Search PubMed⌕ Search

Biomedical subjects

A Haeberli

Publications and source records attributed to A Haeberli.

At least 55 records · Page 3Linked to original sources
PubMed1989

Fibrin formation and platelet activation in patients with myocardial infarction and normal coronary arteries.

Coronary spasm is the mechanism most often postulated to explain the rare combination of myocardial infarction and angiographically normal coronary arteries, although the reported evidence for its role is circumstantial rather than conclusive. Whereas the importance of thrombosis in myocardial infarction is uncontested in the presence of significant coronary artery disease, there is little in vivo evidence for thrombosis in angiographically normal coronary arteries. Among 11 consecutive patients with acute myocardial infarction undergoing thrombolytic therapy with recombinant tissue plasminogen activator (rtPA) 3.2 +/- 0.7 h after onset of chest pain, and angiography 10.2 +/- 4.5 days later, three young men had normal coronary arteries. Their cases are documented electrocardiographically, enzymatically and angiographically. Mean plasma levels of fibrinopeptide A (FPA) and beta-thromboglobulin (BTG) were clearly elevated before and during rtPA therapy: FPA 52 +/- 41 ng ml-1, BTG 257 +/- 46 ng ml-1. They did not differ significantly from corresponding mean plasma levels in the eight patients with severe coronary artery disease: FPA 67 +/- 66 ng ml-1, BTG181 +/- 75 ng ml-1. We conclude that fibrin formation and platelet activation are probably equally important in the early hours of myocardial infarction, whether or not significant coronary artery disease is present.

Adult↗
PubMed1989

Donor safety and plasma quality in automated plasmapheresis. Comparison of two filter materials.

The level of blood cells and differential counts as well as of selected clotting and complement system components and breakdown products were measured in donor plasma of 42 polycarbonate filter (group I) and 7 nylon filter (group II) plasmapheresis procedures. Three different sampling time points were considered: (1) 1 min prior to connecting the donor to the machine (sample A); (2) 1 min after donation by a repeat venipuncture (sample B), and (3) in collected plasma (sample C). The better biocompatibility of the newly introduced nylon filters became evident on the basis of blood cell counts with significant drops of total white blood cell counts, monocytes, lymphocytes and platelets in sample B of group I, but not of group II. Similarly, complement studies revealed significant decrease of CH 50, C4 and C3 in samples B and C of group I, but only in samples C of group II. Coagulation studies showed significant increases of fibrinopeptide A and beta-thromboglobulin in samples B and C of group I; in group II beta-thromboglobulin was significantly increased in sample C compared to sample A. Plasminogen levels were decreased in samples B and C of group I but not of group II. Nonactivated partial thromboplastin time remained normal in group I. Factor VIII:C determinations in group II revealed a recovery of 86% in sample C.

Adult↗
PubMed1989

Coagulation and fibrinolysis in acute mountain sickness and beginning pulmonary edema.

To examine whether intravascular coagulation and/or decreased fibrinolysis precedes high-altitude pulmonary edema (HAPE) we examined 25 male mountaineers (median age 40 yr) at low altitude (550 m) and after 6, 18, and 42 h at an altitude of 4,559 m, which was climbed in 24 h. In 14 subjects, 2 of whom showed radiological evidence of HAPE after 42 h, symptoms of acute mountain sickness (AMS) were mild or absent. Eleven subjects suffered from AMS, six of whom developed radiologically documented HAPE after 18 or 42 h. In the absence of AMS there were no significant changes at high altitude, with the exception of a decrease in bleeding time from 246 +/- 18 to 212 +/- 13 (SE) (P less than 0.05). In AMS, partial thromboplastine time decreased from 34.2 +/- 0.8 to 31.1 +/- 0.5 s (P less than 0.001) and factor VIII procoagulant activity and von Willebrand factor antigen were increased by 57 +/- 12 and 70 +/- 13%, respectively (P less than 0.001), whereas there were no significant changes in beta-thromboglobulin (BTG), fibrinopeptide A (FPA), and fibrin fragment B beta 15-42. In subjects with HAPE, BTG, FPA, and B beta 15-42 were normal before and in beginning HAPE. Preceding HAPE, euglobulin clot lysis time declined at high compared with low altitude from 289 +/- 48 to 201 +/- 42 min without venous occlusion (VO) and from 107 +/- 36 to 86 +/- 31 min after VO (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Contact phase of blood coagulation is not activated in edema of high altitude.

