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D C Gulba

Publications and source records attributed to D C Gulba.

At least 37 records · Page 2Linked to original sources
PubMed1997

Sixty-minute alteplase protocol: a new accelerated recombinant tissue-type plasminogen activator regimen for thrombolysis in acute myocardial infarction.

OBJECTIVES: Our aim was to design and evaluate a new and easily administered recombinant tissue-type plasminogen activator (rt-PA) regimen for thrombolysis in acute myocardial infarction (AMI) based on established pharmacokinetic data that improve the reperfusion success rate. BACKGROUND: Rapid restoration of Thrombolysis in Myocardial Infarction (TIMI) grade 3 flow is a primary predictor of mortality after thrombolysis in AMI. However, TIMI grade 3 patency rates 90 min into thrombolysis of only 50% to 60% indicate an obvious need for improved thrombolytic regimens. METHODS: Pharmacokinetic simulations were performed to design a new rt-PA regimen. We aimed for a plateau tissue-type plasminogen activator (t-PA) plasma level similar to that of the first plateau of the Neuhaus regimen. These aims were achieved with a 20-mg rt-PA intravenous (i.v.) bolus followed by an 80-mg i.v. infusion over 60 min (regimen A). This regimen was tested in a consecutive comparative trial in 80 patients versus 2.25 10(6) IU of streptokinase/60 min (B), and 70 mg (C) or 100 mg (D) of rt-PA over 90 min. Subsequently, a confirmation trial of regimen A in 254 consecutive patients was performed with angiographic assessment by independent investigators of patency at 90 min. RESULTS: The comparative phase of the trial yielded, respectively, TIMI grade 3 and total patency (TIMI grades 2 and 3) of 80% and 85% (regimen A), 35% and 50% (B), 50% and 55% (C) and 60% and 70% (D). In the confirmation phase of the trial, regimen A yielded 81.1% TIMI grade 3 and 87.0% total patency. At follow-up angiography 7 (4.1%) of 169 vessels had reoccluded. In-hospital mortality rate was 1.2%. Nadir levels of fibrinogen, plasminogen and alpha2-antiplasmin were 3.6 +/- 0.8 mg/ml, 60 +/- 21% and 42 +/- 16%, respectively (mean +/- SD). Fifty-seven patients (22.4%) suffered from bleeding; 3.5% needed blood transfusions. CONCLUSIONS: The 60-min alteplase thrombolysis in AMI protocol achieved a TIMI grade 3 patency rate of 81.1% at 90 min with no indication of an increased bleeding hazard; it was associated with a 1.2% overall mortality rate. These results are substantially better than those reported from all currently utilized regimens. Head to head comparison with established thrombolytic regimens in a large-scale randomized trial is warranted.

Blood Coagulation Tests↗
PubMed1997

Stent implantation in patients with superior vena cava syndrome.

OBJECTIVE: The purpose of this study was to determine the feasibility of using Wallstent implantation to treat superior vena cava syndrome due to malignant tumors. SUBJECTS AND METHODS: Digital subtraction angiography showed obstruction of the superior vena cava in 13 patients who then underwent transluminal dilatation and Wallstent implantation. The patients were treated with IV heparin and monitored in the emergency department. Thereafter, they were treated with a platelet inhibitor for 4 weeks. RESULTS: Because their signs and symptoms improved, patients were able to resume radiation therapy, chemotherapy, or both. One patient died of cardiac arrhythmia 1 day after stent placement. Although eight patients have subsequently died of their bronchial or thyroid gland tumors, superior vena cava syndrome did not recur in any patient. CONCLUSION: Percutaneous implantation of Wallstent endoprostheses provides excellent palliation for superior vena cava syndrome.

Aged↗
PubMed1996

-Anticoagulant drugs-.

