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Biomedical subjects

G Hafner

Publications and source records attributed to G Hafner.

At least 73 records · Page 4Linked to original sources

Recombinant hirudin (HBW 023) prevents troponin T release after coronary angioplasty in patients with unstable angina.

OBJECTIVES: This study was performed to evaluate the efficacy of peri-interventional treatment with recombinant hirudin (r-hirudin [HBW 023]) compared with heparin in the prevention of troponin T release in patients with unstable angina. BACKGROUND: Percutaneous transluminal coronary angioplasty in patients with unstable angina is associated with a high risk of acute thrombotic complications. METHODS: Serial troponin T measurements were performed in 61 patients with unstable angina during the 48-h observation period after coronary angioplasty of the ischemia-related lesion. Patients were randomly assigned to peri-interventional intravenous treatment with either r-hirudin (dosage group I: 0.3-mg/kg body weight bolus, 0.12 mg/kg per h for 24 h; dosage group II: 0.5-mg/kg bolus, 0.24 mg/kg per h for 24 h) or heparin (150-IU/kg bolus, 20 IU/kg per h for 24 h). All patients received acetylsalicylic acid before coronary angiography. After 24 h, patients received a constant low dose infusion of either hirudin (0.04 mg/kg per h) or heparin (7 IU/kg per h) for another 24 h. The power of the study to detect a decrease in abnormal troponin T levels from 60% (heparin group) to 20% (combined r-hirudin groups) was 88%. RESULTS: Serial troponin T measurements revealed two peaks within the 48 h after coronary angioplasty in the heparin but not the hirudin groups. An elevated serum troponin T concentration (> 0.2 ng/ml) within 48 h of coronary angioplasty was found in 9 (24%) of 38 patients in the hirudin groups (5 [25%] of 20 in dosage group I; 4 [22%] of 18 in dosage group II) compared with 11 (58%) of 19 in the heparin group (p = 0.01). We observed major cardiac events (death, myocardial infarction, abrupt vessel closure) in 1 (4.8%) of 21 patients in dosage group I, 1 (5.3%) of 19 in dosage group II and 3 (14.3%) of 21 in the heparin group (p = 0.33). CONCLUSIONS: In this pilot trial, hirudin appears to be superior to heparin in preventing troponin T release after coronary angioplasty.

Angina, Unstable↗

[The use of low-molecular heparin for anticoagulation in pregnancy].

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 complications. The patient was delivered of a healthy girl (2,660 g, 48 cm) by caesarean section in the 37th week. Immediately post-partum LMWH was demonstrated with an anti-Xa activity of 0.3 U/ml in maternal blood, but none in simultaneously obtained cord venous blood. This case suggests that treatment of phlebothrombosis with LMWH is a reasonable measure even during pregnancy.

Abortion, Threatened↗

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

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 (Group 1) only small clots were detected at the end of haemodialysis, and in 13 cases (Group 2) larger clots (exceeding a diameter of 1 cm) were found. In eight cases (Group 3) partial or complete clot formation occurred in the tubing. No haemorrhagic complications were observed. Anti-Xa activity, thrombin-antithrombin III complex (TAT) and D-dimer were determined before haemodialysis, 2 h after the start of haemodialysis and on completion of the procedure. The anti-Xa activities ranged between < 0.2 and 0.56 U/ml. In contrast, at 2 h there were significant differences (P < 0.05) in the TAT concentrations between Group 0 and the other groups, as well as between Group 1 and Group 2 and 3. Significant differences (P < 0.05) in D-dimer levels occurred only at the end of haemodialysis. Minimal heparinization in haemodialysis is a practicable alternative in patients with a high risk of haemorrhage and extended coagulation monitoring is helpful in adjusting heparin dosage.

Adult↗

[Minimal heparinization in dialysis patients with increased risk of bleeding].

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 932 units as an initial bolus and 234 units/h as a continuous infusion. In the group of chronic dialysis patients (n = 72) this meant (standard heparin units = 2/3 LMWH units) a reduction to 45 +/- 11% from the previously used routine heparin dosage for a 4-hour dialysis. All dialyses were completed without bleeding complications. Considerable clotting formation in the extracorporeal circulation occurred in 11 dialyses (6.3%). TAT, D-dimer and elastase values proved to be suitable for determining individual clotting activity and for reducing anticoagulation to the minimum.

Adult↗

Troponin T.

