.17; Kivisildnik, Sven. Intuitiivne geneetika ja ustavuse piirid // Postimees. - 1996. - 4.märts. - Lk.18

A 6-month trial of simvastatin (HMG-CoA reductase inhibitor) in the ...

African Journals Online (AJOL)

1991-06-01

Jun 1, 1991 ... minations the neutral fat kit, also from Boehringer Mannheim, was used. ..... burn, abdominal discomfort, flatulence, constipation and loose stools. Many of these .... reported participating in regular heavy physical exercise. No.

Aversion to ambiguity and willingness to take risks affect therapeutic decisions in managing atrial fibrillation for stroke prevention: results of a pilot study in family physicians

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Raptis S

2017-09-01

Full Text Available Stavroula Raptis,1,* Jia Ning Chen,2,* Florencia Saposnik,2 Roman Pelyavskyy,2 Andrew Liuni,3 Gustavo Saposnik2,4 On behalf of the Stroke Outcomes Research Canada Working Group (SORCan- www.sorcan.ca 1Applied Health Research Centre, Li Ka Shing Knowledge Institute, 2Stroke Outcomes and Decision Neuroscience Research Unit, Department of Medicine, St. Michael’s Hospital, University of Toronto, Toronto, 3Medical Department, Boehringer Ingelheim (Canada Ltd., Burlington, ON, Canada; 4Neuroeconomics and Decision Neuroscience, Department of Economics, University of Zurich, Zurich, Switzerland *These authors contributed equally to this work Background: Anticoagulation is the therapeutic paradigm for stroke prevention in patients with atrial fibrillation (AF. It is unknown how physicians make treatment decisions in primary stroke prevention for patients with AF. Objectives: To evaluate the association between family physicians’ risk preferences (aversion risk and ambiguity and therapeutic recommendations (anticoagulation in the management of AF for primary stroke prevention by applying concepts from behavioral economics. Methods: Overall, 73 family physicians participated and completed the study. Our study comprised seven simulated case vignettes, three behavioral experiments, and two validated surveys. Behavioral experiments and surveys incorporated an economic framework to determine risk preferences and biases (e.g., ambiguity aversion, willingness to take risks. The primary outcome was making the correct decision of anticoagulation therapy. Secondary outcomes included medical errors in the management of AF for stroke prevention. Results: Overall, 23.3% (17/73 of the family physicians elected not to escalate the therapy from antiplatelets to anticoagulation when recommended by best practice guidelines. A total of 67.1% of physicians selected the correct therapeutic options in two or more of the three simulated case vignettes. Multivariate

Increase in skeletal muscle protein content by the ß-2 selective adrenergic agonist clenbuterol exacerbates hypoalbuminemia in rats fed a low-protein diet

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A.L. Sawaya

1998-06-01

Full Text Available This investigation examined how the nutritional status of rats fed a low-protein diet was affected when the animals were treated with the ß-2 selective agonist clenbuterol (CL. Males (4 weeks old from an inbred, specific-pathogen-free strain of hooded rats maintained at the Dunn Nutritional Laboratory were used in the experiments (N = 6 rats per group. CL treatment (Ventipulmin, Boehringer-Ingelheim Ltd., 3.2 mg/kg diet for 2 weeks caused an exacerbation of the symptoms associated with protein deficiency in rats. Plasma albumin concentrations, already low in rats fed a low-protein diet (group A, were further reduced in CL rats (A = 25.05 ± 0.31 vs CL = 23.64 ± 0.30 g/l, P<0.05. Total liver protein decreased below the level seen in either pair-fed animals (group P or animals with free access to the low-protein diet (A = 736.56 ± 26 vs CL = 535.41 ± 54 mg, P<0.05, whereas gastrocnemius muscle protein was higher than the values normally described for control (C animals (C = 210.88 ± 3.2 vs CL = 227.14 ± 1.7 mg/g, P<0.05. Clenbuterol-treated rats also showed a reduction in growth when compared to P rats (P = 3.2 ± 1.1 vs CL = -10.2 ± 1.9 g, P<0.05. This was associated with a marked decrease in fat stores (P = 5.35 ± 0.81 vs CL = 2.02 ± 0.16 g, P<0.05. Brown adipose tissue (BAT cytochrome oxidase activity, although slightly lower than in P rats (P = 469.96 ± 16.20 vs CL = 414.48 ± 11.32 U/BAT x kg body weight, P<0.05, was still much higher than in control rats (C = 159.55 ± 11.54 vs CL = 414.48 ± 11.32 U/BAT x kg body weight, P<0.05. The present findings support the hypothesis that an increased muscle protein content due to clenbuterol stimulation worsened amino acid availability to the liver and further reduced albumin synthesis causing exacerbation of hypoalbuminemia in rats fed a low-protein diet.

SU-E-J-266: Cone Beam Computed Tomography (CBCT) Inter-Scan and Inter-Observer Tumor Volume Variability Assessment in Patients Treated with Stereotactic Body Radiation Therapy (SBRT) for Early Stage Non-Small Cell Lung Cancer (NSCLC)

Energy Technology Data Exchange (ETDEWEB)

Hou, Y; Aileen, C; Kozono, D; Killoran, J; Wagar, M; Lee, S; Hacker, F; Aerts, H; Lewis, J; Mak, R [Brigham and Women’s Hospital, Boston, MA (United States)

2015-06-15

award; Disclosure/Conflict of interest: Raymond H. Mak: Stock ownership: Celgene, Inc. Consulting: Boehringer-Ingelheim, Inc.

Disability related to COPD tool (DIRECT: towards an assessment of COPD-related disability in routine practice

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Aguilaniu B

2011-07-01

Full Text Available B Aguilaniu1, J Gonzalez-Bermejo2, A Regnault3, C Dias Barbosa3, B Arnould3, M Mueser4, G Granet5, M Bonnefoy6, T Similowski2,71HYLAB, Physiologie Clinique, Grenoble, France; 2Assistance Publique – Hôpitaux de Paris, Groupe Hospitalier Pitié-Salpêtrière, Service de Pneumologie et Réanimation, Paris, France; 3Mapi Values, Lyon, France; 4Formerly Boehringer Ingelheim, Paris, France; 5General Practitioner, Sainte-Foy-lès-Lyon, Paris, France; 6Centre Hospitalier Lyon Sud, Lyon, France; 7Université Paris 6 Pierre et Marie Curie, ER10, Paris, FranceBackground: Chronic Obstructive Pulmonary Disease (COPD is a worldwide public health concern. It is also a major source of disability that is often overlooked, depriving patients of effective treatments. This study describes the development and validation of a questionnaire specifically assessing COPD-related disability.Methods: The DIsability RElated to COPD Tool (DIRECT was developed according to reference methods, including literature review, patient and clinician interviews and test in a pilot study. A 12-item questionnaire was included for finalization and validation in an observational cross-sectional study conducted by 60 French pulmonologists, who recruited 275 COPD patients of stage II, III and IV according to the GOLD classification. Rasch modeling was conducted and psychometric properties were assessed (internal consistency reliability; concurrent and clinical validity.Results: The DIRECT score was built from the 10 items retained in the Rasch model. Their internal consistency reliability was excellent (Cronbach's alpha = 0.95. The score was highly correlated with the Saint George's Respiratory Questionnaire Activity score (r = 0.83 and the London Handicap Scale (r = –0.70, a generic disability measure. It was highly statistically significantly associated to four clinical parameters (P < 0.001: GOLD classification, BODE index, FEV1 and 6-minute walk distance.Conclusion: DIRECT is a

Randomized noninferiority clinical trial evaluating 3 commercial dry cow mastitis preparations: II. Cow health and performance in early lactation.

Science.gov (United States)

Arruda, A G; Godden, S; Rapnicki, P; Gorden, P; Timms, L; Aly, S S; Lehenbauer, T W; Champagne, J

2013-10-01

The objective of this randomized noninferiority clinical trial was to compare the effect of treatment with 3 different dry cow therapy formulations at dry-off on cow-level health and production parameters in the first 100 d in milk (DIM) in the subsequent lactation, including 305-d mature-equivalent (305 ME) milk production, linear score (LS), risk for the cow experiencing a clinical mastitis event, risk for culling or death, and risk for pregnancy by 100 DIM. A total of 1,091 cows from 6 commercial dairy herds in 4 states (California, Iowa, Minnesota, and Wisconsin) were randomly assigned at dry-off to receive treatment with 1 of 3 commercial products: Quartermaster (QT; Zoetis Animal Health, Madison, NJ), Spectramast DC (SP; Zoetis Animal Health) or ToMorrow Dry Cow (TM; Boehringer Ingelheim Vetmedica Inc., St Joseph, MO). All clinical mastitis, pregnancy, culling, and death events occurring in the first 100 DIM were recorded by farm staff using an on-farm electronic record-keeping system. Dairy Herd Improvement Association test-day records of milk production and milk component testing were retrieved electronically. Mixed linear regression analysis was used to describe the effect of treatment on 305ME milk production and LS recorded on the last Dairy Herd Improvement Association test day before 100 DIM. Cox proportional hazards regression analysis was used to describe the effect of treatment on risk for experiencing a case of clinical mastitis, risk for leaving the herd, and risk for pregnancy between calving and 100 DIM. Results showed no effect of treatment on adjusted mean 305 ME milk production (QT=11,759 kg, SP=11,574 kg, and TM=11,761 kg) or adjusted mean LS (QT=1.8, SP=1.9, and TM=1.6) on the last test day before 100 DIM. Similarly, no effect of treatment was observed on risk for a clinical mastitis event (QT=14.8%, SP=12.7%, and TM=15.0%), risk for leaving the herd (QT=7.5%, SP=9.2%, and TM=10.3%), or risk for pregnancy (QT=31.5%, SP=26.1%, and TM=26

SU-E-J-266: Cone Beam Computed Tomography (CBCT) Inter-Scan and Inter-Observer Tumor Volume Variability Assessment in Patients Treated with Stereotactic Body Radiation Therapy (SBRT) for Early Stage Non-Small Cell Lung Cancer (NSCLC)

International Nuclear Information System (INIS)

Hou, Y; Aileen, C; Kozono, D; Killoran, J; Wagar, M; Lee, S; Hacker, F; Aerts, H; Lewis, J; Mak, R

2015-01-01

award; Disclosure/Conflict of interest: Raymond H. Mak: Stock ownership: Celgene, Inc. Consulting: Boehringer-Ingelheim, Inc

Sluggish glucose tolerance in tuberculosis patients | Bell | South ...

African Journals Online (AJOL)

Standard oral glucose tolerance tests (OGTTs) were performed in both groups in the morning after an overnight fast. Anticoagulant-treated blood was analysed for glucose and insulin using Peridochrome Glucose (Boehringer Mannheim, Mannheim, Germany) and radioimmunoassay (RIA) (Diagnostic Products Corporation, ...

2012 edition JMBR - CORRECTION.cdr

African Journals Online (AJOL)

FinePrint

Boehringer spectrophometer 4010) at appropriate wavelengths. The concentration of plasma low density lipoprotein cholesterol (LDLc) was. 1 estimated according to Okwusidi (1988) as the difference between TPC and HDLc to obtain summed LDLc + VLDLc; with subsequent adjustment for determined. TRG concentration ...

128 - 131 Abdu Anticholinester

African Journals Online (AJOL)

DR. AMIN

shown in the equation below (Boehringer, 1991). The study was set out to investigate the effect of the leaves extract of Anogeisus leiocarpus on the cholinesterase enzyme which serves as an indicator system whose analysis always correspond to the bioluminescence Mycobacterium aurum or tuberculosis expressing firefly.

Inhalation and Percutaneous Toxicokinetics of Sulfur Mustard and Its Adducts in Hairless Guinea Pigs and Marmosets. Efficacy of Naval Scavengers

Science.gov (United States)

2005-08-01

activity ca. 40 units/mg protein) from Boehringer (Mannheim, Germany); RNase A, and Tween 20 from Sigma Chemical Co. (St. Louis, MO, USA); and skimmed milk ...al. 1997). This hypothesis is still awaiting falsification . Measurement of the concentration-time course of the adduct of sulfur mustard to hemoglobin

Biodegradation of 2,4-dichlorophenol originating from ...

African Journals Online (AJOL)

STORAGESEVER

2009-06-03

Jun 3, 2009 ... of high concentration of chlorophenols. Appl. Microbiol. Biotechnol. 59: 599-604. Louie TM, Webster CM, Xun L (2002). Genetic and biochemical characterization of a 2,4,6- trichlorophenol degradation pathway in. Ralstonia eutropha JMP 134. J. Bacteriol. 184: 3492-3500. Lysetska M, Knoll A, Boehringer D ...

Molecular characterisation of Mycovellosiella koepki, the causal ...

African Journals Online (AJOL)

KEN

2007-02-05

Feb 5, 2007 ... then annealing at 52°C for 1 min and finally 72°C for primer extension. The final primer elongation segment of the run was extended to 10 min at 72°C. Amplified products were digested with restriction enzymes according to the manufacturer's instructions. (Boehringer Mannheim). Digested DNA fragments ...

Dual Antithrombotic Therapy with Dabigatran after PCI in Atrial Fibrillation.

Science.gov (United States)

Cannon, Christopher P; Bhatt, Deepak L; Oldgren, Jonas; Lip, Gregory Y H; Ellis, Stephen G; Kimura, Takeshi; Maeng, Michael; Merkely, Bela; Zeymer, Uwe; Gropper, Savion; Nordaby, Matias; Kleine, Eva; Harper, Ruth; Manassie, Jenny; Januzzi, James L; Ten Berg, Jurrien M; Steg, P Gabriel; Hohnloser, Stefan H

2017-10-19

lower among those who received dual therapy with dabigatran and a P2Y 12 inhibitor than among those who received triple therapy with warfarin, a P2Y 12 inhibitor, and aspirin. Dual therapy was noninferior to triple therapy with respect to the risk of thromboembolic events. (Funded by Boehringer Ingelheim; RE-DUAL PCI ClinicalTrials.gov number, NCT02164864 .).

COPD patient satisfaction with ipratropium bromide/albuterol delivered via Respimat: a randomized, controlled study

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Ferguson GT

2013-03-01

Full Text Available Gary T Ferguson,1 Mo Ghafouri,2 Luyan Dai,2 Leonard J Dunn31Pulmonary Research Institute of Southeast Michigan, Livonia, MI, USA; 2Boehringer Ingelheim Pharmaceuticals, Inc, Ridgefield, CT, USA; 3Clinical Research of West Florida, Inc, Clearwater, FL, USABackground: Ipratropium bromide/albuterol Respimat inhaler (CVT-R was developed as an environmentally friendly alternative to ipratropium bromide/albuterol metered-dose inhaler (CVT-MDI, which uses a chlorofluorocarbon propellant.Objective: The objective of this study was to evaluate patient satisfaction, device usage, and long-term safety of CVT-R compared to CVT-MDI, and to the simultaneous administration of ipratropium bromide hydrofluoroalkane (HFA; I and albuterol HFA (A metered-dose inhalers as dual monotherapies (I + A.Design: This is a 48-week, open-label, randomized, active-controlled, parallel-group study (n = 470 comparing CVT-R to CVT-MDI and to I + A.Participants: Patients were at least 40 years of age, diagnosed with chronic obstructive pulmonary disease (COPD, and current or exsmokers.Interventions: Patients were randomized to receive: (1 CVT-R, one inhalation four times daily (QID; or (2 CVT-MDI, two inhalations QID; or (3 I + A two inhalations of each inhaler QID.Main measures: Patient Satisfaction and Preference Questionnaire (PASAPQ performance score (primary endpoint and adverse events.Key results: PASAPQ performance score was significantly higher (CVT-R versus CVT-MDI, 9.6; and CVT-R versus I + A, 6.2; both P < 0.001 when using CVT-R compared to CVT-MDI or I + A at all visits starting from week 3, while CVT-MDI and I + A treatment groups were similar. Time to first COPD exacerbation was slightly longer in the CVT-R group compared to the other treatment groups, although it did not reach statistical significance (CVT-R versus CVT-MDI, P = 0.57; CVT-R versus I + A, P = 0.22. Rates of withdrawal and patient refusal to continue treatment were lower in CVT-R compared with CVT

Intramuscular Immunization of Mice with the Live-Attenuated Herpes Simplex Virus 1 Vaccine Strain VC2 Expressing Equine Herpesvirus 1 (EHV-1) Glycoprotein D Generates Anti-EHV-1 Immune Responses in Mice.

