Acute dialysis: PMN-elastase as a new parameter for controlling individual anticoagulation with low molecular weight heparin (Fragmin).

Despite the improvements in the development of dialyzer membranes with greater hemocompatibility, an activation of the coagulation system occurs when blood comes into contact with exogenous surfaces. The large number of heparin dosage regimens demonstrate the difficulty to adapt general therapeutic guidelines. Low molecular weight heparin (Fragmin®) was administered as a single bolus dose for anticoagulation during 58 acute dialyses. Anti-Xa-activity, the plasma levels of the lysosomal elastase of the polymorphnuclear granulocytes (“PMN-elastase”) and of the thrombin-antithrombin III-complex (TAT) were measured at hourly intervals. Therapeutic anti-Xa-levels did not show evidence of suffici…

Postoperative Reduction of Fibrinolysis as a Prognostic Factor of Fatal Outcome

For the resection of an esophagus carcinoma a mortality rate of 2 to 30% was described, It is still unclear whether an abdominothoracic or transhiatal intervention is superior regarding the outcome. To investigate the prognostic value of fibrinolytic markers, plasmin-α2-antiplasmin (PAP) and D-dimer (DD) values were determined daily in the early postoperative period for 11days. In addition, the course of PAP and DD concentrations was compared with the method of esophagectomy. Of the 28 patients enclosed in the study, 5 died between day 10 and day 34 owing to adult respiratory distress syndrome and septicemia. The PAP and DD concentrations increased in survivors after surgery until day 5 an…

Immunonephelometric determination of the apolipoprotein A-II.

A fully mechanized immunonephelometric method is described for the rapid and specific determination of apolipoprotein A-II in serum. The method utilizes commercially available sheep antiserum against human apolipoprotein A-II. Nephelometry was performed with the Behring Nephelometer Analyzer (BNA). A single determination can be performed in 12 minutes, requiring 10 microliters sample volume. The measuring range is about 0.08 to 1.25 g/l apolipoprotein A-II. Precision is characterized by intra-assay coefficients of variation of 3.37%, 3.93% and 4.49% for apolipoprotein A-II concentrations of 1.22 g/l, 0.376 g/l and 0.185 g/l, and inter-assay coefficients of variation of 4.27% for an apolipop…

Are Morphological or Functional Changes in the Carotid Artery Wall Associated With Chlamydia pneumoniae, Helicobacter pylori, Cytomegalovirus, or Herpes Simplex Virus Infection?

Background and Purpose —Chronic infection with Chlamydia pneumoniae , Helicobacter pylori , cytomegalovirus (CMV), and herpes simplex virus (HSV) has been implicated in the pathogenesis of atherosclerosis. The carotid intima-media thickness (IMT) can be taken to indicate early atherosclerosis, the presence of a carotid stenosis is a marker of a manifest carotid atherosclerosis, and an increase in arterial stiffness is used as marker of structural and functional changes in an atherosclerotic vessel wall. Methods —In 504 patients (75% men; mean age 62.9 [SD 10] years), we measured the IMT and the elastic pressure modulus (EP; n=445) of the common carotid artery and the prevalence of a intern…

Serum uric acid as an independent predictor of mortality in patients with angiographically proven coronary artery disease.

It is a matter of controversy as to whether uric acid is an independent predictor of mortality in patients with coronary artery disease (CAD) or whether it represents only an indirect marker of adverse outcome by reflecting the association between uric acid and other cardiovascular risk factors. Therefore, we studied the influence of uric acid levels on mortality in patients with CAD. In 1,017 patients with angiographically proven CAD, classic risk factors and uric acid levels were determined at enrollment. A follow-up over a median of 2.2 years (maximum 3.1) was performed. Death from all causes was defined as an end point of the study. In CAD patients with uric acid levels303 micromol/L (5…

Influence of HMG-CoA reductase inhibitors on markers of coagulation, systemic inflammation and soluble cell adhesion.

Abstract Background: Beneath its lipid-lowering properties additional non-lipid effects of statin therapy are discussed. We therefore examined the impact of statins on laboratory markers of coagulation, inflammation and soluble cell adhesion to further explore these effects in 950 hospitalised patients with angiographically proven CAD. Methods and results: Although no significant differences were found in total cholesterol, LDL and HDL and triglyceride levels a statistically lower value in 277 statin-treated patients was found for von Willebrand factor [162(130/224) vs. 208(154/283)%, P =0.0001], leukocyte count [6.9(5.8/8.4) vs. 7.3(6.1/9.4)/nl, P =0.0005], high sensitive CRP [4.3(1.8/10.8…

The presence of infection-related antiphospholipid antibodies in infective endocarditis determines a major risk factor for embolic events.