In todays medicine, anticoagulant drugs like heparin and coumadin derivatives have become indispensable for the treatment of thrombo-embolic diseases. Heparin, consisting of long poly-sulfated polysaccharide chains of variable length and sequences is mostly derived from porcine mucosa. Its bioavailability by other than the parenteral way of administration is almost negligible. Therefore, with only few exceptions, it is almost exclusively applied in hospitalized patients (short-term therapy) or to bridge 2 phases of treatment with oral anticoagulant drugs. Today, besides the conventional high-molecular weight heparins, new fractionated heparins are gaining more and more attention. They offer the advantage of a more reliable resorption from the subcutaneous tissue and thus warrant reliable plasma levels. In many recent randomized trials of deep vein thrombosis and pulmonary embolism, those fractionated heparins have proven to successfully substitute for intravenously applied, aPTT-controlled unfractionated heparin. It remains however open, whether this also translates into the prevention of arterial thrombo-embolic diseases. Heparin may not pass through the placental barrier nor into the milk and is regarded non-teratogenic. Therefore, it may be regarded the ideal anticoagulant for pregnant women and lactating mothers. Those women, however, still carry the heparin-associated risk of bleeding and osteoporosis. In comparison: Coumadin derivatives interfere with the carboxylation of the clotting factors II, VII, IX, and X as well as proteins C and S. By inhibiting the synthesis of these proteins they shift the haemostatic balance to a lower level. In addition, they are almost completely bioavailable by the enteral pathway. They are, therefore, regarded the drugs of choice for long-term anticoagulant therapy in patients at particular thromboembolic risk. For their therapeutic range, being extremely narrow, meticulous drug monitoring by repeated INR-measurements as well as a reliable compliance of the patient to drug intake and dietary restrictions are mandatory to exclude phases with over- or under-anticoagulation. Above all, coumadin therapy is characterized by numerous drug interactions. Thus, whenever the basal medication is changed, for whatever reason, more intense care must be laid to drug monitoring, and the intervals for INR determinations must transiently be shortened. Coumadin derivatives do pass through the placental barrier and in minor amounts also into the milk of breast feeding mothers. Furthermore, they are highly teratogenic. If taken during pregnancy, malformations of the central nervous system are reported to occur in some 10% to 30% of the infants. Thus during pregnancy and in the lactation period, coumadin therapy should be avoided. Bleeding episodes of different severity are the most frequent adverse effects of anticoagulant therapy, no matter whether heparin or coumadin is given. There is a direct relation between the intensity of anticoagulant therapy and the frequency of bleeds. Luckily, most bleeding episodes do not create major therapeutic problems. In case of severe bleeds, however, the anticoagulant therapy must immediately be suspended. In case of coumadin therapy the immediate administration of 4 packs of PPSB (prothrombin-complex-concentrates) or FFP (fresh-frozen-plasma) with concomitant low doses of heparin is additionally advised. Allopecia diffusa, urticartia and allergic reactions are known side effects of anticoagulant therapy. Patients on long-term heparin may also suffer from severe osteoporosis. On the other hand, heparin treatment raises the hazzards of a HAT-Syndrome (heparin-associated thrombocytopenia) (estimated frequency 0.01% to 0.1% of treated patients), giving rise to severe and life-threatening thrombo-embolic side effects predominantly in the arterial tree. In these cases, heparin must be suspended despite those severe thrombo-embolic episodes.

Abnormalities, Drug-Induced↗
PubMed1996

Thrombolytic agents--an overview.

Thrombolysis today has become a routine option not only in the treatment of acute myocardial infarction but also in many other manifestations of thromboembolic disease. Until one decade ago, only two plasminogen activators, streptokinase and urokinase, were available for clinical use. They were characterized by limited thrombolytic potencies and major side effects including systemic fibrinogen breakdown, bleeds and stroke. This has prompted the search for new plasminogen activators with better pharmacological and clinical profiles. The first such new plasminogen activators were Anistreplase, a chemically modified version of the streptokinase-plasminogen-activator-complex and tissue-type plasminogen-activator produced by recombinant technology. Both new substances have fueled the development in modern thrombolytic treatment. While the clinical progress with t-PA was confirmed in large, double-blind, randomized, multicenter trials, no real superiority of anistreplase over the traditional plasminogen activators urokinase and streptokinase has been substantiated. While the clinical use of t-PA today has been established for acute myocardial infarction, pulmonary embolism and deep vein thrombosis, current research is focused on further plasminogen activators with further improved thrombolytic properties. This review summarizes the current knowledge on the biochemical and pharmacological properties of the first, second and future generation of plasminogen activators.

Fibrinolytic Agents↗
PubMed1994

Medical compared with surgical treatment for massive pulmonary embolism.

We compared embolectomy (when available) with thrombolysis in patients with shock and massive pulmonary embolism. 13 patients were operated on, 10 (77%) of whom survived. The inferior vena cava was routinely clipped. The 24 medically treated patients were given alteplase until systemic and pulmonary artery pressures stabilised and heparin thereafter; 16 (67%) survived. Major haemorrhage occurred in 28% of medically treated patients, but was not fatal. 1 patient had a small cerebral haemorrhage that resolved without drainage. One-fifth of the medical group had a re-embolism, which suggests that temporary caval umbrellas are indicated in medically treated patients. Thrombolysis may provide a life-saving option and a randomised trial is warranted.

Adult↗
PubMed1994

Thrombolysis in thromboembolic diseases.