To examine whether bradykinin generated by the activation of the contact phase of blood coagulation is involved in the pathogenesis of edema occurring after acute exposure to high altitude, 15 mountaineers were examined at 490 m and 1, 3, and 5 days after arrival at 4,559 m. The clotting activity levels of factor XII, factor XI, plasma prekallikrein, and high-molecular-weight kininogen (HMWK) were measured, and plasma kallikrein-induced proteolytic cleavage of HMWK was assessed by ligand blotting by use of radiolabeled factor XI. After an ascent on foot from 1,170 to 4,559 m in 3 days, three subjects developed high-altitude pulmonary edema, and four subjects presented facial edema. There was no evidence for activation of the contact system in any subject as demonstrated by the lack of proteolytic cleavage of HMWK at high altitude. The absence of contact system activation was further supported by stable plasma levels of the individual factors of contact activation. Therefore, we conclude that bradykinin generated by plasma kallikrein-induced cleavage of HMWK is not involved in the pathogenesis of edema due to acute exposure to high altitude.

Altitude Sickness↗
PubMed1989

Monitoring of fibrin generation during thrombolytic therapy of acute myocardial infarction with recombinant tissue-type plasminogen activator.

Fibrinopeptide A (FPA) is a very sensitive marker of fibrin generation in vivo. Because an imbalance between thrombogenic and thrombolytic forces may be responsible for the failure to recanalize and for reocclusion of coronary arteries, such a marker could be of eminent value during thrombolytic treatment of acute myocardial infarction. Thirty-four consecutive patients with acute myocardial infarction (peak creatine kinase level, 1,869 +/- 1,543 IU/l) were treated with 100 mg recombinant tissue-type plasminogen activator (rt-PA) 3.1 +/- 1.1 hours after onset of chest pain. Angiography 12.5 +/- 6.1 days later revealed an 81% patency rate of the infarct-related vessel. FPA plasma levels (normal, 1.9 +/- 0.5 ng/ml) were 34 +/- 46 ng/ml on admission and 93 +/- 86 ng/ml (538 +/- 674% with respect to each patient's admission level) after 90 minutes of rt-PA infusion (p less than 0.01). In patients without evidence of reocclusion (including three primary failures), FPA levels fell under continuous heparin infusion to 6.7 +/- 9.7 ng/ml (24 +/- 33%, p less than 0.01) within 30 minutes and were 3.1 +/- 2.2 ng/ml (15 +/- 15%, p less than 0.01), 1.6 +/- 1.1 ng/ml (8 +/- 10%, p less than 0.01), and 2.5 +/- 3.0 ng/ml (12 +/- 16%, p less than 0.01) 30 minutes, 9 hours, and 21 hours, respectively, after completion of rt-PA therapy. Five patients sustained intermittent or permanent coronary reocclusion after primary thrombolytic success. Their early postlytic FPA levels (13-51 ng/ml) remained high or increased again despite adequate anticoagulation. FPA allows the monitoring of fibrin generation during acute myocardial infarction and thrombolytic therapy. Despite successful recanalization, fibrin generation is increased under rt-PA administration before anticoagulation. Patients under anticoagulation with postlytic FPA levels less than 5 ng/ml or below their admission value seem to be at low risk of reocclusion for several days. FPA levels that are persistently high or that increase again despite adequate anticoagulation indicate ongoing fibrin generation. However, whether FPA can indeed be considered a useful marker of reocclusion remains to be confirmed in a larger population of patients with acute myocardial infarction.

Coronary Angiography↗
PubMed1988

Molecular morphology of fibrin monomers and early oligomers during fibrin polymerization.

