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Biomedical subjects

G Hafner

Publications and source records attributed to G Hafner.

At least 55 records · Page 3Linked to original sources
PubMed1998

In vitro effects of anticalcification treatment on the calcium uptake of bioprosthetic materials.

BACKGROUND AND AIM OF THE STUDY: The frequent need for re-replacement of tissue valves due to calcification remains their major disadvantage compared with mechanical implants. A variety of anticalcification treatments has been proposed but none has proved to prevent calcific degeneration. The study aim was to evaluate, in vitro, the time course of calcium uptake of procine and bovine biomaterials and the efficacy of anticalcification treatments. METHODS: Samples of glutaraldehyde-tanned biomaterials with (Carpentier-Edwards, Medtronic Intact, Hancock II, MZGTB) or without anticalcification treatment (Mitroflow) were incubated with culture medium containing physiological calcium levels. Specimens were then analyzed at two, four or eight weeks for their calcium content (mg/g wet weight). RESULTS: All specimens calcified over time, though the time courses for each were significantly different. Mitroflow and Intact valves accumulated high calcium levels rapidly during the first two weeks, with small further increases thereafter. Anticalcification treatment reduced calcium uptake of Carpentier-Edwards material during the first two weeks of incubation, but the material gradually attained comparable calcium levels at eight weeks. Hancock valves and the self-customized MZGTB valve showed the lowest calcium levels over the test period. CONCLUSIONS: This in vitro study documented major differences in calcium uptake of different biomaterials. Some anticalcification treatments render the material temporarily less susceptible to calcium binding but none can prevent calcification. In vitro testing has proved to be a valuable instrument for evaluating anticalcification treatments, but should be combined with evaluation of bioprosthesis surface interaction with circulating blood.

Animals↗
PubMed1998

[Value of molecular markers for administration of anticoagulant therapy after heart valve replacement].

In a prospective study, 39 patients following aortic or mitral valve replacement underwent investigation of molecular markers (prothrombin fragment F1+2, Factor II) in the initial phase of oral anticoagulation therapy (OAT). The results demonstrate that, despite INR being in the depicted range, the levels of the molecular markers remained high, indicating an increased risk of thromboembolic events. This leads to the conclusion that molecular markers are superior to INR in the monitoring of the early phase of OAT.

Anticoagulants↗
PubMed1997

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 Compared with the NaCl controls, C1-INH reduced myocardial injury (48.8 +/- 7.8% versus 73.4 +/- 4.0% necrosis of area at risk, P < or = .018). C1-INH treatment significantly reduced circulating C3a and slightly attenuated C5a plasma concentrations. Myocardial protection was accompanied by reduced plasma concentration of creatine kinase and troponin-T. C1-INH had no effect on global hemodynamic parameters, but local myocardial contractility was markedly improved in the ischemic zone. In the short-axis view, 137 degrees of the anteroseptal region showed significantly improved wall motion at early and 29 degrees at late reperfusion with C1-INH treatment. CONCLUSIONS: C1-INH significantly protects ischemic tissue from reperfusion damage, reduces myocardial necrosis, and improves local cardiac function.

Anaphylatoxins↗
PubMed1997

[D-dimer, thrombin-antithrombin III-complex (TAT) and prothrombin fragment 1+2 (PTF). Parameters for monitoring therapy with low molecular-weight heparin in coagulation disorders].

Two groups of 15 patients each with disseminated intravascular coagulation in association with septic disease were treated with low-molecular-weight heparin (lmw-heparin) in different dosages (group I: 1.5-5 IE/kg body weight (BW) per hour; group II: 8-15 IE/kg BW). We studied the levels of D-dimer, thrombin-antithrombin III complex (TAT), prothrombin fragments 1 and 2 (PTF), and global tests of coagulation like prothrombin time (PT), activated partial thromboplastin time (PTT), thrombin time (TT) and platelet count, plasminogen activation (PA) and fibrinogen concentration to estimate the success of heparin therapy in the two groups. TT and fibrinogen concentration were not suitable to follow the course of the coagulation disorder, PT, PTT, platelet count progressively PA, D-dimer, TAT, and PTF normalised progressively after heparinisation. However, only the last three parameters were sensitive enough to show different effects of variable dosages of lmw-heparin. D-dimer, TAT, and PTF levels declined in proportion with heparin concentrations, and thus appear to be the most useful parameters for monitoring the therapeutic effect of heparin in septic coagulopathies.

Anticoagulants↗
PubMed1997

Evaluation of a rapid, quantitative cardiac troponin I immunoassay.