Science.gov (United States)

Liu, Shiliang A; Stanfield, Brent A; Chouljenko, Vladimir N; Naidu, Shan; Langohr, Ingeborg; Del Piero, Fabio; Ferracone, Jacqueline; Roy, Alma A; Kousoulas, Konstantin G

2017-06-15

Vaccination remains the best option to combat equine herpesvirus 1 (EHV-1) infection, and several different strategies of vaccination have been investigated and developed over the past few decades. Herein, we report that the live-attenuated herpes simplex virus 1 (HSV-1) VC2 vaccine strain, which has been shown to be unable to enter into neurons and establish latency in mice, can be utilized as a vector for the heterologous expression of EHV-1 glycoprotein D (gD) and that the intramuscular immunization of mice results in strong antiviral humoral and cellular immune responses. The VC2-EHV-1-gD recombinant virus was constructed by inserting an EHV-1 gD expression cassette under the control of the cytomegalovirus immediate early promoter into the VC2 vector in place of the HSV-1 thymidine kinase (UL23) gene. The vaccines were introduced into mice through intramuscular injection. Vaccination with both the VC2-EHV-1-gD vaccine and the commercially available vaccine Vetera EHV XP 1/4 (Vetera; Boehringer Ingelheim Vetmedica) resulted in the production of neutralizing antibodies, the levels of which were significantly higher in comparison to those in VC2- and mock-vaccinated animals ( P < 0.01 or P < 0.001). Analysis of EHV-1-reactive IgG subtypes demonstrated that vaccination with the VC2-EHV-1-gD vaccine stimulated robust IgG1 and IgG2a antibodies after three vaccinations ( P < 0.001). Interestingly, Vetera-vaccinated mice produced significantly higher levels of IgM than mice in the other groups before and after challenge ( P < 0.01 or P < 0.05). Vaccination with VC2-EHV-1-gD stimulated strong cellular immune responses, characterized by the upregulation of both interferon- and tumor necrosis factor-positive CD4 + T cells and CD8 + T cells. Overall, the data suggest that the HSV-1 VC2 vaccine strain may be used as a viral vector for the vaccination of horses as well as, potentially, for the vaccination of other economically important animals. IMPORTANCE A novel virus

Association between adherence to medications for COPD and medications for other chronic conditions in COPD patients

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Dhamane AD

2016-12-01

Full Text Available Amol D Dhamane,1 Phil Schwab,2 Sari Hopson,2 Chad Moretz,2 Srinivas Annavarapu,2 Kate Burslem,1 Andrew Renda,3 Shuchita Kaila1 1Health Economics and Outcomes Research, Boehringer Ingelheim Pharmaceuticals Inc, Ridgefield, CT, 2Comprehensive Health Insights Inc, Louisville, 3Humana Inc, Louisville, KY, USA Background: Patients with COPD often have multiple comorbidities requiring use of multiple medications, and adherence rates for maintenance COPD (mCOPD medications are already known to be suboptimal. Presence of comorbidities in COPD patients, and use of medications used to treat those comorbidities (non-COPD medications, may have an adverse impact on adherence to mCOPD medications. Objective: The objective of the study was to evaluate the association between non-adherence to mCOPD medications and non-COPD medications in COPD patients. Methods: COPD patients were identified using a large administrative claims database. Selected patients were 40–89 years old and continuously enrolled for 12 months prior to and 24 months after the first identified COPD diagnosis (index date during January 1, 2009 to December 31, 2010. Patients were required to have ≥1 prescription for a mCOPD medication within 365 days of the index date and ≥1 prescription for one of 12 non-COPD medication classes within ±30 days of the first COPD prescription. Adherence (proportion of days covered [PDC] was measured during 365 days following the first COPD prescription. The association between non-adherence (PDC <0.8 to mCOPD and non-adherence to non-COPD medications was determined using logistic regression, controlling for baseline patient characteristics. Results: A total of 14,117 patients, with a mean age of 69.9 years, met study criteria. Of these, 40.9% were males and 79.2% were non-adherent to mCOPD medications with a mean PDC of 0.47. Non-adherence to mCOPD medications was associated with non-adherence to 10 of 12 non-COPD medication classes (odds ratio 1.38–1

Increase energy efficiency in the cold production; Steigerung der Energieeffizienz in der Kaelteerzeugung

Energy Technology Data Exchange (ETDEWEB)

Paatzsch, Rene [Institut fuer Luft- und Kaeltetechnik gGmbH, Dresden (Germany). Hauptbereich Kaelte- und Waermepumpentechnik; Berg, Hans-Peter [Boehringer Ingelheim Pharma GmbH und Co. KG, Ingelheim (Germany)

2011-12-15

According to a study by ILK Dresden the cold production in the field of pharmaceutical manufacturing at Boehringer has been adjusted. By installing a turbo chiller and the sliding control of the cooling water temperature depending on the wet bulb temperature the COP of the cold production was improved of 3.1 to 4.5 currently. (orig.)

Characterisation of penA and tetM resistance genes of Neisseria ...

African Journals Online (AJOL)

20 mM EDTA, pH 7,4) containing 25 IJg of lysozyme. After 10 minutes at room temperature 0,5 ml of 2% Triton-X 100 and. 12,5 IJg of Proteinase K (Boehringer) were added. ... the exception that 4 IJg of mutanolysin (Sigma) and 10 IJg lysozyme (Sigma) were added to aid lysis. Plasmid. Volume 85 No. 8 August 1995 SAMJ ...

Monitoring paneer for Listeria monocytogenes- A high risk food ...

African Journals Online (AJOL)

Dr.Batish

2012-05-15

May 15, 2012 ... Taq DNA polymerase (Boehringer Mannheim). Appropriate positive and negative controls with each reaction were also set up. The PCR parametres included initial denaturation at 95°C for 4 min followed by. 25 cycles of denaturation at 95°C for 30 s, annealing at 60°C for 30 s, extension at 72°C for 30 s ...

A simplified radioimmunoassay for digoxin determination using a 125-I-labelled solid-phase kit

International Nuclear Information System (INIS)

Doering, W.; Bluemel, E.

1978-01-01

Our experience with a commercially available kit (Radioimmunoassay DIGOXIN, Boehringer, Mannheim) using ( 125 J)-labelled digoxin and antibody-coated tubes is reported. This simplified method requires only two pipetting steps per sample and results can be obtained in 70 min. The intra- and interassay coefficient of variation ranged between 7% and 8%. The specific digoxin antibody antibody gave no clinical relevant cross-reactions with spironolactone or prednisone ( [de

The burden of chronic obstructive pulmonary disease associated with maintenance monotherapy in the UK

Directory of Open Access Journals (Sweden)

Edwards SC

2016-11-01

Full Text Available Susan C Edwards,1 Sian E Fairbrother,2 Anna Scowcroft,3 Gavin Chiu,4 Andrew Ternouth,3 Brian J Lipworth5 1Department of Market Access Pricing & Outcomes Research, 2Department of Medical Affairs - Respiratory, 3Department of Market Access, 4Department of Prescription Medicine - Respiratory, Boehringer Ingelheim, Bracknell, UK; 5Asthma and Allergy Research Group, Division of Cardiovascular and Diabetes Medicine, Scottish Centre for Respiratory Research, University of Dundee, Ninewells Hospital and Medical School, Dundee, UK Background: This study characterized a cohort of chronic obstructive pulmonary disease (COPD patients on maintenance bronchodilator monotherapy for ≥6 months to establish their disease burden, measured by health care utilization.Methods: Data were extracted from the UK Clinical Practice Research Datalink and linked to Hospital Episode Statistics. The monotherapy period spanned the first prescription of a long-acting β2-adrenergic agonist or a long-acting muscarinic antagonist until the end of the study (December 31, 2013 or until step up to dual/triple therapy, for example, addition of another long-acting bronchodilator, an inhaled corticosteroid, or both. A minimum of four consecutive prescriptions and 6 months on continuous monotherapy were required. Patients <50 years old at first COPD diagnosis or with another significant respiratory disease before starting monotherapy were excluded. Disease burden was evaluated by measuring patients’ rate of face-to-face interactions with a health care professional (HCP, COPD-related exacerbations, hospitalizations, and referrals.Results: A cohort of 8,811 COPD patients (95% Global initiative for chronic Obstructive Lung Disease stage A/B on maintenance monotherapy was identified between 2002 and 2013; 45% of these patients were still on monotherapy by the end of the study. Median time from first COPD diagnosis to first monotherapy prescription was 56 days, while the median time on

Three-minute constant rate step test for detecting exertional dyspnea relief after bronchodilation in COPD

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Borel B

2016-11-01

Full Text Available Benoit Borel,1,2 Courtney A Wilkinson-Maitland,3 Alan Hamilton,4 Jean Bourbeau,5 Hélène Perrault,6 Dennis Jensen,3,5,7 François Maltais2 1Laboratoire HAVAE, Université de Limoges, Limoges, France; 2Centre de Recherche, Institut Universitaire de Cardiologie et de Pneumologie de Québec, Université Laval, Québec, 3Clinical Exercise and Respiratory Physiology Laboratory, Department of Kinesiology and Physical Education, McGill University, Montréal, QC, 4Boehringer Ingelheim (Canada Limited, Burlington, ON, 5Respiratory Epidemiology and Clinical Research Unit, Montreal Chest Institute, McGill University Health Center, Montreal, QC, 6Faculty of Health Sciences, University of Ottawa, Ottawa, ON, 7Translational Research in Respiratory Diseases Program, Research Institute of the McGill University Health Centre, Montreal, QC, Canada Background: The aim of this study was to evaluate the responsiveness of the 3-minute constant rate step test (3-MST to detect the relief of exertional dyspnea (respiratory discomfort after acute bronchodilation in COPD patients. Patients and methods: A total of 40 patients with moderate-to-severe COPD (mean forced expiratory volume in 1 second: 45.7 (±14.7, % predicted performed four 3-MSTs at randomly assigned stepping rates of 14, 16, 20 and 24 steps/min after inhalation of nebulized ipratropium bromide (500 µg/salbutamol (2.5 mg and saline placebo, which were randomized to order. Patients rated their intensity of perceived dyspnea at the end of each 3-MST using Borg 0–10 category ratio scale. Results: A total of 37 (92.5%, 36 (90%, 34 (85% and 27 (67.5% patients completed all 3 minutes of exercise at 14, 16, 20 and 24 steps/min under both treatment conditions, respectively. Compared with placebo, ipratropium bromide/salbutamol significantly decreased dyspnea at the end of the third minute of exercise at 14 steps/min (by 0.6±1.0 Borg 0–10 scale units, P<0.01 and 16 steps/min (by 0.7±1.3 Borg 0–10 scale

Holter-electrocardiogram-monitoring in patients with acute ischaemic stroke (Find-AFRANDOMISED): an open-label randomised controlled trial.

Science.gov (United States)

Wachter, Rolf; Gröschel, Klaus; Gelbrich, Götz; Hamann, Gerhard F; Kermer, Pawel; Liman, Jan; Seegers, Joachim; Wasser, Katrin; Schulte, Anna; Jürries, Falko; Messerschmid, Anna; Behnke, Nico; Gröschel, Sonja; Uphaus, Timo; Grings, Anne; Ibis, Tugba; Klimpe, Sven; Wagner-Heck, Michaela; Arnold, Magdalena; Protsenko, Evgeny; Heuschmann, Peter U; Conen, David; Weber-Krüger, Mark

2017-04-01

months, we detected atrial fibrillation in 14% of 200 patients in the enhanced and prolonged monitoring group (27 patients) versus 5% in the control group (nine of 198 patients, absolute difference 9·0%; 95% CI 3·4-14·5, p=0·002; number needed to screen 11). Enhanced and prolonged monitoring initiated early in patients with acute ischaemic stroke aged 60 years or older was better than standard care for the detection of atrial fibrillation. These findings support the consideration of all patients aged 60 years or older with stroke for prolonged monitoring if the detection of atrial fibrillation would result in a change in medical management (eg, initiation of anticoagulation). Boehringer Ingelheim. Copyright © 2017 Elsevier Ltd. All rights reserved.

Impact of comorbid conditions in COPD patients on health care resource utilization and costs in a predominantly Medicare population

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Schwab P

2017-02-01

Full Text Available Phil Schwab,1 Amol D Dhamane,2 Sari D Hopson,1 Chad Moretz,1 Srinivas Annavarapu,1 Kate Burslem,2 Andrew Renda,3 Shuchita Kaila2 1Comprehensive Health Insights Inc., Louisville, KY, 2Health Economics and Outcomes Research, Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, CT, 3Humana Inc., Louisville, KY, USA Background: Patients with chronic obstructive pulmonary disease (COPD often have multiple underlying comorbidities, which may lead to increased health care resource utilization (HCRU and costs.Objective: To describe the comorbidity profiles of COPD patients and examine the associations between the presence of comorbidities and HCRU or health care costs.Methods: A retrospective cohort study utilizing data from a large US national health plan with a predominantly Medicare population was conducted. COPD patients aged 40–89 years and continuously enrolled for 12 months prior to and 24 months after the first COPD diagnosis during the period of January 01, 2009, through December 31, 2010, were selected. Eleven comorbidities of interest were identified 12 months prior through 12 months after COPD diagnosis. All-cause and COPD-related hospitalizations and costs were assessed 24 months after diagnosis, and the associations with comorbidities were determined using multivariate statistical models.Results: Ninety-two percent of 52,643 COPD patients identified had at least one of the 11 comorbidities. Congestive heart failure (CHF, coronary artery disease, and cerebrovascular disease (CVA had the strongest associations with all-cause hospitalizations (mean ratio: 1.56, 1.32, and 1.30, respectively; P<0.0001; other comorbidities examined had moderate associations. CHF, anxiety, and sleep apnea had the strongest associations with COPD-related hospitalizations (mean ratio: 2.01, 1.32, and 1.21, respectively; P<0.0001; other comorbidities examined (except chronic kidney disease [CKD], obesity, and osteoarthritis had moderate associations. All

Effects of telmisartan on office and 24-hour ambulatory blood pressure: an observational study in hypertensive patients managed in primary care

Directory of Open Access Journals (Sweden)

Frederic Kontny

2010-01-01

Full Text Available Frederic Kontny1, Terje Risanger2, Arne Bye3, Øyvind Arnesen4, Odd Erik Johansen4 for the TELMIMORE Study Investigators51Dept of Cardiology, Volvat Medical Centre, Oslo, Norway; 2Prinsdal Health Centre, Oslo, Norway; 3Frosta Health Centre, Frosta, Norway; 4Medical Department, Boehringer-Ingelheim Norway KS, Asker, Norway; 5The TELMIMORE Study Investigators are listed at the end of the paperPurpose: Although elevated blood pressure (BP predicts future cardiovascular events, recommended BP targets often is not reached in the general community. In a clinical real-life setting we evaluated BP impact and tolerability of the angiotensin-II receptor blocker telmisartan in patients with essential hypertension.Patients and methods: Patients in this observational study not at target BP started or switched to telmisartan monotherapy (40 or 80 mg or a fixed-dose combination of telmisartan and hydrochlorothiazide (HCT 80 mg/12.5 mg. Office and 24-hour ambulatory BP (AMBP were measured before and after 8 weeks of treatment and physicians reported perceived drug efficacy and tolerability as “Very good”, “Good”, “Moderate” or “Bad”.Results: 100 patients (34% female, 60 years, BMI 29.4 kg/m2, mean office BP 159/92 mmHg of whom 38% were treatment naïve and 30%, 17%, 9% and 6% respectively were on 1, 2, 3 or 4 BP-lowering drugs, completed 8 weeks of treatment. The proportion of patients with office BP < 140/90 mmHg increased from 3% to 54% for systolic (P < 0.001, 38% to 75% for diastolic (P < 0.001, and 2% to 45% for systolic and diastolic BP (P < 0.001. A significant effect on BP levels was seen in patients being either treatment naïve or on 1 to 3 BP-lowering drugs at study entry, whereas no BP improvement occurred in those who switched from 4 drugs. Overall, mean 24-hour AMBP was reduced from 141/85 to 131/79 mmHg (P < 0.001. Drug efficacy and tolerability were perceived as “Very good” or “Good” by 44%/34% and 66%/27%, respectively

Comparative studies on the determination of alphafetoprotein by enzyme immunoassay and by radioimmunoassay

International Nuclear Information System (INIS)

Haller, G.; Linneke, P.; Voss, P.; Jeske, W.

1987-01-01

Alphafetoprotein (AFP) was determined in serum of pregnant women in the tenth till sixteenth week of pregnancy by means of two enzyme immunoassays (Enzymun-Test AFP, Boehringer Mannheim, FRG and AFP EIA 'Dessau' 1000, Research Institute for Vaccine Dessau, GDR) and a radioimmunoassay (Radioimmunoassay Kit, AFP-PR, CIS, France). Parallel determinations in sera of 438 patients, who had come to surveillance for the first consultation were estimated. A comparison between the methods showed a good correlation. (author)

VizieR Online Data Catalog: REFLEX Galaxy Cluster Survey catalogue (Boehringer+, 2004)

Science.gov (United States)

Boehringer, H.; Schuecker, P.; Guzzo, L.; Collins, C. A.; Voges, W.; Cruddace, R. G.; Ortiz-Gil, A.; Chincarini, G.; de Grandi, S.; Edge, A. C.; MacGillivray, H. T.; Neumann, D. M.; Schindler, S.; Shaver, P.

2004-05-01

The following tables provide the catalogue as well as several data files necessary to reproduce the sample preparation. These files are also required for the cosmological modeling of these observations in e.g. the study of the statistics of the large-scale structure of the matter distribution in the Universe and related cosmological tests. (13 data files).

AMCP Partnership Forum: Improving Quality, Value, and Outcomes with Patient-Reported Outcomes.

Science.gov (United States)

2018-03-01

manufacturers should engage key stakeholders early and throughout the drug development process to ensure the most valid and representative PROs and patient populations will be included. To streamline the PRO collection process, participants suggested engaging pharmacists and other providers who may have more frequent interaction with patients. Participants also recommended that PRO collection and analysis should use common technology platforms, streamline components of clinician care to reduce workflow, and be integrated with claims data to provider payers a better understanding of patient health in real time. Finally, additional work should be done to develop patient-reported outcome measures that contain relevant measures for all healthcare stakeholders. While significant challenges remain in PRO development and adoption, participants agreed that greater use can only be achieved through collaboration and patient-centered care. The AMCP Partnership Forum titled "Improving Quality, Value, and Outcomes with Patient-Reported Outcomes" and the development of this proceedings report were supported by Amgen, Boehringer Ingelheim Pharmaceuticals, Genentech, GlaxoSmithKline, Novartis Pharmaceuticals, Novo Nordisk, Precision for Value, Premier, Sanofi, Takeda Pharmaceuticals USA, and Xcenda.

Randomized noninferiority clinical trial evaluating 3 commercial dry cow mastitis preparations: I. Quarter-level outcomes.

