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Biomedical subjects

U Zeymer

Publications and source records attributed to U Zeymer.

At least 19 recordsLinked to original sources
PubMed1996

Diltiazem improves cardiac function and exercise capacity in patients with idiopathic dilated cardiomyopathy. Results of the Diltiazem in Dilated Cardiomyopathy Trial.

BACKGROUND: Evidence is arising that calcium antagonists in idiopathic dilated cardiomyopathy (IDC) may have beneficial effects on virus-induced cardiopathology, alcohol toxicity, micro-circulatory disorders, and impaired calcium cycling, all possibly involved in the pathogenesis of the disease. Thus, the effect of adjunct diltiazem (60 to 90 mg TID) on standard treatment was investigated. METHODS AND RESULTS: The Diltiazem in Dilated Cardiomyopathy (DiDi) trial was a randomized, double-blind, placebo-controlled, multicenter trial of 186 patients (92 receiving diltiazem, 94 receiving placebo) with IDC diagnosed by coronary angiography, catheterization of the left side of the heart, and a left ventricular ejection fraction of < 0.50 (mean, 0.34 +/- 0.11). The effect of adjunct diltiazem treatment on transplant listing-free survival, hemodynamics, exercise capacity, and subjective status was investigated. During the 24-month study period, 33 patients dropped out of the study; 153 patients finished the study protocol. Twenty-seven patients died or had a listing for heart transplantation: 16 in the placebo group and 11 in the diltiazem group. The transplant listing-free survival rate was 85% for diltiazem and 80% for placebo recipients (P = .444). After 24 months, only diltiazem significantly increased cardiac index at rest (P = .01) and under a workload (P = .02), systolic and diastolic pressures (P = .003 and P = .004), stroke volume index (P = .003), and stroke work index (P = .000) and decreased both pulmonary artery pressure under workload (P = .007) and heart rate (P = .001). Diltiazem also increased exercise capacity (P = .002) and subjective well-being (P = .01). Adverse reactions were minor and evenly distributed in both groups, except for an increase in the PQ interval in the diltiazem group. CONCLUSIONS: In patients with IDC, the adjunct therapy of diltiazem improves cardiac function, exercise capacity, and subjective status without deleterious effects on transplant listing-free survival.

Calcium Channel Blockers↗
PubMed1996

Recombinant hirudin (HBW 023) produces stable anticoagulation unaffected by circadian variation in patients with thrombolysis for acute myocardial infarction.

BACKGROUND: Circadian variations have been described for a number of haemostatic and physiological factors, all of which might predispose towards clotting in the late morning. The anticoagulation effect of heparin has been shown to respond in a circadian manner, resulting in minimal prolongation of the activated partial thromboplastin time (aPTT) in the morning. METHODS: Recombinant hirudin (HBW 023) given as a bolus of 0.07, 0.1, 0.2 or 0.4 mg.kg-1 followed by an infusion of 0.05, 0.06, 0.1 or 0.15 mg.kg-1 over 48 h was used as conjunctive therapy to thrombolysis with front-loaded recombinant tissue-type plasminogen activator (100 mg.90 min-1) in 40 patients with acute myocardial infarction. APTT, activated clotting time and free hirudin plasma levels were determined at baseline and at 8, 12, 16, 20, 24, 32, 40 and 48 h. RESULTS: The prolongation of aPTT and activated clotting time was dose-dependent and stable. In 82.5% of the patients, aPTT values were ranged between the highest and the lowest aPTT of < 30 s. When the results were divided into four time intervals (0000-0600, 0600-1200, 1200-1800, 1800-2400) neither in the individual patients nor in the mean values of the four different dose groups was any significant circadian variation in aPTT or activated clotting time prolongation observed. The pharmacokinetic studies of free hirudin plasma levels revealed no circadian rhythm either. All but one patient (97.5%) had a patent vessel (TIMI grade 2/3) at the end of the hirudin infusion. CONCLUSIONS: Recombinant hirudin, in contrast to heparin, does not show any circadian variation in its anticoagulation effect. This might, in part, explain the more stable and predictable anticoagulation achieved by hirudin, which is associated with a reduced rate of reocclusions after thrombolysis.

