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Biomedical subjects

C Bode

Publications and source records attributed to C Bode.

At least 145 records · Page 8Linked to original sources
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↗
PubMed1991

Effects of lipoprotein (a) on success rate of thrombolytic therapy in acute myocardial infarction.

Lipoprotein (a) [Lp(a)] and plasminogen share a high degree of homology as recently evidenced by amino acid and deoxyribonucleic acid analysis. As Lp(a) is enzymatically inactive, it has been suggested that high levels of Lp(a) may suppress the profibrinolytic activity at the cell surface and increase the risk for arteriosclerosis and thrombosis by competitive inhibition of plasminogen. The present study evaluated whether high levels of Lp(a) influence thrombolytic therapy in patients with acute myocardial infarction. Forty-one patients with acute myocardial infarction received a combination low-dose thrombolytic therapy with recombinant tissue-type plasminogen activator (rt-PA) and human single-chain urokinase-type plasminogen activator (scu-PA). This regimen did not induce plasminemia or a lytic state as indicated by well-maintained levels of fibrinogen. Coronary patency was assessed angiographically 90 minutes after initiation of treatment. Thrombolysis was successful in 30 and unsuccessful in 11 patients. Patients with high Lp(a) levels (greater than or equal to 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 greater than 0.1). Lp(a) levels did not differ significantly between patients with successful and unsuccessful thrombolysis. Our results demonstrate that high levels of Lp(a) do not affect thrombolysis in patients with acute myocardial infarction when low-dose pharmacologic concentrations of rt-PA and scu-PA are applied in combination.

Aged↗
PubMed1991

Plasma endotoxin concentrations in patients with alcoholic and non-alcoholic liver disease: reevaluation with an improved chromogenic assay.

Plasma endotoxin concentration was measured in 85 patients with alcoholic liver disease (alcoholic cirrhosis (n = 64), alcoholic hepatitis without cirrhosis (n = 11), fatty liver (n = 10), and in patients with non-alcoholic cirrhosis (n = 15]. Endotoxin concentration was determined with an improved chromogenic substrate assay, using individual standard curves for each plasma sample. In patients with alcoholic cirrhosis the mean endotoxin concentration was significantly higher than in patients with non-alcoholic cirrhosis (p less than 0.05). In addition, distinctly higher endotoxin concentrations (greater than 20 pg/ml) were more frequently observed in patients with alcoholic cirrhosis than in non-alcoholic cirrhosis (34.4 vs. 14.3%, p less than 0.05). Mean endotoxin concentration was not significantly higher in cirrhotics with ascites or esophageal varices as compared with the subgroup without ascites or esophageal varices. The endotoxin concentration did not correlate with serum bilirubin, prothrombin concentration or serum enzyme activities. In patients with alcoholic liver disease, however, endotoxin concentration revealed a negative correlation (p less than 0.05) with the concentration of high density lipoprotein cholesterol. On admission endotoxin concentrations in alcoholics with fatty liver were similarly elevated as observed in alcoholic cirrhosis. In six out of 12 patients with fatty liver or alcoholic hepatitis, in whom a second sample of plasma was investigated after 6 to 8 days, endotoxemia was no longer detectable; in the remaining patients, the endotoxin concentration decreased markedly. The results indicate that, irrespective of the stage of liver disease, alcohol abuse favours the development of endotoxemia. They support the hypothesis that gut-derived endotoxins might play a role in the initiation and aggravation of alcohol-induced liver disease.

Adult↗
PubMed1991

High incidence of antibodies to hepatitis C virus in alcoholic cirrhosis: fact or fiction?

An enzyme immunoassay (Ortho-HCV ELISA) for antibodies against the hepatitis C virus was used to test serum samples from 39 patients with alcoholic cirrhosis and 34 patients with alcoholic hepatitis or fatty liver. The frequency of a positive result in the cirrhotics was significantly higher than in the alcoholics without cirrhosis (38.5% vs 8.8%, P less than 0.01). However, the positive results in the cirrhotics were associated with high gammaglobulin concentrations, and optical density values in the assay correlated closely with serum globulin (r = 0.73, P less than 0.01). The findings suggest that serum from patients with alcoholic cirrhosis may contain a component that give false-positive results in the assay.

Biopsy↗
PubMed1991

Platelet-targeted fibrinolysis enhances clot lysis and inhibits platelet aggregation.

BACKGROUND: Although plasminogen activator therapy has been shown to reduce mortality in patients with severe myocardial infarction, several problems fuel the search for more potent and specific thrombolytic agents. METHODS AND RESULTS: To explore the effect of plasminogen activator targeting to platelets, we covalently linked urokinase that had been modified with N-succinimidyl-3-(2-pyridyldithio)propionate to the Fab' of a monoclonal antibody (7E3) that selectively binds to platelet membrane glycoprotein (GP) IIb/IIIa. In an assay measuring (as reflected by plasmin generation) a plasminogen activator's ability to bind GP IIb/IIIa immobilized on plastic, urokinase-7E3 Fab' produced 31-fold more plasmin than did urokinase (p = 0.0001). The addition of solubilized GP IIb/IIIa blocked this enhancement of plasmin generation, indicating that binding was impaired. Plasmin generation reflecting binding to immobilized intact platelets was 2.4-fold greater for urokinase-7E3 Fab' than for unconjugated urokinase (p = 0.002). In a plasma clot lysis assay, urokinase-7E3 Fab' was at least 25-fold more potent than either urokinase alone or a mixture of urokinase and 7E3 (Fab')2 (p less than 0.009), and potency could be related to platelet concentration in the clot. Ex vivo, ADP-induced platelet aggregation was inhibited by a urokinase-7E3 IgG conjugate at a concentration of 8 nM, whereas a mixture of urokinase and 7E3 (Fab')2 in equimolar amounts required 60 nM and urokinase alone required 1 microM to achieve the same effect. CONCLUSIONS: Therefore, the targeting of urokinase to the GP IIb/IIIa platelet receptor both accelerates clot lysis (when platelets are associated with a fibrin clot) and inhibits platelet aggregation.

Antigens↗