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Humans↗

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 = 0.863, y = 0.909x+7.091, n = 79). C4b-BP concentrations (143%, 96-223%; median and 2.5th-97.5th percentile) from 83 subjects with increased inflammation markers C-reactive protein (> 10 mg/l), and fibrinogen (> 4.5 g/l) showing significantly higher C4b-BP concentrations compared to 151 obviously healthy subjects (97%, 68-141%; p < 0.001). In contrast to 81 patients with therapeutic heparinisation (90%, 60-131%) significant decreased concentrations were found in 90 subjects under oral anticoagulant therapy (OAT) in the stable state (78%, 44-125%; p < 0.001). Depending on different INR levels (< 2.5, n = 40: 71%, 63-85%; > 2.5, n = 50: 81%, 68-92%; median and 25th-75th percentile) no significant differences of C4b-BP concentrations could be measured.

Administration, Oral↗

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 taken from venipunctures. When delta mean values (catheter - venipuncture) were calculated negative results were obtained, indicating lower concentrations measured from blood sampled through central catheters with the exception of blood that taken from Shaldon catheters. Only for TAT concentrations significantly were lower values measured in blood samples taken from internal jugular catheters when compared with blood samples obtained from direct venipunctures. Significantly higher TAT concentrations were determined in blood samples obtained from Shaldon catheters. For both coagulation markers correlations were found between concentrations in blood samples from central catheters and venipunctures. In blood samples taken from peripheral venous cannulas only F1 + 2 concentrations correlated with the concentrations found in samples from direct venipuncture. In contrast to F1 + 2, TAT concentrations measured from blood samples via peripheral cannulas were determined significantly higher than those taken from direct venipunctures.(ABSTRACT TRUNCATED AT 250 WORDS)

Antithrombin III↗

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 of CK-MB were measured 6, 12, 24 and 48 h after aortic unclamping. The course of CK-MB activity was compared to a profile and values derived from patients with unchanged (n = 1312) or new Q-wave ECGS (n = 89). In 72 patients (80.0%) with unchanged postoperative ECG (group I) serial troponin T levels remained constantly low and reached a median peak value of 0.37 microgram/l (quartile 0.13-0.50 microgram/l) after 24 h. Serial CK-MB activities demonstrated the typical non-ischemic course with a monoexponential decline from an initial median peak value of 15.5 U/l (quartile 12.0-21.0 U/l) to 7.0 U/l (quartile 6.0-9.0 U/l). In seven patients (7.8%) with new Q-waves and a pathologic CK-MB profile (group II) troponin T reached median levels of 10.47 micrograms/l (quartile 6.34-12.50 micrograms/l) (P < 0.001 I vs II). Four of five patients with a new right bundle branch block demonstrated low troponin T levels below 1 microgram/l and a normal CK-MB profile. Among six patients with unchanged QRS-configuration and elevated troponin T levels between 0.84 and 4.99 micrograms/l CK-MB activity showed a characteristic PMI pattern in two patients. Troponin T is characterized by a very narrow margin of normal values represented by a maximum third quartile of 0.50 microgram/l. A singular value of troponin after 6 h or 24 h may be sufficient evidence to confirm the diagnosis of a PMI.

Aged↗

Nucleotide sequence of one component of the banana bunchy top virus genome contains a putative replicase gene.

One DNA component of the banana bunchy top virus (BBTV) genome was cloned and sequenced. This component is present as a circular, ssDNA in the virions and consists of 1111 nucleotides. It contains one large open reading frame (ORF) of 858 nucleotides in the virion sense; this ORF encodes a putative replicase based on the presence of a dNTP-binding motif (GGEGKT). Two smaller ORFs (249 and 366 nucleotides), in the complementary orientation, could not be assigned any obvious function. Neither of these ORFs had significant sequence homology with any known DNA plant virus gene or gene product. Computer analysis of this component-predicted a strong stem-loop structure in the virion sense putative untranslated region; a nonanucleotide sequence in the loop was nearly identical to the nonanucleotide invariant loop sequence of geminiviruses and coconut foliar decay virus. There is strong evidence that the genome of BBTV consists of more than one component because no ORF was found that would encode a protein the size of the BBTV coat protein. BBTV has some characteristics in common with geminiviruses but cannot be classified as one. Rather, BBTV probably belongs to an undescribed plant virus group which could also include subterranean clover stunt virus and coconut foliar decay virus.

