bluuebunny/crossref_metadata_2025 huggingface dataset:
Intrakranielle Blutungen und Hämostase
Authors: Menges T. , Lessen A.v. , Welters I. , Wagner R.-M. , Ruwoldt R. , Boldt I. , Hempelmann G.
Published: May 2009

Ziel: Die verbesserte Erfassung auch kleiner, symptomarmer Blutungen und nichtrupturierter Aneurysmen durch Kontrolle von Aktivierungsprodukten der plasmatischen Gerinnung. Design: Prospektiv offene Studie. Rahmen: Neurochirurgische Intensivstation einer Universitätsklinik. Patienten: 44 Patienten, die sich einer kranialen Trepanation unterziehen muβten. Gruppe 1 waren Patienten mit intrasellär liegenden Hypophysentumoren (Kontrollgruppe, n=ll), Gruppe 2 (n = 12) Patienten mit nichttraumatisch bedingten, chronisch subduralen Hämatomen und Gruppe 3 (n=15) Patienten mit aneurysmatisch bedingten subarachnoidalen Blutungen. Interventionen: Nach kranialer Trepanation wurden Veränderungen der plasmatischen Hämostase anhand von immunologischen Gerinnungsparametern bestimmt. Die Narkose, das operative Verfahren (kraniale Trepanation), die Probenentnahme zu definierten Zeitpunkten und das Infusionsregime waren für alle Gruppen ver-gleichbar. Ergebnisse: Im Vergleich zur Kontrollgruppe kam es in den Gruppen 2 und 3 zu signifikanten Veränderungen (p < 0,001) von Thrombin-Antithrombin III (TAT), Fibrinopeptid A (FPA), Protein C und der Antithrombin-(AT-)III-Aktivität. Bei sonst normalen Gerinnungsparametern ergeben sowohl die erhöhten TAT- und FPA-Spiegel als auch die verminderte AT-IΠ-Aktivität und die erniedrigten Protein-C-Spiegel den Hinweis auf eine gesteigerte, nicht vollständig kompensierte intrava-sale Thrombinbildung. Die verminderte Faktor-XIII-Aktivität (Gruppe 2: 40%, Gruppe 3: 44%) deutet dabei auf einen thrombininduzierten Umsatz von Gerin-nungsfaktoren hin. Bei 8 Patienten (Gruppe 2: 5 Patienten und Gruppe 3: 3 Patienten) trat während des Untersuchungszeitraums eine Nachblutung auf. Alle 8 Patienten hatten bei Zeichen einer intravasalen Gerinnungsaktivierung zum Zeitpunkt der Nachblutung eine Faktor-XIII-Aktivität von weniger als 40%. Schluβfolgerung: Durch die Erfassung immunologischer Gerinnungsparameter wie Faktor-XIII-Aktivität, FPA, TAT und Protein C ist eine bessere Uberwachung der plasmatischen Gerinnung bei Patienten mit einem Blutungsereignis möglich. Das Risiko einer wiederholten Blutung ist unter Berücksichtigung dieser Meβparameter
Circulatory Clearance of Transfused Antibody-Sensitized Red Cells in an Entirely Allogenic Rabbit Model
Authors: Faust A. , Kissel K. , Neppert J.
Published: May 2009

Background: Antibodies against histocompatibility antigens on phagocytes abrogate their Fcγ-receptor-mediated functions in vitro. Studies were carried out to determine whether this phenomenon also exists in vivo. Methods: An allogenic blood group antibody was generated in rabbits. Red cells sensitized with this antibody were internalized in vitro by rabbit phagocytes. Another allogenic antibody specific for major histocompatibility complex (MHC) antigens of rabbits was produced. Plasma containing this antibody was infused into rabbits with phagocytes expressing the corresponding MHC antigens. Thereafter, the sensitized rabbit red blood cells were transfused into the rabbits. Results: The following 3 phases of the circulatory clearance of transfused sensitized red cells could be observed when MHC antibodies were not given prior to the transfusion: 1. initial rapid clearance of the cells (t/2 = 1.7 – 3.3 min), 2. release of the cells back into the circulation after 0.5-24 h and 3. terminal slow clearance which was, however, faster than that with unsensitized cells. Two independent experiments carried out on the same recipient out of the 3 recipients analysed showed that the prior treatment of the recipient with MHC-alloantibodies extended the circulatory half-life of the sensitized red cells during the terminal phase from t/2=l day to t/2=3 and 4 days, respectively. Conclusion: Antibodies against MHC antigens on phagocytes can reduce the Fcγ-receptor-mediated immune elimination of sensitized red cells. This corresponds to the observation that many cases of morbus haemolyticus neonatorum show unexpectedly reduced levels of foetal red cell destruction and a good clinical outcome if mothers not only produce antibodies to Rh (D) but also to foetal MHC antigens.
Influence of Pall PI-50 Platelet Filters on Lactate Dehydrogenase, Platelet Factor 4, and Complement Factor 3 in Stored Platelet Concentrates
Authors: Järemo P.
Published: May 2009

Background: The study examines Pall Pl-50 platelet filters with respect to their influence on some biochemical properties of platelet concentrates. Material and Methods: Ten pairs of pooled platelet preparations, each consisting of 3 platelet concentrates, were studied. On day 1, one of the preparations was filtered and the other served as an identical non-filtered control. Immediately after filtration platelet counts, the levels of desarginated activated complement factor 3 (C3a), extracellular levels of lactate dehydrogenase (LDH) and extracellular and total concentrations of platelet factor 4 (PF4) were determined in both concentrates. After 5 days sterility testing and determination of extracellular levels of PF4 and LDH were performed. Results: Extracellular concentrations of PF4 and C3a decreased immediately after filtration (p < 0.01). Furthermore, Pall Pl-50 filters caused cellular instability reflected by an increased release of PF4 (p < 0.01) during subsequent storage. Conclusion: Platelet concentrates filtered with Pall Pl-50 would not appear suitable for storage.
Effect of Two Lipid Emulsions on Platelet Function
Authors: Porta I. , Planas M. , Padró J.B. , Picó M. , Valls M. , Schwartz S.
Published: May 2009

