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Biomedical subjects

H Teufelsbauer

Publications and source records attributed to H Teufelsbauer.

At least 19 recordsLinked to original sources

Hemostasis activation in patients with liver cirrhosis.

In patients with liver cirrhosis a decrease of the coagulant potential is well-documented and has been linked to the high bleeding tendency among these patients. Whether the decrease of the coagulant potential is only due to a reduced hepatic synthesis of coagulation factors or also to its consumption by disseminated intravascular coagulation is debatable. We investigated hemostasis activation markers thrombin-antithrombin III complexes (TAT), fibrin degradation products (D-Dimer) and plasmin-alpha 2-antiplasmin complexes (PAP) in 41 outpatients with liver cirrhosis (Child-Pugh index 1 n = 18, 2 n = 15, 3 n = 8). Compared to controls similar in terms of age and sex, TAT, D-Dimer and PAP was elevated in the whole group of patients. A progressive increase of D-Dimer and PAP from Child 1 to 3 indicates a relationship between the severity of cirrhosis and the amount of hemostasis activation. Investigation of the natural anticoagulant potential showed significant decreases of antithrombin III (AT III), protein C, and protein S, most pronounced in Child 3 patients. Statistical analysis revealed significant negative correlations between levels of D-Dimer and both AT III and protein C, indicating that hemostasis activation is linked to the loss of anticoagulant potential.

Adult

Comparison of serum fluoride levels after administration of monofluorophosphate-calcium carbonate or sodium fluoride: differences in peak serum concentrations.

Fluoride salts are widely used in Europe in the treatment of established osteoporosis with crush fractures for their ability to increase trabecular bone mass. However, in the United States fluorides are still regarded as an experimental drug. In a prospective, randomized study we compared the fluoride pharmacokinetics of enteric-coated sodium fluoride and disodium monofluorophosphate calcium carbonate (MFP-Ca) over the period of 76 h. Twenty subjects (12 females, 8 males), aged 35-80 years, free of gastrointestinal disorders, renal impairment, and liver disease and without prior fluoride intake entered the study. Ten subjects received NaF (11.3 mg fluoride) twice a day and the other ten MFP-Ca (13.2 mg fluoride) twice a day. During the study period of 76 h the patient's usual food intake was not changed. Serum fluoride levels were determined using an ion sensitive electrode. After intake of a single drug preparation of MFP-Ca or NaF, MFP-Ca showed a significantly shorter lag time of absorption and a significantly higher maximal serum fluoride concentration than NaF (P < 0.01). A comparison of fluoride cumulative characteristics of both drugs showed virtually identical serum fluoride levels before intake of the morning dose on all 4 study days, whereas serum fluoride concentrations measured 4 h afterwards were significantly higher for MFP-Ca than for NaF. These data provide evidence of high "peak" serum fluoride levels for MFP-Ca, whereas only small peak-to-trough fluctuations are seen for NaF.

Adult

Aprotinin does not decrease early graft patency after coronary artery bypass grafting despite reducing postoperative bleeding and use of donated blood.

Forty-five male patients with planned coronary artery bypass operation were randomized in a double blind fashion to receive either 6 million kallikrein inactivator units of aprotinin (high-dose group), 2 million kallikrein inactivator units of aprotinin (low-dose group), or placebo (control group). Postoperative bleeding was significantly decreased in both aprotinin groups in comparison to that in the control group (590 ml [290 to 1800 ml] high-dose group and 650 ml [280 to 1900 ml] low-dose group versus 920 ml (350 to 2700 ml) control group, p < 0.001). There was no difference between the two aprotinin groups. The need for postoperative blood transfusion was significantly lower in the aprotinin groups (1.46 [0 to 4] blood units high-dose group and 1.65 [0 to 5] blood units low-dose group versus 2.43 [0 to 7] blood units control group, p < 0.05). All patients underwent coronary angiography between the seventh and twelfth postoperative day. No difference was found among the three groups in patency of vein grafts-93.8% in the high-dose group, 94.5% in the low-dose groups, and 93.3% in the control group. Therefore, aprotinin significantly reduced postoperative bleeding and transfusion requirement after coronary artery bypass grafting without influencing early graft patency.

