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  • 1
    Electronic Resource
    Electronic Resource
    Die intraindividuelle Streuung der fibrinolytischen Aktivität bei Probanden (1978)
    Springer
    Journal of molecular medicine 56 (1978), S. 445-448 
    Details
    ISSN: 1432-1440
    Keywords: Fibrinolysis ; Circadian rhythms ; Clinical trial ; Euglobulinlysis-time ; Fibrinolyse ; circadiane Rhythmik ; klinische Prüfung ; Euglobulinlyse-Zeit
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Bei 5 Probanden wurde über einen Zeitraum von 6 Wochen fünfmal die Anstiegsphase im Tagesrhythmus der fibrinolytischen Aktivität untersucht. Als Parameter wurden die Euglobulinlyse-Zeit und die Papierfibrinolyse, die Plasmaproteine, Fibrinogen, Plasminogen, α1-Antitrypsin und α2-Makroglobulin sowie die Thrombinocoagulase-Zeit und die Fibrinspaltprodukte erfaßt. Es zeigte sich bei allen Probanden der Anstieg der Fibrinolyse am Vormittag. Die Schwankungsbreite der fibrinolytischen Aktivität ist intraindividuell kleiner als bei einem interindividuellen Vergleich. Weiterhin zeigt sie mittags eine geringere Streuung als vormittags. Bei Untersuchungen zur klinischen Prüfung eines Soforteffektes von Arzneimitteln auf die Fibrinolyse sollte der Zeitraum der Plateauphase der fibrinolytischen Aktivität gewählt werden, um die Streuung der Ausgangswerte möglichst gering zu halten. Weiterhin ist die intraindividuelle Streuung der fibrinolytischen Aktivität in diesem Zeitraum geringer als während der Anstiegsphase im Rahmen des circadianen Rhythmus der Fibrinolyse. Eine intraindividuelle Kontrolle muß gewährleistet werden.
    Notes: Summary In five volunteers fibrinolytic activity has been measured five times over a period of six weeks during increasing values of circadian rhythm. Euglobulinlysis-time, paper fibrinolysis, fibrinogen, plasminogen, α1-antitrypsin, α2-makroglobulin, thrombinocoagulase-time and fibrin-split-products were used in one study. An increase of fibrinolytic activity in the mooning was observed in all volunteers. Intraindividual variation of values is considerable but less than variation of values compared interindividually. Moreover variation was smaller at noon than in the time before noon. In clinical trial of the short-time effect of drugs the period of the plateau of the fibrinolytic activity should be used because of its smaller variation of values. Furthermore, in this period the intraindividual variation of the fibrinolytic activity is smaller than during increasing slope of the circadian rhythm of fibrinolysis. Intraindividual control should be granted.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01477058
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  • 2
    Electronic Resource
    Electronic Resource
    Neutralisierung von niedermolekularem Heparin Kabi 2165 mit Protaminchlorid (1986)
    Springer
    Journal of molecular medicine 64 (1986), S. 1171-1175 
    Details
    ISSN: 1432-1440
    Keywords: Heparin ; Low molecular weight heparin ; Protamine chloride ; Antidot ; Factor XA
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Low molecular weight (LMW) heparin Kabi 2165 possesses improved pharmacodynamic properties compared with conventional heparin. It is currently investigated in the prophylaxis of thromboembolism. The neutralization of Kabi 2165 by protamine chloride was analysed after i.v. injection of both the agent and the antidot in healthy persons. The anticoagulant effects of the LMW heparin on the activated partial thromboplastin time, thrombin, and thromboelastography are completely and immediately suppressed by protamine chloride. The inhibition of factor X a is antagonized up to 50%–60%. The bleeding time remained unaffected. The data indicate that protamine chloride may be used in clinical situations as an antidot to the LMW heparin Kabi 2165. A rebound phenomenon of the anticoagulant effect does not occur.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01728455
