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C Bode

Publications and source records attributed to C Bode.

At least 145 records · Page 8Linked to original sources
PubMed1994

Thrombolytic therapy in acute myocardial infarction--selected recent developments.

Thrombolytic therapy is the established treatment of choice for most eligible patients with acute myocardial infarction. Early initiation of treatment and early, complete and maintained patency of the infarct-related coronary artery are desirable, because these variables correlate with a reduction in mortality. As a consequence, considerable efforts have been undertaken to develop new pharmacological agents that serve these purposes. Among these, new plasminogen activators such as reteplase (r-PA), saruplase (scuPA), and staphylokinase are in clinical development, and DSPA (bat t-PA) and antibody-targeted plasminogen activators (ScuPA-59D8) have undergone extensive animal testing. Anticoagulants such as recombinant hirudin, hirulog, argatrobane, and Factor Xa inhibitors, as well as antiplatelet agents on the basis of monoclonal antibody 7E3 offer promise as adjunctive therapy to thrombolysis or to invasive intracoronary procedures.

Enzyme Precursors↗
PubMed1994

Effects of lipoprotein(a) on thrombolysis.

Lipoprotein(a) (Lp(a)) and plasminogen share a high degree of structural homology. Therefore it has been suggested that elevated levels of Lp(a) may inhibit the profibrinolytic activity at the cell surface and increase the risk of thrombosis by competitive inhibition of plasminogen. In the present study we evaluated whether high levels of Lp(a) affect thrombolytic therapy in patients with acute myocardial infarction. Forty-one patients with acute myocardial infarction were treated with a combination of recombinant tissue-type plasminogen activator and human single-chain urokinase-type plasminogen activator. Coronary patency was assessed angiographically 90 min after initiation of treatment. Thrombolysis was successful in 30 and unsuccessful in 11 patients. Patients with high Lp(a) levels (> 25 mg/dl) (n = 9) responded equally well to thrombolytic therapy (8 of 9, patency 89%) as did patients with normal or low levels of Lp(a) (22 of 32, patency 70%, difference P > 0.1). The results demonstrate that high levels of Lp(a) do not influence thrombolysis in patients with acute myocardial infarction when low-dose pharmacologic concentrations of recombinant tissue-type plasminogen activator and human single chain urokinase-type plasminogen activator are applied in combination.

Drug Therapy, Combination↗
PubMed1994

Assessment of reperfusion of the infarct zone after acute myocardial infarction by serial cardiac troponin T measurements in serum.

BACKGROUND: The purpose of this study was to derive indices of reperfusion and non-reperfusion after acute myocardial infarction (AMI) from changes in serum concentrations of cardiac troponin T and to test the predictive value of these indices. METHODS: The indices were derived from a retrospective analysis of changes in serum troponin T concentration in 71 patients given thrombolytic treatment who had immediate and late angiography (group 1). These troponin T indices were first tested in a blinded and prospective study of 53 consecutive patients eligible for thrombolytic therapy (group 2). They were then used for the non-invasive assessment of reperfusion of AMI in 48 patients (group 3). RESULTS: In group 1 troponin T serum concentration curves were biphasic in patients who had reperfusion < or = 5.8 h after the onset of symptoms. Release of the cytosolic troponin T pool resulted in a peak at 14 h and ended at 38 h. The probability of reperfusion was > 95% when the ratio of peak cytosolic troponin T concentration to concentration at 38 h (PV1/38) exceeded 1.42 or the ratio of troponin T concentration at 14 h to that at 38 hours (14/38) exceeded 1.09. The probability of the presence of non-reperfused AMI was < 5% when troponin T PV1/38 and 14/38 ratios were < 0.99 and < 0.84 respectively. These discriminatory values of troponin T indices correctly classified (efficiency 96%) 48 of the 53 group 2 patients in whom immediate and late angiography were performed. When troponin T indices were used to classify 48 group 3 patients who were not studied by immediate angiography, thrombolytic therapy was deemed to have been successful in 82% of the treated patients, with spontaneous recanalisation in 11% and 23% of the non-treated patients assessed by PV1/38 and 14/38 respectively. CONCLUSION: The PV1/38 or 14/38 ratios of serum troponin T concentration indicated the effectiveness of thrombolytic therapy in achieving reperfusion of AMI.

Aged↗
PubMed1994

Fibrin-targeted recombinant hirudin inhibits fibrin deposition on experimental clots more efficiently than recombinant hirudin.