Aprotinin

Early activation of hemostasis during cardiopulmonary bypass: evidence for thrombin mediated hyperfibrinolysis.

In 14 consecutive patients undergoing cardiopulmonary bypass for coronary bypass surgery the time course of coagulation and fibrinolysis markers were measured, e. g. plasma levels of thrombin-antithrombin III (TAT) complexes, cross-linked fibrin degradation products (XIFDP) and plasmin-alpha 2-antiplasmin complexes (PAP). TAT levels exceeded the 90% baseline percentile already during CPB (after opening of aortic clamp) in 10 patients, whereas PAP and XIFDP exceeded their 90% percentile in only one patient at this time. Concerning fibrinolysis markers PAP and XIFDP the majority of patients showed elevations higher than their 90% baseline percentile only 1 h postoperation. Correlation analysis revealed significant dependencies between TAT levels during and at the end of CPB and PAP levels 1 h postoperation (R = 0.55 and R = 0.56 respectively). Furthermore, 1 h postoperation XIFDP levels were significantly correlated with both TAT and PAP. Peak XIFDP levels at the same time correlated with blood loss via thoracic drains (R = 0.56). Thus, we suggest that hyperfibrinolysis in patients undergoing CPB is at least partly due to hypercoagulation. Clinically, this may implicate that intensified anticoagulation could prevent hyperfibrinolysis and reduce postoperative blood loss.

Adult

The effect of insulin treatment on the balance between tissue plasminogen activator and plasminogen activator inhibitor-1 in type 2 diabetic patients.

Beside hypercoagulation and hyperactivated platelets disturbances of the fibrinolytic system towards hypofibrinolysis have been reported to be associated with both glycemic and lipidemic derangement in diabetic patients. In the present prospective follow-up study the effect of 16 weeks insulin treatment and glycemic regulation on plasma levels of tissue plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1), the main regulators of fibrinolysis, was investigated in 19 type-2 diabetic patients with secondary failure to sulphonylureas. A similar glycemic regulation was obtained in a control group of 10 type 2 diabetic patients with sufficient metabolic response to strict dietary treatment and continuation of sulphonylurea treatment. Compared to 27 healthy subjects levels of tPA and PAI-1 were not significantly increased in type 2 diabetic patients before metabolic intervention. Although a hypofibrinolytic state due to an increase of PAI-1 levels was previously reported in obese hyperinsulinemic patients, no effect of insulin treatment on both tPA- and PAI-1 levels was observed in the present study including patients with only slightly increased body mass index (median 26.0 kg/m2). By correlation analysis PAI-1 levels were significantly related to serum cholesterol (R = 0.52) and glycemic control (glucose R = 0.41) in the whole group of diabetic patients at entry and in both subgroups after 16 weeks of treatment (insulin group: cholesterol R = 0.46, HbA1c R = 0.51; sulphonylurea group: cholesterol R = 0.59, HbA1c R = 0.58). In healthy subjects tPA and PAI-1 was correlated to serum insulin (R = 0.54, R = 0.56) and triglycerides (R = 0.46, R = 0.40).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Laboratory monitoring of thromboprophylaxis with low molecular weight and standard heparin.