Adult↗
PubMed1995

Frequency of "optimal anticoagulation" for acute myocardial infarction after thrombolysis with front-loaded recombinant tissue-type plasminogen activator and conjunctive therapy with recombinant hirudin (HBW 023). ALKK Study Group.

This retrospective analysis reviewed 183 patients with acute myocardial infarction who were given front-loaded recombinant tissue-type plasminogen activator (rt-PA) and r-hirudin (HBW 023) in 1 of 4 dose groups (bolus dose of 0.07, 0.1, 0.2, or 0.4 mg/kg, followed by an infusion of 0.05, 0.06, 0.1, or 0.15 mg/kg/hour over 48 hours). Activated partial thromboplastin time (aPTT) levels were determined at baseline and at 4, 8, 12, 16, 20, 24, 32, 40, and 48 hours. Of the 178 patients with r-hirudin treatment for > or = 12 hours, anticoagulation was optimal in 55.1% (all aPTTs > 2 x baseline), suboptimal in 33.7% (lowest aPTT > 1.5 but < 2 x baseline), and inadequate in 11.2% (> or = 1 aPTT but < 1.5 x baseline). Optimal anticoagulation was observed more frequently in the higher dose groups (dose 1, 15%; dose 2, 44.4%; dose 3, 63.4%; dose 4, 73.4%; p for trend < 0.0001). Patency (according to Thrombolysis in Myocardial Infarction trial grade 2 or 3) of the infarct artery after 36 to 48 hours was higher in the group with optimal anticoagulation compared with those with suboptimal or inadequate anticoagulation: 97.9%, 88.4%, and 85%, respectively (p = 0.03 optimal vs suboptimal or inadequate anticoagulation). In conclusion, r-hirudin in a dose of 0.1 or 0.15 mg/kg/hour achieves an optimal anticoagulation in about 63% or 74% of patients, which is associated with an enhanced patency 24 to 48 hours after rt-PA. A subsequent study revealed that this effective anticoagulation may be accompanied by an increased risk of severe bleeding complications after thrombolysis.

Adult↗
PubMed1995

Recombinant hirudin and front-loaded alteplase in acute myocardial infarction: final results of a pilot study. HIT-I (hirudin for the improvement of thrombolysis).

Recombinant hirudin, a specific thrombin inhibitor, has been shown to accelerate thrombolysis and reduce reocclusions in experimental models. In a pilot trial recombinant hirudin (HBW 023) was used as an adjunctive therapy to thrombolysis with front-loaded tissue plasminogen activator (t-PA) (100 mg.90 min-1) in 40 patients with acute myocardial infarction whose duration of symptoms was less than 6 h. Patients received a bolus of r-hirudin of 0.07 mg.kg-1 b.w. followed by an infusion of 0.05 mg.kg-1.h-1 over 48 h. Complete patency (TIMI grade 3) of the infarct-related artery at 30, 60 and 90 min after the start of thrombolytic therapy was seen in 38.5%, 64.1% and 71.0% of patients, respectively. After 24-48 h, 80% of patients had a complete patent infarct vessel. A very early, complete and sustained patency (TIMI grade 3 at 60 and 90 min and at 24-48 h) was observed in 55% of patients. Reocclusions during the hirudin therapy appeared in six (16.1%) patients, two of whom had a PTCA at 90 min. The only reinfarction was seen after 6 h; this was successfully treated with additional thrombolysis. Major bleedings, mostly related to the invasive procedure, were observed in three patients. Spontaneous organ bleedings and intracerebral haemorrhages did not occur. There was one in-hospital death due to a late retroperitoneal bleeding. In was concluded that, with regard to safety and efficacy, the general feasibility of r-hirudin as adjunctive therapy to thrombolysis with front-loaded t-PA, has been demonstrated.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Prevention and management of thrombotic complications during coronary interventions. Combination therapy with antithrombins, antiplatelets, and/or thrombolytics: risks and benefits.