Science.gov (United States)

Arruda, A G; Godden, S; Rapnicki, P; Gorden, P; Timms, L; Aly, S S; Lehenbauer, T W; Champagne, J

2013-07-01

The study objective was to compare the efficacy of 3 commercial dry cow mastitis formulations regarding quarter-level prevalence of intramammary infections (IMI) postcalving, cure of preexisting infections over the dry period, prevention of new infections during the dry period, and risk for a clinical mastitis case between calving and 100d in milk (DIM). A total of 1,091 cows (4,364 quarters) from 6 commercial dairy herds in 4 different states (California, Iowa, Minnesota, and Wisconsin) were enrolled and randomized to 1 of the 3 treatments at dry-off: Quartermaster (QT; 1,000,000 IU of procaine penicillin G and 1 g of dihydrostreptomycin; Pfizer Animal Health, New York, NY), Spectramast DC (SP; 500 mg of ceftiofur hydrochloride; Pfizer Animal Health), or ToMorrow Dry Cow (TM; 300mg of cephapirin benzathine; Boehringer Ingelheim Vetmedica Inc., St. Joseph, MO). Quarter milk samples were collected for routine bacteriological culture before dry cow therapy treatment at dry-off, 0 to 6 DIM, and 7 to 13 DIM and an on-farm record-keeping system was used to retrieve data on clinical mastitis cases. Noninferiority analysis was used to evaluate the effect of treatment on the primary outcome, risk for a bacteriological cure during the dry period. Multivariable logistic regression techniques were used to describe the effect of treatment on risk for presence of IMI postcalving and risk of a new IMI during the dry period. Cox proportional hazards regression was used to describe the effect of treatment on the risk and time for quarters to experience an episode of clinical mastitis between calving and 100 DIM. The overall crude quarter-level prevalence of infection at dry-off was 19.2%. The most common pathogen isolated from milk samples at dry-off was coagulase-negative Staphylococcus, followed by Aerococcus spp. and other Streptococcus spp. Noninferiority analysis showed no effect of treatment on risk for a cure between dry-off and calving [least squares means (LSM): QT=93

Analysis of pramipexole dose–response relationships in Parkinson's disease

Directory of Open Access Journals (Sweden)

Wang Y

2016-12-01

Full Text Available Ying Wang,1 Sheng-Gang Sun,2 Sui-Qiang Zhu,3 Chun-Feng Liu,4 Yi-Ming Liu,5 Qing Di,6 Hui-Fang Shang,7 Yan Ren,8 Wei Xiang,9 Sheng-Di Chen1 1Department of Neurology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 2Department of Neurology, Union Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology, Wuhan, 3Department of Neurology, Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology, Wuhan, 4Department of Neurology, The Second Affiliated Hospital of Soochow University, Suzhou, 5Department of Neurology, Qilu Hospital Affiliated to Shandong University, Jinan, 6Department of Neurology, Nanjing Brain Hospital, Nanjing, 7Department of Neurology, West China Hospital Affiliated to Sichuan University, Chengdu, 8Department of Neurology, First Affiliated Hospital of China Medical University, Shenyang, 9Medical Department, Boehringer Ingelheim (China Investment Co., Ltd., Shanghai, People’s Republic of China Background: Pramipexole (PPX, a non-ergot dopamine receptor agonist, is a first-line treatment for Parkinson’s disease (PD. A critical dose level above which a better benefit-to-harm ratio exists has not been examined.Methods: Chinese PD patients (n=464 were retrospectively analyzed by PPX maintenance dose, PD stage, combined levodopa dose, and baseline tremor contribution. The sum score of Baseline Activities of Daily Living (part II and Motor Examination (III of the Unified Parkinson’s Disease Rating Scale (UPDRS II+III was used as a covariate for final score adjustment.Results: Sustained-release (SR and immediate-release (IR PPX showed similar efficacy based on score changes at 18 weeks, with comparable tolerability. Approximately two-third of patients received PPX at ≥1.5 mg/d, and one fourth of patients had ≥20% tremor contribution to UPDRS II+III. After treatment, patients receiving PPX ≥1.5 mg/d showed

A critical appraisal of a further three new commercial digoxin radioimmunoassay kits with reference to cross-reacting substances

International Nuclear Information System (INIS)

Wood, W.G.; Wachter, C.

1979-01-01

A further 3 digoxin radioimmunoassay (RIA) kits have been evaluated for performance and cross-reaction with digitoxin, spironolactone, canrenone and furosemide (Lasix-Hoechst). Effects of serum protein concentrations have also been tested. The kits tested were from the following manufacturers: A) Diagnostic Products Corporation Digoxin RIA Kit. B) Byk-Mallinckrodt SPAC Digoxin Kit. C) Boehringer-Mannheim Digoxin RIA Kit. All kits used a 125 I-labelled tracer. Kit A used a conventional liquid phase system using double-antibody separation for bound and free drug. Kits B and C used a solid-phase antibody coated tube method. All kits showed a lower cross-reaction to digitoxin than quoted by the manufacturer. Cross-reaction to spironolactone (Aldactone - Boehringer-Mannheim) was less than 1.50 nmol/l at a serum concentration of 125 mg/l Aldactone in all 3 kits. The cross-reaction to canrenone was somewhat higher, 5.2 nmol/l 'digoxin' being measured in one kit at a serum canrenone concentration of 125 mg/l. There was no cross-reaction with furosemide in any kit, even at a serum concentration of 5 g/l. The coated-tube assays were affected by serum albumin and globulin concentration changes, one kit showing a difference of over 50% binding in the range 1-20% albumin. The double-antibody kit did not show dependence on the concentration of these proteins. All kits measured digoxin with good reproducibility in the range 0.40-10.0 nmol/l. (orig.) [de

VizieR Online Data Catalog: REFLEX II. Properties of the survey (Boehringer+ 2013)

Science.gov (United States)

Boehringer, H.; Chon, G.; Collins, C. A.; Guzzo, L.; Nowak, N.; Bobrovskyi, S.

2013-06-01

Like REFLEX I, the extended survey covers the southern sky outside the band of the Milky Way (|bII|>=20°) with regions around the Magellanic clouds excised (3 in LMC, 3 in SMC). The total survey area after this excision amounts to 4.24 steradian (or 13924°2) which corresponds to 33.75% of the sky. Different from REFLEX I, we use the refined RASS product RASS III (Voges et al. 1999, Cat. IX/10). (2 data files).

[The effect of exogenous iron on levels of adenosinetriphosphate and 2,3-diphosphoglycerate in erythrocytes of men during extreme physical exertion].

Science.gov (United States)

Pedzikiewicz, J; Sobiech, K A

1995-01-01

Nine men were examined during a three-week training requiring much physical effort. They were given nutrient, "LIVEX", enriched with iron. Hematological parameters as well as concentration of erythrocyte ATP and 2,3-DPG were determined before and after the experiment. Hematological parameters were determined using standard methods while Boehringer's test (Germany) was used for determining ATP and 2,3-DPG. The level of reticular cells was statistically higher after the experiment, and the increase in ATP and 2,3-DPG concentration was insignificant. A positive adaptation of energy metabolism after exogenous iron administration during physical effort was discussed.

Efficacy and safety of dabigatran compared with warfarin at different levels of international normalised ratio control for stroke prevention in atrial fibrillation: an analysis of the RE-LY trial.

Science.gov (United States)

Wallentin, Lars; Yusuf, Salim; Ezekowitz, Michael D; Alings, Marco; Flather, Marcus; Franzosi, Maria Grazia; Pais, Prem; Dans, Antonio; Eikelboom, John; Oldgren, Jonas; Pogue, Janice; Reilly, Paul A; Yang, Sean; Connolly, Stuart J

2010-09-18

cardiovascular events (interaction p=0·036 and p=0·0006, respectively) and total mortality (interaction p=0·066 and p=0·052, respectively) with reduced event rates at low cTTR, and similar rates at high cTTR. The benefits of 150 mg dabigatran at reducing stroke, 110 mg dabigatran at reducing bleeding, and both doses at reducing intracranial bleeding versus warfarin were consistent irrespective of centres' quality of INR control. For all vascular events, non-haemorrhagic events, and mortality, advantages of dabigatran were greater at sites with poor INR control than at those with good INR control. Overall, these results show that local standards of care affect the benefits of use of new treatment alternatives. Boehringer Ingelheim. Copyright © 2010 Elsevier Ltd. All rights reserved.

Model-independent X-ray Mass Determinations for Clusters of Galaxies

Science.gov (United States)

Nulsen, Paul

2005-09-01

We propose to use high quality X-ray data from the Chandra archive to determine the mass distributions of about 60 clusters of galaxies over the largest possible range of radii. By avoiding unwarranted assumptions, model-independent methods make best use of high quality data. We will employ two model-independent methods. That used by Nulsen & Boehringer (1995) to determine the mass of the Virgo Cluster and a new method, that will be developed as part of the project. The new method will fit a general mass model directly to the X-ray spectra, making best possible use of the fitting errors to constrain mass profiles.

Labelled antibody assays for measuring free triiodothyronine: evaluation and comparison with a labelled analog method

International Nuclear Information System (INIS)

Sapin, R.; Gasser, F.; Schlienger, J.L.; Chambron, J.

1993-01-01

We evaluated analytically and clinically two new one-step labelled antibody assays for measuring free triiodothyronine (FT3): the first, radiolabelled with 125 I, Amerlex-MAB (MAB) from Kodak diagnostic, and the second, labelled with peroxidase, Enzymum-test FT3 (BM) from Boehringer Mannheim adapted for the Boehringer ES 600 analyzer. The clinical results were compared with those obtained with a radiolabelled analog tracer kit, Amerlex-M (M) from Kodak diagnostic. The latter kit is known to give low FT3 results in sera with low albumin concentrations. Analytical performances of the automated method (BM) were better than those obtained with the manual method (MAB): intra-assay reproducibility (CV<3% vs CV about 5%), inter-assay reproducibility (CV<4% vs CV between 4 and 8%) and mean drift (+1.25% vs -4.3%). The detection limit was low for both kits (<1 pmol/l). In the euthyroid reference group (n = 98) we observed a significant difference between outpatient and hospitalized patient FT3 concentrations as measured with the M kit only. Clinical sensitivity for hyperthyroidism (n = 38) was better for the MAB (92%) than for the BM kit (76%). Specificity in euthyroid L-thyroxine (T4) treated patients (n = 26) was good for both kits (MAB: 92%; BM: 88%) . Hypoalbuminemia (n = 8) decreased FT3 results as follows: M, very significantly; BM, significantly; MAB, only slightly. In patients treated with amiodarone (n = 5), a drug known to lower the metabolic conversion of T4 to T3, the increase of the MAB FT3 results contrasted with the decrease of the BM and M results. In conclusion, results of the two new kits were not strongly influenced by hypoalbuminemia. The MAB results showing lack of decrease in patients with non-thyroidal illness without hypoalbuminemia and in amiodarone-treated patients were unexpected

Patient education programmes in obstructive airway disease. The Ingelheim Model for promoting health through patient education.

Science.gov (United States)

Klein, K; Troglauer, K G; Ahlstich, G; Schunke, B; Theissen, E; Voss, H W; Clausen, V

1992-06-01

Chronic obstructive airway diseases (COAD) can be regarded as one of the major health problems needing environmental actions and screening programs for early detection and intensive patient education programs to cope with the needs of tertiary prevention. On the basis of our epidemiological study focused on COAD carried out in FRG (sample size August 1988: 63,000 participants) a patient education program has been developed and evaluated. In cooperation with general practitioners and pneumologists the program has been installed at practice and community level. The need for a patient education program has been assessed during the three years of the PNEUMOBIL-Project. It is not just a matter of cutting costs, but to a large extent a matter of the wellbeing of the patients and of reducing side effects to a minimum. The objective of the project can be split into three dimensions: (1) The cognitive aspect. Here significant lack of knowledge has to be overcome. At this point it has to be stated clearly that at the present time the medical community is not able to solve this problem on their own. (2) The psychomotoric aspect. Here the competent use of medication has to be trained. (3) The emotional aspect. The patient has to be motivated and integrated into the therapeutic process in a way that his compliance contributes significantly. The didactical concept consists of modules that can be used in varying sequences according to the needs of the target audience.(ABSTRACT TRUNCATED AT 250 WORDS)

Patent Pooling for Promoting Access to Antiretroviral Drugs (ARVs) - A Strategic Option for India.

Science.gov (United States)

Satyanarayana, Kanikaram; Srivastava, Sadhana

2010-01-19

The current HIV/AIDS scenario in India is quite grim with an estimated 2.4 million people living with HIV/AIDS (PLHA) in 2008, just behind South Africa and Nigeria. The anti-retroviral drugs (ARVs) remain the main stay of global HIV/AIDS treatment. Over 30 ARVs (single and FDCs) available under six categories viz., NRTIs (nucleoside reverse transcriptase inhibitors), NNRTIs (non-nucleoside reverse transcriptase inhibitors), Protease inhibitors, the new Fusion inhibitors, Entry inhibitors-CCR5 co-receptor antagonists and HIV integrase strand transfer inhibitors. The major originator companies for these ARVs are: Abbott, Boehringer Ingelheim (BI), Bristol-Myers Squibb (BMS), Gilead, GlaxoSmithKline (GSK), Merck, Pfizer, Roche, and Tibotec. Beginning with zidovidine in 1987, all the drugs are available in the developed countries. In India, about 30 ARVs are available as generics manufactured by Aurobindo, Hyderabad, Andhra Pradesh; Cipla Limited, Goa; Emcure Pharmaceuticals, Pune, Maharashtra; Hetero Drugs, Hyderabad, Andhra Pradesh; Macleods Pharmaceuticals, Daman; Matrix Laboratories, Nashik, Maharashtra; Ranbaxy, Sirmour, Himachal Pradesh; and Strides Arcolab, Bangalore, Karnataka. The National AIDS Control Organization (NACO) set up in 1992 by the Govt. of India provides free ARVs to HIV positive patients in India since 2004. The drugs available in India include both single drugs and FDCs covering both first line and second line ARVs. Even while there are claims of stabilization of the disease load, there is still huge gap of those who require ARVs as only about 150,000 PLHA receive the ARVs from the Govt. and other sources. Access to ARVs therefore is still a cause of serious concern ever since India became fully Trade Related Aspects of Intellectual Property Rights (TRIPS)-complaint in 2005. Therefore, the Indian pharmaceutical companies cannot make generics for those for drugs introduced post-2005 due to product patent regime. Other concerns include heat stable

Determination of serum digosin. A comparison between RIA and EIA

International Nuclear Information System (INIS)

Spitz, J.; Braun, J.S.; Schmidt, M.; Krankenhausstiftung Bamberg

1979-01-01

The results of two radioimmunoassays (RIA, precipitating technique), of a homogenous (EMIT) and a heterogenous (ELISA) enzyme immunoassay (EIA) for ascertaining the amounts of digoxin showed a good correlation in precision and a reasonably AK satisfying correlation in the recovery. However, there was a clear discrepancy in the amounts of digoxin concentrate in the serum of patients. Only the RIA of Abbott and the EIA of Boehringer showed no significant differences. Particularly noticeable was the tendency towards lower values in the EMIT-technique as well as its liability to unspecific serum changes (lipaemia etc.), which often made the detection of digoxin impossible. The routine use of this technique appears problematic. The need for establishing one's own laboratory and test-specific therapeutical range is pointed out. (orig.) [de

Determination of serum digosin. A comparison between RIA and EIA

Energy Technology Data Exchange (ETDEWEB)

Spitz, J; Braun, J S; Schmidt, M [Krankenhausstiftung Bamberg (Germany, F.R.). Nuklearmedizinische Abt.; Abt fuer Labormedizin, Krankenhausstiftung Bamberg [Germany, F.R.

1979-12-01

The results of two radioimmunoassays (RIA, precipitating technique), of a homogenous (EMIT) and a heterogenous (ELISA) enzyme immunoassay (EIA) for ascertaining the amounts of digoxin showed a good correlation in precision and a reasonably AK satisfying correlation in the recovery. However, there was a clear discrepancy in the amounts of digoxin concentrate in the serum of patients. Only the RIA of Abbott and the EIA of Boehringer showed no significant differences. Particularly noticeable was the tendency towards lower values in the EMIT-technique as well as its liability to unspecific serum changes (lipaemia etc.), which often made the detection of digoxin impossible. The routine use of this technique appears problematic. The need for establishing one's own laboratory and test-specific therapeutical range is pointed out.

A Maximum Power Point Tracking Control Method of a Photovoltaic Power Generator with Consideration of Dynamic Characteristics of Solar Cells

Science.gov (United States)

Watanabe, Takashi; Yoshida, Toshiya; Ohniwa, Katsumi

This paper discusses a new control strategy for photovoltaic power generation systems with consideration of dynamic characteristics of the photovoltaic cells. The controller estimates internal currents of an equivalent circuit for the cells. This estimated, or the virtual current and the actual voltage of the cells are fed to a conventional Maximum-Power-Point-Tracking (MPPT) controller. Consequently, this MPPT controller still tracks the optimum point even though it is so designed that the seeking speed of the operating point is extremely high. This system may suit for applications, which are installed in rapidly changeable insolation and temperature-conditions e.g. automobiles, trains, and airplanes. The proposed method is verified by experiment with a combination of this estimating function and the modified Boehringer's MPPT algorithm.

Transluminal laser angioplasty

Science.gov (United States)

Otto, Wlodzimierz

1996-03-01

Twenty seven patients with femoral artery occlusion were treated by transluminal Nd:YAG laser angioplasty, in 16 patients the procedure was combined with intraarterial infusion of rTPA (actilyse-Boehringer Ing). In 5 out of 11 patients from the initial group recanalization was not successful. In 16 patients from the rTPA group satisfactory immediate results were achieved in all cases. In long time observations ranging from 9 to 24 months all patients remained free from symptoms, although in 4 of them angiography and Doppler ultrasound examination reveal no flow in the femoral artery. In the remaining 12 patients (75%), the previously occluded artery is patent. No complications of laser angioplasty nor intraarterial infusion of rTPA were noted in this series.