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  • 3
    Electronic Resource
    Electronic Resource
    The effects of a combination of cigarette smoking and oral contraception on coagulation and fibrinolysis in human females (1985)
    Springer
    Journal of molecular medicine 63 (1985), S. 221-224 
    Details
    ISSN: 1432-1440
    Keywords: Smoking ; Oral contraception ; Coagulation ; Fibrinolysis ; Fibrinopeptides
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Oral contraception as well as cigarette smoking influence haemostasis. The simulataneous effect of both on blood coagulation and fibrinolysis was studied in nine female smokers. While continuing oral contraception after a 4-week abstinence from smoking the concentration of fibrinogen, antithrombin III and alpha1-Antitrypsin decreased (P〈0.01 orP〈0.04) and of plasminogen increased (P〈0.03). The other coagulation parameters remained unchanged. Although all determinations of these parameters were in the normal range, the observed trends were statistically significant. The concentrations of the fibrinopeptide A and B 15–42 did not differ. It is concluded that the observed alteration is caused by cessation from cigarette smoking.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01731173
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  • 4
    Electronic Resource
    Electronic Resource
    Thrombolytische Therapie der tiefen Beinvenenthrombose mit Urokinase (1982)
    Springer
    Journal of molecular medicine 60 (1982), S. 489-496 
    Details
    ISSN: 1432-1440
    Keywords: Thrombosis ; Deep vein thrombosis ; Urokinase ; Fibrinolysis ; Thrombolysis ; Thrombose ; Beinvenenthrombose ; Urokinase ; Fibrinolysetherapie
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Bei 81 Patienten mit tiefen venösen Thrombosen der unteren Extremität wurde eine Fibrinolysebehandlung mit Urokinase nach einem neuen, höher dosierten Therapieschema in Kombination mit Heparin durchgeführt. Unter Gabe einer Urokinasedosis von 1000–2000 IE/kg/h (Initialdosis 150000–250000 IE) konnte bei frischen, bis zu 10 Tage alten Thrombosen eine komplette oder Teileröffnung bei 68% der Patienten erzielt werden. Dabei zeigte die höhere Urokinasedosierung im Beckenvenenbereich mit einer Wiedereröffnungsrate von 67% im Vergleich zur niedrigeren Dosis mit einer Rekanalisierungsrate von nur 43% einen deutlich stärkeren thrombolytischen Effekt. Bei den Thrombosen im V. poplitea- oder Wadenvenenbereich konnte dagegen mit einer Befundbesserung von 80 und 78% bzw. 75 und 62% ein nur gering differierender Behandlungserfolg beobachtet werden. Die Ergebnisse weisen darauf hin, daß die hier angewendete höhere Urokinasedosierung (Erhaltungsdosis 2000 IE/kg/h) der niedrigeren bei Vorliegen langstreckiger Thrombosen überlegen ist. Unter der höheren Dosierung richtete sich die weitere Urokinasedosis nach der Fibrinogenkonzentration nach Clauss, wobei ein Wert von 50–100 mg% angestrebt wurde und ein Wert von 50 mg% nicht unterschritten werden sollte. Die Steuerung der Therapie gestaltete sich dabei problemlos. An Nebenwirkungen wurden bei 8,6% der Patienten Makrohämaturien und nur in 6% der Fälle ein Hb-Abfall von mehr als 2 g% beobachtet. Lebensbedrohliche oder cerebrale Blutungen traten nicht auf. Der hohe Anteil älterer Phlebothrombosen und die dann wesentlich geringeren therapeutischen Erfolgsaussichten (Rekanalisierung in nur 23% der Fälle) unterstreichen die Notwendigkeit einer möglichst frühzeitigen Klinikeinweisung.