Acute occlusions after percutaneous transluminal coronary intervention occur in about 5% of cases. The incidence of these serious adverse events may be reduced by the identification of risk factors, appropriate indication for the intervention, and by medical therapy with antiplatelets and antithrombins. The medical management of complications during percutaneous transluminal interventions also may include thrombolytics. Aspirin has been shown to significantly reduce the incidence of procedure-related coronary occlusion and ischaemic events. Available data suggest pre-treatment with 250-500 mg followed by 100-300 mg aspirin after the intervention. Ticlopidine seems to be equally effective; however, because of its side effects it should be used only in cases of a contra-indication to aspirin. The second indispensable therapeutic concept in the prevention of acute thrombotic events during PTCA is thrombin inhibition. The level of anticoagulation achieved by heparin seems to be critically important. Therefore the recommendation for heparin dosing is a bolus of 10,000 U followed by an intravenous infusion over 24 h of either 1000 U.h-1 or an infusion adjusted to keep the aPTT above 3 times control, but lower doses of shorter duration may be equally effective in uncomplicated cases. Prolonged pre-treatment with heparin may be useful if the pre-intervention angiogram is suggestive of intracoronary thrombus. Thrombolysis as an adjunct to PTCA did not reduce the rate of periprocedural coronary occlusions, but pre-treatment with thrombolysis may be useful in patients with recanalization of occluded vein grafts or in patients with large amounts of thrombotic material. In acute coronary occlusion, thrombolysis has rarely been used as a sole rescue therapy and results have not been encouraging, although a thrombotic process often is involved. Thrombolysis as an adjunct to rescue angioplasty showed no better clinical outcome than prolonged balloon inflation or stenting. Because of serious bleeding complications, thrombolysis should only be considered as a treatment option if thrombosis is unequivocally the major cause of the acute occlusion.

Angioplasty, Balloon, Coronary↗
PubMed1994

[Development of new thrombolytic substances].

Early treatment with thrombolytic drugs has been shown to reduce mortality in patients with acute myocardial infarction. Thrombolytic therapy with early, complete and sustained patency of the infarct related artery is associated with a low inhospital mortality of 3 to 4% (Figure 1). Even with the most effective thrombolytic regimens this aim at present is achieved in only about 50% of the patients. The optimal thrombolytic drug should be effective (rapid, complete and sustained recanalization of the infarct related artery), safe (low incidence of severe bleedings), easy to administer (e.g. bolus application) and cost effective. Attempts to improve thrombolytic treatment include the search for better fibrinolytic agents and more effective adjunctive therapies. In the field of adjunctive therapy new more specific thrombininhibitors appear promising and are currently under investigation. In dose-finding studies recombinant hirudin reduced reocclusions and reinfarctions after t-PA thrombolysis. There are several approaches for the improvement of plasminogen activation (Table 1). While new improved dose regimens (e.g. "front-loaded" t-PA) and combination therapies are not subject of this article, it will deal with the recombinant production of naturally occurring plasminogen activators and the development of "designer drugs", which were created in the laboratory by altering the natural occurring molecules t-PA and scu-PA. t-PA contains four domains with different functional properties (Figure 3). Of a variety of mutants and variants of t-PA with altered fibrin-affinity half-life or fibrin specificity one recombinant plasminogen activator (r-PA) is under clinical investigation. r-PA, a deletion mutant of t-PA consisting of the kringle-2 and protease domains, in a dose escalation study (GRECO) showed high early patency rates (Table 2), while there was a trend to a higher incidence of very early reocclusions. In a randomised trial (RAPID), comparing three different r-PA regimens with standard t-PA (100 mg/3 h) a double bolus of 10 MU+ 10 MU r-PA was most effective with regard to early patency (Table 3). Chimeric plasminogen activators (Figure 4) consisting of parts of t-PA and the single-chain urokinase-type plasminogen activator (scu-PA) did not significantly improve at the same time fibrin specificity and thrombolytic potency of the natural occurring molecules. Complexes of plasminogen activators and monoclonal antibodies against platelets or fibrin improve the specificity and thrombolytic activity of the plasminogen activators (Figure 5). However, these molecules are potentially antigenic, costly and not in clinical use yet. Recombinant production of naturally occurring plasminogen activators seems at least as promising as the production of the above mentioned socalled designer drugs.(ABSTRACT TRUNCATED AT 400 WORDS)