Objective: To examine the effect of two lipid emulsions administered with total parenteral nutrition (TPN) on platelet aggregation and activation and the production of eicosanoids in nonseptic critically ill patients. Design: Prospective, randomized, unblinded, non-crossover study. Setting: ICU of a general teaching hospital. Patients: 23 adult, critically ill, nonseptic patients, who were in need of TPN for at least 7 days. Interventions: The patients were randomly distributed into 2 groups each of which received TPN with a different essential fatty acid content. The 2 lipid emulsions, Intralipid® 20% (long-chain triglycerides) and Lipofundin® MCT/LCT 20% (10% each of long- and medium-chain triglycerides) provided 43% of the nonprotein caloric requirements calculated for each patient. Parameters demonstrating platelet function (plasma β-thromboglobulin, platelet factor 4, platelet aggregation, 6-keto-PGFια) were assessed before starting TPN and after 4 and 7 days of initiation. Results: Before beginning lipid perfusion, platelet activation evaluated by βTG and PF4 levels was notable, 6-keto-PGFlct production was elevated and no hyperaggregation of platelets was observed in patients. The studies of platelet function at 4 and 7 days of TPN did not show significant changes with respect to the basal data or between the 2 groups. Conclusion: Our results indicate that platelet function was not affected by either of the 2 lipid emulsions administered to patients during the study period.
Detection of Primary HIV Infection by a Second-Generation HIV(p24) Antigen Test
Authors: Thies K. , Anders C. , Baldus M. , Schleiffer T. , Weber B. , Rabenau H. , Hellstern P.
Published: May 2009

We studied the course of a primary HIV infection in a 54-year-old woman. Probably the source of infection was sexual intercourse, since other risks, such as i. v. drug use, acupuncture and transfusion were excluded. On admission she presented with fever, a maculopapular rash, and moderate enlargement of nuchal lymph nodes. At that time the anti-HIV 1,2 enzyme immunoassay was negative. However, the HIV-p24 Ag test, which was performed in every HIV screening in our laboratory, was positive. The suspicion of an acute HIV infection was supported by a positive HIV-cDNA-PCR and confirmed by Western blot after seroconversion. As additional finding, the blood smear showed abnormal white cell differential count, indicating viral infection. Aminotransferases were slightly increased, and antibodies to hepatitis B surface and core antigens demonstrated former hepatitis B infection. It is concluded that in this case the HIV-p24 Ag test proved its suitability for early diagnosis of an acute HIV infection. In case of testing blood donors, none of the compulsory sero-logical screening methods would have detected the HIV infection.
Autologe Transfusion bei Tumoroperationen
Authors: Hansen E. , Hofstädter E. , Taeger K.
Published: May 2009

Ziel: Anh der aktuellen Literatur werden Möglichkeiten und Grenzen autologer Transfusionsmethoden zur Deckung des Blutbedarfs bei Tumoroperationen darge-stellt und basierend auf eigenen Untersuchungen neue Möglichkeiten aufgezeigt. Quellen und Auswahlkriterien: Die kritische Auseinandersetzung mit der vorhan-denen deutsch- und englischsprachigen Literatur stützt sich auf eine die letzten 20 Jahre umfassende Medline- und DIMDI-Recherche. Eigene aktuelle bisher nur in Form von Kongreβmitteilungen veröffentlichte Ergebnisse werden vorgestellt. Ergebnisse: Präoperative Eigenblutabnahmen stellen auch für Tumorpatienten eine wichtige und praktikable Alternative zur homologen Transfusion mit ihren vielfältigen Risiken dar. Tumoranämie der drängende Operationstermin und ein wechselnder Blutbedarf limitieren Eigenblutspendeprogramme. Die intraoperative Autotransfusion ist bisher kontraindiziert. Eigene systematische Untersuchungen über Tumorzellen im Wundblut bei einer Reihe unterschiedlicher Tumoroperationen bestätigen die Gefahr einer Tumorzellaussaat bei einer Retransfusion. Deshalb müssen Ansätze einer Tumorzellelimination weiterverfolgt werden. Im Gegensatz zur Literatur zeigten in eigenen Untersuchungen Leukozytendepletionsfilter keine ausreichende Retention. Ihre Rückhalterate für Tumorzellen konnte zu etwa 3 log10 bestimmt werden. Dagegen lieβ sich die Teilungsfähigkeit von Tumorzellen im Blut durch Bestrahlung mit Gammastrahlen sicher unterbinden. Schluβfolgerungen: Eine Bestrahlung mit 50 Gy erlaubt eine gefahrlose Retransfusion von intraoperativem Wundblut. Dadurch eröffnen sich neue Möglichkeiten der autologen Transfusion bei Tumorpatientendie nun im Rahmen klinischer Stu-dien zu prüfen sind.
HLA-DPB1 Typing by PCR-SSO Reverse Dot Blot Hybridization after Group-Specific Amplification
Authors: Blasczyk R. , Mohr M. , Zimmermann R. , Schwella N. , Huhn D.
Published: May 2009

