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2. Identification of regulatory variants associated with genetic susceptibility to meningococcal disease

Author

Borghini, Lisa, Png, Eileen, Binder, Alexander, Wright, Victoria J, Pinnock, Ellie, de Groot, Ronald, Hazelzet, Jan, Emonts, Marieke, Van der Flier, Michiel, Schlapbach, Luregn J, Anderson, Suzanne, Secka, Fatou, Salas, Antonio, Fink, Colin, Carrol, Enitan D, Pollard, Andrew J, Coin, Lachlan J, Kuijpers, Taco W, Martinon-Torres, Federico, Zenz, Werner, Levin, Michael, Hibberd, Martin L, Davila, Sonia, Gormley, Stuart, Hamilton, Shea, Herberg, Jethro, Hourmat, Bernardo, Hoggart, Clive, Kaforou, Myrsini, Sancho-Shimizu, Vanessa, Abdulla, Amina, Agapow, Paul, Bartlett, Maeve, Bellos, Evangelos, Eleftherohorinou, Hariklia, Galassini, Rachel, Inwald, David, Mashbat, Meg, Menikou, Stefanie, Mustafa, Sobia, Nadel, Simon, Rahman, Rahmeen, Thakker, Clare, Bokhandi, S, Power, Sue, Barham, Heather, Pathan, N, Ridout, Jenna, White, Deborah, Thurston, Sarah, Faust, S, Patel, S, McCorkell, Jenni, Davies, P, Cratev, Lindsey, Navarra, Helen, Carter, Stephanie, Ramaiah, R, Patel, Rekha, Tuffrey, Catherine, Gribbin, Andrew, McCready, Sharon, Peters, Mark, Hardy, Katie, Standing, Fran, O'Neill, Lauren, Abelake, Eugenia, Deep, Akash, Nsirim, Eniola, Willis, Louise, Young, Zoe, Royad, C, White, Sonia, Fortune, PM, Hudnott, Phil, Alvez Gonzalez, Fernando, Barral-Arca, Ruth, Cebey-Lopez, Miriam, Jose Curras-Tuala, Maria, Garcia, Natalia, Garcia Vicente, Luisa, Gomez-Carballa, Alberto, Gomez Rial, Jose, Grela Beiroa, Andrea, Justicia Grande, Antonio, Leborans Iglesias, Pilar, Martinez Santos, Alba Elena, Martinon-Torres, Nazareth, Martinon Sanchez, Jose Maria, Mosquera Perez, Belen, Obando Pacheco, Pablo, Pardo-Seco, Jacobo, Pischedda, Sara, Rivero Calle, Irene, Rodriguez-Tenreiro, Carmen, Redondo-Collazo, Lorenzo, Seren Fernandez, Sonia, Porto Silva, Maria del Sol, Vega, Ana, Beatriz Reyes, Susana, Leon Leon, Maria Cruz, Navarro Mingorance, Alvaro, Gabaldo Barrios, Xavier, Onate Vergara, Eider, Concha Torre, Andres, Vivanco, Ana, Fernandez, Reyes, Gimenez Sanchez, Francisco, Sanchez Forte, Miguel, Rojo, Pablo, Ruiz Contreras, J, Palacios, Alba, Navarro, Marisa, Alvarez Alvarez, Cristina, Jose Lozano, Maria, Carreras, Eduardo, Brio Sanagustin, Sonia, Neth, Olaf, Martinez Padilla, Ma del Carmen, Prieto Tato, Luis Manuel, Guillen, Sara, Fernandez Silveira, Laura, Moreno, David, van Furth, AM Tutu, van der Flier, M, Boeddha, NP, Driessen, GJA, Pajkrt, D, Sanders, EAM, van de Beek, D, van der Ende, A, Philipsen, HLA, Adeel, AOA, Breukels, MA, Brinkman, DMC, de Korte, CCMM, de Vries, E, de Waal, WJ, Dekkers, R, Dings-Lammertink, A, Doedens, RA, Donker, AE, Dousma, M, Faber, TE, Gerrits, GPJM, Gerver, JAM, Heidema, J, Homan-van der Veen, J, Jacobs, MAM, Jansen, NJG, Kawczynski, P, Klucovska, K, Kneyber, MCJ, Koopman-Keemink, Y, Langenhorst, VJ, Leusink, J, Loza, BF, Merth, IT, Miedema, CJ, Neeleman, C, Noordzij, JG, Obihara, CC, van Overbeek-van Gils, ALT, Poortman, GH, Potgieter, ST, Potjewijd, J, Rosias, PPR, Sprong, T, ten Tussher, GW, Thio, BJ, Tramper-Stranders, GA, van Deuren, M, van der Meer, H, van Kuppevelt, AJM, van Wermeskerken, AM, Verwijs, WA, Wolfs, TFW, Agyeman, Philipp, Aebi, Christoph, Berger, Christoph, Giannoni, Eric, Stocker, Martin, Posfay-Barbe, Klara