BACKGROUND: Although the indirect thrombin inhibitor heparin and the more potent direct inhibitor hirudin are useful in preventing thrombosis, a substantial opportunity remains for improving the thrombus selectivity of thrombin inhibitors. METHODS AND RESULTS: To explore the effect of targeting an antithrombin to the surface of a clot, we covalently linked recombinant hirudin to the Fab' (or IgG) of a monoclonal antibody (59D8) that selectively binds to an epitope on fibrin that becomes exposed only after thrombin cleaves fibrinopeptide B. Antibody-coupled hirudin bound to an immobilized peptide of the fibrin beta-chain amino-terminal sequence and inhibited the peptidolytic activity of thrombin more efficiently than free hirudin. Thrombin inhibition dependent on binding to immobilized fibrin monomer was enhanced 1100-fold (P < .0001). Hirudin-59D8 Fab' was 10 times more effective than hirudin in inhibiting fibrin deposition on experimental clot surfaces in fibrinogen solution (P < .0001) and human plasma (P < .0001). The more effective inhibition of thrombin by the conjugate was supported by significantly diminished concentrations of fibrinopeptide A in the plasma supernatant of the clot (P = .0001). Inhibition of clotting by an uncoupled mixture of hirudin and 59D8 Fab' was indistinguishable from that by hirudin alone, indicating that the conjugate's greater inhibitory activity was due to the covalent linkage between antibody and hirudin. CONCLUSIONS: Fibrin-targeted hirudin (in comparison with unmodified hirudin) significantly reduces fibrin deposition on the surface of experimental clots.

Antibodies, Monoclonal↗
PubMed1994

Parallel determination of gut permeability in man with M(r) 400, M(r) 1500, M(r) 4000 and M(r) 10,000 polyethylene glycol.

Polyethylene glycol has been in use for a number of years for the assessment of gut permeability. The methods so far employed are usually limited to polyethylene glycols in the low relative molecular mass range (up to M(r) 1300). We developed a method for the simultaneous determination of gut permeability to M(r) 400, M(r) 1500, M(r) 4000 and M(r) 10,000 polyethylene glycol, by applying a single oral dose of an appropriate mixture of these polyethylene glycols. After extraction from 24 h-urine, M(r) 1500, M(r) 4000 and M(r) 10,000 polyethylene glycol were quantified by size exclusion chromatography, while M(r) 400 polyethylene glycol was determined by reversed phase chromatography. The detection limit of polyethylene glycol in the relative molecular mass range between M(r) 1500 and M(r) 10,000 was found to be 0.2 mg/l urine, and the detection limit of M(r) 400 polyethylene glycol 5 mg/l urine. Recovery of the polyethylene glycols (N = 6) were 86.6% (CV: 4.8%) for M(r) 400, 94.1% (CV: 7.2%) for M(r) 1500, 97.1% (CV: 5.5%) for M(r) 4000 and 97.4% (CV: 5.6%) for M(r) 10,000. No significant difference was found between the excretion rates in 24 h-urine of M(r) 400 and M(r) 1500 polyethylene glycols in patients with Crohn's disease (M(r) 400: 34.4 +/- 5.5%; M(r) 1500: 5.22 +/- 2.27%; mean +/- SEM, N = 10) and healthy controls (M(r) 400: 33.6 +/- 3.2%, M(r) 1500: 1.09 +/- 0.26%; N = 21). The excretion rate of M(r) 4000 polyethylene glycol was markedly higher in patients with Crohn's disease (0.462 +/- 0.177%) than in healthy controls (0.049 +/- 0.012%, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

[Aggressive thrombolytic therapy of myocardial infarct--limits and possibilities].

Several large-scale, placebo-controlled studies have shown a significant reduction in mortality for patients with acute myocardial infarction treated with thrombolytic therapy. Early initiation of treatment and a high, early patency rate of the infarct-related coronary artery are desirable because several studies have documented a direct correlation between the reduction of mortality achieved by thrombolytic therapy and the timeliness and completeness of reperfusion. As a consequence, a number of ways to possibly improve thrombolytic therapy can be identified: 1) organizational improvement such as education of the population in order to shorten the time to inform the emergency system, and to initiate treatment in the prehospital phase in order to shorten the ischemic period. 2) Patient selection with the aim to make thrombolysis available to all patients who can derive benefit from this form of treatment. 3) Optimized use of anticoagulants and antiplatelet agents as adjuvant therapy and of thrombolytic agents. New therapeutic regimens and new agents have shown promising results in this area. The promise and the problems of thrombolytic therapy must be weighted against the therapeutic alternatives of conservative therapy on the one hand, and emergency PTCA without thrombolysis on the other hand.

Angioplasty, Balloon, Coronary↗
PubMed1993

[Successful lysis therapy in acute unilateral renal vein thrombosis].