Abstract OBJECTIVES The impact of infection-associated antiphospholipid antibodies (APA) on endothelial cell activation, blood coagulation and fibrinolysis was evaluated in patients with infective endocarditis with and without major embolic events. BACKGROUND An embolic event is a common and severe complication of infective endocarditis. Despite the fact that APAs are known to be associated with infectious diseases, their pathogenic role in infective endocarditis has not been clearly defined. METHODS The relationship among the occurrence of major embolic events, echocardiographic vegetation size, endothelial cell activation, thrombin generation, fibrinolysis and APA was examined in 91 patie…

Recombinant hirudin as a periprocedural antithrombotic in coronary angioplasty for unstable angina pectoris

Percutaneous transluminal coronary angioplasty is often complicated by thrombotic abrupt vessel closure in patients with unstable angina pectoris. The present multicentre trial was performed to determine the feasibility of two-dose regimens of recombinant hirudin (r-hirudin) compared to standard heparin in patients undergoing coronary angioplasty for unstable angina, and to investigate the effects of the different treatment regimen on markers of coagulation activation. At five participating centres, 61 patients were randomly enrolled in one of two sequential groups of r-hirudin (group 1: 0.3 mg.kg-1 i.v. bolus, 0.12 mg.kg-1.h-1 i.v. infusion; 21 patients; group 2: 0.5 mg.kg-1 i.v. bolus, 0.…

Die Rolle von Inflammation und Infektion bei akutem Koronarsyndrom

Ein entzundlicher Prozess innerhalb der Gefaswand wird heute weitgehend als Ursache fur Beginn und Progression der Atherosklerose angesehen. Als Reaktion auf eine Endothelzellverletzung kommt es zu einer fokalen Entzundungsreaktion, die eine Vulnerabilitat der Plaque mit moglicher Ruptur und schlieslich das klinische Bild eines akuten Koronarsyndroms zur Folge haben kann.

Evaluation of an automated chromogenic substrate assay for the rapid determination of hirudin in plasma.

Abstract A fully mechanized chromogenic substrate assay method for the rapid and specific determination of recombinant hirudin (r-hirudin) in citrated plasma on clinical chemistry analyzers (Hitachi 911 and Cobas Mira) is described. In a first step, 12 μl sample volume is mixed with the chromogenic substrate. Due to the almost immediate action of hirudin the inhibitory reaction and the cleavage of the substrate is started simultaneously when bovine thrombin is added in excess. This excludes interferences by antithrombin III or heparin cofactor II. The change in absorbance/min is recorded at 405 nm. The measuring range is about 0.2 – 4.0 mg/l r-hirudin on both analyzers. Precision is charact…

Manifestationen der Atherosklerose in verschiedenen Gefäßregionen

Aus pathologischen Untersuchungen ist bekannt, dass es sich bei der Atherosklerose um eine Erkrankung handelt, die den gesamten Gefasbaum betrifft. In der Framingham-Studie wurden Risikofaktoren der Atherosklerose ermittelt, die fur die Lokalisation der Atherosklerose in verschiedenen Gefasprovinzen eine unterschiedliche Wertigkeit besitzen. Patienten mit Manifestationen der Atherosklerose in Herz-, Hals- und Beinschlagadern haben im Vergleich zu einem Normalkollektiv eine schlechtere Prognose. Auserdem liegt eine hohe Koinzidenz von atherosklerotischen Lasionen in den verschiedenen Gefasregionen vor. Besonders ungunstig ist die Prognose fur Patienten, die zum Zeitpunkt der Untersuchung ber…

Reoperation and the centrifugal pump?

Postperfusion syndrome is still a problem in long cardiac operations using extracorporeal circulation (ECC). To evaluate whether or not centrifugal blood pumping during open heart surgery is beneficial, a randomized, prospective study was undertaken of 50 consecutive patients undergoing elective coronary artery bypass grafting. The patients were divided into two groups of 25 each. In group 1 a centrifugal pump (Biomedicus) was used as arterial blood pump, while in group 2 a roller pump (Stockert) was used. The two groups did not differ significantly and the number of variables during surgery was kept low (identical perfusion set, two surgeons, minimal cardiotomy suction). The parameters stu…

Genetic and environmental influences on the fibrinolytic system: a twin study.

SummaryThe determination of heritability is a key issue to assess the predictive power of polymorphisms for disease in clinical studies. The aim of this study was to determine the heritability of proteins and activation markers of the fibrinolytic system in a large cohort of healthy twins. Heritability was calculated as 0.76 for thrombin activatable fibrinolysis inhibitor (TAFI), 0.44 for plasminogen activator inhibitor-1 (PAI-1), and 0.43 for tissue plasminogen activator. No significant genetic influence was observed for α2-antiplasmin-plasmin-complex and D-dimer. Heritability explained by single gene polymorphisms was 25.2% for TAFI 505G>A, 31.5% for 1542C>G, and 50.0% for combinati…

Increased plasma concentration of fibrin monomer in acute myocardial infarction with early reperfusion.