M, Heininger, Ulrich, Bernhard-Stirnemann, Sara, Niederer-Loher, Anita, Kahlert, Christian, Hasters, Paul, Relly, Christa, Baer, Walter, Paulus, Stephane, Frederick, Hannah, Jennings, Rebecca, Johnston, Joanne, Kenwright, Rhian, Agbeko, Rachel, Bojang, Kalifa, Sarr, Isatou, Kebbeh, Ngane, Sey, Gibbi, Saidykhan, Momodou, Cole, Fatoumatta, Thomas, Gilleh, Antonio, Martin, Walcher, Wolfgang, Geishofer, Gotho, Klobassa, Daniela, Martin, Mueller, Pfurtscheller, Klaus, Reiter, Karl, Roedl, Siegfried, Zobel, Gerfried, Zoehrer, Bettina, Toepke, Baerbel, Fucik, Peter, Gabriel, Markwart, Penzien, Johann M, Diab, Gedeon, Miething, Robert, Deeg, KH, Hammer, Jurg, Varnholt, Verena, Schmidt, Andreas, Bindl, Lutz, Sillaber, Ursula, Huemer, Christian, Meier, Primrose, Simic-Schleicher, G, Markart, Markus, Pfau, Eberhard, Broede, Hans, Ausserer, Bernd, Kalhoff, Hermann, Arpe, Volker, Schweitzer-Krantz, Susanne, Kasper, Johannes-Martin, Loranth, Kathrin, Bittrich, Hans J, Simma, Burkhard, Klinge, Jens, Fedlmaier, Michael, Weigand, Nicola, Herting, Egbert, Grube, Regina, Fusch, Christoph, Gruber, Alois, Schimmel, Ulf, Knaufer-Schiefer, Suzanne, Laessig, Wolfgang, Hennenberger, Axel, von der Wense, Axel, Tillmann, Roland, Schwarick, Juergen, Sitzmann, Friedrich C, Streif, Werner, Mueller, Herbert, Kurnik, Peter, Groneck, Peter, Weiss, Ute, Groeblacher-Roth, Helene, Bensch, Juergen, Moser, Reinhard, Schwarz, Rudolf, Lenz, Kurt, Hofmann, Thomas, Goepel, Wolfgang, Schulz, Dietrich, Berger, Thomas, Hauser, Erwin, Foerster, Kai Martin, Peters, Jochen, Nicolai, T Homas, Kumlien, Bjoern, Beckmann, Regina, Seitz, Christiane, Hueseman, D, Schuermann, Roland, Ta, Van Hop, Weikmann, Eckart, Evert, W, Hautz, Juergen, Seidenberg, Juergen, Wocko, Lucia, Luigs, Petra, Reiter, Hans-Ludwig, Quietzach, J, Koenig, Michael, Herrmann, Johanna, Mitter, Horst, Seidler, Ekkehard, Maak, Bernhard, Sperl, Wolfgang, Zwiauer, Karl, Meissl, Manfred, Koch, Reinhard, Cremer, Manfred, Breuer, HA, Goerke, W, Nossal, Robert, Pernice, Walter, Brangenberg, Ralf, Salzer, Hans R, Koch, Hartmut, Schaller, Gerhard, Paky, Franz, Strasser, Friedrich, Eitelberger, Franz, Sontheimer, D, Lischka, Andreas, Kronberger, Martina, Dilch, Alfred, Scheibenpflug, Christian, Bruckner, Robert, Mahler, Klaus, Runge, Klaus, Kunze, Wolfgang, Schermann, Peter, Consortium, EUCLIDS, European Commission, Meningitis Research Foundation, National Institute for Health Research (UK), Newcastle Biomedical Research Centre, Newcastle University, Newcastle upon Tyne Hospitals NHS Foundation Trust, Instituto de Salud Carlos III, Xunta de Galicia, Wyeth Farma, Fundación Instituto de Investigación Sanitaria de Santiago de Compostela, Novartis, Swiss National Science Foundation, Swiss Society of Intensive Care Medicine, Gottfried und Julia Bangerter-Rhyner-Stiftung, Vinetum and Borer Foundation, Foundation for the Health of Children and Adolescents, Austrian National Bank, University of Zurich, Borghini, Lisa, Universidade de Santiago de Compostela. Departamento de Ciencias Forenses, Anatomía Patolóxica, Xinecoloxía e Obstetricia, e Pediatría, Png, Eileen [0000-0001-5586-6395], Wright, Victoria J [0000-0001-7826-1516], Schlapbach, Luregn J [0000-0003-2281-2598], Salas, Antonio [0000-0002-2336-702X], Martinon-Torres, Federico [0000-0002-9023-581X], Apollo - University of Cambridge Repository, ARD - Amsterdam Reproduction and Development, AII - Infectious diseases, Paediatric Infectious Diseases / Rheumatology / Immunology, Neurology, ANS - Neuroinfection & -inflammation, Medical Microbiology and Infection Prevention, Pediatrics, Public Health, Posfay Barbe, Klara, Critical care, Anesthesiology, Peri-operative and Emergency medicine (CAPE), APH - Aging & Later Life, Amsterdam Reproduction & Development (AR&D), and Pediatric surgery