We evaluated a rapid, quantitative immunoassay for the detection of cardiac troponin I. Coefficient of variation is between 1.29 and 13.63% for intra-assay and between 3.88 and 10.15% for inter-assay imprecision. Linearity is given up to 35 micrograms/l. Possible interfering substances (haemoglobin, bilirubin, triacylglycerol and rheuma factors) do not disturb the assay. The analyte is stable under normal storage conditions (+20 degrees C/48 h and +4 degrees C/l week) with decrease up to 30% after 3 months at -20 degrees C. Reference value for apparently healthy individuals is < 0.1 microgram/l. In plasma cardiac troponin I is measured up to 30% depressed compared to serum. Comparison with another cardiac troponin I assay (y = 0.92x + 2.42, r = 0.940) and cardiac troponin T is good with y = 6.61x - 1.94, r = 0.91 for the first generation cardiac troponin T assay and y = 5.59x - 0.68, r = 0.87 for the second generation cardiac troponin T assay. In summary, the evaluated assay is fast, easy to perform, and can be used not only in a specialized laboratory, but is also suitable for emergency laboratory or smaller laboratory units.

Drug Stability↗
PubMed1997

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

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 partial thromboplastin time, which currently allow only a screening for increased risk for bleeding but not for venous thromboembolism. A new functional screening test for the protein C system such as the presented ProC Global should therefore facilitate detection of FV Leiden as well as deficiency of protein C and protein S. The results of the present evaluation indicate that ProC Global is highly sensitive to activated protein C resistance/FV Leiden (100%) and protein C deficiency (90%) and sensitive to protein S deficiency (63%). Furthermore, the assay gives a quantitative measure of the net potential of the protein C pathway in relation to the intrinsic procoagulant system. The use of this assay for a prospective assessment of thromboembolic risk is the subject of current studies.

Blood Coagulation Disorders↗
PubMed1997

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

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 microg/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 showed highly increased values with the unspecific first-generation assay. In Duchenne disease cTnT was still increased, but to a much lower extent. cTnT remains increased in renal failure, but to a lesser degree than with the first-generation assay. The cause of this increase remains unclear. Although a cross-reactivity of skeletal muscle TnT in the second-generation assay could be excluded by our findings, minor myocardial damage or expression of the cardiac isoform of TnT in regenerating muscles cannot be ruled out in those cases with apparently falsely increased cTnT values. The second-generation cTnT assay is a step forward in the combination of cardiosensitivity and cardiospecificity in biochemical markers for diagnosis of heart disease.

Artifacts↗
PubMed1996

[Diagnostic and differential diagnostic value of troponins].

PATIENTS AND METHOD: In consideration of own investigations and analysis of the most important publications of other authors, a critical interpretation of the concentrations of Troponin T (cut off: < 1 microgram/l) and Troponin I (cut off: < 0.4 microgram/l) was done in patients with acute and chronic muscle diseases, with chronic renal failure, with acute myocardial infarction, and stable and unstable angina pectoris, after coronary angioplasty, following cardiac surgery and critical care patients. RESULTS: In all cases with acute damage of the skeletal muscles (post operationem) the concentrations of TnT and TnI were in normal ranges. - In patients with chronic muscle diseases (M. Duchenne, Dermatomyositis) in 75% the TnT concentrations increased, while TnI concentrations were < 0.4 microgram/l. - In end stage renal disease patients undergoing chronic maintenance hemodialysis we found in 39% constantly elevated concentrations of TnT. TnI in all cases were in normal range. - In acute myocardial infarction in 97% of all patients both Troponins were increased, beginning 2 to 4 hours after onset. A normalization was observed between the 5th and 9th day. Very important is the differentiation between stable, and instable angina pectoris. In stable angina the concentration of both Troponins were in normal range, in contrast in 33 to 41% of all patients with unstable angina TnT and TnI were increased, in 9 to 16% even if the ECG showed no alteration. Elevated TnT or TnI concentrations predicted a significantly increased mortality. After coronary angioplasty and heparin treatment all patients had once more an elevation of TnT and TnI 8 and 27 hours after the invasive therapy. One of these substantial reasons for these minor myocardial cell necrosis is beside the endothelial injury the activation of the platelets and the coagulation system. - During the therapy with hirudin increases of TnT and TnI was not observed. Following cardiac surgery (ACVB) 6 to 48 hours after aortic unclamping 76 patients with TnI < 1 microgram/l had no perioperative myocardial infarction, while 14 patients with TnI concentrations > 1 microgram/l in 71.4% (n = 10) developed an acute infarction. - In patients in critical care units we observed only increased TnI concentrations in shock, especially in septic shock with multiple organ failures.

Adolescent↗
PubMed1996

Purpura fulminans in severe congenital protein C deficiency: monitoring of treatment with protein C concentrate.