A nephrotic syndrome developed in a 50-year-old man who, because of rheumatoid arthritis for the last three years, had been receiving gold therapy (30-50 mg sodium aurothiomalate weekly for 10 months). Treatment for the nephrotic syndrome was initiated with 100 mg prednisone daily. Ten days later he complained of severe pain in his right flank and haematuria was noted. Serum creatinine concentration increased from 1.0 to 1.8 mg/dl, while creatinine clearance fell to 62 ml/min. Computed tomography demonstrated significant enlargement of the right kidney and a thrombus in the right renal vein which extended cranial into the inferior vena cava. High dosage infusion of urokinase (4.5-7.5 mill. IU daily for nine days) achieved complete lysis of the thrombus. The creatinine concentration fell to 1.1 mg/dl, while creatinine clearance rose to 104 ml/min. On the 5th day the right kidney had 25% of total function, several days later 40%.--This case illustrates that, as long as there are no contraindications, adequately high doses of urokinase can be appropriate treatment of acute renal vein thrombosis associated with the nephrotic syndrome.

Acute Disease↗
PubMed1993

Structure and expression of the mouse testicular H1 histone gene (H1t).

A mouse genomic library was screened with a human testicular H1 (H1t) gene fragment. One phage containing the testis specific mouse H1t histone gene and its flanking regions was isolated. Northern blot analysis showed that the mouse H1t gene is expressed only in mouse testis at the stage of pachytene spermatocytes and that the H1t mRNA is not polyadenylated. This mouse H1t gene encodes a protein which differs from the somatic mouse H1 proteins, but is similar to the known H1t proteins from rat, and man.

Amino Acid Sequence↗
PubMed1993

[Myocardial infarct: acute intervention].

Treatment strategies in acute myocardial infarction are directed toward limitation of infarct size and reduction of frequency of complications. This goal is best achieved by early reperfusion of ischemic myocardium. All trials comparing thrombolytic treatment in acute myocardial infarction indicate that either streptokinase, APSAC, or rtPA reduce mortality significantly. Particularly patients at high risk (old patients, women) benefit most from thrombolytic treatment. Although, conservation of left ventricular function and risk reduction is best achieved by very early treatment, a reduction of mortality has even been shown if thrombolytic agents are if given before 12 hours after onset of symptoms. Primary PTCA is an attractive alternative to thrombolytic therapy particularly in patients with anterior wall myocardial infarction or cardiogenic shock. Routine PTCA early or late after thrombolytic treatment however does not alter the outcome of the patients. The value of rescue PTCA remains to be settled. Heparin as an adjunctive treatment of rtPA improves patency of the coronary arteries and reduces mortality. Newer anti-thrombotic agents like hirudin, argotraban, or monoclonal antibody 7E3 are even more promising for prevention of reocclusion after thrombolytic treatment. Of the conservative medical treatment aspirin, beta-blockade, nitrates, and magnesium all have been shown reduce mortality. Similar effects could not be proven for calcium antagonists or routine antiarrhythmic drugs. ACE-inhibitors are of value if given 3 days after onset of symptoms.

Aged↗
PubMed1993

Combinations of thrombolytic agents in acute myocardial infarction.

Combination thrombolytic therapy aims to achieve higher efficacy, higher specificity, better maintained patency of initially successfully reperfused vessels, less bleeding complications and cost containment by exploiting synergistic mechanisms of action and by using much lower doses of two drugs as in monotherapy. However, so far, no combination has been reported to yield significantly higher patency rates than rt-PA monotherapy. The combination of rt-PA and scuPA achieved high patency rates, and that with exquisite specificity. A combination of rt-PA and UK appears to prevent early reocclusion effectively, resulting in an overall improved clinical outcome versus monotherapy with either UK or rt-PA. The use of nonspecific plasminogen activators for the prevention of reocclusion may become obsolete, however, with the advent of more potent antithrombin and antiplatelet agents. Besides improved dosing regimens for monotherapy (front-loading), combination therapy has emerged as another possible means of enhancing thrombolytic efficacy by achieving effects that no single agent can produce. However, to date, no combination regimen has been documented to be clearly superior to monotherapy in a mortality trial.

Drug Therapy, Combination↗
PubMed1993

[Future developments in thrombolytic therapy].

A primary failure rate to achieve reperfusion by thrombolytic therapy in acute myocardial infarction of 20-40%, an early reocclusion rate of 5-20%, as well as an increased risk of bleeding that excludes many patients from this form of therapy are today considered main problems. Better application of conventional thrombolytic agents, new conjunctive therapies and development of improved plasminogen activators are investigated with the aim of minimizing these problems.

Anticoagulants↗
PubMed1993

Inhibition of platelets and thrombin: implications for treatment of coronary artery thrombosis.