Subjects
0301 basic medicine, Candidate gene, Hypopharyngeal Neoplasms / microbiology, Meningococcal Infections / microbiology, Vascular damage Radboud Institute for Health Sciences [Radboudumc 16], MathematicsofComputing_GENERAL, lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], lcsh:Medicine, Neisseria meningitidis, Regulatory Sequences, Nucleic Acid, Cohort Studies, 0302 clinical medicine, ComputingMethodologies_SYMBOLICANDALGEBRAICMANIPULATION, Hypopharyngeal Neoplasms / pathology, BINDING, Tumor Cells, Cultured, lcsh:Science, Genetics, Multidisciplinary, ddc:618, Cultured, TheoryofComputation_GENERAL, High-Throughput Nucleotide Sequencing, Genomics, Phenotype, 3. Good health, ddc, Tumor Cells, Multidisciplinary Sciences, GENOME, Science & Technology - Other Topics, Neisseria meningitidis / isolation & purification, Single-nucleotide polymorphism, 610 Medicine & health, KAPPA-B, Biology, Hypopharyngeal Neoplasms / genetics, Polymorphism, Single Nucleotide, Article, Meningococcal Infections / epidemiology, 03 medical and health sciences, SEQUENCE VARIATION, Genetic predisposition, Journal Article, Humans, Meningitis, Meningococcal Infections / genetics, Genetic Predisposition to Disease, Nucleic Acid, Polymorphism, General, Gene, Genotyping, Neisseria meningitidis / genetics, Genetic Association Studies, Genetic association, Genetic association study, 1000 Multidisciplinary, Science & Technology, Hypopharyngeal Neoplasms, genetic variants, meningococcal disease, lcsh:R, Single Nucleotide, EUCLIDS consortium, Gene regulation, Meningococcal Infections, 030104 developmental biology, 10036 Medical Clinic, Case-Control Studies, lcsh:Q, Software_PROGRAMMINGLANGUAGES, Regulatory Sequences, 030217 neurology & neurosurgery
Abstract