OBJECTIVE To assess whether plasma fibrin monomer (FM) concentration, a marker of thrombin activity, is increased in the first hours after acute coronary occlusion and whether there are differences between patients with and without early reperfusion. DESIGN Thirty-five consecutive patients with acute myocardial infarction (AMI) and early coronary angiography were studied prospectively. METHODS Plasma FM samples taken on admission (< 6 h after onset of chest pain) and 6-14 h after onset of chest pain were analysed using a specific enzyme immunoassay. All of the patients were anticoagulated with heparin intravenously. RESULTS Of the 35 patients, 28 had angiographically documented reperfusion …

Verbesserung der postoperativen Thromboseprophylaxe in der Unfallchirurgie durch Dosisanpassung niedermolekularen Heparins anhand TAT- und D-Dimer-Verlauf

Von Februar 197 bis Februar 1998 wurde bei 518 Patienten die postoperative Thromboseprophylaxe mit niedermolekularem Heparin anhand der Laborparameter TAT und D-Dimer dosisadaptiert vorgenommen. Es traten vier Thrombosen (1,6%) ohne embolische Komplikation auf. Die praoperativen TAT- und D-Dimer-Werte aller im Gesamtverlauf dosisangepasten lagen im Mittel signifikant hoher als die der ubrigen Patienten. 83% aller Adaptierungen erfolgten dabei zwischen dem vierten und siebten postoperativen Tag.

Glutathione Peroxidase 1 Activity and Cardiovascular Events in Patients With Coronary Artery Disease

Along with superoxide dismutase, glutathione peroxidase 1 is one of the cellular antioxidant enzymes that have a key role in controlling reactive oxygen species. It uses glutathione to reduce hydrogen peroxide to water and lipid peroxides to their respective alcohols. There are suggestions from in vitro and animal studies that these enzymes could protect against atherosclerosis. This prospective study examined the possibility that relatively high activity of antioxidant enzymes protects against cardiovascular events. The study population included 636 patients suspected of having coronary artery disease who were followed for a median period of 4.7 years. Stable angina was present in 510 pati…

Circulating Cell Adhesion Molecules and Death in Patients With Coronary Artery Disease

Background —Vascular cell adhesion molecule (VCAM)-1, intercellular adhesion molecule (ICAM)-1, and E-selectin mediate adhesion and transmigration of leukocytes to the vascular endothelial wall and may promote plaque growth and instability. In a prospective study, we evaluated the effect of soluble adhesion molecules on the risk of future cardiovascular events among patients with angiographically documented coronary artery disease (CAD). Methods and Results —We obtained baseline samples from a prospective cohort of 1246 patients with CAD. Besides various markers of inflammation, soluble VCAM-1 (sVCAM-1), sICAM-1, and sE-selectin were determined. Follow-up information on cardiovascular even…

Intracoronary application of C1 esterase inhibitor improves cardiac function and reduces myocardial necrosis in an experimental model of ischemia and reperfusion.

Background Myocardial injury from ischemia can be aggravated by reperfusion of the jeopardized area. The precise underlying mechanisms have not been clearly defined, but proinflammatory events, including complement activation, leukocyte adhesion, and infiltration and release of diverse mediators, probably play important roles. The present study addresses the possibility of reducing reperfusion damage by the application of C1 esterase inhibitor (C1-INH). Methods and Results Cardioprotection by C1-INH 20 IU/kg IC was examined in a pig model with 60 minutes of coronary occlusion, followed by 120 minutes of reperfusion. C1-INH was administered during the first 5 minutes of coronary reperfusion…

Monitoring prothrombin fragment 1+2 during initiation of oral anticoagulant therapy after intracoronary stenting

Patients with intracoronary stent implantation are treated with aggressive anticoagulant and antiplatelet therapy consisting of high-dose heparin, phenprocoumon, acetylsalicylic acid, dipyridamole, and the infusion of dextran to prevent a subacute thrombotic occlusion of the stented segment. In an effort to optimize this treatment by reducing both imminent bleeding complications and subacute thrombotic occlusion, the concentrations of prothrombin fragment 1 + 2 (F 1 + 2) were determined after intracoronary Palmaz-Schatz stent implantation in 19 consecutive patients. The F 1 + 2 concentrations after stent implantation and before the initiation of oral anticoagulant therapy (OAT) were 0.35 nm…

Fatal Late Vitamin K-Deficiency Bleeding After Oral Vitamin K Prophylaxis Secondary to Unrecognized Bile Duct Paucity

Influence of blood sampling from venipunctures and catheter systems on serial determinations of prothrombin activation fragment 1 + 2 and thrombin-antithrombin III complex

To evaluate the influence of different blood sampling techniques on test results of thrombin-antithrombin III complex (TAT) and prothrombin fragment 1 + 2 (F1 + 2) serial determinations were performed. In six groups of nonrandomized patients (ten patients each) the concentrations of the coagulation markers of blood samples from central catheters (internal jugular, caval, Shaldon, pulmonary artery) and peripheral cannulas (17G and 18G) were compared with those of blood samples obtained simultaneously from direct venipunctures of the contralateral arm. Medians and 25th-75th percentiles of TAT and F1 + 2 concentrations of plasmas obtained from central catheters were not different from those ta…

ProC Global: the first functional screening assay for the complete protein C pathway.