Determination of triiodothyronine in serum by enzyme- and radioimmunoassay

International Nuclear Information System (INIS)

Oellerich, M.; Haindl, H.; Medizinische Hochschule Hannover

1981-01-01

An evaluation of a heterogeneous enzyme immunoassay for determination of triiodothyronine in serum (Enzymun-Test T 3 , Boehringer Mannheim) is presented. The enzyme immunoassay was compared with the laboratory routine radioimmunoassay. The precision of both assays was satisfactory at triiodothyronine concentrations between 1.0 and 8.0 nmol/l (coefficients of variation from day to day 3 from 96-104% and with the radioimmunoassay from 88-111%. A comparison of the results obtained by Enzymun-Test T 3 and the radioimmunoassay in a series of 103 patients showed a good correlation between both methods. L-thyroxine did not cause a relevant cross-reaction in the enzyme immunoassay. About 20 unknown samples can be analyzed in triplicate by Enzymun-Test T 3 within 260 minutes. (orig.) [de

Studies of Interactions of Positive Helium Ions with Small Neutrals at Temperatures Below 50K

Science.gov (United States)

Schauer, Martin Michael

1990-01-01

Interactions of He^+ ions with small neutrals are important because of their fundamental nature and applicability to other areas of research. In the past, very little work has been done on such systems at very low temperatures (T Boehringer and Arnold (1986) and Johnsen, Chen, and Biondi (1980). A new method of detecting the ions in the trap was also developed and implemented. The Fourier Transform Ion Z-resonance (FTIZR) technique took advantage of an induced coherence in the oscillations of the ions in the trap. This method allowed for measurement of faster ion -neutral reactions. This method was demonstrated by studying the non -resonant charge transfer process ^3He ^+{+}^4He{toatop >=ts}^3He{+}^4He^+. These measurements confirmed that the forward reaction is endothermic by about 1.1 meV.

Dabigatran for the prevention of stroke and systemic embolism in atrial fibrillation: A NICE single technology appraisal.

Science.gov (United States)

Faria, Rita; Spackman, Eldon; Burch, Jane; Corbacho, Belen; Todd, Derick; Pepper, Chris; Woolacott, Nerys; Palmer, Stephen

2013-07-01

The National Institute for Health and Clinical Excellence (NICE) invited the manufacturer of dabigatran etexilate (Boehringer Ingelheim Ltd, UK) to submit evidence for the clinical and cost-effectiveness of this drug for the prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation (AF) as part of the NICE single technology appraisal process. The Centre for Reviews and Dissemination and the Centre for Health Economics at the University of York were commissioned to act as the evidence review group (ERG). This article presents a summary of the manufacturer's submission, the ERG report and the subsequent development of NICE guidance for the use of dabigatran within the UK National Health Service. Dabigatran was granted marketing authorisation by the European Medicines Agency for a sequential dosing regimen (DBG sequential), in which patients under 80 years are treated with dabigatran 150 mg twice daily (DBG150) and patients 80 years and over are given dabigatran 110 mg twice daily (DBG110). NICE decisions are bound by the marketing authorisation; therefore, the decision problem faced by the committee was whether the DBG sequential regimen was effective and cost-effective compared with warfarin or aspirin for patients with non-valvular AF and one or more risk factors. The RE-LY trial, a large multi-centre non-inferiority randomised clinical trial, was the primary source of clinical evidence. DBG150 was shown to be non-inferior, and subsequently superior to warfarin, for the primary outcome of all stroke/systemic embolism. DBG110 was found to be non-inferior to warfarin. Results were presented for a post hoc subgroup analysis for patients under and over 80 years of age, where DBG110 showed a statistically significant reduction of haemorrhagic stroke and intracranial haemorrhage in comparison to warfarin in patients over 80 years of age. This post hoc subgroup analysis by age was the basis for the licensed DBG sequential regimen

Extracellular cAMP activates molecular signalling pathways associated with sperm capacitation in bovines.

Science.gov (United States)

Alonso, Carlos Agustín I; Osycka-Salut, Claudia E; Castellano, Luciana; Cesari, Andreína; Di Siervi, Nicolás; Mutto, Adrián; Johannisson, Anders; Morrell, Jane M; Davio, Carlos; Perez-Martinez, Silvina

2017-08-01

-AM (intracellular Ca2+ chelator, 50 μM), EGTA (10 μM) and Probenecid (MRPs general inhibitor, 500 μM). In addition, assays for binding to oviductal epithelial cells and IVF were carried out to test the effect of cAMP compared with other known capacitant agents such as heparin (60 μg/ml) and bicarbonate (40 mM). Straws of frozen bovine semen (20-25 × 106 spermatozoa/ml) were kindly provided by Las Lilas, CIALE and CIAVT Artificial Insemination Centers. The methods used in this work include western blot, immunohistochemistry, flow cytometry, computer-assisted semen analysis, live imaging of Ca2+ and fluorescence scanning. At least three independent assays with bull samples of proven fertility were carried. In the present study, we elucidate the molecular events induced by extracellular cAMP. Our results showed that external cAMP induces sperm capacitation, depending upon the action of PLC. Downstream, this enzyme increased ERK1-2 activation through PKC and elicited a rise in sperm Ca2+ levels (P Investigaciones Científicas y Técnicas [PIP0 496 to S.P.-M.], Agencia Nacional de Promoción Científica y Tecológica [PICT 2012-1195 and PICT2014-2325 to S.P.-M., and PICT 2013-2050 to C.D.], Boehringer Ingelheim Funds, and the Swedish Farmers Foundation [SLF-H13300339 to J.M.]. The authors declare there are no conflicts of interests. © The Author 2017. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com

PDT-induced apoptosis in bladder carcinoma cells

Science.gov (United States)

Bachor, Ruediger; Reich, Ella D.; Kleinschmidt, Klaus; Repassy, Denes; Hautmann, Richard E.

1999-02-01

Photodynamic therapy (PDT) is a highly efficient inducer of apoptosis in EY-28 bladder carcinoma cells, resulting in extensive DNA fragmentation. Bladder carcinoma cells EY-28 (Tumorbank Heidelberg, Germany) were incubated for 1 h with 1 (mu) g AamTPPn/ml or 2 (mu) g AamTPPn/ml. After incubation cells were refed with complete medium and irradiated with 0.75 J/cm2. To identify apoptotic cells, a in situ cell death detection kit POD (Boehringer Mannheim, Germany) was used. The chromatin condensation characteristic to apoptotic cells was detected by transmission electron microscopy. Using 1 (mu) g AamTPPn/ml and 2 (mu) g AamTPPn/ml (9-Acetamido-2,7,12,17- tetra-n-Porpylporphycene), respectively, and irradiation at 0.75 J/cm2, a percentage of 36.9% and 54.7%, respectively, of apoptotic cells was detected.

Comparison of serum copper determination by colorimetric and atomic absorption spectrometric methods in seven different laboratories. The S.F.B.C. (Société Française de Biologie Clinique) Trace Element Group.

Science.gov (United States)

Arnaud, J; Chappuis, P; Zawislak, R; Houot, O; Jaudon, M C; Bienvenu, F; Bureau, F

1993-02-01

An interlaboratory collaborative trial was conducted on the determination of serum copper using two different methods, based on colorimetry (test combination Copper, Boehringer Mannheim, Mannheim, Germany) and flame atomic absorption spectrometry (FAAS). The general performance of the colorimetric method was below that of FAAS, except for sensitivity and linear range, as assessed by detection limit (0.44 versus 1.32 mumol/L) and upper limit of linearity (150 versus 50 mumol/L). The range of the between-run CVs and the recovery of standard additions were, respectively, 2.3-11.9% and 92-127% for the colorimetric method and 1.1-6.0% and 93-101% for the FAAS method. Interferences were minimal with both methods. The two techniques correlated satisfactorily (the correlation coefficients ranged from 0.945-0.970 among laboratories) but the colorimetric assay exhibited slightly higher results than the FAAS method. Each method was transferable among laboratories.

Effect of gamma radiation on levels of adenine nucleotides in erythrocytes of healthy individuals after submaximum physical exertion

International Nuclear Information System (INIS)

Zagorski, T.; Dudek, I.; Mazurek, M.; Berkan, L.; Chmielewski, H.; Kedziora, J.

1994-01-01

The authors studied the effect of gamma radiation and submaximum physical exercise on adenosine-5'-triphosphate (ATP), adenosine-5'-diphosphate (ADP) and adenosine-5'-monophosphate (AMP) contents in erythrocytes of healthy males. Twenty one men aged 20-22 years were examined. They underwent physical exercise at doses of 2 w/kg body weight for 15 min. Erythrocytes were exposed to gamma radiation (500 Gy doses) from 60 Co source. The concentration of adenine nucleotides in erythrocytes was measured by the Boehringer Mannheim tests. The submaximum physical exercise was found to decrease ATP content and to increase ADP and AMP in erythrocytes. Gamma radiation at 500 Gy dose was found to decrease ATP concentration in erythrocytes both at rest and after submaximum exercise and to increase AD content. It was revealed that AMP content increased at rest and decreased after submaximum exercise in irradiated erythrocytes. (author). 20 refs, 1 tab

Brightest Cluster Galaxies in REXCESS Clusters

Science.gov (United States)

Haarsma, Deborah B.; Leisman, L.; Bruch, S.; Donahue, M.

2009-01-01

Most galaxy clusters contain a Brightest Cluster Galaxy (BCG) which is larger than the other cluster ellipticals and has a more extended profile. In the hierarchical model, the BCG forms through many galaxy mergers in the crowded center of the cluster, and thus its properties give insight into the assembly of the cluster as a whole. In this project, we are working with the Representative XMM-Newton Cluster Structure Survey (REXCESS) team (Boehringer et al 2007) to study BCGs in 33 X-ray luminous galaxy clusters, 0.055 < z < 0.183. We are imaging the BCGs in R band at the Southern Observatory for Astrophysical Research (SOAR) in Chile. In this poster, we discuss our methods and give preliminary measurements of the BCG magnitudes, morphology, and stellar mass. We compare these BCG properties with the properties of their host clusters, particularly of the X-ray emitting gas.

Effect of gamma radiation on the concentration of pyruvate and lactate in erythrocytes of healthy men after submaximal physical exercise

International Nuclear Information System (INIS)

Zagorski, T.; Dudek, I.; Berkan, L.; Chmielewski, H.; Kedziora, J.

1993-01-01

The aim of this work was to study the effect of gamma radiation and submaximal physical exercise on the concentration of final products of anaerobic glycolytic pathway in erythrocytes of healthy men. Twenty one men aged 20-22 were examined. They underwent physical exercise at doses of 2 w/kg body weight for 15 min. Erythrocytes were taken in the rest and after physical exercise and were exposed to gamma radiation (500 Gy doses) from 60 Co source. The concentration of pyruvate was estimated by Fermognost tests and the concentration of lactate by Boehringer Mannheim tests. The submaximal physical exercise was found to cause a significantly increased concentration of pyruvate and lactate in the non-radiated and irradiated erythrocytes. Gamma radiation at 500 Gy dose was found to increase concentration of pyruvate in erythrocytes (in the rest and after physical exercise) with simultaneous decrease of lactate concentration. (author). 17 refs, 1 tab

Enzimatik Yöntemle Bazı Sebze ve Meyvelerde Nitrat Düzeyinin Belirlenmesi

Directory of Open Access Journals (Sweden)

Nevzat Artık

2015-02-01

Full Text Available Bu çalışmada Ankara ve çevresinde 2000 yılı içerisinde yetiştirilen bazı taze sebze ve meyve örnekleri materyal olarak kullanıldı. Bu örneklere ait nitrat miktarları enzimatik Boehringer Mannheim GmbH metodu ile belirlendi. Nitrat içeriğinin taze sebzelerde 0.00-3019.41 mg/kg, taze meyvelerde ise 0.00-126.19 mg/kg arasında değiştiği saptandı. Nitrat miktarı, kereviz (3667.40 mg/kg, roka (3019,41 mg/kg ve pazı (2621.79 mg/kg örneklerinde yüksek bulunurken, kavun (0.00-47.93 mg/kgt karpuz (47.21-126.19 mg/kg gibi meyveler ile havuç (0.00-47.71 mg/kg, domates (0.00-71.10 mg/kg gibi meyve benzeri sebzelerde düşük düzeyde bulundu.

Biosensor technology for the detection of illegal drugs I: objectives, preparatory work, and drug enrichment

Science.gov (United States)

Hilpert, Reinhold; Binder, Florian; Grol, Michael; Hallermayer, Klaus; Josel, Hans-Peter; Klein, Christian; Maier, Josef; Oberpriller, Helmut; Ritter, Josef; Scheller, Frieder W.

1994-10-01

In a joint project of Deutsche Aerospace, Boehringer Mannheim and the University of Potsdam portable devices for the detection of illegal drugs, based on biosensor technology, are being developed. The concept enrichment of the drug from the gas phase and detection by immunological means. This publication covers the description of our objectives, preparatory work and results concerning enrichment of drugs from the gas phase. Vapor pressures of cocaine and cannabinoids have been determined. A test gas generator has been constructed which allows for reproducible preparation of cocaine concentrations between 2 ng/l and 2 pg/l. Coupling of a thermodesorption unit with GC/MS has been established for reference analysis. As another analytical tool, an ELISA with a lower detection limit of about 0,5 pg cocaine/assay has been developed. Applying fleece-type adsorbers, enrichment factors for cocaine in the range of 105 have been realized. No significant interference was found with potentially disturbing substances.

Vol. 4 in the series: Site profiles of persistent chlorinated hydrocarbons - cause-oriented monitoring in aquatic media; Pestizide aus der Reihe der persistenten chlorierten Kohlenwasserstoffe in Gewaessern der Rhein-Region - Ergebnisse nachhaltiger Steuerungen von Wirtschaft und Politik. Bd. 4 der Reihe: Standortprofile persistenter chlorierter Kohlenwasserstoffe - ursachenorientiertes Monitoring in aquatischen Medien

Energy Technology Data Exchange (ETDEWEB)

Heinisch, E.; Kettrup, A.; Bergheim, W.; Wenzel, S.

2003-07-01

Evaluating the analytical data of DDT and its metabolites, the isomers of HCH as well as (sometimes) of aldrin and dieldrin in surface water, suspended matter, eels, breams and roaches from the rivers Rhine, Neckar, Kocher, Enz, Main (upto km 360), Weschnitz, Modau, Schwarzbach, Hengstbach, Grundbach, Nidda, Rodau, Kinzig, Werra, Diemel, Lahn, Nahe, Mosel, Sauer, Saar, Ahr, Kyll, Sieg and Laacher See distance profiles (partly from Konstanz till Markermeer) and time series (partly from 1984-2001) were elaborated. The primary data come from about 15 mainly regional investigation departments, the IKSR and the Environmental Specimen Bank. The chemical enterprises in Rheinfelden, Grenzach, Ludwigshafen, Lampertheim, Gernsheim, Darmstadt, Hoechst, Kelsterbach, Offenbach, Ingelheim, Loelsdorf, Leverkusen, Elberfeld, Krefeld-Uerdingen and Huels could partly be made transparent by the course of the sDDT and sHCH values and the profiles of the constituents and isomers, resp., in the distance profiles (especially from the river Rhine) mainly from 1990/92. The corresponding graph for the year 2000 shows that there is no longer a human and ecotoxicological relevance of the compounds to be expected. (orig.)

Effects of empagliflozin on the urinary albumin-to-creatinine ratio in patients with type 2 diabetes and established cardiovascular disease: an exploratory analysis from the EMPA-REG OUTCOME randomised, placebo-controlled trial.

Science.gov (United States)

Cherney, David Z I; Zinman, Bernard; Inzucchi, Silvio E; Koitka-Weber, Audrey; Mattheus, Michaela; von Eynatten, Maximilian; Wanner, Christoph

2017-08-01

and 1338 assigned to empagliflozin) had microalbuminuria, and 769 (11%; 260 assigned to placebo and 509 assigned to empagliflozin) had macroalbuminuria. Median treatment duration was 2·6 years (IQR 2·0-3·4; 136 weeks) and median observation time was 3·1 years (2·2-3·6; 164 weeks). After short-term treatment at week 12, the placebo-adjusted geometric mean ratio of UACR change from baseline with empagliflozin was -7% (95% CI -12 to -2; p=0·013) in patients with normoalbuminuria, -25% (-31 to -19; pratio of relative change from baseline with empagliflozin: -22%, 95% CI -32 to -11; p=0·0003) or macroalbuminuria (-29%, -44 to -10; p=0·0048), but not for patients with baseline normoalbuminuria (1%, -8 to 10; p=0·8911). Patients treated with empagliflozin were more likely to experience a sustained improvement from microalbuminuria to normoalbuminuria (hazard ratio [HR] 1·43, 95% CI 1·22 to 1·67; p<0·0001) or from macroalbuminuria to microalbuminuria or normoalbuminuria (HR 1·82, 1·40 to 2·37; p<0·0001), and less likely to experience a sustained deterioration from normoalbuminuria to microalbuminuria or macroalbuminuria (HR 0·84, 0·74 to 0·95; p=0·0077). The proportions of patients with any adverse events, serious adverse events, and adverse events leading to discontinuation increased with worsening UACR status at baseline, but were similar between treatment groups. The proportion of patients with genital infections was greater with empagliflozin than placebo in all subgroups by UACR status. These results support short-term and long-term benefits of empagliflozin on urinary albumin excretion, irrespective of patients' albuminuria status at baseline. Boehringer Ingelheim & Eli Lilly and Company Diabetes Alliance. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effect of ADRB2 polymorphisms on the efficacy of salmeterol and tiotropium in preventing COPD exacerbations: a prespecified substudy of the POET-COPD trial.