EUCLIDS consortium., Non-coding genetic variants play an important role in driving susceptibility to complex diseases but their characterization remains challenging. Here, we employed a novel approach to interrogate the genetic risk of such polymorphisms in a more systematic way by targeting specific regulatory regions relevant for the phenotype studied. We applied this method to meningococcal disease susceptibility, using the DNA binding pattern of RELA – a NF-kB subunit, master regulator of the response to infection – under bacterial stimuli in nasopharyngeal epithelial cells. We designed a custom panel to cover these RELA binding sites and used it for targeted sequencing in cases and controls. Variant calling and association analysis were performed followed by validation of candidate polymorphisms by genotyping in three independent cohorts. We identified two new polymorphisms, rs4823231 and rs11913168, showing signs of association with meningococcal disease susceptibility. In addition, using our genomic data as well as publicly available resources, we found evidences for these SNPs to have potential regulatory effects on ATXN10 and LIF genes respectively. The variants and related candidate genes are relevant for infectious diseases and may have important contribution for meningococcal disease pathology. Finally, we described a novel genetic association approach that could be applied to other phenotypes., This work has been partially funded by the European Seventh Framework Programme for Research and Technological Development (FP7) under EUCLIDS Grant Agreement No. 279185. The UK meningococcal cohort was established with support from Meningitis Research Foundation through grants to Imperial College London. The Research from Newcastle partners was supported by the National Institute for Health Research Newcastle Biomedical Research Centre based at Newcastle Hospitals NHS Foundation Trust and Newcastle University. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. The ESIGEM Research group activities were supported by grants from Instituto de Salud Carlos III (Proyecto de Investigación en Salud, Acción Estratégica en Salud: proyecto GePEM PI16/01478) (A.S.); Consellería de Sanidade, Xunta de Galicia (RHI07/2-intensificación actividad investigadora, PS09749 and 10PXIB918184PR), Instituto de Salud Carlos III (Intensificación de la actividad investigadora 2007–2016), Convenio de colaboración de investigación (Wyeth España-Fundación IDICHUS 2007–2011), Convenio de colaboración de investigación (Novartis España-Fundación IDICHUS 2010–2011), Fondo de Investigación Sanitaria (FIS; PI070069/PI1000540) del plan nacional de I + D + I and ‘fondos FEDER’ (F.M.T.). The Swiss Pediatric Sepsis study was funded by grants from the Swiss National Science Foundation (342730_153158/1), the Swiss Society of Intensive Care, the Bangerter Foundation, the Vinetum and Borer Foundation, and the Foundation for the Health of Children and Adolescents. The Western Europe Meningococcal Study was supported by grants no 8842, 10112 and 12710 of the Oesterreichische Nationalbank (Austria), grants A3-16.K-8/2008-11 and A3-16.K-8/2006–9 of the Department for Science and Research of the Styrian federal government (Austria) and the non for profit association ‘In Vita’, Graz (Austria).

Published
2019

7. Increased renal production of transforming growth factor-beta 1 in patients with type II diabetes

Author

Sharma, Kumar, Ziyadeh, Fuad N., Alzahaibi, Bashar, McGowan, Tracy A., Kapoor, Shiv, Kurnik, Brenda R.C., Kurnik, Peter B., and Weisberg, Lawrence S.

Subjects
Diabetes -- Physiological aspects, Diabetic nephropathies -- Physiological aspects, Health, Physiological aspects
Abstract

Diabetic nephropathy is a common complication in patients with either type I or type II diabetes. The pathogenesis of diabetic nephropathy is thought to involve both metabolic and vascular factors [...]

Published
1997

8. Myocardial infarct artery patency and reocclusion rates after treatment with duteplase at the dose used in the International Study of Infarct Survival-3

Author

Kalbfleisch, John M., Kurnik, Peter B., Thadani, Udho, DeWood, Marcus A., Kent, Richard, Magorien, Raymond D., Jain, Abnash C., Spaccavento, Leo J., Morris, D. Lynn, Taylor, George J., Perry, James M., Kutcher, Michael A., Gorfinkel, H. Joel, and LittleJohn, Judith K.

Subjects
Tissue plasminogen activator -- Dosage and administration, Heart attack -- Drug therapy, Thrombolytic therapy -- Methods, Health
Abstract