UNLABELLED: This report describes the successful use of protein C concentrate to treat severe purpura fulminans in a homozygous protein C-deficient infant for 8 months until oral anticoagulation was initiated. While fresh frozen plasma was previously used in such cases to replace protein C in the acute phase, the availability of a monoclonal antibody purified protein C concentrate now allows specific replacement of protein C, avoiding problems of fluid overload. An occlusive-hydrocolloid bandage proved to be effective in local treatment of skin lesions. D-dimer, fibrin monomer, thrombin-antithrombin complex and prothrombin fragment 1 + 2 were useful markers in monitoring and optimizing protein C replacement therapy. CONCLUSION: Diagnosis of protein C deficiency should be considered in a newborn with purpura fulminans. Early diagnosis and adequate replacement therapy is life-saving. Today, administration of protein C is the acute as well as long-term therapy of choice.

Antibodies, Monoclonal↗
PubMed1996

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, 0.24 mg.kg-1.h-1 i.v. infusion; 19 patients) or in a heparin control group (150 IU.kg-1 i.v. bolus, 20 IU.kg-1.h-1 i.v. infusion; 21 patients). Antithrombotic therapy was started immediately before coronary angioplasty and continued for 24 h. This was followed by a low-dose anticoagulant infusion for another 24 h (r-hirudin: 0.04 mg . kg-1 . h-1; heparin: 7 IU . kg-1 . h-1). Activated partial thromboplastin time, r-hirudin plasma concentrations by both immunological and functional assay, thrombin-hirudin complex, thrombin-antithrombin III complex, soluble fibrin, and prothrombin fragment 1 + 2 were closely monitored. The median partial thromboplastin time prolongations at 24 h vs baseline were found to be 1.9-fold and 2.3-fold in r-hirudin group 1 and dose group 2, respectively, and 3.0-fold in the heparin group. There was a dose-dependent correlation between partial thromboplastin time and the r-hirudin plasma levels (r = 0.61). In five of 21 patients of dose group 1, three of 19 patients of dose group 2, and 10/21 patients of the heparin group, partial thromboplastin time values exceeding the predefined target range prompted an interruption of the infusion. One major bleeding complication occurred in dose group 2. The functional assay for the estimation of r-hirudin plasma concentrations showed excellent correlations to the immunological technique (r = 0.99). Differences between the thrombin-hirudin complex levels could not be observed. Increased concentrations of thrombin-antithrombin III complex, soluble fibrin, and prothrombin fragment 1 + 2 were seen 4-8 h after coronary angioplasty and after reduction of the high-dose therapy in dose group 1 when compared with dose group 2 and the heparin group, respectively. Based on coagulation tests the present study showed the feasibility of a periprocedural antithrombotic regimen with r-hirudin for patients undergoing coronary angioplasty for unstable angina. In addition to the partial thromboplastin time the determination of r-hirudin plasma levels by a chromogenic substrate assay considerably improves the monitoring of therapy. The lower dose r-hirudin regimen seems to be suboptimal as periprocedural anticoagulation in coronary angioplasty patients as indicated by markers of thrombin generation and thrombin activity.

Adult↗
PubMed1996

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 within the first 6 h, whereas seven patients had no early reperfusion. FM concentrations were measured in the reference range (< or = 3.6 mg/l) within the first 6 h in 32 of the 35 patients. At 6-14 h FM concentrations were elevated in the reperfusion group (median 4.56 mg/l), but not in the group without reperfusion (median 1.6 mg/l, P = 0.0063). Using a threshold value of 3.0 mg/l, sensitivity and specificity of FM for the non-invasive recognition of early reperfusion were 78 and 83%, respectively. The specificity was similar to that for troponin T and higher than the creatinine kinase MB specificity. CONCLUSIONS: FM plasma concentrations are elevated in patients with AMI and early reperfusion. With a single blood sample 6-14 h after onset of chest pain, FM analysis is useful for the non-invasive detection of early reperfusion after AMI.

Anticoagulants↗
PubMed1996

Effects of surface seeding with vital cells on the calcium uptake of biological materials for heart valve replacement.

BACKGROUND AND AIMS OF THE STUDY: Up to 35% of bioprosthetic heart valves need to be replaced during the first decade after implantation because of tissue degeneration or calcification. The aim of the studies was to evaluate the influence of surface seeding with viable cells on the calcium uptake of biomaterials. MATERIALS AND METHODS: Samples of glutaraldehyde tanned bovine pericardium (GBP, n = 52) or porcine valves (GPV, n = 50), or glycerol treated bovine pericardium (GlyBP, n = 35), which had either been rinsed with saline (GBP, n = 30; GPV, n = 26; GlyBP, n = 18) or seeded with rat fibrocytes (GBP, n = 22; GPV, n = 24; GlyBP, n = 17) were incubated with cell culture medium containing physiologic levels of calcium. Similarly treated material was implanted into the abdominal muscles of 88 rats (seeded: GBP, n = 16; GPV, n = 16; GlyBP, n = 14; non-seeded: GBP, n = 6; GPV, n = 8; GlyBP, n = 7). The specimens were analyzed two and four weeks later for their calcium content. RESULTS: Over time untreated GBP and GlyBP calcified in vitro and in vivo while GPV retained low calcium levels in vivo. Surface seeding with rat fibrocytes significantly reduced the calcium accumulation in GBP and GlyBP in vitro and in vivo (p < 0.05). CONCLUSIONS: Seeding with viable cells might be a promising method of reducing calcium accumulation in bovine pericardial implants.