Background: The allelic diversity of HLA-DPBl antigens can be determined at the DNA level after PCR amplification. The pattern of polymorphism at the DPB1 locus makes it difficult to unambiguously assign all genotypes in a typing system using one single pair of generic primers. Materials and Methods: We apply here a simple technique based on the reverse dot blot analysis to the typing of HLA-DPBl alleles. In order to increase its resolution, a group-specific amplification based on sequence variations of the polymorphic region F was used subdividing the HLA-DPBl alleles in 2 nonoverlapping families. A separate analysis was then performed within each group of alleles. Results: Using these 2 primer pairs, 21 group 1 and 30 group 2 alleles were separately amplified. From 1,378 possible allele combinations for DPB 1*0101-5301 only 33 gave ambiguous typing results compared to 61 using a single pair of generic primers. Conclusions: This procedure provides a rapid and simple HLA-DPBl genotyping. Especially in heterozygotes the hybridization patterns were easier to interpret. The utilization of group-specific amplification substantially reduced ambiguous typing results.
Activation of Complement by Cold Agglutinins
Authors: Kirschfink M. , Knoblauch K. , Roelcke D.
Published: May 2009

Objective: To review recent reports on the interaction of cold agglutinins with the complement system and its relevance to cold agglutinin disease. Data Sources: Review articles and original papers have been selected for this contribution. Selection Criteria: The report focuses on experimental data available from in vitro studies as well as clinical findings regarding the mechanisms of cold agglutinin-induced complement activation. Results: Despite the observation that only few cold agglutinins (almost exclusively IgM molecules with anti-I specificity) induce in vitro hemolysis of human red blood cells with human serum (homologous system), the vast majority of these autoanti-bodies are able to initiate the classical pathway sequence with the fixation of Cl and to a lesser degree of C4. The ability of IgM cold agglutinins to activate, in principle, complement is demonstrated by their hemolytic efficiency in the presence of animal serum as a source of heterologous complement. In addition to the thermal amplitude of cold agglutinin binding, a possible interference with membrane regulatory proteins may render certain cold agglutinins hemolytically active in a homologous system. Conclusion: Despite a hemolytic inefficiency, cold agglutinin-induced fixation of early complement components up to C3 leads to an accelerated clearance of red cells from the circulation by hepatic sequestration. However, it is not yet clear, to what degree these cells are eliminated by the reticuloendothelial system or whether they return to the circulation. Dependent on the amount of membrane-bound C3 fragments these cells may even be protected against further cold agglutinin-induced complement attack.
Transfusionsassoziierte HIV-Infektion
Authors: Gürtler L.G. , Eberle J. , Bader L.
Published: May 2009

Ziel: Das verbleibende Restrisiko abzuschätzen, durch Blut- oder Plasmatransfusion HIV zu übertragen. Verfahren und Techniken zur Diagnostik der HIV-Infektion bei Blutspendern darzustellen. Quellen: Die deutsch- und englischsprachige medizinische Literatur zum Thema sowie eigene Erfahrungen der Autoren. Auswahlkriterien: Keine speziellen Auswahlkriterien. Ergebnisse: Transfusionsbedingte HIV-Infektionen sind in Deutschland durch konsequentes Spenderscreening, Durchführung des Anti-HIV-Tests und Tests, die andere Infektionserreger erkennen, wesentlich vermindert worden. Die Wertigkeit des p24-Antigentests bleibt offen. Polymerase-Kettenreaktion (PCR) und Multi-primer-Amplifikationstests (SAA) bringen bis heute keine Verbesserung der HIV-Erkennung in der Frühphase der Infektion und können aus technischen Gründen nicht in Serie durchgeführt werden. Klinische Studien zur Effektivität von Versuchen, Viren durch Psoralen, Methylenblau und UV-Bestrahlung zu inaktivieren, stehen noch aus. Schluβfolgerungen: Verbesserungen der HIV-Sicherheit können erreicht werden durch weiterhin konsequentes Testen auf Antikörper von Infektionserregern, durch strikte Spenderselektion und durch Regionalisierung des Spendenaufkommens. Eine 100%ige Sicherheit gegen Infektionserreger wird es bei Blutkonserven nicht geben, besonders unter dem Aspekt, daβ geographisch eingegrenzte Infektionserreger ihr angestammtes Habitat verlassen.
Übertragung von Parvovirus B19 durch Blut und Blutkomponenten
Authors: Schwarz T.F.
Published: May 2009

Ziel: Untersucht wurden die klinische Relevanz und das Risiko der Ubertragung von Parvovirus B19 (B19) durch Blut oder Plasmaprodukte. Maßnahmen zur Vermeidung dieser Ubertragung wurden diskutiert. Quellen und Auswahlkriterien: Publizierte physikalisch-chemische Daten der autonomen Parvoviren sowie Literaturangaben zur Inzidenz von B19-kontaminierten Blut- und Plasmaspenden wurden zusammengefaßt. Forschungsergebnisse des Autors und anderer Untersucher wurden berücksichtigt. Ergebnisse: B19 tritt in Deutschland endemisch auf. Die Inzidenz viruskontaminierter Blutspenden beträgt 0,01-0,03%. Trotz Anwendung virusinaktivierender Verfahren kann die Ubertragung von B19 durch Gerinnungsfaktorpräparate derzeit nicht ausgeschlossen werden. Schlußfolgerung: Die Ubertragung von B19 durch Blut oder Plasmaprodukte läßt sich durch die Testung der Einzelspenden auf B19-spezifische Antikörper mit Hilfe von Enzymimmunoassays oder auf B19-DNS mit der Polymerase-Kettenreaktion vermeiden.
Problematik der bakteriellen Infektion im Rahmen der Hämotherapie
Authors: Bösenberg A. , Bösenberg E. , Sibrowski W.
Published: May 2009