Thrombolysis in many manifestations of thromboembolic disease offers a valuable alternative to surgery. However, as thrombolysis is always associated with a bleeding hazard (though low) one should always weigh the risks against the expected benefits when the decision for or against this therapeutic option is made. Furthermore, in selecting the appropriate thrombolytic agent, one should be led by the urgency of reperfusion to maintain organ function. If one decides on an aggressive, high-dose, brief-duration regimen, reperfusion may be achieved more rapidly but may be incomplete in the majority of cases. On the other hand, by selecting an intermediate- or long-duration, low-dose regimen, reperfusion may happen too late to improve the patient's prognosis. Above all, one should keep in mind that the hazard of serious bleeding constantly increases with duration of thrombolysis. No matter which strategy is regarded as the best to resolve a clot in a particular patient with a particular type of thromboembolic disease, thrombolysis should be accompanied by high doses of i.v. heparin. Finally, if bleeding occurs in spite of all precautions taken, the new generation of fibrin-specific thrombolytic agents offers the advantage of short half-lives. In addition--in contrast to streptokinase--the hemostatic defect that they cause may be rapidly reversed by the infusion of antagonist drugs such as aprotinin, tranexamic acid, or epsilon-aminocaproic acid. This adds to the clinical safety profile of these thrombolytic agents.

Contraindications↗
PubMed1993

[The value of late thrombolytic perfusion in acute myocardial infarct].

Contradicting previous views that reperfusion therapy in acute myocardial infarction has to be restricted to the first 4 to 6 h, the paradigm of thrombolysis in acute myocardial infarction has to be expanded to 12 h, since the results of the LATE study have been published. While early thrombolysis (up to 90 min) aims towards myocardial salvage, the benefit of late reperfusion seems to depend on an improved myocardial remodeling and on rhythmic stabilization (open artery hypothesis). Today the value of late reperfusion therapy can be regarded as proven in a clinical setting, the mechanisms of late reperfusion therapy, however, still remain to be settled.

Coronary Circulation↗
PubMed1993

[Thrombolytic therapy of pulmonary embolism--a therapeutic alternative?].

The spontaneous prognosis of pulmonary embolism is mainly dependent on the degree of pulmonary artery obstruction. As for the cause of spontaneous lysis, submassive pulmonary embolism generally will be survived with complete restitution of the pulmonary artery trunk. On the other hand, the hallmark of massive pulmonary embolism is a tremendously high early mortality. In the decision for thrombolysis in patients with pulmonary embolism, major attention must therefore be paid to the severity of pulmonary obstruction. Up to now, neither a reduction in mortality nor in secondary morbidity by thrombolysis has convincingly been shown in patients with submassive pulmonary emboli. In the rare cases with submassive pulmonary emboli, when one still tends to decide in favor of thrombolysis, beyond the thrombus obstructing the pulmonary artery, the thrombus identified as the source of the emboli should also be attacked. In these patients, careful attention has to be paid to the contraindications of thrombolysis, and low-dose continuous infusion regimens like the ones used in deep venous thrombosis should be selected. In patients with massive and life-threatening pulmonary embolism, however, thrombolysis has the potential to save lives and, therefore, must be judged in a different way. In spite of their high frequency, for the critical prognosis of these patients only minor attention must be paid to the contraindications of thrombolysis. In these critically ill patients, high-dose intravenous, brief duration infusions of the thrombolytics therefore can be considered as the best option. The far lower cost (about one-tenth) and the comparable success rates with embolectomy makes thrombolysis the regimen of choice, especially when embolectomy is not readily available.

Angiography↗
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↗
PubMed1992

Systemic recombinant tissue plasminogen activator lysis for left atrial thrombus formation after single-lung retransplantation.

This report describes a recipient of single-lung transplantation surviving extraordinary complications: (1) early graft failure mandating retransplantation; (2) left atrial thrombus formation, which resolved by recombinant tissue plasminogen activator lysis; (3) and development of a "locked-in-syndrome." Possible underlying mechanisms are discussed.

Extracorporeal Membrane Oxygenation↗
PubMed1991

Angioplasty of subacute and chronic total coronary occlusions: success, recurrence rate, and clinical follow-up.

Angioplasty of single total, subacute, or chronic coronary occlusions was performed in 90 patients. It was successful in 54 occlusions (60%), in 77% of those less than 6 weeks old, and in 44% of those of greater than 6 weeks' duration (p less than 0.005). All procedures were uneventful. Control angiography was performed in 53 (98%) patients with successful angioplasty after an average interval of 97 +/- 53 days. Stenosis had recurred in 16 patients (30%). During a follow-up period of 36 +/- 13 months, three patients died, five patients underwent coronary bypass operation, and 10 had reangioplasty. Despite an additional late angiographic recurrence of stenosis in seven patients, 36 patients revealed angiographic long-term success. In the 46 nonoperated patients, angina pectoris and exercise stress tests were substantially improved. Thus angioplasty of subacute and chronic total coronary occlusions is an uneventful procedure, the success rate depending on the duration of the occlusions. Despite a high angiographic recurrence rate, the angiographic and clinical long-term results are favorable.

Adult↗