    Notes: Summary In 81 patients with deep vein thrombosis of the lower limb, urokinase therapy was performed in combination with heparin according to a new regimen at higher dosages. When urokinase was administered at an initial maintenance dosage of 1,000–2,000 IU/kg/h (loading dose 150,000–250,000 IU), phlebographically documented complete or partial recanalization could be observed in 68% of the cases. The higher dosage schedule induced a more pronounced deobliteration expecially in treatment of iliac vein thromboses (67% recanalization) in comparison to the lower dosage regimen (only 43% recanalization). Nearly comparable therapeutic results could be achieved in therapy of popliteal or saphenous vein thromboses. The data suggest that the higher dosage schedule examined here is indicated in treatment of extensive and large volume thromboses. The dosage of urokinase was further adjusted to attain a reduction of fibrinogen to 50–100 mg/dl. The concentration should not fall below 50 mg/dl. Therapy with urokinase proved practicable. Serious side effects did not occur. 8.6% of the patients showed hematuria and 6% a decrease of the Hb by more than 2 g/dl. The high proportion of older thromboses and the only low rate of recanalization (23%) in these cases suggest the necessity of an early commencement of fibrinolyses in therapy of deep vein thrombosis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01756094
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  • 5
    Electronic Resource
    Electronic Resource
    Urokinase therapy of subclavian-axillary vein thrombosis (1981)
    Springer
    Journal of molecular medicine 59 (1981), S. 851-856 
    Details
    ISSN: 1432-1440
    Keywords: Subclavian-axillary vein thrombosis ; Thrombosis ; Urokinase ; Fibrinolysis ; Achselvenenthrombose ; Thrombose ; Urokinase ; Fibrinolyse
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Bei 18 Patienten mit einer Achselvenenthrombose wurde eine fibrinolytische Therapie mit Urokinase in Kombination mit Heparin durchgeführt. Der thrombolytische Effekt war dabei eindeutig vom Alter der Thrombose und der Höhe der Urokinasedosis abhängig. Unter Gabe einer anfänglichen Erhaltungsdosis von 1000–2000 IE/kg/h (Initialdosis 150 000–250 000 IE Urokinase) in Kombination mit Heparin (15–17 E/kg/h) konnte bei neun der 11 Patienten (82%) mit frischen Thrombosen ein nahezu kompletter Behandlungserfolg erzielt werden. Bei einem Thrombusalter von mehr als 10 Tagen war keine phlebographische Befundänderung nachweisbar. Wesentliche Nebenwirkungen wurden nicht beobachtet. Auf Grund der hier mitgeteilten Behandlungsergebnisse sollte bei frischen Thrombosen der V. subclavia oder axillaris eine thrombolytische Therapie mit Urokinase durchgeführt werden. Der hier vorgelegte Erfahrungsbericht erlaubt darüber hinaus generelle Rückschlüsse zur Dosierung und Wirksamkeit der fibrinolytischen Substanz Urokinase.
    Notes: Summary In 18 cases with primary subclavian-axillary vein thrombosis fibrinolytic therapy was performed with urokinase in combination with heparin. The thrombolytic efficacy clearly depended on the thrombus age and the dose of urokinase applied. Under treatment with a median initial maintenance dosage of urokinase of 1,000–2,000 IU/kg/h (loading dose 150,000–250,000 IU urokinase) in combination with heparin (15–17 U kg/h) in nine of 11 patients (82%) with recently developed (8 days or less) thrombosis, a nearly complete deobliteration of the venous system was observed. In the cases with thrombosis of more than 10 days no alteration of the venous occlusions could be seen. Relevant side effects did not occur. Our results emphasize urokinase therapy of acute subclavian-axillary vein thrombosis and permit general inferences concerning the efficacy and the dosage requirements of the thrombolytic substance urokinase.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01721055
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  • 6
    Electronic Resource
    Electronic Resource
    Ambulante Langzeitprophylaxe der Thromboembolie mit niedermolekularem Heparin (1987)
    Springer
    Journal of molecular medicine 65 (1987), S. 331-337 
    Details
    ISSN: 1432-1440