Amino Acid Sequence↗

[Prevention of thrombosis in protein C deficiency].

In a 14-years old girl, suffering from deep venous thrombosis protein C deficiency (activity: 55-58%) was diagnosed. Following rethrombosis oral anticoagulant therapy (OAT) with Phenprocoumon (Marcumar) was started. To find the required dosage for OAT the concentrations of prothrombin fragment (F1+2; < 0.5 nM/l) and fibrin monomers (< 2.5 mg/l) were measured. With this procedure an unusually high thromboplastin time (40-45%) was found to be safe.

Adolescent↗

[Multicenter results of coronary implantation of balloon expandable Palmaz-Schatz vascular stents].

Intracoronary stenting was designed to handle acute vessel closure after balloon angioplasty and to reduce the rate of restenosis. In three cardiology centers the implantation of 200 balloon-expandable Palmaz-Schatz stents was attempted in 179 patients. The implantation was successful in 170 patients (95%). During bail-out implantation for acute vessel closure or symptomatic dissections after balloon angioplasty, implantation succeeded in 60 (91%) of 66 attempted patients, who recovered immediately from ischemia. Three patients received emergency bypass surgery and three patients were kept on medical therapy. Restenosis after 4 to 6 months, defined as > 50% diameter reduction, was documented angiographically in 18 (15.3%) of 118 presently controlled patients. Patients with single stent implantation (n = 106) presented a late restenosis rate of 10.4% in contrast to patients with multiple stent implantation (n = 12), who presented a restenosis rate of 58.4%. Similar results on restenosis were found for patients with elective and bail-out stent implantation. Acute thrombotic stent occlusion occurred in three patients (1.8%) during the first 24 h after stenting. Three to 9 days after implantation subacute stent thrombosis occurred in 15 (8.8%) of 170 patients. Despite adequate therapy including thrombolysis, balloon angioplasty or emergency bypass surgery in 14 of 15 patients Q-wave myocardial infarction was documented in six patients and non Q-wave myocardial infarction in five patients. The following parameters were identified as risk factors for the development of subacute stent thrombosis: bail-out indication, unstable angina, type C lesion, stenosis length > 1.5 cm, plaque area > 3.5 mm2, symptomatic dissection after balloon angioplasty, incomplete wrapping of the dissection after stenting and residual distal vessel irregularities after stenting. Bleeding complications occurred in 12.4% of the patients and were related to the anticoagulation and antiaggregation therapy. In conclusion, the implantation of Palmaz-Schatz stents is an excellent bail-out device to treat acute vessel closure or symptomatic dissections after angioplasty. Elective and bail-out single stent implantation is associated with a reduced rate of restenosis when compared to conventional balloon angioplasty. At present, subacute stent thrombosis and bleeding complications are the major limitations with a combined rate of 15.9%.

Adult↗

[Coronary vascular stent implantation--experiences with the first 100 implants].

Coronary stent implantation was performed for blocking elastin recoil, reducing acute complications and restenosis. In 89 (95%) of 91 patients successful stent implantation was possible. No stent embolization occurred. Coronary luminal diameter measured 1.05 +/- 0.57 before PTCA and 1.9 +/- 0.2 mm post PTCA. After stent implantation mean diameter of the coronary artery measured 3.05 +/- 0.2 mm, with a balloon diameter of 3.0. Thus, elastic recoil is nearly completely blocked. In 28 (31%) of 91 patients stent implantation was performed for acute symptomatic dissection in 27 patients and occlusion in one patient. Stent delivery was successful in all. There was no acute occlusion, one acute thrombosis which could be treated with urokinase, no Q-wave-infarct, 4 (14%) non-Q-wave-infarcts and 14 (20%) CK-elevations without ECG changes. Coronary bypass surgery was necessary in 2 patients on an elective base during follow-up. In 72 (90%) of 80 patients follow-up coronary angiograms after 4 to 6 months were performed. Restenosis rate measured 21% overall, 14% for single stent, 60% for multiple stent implantation, and 14% in bail-out situations. Subacute thrombosis occurred in 10 (12%) of 89 patients, 7 (70%) of 10 events after bail-out stenting. Recanalization by thrombolytic and/or PTCA was possible in 9/10 patients. By improving monitoring of anticoagulation, the subacute thrombosis rate could be reduced to 3% even in bail-out situations. Bleeding complication occurred in 10% of the patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Increase in endogenous fibrinolysis and platelet activity during exercise in young volunteers.