Molecular biology approaches have brought considerable progress to the development of novel plasminogen activators and antithrombin agents. While the modification of t-PA itself and the construction of chimeras between t-PA and pro-urokinase by molecular techniques have not resulted in enhanced efficacy, this can be achieved by constructing hybrids consisting of plasminogen activator domains and domains of monoclonal "targeting" antibodies. This and alternative approaches offer the promise of improved therapy in the future. Of equal importance is effective anticoagulant therapy through new antithrombin agents, platelet fibrinogen receptor inhibitors, or alternative approaches, among them gene therapy. Prevention of short-term thrombotic complications of invasive procedures such as PTCA or stent implantation may be better attained with the new antithrombins, while prevention of longer term complications (restenosis) may require inhibition of the thrombin receptor.

Angioplasty, Balloon, Coronary↗
PubMed1993

Breath hydrogen excretion in patients with alcoholic liver disease--evidence of small intestinal bacterial overgrowth.

The hydrogen breath test has been used to investigate the incidence of small-bowel bacterial overgrowth in 45 chronic alcoholics and in 60 controls with no history of alcohol abuse. In the group of patients with alcoholic liver disease, the percentage of cases with bacterial overgrowth was almost three times (37.8%) that of controls not abusing alcohol (13.3%; p < 0.001). A separate evaluation of alcoholics with cirrhosis in comparison with those without cirrhosis, revealed no significant difference in the incidence of bacterial overgrowth (42.9% and 33.3%; p > 0.05). Some 16.7% of the controls and 8.9% of the patients with alcoholic liver disease were classified as "non-excreters". Among patients with alcoholic liver disease, the mouth-to-caecum transit time was prolonged by 21.5% in comparison with the controls not abusing alcohol (p < 0.025). The results suggest that bacterial overgrowth might contribute to the functional and/or morphological abnormalities of the small intestine commonly found in patients with chronic alcohol abuse.

Adult↗
PubMed1992

Multicenter dose-finding trial for thrombolysis with urokinase preactivated pro-urokinase (TCL 598) in acute myocardial infarction. German Preactivated Pro-Urokinase Study Group.

In a multicenter dose-finding study, the thrombolytic potency of urokinase preactivated pro-urokinase was evaluated. Sixty-two patients were randomly assigned to receive 250,000 U of urokinase plus either 4.5 mega U (group I: n = 33) or 6.5 mega U (group II: n = 29) of pro-urokinase. Patency rates were 36.4% (20.4-54.9%) vs. 54.5% (36.3-71.9%) (n = 27) at 60 minutes and 55.6% (32.5-70.6%) vs. 62.1% (42.3-79.3%) at 90 min into thrombolysis (n.s.). In a third group of 12 patients treated with 500,000 U of urokinase plus 6.5 mega U of pro-urokinase patency was achieved in 33.3% (9.9-65.1%) and 41.7% (15.2-72.3%) at 60 and 90 min, respectively. Patency rates at 24 hr follow-up angiography (n = 35) were 78.6% (49.2-95.3%), 85.7% (57.2-98.2%), and 85.7% (42.1-99.6%). Coagulation analysis in 37 patients revealed similar alterations in the three treatment groups with minor decreases in fibrinogen levels, moderate drops in plasminogen and alpha-2-antiplasmin levels, and moderate increases in the concentrations of the total fibrinogen/fibrin degradation products, the differences between the groups not being significant. Bleeding complications were observed in 12.9%, 13.8%, and 25% of patients in groups I, II, and III, respectively, mainly related to catheter sites. Hence, the safety profile of urokinase preactivated pro-urokinase seems comparable to other thrombolytic regimens. Reopening of occluded coronary arteries, however, is achieved relatively slowly. Thus, in its use for thrombolysis in myocardial infarction, urokinase preactivated pro-urokinase does not seem to offer superior advantages.

Coronary Angiography↗
PubMed1991

A recombinant chimeric plasminogen activator with high affinity for fibrin has increased thrombolytic potency in vitro and in vivo.

A recombinant plasminogen activator with high fibrin affinity and specificity was expressed by transfecting hybridoma cells with a plasmid that combines sequence coding for low molecular mass (32 kDa) single-chain urokinase-type plasminogen activator [scuPA(32kDa)] and anti-fibrin monoclonal antibody 59D8. The expression of the recombinant molecule [r-scuPA(32kDa)-59D8] was optimized by replacing the 3' untranslated region (initially that of high molecular mass scuPA) in the plasmid with the 3' untranslated region of either beta-globin or mouse immunoglobulin. This modification resulted in a greater than 100-fold improvement in the level of protein expression. The 103-kDa r-scuPA(32kDa)-59D8 protein displayed catalytic activity indistinguishable from that of high molecular mass scuPA and fibrin binding comparable to that of native antibody 59D8. r-scuPA(32kDa)-59D8 was 6 times more potent than high molecular mass scuPA in lysing a human plasma clot in vitro and was 20 times more potent than high molecular mass scuPA in the rabbit jugular vein model of thrombolysis. Molecules of this type may serve as prototypes for highly specific, antibody-targeted enzymes suitable for human use.

Animals↗