Designer Drugs↗
PubMed1994

[Different therapeutic regimens in thrombolysis of acute myocardial infarct].

An early, complete, and sustained patency of the infarct related artery achieved by thrombolytic therapy reduces mortality in patients with acute myocardial infarction. In the ISIS-3-study there was no difference in mortality between t-PA, APSAC, and streptokinase. In contrast, in the GUSTO-trial, a "front-loaded" regimen of t-PA (100 mg/90 min) lead to a reduced inhospital mortality compared to streptokinase. This was most likely due to the higher early patency-rate of the infarct-related artery after the front-loaded t-PA. The search for new, more effective, thrombolytic regimens lead to a double-bolus injection of t-PA (2 x 50 mg) which revealed high early patency rates (> 80% TIMI-3 after 90 min). R-PA, a new recombinant plasminogen activator with a prolonged half-life, given as double bolus (2 x 10 MU), also produced high patency rates after 90 min without an increased incidence of reocclusions. Acetylsalicylic acid should be given routinely in every thrombolytic therapy. An anticoagulation with heparin seems to improve the efficacy of the more fibrin-specific thrombolytics t-PA, r-PA, and pro-urokinase. In dose-finding studies the specific thrombin inhibitor hirudin has been shown to significantly reduce reocclusions and reinfarctions compared to heparin. An "optimal thrombolysis" most likely can only be achieved by a thrombolytic agent with a very high early patency combined with an effective adjunctive therapy with platelet aggregation- and thrombin-inhibition.

Fibrinolytic Agents↗
PubMed1993

[The use of a percutaneously connected heart-lung machine during resuscitation in cardiogenic shock after acute myocardial infarct].

A 47-year-old man was referred by an emergency physician to the intensive care unit of a hospital under resuscitation conditions while having recurrent attacks of ventricular fibrillation. Coronary angiography, performed while resuscitation measures had to be maintained, revealed severe three-vessel disease with occlusion of the anterior interventricular branch at its origin. Electrical and haemodynamic instability persisted even after thrombolysis with urokinase and introduction of an intraaortic balloon pump. Percutaneous partial cardiopulmonary bypass (CPB) was, therefore, instituted and a cardiac output of 2.5 1 achieved together with a stable sinus rhythm and a systolic pressure of 60-80 mm Hg. After 9 h on CPB, drug administration could be levelled off and he was mobilised. He showed no neurological deficits and 4 months later he underwent an elective coronary bypass operation. This report demonstrates that even in conditions of resuscitation mechanical circulatory support can be undertaken rapidly and successfully, in the face of electrical instability, to achieve at least temporarily a stable circulation.

Combined Modality Therapy↗
PubMed1993

[Ischemia--reliable results of therapy, operation and angioplasty--in coronary disease].

Randomized studies have shown that coronary bypass-surgery is effective in prolonging survival and reducing symptoms in various groups of patients with coronary artery disease, when compared with medical therapy alone. This effect is most pronounced and stable in patients who received an internal-mammary-artery graft. Therefore internal-mammary-artery grafting for lesions of the left anterior descending coronary artery is preferable whenever indicated and technically feasible. While percutaneous transluminal coronary angioplasty is effective in improving symptoms of angina pectoris, beneficial effects on survival have not yet been shown. In randomized trials of PTCA versus bypass-surgery acute results were comparable. During follow-up significantly less re-interventions and more angina-free patients were seen in the bypass-groups, indicating a more stable result after bypass surgery. In older patients with a higher mortality and rate of cerebral vascular events during surgery, a palliative PTCA of the culprit lesion may be superior to the bypass-operation. For the often used "unproven" indications for PTCA (silent ischemia, infarct-related artery in asymptomatic patients, isolated proximal LAD-stenosis, acute myocardial infarction, cardiogenic shock) larger randomized trials should be awaited to prove the effectiveness of PTCA in these settings.