The influence of physical exercise and intake of oral contraceptives on endogenous fibrinolytic activity and platelet aggregation behaviour was studied in young healthy women and compared to an age matched group of male volunteers. Physical exercise beyond the anaerobic threshold significantly increased the activity of tissue-plasminogen activator (t-PA) in male and female volunteers from initial values of 1.6 +/- 0.1 and 1.8 +/- 0.2 IU/ml to 5.5 +/- 1.0 and 5.3 +/- 0.9 IU/ml (P less than 0.01), respectively. In women taking low-dose estrogen oral contraceptives t-PA increased from 1.5 +/- 0.2 to 3.8 +/- 0.5 (P less than 0.01). There were no major alterations in plasminogen activator inhibitor - I (PAI-I) plasma activities. Platelet activity during exercise was significantly enhanced in male test persons indicated by a significant decrease in the ED50 values for ADP. In contrast, in women ED50 values were basically unaltered, irrespective of the intake of oral contraceptives.

Adolescent↗

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/l and 0.25-0.53 nm/l (median and 25th-75th percentile), versus 0.74 nm/l and 0.52-0.78 nm/l, in healthy subjects and 0.61 nm/l and 0.30-1.02 nm/l in 15 patients with ongoing proximal DVT. Nine days after initiation of OAT, F 1 + 2 concentrations in both patient groups had not yet reached levels observed in patients with OAT in the stable state (0.16 nm/l, 0.12-0.26 nm/l; n = 76; P less than 0.0001 compared with healthy subjects; INR 2.0-4.5). Despite an INR greater than 2.0, accompanying heparinization was terminated on day 9. In two stented patients a minor bleeding complication arose after the removal of the arterial catheter. Subacute thrombotic occlusions were not observed. Since F 1 + 2 concentrations did not exceed the upper limit of normal range (1.11 nm/l) in any of the 19 patients, the therapeutic regimen was not changed. Monitoring F 1 + 2 may thus be helpful in introducing a more individual treatment if aggressive anticoagulation has to be performed.

Administration, Oral↗

The control of anti-coagulation in acute dialyses with sensitive laboratory parameters.

In seven patients who had to be dialysed between four and 13 times due to acute renal failure, low molecular weight heparin (LMWH) Fragmin was used for anticoagulation. According to dose-finding studies, 80-90 U kg-1 body weight of LMWH as a single bolus were administered initially, producing dose-related levels of 0.3-1.5 anti-factor Xa U ml-1 in plasma. Apart from the anti-Xa activity in the plasma, the thrombin anti-thrombin III complex (TAT complex) and a fibrin degradation product (D-dimer) were measured as parameters of a coagulation activation. A sufficient anti-coagulation during dialysis was supposed to exist at a normal range (5.0 micrograms l-1 or below) of TAT complex. Pathological TAT concentrations at the end of dialysis indicated the requirement of an increased dose for the next dialysis. These concentrations reflected a need for more heparin if, for example, inflammation, indicated by increasing C-reactive protein levels (CRP), occurred. The increase of TAT complex and D-dimer during dialysis showed a good agreement (p less than 0.001). Due to a single bolus application before dialysis, one measurement of TAT at the end of the dialysis was sufficient. The determination of the TAT complex concentration enabled a heparinization better adapted to the clinical situation of intensive-care patients undergoing acute dialyses, so that the coagulation system was not additionally activated by the extracorporeal circulation.

Acute Kidney Injury↗

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 (Stöckert) 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 studied included the cellular elements of the blood and components indicating their functional integrity, such as PMN-elastase, plasma hemoglobin, beta-thromboglobulin, and thrombin-antithrombin III complex and D-dimer as representatives for activated coagulation and secondary fibrinolysis. Blood and urine samples were taken every 15 min during ECC, on arrival in the intensive care unit, and 1, 3, 6, 12, and 24 h thereafter. No difference between the groups was found in regard to bypass time, ECC flow and volume, fluid balance, and clinical outcome. Significant differences in favor of group 1 were found in plasma hemoglobin (P less than 0.05), beta-thromboglobulin (P less than 0.01), D-dimer (P less than 0.05), and platelet counts (P less than 0.5). These differences were clearly ECC-time-dependent and became statistically significant after 90 min bypass. We conclude that roller pumps still can be safely used for standard cardiac procedures.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