Duteplase, 98% double-chain recombinant tissue-type plasminogen activator, was administered intravenously in 488 patients with acute myocardial infarction in a multicenter, open, safety and patency study. Duteplase dosing was based on body weight. Duteplase was administered as a bolus of 0.04 MIU/kg of thrombolytic activity followed by 0.36 MIU/kg over 1 hour and 0.067 MIU/kg/hour for 3 additional hours. The patency rate of the infarct-related artery at 90 minutes was 69% (330 of 478). The reocclusion rate at 3 to 48 hours was 6% (18 of 301). Reinfarction occurred in 7.6% of patients (37 of 488), but 12 reinfarctions occurred after coronary angioplasty. Serious bleeding occurred in 7.6% of patients (37 of 488), predeminantly at the catheterization entry site. Them were 3 instances of central nervous system bleeding, 1 fatal. Fibrinogen levels declined to 83% of baseline at 24 hours. Weight-based dosing may explain the low incidence of serious bleeding in this study. The in-hospital mortality was 6.6% (32 of 488). This study documents that the dose of duteplase used in the international Study of Infarct Survival-3 results in a 90-minute coronary artery patency rate and safety profile comparable to those reported in published studies on the approved dose of alteplase. (Am J Cardiol 1993;71:386-392)

Published
1993

9. Frequency of low-grade residual coronary stenosis after thrombolysis during acute myocardial infarction

Author

Marshall, James C., Waxman, Harvey L., Sauerwein, Anthony, Gilchrist, Ian, and Kurnik, Peter B.

Subjects
Thrombolytic drugs -- Evaluation, Coronary heart disease -- Complications, Atherosclerosis -- Diagnosis, Heart attack -- Complications, Coronary heart disease -- Relapse, Heart attack -- Risk factors, Heart attack -- Drug therapy, Health
Abstract

The clinical, angiographic and demographic characteristics of 42 patients with low-grade (0.10) but were significantly older (52 [+ or -] 12 vs 56 [+ or -] 10 years, p = 0.02). Prior acute MI or angina was unusual in group I. Sixty percent had no significant (>50%) residual coronary artery disease while 25% had residual single artery disease. Average significant (>50% diameter stenosis) residual vessel disease was 0.6 [+ or -] 1.0 for group I and 1.9 [+ or -] 0.9 for group II (p (Am J Cardiol 1990;66:773-778), Most heart attacks are caused by a clot blocking a coronary artery narrowed by atherosclerotic (fatty) plaques. It is not known how well patients recover after acute myocardial infarction (AMI) when they have arterial narrowing of less than 50 percent and receive thrombolytic (clot-dissolving) therapy. Although occlusion does not usually occur until the inner diameter of the artery is narrowed by 70 percent or more, 10 to 20 percent of patients requiring thrombolytic therapy after AMI have noncritical stenosis (narrowing) of 50 percent or less. This is an indication of the limitations of coronary angiography (an invasive technique for X-ray visualization of the heart and blood vessels) for predicting the potential for AMI. To measure the effects of low-grade versus critical residual stenosis after AMI, 198 patients with AMI who received thrombolytic therapy were divided into two groups, based on degree of stenosis. The 42 patients with low-grade (less than 50 percent) stenosis were predominantly male smokers; these patients are discussed. Follow-up was terminated in the event of subsequent coronary bypass, angioplasty (mechanical dilatation of the affected artery), total blockage of the infarct site, or death. Patients were monitored for a minimum of 6 months, and an average of 18 months. Data was gathered on symptoms, including typical and atypical angina (chest pain due to inadequate oxygen supply to the heart), dyspnea (difficulty breathing), medical regimen, other risk factors for heart disease, subsequent hospitalizations, and repeat coronary angiography or exercise testing. Although only 1 of the 42 patients died during follow-up, the data suggest a strong likelihood of further heart problems for these patients. Compared with greater atherosclerosis, recurrent clotting at the site of the infarction is more likely to explain total blockages or rapid narrowing of the affected artery. Because this is a small retrospective study, and variables such as type, dosage, and route of thrombolysis, duration and intensity of heparinization (anti-clotting medication), and time to angiography were not measured, it is difficult to draw firm conclusions. The authors report that they found no clear advantage with any given combination of treatments. (Consumer Summary produced by Reliance Medical Information, Inc.)