    Keywords: Thromboembolism-prophylaxis ; Bleeding complications ; Oral anticoagulants ; Heparin ; Low molecular weight heparin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Patients with severe bleeding complications and other side effects on conventional anticoagulants and strong indication for further anticoagulation were treated with a low molecular weight heparin fragment (Tedelparin). In this paper we report the experiences in 30 patients, who were anticoagulated 1–11 months with this compound. All patients injected themselves a dose ranging from 1 × 2,500 to 1 × 20,000 anti factor Xa units per day. Within 132 months of treatment one patient with good compliance developed thromboembolism. Four patients had bad compliance. Two of them experienced rethrombosis 1 and 8 weeks after starting therapy. Severe haemorrhages did not occur. Two patients had one minor bleeding complication each. Both patients developed several times per year severe haemorrhages with conventional anticoagulants. All excessive subcutaneous haematomas and indurations of the adipose tissue at the injection site of conventional heparin disappeared completely. Low molecular weight heparin can be regarded as an alternative anticoagulant in patients with severe bleeding and other complications on oral anticoagulants and conventional heparin.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01745389
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  • 7
    Electronic Resource
    Electronic Resource
    A fatal complication in a patient with heparin-induced thrombocytopenia type II re-exposed to heparin (1999)
    Springer
    European journal of orthopaedic surgery & traumatology 9 (1999), S. 205-207 
    Details
    ISSN: 1432-1068
    Keywords: Hip-replacement ; Reexposition ; Heparin ; Thrombocytopenia ; Arthroplastie de hanche ; Réexposition ; Thrombocytopénie
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé La thrombopénie type II provoquée par l'héparine est une complication liée à ce médicament rare mais importante, associée à une thrombopénie et des thromboses. Nous présentons ici un patient après une révision élective d'une plastie dé l'articulation coxo-fémorale. Avant l'opération, le patient a obtenu 5000 IU d'héparine non fractionnée trois fois par jour durant dix-neuf jours. Après l'opération, le patient a eu un abaissement du nombre de plaquettes sanguines de 236'000/μl à 69'000/μl, il a développé une thrombose de la veine iliaque ainsi qu'une embolie pulmonaire. L'héparine étant supposée être à l'origine de la thrombopénie, celle-ci a été remplacée par du Sodium-Danaparoid en application sous-cutanée comme anticoagulant. Le nombre de plaquettes est alors remonté à un niveau normal pour trois jours. Suite à un test d'agrégation liée à l'héparine négatif, la thérapie aux anticoagulants a été poursuivie avec de l'héparine non fractionnée appliquée par voie intraveineuse à haute dose, la capacité de coagulation ayant été contrôlée par le test PTT (temps de thrombine partiel). Deux jours après réexposition à l'héparine, les plaquettes ont rechuté à 34'000/μl. is jours après réexposition à l'héparine le patient est mort â la suite d'une insuffisance cardiopulmonaire. Une analyse du sang a démontré la présence d'immunoglobuline contre l'héparine et le facteur de plaquette 4. Mots-clés: Arthroplastie de hanche - Réexposition - Thrombocytopénie
    Notes: Summary The heparin-induced thrombocytopenia type II is a rare but important drug related complication associated with thrombocytopenia and thrombosis. We report on a patient with elective revision of the total hip arthroplasty. Preoperatively for nineteen days, the patient received unfractionated heparin 5000 IU three times daily for thromboprophylaxis. Postoperatively the patient developed a platelet drop from 236000/μl to 69000/μl an iliac vein thrombosis and pulmonary embolism. In assumption of heparin induced thrombocytopenia anticoagulation was switched to danaparoid-sodium subcutaneously. Platelet count rised to normal values while three days. Because of a negative heparin-induced platelet aggregation assay, anticoagulation was switched to a PTT controlled high dose intravenous unfractionated heparin. Two days after re-exposition to heparin platelet counts dropped to 34000/μl blood. The patient died 12 days after readministration of heparin due to respiratory and circulatory failure. Postmortem analysis of serum revealed positive heparin/platelet factor 4 IgG-antibodies.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00542596
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  • 8
    Electronic Resource
    Electronic Resource
    Lack of effect of cimetidine on action of phenprocoumon (1982)
    Springer
    European journal of clinical pharmacology 23 (1982), S. 365-367 
    Details
    ISSN: 1432-1041