This study was made to evaluate assays for monitoring of low dose heparin thromboprophylaxis and to evaluate its efficacy in reduction of hypercoagulation. Patients with medical diseases scheduled for routine thromboprophylaxis were subcutaneously treated with either 5.000 anti XaU low molecular weight (LMW) heparin once daily (n = 20) or 5.000 IU standard (ST) heparin 3 times daily (n = 19). On days 1,2,3, before, 1 and 4 hours after heparin injection APTT, TCT, anti Xa, Heptest, thrombin-antithrombin complexes (TAT), and D-Dimer levels were measured. In the LMW heparin group, median values of APTT and TCT slightly increased after heparin and the ranges of pre- and postinjection values showed extensive overlap. However, values of anti Xa and Heptest markedly increased, showing complete separation of ranges. In the ST heparin group neither APTT, TCT, anti Xa, nor Heptest were significantly different comparing pre- and postheparin values. Half of the patients in both groups had subclinical hypercoagulation at baseline (TAT greater than 5 ng/ml, D-Dimer greater than 200 ng/ml). On day 3 of prophylaxis this percentage was not significantly decreased. Moreover, several patients in both groups increased in TAT and D-Dimer. In the LMWheparin group, negative correlations between body weight and 4 h postinjection heparin levels were found (anti Xa R = -0.50, Heptest R = -0.31) and between 1 h postinjection heparin and TAT and D-Dimer levels 3 h later (TAT-anti Xa R = -0.58, TAT-Heptest R = -0.64, D-Dimer-anti Xa R = -0.32, D-Dimer-Heptest R = -0.33).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged

Aprotinin increases release of von Willebrand factor in cultured human umbilical vein endothelial cells.

Through the perioperative administration of the proteinase inhibitor aprotinin, hemostasis can be improved and postoperative bleeding reduced after cardiac operations. The mechanism of action has been only partially clarified. The goal of our study was to investigate the influence of aprotinin on the synthesis of von Willebrand factor (vWF) in human endothelial cells. Human umbilical vein endothelial cells (HUVEC) were cultivated in vitro and incubated with different aprotinin concentrations (55, 100, and 215 mol/L). With all investigated aprotinin concentrations, there was an increase in vWF synthesis compared with basal secretion (p less than 0.001). When the HUVEC were preincubated with aprotinin and stimulated with thrombin, there was a further significant increase in vWF synthesis. HUVEC that, were first incubated with aprotinin and then stimulated with thrombin demonstrated a significant increase in vWF synthesis compared with basal secretion in nonincubated cells (p less than 0.0001). Also, compared with the cells that had received thrombin stimulation alone, the combination of aprotinin incubation and thrombin stimulation led to a significantly higher vWF concentration (p less than 0.05). Because vWF is necessary for the interaction with platelet factor glycoprotein Ib and platelet adhesion, the demonstrated increase in vWF synthesis could be one of the mechanisms of action of aprotinin leading to its blood-sparing effect.

Aprotinin

A beat-by-beat analysis of electrocardiograms from cardiac transplant recipients.

A software system is described for producing a beat-by-beat analysis of the electrocardiograms from patients after heart transplantation. Pacemaker spikes are automatically detected and eliminated from the signals. R waves are located by a robust and accurate two-step algorithm. Based on the variable length of single heart beats, the Fourier coefficients of three orthogonal surface leads and of two intracardiac leads are calculated beat-by-beat. Power spectra are then obtained by combining contributions from the variable fundamental frequency and its multiples (harmonics) into fixed frequency classes of 1 Hz width and averaging over 60-120 cardiac cycles. Additionally, averaged beat-by-beat power spectra are calculated for windowed QRS complexes and T waves. As by-products, single beat quantities, such as R-R and R-T intervals, averaged signals for all leads, and the orientational autocorrelation function of the electrical vector of the heart, are obtained. Following beat-by-beat evaluation, mean values and standard deviations are obtained for all quantities.

Algorithms

Effect of intraoperative aprotinin administration on postoperative bleeding in patients undergoing cardiopulmonary bypass operation.

To study the hemostyptic effect of aprotinin (Trasylol) in patients undergoing extracorporeal circulation for coronary artery bypass operations, we randomized 12 of 24 patients to receive aprotinin in high dosage (about 800 mg) during extracorporeal circulation. From the resulting two groups each, one patient was excluded from the study because of postoperative myocardial infarction (control group) and surgical hemorrhage (aprotinin group) leading to a second operation. Although heparin was used for anticoagulation in all 22 patients, all had a marked increase in plasma levels of thrombin-antithrombin III complexes during extracorporeal circulation, indicating an intravasal activation of coagulation. By monitoring the plasma levels of fibrin degradation products in patients without aprotinin therapy, we recorded a concomitant hyperfibrinolysis significantly less pronounced in patients receiving aprotinin (p less than 0.005). The mean total postoperative blood loss was lower in patients receiving aprotinin (620 ml) than in control patients (1000 ml; p less than 0.03). The results confirm previous reports of a hemostyptic effect of aprotinin in cardiac operations. This effect is probably due to a prevention of hyperfibrinolysis.

