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Biomedical subjects

D C Gulba

Publications and source records attributed to D C Gulba.

51 records · Page 3Linked to original sources
PubMed1991

Increased thrombin levels during thrombolytic therapy in acute myocardial infarction. Relevance for the success of therapy.

BACKGROUND: It has been suggested that thrombolysis in a feedback reaction may generate pro-coagulant activities. METHODS AND RESULTS: Fifty-five patients were treated with urokinase-preactivated prourokinase (n = 35) or tissue-type plasminogen activator (n = 20) for acute myocardial infarction and underwent coronary angiography at 90 minutes and at 24-36 hours into thrombolysis, and fibrinogen (Ratnoff-Menzie), D-dimer (ELISA) and thrombin-antithrombin III complex levels (ELISA) were measured. Primary patency was achieved in 39 patients (70.9%), 13 of whom (33.3%) suffered early reocclusion. Nonsignificant decreases in fibrinogen levels were observed while D-dimer levels increased +3,008 +/- 4,047 micrograms/l (p less than 0.01), differences not being significant in respect to the thrombolytic agents or to the clinical course. In contrast, while thrombin-antithrombin III complex levels decreased -4.4 +/- 13.0 micrograms/l in patients with persistent patency, they increased +7.5 +/- 13.6 micrograms/l in case of nonsuccessful thrombolysis (p less than 0.02) and +11.9 +/- 23.8 micrograms/l in case of early reocclusion (p less than 0.001). For patients with thrombin-antithrombin III complex levels greater than 6 ng/l 120 minutes into thrombolysis, the unfavorable clinical course was predicted with 96.2% sensitivity and 93.1% specificity. CONCLUSION: Generation of thrombin, occurring during thrombolysis, is a major determinant for the success of therapy and thrombin-antithrombin III levels may serve as predictors for the short-term prognosis.

Antithrombin III↗
PubMed1991

[Percutaneous, transluminal angioplasty of aortocoronary venous bypass grafts--acute success, angiography and clinical follow-up].

In 41 consecutive patients with 49 stenoses of aorto-coronary venous bypass (ACVB) grafts percutaneous transluminal angioplasty (PTA) was attempted. PTA was successful, i.e., the percent area stenosis was reduced by greater than 20% to less than 70% (quantitative measurement with a precision magnifying lens from two orthogonal angiographic views) in 46 stenoses (94%) of 38 patients (93%). In 35 patients (92%) with 42 stenoses control coronary angiography was performed after a mean interval of 189 +/- 186 days. Recurrence, defined as an increase of percent area stenosis to greater than or equal to 70%, was found in nine stenoses (21%) of nine patients (26%). Recurrence correlated with a stenosis length greater than 10 mm before PTA (5/8 vs 4/32 stenoses: p less than 0.01). In recurrent stenoses, the average diameter of the grafted native coronary artery was significantly smaller than in recurrence-free stenoses (1.92 +/- 0.52 mm vs 2.45 +/- 0.50 mm; p less than 0.01). Clinical data were collected from all 38 patients with successful PTA after an average of 30 +/- 17 months following PTA. In this interval, 11 patients had undergone re-angioplasty and eight patients were re-operated; in addition, there were three cardiac deaths. In the 27 surviving patients without re-operation (71%), angina pectoris had improved from a mean of 3.0 +/- 0.7 before PTA to 1.8 +/- 1.0 (CCS-classification) (p less than 0.001). In 19 of the 27 patients (70%) the exercise stress test was negative, in contrast to only three patients (11%) before PTA. Thus, in the majority of patients PTA of ACVB-graft stenoses improves quality of life.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1990

Role of thrombolysis and thrombin in patients with acute coronary occlusion during percutaneous transluminal coronary angioplasty.

In a series of 447 patients with single vessel angioplasty, 27 (6.0%) had acute thrombotic occlusion early after the procedure. They were treated with combined intracoronary (20 mg)/intravenous (50 mg) thrombolysis with recombinant tissue-type plasminogen activator (rt-PA) and repeat mild balloon inflations. Reopening of the vessel was achieved in 22 patients (81.5%). Follow-up coronary angiography 24 to 36 h later revealed reocclusion in 12 patients (54.5%). Thrombin levels measured as thrombin-antithrombin-III complex in patients with successful thrombolysis and persistent patency decreased from 8.5 +/- 11.4 micrograms/liter at baseline to 3.5 +/- 1.4 micrograms/liter 120 min after the start of thrombolysis; these levels increased from 9.4 +/- 15.0 micrograms/liter at baseline to 15.7 +/- 13.5 micrograms/liter 120 min after the start of thrombolysis in the patients with unsuccessful thrombolysis or early reocclusion (p less than 0.05). When a borderline value for thrombin-antithrombin-III complex level of 6 micrograms/liter was selected to separate the two groups of patients, patients with an unfavorable clinical course were identified 120 min after the start of thrombolysis by levels greater than 6 micrograms/liter (sensitivity 100%, specificity 92.8%). Thus, after abrupt thrombotic vessel closure during coronary angioplasty, the short-term results of thrombolysis seem to be governed by the release of thrombin. In two thirds of patients, however, the thrombin release cannot be suppressed by concomitant aspirin and heparin therapy. Even after successful reopening of the vessel these patients should therefore undergo immediate aortocoronary bypass grafting.