The structural features of early fibrin oligomers produced during the initial stages of polymerization were investigated by rotatory shadowing after cryotechnical preparation. The building blocks of polymerization, namely fibrin monomer units (in analogy to fibrinogen itself), were found to exhibit a high degree of flexibility which is independent of fibrinopeptide A and B removal. Early polymers exhibited directed longitudinal growth and were frequently branched. Along the main oligomer axis, fibrin monomer units were randomly orientated. Within early oligomers, a given fibrin monomer unit was found to establish a single contact with each of its two neighbors, suggesting that during the early stages of polymerization, only one polymerization and one binding site are activated per fibrinogen molecule (becoming an AB2 fibrin monomer unit). This morphological feature was corroborated by the finding that early oligomer fractions are deficient in only 50% of releasable fibrinopeptide A. Early associations between AB2 fibrin monomer units were demonstrated to be reversible and to occur in the absence of direct domainal contact; interactions thus presumably occur via fine molecular protrusions on either D or E domains. The arrangement of AB2 fibrin monomer units within early oligomers suggests that, with respect to their structural organization, fibrinogen molecules are radially symmetrical through the E domain (implying an antiparallel organization of polymerization and binding sites). This pattern is inconsistent with a "top-bottom" model, and thus with "half-staggered double-stranded" polymer growth. The methodological problems responsible for the apparent conflict with previous morphological findings are discussed.

Fibrin↗
PubMed1988

Histidine-rich glycoprotein binding to activated human platelets.

Specific binding of purified histidine rich glycoprotein (HRGP) to human platelets stimulated with either bisdiazoniumbenzidine-crosslinked immunoglobulin G (BDB-IgG), with thrombin or with collagen was dose- and divalent cation dependent. A 5-10-fold increase of platelet bound 125I-HRGP was obtained when 0.5-0.8 x 10(9) platelets/ml were activated with 100 micrograms BDB-IgG/ml, 0.1 U thrombin/ml or 15 micrograms collagen/ml. At maximal binding tested 16,000 molecules of HRGP became bound per platelet, but saturation was not achieved. Such platelet inhibitors as acetylsalicylic acid, prostaglandin E1 and cytochalasin B reduced the capacity of platelets to bind ligand, and by kinetic experiments involving enzymatic digestion of radiolabelled bound HRGP the ligand revealed to remain surface bound rather than being taken up to inner parts of the cell.

Benzidines↗
PubMed1988

Fibrinogenolysis in the absence of fibrin formation in severe hypobaric hypoxia.

Acute exposure to hypoxia causes acceleration of activated partial thromboplastin time (aPTT) and a rise in factor VIII precoagulant activity (F VIII:C). To determine whether this activation of coagulation leads to in vivo fibrin formation we investigated 15 army pilots before and at the end of 21 min (range 14-29) of hypobaric hypoxia. Mean final pressure in the decompression chamber was 283 (250-310) mm Hg causing a fall in oxygen saturation to 61.5% (53-69). Hypobaric hypoxia caused acceleration of thrombin time (p less than 0.05), aPTT (p less than 0.01), and euglobulin lysis time (p = 0.05), as well as a rise of F VIII:C (p less than 0.05), beta-thromboglobulin (p less than 0.005), fibrin(ogen) degradation products E (p less than 0.005) and B beta 15-42 (p less than 0.001), as well as lactate (p less than 0.001). Fibrinopeptide A, a marker of in vivo fibrin formation, did not change significantly. It is concluded that severe hypoxemia due to rapid decompression going to the limit of tolerance does not lead to fibrin formation, whereas the rise in fibrin(ogen) degradation products demonstrates activation of the fibrinolytic system.

Adult↗
PubMed1987

Relationship between fibrinopeptide A and fibrinogen/fibrin fragment E in thromboembolism, DIC and various non-thromboembolic diseases.