Abstract In clinical practice, venous thromboembolic complications are much more frequent than bleeding disorders. In fact, disturbances within the protein C pathway due to coagulation factor V (FV) Leiden mutation and deficiency of protein C or protein S are the most frequent abnormalities in hereditary thrombophilia. Furthermore, acquired dysfunctions of the protein C system may predispose the single individual to an increased thrombotic risk. A routine-suited screening assay that would allow the monitoring of the proper interplay of factors in the protein C pathway could add an important factor to the basic coagulation profile. This consists of the prothrombin time and of the activated p…

Cytomegalovirus infection with interleukin-6 response predicts cardiac mortality in patients with coronary artery disease.

Background —Prospective data relating previous exposure to cytomegalovirus (CMV) to the risk of cardiac mortality are controversial. We investigated the effect of previous exposure to CMV infection on the risk of future cardiac disease–related death in relation to an underlying inflammatory response. Methods and Results —Coronary angiography was performed in 1134 subjects, and 989 patients with documented coronary artery disease were studied prospectively. CMV-IgG titers and interleukin (IL)-6 levels were measured before angiography. Increasing titers of CMV correlated with the elevation of IL-6 levels ( P &lt;0.001) after adjustment for possible confounders. All patients were followed up …

HPLC-Bestimmung von Retinol, Retinal und Retinylestern sowie ihren isomeren Konfigurationen in biologischen Proben

Die HPLC-Bestimmung von Retinol, Retinal, Retinylestern und ihren isomeren Konfigurationen erfolgt mit Hilfe von zwei Detektoren bei verschiedenen Wellenlangen. Der reine Retentionszeiten- und Spektrenvergleich bringt keine hinreichende Genauigkeit.

Minimalheparinisierung bei Dialysepatienten mit erhöhter Blutungsgefährdung

Abstract In 78 patients (47 men, 31 women; mean age 53 [22-78] years) 174 dialyses were undertaken within one week of a bleeding episode or a diagnostic or therapeutic procedure which may cause bleeding. Minimal anticoagulation with low molecular weight heparin (LMWH) was the aim, using a biocompatible dialyser. During the dialysis coagulation was controlled by global tests (Quick value/international normalized ratio [INR], partial thromboplastin time, thrombin time, antifactor Xa activity), by molecular markers of clotting activity (thrombin-antithrombin III complex [TAT], D-dimers), as well as measurement of elastase (elastase-alpha 1-protein inhibitor complex). The LMWH dosage averaged 9…

Einsatz von niedermolekularem Heparin zur Antikoagulation in der Schwangerschaft

A 26-year-old woman, on bedrest since the 6th week of pregnancy because of threatened abortion, developed thrombosis in the left iliac, superficial femoral and common femoral veins with small pulmonary emboli in the 11th week. Inhibitor deficiency was excluded. The thrombosis was only partially recanalized by unfractionated heparin at therapeutic dosage (38,400 IU per 24 h). As thrombolysis treatment and oral anticoagulation were contraindicated because of the threatened abortion, coagulation with low molecular weight heparin (LMWH) was started in the 18th week (5000 anti-Xa units daily subcutaneously). Maximal anti-Xa activity in plasma never exceeded 0.3 U/ml and there were no complicatio…

Reference Values for a Homogeneous Ferritin Assay and Traceability to the 3rd International Recombinant Standard for Ferritin (NIBSC Code 94/572)

Abstract Reference values for two ferritin assays (Tina-quant®a Ferritin, Enzymun®, both Roche Diagnostics, Mannheim, Germany) were established (136 males and 139 females). To rule out inflammation as well as iron deficiency in the reference population, subjects with the C-reactive protein concentration &lt; 5 mg/l, and zinc protoporphyrin &lt; 40 µmol/mol heme and the soluble transferrin receptor &lt; 3 mg/l were selected. Taking into account latent iron deficiency as well as hereditary hemochromatosis the 5–95 percentile range was as follows: male, 27–365 μg/l; female, 13–148 μg/l for Tina-quant®a and 12–151 μg/l for Enzymun®. The Tinaquant® a Ferritin assay showed a very good correlation…

Dose-Adjusted Thrombosis Prophylaxis in Trauma Surgery According to Levels of D-Dimer

In 234 trauma surgery patients, thrombosis prophylaxis with Nadroparin-Calcium low-molecular-weight heparin (LMWH) was adjusted according to levels of D-Dimer. Basic prophylaxis was 2,850 IU per day. If D-Dimer concentrations rose above 2 mg/L after the fourth postoperative (p.o.) day, LMWH was administered twice a day. Color Doppler ultrasound was performed between the fifth and seventh p.o. days. Patients were divided into a high-risk (group 1: hip, femur, or knee replacement surgery, n=102) and a moderate-risk group (group 2: other surgery of the knee, tibia, fibula, or foot, n=132). Group 1 showed significantly higher D-Dimer levels than group 2 (p0.001). Measurement of D-Dimer on days …

Akuter Mesenterialarterienverschluß als seltene Manifestation eines primären Antiphospholipid-Antikörpersyndroms