Ziel: Das Ziel der Arbeit besteht darin, eine Übersicht über die derzeitigen Erkenntnisse bezüglich bakterieller Infektionen im Rahmen der Hämotherapie zu geben. Quellen: Berichte aus dem internationalen Schrifttum, insbesondere aufgrund EDV-gestützter Literaturrecherchen. Auswahlkriterien: Berücksichtigung fanden Autoren, die über eigene Untersuchungen berichten. Vermutungen über mögliche Übertragungen extrem seltener Keimarten fanden keine Erwähnung. Ergebnisse: Mangels systematischer Erhebungen wird über bakterielle Transfusionszwischenfälle nur sporadisch im Schrifttum berichtet. Sicher ist, daβ abwehrge-schwächte Patienten leicht geschädigt werden können. Das Keimspektrum ist breit, jedoch kommen Staphylokokken, Yersinien, Serratia und Pseudomonaden häufig als Krankheitserreger in Betracht. Insbesondere Thrombozytenkonzentrate bergen ein höheres Infektionsrisiko, da die obligatorische Lagerung bei Zimmertemperatur ein schnelleres Keimwachstum ermöglicht. Strikte Einhaltung der Hygieneregeln bei der Produktion, eine intensive Anamneseerhebung bei den Spendern und gezielte Qualitätskontrollen vermögen das Risiko für Transfusionszwischenfälle zu senken. Schluβfolgerungen: Die Hämotherapie erfordert eine exakte Indikationsstellung und eine klare Strategic durch Bewertung der Transfusionsberichte und routinemäβige bakteriologische Kontrollen zur Verhütung von Infektionen.
Das Infektionsrisiko in der Hämotherapie
Authors: Sibrowski W. , Wüllenweber J.
Published: May 2009

Seit einigen Jahren ist die HIV-Infektion durch Blutprodukte im Mittelpunkt öffentlicher Diskussion. Entgegen dabei oft geäußerten Befürchtungen liegt das Risiko der transfusionsassoziierten HIV-Infektion unter 1:1 Mio. Ob bei dieser niedrigen Rate weitere serologische Tests (z. B. P24-Antigentest) Verbesserungen bringen, ist eher fraglich. Das Restrisiko der Posttransfusionshepatitis ist mit 1:10000 bis 1:100000 höher. Hier lassen die neu eingeführten Anti-HCV-Tests sowie die Untersuchung auf Anti-Hbc weitere Verbesserungen erwarten.
Möglichkeiten der Familienblutspende bei Kindern und Erwachsenen
Authors: Sibrowski W. , Schneider C.
Published: May 2009

Gerichtete Blutspenden werden – abgesehen von wenigen Ausnahmen – von den meisten Blutspendediensten abgelehnt. Gründe dafür sind das Infektionsrisiko, immunologische und wirtschaftliche Aspekte. Werden dennoch gerichtete Blutspenden zugelassen, so sind sie wie jede Fremdblutspende herzustellen, die Spender und Empfänger über mögliche Risiken zu informieren und die Frage der höheren Kosten zu klären.
Virusinaktiviertes Plasma
Authors: Köhler M. , Wieding J.U.
Published: May 2009

In Deutschland sind zwei virusinaktivierte Plasmen als Arzneimittel erhältlich. Beim Methylenblau-photooxidierten Plasma (MB-Plasma) handelt es sich um Plasma einer Einzelspende, das mittels Methylenblau (1 µM) und sichtbarem Licht (1 h 60000 Lux) photoinaktiviert wird. Diese Behandlung führt zu einer Reduktion von HIV um mindestens 5 log-Stufen, aber auch Fibrinogen wird alteriert. Die klinische Bedeutung dieses Phänomens ist unklar, da klinische, prospektive Studien zur Zeit noch fehlen. Beim Solvent-Detergent-behandelten Plasma (SD-Plasma) wird ein Plasmapool aus etwa 2000 Einheiten mit TNBP (Tri-n-butylphosphat) und Triton-X 100 behandelt. Diese Behandlung reduziert Hepatitisviren um 5-6 log-Stufen und HIV um 6 log-Stufen. Von den wirksamen Bestandteilen werden Protein S und Alpha-2-Antiplasmin um etwa 40% reduziert. In klinischen Studien konnte gezeigt werden, daβ SD-Plasma hinsichtlich der Wirksamkeit nativem, gefrorenem Human-plasma vergleichbar ist.
HIV-Sicherheit industriell hergestellter humaner Plasmaproteine
Authors: Hilfenhaus J.
Published: May 2009

Ein vorrangiges Ziel der industriellen Herstellung von humanen Plasmaproteinen als Therapeutika ist die Virussicherheit, insbesondere die HIV-Sicherheit dieser Produkte. Dieses Ziel wird dadurch erreicht, daβ 1. die Plasmen nur von gesunden, sorgfältig ausgewählten Spendern gewonnen werden, 2. die Einzelspenden vorschriftsmäβig auf Antikörper bzw. Antigene spezieller Viren getestet werden, 3. Viren durch verschiedene Reinigungsmethoden im Rahmen des Herstellungsverfahrens eliminiert und 4. durch eine spezielle Methode im Herstellungsverfahren inaktiviert werden. Aus aktuellem Anlaβ konzentriert sich der vorliegende Artikel auf HIV. Am Beispiel von pasteurisiertem Faktor VIII werden speziell für HIV experimentelle Untersuchungen zur Eliminierung dieses Virus durch verschiedene Verfahrensschritte und seine komplette Inaktivierung durch die Pasteurisierung (lOstündige Erhitzung der stabilisierten, wäβrigen Faktor-VIII-Lösung bei 60 °C) diskutiert. Virusinaktivierung und -eliminierung durch das gesamte Herstellungsverfahren von pasteurisiertem Faktor VIII führen zu einem kumulierten Reduktionsfaktor für HIV von > 1016. Dabei ist nicht berücksichtigt, daβ die tatsächliche Wirkung der Pasteurisierung gegenüber HIV um viele Zehnerpotenzen höher ist als im Experiment belegt, da die Erhitzungsdauer im Produktionsverfahren 10 Stunden beträgt, d.h. lOmal länger ist als im Inaktivierungsexperiment erforderlich. Herstellungsverfahren, die einen Verfahrensschritt enthalten, der HIV komplett inaktiviert und für das Gesamtverfahren in einem kumulierten HIV-Reduktionsfaktor von > 1012 resultieren, führen zu Produkten, die frei sind von infektiösem HIV.
Transfusionsmedizin im geeinten Europa. Kurzbericht über den Stand der Transfusionsmedizin in den zentralen und osteuropäischen Ländern
Authors: Brüster H.Th. , Lehnert E.
Published: May 2009