Increased fibrinopeptide A (FPA) levels have been reported in various non-thrombotic disorders, including cancer, acute myocardial infarction, liver cirrhosis and collagen vascular diseases. To investigate the significance of these findings, the present study combined the radioimmunoassay of FPA with that of fibrinogen/fibrin degradation fragment E (FgE) in the aforementioned disorders and compared the results with those observed in healthy subjects as well as in patients with thromboembolism and overt disseminated intravascular coagulation (DIC). Mean FPA and FgE in malignancy were 6.3 and 305 ng/ml, in myocardial infarction 5.6 and 98 ng/ml, in liver cirrhosis 2.7 and 132 ng/ml and in collagen vascular diseases 5.6 and 142 ng/ml. All these values were significantly higher than in healthy controls (mean FPA 1.6 ng/ml, mean FgE 49 ng/ml) but significantly lower than in thromboembolism (mean FPA 10.7 ng/ml, mean FgE 639 ng/ml). and DIC (mean FPA 22.0 ng/ml, mean FgE 1041 ng/ml). The overall correlation between FPA and FgE was highly significant. However, different disorders showed peculiar patterns in FPA, FgE and fibrinogen levels. In malignancy, a definite increase of FPA, FgE and plasma fibrinogen levels was observed. This finding probably indicates a compensated state of (intra- or extravascular) fibrin formation and lysis. Acute myocardial infarction was characterized by a high FPA to FgE ratio, which is interpreted to reflect acute thrombin generation and fibrin formation. FPA in cirrhosis was only marginally elevated with most single values within the normal range, indicating that intravascular coagulation was infrequent and unimportant in quantitative terms.

Collagen Diseases↗
PubMed1987

Excessive deposition of fibrin, platelets and platelet thrombi on vascular subendothelium during contraceptive drug treatment.

We investigated the effect of oral contraceptives on thrombogenesis induced by subendothelium of rabbit aorta (SE), exposed to flowing non-anticoagulated blood in an annular flow chamber. Six healthy women on sequential contraceptive drugs (0.05 mg aethinylestradiol/day, 0.125 mg desogestrel/day) were compared with 6 women without hormonal contraception and 6 men. On contraceptive drug treatment, blood values were significantly increased for fibrinogen (2.6 +/- 0.2 vs 1.9 +/- 0.1 g/l) and fibrinopeptide A (3.9 +/- 0.9 vs 0.9 +/- 0.1 ng/ml), whereas antithrombin III was decreased (81 +/- 4 vs 97 +/- 6%). Fibrin deposition on vascular subendothelium was more than four-fold increased when measured morphologically (63.4 +/- 2.5 vs 14.6 +/- 6.8% coverage of SE surface with fibrin) as well as immunologically (29.3 +/- 2.2 vs 4.5 +/- 1.9 micrograms fibrin/cm2 of SE). Thrombus volumes were more than two-fold increased in women with contraceptives (9.0 +/- 1.4 vs 3.7 +/- 1.0 micron 3/micron 2). Our study shows that during contraceptive drug treatment the exposure of flowing blood to vascular subendothelium leads to excessive deposition of fibrin and platelet thrombi. Measurement of blood interactions with subendothelium might be of predictive value in hypercoagulable states such as contraceptive treatment.

Adult↗
PubMed1987

Enhanced fibrin formation in high-altitude pulmonary edema.

Blood coagulation, fibrinolysis, and arterial blood gases were examined in 66 nonacclimatized mountaineers at 4,557 m. Subjects were classified according to a clinical score as healthy (n = 25), having mild acute mountain sickness (AMS) (n = 24), showing severe AMS (n = 13), and suffering from high-altitude pulmonary edema (HAPE) (n = 4). Coagulation times, euglobulin lysis time, and fibrin(ogen) fragment E were normal in all groups without significant changes. Fibrinopeptide A (FPA), a molecular marker of in vivo fibrin formation, was elevated in HAPE to 4.2 +/- 2.7 ng/ml (P less than 0.0001) compared with the other groups showing mean values between 1.6 +/- 0.4 and 1.8 +/- 0.7 ng/ml. FPA was normal in one patient with HAPE, however. Severe AMS was accompanied by a significant decrease in arterial PO2 due to an increase in alveolar-arterial O2 difference, whereas arterial PCO2 did not change significantly. We conclude that activation of blood coagulation is not involved in the pathogenesis of AMS and the impairment of gas exchange in this disease. Fibrin generation occurring in HAPE is probably an epiphenomenon of edema formation.

Adult↗
PubMed1986

Oxidative radioiodination damage to human lactoferrin.