Aged↗
PubMed1993

[New substances and dosages for thrombolysis in acute myocardial infarct].

The aim of thrombolytic therapy in acute myocardial infarction is the early, complete and sustained restoration of bloodflow in the infarct-related artery. In a randomized trial in 421 patients with acute myocardial infarction front-loaded rt-PA (100 mg in 90 min) showed a significantly higher 90-min patency (84.4%) in comparison with APSAC (70.3%). In-hospital mortality was significantly lower after rt-PA (2.4%) versus 8.1% after APSAC. While a single bolus injection of rt-PA produced lower patency and higher reocclusion rates, double bolus injections showed more promising results (90 min patency > 70%). A new recombinant plasminogen activator BM 06.022 (r-PA) with a longer half life can be given as a single bolus injection. In a dose-finding study r-PA produced rapid thrombolysis with a 90-min patency of 66% (10 MU) and 76% (15 MU). There was no excess in re-occlusions or bleeding complications. Although these results are quite promising, the search for the ideal thrombolytic strategy is still ongoing.

Coronary Circulation↗
PubMed1992

[Mitral insufficiency after percutaneous balloon valvuloplasty in mitral stenosis. Incidence and progression].

Percutaneous balloon valvoplasty of the mitral valve was performed in 126 patients (24 men, 102 women; mean age 55.0 +/- 12.1 years) with mitral stenosis. The mean transmitral valve gradient fell from 12.4 +/- 6.1 to 6.0 +/- 3.2 mmHg, while the valve opening area increased from 1.0 +/- 0.2 to 1.55 +/- 0.3 cm2. After percutaneous balloon valvoplasty 36 patients still had no mitral regurgitation, while the grade of mitral regurgitation remained the same in 47 (grade I: n = 35; grade I: n = 12). Mitral regurgitation, previously not present, occurred in 25 patients, but was severe in only three (grade III: n = 1; grade IV: n = 2). Previously present mitral regurgitation increased in 18 of 65 patients, in four to grade III, in one to grade IV. In three patients acute grade IV mitral regurgitation resulted from a tear in a leaflet of a fibrotic valve which was not or only slightly calcified, requiring emergency surgery. Followup observations over 16.9 (1-60) months showed no change in most patients, but three developed mitral regurgitation. The latter underwent elective surgery, as did one patient with acute mitral regurgitation. Thus a total of seven patients (5.6%) required surgery for mitral regurgitation after percutaneous balloon valvoplasty.

Adolescent↗
PubMed1992

Left main coronary stenosis by a mediastinal lymphoma.

A 50-year-old patient presented with a 3-month history of chest pain, a pathological result on electrocardiogram stress test, and signs of coronary heart disease on myocardial scintigraphy. Coronary angiography showed an isolated, moderate tubular stenosis of the left main coronary artery. Coronary bypass surgery was carried out, and intraoperative examination revealed a mediastinal lymphoma which caused the stenosis of the left main artery by external compression.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Proliferating cell nuclear antigen immunohistochemistry in rat aorta after balloon denudation. Comparison with thymidine and bromodeoxyuridine labeling.