Published
1990

10. Izbira informacijskega sistema za manjše lesno podjetje

Author

Kurnik, Peter and Kropivšek, Jože

Subjects
lesna industrija, wood industry, information system, informacijski sistem, večkriterijsko odločanje, multi-criteria decision-making, udc:658.51:674, odločitveni model, selection model
Abstract

Problem majhnih lesnih podjetij je, da ne poznajo svojih informacijskih potreb prav tako ne poznajo sodobnih informacijskih rešitev in njihovih ponudnikov. Izbira primernega informacijskega sistema je zato še bolj zapleten postopek. S ciljem oblikovanja ustreznega odločitvenega modela, ki bi podjetjem lahko bil v pomoč pri tej izbiri, smo v raziskavi najprej opravili analizo informacijskih potreb v manjših in v preučevanem podjetju. Ugotovili smo, da se le-te povsem ujemajo. Na osnovi ugotovljenih informacijskih potreb smo v nadaljevanju določili merila za izbor najustreznejšega informacijskega sistema za manjša lesna podjetja in pridobili ponudbe za 10 različnih informacijskih sistemov. Po metodi večkriterijskega odločanja smo postavili odločitveni model in izbrali informacijski sistem, ki najbolj ustreza potrebam tako preučevanega kot tudi ostalih, podobnih manjših lesnih podjetij. One of the problems most small wood-industry companies face is not being aware of their own information needs. They are also not familiar with the up-to-date information solutions and their providers. These facts make the selection of a suitable information system an even more complicated process. The purpose of our research was to form an appropriate decision model, helping companies with decision-making. With this aim in mind, we first carried out an analysis of information needs in small wood-industry companies as well as in the resarched one. We discovered that these needs do not differ much. Based on the results, we then determined the criteria for choosing the most suitable information system for smaller wood-industry companies and we received offers for 10 different information systems. Using the method of multi-criteria decision-making, we set up a decision model and we chose the information system best suited for the needs of the resarched company, as well as for other, similar small wood-industry companies.

Published
2014

11. Stanje poslovne informatike v manjših lesnih podjetjih: The condition of business informatics in small wood industry companies

Author

Kropivšek, Jože and Kurnik, Peter

Abstract

The research studied the condition of business informatics in small wood industry companies. On one hand we were interested in how much the companies use computers, the internet and information systems to support their business activities, on the other hand we tried to find out which field of work they control with this kind of information solutions. It was found out that the companies, which already use integrity information systems (Enterprise Resource Planning systems), are mostly satisfied with them and that they use them to control their most important business activities. The research confirmed that the condition of information technology in studied companies gives them the opportunity for development in the field of introducing information systems and tools. Raziskovali smo, kakšno je stanje poslovne informatike v manjših lesnoindustrijskih podjetjih. Na eni strani nas je zanimalo, koliko podjetja uporabljajo računalnike, internet in informacijske sisteme za podporo svojim poslovnim aktivnostim, na drugi strani pa, katera področja pokrivajo s tovrstnimi informacijskimi rešitvami. Ugotovili smo, da so podjetja, ki že uporabljajo celovite informacijske sisteme, z njimi večinoma zadovoljna in jih uporabljajo predvsem za podporo ključnim poslovnim aktivnostim. Raziskava je potrdila, da stanje informacijske tehnologije v preučevanih podjetjih omogoča razvoj podjetij tudi na področju uvajanja informacijskih sistemov in orodij.

Published
2011

34. Electrophysiological-anatomic correlates of ATP-triggered vagal reflex in the dog. V. Role of purinergic receptors.

Author

Jiang Xu, Kussmaul, William, Kurnik, Peter B., Al-Ahdav, Mohamad, and Pelleg, Amir

Subjects
ADENOSINE triphosphate, PURINERGIC receptors, CELL receptors, ISCHEMIA, MYOCARDIAL infarction, PHYSIOLOGY
Abstract

The mechanism of extracellular ATP-triggered vagal depressor reflex was further studied in a closed-chest canine model. Adenosine and ATP were administered individually in equimolar doses (0.01-1.0 µmol/kg) into the right coronary artery (RCA) and left circumflex coronary artery (LCA). When administered into the RCA, adenosine and ATP exerted an identical and relatively small negative chronotropic effect on sinus node automaticity; the time to peak negative chronotropic effect was ≥7 s. When administered into the LCA, adenosine had no effect on sinus node automaticity, whereas ATP markedly suppressed sinus node automaticity. This effect of ATP 1) reached its peak in <2 s after its administration, 2) was short lasting, and 3) was completely abolished by either intravenous administration of the muscarinic cholinergic blocker atropine (0.2 mg/ kg) or intra-LCA administration of 2',3'-O-(2,4,6-trinitrophenyl)ATP (TNP-ATP), a potent P2X2/3 purinergic receptor (P2X2/3R) antagonist, but not by diinosine pentaphosphate (Ip5I), a potent inhibitor of P2X1R and P2X3R. Repetitive administrations of ATP were not associated with reduced effects, indicative of receptor desensitization, thereby excluding the involvement of the rapidly desensitized P2X1R in the action of ATP. It was concluded that ATP triggers a cardio-cardiac vagal depressor reflex by activating P2X2/3R located on vagal sensory nerve terminals localized in the left ventricle. Because these terminals mediate vasovagal syncope, these data could suggest a mechanistic role of extracellular ATP in this syndrome and, in addition, give further support to the hypothesis that endogenous ATP released from ischemic myocytes is a mediator of atropine-sensitive bradyarrhythmias associated with left ventricular myocardial infarction. [ABSTRACT FROM AUTHOR]