Oxidative iodination of human lactoferrin (Lf) as commonly performed by using the chloramine-T, the Iodogen or the lactoperoxidase method produces an unreliable tracer protein because of excessive and heterogeneous polymer formation. Before iodination a minor tetramer fraction may be demonstrable in iron-saturated Lf only. Iodination-induced polymerization of iron-poor as well as iron-saturated Lf occurs independently of the presence or absence of 10 mM-EDTA and the 125I-/Lf molar ratio used for iodination. 125I-Lf polymers are mainly covalently linked, as suggested by the lack of substantial dissociation in SDS/polyacrylamide-gel electrophoresis. Damage to the 125I-Lf monomer may be another consequence of oxidative iodination. This is demonstrated in SDS/polyacrylamide-gel electrophoresis where 50% of the radioactivity of apparently normal monomer (Mr 75,000) is displaced to a lower-Mr region (30,000-67,000) after reduction with dithiothreitol. Non-oxidative iodination by the Bolton-Hunter technique produces an antigenetically stable tracer that is not being subjected to polymerization and monomer degradation as judged by high-performance gel chromatography and SDS/polyacrylamide-gel electrophoresis with and without dithiothreitol treatment. It is concluded that oxidation in itself leads to covalent non-disulphide cross-linking between human Lf molecules and, possibly, to intramolecular peptide-bond breaking becoming unmasked under reducing conditions. In biological experiments with human 125I-Lf this problem should be carefully considered.

Antibody Affinity↗
PubMed1986

Fibrin formation and platelet aggregation in patients with acute myocardial infarction: effects of intravenous and subcutaneous low-dose heparin.

Fibrinopeptide A (FPA) and beta thromboglobulin (BTG) were measured in 42 patients with acute myocardial infarction (AMI) allocated on admission to one of three groups: 14 patients received a heparin bolus injection of 5000 IU intravenously followed by a 2-hour intravenous infusion (830 IU/hr) (group 1), 14 patients received a heparin bolus of 5000 IU subcutaneously (group 2), and the remaining 14 patients received no anticoagulant treatment (group 3). In group 1 the initially elevated FPA level of 5.8 +/- 1.8 ng/ml dropped to 2.0 +/- 1.5 ng/ml 30 minutes after the intravenous heparin bolus injection of 5000 IU (p less than 0.001) and returned to normal (1.9 +/- 0.8 ng/ml) in 8 of 14 patients. The initially elevated BTG level of 64 +/- 21 ng/ml did not change significantly during intravenous heparin treatment, whereas there was a rapid but only transitory increase in platelet factor 4, (PF4) from 25 +/- 9 to 74 +/- 16 ng/ml (p less than 0.01) after the intravenous heparin bolus. In group 2 the initial FPA of 5.0 +/- 2.3 ng/ml was similarly elevated as in group 1 and dropped to 2.7 +/- 1.7 and 3.3 +/- 1.5 ng/ml 2 and 4 hours after 5000 IU subcutaneously (p less than 0.05), whereas 6 and 8 hours after subcutaneous heparin bolus the mean FPA levels were 4.2 +/- 1.7 and 5.5 +/- 2.0 ng/ml and no more significantly different from the initial FPA values. BTG and PF4 did not change significantly after the subcutaneous heparin bolus. In group 3 the initially elevated mean FPA level of 4.9 +/- 2.4 ng/ml did not change significantly during the first 8 hours after admission, whereas the FPA level 24 hours after admission was 8.4 +/- 3.9 ng/ml and higher than the initial value (p less than 0.01). We conclude that heparin may reduce the elevated FPA level in plasma found in patients with AMI; however, neither subcutaneous nor intravenous heparin in a dosage frequently used is sufficient to consistently normalize the elevated rate of fibrin formation found in these patients.

Aged↗
PubMed1986

Iodination of thyroglobulin molecules depends on their diffusion velocity in follicular colloid.

We have studied in vitro the effects of altered physicochemical properties of thyroglobulin molecules in solution and of the solution itself on iodination kinetics and hormone synthesis. Any change in hydrodynamic properties had a far greater effect in compartmentalized systems, obtained by coating the test tubes with peroxidase, than in conventional homogeneously mixed systems. Increasing thyroglobulin concentration in a range still far below that existing in vivo greatly retarded iodination and hormone synthesis. In contrast, a number of physiological and non-physiological changes of thyroglobulin structure, such as desialylation, preiodination, oxidation and denaturation, strikingly accelerated iodination. The highly variable physical-chemical state of thyroglobulin molecules appears to be a main determinant of protein diffusion within the colloid and, thereby, of iodination kinetics and rate of hormone synthesis. Moreover, alterations of the physicochemical state of thyroglobulin molecules may explain some hitherto ill-understood diffusion phenomena in live follicles.

