The safety of treatment with recombinant human erythropoietin in clinical use: a review of controlled studies.

Recombinant human erythropoietin (rhEPO) has now been approved for the treatment of renal anemia, anemia of prematurity, cancer-associated anemia, AIDS-associated anemia and as concomitant treatment for patients with or without autologous blood donation awaiting elective surgery. The purpose of this review is to provide an overview, based on the results of controlled studies, of the anticipated safety profile of rhEPO in various indications and to assess whether treatment with rhEPO influences the incidences of certain adverse events in these indications. The anticipated adverse events differ from indication to indication and generally reflect the corresponding underlying illness.

The estimation of efficacy of oral iron supplementation during treatment with epoetin beta (recombinant human erythropoietin) in patients undergoing cardiac surgery.

We estimated the efficacy of oral iron therapy during treatment with rhEPO in patients undergoing cardiac surgery who were contraindicated for autologous blood donation. Seventy-six patients were enrolled in this double-blind, placebo-controlled trial and assigned to the 2 treatment groups (5x500 U/kg body weight rhEPO or placebo intravenously over 14 d before surgery). During the treatment period all patients received 300 mg Fe2+ (iron glycine sulfate) orally per day.

Evaluation of erythropoietic activity on the basis of the red cell and reticulocyte distribution widths during epoetin beta therapy in patients undergoing cardiac surgery.

The changes in the red cell and reticulocyte distribution widths during preoperative treatment with recombinant human erythropoietin (rhEPO) were evaluated in a double-blind, placebo-controlled trial in cardiac surgery patients. The increases in the reticulocyte count, in the hemoglobin and in all distribution widths are the expression of the marked preoperative stimulation of erythropoiesis in the patients treated with rhEPO. Only placebo patients with a hemoglobin < or = 7.

Kinetics of reticulocyte maturity fractions and indices and iron status during therapy with epoetin beta (recombinant human erythropoietin) in cardiac surgery patients.

We evaluated the changes in reticulocyte maturity fractions and indices, as measured by flow cytometry, during preoperative treatment with recombinant human erythropoietin (epoetin beta) in cardiac surgery patients. A total of 72 patients was enrolled in this double-blind, randomized, placebo-controlled clinical trial and assigned to the two treatment groups (5 x 500 U/kg bodyweight epoetin beta or placebo intravenously over 14 days preoperatively). Therapy with epoetin beta produced continuous increases in hematocrit/hemoglobin, in the most mature fraction of reticulocytes (LR), and in reticulocyte count.

The effect of preoperative recombinant human erythropoietin therapy on platelets and hemostasis in patients undergoing cardiac surgery.

In a double-blind, randomized, placebo-controlled trial we evaluated the effects of the administration of recombinant human erythropoietin (5 x 500 U epoetin beta/kg body weight intravenously over a 14-day period before surgery) in patients undergoing cardiac surgery and in whom autologous blood donation was contraindicated on platelet count, platelet distribution width, mean platelet volume (MPV), and certain hemostaseologic parameters. All patients received 3 x 70 IU heparin/kg per day s.c.

Avoidance of allogeneic blood transfusions by treatment with epoetin beta (recombinant human erythropoietin) in patients undergoing open-heart surgery.

In a double-blind, randomized, placebo-controlled trial, we evaluated the ability of epoetin beta (recombinant human erythropoietin) to avoid allogeneic blood transfusions (ABT) and the associated risks in patients undergoing primary elective open-heart surgery and in whom autologous blood donation (ABD) was contraindicated. Seventy-six patients overall were enrolled onto the trial and were randomly assigned to the two treatment groups, 5 x 500 U/kg body weight (BW) epoetin beta or placebo intravenously over 14 days preoperatively. All patients received 300 mg Fe2+ orally per day during the treatment period.

Evaluation of oxygen availability with oxygen status algorithm in patients undergoing open heart surgery treated with epoetin beta.