Antithrombin III

[Quality of life and personal satisfaction following heart transplantation: an indicator of treatment results].

Cardiac transplantation is an established method of treatment to prolong survival in terminally-ill patients with severe heart disease. This study was undertaken to evaluate the quality of life and its best expression as satisfaction in patients who had undergone cardiac transplantation one year previously. From a total of 47 patients (14 with coronary artery disease, 27 with dilated cardiomyopathy and six with valvular heart disease), self-assessment questionnaires were completed to judge postoperative improvement/deterioration (change of status) and satisfaction with the level achieved as designated on the basis of visual analogue scales. Quality of life and satisfaction were assessed in nine categories: physical, emotional, mental, vocational, sexual status, financial situation, leisure activities, partnership and overall quality of life. The data was analyzed with the Wilcoxon and Kruskal-Wallis tests. The patients reported a consistent improvement in quality of life and satisfaction with respect to all categories except financial situation. Accordingly, quality of life after cardiac transplantation can be regarded as substantially improved. While most marked improvement was incurred in physical status and, consequently, overall quality of life, there was also a meaningful salutary effect on psychosocial aspects of life such as emotional well-being and leisure time activities. There were significant differences between change of status postoperatively and satisfaction with the level achieved in the categories of mental and vocational status, financial situation and partnership as well as family relations. Statistical analysis showed that outcome with respect to quality of life and satisfaction was not dependent on the underlying disease or the age of the patient at the time of transplantation.

Activities of Daily Living

Beta 2-microglobulin. A reliable parameter for differentiating between graft rejection and severe infection after cardiac transplantation.

We investigated the role of beta 2-microglobulin as a noninvasive parameter to monitor acute rejection and severe infection in 45 consecutive heart transplant recipients. Endomyocardial biopsy revealed moderate (41 patients) or severe (three patients) rejection in 44 patients. Severe infections of bacterial septicemia (11 patients), bronchopneumonia (two patients), and viral infection (seven patients) were detected by a meticulous schedule of various clinical and laboratory tests. beta 2-Microglobulin levels in serum, generally corrected for serum creatinine, were significantly elevated in patients with infections (median, 6.3 mg/l; range Q10-Q90, 3.47-10.27 mg/l) compared with levels in patients with rejection (p less than 0.0001) or in patients in obviously good condition (p less than 0.0001). At the onset of acute rejection, the median corrected beta 2-microglobulin serum level was 1.56 mg/l (range Q10-Q90, -0.05-3.46 mg/l) and was significantly different from the control group (p less than 0.01). In addition, density function and empirical quantile analyses allowed us to define ranges of beta 2-microglobulin levels that would differentiate between rejection (2.05-3.46 mg/l) and infection (greater than 3.46 mg/l). With these values, sensitivity and specificity were 0.9 and 0.938 for detection of infection and 0.23 and 0.925 for detection of rejection, respectively. By means of beta 2-microglobulin, two cases of infection were misinterpreted as rejection (10%), and four of 44 rejections were mistaken for infections (9%). We conclude that measurements of beta 2-microglobulin may improve the management of heart transplant patients.

Adult

[Orthotopic heart transplantation--experiences at the University Surgical Clinic II in Vienna (status: June 1986)].