Science.gov (United States)

Rabe, Klaus F; Fabbri, Leonardo M; Israel, Elliot; Kögler, Harald; Riemann, Kathrin; Schmidt, Hendrik; Glaab, Thomas; Vogelmeier, Claus F

2014-01-01

exacerbation risk compared with patients with Arg16Gly (p=0·0130) and Gly16Gly (p=0·0018) genotypes (proportion of patients with at least one exacerbation was 32·3% in Arg16Arg, 39·8% in Arg16Gly, and 42·1% in Gly16Gly). By contrast, exacerbation risk was not modified by polymorphisms at aminoacid 16 in the tiotropium group. The effect of the Arg16Gly polymorphism on treatment response to salmeterol was dependent on the use of inhaled corticosteroids (ICS). In patients untreated with ICS at baseline, Arg16Gly and Arg16Arg genotypes were associated with significantly prolonged time to first exacerbation compared with Gly16Gly (vs Arg16Gly p=0·0164; Arg16Arg p=0·0316; proportion of patients with at least one exacerbation was 28·3% in Arg16Arg, 31·6% in Arg16Gly, and 39·2% in Gly16Gly), whereas in patients on ICS at baseline, only the Arg16Arg genotype was associated with significantly prolonged time to first exacerbation compared with Gly16Gly (p=0·0198; not Arg16Gly p=0·64; proportion of patients with at least one exacerbation was 35·9% in Arg16Arg, 46·7% in Arg16Gly, and 44·8% in Gly16Gly). The respiratory disorders, in particular worsening of COPD, were the most common serious adverse events. Patients with the Arg16Arg genotype had better exacerbation outcomes in response to salmeterol than Gly16Gly and Arg16Gly genotypes, suggesting a potential differential Arg16Gly genotype effect on treatment response to longacting β-agonists (LABAs). However, the use of ADRB2 polymorphisms for predicting LABA treatment response is still limited and further prospective validation will be needed to advance the mechanistic understanding of β-adrenergic polymorphisms and their association with clinical features of COPD. Boehringer Ingelheim and Pfizer. Copyright © 2014 Elsevier Ltd. All rights reserved.

Intravenous Alteplase for Acute Ischemic Stroke in Taiwan: Can We Expand the National Health Insurance's Reimbursement Criteria?

Science.gov (United States)

Hsieh, Cheng-Yang

2017-03-15

individualized selection of stroke patients for appropriate early recanalization therapy to improve their outcomes. Conflict of Interest Disclosure: I received speaker fee from Boehringer Ingelheim for Actilyse® (http://grsp2013.innovarad.tw/2016/07/rt-pa_ forum_hsiehcy_share.html). Acknowledgements: I thank Dr. Chan-Shan Chen for his critical review of this manuscript.

AMCP Partnership Forum: FDAMA Section 114-Improving the Exchange of Health Care Economic Data.

Science.gov (United States)

2016-07-01

harbor by using the consensus recommendations developed during the forum. Speakers, panelists, and attendees focused on 4 terms in Section 114 that remain open to interpretation by companies and enforcement bodies: (1) the scope of HCEI, (2) the scope of "formulary committee or similar entity," (3) the definition of "competent and reliable scientific evidence (CRSE)," and (4) the parameters of how information "directly relates to an approved indication." Based on the forum results, it was recommended that the safe harbor for companies' proactive dissemination of information under Section 114 should include health care decision makers beyond health plan formulary committees, including organizations, or individuals in their role in an organization, who make health care decisions for patient populations. Recommendations also suggested expansion to organizations that evaluate HCEI or develop value frameworks and compendia and individuals in such organizations. Forum participants also recommended that HCEI be truthful, and not misleading, and be based on the expertise of professionals in the relevant area. HCEI must also be developed and disclosed in a transparent, reproducible, and accurate manner. Forum participants also discussed and agreed on the types of information, format, and processes by which managed care pharmacy and other health care decision makers seek to receive HCEI from biopharmaceutical companies. Finally, participants encouraged the FDA, Congress, and other stakeholders to find ways to ensure that patients or their representative organizations have appropriate access to a full range of information about their medications and that information related to the medication pipeline is communicated to appropriate stakeholders in a timely manner. The AMCP Partnership Forum on FDAMA Section 114-Improving the Exchange of Pharmacoeconomic Data and the development of this proceedings document were supported by AbbVie, Amgen, Boehringer Ingelheim Pharmaceuticals, Merck

Clinical effectiveness and patient perspectives of different treatment strategies for tics in children and adolescents with Tourette syndrome: a systematic review and qualitative analysis.

Science.gov (United States)

Hollis, Chris; Pennant, Mary; Cuenca, José; Glazebrook, Cris; Kendall, Tim; Whittington, Craig; Stockton, Sarah; Larsson, Linnéa; Bunton, Penny; Dobson, Suzanne; Groom, Madeleine; Hedderly, Tammy; Heyman, Isobel; Jackson, Georgina M; Jackson, Stephen; Murphy, Tara; Rickards, Hugh; Robertson, Mary; Stern, Jeremy

2016-01-01

in the UK. For part 1, 70 studies were included in the quantitative systematic review. The evidence suggested that for treating tics in children and young people with TS, antipsychotic drugs [standardised mean difference (SMD) -0.74, 95% confidence interval (CI) -1.08 to -0.41; n = 75] and noradrenergic agents [clonidine (Dixarit(®), Boehringer Ingelheim) and guanfacine: SMD -0.72, 95% CI -1.03 to -0.40; n = 164] are effective in the short term. There was little difference among antipsychotics in terms of benefits, but adverse effect profiles do differ. Habit reversal training (HRT)/comprehensive behavioural intervention for tics (CBIT) was also shown to be effective (SMD -0.64, 95% CI -0.99 to -0.29; n = 133). For part 2, 295 parents/carers of children and young people with TS contributed useable survey data. Forty young people with TS participated in in-depth interviews. Four studies were in the qualitative review. Key themes were difficulties in accessing specialist care and behavioural interventions, delay in diagnosis, importance of anxiety and emotional symptoms, lack of provision of information to schools and inadequate information regarding medication and adverse effects. The number and quality of clinical trials is low and this downgrades the strength of the evidence and conclusions. Antipsychotics, noradrenergic agents and HRT/CBIT are effective in reducing tics in children and young people with TS. The balance of benefits and harms favours the most commonly used medications: risperidone (Risperdal(®), Janssen), clonidine and aripiprazole (Abilify(®), Otsuka). Larger and better-conducted trials addressing important clinical uncertainties are required. Further research is needed into widening access to behavioural interventions through use of technology including mobile applications ('apps') and video consultation. This study is registered as PROSPERO CRD42012002059. The National Institute for Health Research Health Technology Assessment

Alpha-2 agonists for sedation of mechanically ventilated adults in intensive care units: a systematic review.

Science.gov (United States)

Cruickshank, Moira; Henderson, Lorna; MacLennan, Graeme; Fraser, Cynthia; Campbell, Marion; Blackwood, Bronagh; Gordon, Anthony; Brazzelli, Miriam

2016-03-01

Care of critically ill patients in intensive care units (ICUs) often requires potentially invasive or uncomfortable procedures, such as mechanical ventilation (MV). Sedation can alleviate pain and discomfort, provide protection from stressful or harmful events, prevent anxiety and promote sleep. Various sedative agents are available for use in ICUs. In the UK, the most commonly used sedatives are propofol (Diprivan(®), AstraZeneca), benzodiazepines [e.g. midazolam (Hypnovel(®), Roche) and lorazepam (Ativan(®), Pfizer)] and alpha-2 adrenergic receptor agonists [e.g. dexmedetomidine (Dexdor(®), Orion Corporation) and clonidine (Catapres(®), Boehringer Ingelheim)]. Sedative agents vary in onset/duration of effects and in their side effects. The pattern of sedation of alpha-2 agonists is quite different from that of other sedatives in that patients can be aroused readily and their cognitive performance on psychometric tests is usually preserved. Moreover, respiratory depression is less frequent after alpha-2 agonists than after other sedative agents. To conduct a systematic review to evaluate the comparative effects of alpha-2 agonists (dexmedetomidine and clonidine) and propofol or benzodiazepines (midazolam and lorazepam) in mechanically ventilated adults admitted to ICUs. We searched major electronic databases (e.g. MEDLINE without revisions, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE and Cochrane Central Register of Controlled Trials) from 1999 to 2014. Evidence was considered from randomised controlled trials (RCTs) comparing dexmedetomidine with clonidine or dexmedetomidine or clonidine with propofol or benzodiazepines such as midazolam, lorazepam and diazepam (Diazemuls(®), Actavis UK Limited). Primary outcomes included mortality, duration of MV, length of ICU stay and adverse events. One reviewer extracted data and assessed the risk of bias of included trials. A second reviewer cross-checked all the data extracted. Random-effects meta

VizieR Online Data Catalog: Cool-core clusters with Chandra obs. (Andrade-Santos+, 2017)

Science.gov (United States)

Andrade-Santos, F.; Jones, C.; Forman, W. R.; Lovisari, L.; Vikhlinin, A.; van Weeren, R. J.; Murray, S. S.; Arnaud, M.; Pratt, G. W.; Democles, J.; Kraft, R.; Mazzotta, P.; Bohringer, H.; Chon, G.; Giacintucci, S.; Clarke, T. E.; Borgani, S.; David, L.; Douspis, M.; Pointecouteau, E.; Dahle, H.; Brown, S.; Aghanim, N.; Rasia, E.

2018-02-01

The main goal of this work is to compare the fraction of cool-core (CC) clusters in X-ray-selected and SZ-selected samples. The first catalog of 189 SZ clusters detected by the Planck mission was released in early 2011 (Planck Collaboration 2011, VIII/88/esz). A Chandra XVP (X-ray Visionary Program--PI: Jones) and HRC Guaranteed Time Observations (PI: Murray) combined to form the Chandra-Planck Legacy Program for Massive Clusters of Galaxies. For each of the 164 ESZ Planck clusters at z<=0.35, we obtained Chandra exposures sufficient to collect at least 10000 source counts. The X-ray sample used here is an extension of the Voevodkin & Vikhlinin (2004ApJ...601..610V) sample. This sample contains 100 clusters and has an effective redshift depth of z<0.3. All have Chandra observations. Of the 100 X-ray-selected clusters, 49 are also in the ESZ sample, and 47 are in the HIFLUGCS (Reiprich & Boehringer 2002ApJ...567..716R) catalog. (2 data files).

Faraday Rotation Measure Study of Cluster Magnetic Fields

Science.gov (United States)

Frankel, M. M.; Clarke, T. E.

2001-12-01

Magnetic fields are thought to play an important role in galaxy cluster evolution. To this end in this study, we looked at polarized radio sources viewed at small impact parameters to the cores of non-cooling flow clusters. By looking at non-cooling flow clusters we hoped to establish what magnetic fields of clusters look like in the absence of the compressed central magnetic fields of the cooling-flow cores. Clarke, Kronberg and Boehringer (2001) examined Faraday rotation measures of radio probes at relatively large impact parameters to the cores of galaxy clusters. The current study is an extension of the Clarke et al. analysis to probe the magnetic fields in the cores of galaxy clusters. We looked at the Faraday rotation of electromagnetic waves from background or imbedded radio galaxies, which were observed with the VLA in A&B arrays. Our results are consistent with previous findings and exhibit a trend towards higher rotation measures and in turn higher magnetic fields at small impact parameters to cluster cores. This research was made possible through funding from the National Science Foundation.

Sunyaev-Zeldovich Predictions for the Atacama Cosmology Telescope

Science.gov (United States)

Menanteau, Felipe; Hughes, J. P.; Jimenez, R.; Barkhouse, W.; Berta, Z.; Hansen, S.; Hernandez-Monteagudo, C.; Kosowsky, A.; Lin, Y. T.; Moodley, K.; Ngeow, C.; Roche, N.; Spergel, D.; Tucker, D.; Verde, L.

2007-05-01

We present predictions for the microwave sky in a low-extinction region centered near RA = 23:00 and Dec = -55:12, which will be surveyed in the coming year at 145 GHz by the Atacama Cosmology Telescope (ACT, PI: Lyman Page) and in the X-ray band by XMM-Newton (PI: Hans Boehringer). The predictions are based on Sunyaev-Zeldovich distortions drawn from optical data collected by the Blanco Cosmology Survey (BCS). We also compare the predictions with X-ray data from the ROSAT All Sky Survey. The BCS (PI: Joe Mohr) is a NOAO large, wide-field survey project that has been awarded 45 nights on the CTIO Blanco 4-meter telescope to image two 50 square-degree patches of the southern sky in four bands (griz). The survey began in 2005 and has completed two (out of three) years of data taking. A preliminary automated image reduction and analysis pipeline for the BCS data is briefly summarized. Financial support was provided by the NSF under the PIRE program (OISE-0530095).

Environment and power; Umwelt und Energie

Energy Technology Data Exchange (ETDEWEB)

Franz, W.; Ramser, H.J.; Stadler, M. (eds.)

2006-07-01

Within the scope of the 35th economic seminar with he title '' Environment and power'' held between 18th and 21st September, 2006, at the monastery Ottobeuren (Federal Republic of Germany), the following lectures were held: (a) Environment and power: introduction into the subject matter (Karl Heinrich Opplaender); (b) Theoretical fundamentals of the sustainability (Wolfgang Buchholz); (c) Ecological fiscal reform and double dividend (Ronnie Schoeb); (d) ''My friend, that is all mere theory'' - Notes to the emission trading (Christoph Boehringer); (e) Environmental policy and locational competition (Michael Rauscher); (f) Dynamical incentives of environment political instruments - a survey (Till Requate); (g) Product differentiation in the presence of environmental concern, network effects and compatibility: The automobile market (Klaus Conrad); (h) The liability right as an instrument of environment policy (Alfred Endres); (i) environment economy and experimental evidence (Joachim Weimann); (j) Market design in the energy economy (Felix Muesgen, Axel Ockenfels); (k) Re-regulation of the liberalized energy markets in Europe (Carl Christian von Weizsaecker).

Dynamic formulation of a top-down and bottom-up merging energy policy model

International Nuclear Information System (INIS)

Frei, Christoph W.; Haldi, P.-A.; Sarlos, G.Gerard

2003-01-01

The impact of energy policy measures is not restricted to the energy system and should therefore be analysed within an economy-wide framework, while keeping the essential details of the energy sector. The aim of this paper is to present new developments in the field of the consistent evaluation of indicators for the sustainability assessment of energy policy measures. Starting from the static concept of Boehringer (Energy Econ. 20 (1998) 233), this paper shows how the complementarity format can be used in computable general equilibrium (CGE) modelling for a dynamic formulation of bottom-up and top-down approach merging models. While a hybrid approach increases the credibility of CGE models in energy policy analysis by replacing the energy sector generic functional forms with a bottom-up activity analysis based on specific technologies, the endogenous formulation of investment decisions makes an explicit description of evolving specific capital stocks and technology mixes possible. Both features are essential when assessing effects of policy measures that may be affected by structural change--which is typically the case in the long-term assessment of energy policy measures

Whole genomic DNA probe for detection of Porphyromonas endodontalis.

Science.gov (United States)

Nissan, R; Makkar, S R; Sela, M N; Stevens, R

2000-04-01

The purpose of the present study was to develop a DNA probe for Porphyromonas endodontalis. Pure cultures of P. endodontalis were grown in TYP medium, in an anaerobic chamber. DNA was extracted from the P. endodontalis and labeled using the Genius System by Boehringer Mannheim. The labeled P. endodontalis DNA was used in dot-blot hybridization reactions with homologous (P. endodontalis) and unrelated bacterial samples. To determine specificity, strains of 40 other oral bacterial species (e.g. Porphyromonas gingivalis, Porphyromonas asaccharolytica, and Prevotella intermedia) were spotted and reacted with the P. endodontalis DNA probe. None of the panel of 40 oral bacteria hybridized with the P. endodontalis probe, whereas the blot of the homologous organism showed a strong positive reaction. To determine the sensitivity of the probe, dilutions of a P. endodontalis suspension of known concentration were blotted onto a nylon membrane and reacted with the probe. The results of our investigation indicate that the DNA probe that we have prepared specifically detects only P. endodontalis and can detect at least 3 x 10(4) cells.

[Effects of balneotherapy on the reactants of acute inflammation phase in ankylosing spondylitis].

Science.gov (United States)

2009-01-01

Ankylosing spondylitis (AS) is a chronic inflammatory disease that affects sacroiliac joints, spinal column and peripheral joints. Beside medication therapy, physical and balneotherapy play an important role in its complex treatment. The aim of the research was to establish serum concentrations of C-reactive protein (CRP), alpha 1-acid glycoprotein (alpha 1-AGP), ceruloplasmine (CP) and erythrocyte sedimentation rate (SE) before and after the balneotherapy in ankylosing spondylitis. The research included 50 AS patients according to the revised New York criteria, of mean age 43 years, who were treated for 14 days on the average at the Clinic for Rheumatology of the Institute "Niska Banja". All the patients received medications and balneotherapy (radioactive oligomineral baths, peloid, massage, kinesitherapy); the serum concentrations of CRP, al-AGP, CP and SE were measured before and after balneotherapy. Serum proteins were determined using original Nor Partigen plates Boehringer. Erythrocyte sedimentation rate was measured by Westergreen method. Balneotherapy was applied individually, intensively or mildly, depending on the AS stage and activity phase. After dosed balneotherapy, a significant decrease in the concentrations of CP (p balneotherapy efficiency in the treatment of ankylosing spondylitis.