Animals↗
PubMed1995

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

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 microliters 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 characterized by intraassay coefficients of variation between 0.63% and 2.78% on the Hitachi 911 and 1.51% and 7.84% on the Cobas Mira, respectively and interassay coefficients of variation of 3.57% to 9.15% (Hitachi 911) and 3.72% to 12.99% (Cobas Mira) for the same r-hirudin plasma concentrations. The described determination of r-hirudin correlates well with an enzyme linked immunosorbent assay method for r-hirudin (Hitachi 911: r = 0.964, y = 0.978x + 0.038, n = 323; Cobas Mira: r = 0.964, y = 0.959x-0.003, n = 323).

Animals↗
PubMed1995

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 an anabolic marker of type-I collagen increased significantly with rising bone density: I 65.0 micrograms/liter (interquartile range: 52.1-78.0 micrograms/liter); II 85.9 micrograms/liter (52.1-115.5 micrograms/liter); III 81.4 micrograms/liter (62.0-101.0 micrograms/liter);P < 0.05. The concentration of urinary pyridinolines (U-PYR) as a marker for degradation of type I collagen decreased. The I-carboxyterminal telopeptide (S-ICTP) and osteocalcin (S-BGP) did not change. The multivariate regression analysis showed no relationship between between bone density and biochemical bone markers. Only the age significantly correlated negatively with bone density measurement. For a better assessment of type I collagen metabolism we created a "b-quotient" by dividing the sum of S-PICP and S-BGP by U-PYR. The median b-quotient increased significantly: I 1.55 (0.97-2.04); II 2.09 (1.57-2.86): III 2.46 (1.58-3.22); P < 0.05. Changes in bone metabolism cannot be identified by the determination of a single marker. However, the improved biochemical diagnostic measurement using the b-quotient may provide early information about the progression of a metabolic disorder within the interval of imaging.

Absorptiometry, Photon↗
PubMed1995

Guidance of anticoagulation after intracoronary implantation of Palmaz-Schatz stents by monitoring prothrombin and prothrombin fragment 1 + 2.

The primary objective of this study was to apply a sophisticated coagulation monitoring system including estimation of the concentration of prothrombin fragment 1 + 2 (PTF 1 + 2) and the activity of prothrombin (coagulation factor II or FII) to cases of stent implantation and to compare the results with those of standard coagulation tests. The secondary objective was to detect the incidence after stenting of subacute thrombosis (SAT) and bleeding complications in these patients and to compare the results with those of a group of patients with stent implantation in whom coagulation was monitored exclusively by standard tests. SAT several days after coronary stenting occurs in up to 20% despite aggressive intravenous and overlapping oral anticoagulation. According to a prospective study protocol 120 consecutive patients with implantation of 155 Palmaz-Schatz stents underwent coagulation monitoring including single daily estimation of the concentration of PTF1 + 2 (target range < 0.5 nmol/L) and of FII activity (15% to 35%) in addition to the standard tests of thrombin time (TT), partial thromboplastin time (aPTT), international normalized ratio (INR), antithrombin III (ATIII), and fibrinogen. Adjustment of heparin and phenprocoumon dosages in this study group was based only on the results of PTF1 + 2 and FII measurements. A control group consisted of 53 patients with implantation of 64 stents who were matched for baseline, angiographic, and procedure-related characteristics. After stenting, anticoagulation was monitored by estimation of TT (target range > 70 seconds), aPTT (> 70 seconds), INR (3.0 to 4.5), AT III (> 80%), and fibrinogen (< 450 mg/dl) in this control group. There was a weak correlation between PTF1 + 2 and aPTT (r = 0.337; PTF1 + 2 = -0.00169aPTT + 0.491) and PTF1 + 2 and TT (r = 0.328; PTF1 + 2 = -0.00142TT + 0.494). A better correlation was found between FII and INR (r = 0.983; FII = -23.8 INR + 134). Stable oral anticoagulation was maintained 2.8 +/- 0.9 days later according to an FII concentration of < 35% compared with an INR > 3. The incidence of SAT was 3.3% with 3.0% for elective versus 3.8% for nonelective stenting. The sensitivity, specificity, and accuracy of the PTF1 + 2 test were 100%, 88%, and 88%, respectively. In the control group the incidence of SAT was 17%, with 16.1% for elective versus 18% for nonelective stenting. Major bleeding complications occurred in 10% (study group) and in 11.3% (control group) of patients (no statistical difference).(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