Angioplasty, Balloon, Coronary↗
PubMed1990

Renal artery embolism: thrombolysis with recombinant tissue-type plasminogen activator.

The case of a patient with acute occlusion of the right renal artery due to an embolus is described. Using transoesophageal echocardiography, the left atrial appendage could be identified as the source of embolism. Twenty hours after the onset of symptoms, the embolus could be successfully dissolved with an intra-arterial low-dose infusion of recombinant tissue-type plasminogen activator (10 mg loading dose, 20 mg continuous infusion within 12 h).

Aged↗
PubMed1990

[Incidence of residual thrombi following successful thrombolytic therapy in acute myocardial infarct and their significance for the rate of early re-occlusion. A report of a multicenter dose-finding study for thrombolytic therapy with urokinase preactivated natural prourokinase (TCL 598)].

Thrombolysis with urokinase preactivated prourokinase was performed in 74 patients. At control angiography, 90 min into thrombolysis, in 39 (52.7%) patients the infarct-related coronary artery was found patent. However, 26 out of the 39 patients (66.7%) with a patent infarct artery demonstrated angiographic signs of residual coronary thrombi. With an estimated average of 75 +/- 25% in both, patients with and without residual thrombus, the severity of the residual stenosis after thrombolysis was found to be independent from the presence of angiographic signs of residual coronary artery thrombosis. In patients with residual coronary thrombi, however, a trend towards poorer coronary perfusion was observed (50% vs 77% of the patients with prompt antegrade [TIMI grade III] perfusion [p less than 0.2]. Control angiography performed 24 to 36h after thrombolysis revealed reocclusion of the infarct artery in 26.3% of the patients with residual coronary thrombi, while none of the infarct vessels without angiographic signs of residual thrombosis had reoccluded (p less than 0.05). At follow-up angiography 17 to 23 days after thrombolysis this difference in the incidence of reocclusions had further increased to 43.8% of patients with vs 12.5% of patients without residual coronary thrombus (p less than 0.01). Thus, after thrombolysis, residual thrombotic material remaining in the infarct related vessel seems to be a major risk factor, indicating early reocclusion of the infarct artery.

Angioplasty, Balloon, Coronary↗
PubMed1989

Low dose urokinase preactivated natural prourokinase for thrombolysis in acute myocardial infarction.

By inducing minimal free-fibrinolytic activity with low dose urokinase, the lag phase of prourokinase can be overcome, and the rate of thrombolysis with this substance can be strongly enhanced. The thrombolytic potency of a combination of 250,000 IU of urokinase and 2 doses of prourokinase (4.5 or 6.5 megaunits) was evaluated in an open-label, nonrandomized dose-finding study. Thirty-one patients participated. With 4.5 megaunits of prourokinase (group 1, 15 patients) patency was demonstrated angiographically at 60 minutes in 33% while with 6.5 megaunits (group II, 16 patients) 75% patency was achieved (p less than 0.01). A second angiogram recorded 24 to 36 hours after thrombolysis revealed reocclusion in 60 versus 8% of primarily patent coronary arteries (p less than 0.05). Hemostatic monitoring in both groups revealed only slight to moderate consumption of fibrinogen (-9 vs -13%), plasminogen (-29 vs -34%) and alpha 2-antiplasmin (-59 vs -63%), and an increase in D-dimers, the split products of cross-linked fibrin, to a maximum of 1.008 +/- 1.211 vs 0.547 +/- 0.684 micrograms/liter. None of these differences was significant. Bleeding complications were more frequently observed in group II (13 vs 37%) (difference not significant), but were mild and related to puncture sites, except in 1 patient with mild oozing from the gum. No major hemorrhage was observed. These results suggest that low dose urokinase preactivation enhances the thrombolytic potency of prourokinase, without affecting its high fibrin specificity. Compared to previous studies using only prourokinase, low dose urokinase preactivation reduces by 50% the prourokinase dose as required for effective thrombolysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMedDate not supplied

Urokinase-induced mitogenesis is mediated by casein kinase 2 and nucleolin.