    Keywords: cimetidine ; phenprocoumon ; warfarine ; drug metabolism interaction ; histamine receptor antagonist ; anticoagulation ; bleeding complication
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In patients on oral warfarin, nicoumalone and phenindione an increase in the anticoagulant effect has been described during concomitant treatment with cimetidine. Therefore the effect of cimetidine on the steady state dynamics of phenprocoumon has been investigated in ten outpatients. No change in the anticoagulant effect of phenprocoumon was observed during or after two weeks on cimetidine, as measured by the thrombotest coagulation method, prothrombin time, fibrinopeptide A concentration and plasma phenprocoumon level. The data show that cimetidine does not interact with the metabolism of phenprocoumon in contrast to warfarin. Thus, phenprocoumon maintenance therapy when combined with concomitant cimetidine treatment can be considered not to carry an increased risk of haemorrhagic complications.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00613622
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  • 9
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of sulphinpyrazone and its major metabolites after a single dose and during chronic treatment (1985)
    Springer
    European journal of clinical pharmacology 28 (1985), S. 97-103 
    Details
    ISSN: 1432-1041
    Keywords: sulphinpyrazone ; metabolism ; single dose ; chronic treatment ; pharmacokinetics ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of sulphinpyrazone and its major metabolites (sulfide, sulfone, p-hydroxysulfone and p-hydroxy-sulphinpyrazone) were investigated in 9 volunteers after a single oral dose as well as after chronic treatment for 23 days. Chronic administration of sulphinpyrazone, in comparison with a single oral dose, led to significant changes in plasma AUC (115.86 to 42.90 mg/l·h), in renal clearance (1.06 to 1.80l/h), in hepatic intrinsic clearance (319.0 to 598.0l/h), and in the unbound fraction in plasma 1.15 to 1.69%) and in tissue (2.73 to 1.31%). The volume of distribution changed from 20.24 to 52.041. The steady state concentrations predicted from the single dose were significantly higher than the values found after chronic treatment. The results suggest that sulphinpyrazone induces its own metabolism. The metabolism of the sulfone, p-hydroxysulfone and the p-hydroxy-sulphinpyrazone to further degradation products was also induced. Chronic treatment with sulphinpyrazone reduced the plasma AUC of the sulfide and caused a decrease in its elimination half-life (20.9 to 14.3 h). Since considerable amounts of the sulfide are formed in the G.I. tract, it is suggested that besides the induction of metabolism, bacteria which reduce sulphinpyrazone to the sulfide may also be responsible for the observed pharmacokinetic changes.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00635715
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  • 10
    Electronic Resource
    Electronic Resource
    Effect of single and multiple doses of sulphinpyrazone on antipyrine metabolism and urinary excretion of 6-beta-hydroxycortisol (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 797-801 
    Details
    ISSN: 1432-1041
    Keywords: sulphinpyrazone ; drug metabolism ; enzyme induction ; 6-beta-hydroxycortisol antipyrine ; antipyrine metabolites
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Sulphinpyrazone decreases the plasma clearance of tolbutamide and S-warfarin and increases the clearance of R-warfarin, theophylline and antipyrine. In order to determine whether sulphinpyrazone is an inducer or inhibitor or both of oxidative drug metabolism, antipyrine and its metabolites as well as 6-beta-hydroxycortisol were measured in urine before, 24 h and after 23 days of chronic administration of sulphinpyrazone (4×200 mg/day). During chronic treatment sulphinpyrazone increased the ratio of 6-beta-hydroxycortisol to the 17-hydroxycorticosteroids by 70% (p〈0.02). The renal clearance of the main oxidative metabolites of antipyrine (4-hydroxyantipyrine, 3-hydroxymethylantipyrine and norantipyrine) were increased after sulphinpyrazone (p〈0.02). Except for norantipyrine, no change in total excretion of antipyrine and its metabolites occurred after 24 h or after 23 days. It is concluded that sulphinpyrazone induces the enzymes which metabolize antipyrine and cortisol.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00542523
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