We evaluated in a double-blind randomized study the effect of epoetin beta (recombinant human erythropoietin) therapy on oxygen status in patients undergoing cardiac surgery who were contraindicated for autologous blood donation. All 76 patients enrolled in this study were randomized to the two treatment groups (5 x 500 U epoetin beta or placebo/kg body weight intravenously over a 14-day period before surgery) and received 300 mg Fe2+ per day orally before surgery. Before and after surgery the lactate level and the following parameters according to the oxygen status algorithm by Siggaard-Andersen were evaluated: arterial oxygen tension (PaO2), effective hemoglobin concentration (ceHb), arterial oxygen saturation (SaO2), oxygen half saturation tension (p50), red cell 2.

[Operations with a heart-lung machine in adult members of Jehovah's Witnesses].

Members of Jehovah's Witnesses refuse blood transfusions and blood products under any circumstances. Because of an improvement in blood salvage techniques in our centre, they are not excluded from open-heart surgery. In recent years recombinant human erythropoietin (rhEPO) has been applied to correct perioperative anemia in these patients.

[Circulatory changes in acute sauna hyperthermia after heart transplantation].

The authors report on the influence of a single sauna-stay of patients following heart transplantation (HTX) during the rehabilitation phase III. Investigations of blood pressure, heart rate, changer in hemodynamics in the small and large vessels in 8 male patients following HTX (medium age: 42 years) showed that sauna-hyperthermia is well tolerated. We watched significant decreases of blood pressure (systolic and diastolic values), an improvement of the microcirculation in the small vessels, an increase of the left ventricular ejection fraction (LVEF) and a decrease of the total peripheric vascular resistance (TPVR).

[Autogenic training in hypertensive dysregulation after aortocoronary venous bypass operation of coronary heart disease].

The authors report on the influence of autogenous training on blood pressure at rest and under stress conditions in patients with coronary heart disease following coronary bypass operation. We investigated the influence of autogenous training on the microcirculation and the left ventricular ejection fraction (LVEF) as well. The results showed a significant decrease in blood pressure at rest and also an increase of muscle circulation F and of LVEF.

[Potential use of the sauna in the long-term treatment of hypertensive cardiovascular circulation disorders--a comparison with kinesiotherapy].

The authors report about the long-term response (one and three years) of blood pressure and heart frequency under rest and load (50 W) in patients with hypertension, coronary heart disease, essential hypertension and after aortocoronary venous-bypass operation (ACVB) (n = 65) under regular visits (twice a week) to the Finnish sauna. In comparison, 68 hypertensive patients who took a regular kinesiotherapy (running and swimming) were studied. Besides the parameters of heart circulation mentioned above, peripheric microcirculation (M.

Treatment of tachyarrhythmias in a patient with the long QT syndrome by autotransplantation of the heart and sinus node-triggered atrial pacing.

The case history of a 37-year-old woman with the long QT syndrome and drug-refractory paroxysmal ventricular tachyarrhythmias is reported. She was resuscitated eight times between 1980 and 1987. The duration of these attacks increased from a few minutes to 8 hours and the interval between them decreased from 2 years to 4 weeks.

Aortocoronary vascular prosthesis made of siliconized homologous vein or bovine sacral artery.

The purpose of our study was to develop and prepare aortocoronary prostheses, test them experimentally in multivascular and coronary reoperations in case of missing autologous grafts and to use them for shunt operations in cardiac surgery. Human vein or bovine sacral artery were used for preparing aortocoronary prostheses. As for metrics of 9-14 Charr.

[Coronary ventricular fistulas in patients with heart transplants].

In detailed angiographic follow-up examinations in patients after heart transplantation, coronary artery-ventricular fistulas were observed in two of ten patients. In one patient, in the first postoperative year, 19 right ventricular biopsy procedures were performed obtaining a total of 71 tissue specimens and one year after transplantation, additionally, three specimens were obtained from the left ventricle. Coronary angiography demonstrated a fistula from the first anterior ventricular branch of the right coronary artery into the right ventricle (Figure 1) as well as a second smaller fistula between from a septal perforator of the left anterior descending artery into the left ventricle.

[Treatment of tachyarrhythmia in a patient with long QT syndrome by autologous heart transplantation and atrial stimulation controlled by the sinoatrial node].

The authors described an operation performed in a female patient aged 37 years who was first examined in 1980. That year she experienced the first ventricular fibrillation episode. The duration of the Q-T interval was 600 msec.