Enhanced throughput for infrared automated DNA sequencing

Science.gov (United States)

Middendorf, Lyle R.; Gartside, Bill O.; Humphrey, Pat G.; Roemer, Stephen C.; Sorensen, David R.; Steffens, David L.; Sutter, Scott L.

1995-04-01

Several enhancements have been developed and applied to infrared automated DNA sequencing resulting in significantly higher throughput. A 41 cm sequencing gel (31 cm well- to-read distance) combines high resolution of DNA sequencing fragments with optimized run times yielding two runs per day of 500 bases per sample. A 66 cm sequencing gel (56 cm well-to-read distance) produces sequence read lengths of up to 1000 bases for ds and ss templates using either T7 polymerase or cycle-sequencing protocols. Using a multichannel syringe to load 64 lanes allows 16 samples (compatible with 96-well format) to be visualized for each run. The 41 cm gel configuration allows 16,000 bases per day (16 samples X 500 bases/sample X 2 ten hour runs/day) to be sequenced with the advantages of infrared technology. Enhancements to internal labeling techniques using an infrared-labeled dATP molecule (Boehringer Mannheim GmbH, Penzberg, Germany; Sequenase (U.S. Biochemical) have also been made. The inclusion of glycerol in the sequencing reactions yields greatly improved results for some primer and template combinations. The inclusion of (alpha) -Thio-dNTP's in the labeling reaction increases signal intensity two- to three-fold.

Stability of Seven Days Sample Storage of Erythrocyte’s SOD and Blood’s GPx

Directory of Open Access Journals (Sweden)

Miswar Fattah

2012-12-01

Full Text Available The research was about SOD erythrocyte activities at day 0, 1, 3, 5, and 7 which centrifuged at room temperature (22.5 0C and storage temperature (-80 0C, SOD activities at day-0 which centrifuged at 4 0C, SOD whole blood activities with one day incubated at 2-8 0C and GPx activities at day 0, 1, 3, 5, and 7 with 2–8 0C storage temperature. Laboratory analysis were performed by using reagent from Randox Laboratories, and Hitachi 917 analyzer from Boehringer Mannheim. SOD activities were measured at 505 nm absorbance meanwhile 340 nm absorbance is used to measure GPx. Data was analyzed by using t-test method and showed that SOD activities at day 0, 1, 3, 5, and 7 with room temperature centrifuged had no significant differences. Significant differences are found at day-0 with centrifuged at 4 0C and one day incubated whole blood at 2–8 0C. GPx activities at day- 3 had no significant differences. Significant differences are found at day-0,1, 5 and 7 after storage.

Determination of Several Clinical Parameters of the Blood for the HealthyEvaluation of the Radiation Worker

International Nuclear Information System (INIS)

Yazid, M; Triyono; Aris-Bastianudin

2000-01-01

Determination of the several clinical parameters of the blood for healthyevaluation of the radiation worker has been done. This research was done forarrangement of the medical general check up of the radiation worker toobserve pathological indicator of several body organs. The blood sample wastaken from vena mediana cubiti and analyzed by reagent using standardprocedure from Boehringer Mainheim. That procedure is specific for eachclinical parameters. That clinical parameters concentration was measured byClinicon Photometer 4010. The clinical data of the radiation worker wascompared to the non radiation worker. The measurement results of 501patients, shown that total protein concentrations for all worker are > 8.00g%, the cholesterol concentration of 25 patient are > 260 mg%. The glucoseconcentration for fasting condition of 7 patients are > 200 mg/dl, the ureumconcentration of all patients are 7mg% and the creatinine of 112 patients are > 1.4 mg%. From those results canbe concluded that the most pathological indicator can be identified fromliver, heart and kidney function respectively. From the clinical aspects canbe seen that there is no significant difference between the health ofradiation worker and non radiation worker. (author)

Biosensor technology for the detection of illegal drugs II: antibody development and detection techniques

Science.gov (United States)

Hilpert, Reinhold; Bauer, Christian; Binder, Florian; Grol, Michael; Hallermayer, Klaus; Josel, Hans-Peter; Klein, Christian; Maier, Josef; Makower, Alexander; Oberpriller, Helmut; Ritter, Josef

1994-10-01

In a joint project of Deutsche Aerospace, Boehringer Mannheim and the University of Potsdam portable devices for the detection of illegal drugs, based on biosensor technology, are being developed. The concept enrichment of the drug from the gas phase and detection by immunological means. This publication covers the development of specific antibodies and various detection procedures. Antibodies with a high affinity for cocaine have been developed with the aid of specially synthesized immunogens. A competitive detection procedure with biosensors based on optical grating couplers and applying particulate labels has been established, showing a lower detection limit of 10-10 mol/l for cocaine. Additionally, a combination of a displacement-immunoreactor and an enzymatically amplified electrode was investigated, which at present still suffers from insufficient sensitivity of the immunoreactor. An alternative, fleece-matrix based test procedure, where enrichment and detection steps are integrated in a single unit, is promising in terms of simplicity and sensitivity. A simple swab-test for the detection of cocaine at surfaces has been developed, which has a lower detection limit of about 10 ng and which can be performed within one minute.

The influence of intravenous canrenoate on the determination of digoxin in serum by radio- and enzyme-immunoassay

International Nuclear Information System (INIS)

Rietbrock, N.; Lichey, J.; Borner, K.; Freie Univ. Berlin

1979-01-01

Ten patients were kept on a constant maintenance dose of digoxin. During a baseline period of 6 days, blood samples were taken daily for analysis of digoxin in serum. On the 6th day the maintenance dose of digoxin was withheld and a single intravenous dose of 200mg potassium-canrenoate (AldactoneR) was administered to all patients. Digoxin in serum was determined by a classical radioimmunoassay with 125 I-digoxin and solid phase technique (RIA-NEN) and partly by a heterogenous enzyme-immunoassay (EnzymunR-Digoxin, Boehringer, Mannheim). Results of the radioimmunoassay indicated a rise of apparent serum digoxin levels with an average maximum of 201% of the mean baseline value 30 min after injection of canrenoate and a gradual return to the baseline value within 6 to 10 hours. Contrary to the radioimmunoassay there was no interference when using the enzyme-immunoassay in a subgroup of identical serum samples: serum digoxin levels remained constant throughout the test. Interference of determinations of digoxin in serum by spironolactone and its metabolites appear to be related to two factors: 1. The mode of administration and the amount of interfering drug, 2. the specifity of the digoxin antibody used in the kit. (orig.) [de

Effect of clonidine on 22Na clearance in the rabbit eye

International Nuclear Information System (INIS)

Obenberger, J.; Rozsival, P.; Babicky, A.

1979-01-01

Effects of clonidine on the intraocular hydrodynamics demonstrated themselves as changes of 22 Na-clearance. This test is based on the principle of the intraocular penetration of contactly applied radioisotope and on monitoring the decreasing ocular radioactivity by means of external gamma detectors. The half-times of 22 Na-clearance were significantly prolonged after the local application of 100 μl of 0.5% clonidine (Isoglaucon Boehringer) as compared with the control group. The control animals displayed a half-time of 38.0+-2.7 in comparison with the treated animals measured at intervals of 30 to 90 min and 90 to 150 min after drug instillation, where half-times were significantly prolonged to 49.3+-4.3 and 63.4+-3.8, respectively. In other groups of rabbits 22 Na-clearance was measured on the contralateral eyes of after the intravenous injection of clonidine (25 μg per kg). In both cases the half-times did not significantly differ from the values found in controls. The observed changes of ocular hydrodynamics caused by clonidine probably reflect the inhibitory influence of this drug on aqueous humour production. Results of present investigations point to the decisive role of the local action of clonidine on the eye. (author)

Using heart rate to predict energy expenditure in large domestic dogs.

Science.gov (United States)

Gerth, N; Ruoß, C; Dobenecker, B; Reese, S; Starck, J M

2016-06-01

The aim of this study was to establish heart rate as a measure of energy expenditure in large active kennel dogs (28 ± 3 kg bw). Therefore, the heart rate (HR)-oxygen consumption (V˙O2) relationship was analysed in Foxhound-Boxer-Ingelheim-Labrador cross-breds (FBI dogs) at rest and graded levels of exercise on a treadmill up to 60-65% of maximal aerobic capacity. To test for effects of training, HR and V˙O2 were measured in female dogs, before and after a training period, and after an adjacent training pause to test for reversibility of potential effects. Least squares regression was applied to describe the relationship between HR and V˙O2. The applied training had no statistically significant effect on the HR-V˙O2 regression. A general regression line from all data collected was prepared to establish a general predictive equation for energy expenditure from HR in FBI dogs. The regression equation established in this study enables fast estimation of energy requirement for running activity. The equation is valid for large dogs weighing around 30 kg that run at ground level up to 15 km/h with a heart rate maximum of 190 bpm irrespective of the training level. Journal of Animal Physiology and Animal Nutrition © 2015 Blackwell Verlag GmbH.

Effect of Low Dose Gamma Radiation on Some Biochemical Indicators in the Blood Plasma of Chickens

International Nuclear Information System (INIS)

Kraljevic, P.; Simpraga, M.; Vilic, M.; Miljanic, S.

2001-01-01

Full text: An attempt was made to determine the effect of irradiation of eggs by low dose ionising radiation before incubation on concentration of total protein, glucose and cholesterol in the blood plasma of chickens hatched from irradiated eggs. The eggs of heavy breeding chickens were irradiated by dose of 0.15 Gy gamma radiation ( 60 Co) before incubation. Along with the chickens which were hatched from irradiated eggs, there was the control group of chickens hatched from nonirradiated eggs. All other conditions were the same for the both groups. After hatching, blood samples were taken from the wing vein on days 1, 3, 5, 7, 10, 20, 30 and 42. The concentration of all three parameters was determined spectrophotometrically using Boehringer Mannheim GmbH optimized kits. The concentration of total protein was significantly decreased in the blood plasma of chickens hatched from irradiated eggs on days 3, 7 and 30 and increased only on day 5. The concentration of glucose in the blood plasma was increased in the same chickens on days 1 and 30. The concentration of the cholesterol was decreased in the same chickens on day 7, and increased on day 10. Obtained results indicate that low-dose of gamma radiation has effects on some metabolic processes in the chickens hatched from eggs irradiated before incubation. (author)

Mg,Ca-ATPase activity under irradiation

International Nuclear Information System (INIS)

Ladutin, V.V.; Orlova, V.V.; Lob, P.A.; Gerasiminko, I.V.; Mack, E.I.

2003-01-01

Full text: The influence of different doses irradiation at the Mg,Ca-ATPase activity at the rat brain has been investigated. The analyses were made at the apparatus of LKB and Carl-Ceis-Jena firm with help of reagents of Sigma and Boehringer firm. Rats decapitated after 1, 3, 6, 24 and 48 h after action of irradiation. Dose 0.206 C/kg. Erythrocytes. 1 and 3h after irradiation influence- decrease of Mg,Ca-ATPase activity to 86-87% relatively control level, 24 and 48 h - increase of activity to the control level. Dose 0.312 C/kg. Large hemispheres. 1h - decrease of ATPase activity to 90% relatively control, 3h - increase to control level, 24h - fall to 86%, after 48h small increase to 93% relatively control. Dose 9.287 C/kg. Large hemispheres. 1h - sharp fall of Mg, Ca-ATPase activity to 67 % relatively control, increase of activity to 96% after 3h and sharp fall of activity to 64% 6h after action of irradiation. Dose 9.287 C/kg. Cerebellum. 1h - sharp decrease of ATPase activity to 80%. After 3h -sharp increase to 160% relatively control level and sharp fall of ATPase activity to 47% relatively control after 6h. The mechanism of radiation pathology of active ion transport has been discussed

Systemic thrombolysis of portal vein thrombosis in cirrhotic patients: a pilot study.

Science.gov (United States)

De Santis, Adriano; Moscatelli, Rosanna; Catalano, Carlo; Iannetti, Antonio; Gigliotti, Francesca; Cristofari, Francesca; Trapani, Silvia; Attili, Adolfo F

2010-06-01

Portal vein thrombosis is a frequent complication in liver cirrhosis. Encouraging reports of systemic thrombolysis in non-cirrhotic patients suffering from acute portal vein thrombosis led us to start a pilot study on the efficacy and safety of systemic low dose recombinant tissue plasminogen activator (Actilyse, Boheringer Ingelheim, Florence, Italy). Nine cirrhotic patients (6 males and 3 females) with recent portal vein thrombosis were enrolled. Exclusion criteria were portal cavernomatosis, recent (30 days) surgery, active bleeding, hepatocellular carcinoma and cancer in other sites. All cases were treated for a maximum of 7 days by continuous i.v. infusion of 0.25mg/kg/die of r-tPA plus subcutaneous low molecular weight heparin. Efficacy was evaluated by colour doppler sonography monitoring and confirmed by contrast enhanced computerized tomography. The combined r-tPA/LMWH treatment was well tolerated without clinically significant side effects. Complete resolution of thrombosis occurred in 4 cases, partial regression in 4 and none in 1. Retreatment of a complete recurrence in 1 patient was successful. Variceal pressure dropped from 30.7+/-4.5 mmHg to 21.2+/-6.6 mmHg (p=0.012). Our preliminary data demonstrate that thrombolytic treatment of recent portal vein thrombosis with i.v. r-tPA and LMWH in patients with cirrhosis appears to be safe and effective and can significantly reduce pressure in oesophageal varices. Copyright 2009 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Global and regional effects of potentially modifiable risk factors associated with acute stroke in 32 countries (INTERSTROKE): a case-control study.

Science.gov (United States)

O'Donnell, Martin J; Chin, Siu Lim; Rangarajan, Sumathy; Xavier, Denis; Liu, Lisheng; Zhang, Hongye; Rao-Melacini, Purnima; Zhang, Xiaohe; Pais, Prem; Agapay, Steven; Lopez-Jaramillo, Patricio; Damasceno, Albertino; Langhorne, Peter; McQueen, Matthew J; Rosengren, Annika; Dehghan, Mahshid; Hankey, Graeme J; Dans, Antonio L; Elsayed, Ahmed; Avezum, Alvaro; Mondo, Charles; Diener, Hans-Christoph; Ryglewicz, Danuta; Czlonkowska, Anna; Pogosova, Nana; Weimar, Christian; Iqbal, Romaina; Diaz, Rafael; Yusoff, Khalid; Yusufali, Afzalhussein; Oguz, Aytekin; Wang, Xingyu; Penaherrera, Ernesto; Lanas, Fernando; Ogah, Okechukwu S; Ogunniyi, Adesola; Iversen, Helle K; Malaga, German; Rumboldt, Zvonko; Oveisgharan, Shahram; Al Hussain, Fawaz; Magazi, Daliwonga; Nilanont, Yongchai; Ferguson, John; Pare, Guillaume; Yusuf, Salim

2016-08-20

-2·67 for high or heavy episodic intake vs never or former drinker; 5·8%, 3·4-9·7 for current alcohol drinker vs never or former drinker), and diabetes mellitus (1·16, 1·05-1·30; 3·9%, 1·9-7·6) were associated with all stroke. Collectively, these risk factors accounted for 90·7% of the PAR for all stroke worldwide (91·5% for ischaemic stroke, 87·1% for intracerebral haemorrhage), and were consistent across regions (ranging from 82·7% in Africa to 97·4% in southeast Asia), sex (90·6% in men and in women), and age groups (92·2% in patients aged ≤55 years, 90·0% in patients aged >55 years). We observed regional variations in the importance of individual risk factors, which were related to variations in the magnitude of ORs (rather than direction, which we observed for diet) and differences in prevalence of risk factors among regions. Hypertension was more associated with intracerebral haemorrhage than with ischaemic stroke, whereas current smoking, diabetes, apolipoproteins, and cardiac causes were more associated with ischaemic stroke (pworld, among ethnic groups, in men and women, and in all ages. However, we found important regional variations in the relative importance of most individual risk factors for stroke, which could contribute to worldwide variations in frequency and case-mix of stroke. Our findings support developing both global and region-specific programmes to prevent stroke. Canadian Institutes of Health Research, Heart and Stroke Foundation of Canada, Canadian Stroke Network, Health Research Board Ireland, Swedish Research Council, Swedish Heart and Lung Foundation, The Health & Medical Care Committee of the Regional Executive Board, Region Västra Götaland (Sweden), AstraZeneca, Boehringer Ingelheim (Canada), Pfizer (Canada), MSD, Chest, Heart and Stroke Scotland, and The Stroke Association, with support from The UK Stroke Research Network. Copyright © 2016 Elsevier Ltd. All rights reserved.

Dynamics of ceruloplasmin amd of some blood parameters in piglets suffering from acute radiation disease

International Nuclear Information System (INIS)

Aladzhov, E.