Die Anliegen des Europarates liegen in einer Harmonisierung der Politik, der Förderung der freiwilligen nichtvergüteten Blutspende, der Selbstversorgung der Blut-spendedienste und der Einführung von EU-Qualitätsstandards. Der derzeitige Stand wurde durch eine Studie in 11 ost- und zentraleuropäischen Ländern erhoben. Die Qualitätskontrollen werden in überwiegendem Maße nach alten UdSSR-Empfehlungen vorgenommen. Besorgniserregend ist der allgemeine Rückgang der Spendenzahlen um 15% innerhalb von 2 Jahren. Die Aufbewahrung des Blutes erfolgt zu 65% noch in Flaschen. Zur Deckung des FVIII-Bedarfes ist nahezu eine Verdreifachung der Plasmaproduktion notwendig. Auch in den westeuropäischen Ländern ist eine Selbstversorgung noch nicht gewährleistet. Insgesamt sollten daher in Ost-, Zentral- und auch Westeuropa alle Anstrengungen unternommen werden, die Selbstversorgung im sich zur Einheit formierenden Gesamteuropa zu erzielen.
Molecular Genetics of Human Platelet Antigens
Authors: Simsek S. , von dem Borne A.E.G.Kr.
Published: May 2009

The purpose of this article is to review the molecular genetics of human platelet antigens, the application of molecular biological techniques to detect mutations underlying polymorphisms and the importance of these techniques for clinical medicine of immunemediated platelet destruction. Review articles, original papers and preliminary (unpublished) observations from our own laboratory are the main source for this article. The nomenclature and phenotype frequency of the platelet alloantigens in different ethnic groups are described. Recent molecular biological advances are also reviewed. It appears that the human platelet antigen systems are due to single base pair substitutions. These mutations create or are responsible for the loss of a target site for a restriction enzyme in one of the alleles. Thus, DNA typing by polymerase chain reaction and subsequently allele-specific restriction enzyme analysis (PCR-ASRA) can be performed.
Clinical Aspects of Platelet Transfusion Therapy
Authors: Murphy M.F.
Published: May 2009

Platelet transfusions are established as effective treatment for thrombocytopenic bleeding. However, the indications for prophylactic platelet transfusions are being reconsidered because of the greatly increased demand for platelet concentrates. Platelet refractoriness is the main clinical problem associated with repeated platelet transfusions. This is most frequently due to HLA alloimmunisation or nonimmune platelet consumption associated with clinical factors such as septicaemia. The initial management of refractory alloimmunised patients is to use HLA-matched platelet transfusions. If there is no improvement with HLA-matched platelet transfusions, platelet crossmatching may identify the cause of the problem and help with the selection of compatible donors. Other measures used to improve responses to platelet transfusions are usually ineffective. There has been considerable interest in methods to prevent HLA alloimmunisation and platelet refractoriness and particularly in leucocyte depletion of blood components. The use of leucocyte-depleted blood components has other benefits for multitransfused patients, but further studies are needed before the routine use of leucocyte-depleted blood components can be recommended for patients likely to receive repeated platelet transfusions.
Technische Aspekte der autologen Knochenmarktransplantation
Authors: Handgretinger R. , Klingebiel T. , Niethammer D.
Published: May 2009

Die autologe Stammzelltransplantation ist ein sich zunehmend etablierendes Verfahren in der Behandlung maligner Erkrankungen. Dabei macht man sich die Tatsache zunutze, daß hämatopoetische Stammzellen unter Beibehaltung ihrer Funktion kryokonserviert werden können. Insbesondere bei Patienten mit malignen hämatologischen Neoplasien, für die kein passender allogener Knochenmarkspender bereitsteht, oder bei Patienten mit soliden Tumoren, bei denen im Rahmen der Dosisintensivierung die Schwelle der Knochenmarktoxizität überschritten wird, erlaubt dieses Behandlungsverfahren die Anwendung einer myeloablativen Hochdosistherapie. Als mögliche autologe Stammzellquellen kommen Knochenmark, periphere Blutstammzellen (PBSZ) und Nabelschnurblut in Frage. Das Risiko von kontaminierenden malignen Zellen bei Knochenmark und PBSZ läßt sich durch eine In-vitro-Reinigung der Stammzellen vermindern. Hierfür stehen prinzipiell zwei Arten der Reinigung zur Verfügung: zum einen die Negativdepletion von kontaminierenden Tumorzellen und zum anderen die Positivselektion von nichtmalignen hämatopoetischen pluripotenten Stammzellen. Welches Reinigungsprinzip sich durchsetzen wird, läßt sich abschließend nur nach Durchführung klinischer Studien beurteilen.
Koloniestimulierende Faktoren der Blutbildung
Authors: Goebel M.
Published: May 2009

Ziel dieser Arbeit ist es, einen Überblick des aktuellen klinischen Einsatzes der koloniestimulierenden Faktoren zu geben. Eigene klinische Erfahrungen und die wesentlichen Veröffentlichungen zur Thematik werden dazu herangezogen. Koloniestimulierende Faktoren werden in einer Vielzahl von Erkrankungen und klinischen Situationen hauptsächlich in der Onkologie erfolgreich eingesetzt. Eine Reihe von Fragen sind jedoch noch ungelöst. Es gibt viele neue, weitgehend unerprobte Einsatzgebiete. Neue Indikationen und offenstehende Fragen müssen in geeigneten Studien geklärt werden.
Vascular Regeneration by Local Growth Factor Release Is Self-Limited by Microvascular Clearance
Authors: Le Kha N. , Hwang Chao-Wei , Tzafriri A. Rami , Lovich Mark A. , Hayward Alison , Edelman Elazer R.
Published: May 2009

Background—

The challenge of angiogenesis science is that stable sustained vascular regeneration in humans has not been realized despite promising preclinical findings. We hypothesized that angiogenic therapies powerfully self-regulate by dynamically altering tissue characteristics. Induced neocapillaries increase drug clearance and limit tissue retention and subsequent angiogenesis even in the face of sustained delivery.