BACKGROUND: Urokinase (uPA) and the urokinase receptor (uPAR) form a multifunctional system capable of concurrently regulating pericellular proteolysis, cell-surface adhesion, and mitogenesis. The role of uPA and uPAR in directed proteolysis is well established and its function in cellular adhesiveness has recently been clarified by numerous studies. The molecular mechanisms underlying the mitogenic effects of uPA and uPAR are still unclear, however. RESULTS: We identified mechanisms that might participate in uPA-related mitogenesis in human vascular smooth muscle cells and demonstrated that uPA induces activation of a unique signaling complex. This complex contains uPAR and two additional proteins, nucleolin and casein kinase 2, which are implicated in cell proliferation. Both proteins were isolated by affinity chromatography on uPA-conjugated cyanogen-bromide-activated Sepharose 4B and were identified using nano-electrospray mass spectrometry and immunoblotting. We used laser scanning and immunoelectron microscopy studies to further demonstrate that nucleolin and casein kinase 2 are located on the cell surface where they colocalize with the uPAR. Moreover, the proteins were co-internalized into the cell as an entire complex. Immunoprecipitation experiments in combination with an in vitro kinase assay demonstrated a specific association of uPAR with nucleolin and casein kinase 2 and revealed a uPA-induced activation of casein kinase 2, which presumably led to phosphorylation of nucleolin. Blockade of nucleolin and casein kinase 2 with specific modulators led to the inhibition of uPA-induced cell proliferation. CONCLUSIONS: We conclude that in human vascular smooth muscle cells, uPA induces the formation and activation of a newly identified signaling complex comprising uPAR, nucleolin, and casein kinase 2, that is responsible for the uPA-related mitogenic response. The complex is not a unique feature of vascular smooth muscle cells, as it was also found in other uPAR-expressing cell types.

Amino Acid Sequence↗
PubMedDate not supplied

[Thrombolytic therapy in the past, present and future].

During the last decade, thrombolysis has developed in a unique and unprecedented way from an outsider method to a well-established standard treatment in acute myocardial infarction. Since the use of thrombolytic techniques in other entities of thromboembolic disease has been prompted by this success. As an introduction into this intriguing and inspiring field in clinical science, the present paper tries to summarise briefly the development of thrombolysis since 1933 when "fibrinolysin" was discovered in the culture medium of beta-haemolysing streptococci, as well as the presence and future of thrombolytic therapy.

Angiography↗
PubMedDate not supplied

[Value of laboratory diagnosis in thrombolytic therapy].

Today, profound insight into the clotting and fibrinolytic systems during therapeutic thrombolysis is offered by a variety of laboratory assays. While the purpose of scientific investigations is to increase the knowledge on changes imposed by the mechanism of thrombolysis, the rationale for performing coagulation assays during thrombolytic therapy is to increase the safety of treatment. To make laboratory monitoring of thrombolytic therapy most effective, the main issues which should be solved should be defined. The main reasons for performing coagulation assays during and after thrombolytic therapy are: 1. To monitor the adjunctive anticoagulant therapy. 2. To detect potential bleeding hazards early, and 3. in case bleeding complications occur, to help to optimise of the therapeutic strategies to avoid excessive diagnostics. Most of the methods affording an insight into coagulation and fibrinolysis are not very helpful in terms of improved therapeutic safety. Too frequent repetition of assays is likewise superfluous. In our opinion, clinical routine monitoring should consist of red blood cell count, aPTT, and fibrinogen according to Clauss' method which should be repeated during the first 48 hours after initiation of therapy at 8- to 12-hour intervals. It must be mentioned in this respect that fibrinogen according to Clauss' method during thrombolytic therapy must be regarded an assay to estimate the global coagulation potential of the blood rather than to quantify fibrinogen levels. In our opinion, it is this that makes the Clauss' method superior to other methods of fibrinogen determination.

Blood Coagulation Tests↗
PubMedDate not supplied

[Undesirable side effects in thrombolytic therapy].

Even with the new fibrin-specific plasminogen activators thrombolytic therapy remains burdened with numerous side effects, some of them being severe or even life threatening, therapists being horrified if in rare cases the patient dies from severe haemorrhage subsequent to thrombolysis. The incidence and severity of bleeding increase with increasing aggressiveness of the therapeutic regimen and with increasing time during which the thrombolytic state is maintained. Furthermore, side effects related either to the plasminogen activator used (allergic reactions and systemic fibrinogen breakdown e.g.) or related to the underlying disease (pulmonary embolism and reperfusion arrhythmias e.g.) have to be considered. In order not to let thrombolysis become a double-edged sword, the risks of thrombolytic therapy should carefully be weighted against the benefits before thrombolysis is commenced.

Blood Coagulation Tests↗