[Non-medicinal therapy tachycardiac arrhythmias].

The conservative antiarrhythmic treatment was improved by the introduction of the Holter-ECG technique, of the serial electrophysiological testing and by new antiarrhythmic drugs. An essential enhancement of the therapeutic possibilities, particularly when ineffectiveness, proarrhythmic action or intolerance of the medicaments are existing, are increasingly the non-medicamentous techniques of the antiarrhythmic therapy. Thus the treatment of arrhythmia has become by far more effective, but at the same time also more complicated and more expensive.

[Significance of echocardiography for the diagnosis and strategy in infectious endocarditis].

The echocardiographic results of 29 patients--clinically suspected of infective endocarditis--were compared with clinical, intraoperative, histologic, autoptic data and the available outcome of cardiac catheterization. The purpose of this retrospective study was to define the potential valence of echocardiography for planning of therapy and success. Valvular vegetations of different histological ages were established on 35 valves.

[Nosocomial infections and sternum osteomyelitis].

A prospective study of the nosocomial infection rate in the Department of Cardiac Surgery of the Surgical Clinic (Charité) was done between January and December 1987. The investigation was performed computer aided. Data were recorded by an infection register.

[Percutaneous coronary angioplasty in chronic coronary disease with single and multiple obstructed vessels (analysis of 315 interventions 1978-1988)].

315 percutaneous transluminal coronary angioplasties performed during 1978-1988 in 261 patients with ischemic heart disease were analyzed for three different variants according to primary effectiveness, failure rate the most frequent complications and costs of materials as well as duration of intervention and fluoroscopy. Only variant 3 of the proceeding (soft-tip-applicators, flat profile balloon catheter, Kaltenbach long-wire technique, streptokinase rinsing of instruments, permanent infusion of instruments during the procedure) is an applicable routine method. It has a primary effectiveness of 86%.

[Castaneda-de Leval's modified Fontan operation in complex cyanotic defects with subsequent percutaneous transluminal embolization of systemic pulmonary collaterals].

The case of a five year old boy with a double-inlet-left-ventricle and the aorta in 1-malposition, large VSD, ASD and pulmonary stenosis is reported, that showed after modified Fontan surgery severe effusions and a severe protein loss syndrome. Aortopulmonary collaterals were detected as the cause of this and successfully treated in several sessions by percutaneous transluminal embolization.

Aortico-ventricular tunnel.

The authors report on three cases of aorticoventricular tunnel in two children and a baby. Clinical experience confirmed the necessity of earliest diagnosis and treatment, closure of both tunnel-ends, using a patch for the aortic stoma to prevent aortic valve incompetence.

[Use of walking and sauna therapy in the rehabilitation of hypertensive patients with ischemic heart disease following aortocoronary venous bypass operation with special reference to hemodynamics].

Rehabilitation results are reported concerning the behavior of blood pressure and heart rate, peripheral and central hemodynamics, after resting and during exercise and physical conditioning by running as training and sauna, respectively, in hypertensive patients with IHD after aortocoronary venous bypass (ACVB) surgery. Bicycle ergometric examinations an xenon wash-out (for the determination of the mean functional vessel cross section A) were performed in 43 male untrained patients before and after physical therapy. The left ventricular ejection fraction (EF) at rest was also determined in these patients.

[Surgical problems of aortic isthmus stenosis].

Operations were performed on 84 infants for coarctation of the aorta between 1970 and 1987. An analysis was made of the results recorded from 45 of them (1983-1987). The youngest child had been two days of age.

[Biochemical studies of the assessment of transplant function following clinical heart transplantation--initial experiences].

Average and specific individual courses of the following parameters are reported in this paper, with reference being made to eight of eleven clinical heart transplantations so far performed at the authors' department: lactate, pyruvate, myoglobin, ASAT, ALAT, GGT, CK, CK-MB, LDH, LDH-1, and glycogen phosphorylase. Glycogen phosphorylase was found to deviate most strongly from normal, with the enzyme exhibiting two initial maxima. The enzyme activity in the serum vanished not later than twelve days from transplantation.