Methods and Results—

We quantified how capillary flow clears fibroblast growth factor after local epicardial delivery. Fibroblast growth factor spatial loading was significantly reduced with intact coronary perfusion. Penetration and retention decreased with transendothelial permeability, a trend diametrically opposite to intravascular delivery, in which factor delivery depends on vascular leak, but consistent with a continuum model of drug transport in perfused tissues. Model predictions of fibroblast growth factor sensitivity to manipulations of its diffusivity and transendothelial permeability were validated by conjugation to sucrose octasulfate. Induction of neocapillaries adds pharmacokinetic complexity. Sustained local fibroblast growth factor delivery in vivo produced a burst of neovascularization in ischemic myocardium but was followed by drug washout and a 5-fold decrease in fibroblast growth factor penetration depth.

Conclusions—

The very efficacy of proangiogenic compounds enhances their clearance and abrogates their pharmacological benefit. This self-limiting property of angiogenesis may explain the failures of promising proangiogenic therapies.
Does Greater Adiposity Increase Blood Pressure and Hypertension Risk?
Authors: Timpson Nicholas J. , Harbord Roger , Davey Smith George , Zacho Jeppe , Tybjærg-Hansen Anne , Nordestgaard Børge G.
Published: May 2009

Elevated blood pressure increases the risk of experiencing cardiovascular events like myocardial infarction and stroke. Current observational data suggest that body mass index may have a causal role in the etiology of hypertension, but this may be influenced by confounding and reverse causation. Through the use of instrumental variable methods, we aim to estimate the strength of the unconfounded and unbiased association between body mass index/adiposity and blood pressure. We explore these issues in the Copenhagen General Population Study. We used instrumental variable methods to obtain estimates of the causal association between body mass index and blood pressure. This was performed using both rs9939609 (
FTO
) and rs17782313 (
MC4R
) genotypes as instruments for body mass index. Avoiding the epidemiological problems of confounding, bias, and reverse causation, we confirmed observational associations between body mass index and blood pressure. In analyses including those taking antihypertensive drugs, but for whom appropriate adjustment had been made, systolic blood pressure was seen to increase by 3.85 mm Hg (95% CI: 1.88 to 5.83 mm Hg) for each 10% increase in body mass index (
P
=0.0002), with diastolic blood pressure showing an increase of 1.79 mm Hg (95% CI: 0.68 to 2.90 mm Hg) for each 10% increase in body mass index (
P
=0.002). Observed associations are large and illustrate the considerable benefits in terms of reductions in blood pressure–related morbidity that could be achieved through a reduction in body mass index.
β2-Adrenoceptor Antagonist ICI 118,551 Decreases Pulmonary Vascular Tone in Mice via a Gi/oProtein/Nitric Oxide-Coupled Pathway
Authors: Wenzel Daniela , Knies Ralf , Matthey Michaela , Klein Alexandra M. , Welschoff Julia , Stolle Vanessa , Sasse Philipp , Röll Wilhelm , Breuer Johannes , Fleischmann Bernd K.
Published: May 2009

β2-Adrenoceptors are important modulators of vascular tone, particularly in the pulmonary circulation. Because neurohormonal activation occurs in pulmonary arterial hypertension, we have investigated the effect of different adrenergic vasoactive substances on tone regulation in large and small pulmonary arteries, as well as in systemic vessels of mice. We found that the β2-adrenoceptor antagonist ICI 118,551 (ICI) evoked a decrease of vascular tone in large pulmonary arteries and reduced the sensitivity of pulmonary arteries toward different contracting agents, eg, norepinephrine, serotonin, or endothelin. ICI proved to act specifically on pulmonary vessels, because it shifted the dose-response curve of norepinephrine to the right in pulmonary arteries, whereas there was no effect in the aorta. Pharmacological experiments proved that the right shift of the norepinephrine dose-response curve by ICI was mediated via a β2-adrenoceptor/Gi/oprotein-dependent pathway enhancing NO production in the endothelium; these results were corroborated in β-adrenoceptor and endothelial NO synthase knockout mice where ICI had no effect. ICI increased vascular lumen diameter in lung sections and reduced pulmonary arterial pressure under normoxia and under hypoxia in the isolated perfused lung model. These effects were found to be physiologically relevant, because ICI specifically decreased pulmonary but not systemic blood pressure in vivo. Thus, the β2-adrenoceptor antagonist ICI is a pulmonary arterial-specific vasorelaxant and, therefore, a potentially interesting novel therapeutic agent for the treatment of pulmonary arterial hypertension.
Circulating and Placental Growth-Differentiation Factor 15 in Preeclampsia and in Pregnancy Complicated by Diabetes Mellitus
Authors: Sugulle Meryam , Dechend Ralf , Herse Florian , Weedon-Fekjaer M. Susanne , Johnsen Guro M. , Brosnihan K. Bridget , Anton Lauren , Luft Friedrich C. , Wollert Kai C. , Kempf Tibor , Staff Anne Cathrine
Published: May 2009