Hintergrund: Das Antiphospholipid-Antikorpersyndrom ist eine thrombophile Erkrankung, in deren Verlauf es zu arteriellen und venosen Thrombosen kommen kann. Wir berichten den seltenen Fall eines akuten Mesenterialarterienverschlusses bei primarem Antiphospholipid-Antikorpersyndrom. Fallbericht: Ein 46jahriger Patient wurde mit starksten, anhaltenden, kolikartigen, rechtsseitigen Oberbauchschmerzen stationar aufgenommen. Unter dem klinischen Bild eines akuten Abdomens wurde laparotomiert. Es erfolgte bei einer Dunndarmgangran im Jejunum eine segmentale Dunndarmresektion. Bei der pathologisch-anatomischen Untersuchung zeigte sich ein partieller, sekundar hamorrhagischer Dunndarminfarkt mit fr…

Pr�vention thromboembolischer Komplikationen in der Unfallchirurgie durch Dosisanpassung von niedermolekularem Heparin anhand TAT- und D-Dimer-Werten

Bei unfallchirurgischen Patienten tritt in bis zu 40% eine tiefe Beinvenenthrombose auf. Das individuelle Risiko kann kaum kalkuliert werden. 518 unfallchirurgische Patienten mit Prophylaxe durch eine tagliche Einzeldosis eines niedermolekularen Heparins (NMH) wurden praoperativ und bis zu 10 Tage postoperativ in einer prospektiven Untersuchung beobachtet. Sie wurden in 2 Gruppen unterteilt: Gruppe I mit Huft- und Oberschenkeloperationen sowie Kniegelenkprothesen und Gruppe II mit Knie- und Unterschenkeloperationen. Bestimmt wurden Thrombin-Antithrombin-Komplex und D-Dimer. Eine 2. Dosis NMH wurde bei Uberschreiten des D-Dimer-Cut-off-Wertes verabreicht. Bei sonographischem Verdacht auf ein…

Immunonephelometric determination of the C4b-binding protein.

A fully mechanised immunonephelometric method for the rapid and specific determination of C4b-binding protein (C4b-BP) in citrated plasma is described. The method utilizes commercially available rabbit antiserum against human C4b-BP and a nephelometer analyser. A single determination can be performed within 6 min, requiring 80 microliters sample volume. The measuring range is about 10 to 200% of normal C4b-BP. Precision is characterized by intraassay coefficients of variation between 1.5% and 2.8%, and interassay coefficients of variation between 4.0% and 4.6% for the same C4b-BP concentrations. The nephelometry of C4b-BP was correlated with electroimmunodiffusion (Laurell technique; r = 0.…

Impact of Viral and Bacterial Infectious Burden on Long-Term Prognosis in Patients With Coronary Artery Disease

Background —The number of infectious pathogens to which an individual has been exposed (infectious burden) may correlate with coronary artery disease (CAD). In a prospective study, we evaluated the effect of 8 pathogens and the aggregate pathogen burden on the risk for future fatal cardiac events among patients with angiographically documented CAD. Methods and Results —In 1018 patients, IgG or IgA antibodies to herpes simplex virus types 1 and 2, cytomegalovirus, Epstein-Barr virus, Haemophilus influenzae , Chlamydia pneumoniae , Mycoplasma pneumoniae , and Helicobacter pylori were determined. Moreover, highly sensitive C-reactive protein was measured. Follow-up information on cardiovascul…

Laboratory control of minimal heparinization during haemodialysis in patients with a risk of haemorrhage

Abstract For patients undergoing dialysis with a high risk of haemorrhage there is no standardized procedure for anticoagulation during extracorporeal circulation. Minimal heparinization with a dose equivalent to half that used for chronic haemodialysis was employed in 49 patients (125 haemodialyses) performed after operative interventions (83.3%), after haemorrhagic events (5.2%) and after invasive investigations (11.5%). Using a biocompatible membrane and a low molecular weight heparin (bolus dose 500-1300 U; continuous infusion 100-400 U) it was possible to complete haemodialysis in 74 cases (Group 0) without clots appearing in the venous bubble trap of the tubing system. In 30 cases (Gr…

False-Positive LSD Drug Screening Induced by a Mucolytic Medication

Since the early 1990s, the ingestion of lysergic acid diethylamide (LSD) as an inexpensive alternative to amphetamine derivatives has once again become widespread (1)(2). Consequently, screening of LSD has gained importance in clinical routine. The drug screening of a patient with a severe craniocerebral trauma showed a positive LSD screening by the homogeneous immunoassay CEDIA® DAU LSD (Boehringer Mannheim). In spite of the 3-h half-life of LSD in plasma (3), the drug screening remained positive for several days. These samples …

Quantification of thrombocyte growth factors in platelet concentrates produced by discontinuous cell separation.