Chemical Phenomena↗
PubMed1986

Hemolytic activity of leukemic sera: the role of complement and sucrose.

In sera of patients with acute myeloblastic leukemia (AML), hemolytic activity can be demonstrated in vitro in the presence of sucrose. To investigate the nature and the mode of action of this hemolytic activity, serum samples from 24 patients with AML were studied by incubation of normal human erythrocytes together with patient serum in the presence of sucrose at low ionic strength (inverse sucrose hemolysis test, ISHT). Fifty-five percent of the serum samples collected during the active stage of the disease gave a hemolysis rate of greater than 4%, whereas in remission only 15% of the samples lysed erythrocytes. Substitution of raffinose, lactose, or polyethylene glycol 400 for sucrose resulted in an almost complete failure of hemolysis under standard conditions, indicating a minor role of the low ionic strength in the ISHT. Heat inactivation, preincubation with inulin, and addition of EDTA, Mg2+-EGTA, or heparin completely abolished hemolytic activities of AML sera when the incubation was carried out for 30 minutes (standard conditions of the ISHT). A prolongation of the incubation time resulted in delayed hemolysis only with the Mg2+-EGTA-treated AML sera. The kinetics of this hemolysis by Mg2+-EGTA-treated AML sera were similar to those of normal human serum in the presence or absence of Mg2+-EGTA. Hemolysis was also obtained by performing the ISHT with normal sera and erythrocytes preincubated with AML sera. These observations suggest a mediation of membrane modification of normal human erythrocytes by AML sera in the presence of sucrose, resulting in an activation of the classical pathway of complement.

Adult↗
PubMed1985

Temperature dependence of fibrin polymerization: a light scattering study.

The aggregation of fibrin occurring in a fibrinogen solution upon addition of the enzyme thrombin has been studied prior to the sol-gel transition at different temperatures by means of dynamic light scattering and simultaneous measurement of the released fibrinopeptide A (FPA). The evolution of the polymer distribution with time was found to be independent of the temperature. The analysis of the experiments yields the explanation: with increasing temperature the rate of FPA release increases because it involves an activation energy, whereas the aggregation rate of the fibrin monomers decreases because it is exothermic. The light scattering experiments show that the state of aggregation is a chemical equilibrium that can be shifted by the addition of the tetrapeptide Gly-Pro-Arg-Pro. From dynamic light scattering data it is possible to derive the probability of bond formation between fibrin molecules and from it the aggregation enthalpy. For 30 degrees C a value of -19 kcal/mol was obtained.

Fibrin↗
PubMed1985

Fibrinopeptide A excretion in urine in patients with atherosclerotic artery disease.

Urinary fpA excretion and fpA in plasma were studied in patients with peripheral artery disease, aortic aneurysm, severe coronary artery disease, acute myocardial infarction and in normal controls. Mean urinary fpA was significantly higher in all groups of patients than in normal controls whose excretion was 1.9 +/- 1.2 micrograms/24 hours (mean +/- SD). We found a good correlation between urinary fpA excretion and plasma fpA (r = 0.68, p less than 0.01, n = 81). The highest levels of urinary fpA were found in 9 patients with aortic aneurysm (11.9 +/- 6.1 micrograms/24 hours). The 10 patients with acute myocardial infarction had also abnormally elevated values (4.3 +/- 1.8 micrograms/24 hours) which were only slightly higher than the levels found in another 10 patients with myocardial infarction receiving subcutaneous heparin in a dosage of 2 X 5000 IU daily (2.9 +/- 1.7 micrograms/24 hours). The 13 patients with peripheral artery disease showed an increase in urinary fpA excretion from 4.0 +/- 1.7 to 10.5 +/- 2.3 micrograms/24 hours after percutaneous angioplasty (p less than 0.001). These data demonstrate that urinary fpA excretion may represent a valid means to detect the cumulative effect of thrombin action on fibrinogen in patients with atherosclerotic vascular disease and after therapeutic intervention.

Aortic Aneurysm↗