1987-01-01

Changes in oxidase activity of ceruloplasmin (CP) were followed up after treatment with gamma rays of 60 Co with a dose of 4 Ey (dose power 0.68 Ey/min) in the blood serum of male piglets of an average life weight of 18+-3 kg. CP level from 217 E/l raised to 376 E/l on the 16th hour after radiation and on the 16th day decreased to 296 e/l. Moreover, serum copper increased from 25 μmol/l to 42.3 μmol/l on the 16th hour following irradiation but on the 14th day its level dropped to 32.5 μmol/l. Erythrocyte and leucocyte count decreased from 5.83x10 12 /l and 19.94x10 12 /l to 2.47x10 12 /l and 2.0x10 9 /l, respectively. Besides, serum albumin decreased, but α-and β-globulins increased. Examination of ailing piglets showed a paraclinical pattern of an inflammatory process by acute radiation disease. CP as an antioxidant participates in reactions with toxic radiacals on radiation. By the rising of its level on radiation it again was characterized as an acute-phase protein. Serum CP was determined according to the method of Ravin using as substrate P-phenylendiamine dihydrochloride; serum copper - by the test of Boehringer Mannheim; serum proteins were studied electrophoretically on agarose gels using veronal buffer, pH 8.6

Resultados cubanos del programa latinoamericano de educación a pacientes diabéticos no insulinodependientes (PEDNID-LA Results of the Latin American education program for non-insulin dependent patients (PEDNID-LA

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Rosario García González

2001-08-01

Full Text Available Se muestran los resultados cubanos del Estudio Multicéntrico Latinoamericano de Educación en Diabetes para evaluar en forma prospectiva los cambios clínicos, bioquímicos y terapéuticos obtenidos en un grupo de personas con diabetes tipo 2, después de participar en un programa de educación grupal estructurado por la Asociación Latinoamericana de Diabetes y auspiciado por la Federación Internacional de Diabetes, la OMS y sus oficinas panamericanas y patrocinado por los Laboratorios Boehringer Mannheim. El proyecto central incluyó, por cada país, 30 - 40 pacientes no insulinodependientes, obesos y preferentemente de reciente inicio de la enfermedad, según el orden cronológico de su asistencia a la consulta ambulatoria. El programa constó de 4 sesiones teórico-prácticas semanales durante un mes y desarrolladas en forma de discusiones grupales y de un seguimiento trimestral en consulta durante 1 año. Los datos se procesaron según el programa Epi-Info y los resultados se compararon antes y un año después de la intervención educativa. Se encontró aumento significativo (p = 0,001 de los conocimientos sobre la enfermedad y disminución del peso corporal, de los síntomas clásicos de la enfermedad y de la dosis diaria de hipoglucemiantes orales. Los niveles medios de hemoglobina glucosilada, al final del estudio, habían mejorado significativamente (p=0,001, similar a lo encontrado en el resto de los países participantes. Se comprobó el impacto de la intervención educativa en la normalización de indicadores clínicos, bioquímicos y terapéuticos y se confirmó la posibilidad de que el continente pueda implementar programas de educación que refuercen y complementen el cuidado clínicoThe results of the Latin America Multicentered Study on Diabetes Education in Cuba are shown. This study was aimed at prospectively assessing the clinical, biochemical and therapeutical changes reached in a group of persons with type 2 diabetes

Radioimmunoassay of serum digoxin levels in digitalis intoxication

International Nuclear Information System (INIS)

Arendt, G.

1981-01-01

For 101 hospitalized patients where clinical symptoms of a glucosidine intoxication as a consequence of oral digoxin treatment were noted, serum digoxin levels were determined using a RIA kit of the Boehringer company (I-125 tracer, solid phase tube separation technique) on a fasted stomach prior to oral drug administration. An ECG was performed simultaneously and in addition kidney function parameters and electrolyte levels were determined. An anamnesis and clinical examination of the patients were also conducted. Interferences in the RIA method and gastro-intestinal illness resulting in changes in resorption behaviour were excluded. The group of patients showed collectively an average serum digoxin level of 2.9 +- 0.9 ng/ml with a range from 1.8 to 6.8 ng/ml, which was statistically significantly higher than the average value for 101 patients receiving long-term oral medication but without symptoms of glycosidine intoxication. According to the manufacture's specifications for the RIA kit, values > 2.0 ng/ml are considered as toxic, with values between 1.6 and 2.0 ng/mg falling into a ''grey zone''. A correlation was found between toxic serum values with changes in ECG pattern and subjective clinical symptoms of intoxication. A limitation of kidney function was responsible for the high serum glycoside levels in 62% of the patients. It was shown that the differing response of patients towards digitalis medication, above all in the case of long-term therapy, warrants an RIA determination of serum glycoside values in order to adjust the digoxin dose to individual requirements. (orig./MG) [de

Concentration of total proteins in blood plasma of chickens hatched from irradiated eggs with low dose gamma radiation

International Nuclear Information System (INIS)

Vilic, M.; Kraljevic, P.; Miljanic, S.; Simpraga, M.

2005-01-01

It is known that low-dose ionising radiation may have stimulating effects on chickens. Low doses may also cause changes in the concentration of blood plasma total proteins, glucose and cholesterol in chickens. This study investigates the effects of low dose gamma-radiation on the concentration of total proteins in the blood plasma of chickens hatched from eggs irradiated with a dose of 0.15 Gy on incubation days 7 and 19. Results were compared with the control group (chickens hatched from non-irradiated eggs). After hatching, all other conditions were the same for both groups. Blood samples were drawn from the heart, and later from the wing vein on days 1, 3, 5, 7,10, 20, 30 and 42. The concentration of total proteins was determined spectrophotometrically using Boehringer Mannheim GmbH optimised kits. The concentration of total proteins in blood plasma in chickens hatched from eggs irradiated with 0.15 Gy on incubation day 7 showed a statistically significant decrease on the sampling day 3 (P less than 0.05) and 7 (P less than 0.01). The concentration of total proteins in blood plasma in chickens hatched from eggs irradiated with 0.15 Gy on incubation day 19 showed a statistically significant increase only on sampling day 1 (P less than 0.05). These results suggest that exposure of eggs to 0.15 Gy of gamma-radiation on the 7th and 19th day of incubation could produce different effects on the protein metabolism in chickens.(author)

Effects of balneotherapy on the reactants of acute inflammation phase in Ankylosing spondylitis

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Stamenković Bojana

2009-01-01

Full Text Available Introduction. Ankylosing spondylitis (AS is a chronic inflammatory disease that affects sacroiliac joints, spinal column and peripheral joints. Beside medication therapy, physical and balneotherapy play an important role in its complex treatment. Objective. The aim of the research was to establish serum concentrations of C-reactive protein (CRP, α 1-acid glycoprotein (α 1-AGP, ceruloplasmine (CP and erythrocyte sedimentation rate (SE before and after the balneotherapy in ankylosing spondylitis. Methods. The research included 50 AS patients according to the revised New York criteria, of mean age 43 years, who were treated for 14 days on the average at the Clinic for Rheumatology of the Institute 'Niška Banja'. All the patients received medications and balneotherapy (radioactive oligomineral baths, peloid, massage, kinesitherapy; the serum concentrations of CRP, α1-AGP, CP and SE were measured before and after balneotherapy. Serum proteins were determined using original Nor Partigen plates Boehringer. Erythrocyte sedimentation rate was measured by Westergreen method. Balneotherapy was applied individually, intensively or mildly, depending on the AS stage and activity phase. Results. After dosed balneotherapy, a significant decrease in the concentrations of CP (p<0.05, α1-AGP (p<0.01 and CRP (p<0.05 was registered in the serums of AS patients. ESR was not significantly reduced. Conclusion. The research proved that α 1-acid glycoprotein, ceruloplasmine and C-reactive protein represent more sensitive inflammation markers as compared to erythrocyte sedimentation rate. The identification of acute phase reactants is important in the evaluation of dosed balneotherapy efficiency in the treatment of ankylosing spondylitis.

Aminotransferases and Leucine Aminopeptidase Activity in Blood Plasma of Chickens

International Nuclear Information System (INIS)

Kraljevic, P.; Stojevic, Z.; Milinkovic-Tur, S.; Simpraga, M.; Miljanic, S.

1998-01-01

It has been reported that irradiation of mammals by gama-rays cause increase of some enzyme activity in their blood plasma (Miller and Gates 1949; Milch and Albaum 1959; Hughes 1958; Miholjcic et al. 1979). In our previous papers (Kraljevic et al., 1982; Kraljevic and Emanovic 1993) it has been shown that activities of some enzymes in the blood plasma of chickens after an intramuscular injection of radioactive isotope 32 P. In this paper an attempt has been made to investigate the influence of gamma-ray irradiation of the whole body of chickens upon activity of some enzymes in their blood plasma. We also wanted to investigate whether the activity of aspartate-aminotransferase (AST), alanine aminotransferase (ALT) and leucine-aminopeptidase (LAP) may serve as an additional test for functional liver damage in chickens caused by gamma-ray. Fifty day old hybrid male chickens of heavy Jata breeds were irradiated by gamma-ray in the dose of 7,23±0,95 Gy. Blood samples were taken from the wing vein on days 1, 3, 5, 7, 9 and 15 after irradiation. Activity of AST, ALT, and LAP in the blood plasma were determined spectrophotometrically using Boehringer Mannheim GmbH optimized kits. At the end of the experiment all birds were sacrificed and, as well as died birds were photomorphologically and histologically investigated. The obtained results showed decrease of activity of all three enzymes during the whole period of investigation, but significant decrease showed only AST and LAP. It seems that both enzymes may serve as additional test for functional liver damage in chickens by external gamma-rays. (author)

Studies on the comparability of the results from different methods for the radioimmunological determination of digoxin

International Nuclear Information System (INIS)

Dwenger, A.; Trautschold, I.

1978-01-01

Three iodine-125-digoxin radioimmunoassay kits (A Amersham Buchler; B Boehringer Mannheim; C Schwarz Mann/Becton Dickinson) were evaluated with respect to assay quality and comparability of the results. Intra- and interassay variances were calculated for the following types of samples: Three media (a pool serum; b artificial human serum; c buffer solution with albumin and globulin) containing pure digoxin, sera from a pharmacokinetic study, sera with different concentrations of proteins, a hemolytic serum and sera with digitoxin and metabolites of spironolactone. The intra-assay precision depended on the medium of the sample and was higher for samples with identical digoxin concentrations in an identical medium (e.g. CV for 2 μg/l in medium a for kit A: 4.3% for kit B: 7.0%; for kit C: 2.2%) than for samples with identical antigen concentrations in different media (CV for 2 μg/l in media a, b and c for kit A: 6.4%; for kit B: 9.1%; for kit C: 4.3%). The mean recovery in the range 0.5-4 μg/l depended on the kind of medium (a, b or c) and varied for kit A from 84.4% to 100.8%, for kit B from 112.0% to 119.6%, and for kit C from 98.0% to 104.5%. Decreasing serum protein concentrations to less than one half of the physiological concentration gave false negative results for kit A and fals positive results for kit C; for kit B this dependency was not be observed, but there was a decrease of reproducibility. (orig./AJ) [de

Lactato sanguíneo em atletas de judô: relato da experiência de coleta durante combates sucessivos em uma competição oficial

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Alexandre Velí Nunes

1998-02-01

Full Text Available Este artigo é um relato de experiência que faz parte de uma investigação sobre a avaliação de atletas de judô de elite. Seu objetivo é comunicar à comunidade científica a metodologia utilizada, assim como descrever os procedimentos e as dificuldades encontradas na execução dessa metodologia. Nessa experiência, foram feitas 155 coletas de lactato sanguíneo em atletas de judô que participaram de uma competição internacional realizada em Porto Alegre, em julho de 1997. Os atletas da seleção gaúcha de judô, previamente selecionados (n = 21, submeteram-se à coleta de sangue do lóbulo da orelha antes e logo após os combates. Além desses, todos os atletas que participaram das lutas finais das respectivas categorias foram incentivados a submeter-se à coleta ao final do combate. Também foi verificada a FC dos atletas através de palpação radial em 15s, no momento da coleta de sangue. Utilizou-se o analisador de lactato portátil AccusportTM (Boehringer Mannheim Corp., Mannheim, Alemanha com Test Strips BM Lactate e caneta com microlancetas descartáveis da mesma marca. Constatou-se que a utilização da metodologia e do equipamento acima descritos é apropriada para esse tipo de população e situação, e que os resultados encontrados podem contribuir para a avaliação da intensidade do esforço desses atletas.

The dynamics of blood biochemical parameters in cosmonauts during long-term space flights

Science.gov (United States)

Markin, Andrei; Strogonova, Lubov; Balashov, Oleg; Polyakov, Valery; Tigner, Timoty

Most of the previously obtained data on cosmonauts' metabolic state concerned certain stages of the postflight period. In this connection, all conclusions, as to metabolism peculiarities during the space flight, were to a large extent probabilistic. The purpose of this work was study of metabolism characteristics in cosmonauts directly during long-term space flights. In the capillary blood samples taken from a finger, by "Reflotron IV" biochemical analyzer, "Boehringer Mannheim" GmbH, Germany, adapted to weightlessness environments, the activity of GOT, GPT, CK, gamma-GT, total and pancreatic amylase, as well as concentration of hemoglobin, glucose, total bilirubin, uric acid, urea, creatinine, total, HDL- and LDL cholesterol, triglycerides had been determined. HDL/LDL-cholesterol ratio also was computed. The crewmembers of 6 main missions to the "Mir" orbital station, a total of 17 cosmonauts, were examined. Biochemical tests were carryed out 30-60 days before lounch, and in the flights different stages between the 25-th and the 423-rd days of flights. In cosmonauts during space flight had been found tendency to increase, in compare with basal level, GOT, GPT, total amylase activity, glucose and total cholesterol concentration, and tendency to decrease of CK activity, hemoglobin, HDL-cholesterol concentration, and HDL/LDL — cholesterol ratio. Some definite trends in variations of other determined biochemical parameters had not been found. The same trends of mentioned biochemical parameters alterations observed in majority of tested cosmonauts, allows to suppose existence of connection between noted metabolic alterations with influence of space flight conditions upon cosmonaut's body. Variations of other studied blood biochemical parameters depends on, probably, pure individual causes.

Transferases activity in blood plasma of chickens hatched from eggs irradiated during incubation by low dose gamma rays

International Nuclear Information System (INIS)

Kraljevic, P.; Vilic, M.; Miljanic, S.; Simpraga, M.

2005-01-01

In our earlier studies chickens hatched from eggs irradiated with 0.15 Gy gamma rays before incubation showed a significantly higher growth than controls during the fattening period (1-42 days). The activity of aspartate-aminotransferase (AST), alanine-aminotransferase (ALT) and plasma glucose in the same chickens were also significantly higher. These results suggested that low-dose gamma-radiation stimulated certain metabolic processes in chickens hatched from eggs irradiated before incubation. The goal of this study was to determine the effects of low-dose ionising radiation on AST and ALT activity in the blood plasma of chickens hatched from eggs irradiated during incubation. The eggs of heavy breeding chickens (Avian, line 34) were exposed to 0.15 Gy of gamma-radiation (6 0C o) on the seventh day of incubation, i.e. at the time when the organogenesis in chickens is completed. The control group of chickens hatched from non-irradiated eggs. All other conditions were the same for both groups. After hatching, blood samples were taken from the wing vein on days 1, 3, 5, 7, 10, 20, 32 and 42. The activity of both enzymes was determined spectrophotometrically using Boehringer Mannheim GmbH optimised kits. On day 10, AST and ALT activity were significantly higher in the blood plasma of chickens hatched from irradiated eggs, but it significantly dropped for both enzymes on day 20. Our results indicate that exposure of eggs to low-dose gamma-radiation on the seventh day of incubation affects AST and ALT activity in the blood plasma of chickens hatched from irradiated eggs. However, this effect is somewhat different from the effects of egg exposure to low-dose gamma radiation before incubation.(author)

The L_X-M relation of Clusters of Galaxies

Energy Technology Data Exchange (ETDEWEB)

Rykoff, E.S.; Evrard, A.E.; McKay, T.A.; Becker, M.R.; Johnston, D.E.; Koester, B.P.; Nord, B.; Rozo, E.; Sheldon, E.S.; Stanek, R.; Wechsler, R.H.

2008-05-16

We present a new measurement of the scaling relation between X-ray luminosity and total mass for 17,000 galaxy clusters in the maxBCG cluster sample. Stacking sub-samples within fixed ranges of optical richness, N200, we measure the mean 0.1-2.4 keV X-ray luminosity, , from the ROSAT All-Sky Survey. The mean mass, , is measured from weak gravitational lensing of SDSS background galaxies (Johnston et al. 2007). For 9 {le} N{sub 200} < 200, the data are well fit by a power-law, /10{sup 42} h{sup -2} ergs{sup -1} = (12.6{sub -1.3}{sup +1.4}(stat) {+-} 1.6 (sys)) (/10{sup 14} h{sup -1} M{sub {circle_dot}}){sup 1.65{+-}0.13}. The slope agrees to within 10% with previous estimates based on X-ray selected catalogs, implying that the covariance in L{sub X} and N{sub 200} at fixed halo mass is not large. The luminosity intercept is 30%, or 2{sigma}, lower than determined from the X-ray flux-limited sample of Reiprich & Boehringer (2002), assuming hydrostatic equilibrium. This slight difference could arise from a combination of Malmquist bias and/or systematic error in hydrostatic mass estimates, both of which are expected. The intercept agrees with that derived by Stanek et al. (2006) using a model for the statistical correspondence between clusters and halos in a WMAP3 cosmology with power spectrum normalization {sigma}{sub 8} = 0.85. Similar exercises applied to future data sets will allow constraints on the covariance among optical and hot gas properties of clusters at fixed mass.

Urinary secretory IgA after nutritional rehabilitation

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M.R. Teodósio

1999-04-01

Full Text Available We studied the secretory IgA (sIgA response of the mucosal urinary tract of malnourished children before and after nutritional rehabilitation. sIgA concentration (mg/l was determined by ELISA in 187 children aged 3 months to 5 years. The children, who frequented a day care center, were divided into four groups, according to nutritional status: 57 were eutrophic, 49 were undergrown, 57 were moderately malnourished and 24 were severely malnourished. In addition, dip slide (Urotube, Roche and dip-stick (Combur 9-Boehringer tests showed that children had no bacteriuria or any other urinary abnormalities. Plasma albumin concentration (g/dl was significantly lower (P<0.005 in the severely malnourished group (mean 3.0 ± 0.3 SD than in the eutrophic group (mean 4.0 ± 0.5 SD. When each nutritional state was analyzed, no significant differences in the sIgA were found between the 0 |-| 1 and 1 -| 5 year age range. In the moderately and severely malnourished groups, sIgA (0.36 and 0.45, respectively was significantly lower than in the eutrophic (0.69 and undergrown (0.75 groups. Ninety-five children were included in the 8-month follow-up study; 30 children were excluded from the follow-up because 4 had bacteriuria, 11 had leukocyturia, 8 had proteinuria and 7 had hematuria. Among the malnourished children, 40% showed nutritional improvement (P<0.05 and significantly increased sIgA as compared to reference values for the eutrophic and undergrown groups. These data suggest that malnourished children have a significantly lower urinary sIgA than eutrophic children. After nutritional rehabilitation, they develop local immunity with a significant increase in sIgA.