Platelet concentrates (PC) are increasingly used to increase bone regeneration in pre-prosthetic surgery. Although it is generally appreciated that certain growth factors (PDGF, TGF, EGF, and ECGF) are present in thrombocyte preparations, relatively little is known about these components in quantitative terms. The study reported here analysed the amounts of growth factors in PC produced under standard conditions from healthy volunteers. All the blood samples (237 in total) were analysed using Quantikine ELISA kits (R and D). The mean +/- SD platelet count in whole blood from these donors was 262,000+/-58,000/microl, while in PC produced by discontinuous cell separation it was 1.419,000+/-33…

Troponin T — a reliable marker of perioperative myocardial infarction?

Following cardiac surgery, electrocardiography and creatine kinase isoenzyme MB (CK-MB) activities are of limited value in diagnosing a non-transmural infarction. With the recent availability of an assay to detect serial levels of the specific cardiocyte contractile protein troponin T the possibility has been increased of closing a diagnostic gap among cardiosurgical patients. Ninety patients with severe diffuse three-vessel disease undergoing myocardial revascularization were grouped by their postoperative electrocardiographic (ECG) findings (group I--unchanged ECG; group II--new Q-waves representing perioperative myocardial infarction (PMI)). Serial levels of troponin T and the activity o…

Multicenter evaluation of a second-generation assay for cardiac troponin T.

Abstract We report on the evaluation of the second-generation assay for cardiac troponin T (cTnT) on the Enzymun®system. This new assay is completely specific for the cardiac isoform of TnT, utilizing two cardiospecific monoclonal antibodies. The assay time is reduced to 45 min. The interassay precision shows a median CV of 5.5%; 20% interassay CV was found between 0.05 and 0.1 μg/L. The cardiosensitivity of the second-generation cTnT assay in patients with ischemic myocardial injury appears equivalent when compared with the first-generation assay. We found no falsely positive results in patients with skeletal muscle damage including multitraumas, surgery patients, and marathon runners who …

Plasma concentrations and genetic variation of matrix metalloproteinase 9 and prognosis of patients with cardiovascular disease.

Background—Matrix metalloproteinase (MMP)-9 secretion by macrophages and other inflammatory cells accelerates atherosclerotic progression and destabilizes vulnerable plaque in animal models. However, epidemiological data evaluating the prognostic impact of circulating concentrations and functional genetic variations of MMP-9 are lacking.Methods and Results—In a prospective study of 1127 patients with documented coronary artery disease, we measured baseline plasma MMP-9 levels and determined the MMP-9/C-1562T and MMP-9/R279Q genotypes. During the follow-up period (mean of 4.1 years), 97 patients died from cardiovascular (CV) causes. Median concentrations of MMP-9 were significantly higher am…

Comparison of platelet, leukocyte, and growth factor levels in point-of-care platelet-enriched plasma, prepared using a modified Curasan kit, with preparations received from a local blood bank

Abstract The potential use of autologous thrombocytic growth factors to accelerate bone regeneration requires improved methods of isolating platelet-rich plasma (PRP). In addition to discontinuous cell separation, a second method by which PRP is produced at the point-of-care has now become available. In this study, growth factor levels in PRP from these two sources were compared. Whole blood was drawn from 115 healthy donors (73 males, 42 females) aged 21 - 62 years (mean 36, SD 10). The PRP was separated by the blood bank (BB) using the discontinuous cell separation method or at the 'point-of-care' by the so-called 'buffy coat' method (analogous to the Curasan PRP Kit). Growth factor conte…

Determination of Human Granulocyte Elastase by the Immunoactivation Method on the Hitachi® 717 Automated Analyser

This paper describes a fully mechanized homogeneous immunoassay using the immunoactivation method for the rapid and specific determination of human granulocyte elastase (EC 3.4.21.37) in plasma. The method uses anti-elastase antibody fragments from sheep, conjugated to horseradish peroxidase. These enzyme-antibody conjugates bind to the elastase-alpha 1-proteinase inhibitor complex present in plasma. A separate sample blank with non-specific sheep antibody fragments conjugated to horseradish peroxidase corrects for errors introduced by the sample matrix. Measurements were performed with the clinical chemistry analyser Hitachi 717. A single determination can be performed in 10 min, requiring…

Growth factor levels in platelet-rich plasma and correlations with donor age, sex, and platelet count.

Abstract Introduction: Platelet-rich plasma contains autologous thrombocyte growth factors and might be promising for acceleration of dentoalveolar bone regeneration. In this study, it was analysed for platelet counts and growth factor concentrations. Material and method: Platelet-rich plasma was isolated by discontinuous cell separation from 158 healthy men and 55 women aged 17–62 years. One hundred and fifteen specimens (stratified for age and gender of the donor) were analysed for growth factor concentrations and platelet count. Results: The platelet count in platelet-rich plasma (1,407,640±320,100/μl) was 5 times higher than in donor blood (266,040±60,530/μl). Platelet-derived growth fa…

Effest of Molsidomine on t-PA and PAI Activity in Man: A Double Blind, Placebo Controlled Study

In Reply: Cardiac Troponin T in End-Stage Renal Disease Patients Undergoing Chronic Maintenance Hemodialysis

The Harvest Smart PRePTMsystem versus the Friadent-Schütze platelet-rich plasma kit

An important reason to improve methods for isolating platelet-rich plasma (PRP) is the potential use of autogenous platelet growth factors. In addition to the Curasan PRP kit (Curasan, Kleinostheim, Germany) and the platelet concentrated collection system (PCCSTM) system, two new methods for the preparation of PRP by the surgeon are now available. This study compared the suitability of these new methods for the preparation of PRP. Whole blood was drawn from 54 healthy donors (33 men and 21 women) aged 23-79 years (38.0 +/- 17.7 years). PRP was prepared from each donor's blood using both the Smart PRePTM system (Harvest Technologies Corporation, Munich, Germany) and the Friadent-Schutze meth…

Impact of pathogen burden in patients with coronary artery disease in relation to systemic inflammation and variation in genes encoding cytokines.