Growth-differentiation factor 15 (GDF-15), a stress-responsive transforming growth factor-β–related cytokine, is emerging as a new risk marker in patients with cardiovascular disease. We explored GDF-15 in preeclampsia and in diabetic pregnancies, because these conditions are associated with augmented risk for cardiovascular disease, both in mother and in offspring. Plasma from pregnant women (n=267; controls: n=59, preeclampsia: n=85, diabetes mellitus: n=112, and superimposed preeclampsia in diabetes mellitus: n=11), fetal plasma (n=72), and amniotic fluid (n=99) were analyzed by immunoassay for GDF-15. Placental GDF-15 mRNA and protein expression levels were analyzed by quantitative real-time PCR and immunoblots in 78 and 18 pregnancies, respectively. Conditioned media from preeclamptic (n=6) and control (n=6) villous placenta explants were analyzed by immunoassay for GDF-15. Median maternal GDF-15 concentration was elevated in those with diabetes mellitus, as compared with controls (91 549 versus 79 875 ng/L;
P
=0.02). Median GDF-15 concentration was higher in patients with preeclampsia than in controls in term maternal blood samples (127 061 versus 80 319 ng/L;
P
<0.001). In the fetal circulation and amniotic fluid, GDF-15 was elevated in preeclampsia and superimposed preeclampsia in diabetes mellitus, as compared with controls. GDF-15 placental mRNA expression was elevated in preeclampsia, as compared with controls (
P
=0.002). Placenta immunoblots confirmed a single GDF-15 protein band, and a time-dependent increase in GDF-15 protein was detected in the conditioned media. Our study is the first to show that GDF-15 is dysregulated, both in preeclampsia and in diabetic pregnancies. The mechanisms and diagnostic implications of these findings remain to be explored.
Connecting Prepaid Cards and Retail Loans: Innovative Practical Solution or Confusing Legal Combination? Implications of the EU Financial Services Law from an Estonian Perspective
Authors: Ulst Ingrid
Published: May 2009

A prepaid card is a fairly new financial product that is part of the global innovations in financial services of the last 10 years. Some non-bank financing companies (e.g., SMS loan providers) have further advanced this product by linking prepaid cards to retail loans, which entails more developed transaction schemes and technical solutions. This combination is seen as a practical solution that broadens the customer base of loan providers and improves consumer convenience. However, from a legal point of view, practicality often entails complexity.This article seeks to address some of the major legal features and positions with regard to the prepaid card and its combination with a retail loan. In doing so, it will review the position of a prepaid card and the status of the issuer within the existing legal framework in Estonia. It also seeks to explain how the idea of linking prepaid cards with retail loans is being carried in practical terms through a complex network of agreements. We shall also discuss treating a prepaid card as an instrument of electronic money or some other form of payment, and examine the functions and licensing of an issuer. In anticipating potential discussion of the above topics from the perspective of a member state, this article compares the principles of EU law and the legal framework of Estonia. While we shall briefly deal with certain aspects of consumer protection, the focus of the article is on examining the relevant financial services legislation.
Diagnosis of the MJO Modulation of Tropical Cyclogenesis Using an Empirical Index
Authors: Camargo Suzana J. , Wheeler Matthew C. , Sobel Adam H.
Published: May 2009

The modulation of tropical cyclone activity by the Madden–Julian oscillation (MJO) is explored using an empirical genesis potential (GP) index. Composite anomalies of the genesis index associated with the different MJO phases are consistent with the composite anomalies in TC genesis frequency that occur in the same phases, indicating that the index captures the changes in the environment that are at least in part responsible for the genesis frequency changes. Of the four environmental variables that enter the genesis potential index, the midlevel relative humidity makes the largest contribution to the MJO composite GP anomalies. The second largest contribution comes from the low-level absolute vorticity, and only very minor contributions come from the vertical wind shear and potential intensity.

When basin-integrated MJO composite anomalies of the GP index are regressed against basin-integrated composite anomalies of TC genesis frequency, the results differ quantitatively from those obtained from the analogous calculation performed on the annual climatologies in the two quantities. The GP index captures the MJO modulation of TC genesis to a lesser degree than the climatological annual cycle of genesis (to which it was originally tuned). This may be due to weaknesses of the reanalysis or indicative of the importance of precursor disturbances, not well captured in the GP index computed from weekly data, to the intraseasonal TC genesis frequency fluctuations.
Implications of Both Statistical Equilibrium and Global Warming Simulations with CCSM3. Part I: On the Decadal Variability in the North Pacific Basin
Authors: d’Orgeville Marc , Peltier W. Richard
Published: May 2009

In the low-resolution version of the Community Climate System Model, version 3 (CCSM3), the modeled North Pacific decadal variability is demonstrated to be independent of the epoch for which a statistically steady control simulation is constructed, either preindustrial or modern; however, it is demonstrated to be significantly affected by the different global warming scenarios investigated.

In the control simulations, the North Pacific basin is shown to be dominated by sea surface temperature (SST) variability with a time scale of approximately 20 yr. This mode of variability is in close accord with the observed characteristics of the Pacific decadal oscillation (PDO). A detailed analysis of the statistical equilibrium runs is performed based on other model variables as well [sea surface salinity (SSS), barotropic circulation, freshwater and heat fluxes, wind stress curl, sea ice, and snow coverage]. These analyses confirm that the underlying mechanism of the PDO involves a basin-scale mode of ocean adjustment to changes of the atmospheric forcing associated with the Aleutian low pressure system. However, they also suggest that the observed sign reversal of the PDO arises from a feedback in the northern part of the basin. In this novel hypothesis, the advection to the Bering Sea of “spice” anomalies formed in the central and western Pacific sets up a typical 10-yr time scale for the triggering of the PDO reversal.