Concentration of Proteins and Protein Fractions in Blood Plasma of Chickens Hatched from Eggs Irradiated with Low Level Gamma Rays

International Nuclear Information System (INIS)

Kraljevic, P.; Vilic, M.; Simpraga, M.; Matisic, D.; Miljanic, S.

2011-01-01

In literature there are many results which have shown that low dose radiation can stimulate many physiological processes of living organism. In our earlier paper it was shown that low dose of gamma radiation has a stimulative effect upon metabolic process in chickens hatched from eggs irradiated before incubation. This was proved by increase of body weight gain and body weight, as well as by increase of two enzymes activities in blood plasma (aspartate aminotransferase and alanine aminotransferase) which play an important role in protein metabolism. Therefore, an attempt was made to determine the effect of eggs irradiation by low dose gamma rays upon concentration of total proteins and protein fractions in the blood plasma of chickens hatched from irradiated eggs. The eggs of heavy breed chickens were irradiated with a dose of 0.15 Gy gamma radiation (60Co) before incubation. Along with the chickens which were hatched from irradiated eggs, there was a control group of chickens hatched from nonirradiated eggs. All other conditions were the same for both groups of chickens. Blood samples were taken from the right jugular vein on the 1 s t and 3 r d day, or from the wing vein on days 5 and 7 after hatching. The total proteins concentration in the blood plasma was determined by the biuret method using Boehringer Mannheim GmbH optimized kits. The protein fractions (albumin, α 1 -globulin, α 2 -globulin, β- and γ-globulins) were estimated electrophoretically on Cellogel strips. The total proteins concentration was significantly decreased in blood plasma of chickens hatched from irradiated eggs on days 3 (P t h day (P 2 -globulin was decreased on days 1 (P t h day of life. Obtained results indicate that low dose of gamma radiation has mostly inhibitory effect upon concentration of total proteins and protein fractions in the blood plasma of chickens hatched from irradiated eggs before incubation. (author)

Estudo comparativo do manuseamento dos vários dispositivos de inalação utilizados em Portugal** Trabalho concotTente ao Premia Thome Villar/Boehringer Ingelhcim, 1999 (Secção A

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António Morais

2001-01-01

Full Text Available RESUMO: A terapêutica inalatória tern urn papel fundamental no tratamento das doençs respiratórias. Esta importância deve-se à administração directa do fármaco na area em tratamento, o que leva à necessidade de menores doses de farmaco, com menores efeitos secundários, um mais rápido início de acção e uma maior eficácia terapêutica do mesmo. Quando prescrevemos urn inalador, temos que ter em conta as varias caracteristicas quer do farmaco, quer do inalador, nomeadamente a facilidade com que este ultimo pode ser manuseado.O objectivo deste estudo foi o de pesquisar o grau de dificuldade exigido na realização da manobra inalat6ria dos vários inaladores existentes em Portugal, alem das preferencias em relação aos mesmos por parte da população estudada. Uma população de 80 individuos, com media de idades de 45 anos (24-78, sendo 49 (61,2% homens e 31 (38,8% mulhercs, sem anterior contacto com inaladores, apos a aprcsentação de 6 inaladores frequentementc utilizados em Portugal (MDI e os DPI's Rotahaler, Turbohaler, Diskus, Diskhaler e Aerolizer, escolhiam qual delcs eque achavam ser esteticamentc o mais c o menos atractivo. Seguidamente cram instruldos sobre a maneira correcta de inalar com os aparelhos de inalação incluidos no estudo. Apos a instrução de cada inalador, tinham 3 tentativas para inalar de forma correcta com o mcsmo. Após as manobras inalat6rias com os 6 inaladorcs, os individuos CSCOlhiam qual deles e que tinha sido o mais fáicil co mais difícil de manusear, e em caso de terem de efectuar terapêutica inalatória qual deles é que escolheriam é qual deles é que rejeitariam.O Disk us - 22 (27,5 % e o Aerolizer - 21 (26,2 % foram considerados os mais atractivos enquanto o Turbuhaler foi considcrado o menos atraente-18 (22,5 %. 0 Turbuhaler- 25 (31,2%, foi considerado como o mais facil de ser manuseado versus o MDI - 36 (45% considerado o mais diflcil. O Turbuhaler seguido pelo Diskus foram aqueles que se revelaram de mais facil manuseamento, enquanto o MDI foi o que provocou mais dificuldades, com 38 (47,5% dos individuos a serem capazes de o manusear de forma correcta nas 3 tentativas dadas. 0 Turbuhaler - 25 (31,2% foi o inalador mais escolhido, seguido pelo Disk us - 23 (28,7%, sendo o MDI- 38 (47,5 % o inalador mais rejeitado. Em relação a algumas características da população, verificou-se que o Turbulzaler foi mais escolhido pelo sexo feminino e pelo grupo com estudos universitarios, enquanto que o Diskus foi o mais preferido pelos homens e pelos individuos com menores habilitações litenirias.Os autores concluem que o Turbuhaler se apresenta como o inalador de mais facil manuseamento, ao contn1rio do MDI que foi o que se associou a maiores dificuldades na realização da sua manobra inalat6ria. A escolha do inalador foi determinada especialmente pelo grau de facilidade na realização·da manobra inalat6ria. Existcm diferen.;as na prefcrencia dos inaladores por parte dos indivlduos que participaram nestc estudo tendo em conta algumas das suas caracteristicas, nomeadamente o scxo e as habilitações literarias.REV PORT PNEU 2001; VII (NōESPECIAT/BRASlL: 9-24 ABSTRACT: The inhalation therapy has a fundamental role in the treatment of respiratory diseases. This importance is related to several facts: through this therapy, the drug has a direct action in the area under treatment, smaller amounts of the drug are needed, there are less side effects and there is a faster efficient result at beginning of the drug's action. When prescribing an inhaler, the physician has to consider several variables, namely their ability to be easily handled.The aim of this work is the study of the individual adjustment to each of the inhalation devices available in Portugal, the difficulty degree detected in the individual use of devices and their preferences about them.The population was constituted by eighty individuals, 49 (61,2% males and 31 (38,8% females, with ages ranging from 24 to 78 (mean 45 years, who never had contact with an inhaler before. After the presentation of the studied inhalers (MDI and the DPI's Rotahaler, Turbulzaler, Diskus, Diskhaler e Aerolizer, each of the individuals chooses the most and the least attractive. Then they were instructed how to handle each of the inhalers properly. They had three chances to handle each inhaler successfully after instruction. After the inhaling act, each individual had to select which inhaler were the easiest and the most difficult to handle and which one he/she would choose and would reject.The Diskus - 22 (27,5 % and Aerolizer - 21 (26,2 % were considered the most attractive; the Turbuhaler - 18 (22,5% was considered the least attractive. The Turbuhaler followed by Diskus were the easiest to handle; on the contrary the MDI was the most difficult to handle. The Turbuhaler - 25 (31,2% was elected as the easiest to handle; the MDI- 36 (45% was selected as the most difficult to use. The Turbuhaler -25 (31,2% followed by Diskus - 23 (28,7% was the inhaler most chosen and the MDI - 38 (47,5% was the most rejected. The study of the inhalers preferences according to some population characteristics showed us that the Turbuhaler is chosen preferentially by females and individuals with university grade while Diskus is chosen predominantly by males and individuals with less academic qualifications.The authors conclude that the Turbuhaler was the easiest to usc and the MDI was the most difficult. The choice of the inhaler was determined mainly by the easiness of the inhalation. There are some differences related to the inhalers preferences according to some population characteristics, namely sex and academic qualilications.REV PORT PNEU 2001; VII (:Nō ESPECIAI/BRASIL: 9-24 Palavras-chave: inaladorcs, manuscamento, manobra inalatória, prefcrências, Key-words: inhalers, handling, inhaling, preferences

Effect of Low Dose Gamma Radiation Upon Phosphatase Activity in Blood Plasma of Chicken Hatched from Eggs Irradiated on the Seventh Day of Incubation

International Nuclear Information System (INIS)

Kraljevic, P.; Vilic, M.; Miljanic, S.; Simpraga, M.

2008-01-01

In our earlier studies chickens hatched from eggs irradiated with 0.15 Gy gamma rays before incubation showed a significantly higher growth than controls during the fattening period (1-42 days). The activity of aspartate-aminotransferase (AST), alanine-aminotransferase (ALT), acid phosphatase (ACP) and plasma glucose in the same chickens were also significantly higher. These results suggested that low-dose gamma-radiation stimulated certain metabolic processes in chickens hatched from eggs irradiated before incubation. Investigating the effect of low dose gamma radiation upon transferases activity in blood plasma of chickens hatched from eggs irradiated on the 7th day of incubation, i.e. in the time when organogenesis is completely finished, we found that on day 10, AST and ALT activity was significantly higher in the blood plasma of those chickens, whereas it significantly dropped for both enzymes on day 20. This time the goal of study was to determine the effect of low-dose gamma radiation on ACP and alkaline phosphatase (ALP) activity in the blood plasma of chickens hatched from eggs irradiated on the 7th day of incubation. The eggs of heavy breeding chickens (Avian, line 34) were exposed to 0.15 Gy of gamma radiation (60Co) on the seventh day of incubation. The control group included chickens hatched from non-irradiated eggs. All other conditions were the same for both groups. After hatching, blood samples were taken from the wing vein on days 1, 3, 5, 7, 10, 20, 32 and 42. The activity of both enzymes was determined spectrophotometrically using Boehringer Mannheim GmbH optimised kits. ACP activity was significantly lower in the blood plasma of chickens hatched from irradiated eggs on day 3 (P<0,01), 5 (P<0,05) and 10 (P<0,05). Throughout the experimental period ALP activity did not statistically significantly change. Our results indicate that exposure of eggs to low-dose gamma radiation on the seventh day of incubation reduces ACP activity in the blood plasma

Perfíl lipídico en una comunidad de Calarcá, Colombia

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Andrea Arias

1997-09-01

Full Text Available Las enfermedades cardiovasculares (EC, en general, y la cardiopatía isquémica, en particular, constituyen un importante problema de salud pública por su alta mortalidad, morbilidad, costos médico-hospitalarios e impacto laboral por su poder incapacitante. Estas patologías constituyen la primera causa de muerte en la población adulta en Colombia después de las muertes por violencia. Dado que, en nuestro país, no se han determinado con exactitud parámetros propios del comportamiento de los Iípidos sanguíneos en la población, se hace necesaria su caracterización para que se puedan establecer politicas de intervención para la prevención y control de EC, tanto a nivel individual como poblacional. Este trabajo intenta contribuir al estudio poblacional del comportamiento de los niveles de Iípidos en poblaciones colombianas. Se determinaron los niveles de colesterol total (CT, colesterol en lipoproteínas de baja densidad (C-LDL, colesterol en lipoproteínas alta densidad (C-HDL y triglicéridos (TG, en sueros de 71 varones escogidos al azar con edades comprendidas entre 20 y 70 años. Se utilizaron métodos enzimáticos con reactivos Boehringer Manheinn. Los resultados de este estudio muestran que 21,1% de la población presenta colesterol mayor de 200 mgldL, 66,2% C-HDL menor de 35 mg/dL, 5,6% presentan C-LDL mayor de 150 mg/dL y 36,6 presenta TG mayor de 150 mg/dL. Estos datos indican que, para esta población, el factor protector para las EC (C-HDL está seriamente afectado y, además, presenta una zipertrigliceridemia aislada. Se encontró una alta incidencia sobre los valores del perfil lipídico de los factores de riesgo no lipídicos como son el índice de masa corporal, el fumar, los antecedentes familiares y la edad. Los resultados obtenidos en el presente estudio se semejan a los encontrados para poblaciones de países en desarrollo y los encontrados en estudios de poblaciones colombianas, por tal motivo deben iniciarse

A 90 minute soccer match decreases triglyceride and low density lipoprotein but not high-density lipoprotein and cholesterol levels

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Nader - Rahnama

2009-11-01

Full Text Available

• BACKGROUND: The association between the lipid profiles level and the incidence and severity of coronary heart disease (CHD is very pronounced in epidemiological studies, and an inverse relation between physical fitness and the incidence of coronary heart disease has been observed in many studies. The aim of this study was to investigate the impact of a soccer match on lipid parameters of professional soccer players.
• METHODS: Twenty two professional soccer players participated in the study. Blood (10ml for determination of lipid profiles was obtained at rest and immediately after a 90 minute soccer match. Lipid parameters were measured using Boehringer Mannheim kits and Clinilab and BioMerieux analyser.
• RESULTS: The results of this study showed that the triglyceride was significantly higher before the match than afterwards (159.09 ± 58.2 vs. 88.63 ± 34.1 mg/dl, p < 0.001, whereas the low-density lipoprotein (LDL was lower before the match than after it (98.04 ± 28.9 vs. 112.31 ± 30.5 mg/dl. Moreover, there were no significant differences in cholesterol concentration (171.4 ± 30.28 mg/dl vs. 173.18 ± 32.75 mg/dl and high-density lipoprotein (HDL concentration (34.04 ± 5.58 mg/dl vs. 34.4 ± 4.6 mg/dl between before and after the match.
• CONCLUSIONS: Although the soccer competitive match has no favourable acute effect on lipid

• Title of paper: the induction of P-53 independent programmed cell death (apoptosis) with ionizing radiation and 5-fluorouracil (5-FU) in the HT-29 human colon carcinoma cell line

  International Nuclear Information System (INIS)

  Blackstock, A. Wm.; Gill, Misha; Hess, Suzanne M.; Fisher, Robert W.; Leadon, Steven A.; Tepper, Joel E.

  1996-01-01

  Purpose/Objective: The role of programmed cell death (apoptosis) as a cellular response to cancer therapy such as radiation or chemotherapy is the subject of much study, and manipulation of the apoptotic response in tumor cells may be valuable in the treatment of a variety of cancers. Both p53 dependent and independent apoptotic pathways have been identified; p53 is mutated in at least 50 % of human cancers and a majority of radiation resistant tumors contain p53 mutations. This study is designed to examine the induction of programmed cell death in a human colon carcinoma cell line that possesses two mutated p53 alleles. Ionizing radiation alone, or in combination with the chemotherapeutic drug 5-fluorouracil (5-FU), were used to elicit the apoptotic response. This study will focus on whether these treatments can induce a significant apoptotic response in cells that have mutated p53 alleles. Materials and Methods: HT-29 cells were assessed for clonogenic survival after being plated at a variety of densities, and treated with single graded doses of radiation (0, 1, 2, 4, 6, 8, 10 Gy) either alone or immediately prior to a 24 hour exposure to 5-FU (2 ug/ml). The extent of radiation and 5-FU-induced apoptosis was determined in the HT-29 cell line after single doses of 0, 2, 5, and 10 Gy either alone or immediately prior to a 24 hour incubation in 5-FU (2 ug/ml). Three separate assays were used to evaluate the apoptotic response. Cells undergoing apoptosis undergo gross morphological changes including a condensation of chromatin, membrane blebbing, and an eventual release of membrane bound cytoplasmic fragments. Hematoxylin and eosin staining were used to visualize some of these morphological changes. Another characteristic of the apoptotic response is the activation of an endonuclease that cleaves DNA into specific fragments. Accordingly, an ELISA cell death assay (Boehringer Mannheim, Indianapolis IN) was used to quantitate cytoplasmic histone-associated DNA

• ROSAT Discovers Unique, Distant Cluster of Galaxies

  Science.gov (United States)

  1995-06-01

  measured (by obtaining spectra of the arcs and measuring their redshift). The masses of galaxy clusters are important for the determination, for instance of the mean density and distribution of matter in the universe. This is because these clusters are the most massive, clearly defined objects known and as such trace these parameters in the universe on very large scales. Another possibility to derive the cluster mass is offered by X-ray observations, because the distribution of the hot, X-ray emitting gas traces the gravitational field of the cluster. Recently, in some clusters there has been a discrepancy between the mass determined in this way and that found from gravitational lensing effects. The team of astronomers now hopes that follow-up X-ray observations of RXJ1347.5-1145 will help to solve this puzzle. Moreover, the combination of extremely high X-ray brightness and the possibility to perform a rather accurate mass determination by the gravitational lensing effect makes this particular cluster a truly unique object. In view of the exceptional X-ray brightness, a very high mass is expected. The exact determination will be possible, as soon as spectra have been obtained of the two arcs. Contrary to what is the case in other clusters, this will not be so difficult, due to their unusual brightness and their ideal geometrical configuration. [1] This is a joint Press Release of ESO and the Max-Planck-Society. It is accompanied by a B/W photo. [2] The investigation described in this Press Release is the subject of a Letter to the Editor which will soon appear in the European journal Astronomy & Astrophysics, with the following authors: Sabine Schindler (Max-Planck-Institut fuer Extraterrestrische Physik and Max-Planck-Institut fuer Astrophysik, Garching, Germany), Hans Boehringer, Doris M. Neumann and Ulrich G. Briel (Max-Planck-Institut fuer Extraterrestrische Physik, Garching, Germany), Luigi Guzzo (Osservatorio Astronomico di Brera, Merate, Italy), Guido Chincarini