The number of infectious pathogens to which an individual has been exposed (pathogen burden) has been linked to the development and the prognosis of coronary artery disease (CAD). The interaction among infection, genetic host susceptibility, and CAD remains unclear. This study was aimed at evaluating the modulation of the association between CAD and pathogen burden, by serum levels of inflammatory markers and polymorphisms of the interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha genes. Immmunoglobulin (Ig) G or IgA antibodies to 8 pathogens were determined in 991 patients with CAD and 333 control subjects. Serum levels of high-sensitivity C-reactive protein, fibrinogen, IL-6, and TNF…

Nickel release after implantation of the Amplatzer occluder.

Background Transcatheter closure of atrial septal defects is a new and less traumatic technique than open heart surgery. In recent years, patients with a patent foramen ovale sustaining potential paradoxical embolism have also become candidates for interventional closure devices. One of the more popular occluding devices is the Amplatzer septal occluder, which, like many other occluders, is made of nitinol. Nitinol-based alloys are widely used in medical products, for example, in orthopedics and orthodontics. However, the clinical use of nitinol, which contains 55% nickel, is still controversial because of concerns about its biocompatibility. Therefore, we examined the systemic nickel relea…

Biochemical bone markers compared with bone density measurement by dual energy X-ray absorptiometry

In contrast to medical imaging, the biochemical markers allow a more frequent determination and are not as invasive as histomorphometric methods. We investigated biochemical markers of type I collagen compared with bone density measurements in 85 females between 41 and 89 years of age (median: 57 years). The bone density measurements were performed by dual energy X-ray absorptiometry (DXA) on the lumbar spine (L1-4). The bone density measurements were stated as a percentage of the norm. All patients were divided into three groups: I =80%; II = 80-130%; III =120%. Based on this classification the median concentration of the I-carboxyterminal propeptide of type I collagen in serum (S-PICP) as…

Prognostic value of lipoproteins and their relation to inflammatory markers among patients with coronary artery disease

Abstract Background Lipoproteins and their subfractions are associated with the incidence of atherosclerotic diseases. In patients with coronary artery disease (CAD), low serum concentrations of high density lipoprotein (HDL) and high low-density lipoproteins (LDL) are correlated to myocardial infarction and cardiovascular death. There is growing evidence indicating that those lipoprotein factors are related to the inflammatory process in atherogenesis. Methods We investigated in a median follow up of 3.9 years the association of HDL, apolipoprotein A-I (apoA-I), LDL, apolipoprotein B (apoB), and triglycerides with the incidence of a combined endpoint (myocardial infarction and cardiovascul…

Troponin I concentrations of shed blood might influence monitoring of myocardial injury after coronary operations.

Abstract In a prospective study we evaluated the concentration of cardiac troponin I (cTnI) and creatine kinase activities (CK) in shed mediastinal blood in the early postoperative period after coronary artery bypass grafting (CABG). Forty seven patients who underwent first time elective CABG were studied. CTnI levels and CK activities in arterial blood and shed mediastinal blood were measured after admission to the intensive care unit (ICU) and 6 h after unclamping the aorta. Mediastinal shed blood samples were drawn from 23 patients (group A) before the filter of the cardiotomy reservoir and from 24 patients (group B) behind. Additionally, both markers were measured in blood samples colle…

Retinal vascular occlusion and deficiencies in the protein C pathway.

Abstract PURPOSE: To report abnormalities in the protein C pathway and other vascular occlusion risk factors in patients with retinal vascular occlusion. METHODS: In a study, we investigated 76 consecutive patients who had in-patient evaluation of venous or arterial retinal vascular occlusion. All patients underwent comprehensive tests for coagulation disorders including determinations of protein C, protein S, lupus anticoagulants, and resistance to activated protein C and were screened for vascular disease risk factors. Resistance to activated protein C was confirmed by a polymerase chain reaction method to detect the specific factor V R506Q mutation. For comparative purposes, we also scre…

Impact of infectious burden on extent and long-term prognosis of atherosclerosis.