Since 1984 27 heart transplantations (HTX) were carried out in 25 patients at the 2nd Department of Surgery, University of Vienna. The classic orthotopic technique of Lower and Shumway was used in all cases. Routine immunosuppression consisted of azathioprine and cyclosporin-A. In order to treat the main complications successfully, i.e. rejection and infections, we were compelled to establish an extensive follow up regimen. The early recognition of acute rejection was based on the findings obtained by cutaneous as well as epicardial ECG leads, in conjunction with cytoimmunological monitoring on the basis of RIA measurements of the serum levels of Neopterin and gamma-Interferon. Furthermore, we recorded some parameters of ventricular performance, such as the isovolumetric relaxation time and the radiologically measured heart volume. An endomyocardial biopsy was carried out to secure the diagnosis. Pulsed doses of methylprednisolone were used for the treatment of rejection, facultatively combined with ATG in the absence of improvements. Infections were pinpointed by comprehensive serum tests and various blood, sputum and urine cultures. The management consisted of treatment with the requisite antibiotics. Of 25 primarily transplanted patients 15 patients are still alive. 5 persons, amongst them 2 children, have survived already for more than 1 year. 6 patients died at an early stage. In 3 cases the cause of death was intractable infection. In 1 case multi-organ failure occurred and 1 patient died due to acute organ failure. 4 patients died at a late stage and acute severe rejection was responsible in all these cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Cyclosporin-A induced heart failure after orthotopic heart transplantation.

Two patients suffering from dilated Cardiomyopathy (CMP) had to undergo orthotopic heart transplantation (HTX). In both cases, the postoperative period was without any complications. The immunosuppression consisted of Cyclosporin-A and Azathioprine including a one week prophylactic treatment with Antithymocyte Globuline (ATG). Four months postoperatively, they developed clinical signs of heart failure. The endomyocardial biopsies showed rejection at stage I according to Billingham's grading plus a fine interstitial fibrosis. Therefore, the Cyclosporin treatment was suspended and replaced by conventional immunosuppression consisting of Prednisolone and Azathioprine. Acute heart failure was managed by catecholamines in combination with aggressive diuretic therapy. After three weeks, both patients recovered. 12 weeks later, one died because of an acute rejection episode. The other is in good condition, with conventional immunosuppression at the present time. A vascular process caused by Cyclosporin-A as the pathogenic mechanism is considered. The absence of rejection signs in the biopsies as well as the remarkable improvement of heart failure after withdrawal of Cyclosporin-A support this possibility.

Coronary Disease

Decreasing use of donated blood and reduction of bleeding after orthotopic heart transplantation by use of aprotinin.

Twenty patients undergoing orthotopic heart transplantation were randomized preoperatively to receive either the serine proteinase inhibitor aprotinin in a low dose (560 mg; n = 10) or a placebo (control group, n = 10) at the time of transplantation. Blood loss 24 and 48 hours after transplantation was significantly lower in the group treated with aprotinin (i.e., 510 ml vs 820 ml, p less than 0.01, and 690 ml vs 1000 ml, p less than 0.03, respectively. Accordingly, the aprotinin group required significantly less transfused blood in the first 48 postoperative hours 0 to 250 ml versus 0 to 1000 ml (p less than 0.04). Seventy percent of the patients treated with aprotinin underwent transplantation without the need of nonautologous blood, compared with only 30% in the control group.

Aprotinin

Quality of life after orthotopic heart transplantation.

During the last decade heart transplantation has become the chosen method to treat terminally ill patients suffering from severe cardiac illness. It was the aim of our study to retrospectively survey life quality of donor organ recipients who underwent heart transplantation during the first years of transplantation at our center (1984 through 1987). Thirty-five patients were asked to evaluate their postoperative improvement or deterioration and their satisfaction with the level reached on visual scales. Life quality was defined in nine areas: physical, emotional, mental, vocational, and sexual status, financial situation, leisure activities, partnership, and overall life quality. The following results were obtained: (1) our former patients informed us about a distinct improvement in almost all dimensions (except financial situation). We found an absolute increase in life quality after heart transplantation. (2) Although improvement was ranked best for physical status, there was also a high amelioration in psychosocial fields. (3) A significant difference was seen between changes in condition and satisfaction in the financial situation (z = 2.3) and in partnership (z = 2.9), in which the latter was ranked higher. (4) The date of transplantation (less/more than 2 years ago) had no influence on the evaluation of postoperative life quality.

Adult