The authors compared detection of proliferating vascular smooth muscle cells (SMC) in vitro and in vivo with proliferating cell nuclear antigen (PCNA) immunohistochemistry and two established methods: [3H]thymidine autoradiography and bromodeoxyuridine immunohistochemistry. Labeling with [3H]thymidine and bromodeoxyuridine of rat vascular SMC in culture stained 11% +/- 2% and 11% +/- 1% of cells, and PCNA immunohistochemistry 22% +/- 2% of cells. Proliferation in the media of the denuded rat aortae was highest 3 days after denudation: 4.2%, 3.8%, and 4.7% of labeled cells with [3H]thymidine, bromodeoxyuridine, and PCNA, respectively. In the intima, proliferation was highest 7 days after denudation with 42% [3H]thymidine, 40% bromodeoxyuridine, and 46% PCNA-positive cells. With double labeling, all [3H]thymidine-positive cells were PCNA positive, whereas some cells were only positive for PCNA. The authors conclude that PCNA immunohistochemistry compares favorably with [3H]thymidine autoradiography, and bromodeoxyuridine immunohistochemistry.

Animals↗
PubMed1991

[Percutaneous balloon valvuloplasty in mitral stenosis].

Between June 1986 and June 1989, percutaneous balloon valvuloplasty (PBV), using the transseptal, single-balloon technique, was performed in 50 consecutive patients (38 women and 12 men; mean age 54 +/- 14 years) with mitral stenosis. The procedure was technically successful in 48 patients (in one patient the atrial septum could not be crossed, in the other cardiac tamponade occurred). The mean diastolic gradient was decreased from 12.5 +/- 6.6 to 6.1 +/- 3.1 mmHg, mean pulmonary artery pressure (PAP) reduced from 29 +/- 12 to 22 +/- 6 mmHg, and valve opening area increased from 1.0 +/- 0.25 to 1.6 +/- 0.4 cm2. Redilatation had to be undertaken in four patients because of restenosis. Commissurotomy had to be performed in one patient, valve replacement in nine (restenosis in 4, poor primary results in 3, increase in regurgitation in 2). One patient died of a noncardiac cause. Follow-up observations for an average of 14 (3-36) months indicated in 30 of the remaining 33 patients without additional intervention a stable clinical improvement of at least one class (NYHA classification), as well as stable haemodynamic findings (gradient: 6.0 +/- 2.7 mmHg, valve opening area 1.5 +/- 0.3 cm, PAP 23 +/- 7 mmHg. Thus PBV achieved, at least in the medium term, clinical improvement in about two thirds of patients, and an operation was avoided.

Adolescent↗
PubMed1990

[Acute coronary thrombosis and myocardial ischemia following chemotherapy of Hodgkin's disease].

A 37 year old man without coronary risk factors or known heart disease showed progression of Hodgkin's disease after radiation and multiple chemotherapy. One day after the first cycle of chemotherapy with methotrexate, Ifosfamide and etoposide, he had an acute myocardial ischemia. The creatinin-kinase was elevated up to 325 U/l. Coronary angiography showed a thrombus in the left anterior descending coronary artery (LAD), while the other coronary arteries were normal. Ventriculography showed an apical akinesia. After 7 days of treatment with heparin coronary angiogram was normalized, without any stenosis in the LAD. To our knowledge this is the first documented case of a coronary artery thrombosis and myocardial ischemia after chemotherapy in a patient without coronary heart disease. We conclude that chemotherapy can cause myocardial ischemia by coronary artery thrombosis in patients without prior heart disease.

Adult↗
PubMed1989

[Infarct-typical changes in the electrocardiogram following chemotherapy with vinblastine].

Left-chest pain and infarct-like ECG changes occurred in a 47-year-old man who had had an orchiectomy for embryonic carcinoma of the testes and was receiving the second cycle of chemotherapy with vinblastine, bleomycin and cisplatin. Only creatine kinase was slightly elevated (90 U/l) among the heart-specific enzymes. Coronary angiography did not demonstrate any coronary abnormalities, but the ventriculogram showed apical akinesia. Chest pain and similar ECG changes again occurred during the third treatment cycle, this time without bleomycin. This sequence would suggest that vinblastine was the cause of the myocardial damage, although its pathogenesis is uncertain.

Antineoplastic Combined Chemotherapy Protocols↗