Published
2005
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35. Expected hemoglobin decrease following percutaneous transluminal coronary angioplasty.

Author

Jauch, Werner and Kurnik, Peter B.

Subjects
*HEMOGLOBINS, *TRANSLUMINAL angioplasty
Abstract

Determines the expected change in hemoglobin after balloon percutaneous transluminal coronary angioplasty (PTCA) and establishes 95% confidence and prediction intervals. Documentation of postprocedural bleeding; Change in hemoglobin during and after PTCA: Explanation for the observed reduction in hemoglobin during PTCA.

Published
1997
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38. Antithrombin activity during the period of percutaneous coronary revascularization Relation to heparin use, thrombotic complications and restenosis

Author

Matthai, William H, Kurnik, Peter B, Groh, William C, Untereker, William J, and Siegel, Jamie E

Abstract

OBJECTIVESThis study evaluated changes in antithrombin (AT) activity around the time of percutaneous transluminal coronary revascularization (PTCR) with unfractionated heparin anticoagulation and the effects these changes had on major thrombotic complications of PTCR.BACKGROUNDHeparin is used during PTCR to prevent thrombosis. However, heparin, a cofactor for AT, causes AT activity to fall. AT activity 20 h after heparin discontinuation. Pre-PTCR use of heparin led to lower AT activity in proportion to duration of heparin use. There was no relationship between AT activity and restenosis.CONCLUSIONSLow AT activity may contribute to major thrombotic complications of PTCR. The way heparin is used before and after PTCR is important to development of low AT activity.

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39. Diastolic stiffening induced by acute myocardial infarction is reduced by early reperfusion

Author

Kurnik, Peter B., Courtois, Michael R., and Ludbrook, Philip A.

Abstract

Reperfusion early during myocardial infarction improves ejection fraction and this improvement may represent myocardial salvage in the injured segment. Alternatively, reperfusion of injured myocardium may cause intramyocardial hemorrhage with resultant increased stiffness causing a dyskinetic segment to become akinetic, thus improving ejection fraction without concomitant myocardial salvage. To evaluate this possibility, diastolic stiffness was assessed in a closed chest, anesthetized, normothermic dog model immediately after a 1 or 3 h occlusion of the left anterior descending coronary artery and during the 4 weeks after occlusion.

Published
1988
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40. Sensitivity of isovolumic relaxation to hypothermia during myocardial infarction

Author

Courtois, Michael R, Kurnik, Peter B, and Ludbrook, Philip A

Abstract

Effects of moderate spontaneous hypothermia on left ventricular systolic and diastolic function during acute myocardial infarction were documented in 17 anesthetized dogs with micromanometric pressure and ventriculographic dimension recordings acquired at baseline and at 1 and 3 h after coronary occlusion. In Group 1 (n = 5), core temperature was allowed to decline spontaneously. In Groups 2 (n = 6) and 3 (n = 6), core temperature was maintained at normothermic levels. Hypothermia impaired isovolumic relaxation markedly despite its lack of effect on ventricular volumes or ejection fraction. At 32.3 °C, τ1/2, defined as the time needed for the left ventricular pressure at the time of peak negative rate of change of left ventricular pressure (dPdt) to fall by 50%, was increased by 129% 3 h after occlusion. In addition, at this temperature significant changes were found in heart rate, cardiac output, minute work, peak positive and peak negative dPdt, systolic ejection time, mean velocity of circumferential fiber shortening, mean aortic pressure and end-diastolic pressure.

Published
1988
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