In all of the global warming simulations described in this paper, the signal represented by the detrended SST variability in the North Pacific displays significant power at multidecadal frequencies. In these simulations, the natural North Pacific decadal variability, as characterized in the control simulations (the PDO), remains the leading mode of variability only for moderate forcing. If the warming is too strong, then the typical 20-yr time scale of the canonical PDO can no longer be detected, except in terms of SSS variability and only prior to a significant change that occurs in the Bering Strait Throughflow.
Implications of Both Statistical Equilibrium and Global Warming Simulations with CCSM3. Part II: On the Multidecadal Variability in the North Atlantic Basin
Authors: d’Orgeville Marc , Peltier W. Richard
Published: May 2009

The nature of the multidecadal variability in the North Atlantic basin is investigated through detailed analysis of multicentury integrations performed using the low-resolution version of the Community Climate System Model, version 3 (CCSM3), a modern atmosphere–ocean coupled general circulation model. Specifically, the results of control simulations under both preindustrial and present-day perpetual seasonal cycle conditions are compared to each other and also to the results of five simulations with increasing CO2 concentration scenarios.

In the absence of greenhouse gas–induced warming, the meridional overturning circulation (MOC) variability is shown to be dependent on the details of the simulation. In the present-day control simulation, the MOC is characterized by a broad spectrum of low frequencies, whereas, in preindustrial control simulations, MOC variability is characterized either by a well-defined periodicity of 60 yr or by a broad spectrum of low frequencies. In all the control simulations, the MOC appears to respond with a delay of 10 yr to synchronous temperature and salinity anomalies in the deep water formation sites located in the subpolar gyre, but salinity dominates the density anomalies. The explanation of the modeled MOC periodicity is therefore sought in the creation of these density anomalies. The influence of increased sea ice coverage under cold/preindustrial conditions is shown to modify the salinity variability, but it is not a sufficient condition for the support of the MOC periodicity. Instead, its source appears to be a modified subpolar gyre circulation resulting from interaction with the bottom bathymetry, which is able to sustain strong coupling between the horizontal and overturning circulations.

Based on the global warming analyses, for the simulations initialized from the cold/preindustrial statistical equilibrium run, the North Atlantic variability continues to be dominated by strong coupling between the horizontal and overturning circulations if the imposed forcing is weak. More generally, the delayed response of the MOC to surface density anomalies in the deep water formation regions is preserved under weak forcing.
Estimating the Proportion of Monthly Precipitation that Falls in Solid Form
Authors: Legates David R. , Bogart Tianna A.
Published: May 2009

In applications where a monthly temporal resolution is employed, an important variable is the proportion of monthly precipitation that falls in solid form. Globally applicable equations for estimating this variable developed by previously published research are reevaluated. A revised equation developed 20 years ago by the lead author for climatological analysis works well for long-term data but not for actual monthly averages. A new equation, therefore, is developed for use with monthly data using an Arctic database of stations above 50°N latitude. These two equations have mean absolute fit errors of 0.0569 and 0.0614, respectively. The data were split into four regions—North America, northern Europe, northern Asia, and Greenland—and were also evaluated for the effect of elevation or seasonality influences. Results suggest that seasonality also is an important variable, particularly to differentiate between midwinter and transition months (i.e., October and April).
A Theory-Based Hydrometeor Identification Algorithm for X-Band Polarimetric Radars
Authors: Dolan Brenda , Rutledge Steven A.
Published: May 2009

Although much work has been done at S band to automatically identify hydrometeors by using polarimetric radar, several challenges are presented when adapting such algorithms to X band. At X band, attenuation and non-Rayleigh scattering can pose significant problems. This study seeks to develop a hydrometeor identification (HID) algorithm for X band based on theoretical simulations using the T-matrix scattering model of seven different hydrometeor types: rain, drizzle, aggregates, pristine ice crystals, low-density graupel, high-density graupel, and vertical ice. Hail and mixed-phase hydrometeors are excluded for the purposes of this study. Non-Rayleigh scattering effects are explored by comparison with S-band simulations. Variable ranges based on the theoretical simulations are used to create one-dimensional fuzzy-logic membership beta functions that form the basis of the new X-band HID. The theory-based X-band HID is applied to a case from the Collaborative Adaptive Sensing of the Atmosphere (CASA) Integrated Project 1 (IP1) network of X-band radars, and comparisons are made with similar S-band hydrometeor identification algorithms applied to data from the S-band polarimetric Next Generation Weather Radar (NEXRAD) prototype radar, KOUN. The X-band HID shows promise for illustrating bulk hydrometeor types and qualitatively agrees with analysis from KOUN. A simple reflectivity- and temperature-only HID is also applied to both KOUN and CASA IP1 data to reveal benefits of the polarimetric-based HID algorithms, especially in the classification of ice hydrometeors and oriented ice crystals.
Portable Raman Lidar PollyXT for Automated Profiling of Aerosol Backscatter, Extinction, and Depolarization
Authors: Althausen Dietrich , Engelmann Ronny , Baars Holger , Heese Birgit , Ansmann Albert , Müller Detlef , Komppula Mika
Published: May 2009

Two versions of the portable aerosol Raman lidar system (Polly) are presented. First, the two-channel prototype is depicted. It has been developed for the independent and simultaneous determination of particle backscatter and extinction coefficient profiles at 532 nm. Second, the 3 + 2 Raman lidar PollyXT (3 + 2: three backscatter and two extinction coefficients), the second generation of Polly, is described. The extended capabilities of PollyXT are due to the simultaneous emission of light with three wavelengths, more laser power, a larger main receiver mirror, and seven receiver channels. These systems are completely remotely controlled and all measurements are performed automatically. The collected data are transferred to a home server via the Internet and are displayed on a Web page. This paper describes the details of the optical setup, the housekeeping of the systems, and the used data retrieval routines. A measurement example taken close to Manaus, Brazil, on 15 August 2008 shows the capabilities of PollyXT.