Background — Recent findings suggest a causative role of infections in the pathogenesis of atherosclerosis. In hypothesizing an association between infectious agents and the development of atherosclerosis, we would expect a correlation to the extent of atherosclerosis. Moreover, this effect could be multiplied by the number of pathogens to which an individual had been exposed. Methods and Results — In 572 patients, IgG or IgA antibodies to herpes simplex virus 1 and 2, cytomegalovirus, Epstein-Barr virus, Hemophilus influenzae , Chlamydia pneumoniae , Mycoplasma pneumoniae , and Helicobacter pylori were measured. The extent of atherosclerosis was determined by coronary angiography, carotid…

Impact of infectious burden on progression of carotid atherosclerosis.

Background and Purpose— Recent findings suggest a causative role of infections in the pathogenesis of atherosclerosis. The extent of atherosclerosis and the prognosis of patients with atherosclerosis seem to be increased by the number of infections to which an individual has been exposed. In a prospective study, we evaluated the effect of 8 pathogens and the aggregate pathogen burden on the progression of carotid atherosclerosis. Methods— In 504 patients (74.9% men; age, 62.9±10 years), we measured intima-media thickness and prevalence of carotid artery stenosis. Follow-up measurements after a mean of 2.5 years were available in 427 patients (85%). Blood samples were taken, and IgG or IgA …

Application of C1-Esterase Inhibitor During Reperfusion of Ischemic Myocardium

Background—Complement activation during reperfusion of ischemic myocardium augments myocardial injury, and complement inhibition with C1-esterase inhibitor (C1-INH) at the time of reperfusion exerts marked cardioprotective effects in experimental studies. Application of C1-INH in newborns, however, was recently reported to have dangerous and even lethal side effects. This study addresses the essential role of dosage in studies using C1-INH.Methods and Results—Cardioprotection by C1-INH was examined in a pig model with 60 minutes of coronary occlusion followed by 120 minutes of reperfusion. C1-INH was administered intravenously 5 to 10 minutes before coronary reperfusion without heparin at a…

Effects of the prostanoid EP3 -receptor agonists M&amp;B 28767 and GR 63799X on infarct size caused by regional myocardial ischaemia in the anaesthetized rat

1. This study investigates the effects of two agonists of the prostanoid EP3-receptor (MB PEEP: 1-2 mmHg) and subjected to occlusion of the left anterior descending coronary artery (LAD, for 7.5, 15, 25, 35, 45 or 60 min) followed by reperfusion (2 h). Infarct size was determined by staining of viable myocardium with a tetrazolium stain (NBT), histological evaluation by light and electron microscopy and determination of the plasma levels of cardiac troponin T. 3. MB saline-control, n=8) to 39+/-6 and 38+/-4% of the area at risk, without causing a significant fall in blood pressure. Pretreatment of rats with 5-hydroxydecanoate (5-HD), an inhibitor of ATP-sensitive potassium channels, attenua…

Reduction of myocardial infarct size with sCR1sLex, an alternatively glycosylated form of human soluble complement receptor type 1 (sCR1), possessing sialyl Lewis x

1 This study investigated the effects of soluble complement receptor type 1 (sCR1) or sCR1sLex, agents which function as a complement inhibitor or as a combined complement inhibitor and selectin adhesion molecule antagonist, respectively, on the infarct size and cardiac troponin T (cTnT) release caused by regional myocardial ischaemia and reperfusion in the rat. 2 Eighty-two, male Wistar rats were subjected to 30 min occlusion of the left anterior descending coronary artery (LAD) followed by 2 h of reperfusion. Haemodynamic parameters were continuously recorded and at the end of the experiments infarct size (with p-nitro-blue tetrazolium) and cTnT release were determined. 3 Infusion of sCR1…

Release of choline in the isolated heart, an indicator of ischemic phospholipid degradation and its protection by ischemic preconditioning: No evidence for a role of phospholipase D

Abstract The release of choline as a water-soluble product of phospholipid hydrolysis was measured in the perfusate of rat hearts to monitor ischemic membrane degradation and its protection by ischemic preconditioning (IPC). Hearts were subjected to global ischemia (GI; 30 min of no-flow) followed by 60 min of reperfusion. To induce IPC, GI was preceded by four no-flow episodes of 5 min each. Deleterious consequences of GI and reperfusion, namely coronary flow reduction, incidence of arrhythmias and release of cardiac troponin T, were significantly attenuated by IPC. The release of choline increased during reperfusion in a biphasic manner: a first phase peaked immediately after GI and was f…

Relation of markers of inflammation (C-reactive protein, fibrinogen, von Willebrand factor, and leukocyte count) and statin therapy to long-term mortality in patients with angiographically proven coronary artery disease

We evaluated a possible interaction between statins and inflammation in 1,246 patients with angiographically diagnosed coronary artery disease. Four different inflammatory markers were determined: high, sensitive C-reactive protein (hs-CRP) (p = 0.001), fibrinogen (p = 0.006), von Willebrand factor (p = 0.006), and leukocyte count (p = 0.03); these levels were significantly higher among the 88 patients who died of cardiac causes during follow-up (median 2.9 years) than among survivors. In a multivariate backward stepwise Cox regression mode, only hs-CRP was evaluated to be a significant predictor of death from coronary artery disease. This prediction was lost in statin-treated patients. Com…