Ciclosporin dose-response relationship in heart transplant recipients as calculated from HPLC determinations.
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Chromatography, High Pressure Liquid↗
Biomedical subjects
A Laczkovics
Publications and source records attributed to A Laczkovics.
[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↗
Total artificial heart bridging: a temporary support for deteriorating heart transplantation-candidates--methods and results.
Since 1975 at the 2. Dept. of Surgery, University of Vienna, Austria, artificial circulation devices and artificial hearts have been constructed and in experimental use. We started a clinical heart transplantation (HTX) program in 1984, and up to now more than 40 HTXs have been performed. Since May 1986, 3 patients--all suffering from end stage dilatative cardiomyopathy--received total artificial heart (TAH) as a temporary support until HTX was possible. Two of them were transplanted after 9 and 10 days. The third patient, who additionally suffered from a postinfarctial lung abscess and had to undergo an indispensable lobectomy contemporary with TAH implantation, could not be transplanted due to an incurable infection, which he died of after 22 days on TAH. The temporary TAH implantation proved to be a valuable measure preventing life-threatening circulatory deterioration. After restoration of a sufficient circulation by the implanted system, the patients' general conditions improved and the concomitant dysfunctions of kidneys, brain, and other vital organs, due to cardiogenic shock, could be rectified in those two patients, who underwent transplantation. Thromboembolic complications were observed only in the third patient, who developed a small infarction in the anterior lobe of the left hemisphere caused by cerebral embolism after 3 weeks of TAH pumping. The use of TAH is liable to severe, even lethal, complications. At present it should be used only as a last resort. If a donor heart is not available, this measure can be a real chance to save the patient's life.
Adult↗
Comparison of cyclosporine A dosage and metabolism in liver and heart transplant recipients.
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Adolescent↗
[Measuring cyclosporin in immunosuppressive treatment following liver and heart transplantation].
Selective suppression of the immune system in graft recipients is now achieved in most cases by treatment with cyclosporine A. Due to large individual differences in absorption, utilization and metabolisation of this drug, therapeutic blood levels (immunosuppression/toxicity) can be maintained only by frequent measurements of the cyclosporine concentrations in blood samples and dosage readjustments. In the present study, we measured cyclosporine in whole blood samples from 37 patients (23 liver and 14 heart transplant recipients) using an high pressure liquid chromatographic method for native cyclosporine A which has been developed in our laboratory and a radioimmunoassay method (cyclosporine A + metabolites). By comparison of the results of HPLC and RIA-measurements (n = 520) we found a relatively stable metabolization rate (RIA/HPLC-ratio) of 4.23 +/- 1.30 for heart transplant recipients. In contrast RIA/HPLC ratios were highly variable in liver graft recipients ranging from 1.3-9 for the same patient in the posttransplant period. The liver recipients could be classified into two groups according to their mean RIA/HPLC-ratios: for 11 patients we observed a mean ratio of 2.65 +/- 0.35, for another 12 patients one of 4.35 +/- 0.75. Lower metabolisation rates seem to be associated with low donor age. No direct correlation was found between changes in RIA/HPLC-ratios and liver function, rejection and infection periods. Rejection treatment with high doses of methylprednisolone had no systematic influence on cyclosporine metabolisation in our patients. Since cyclosporine metabolites, at least those ones which are most abundant, have less immunosuppressive and toxic effects we recommend measurements of cyclosporine blood concentrations with any HPLC-method specific for the unchanged drug.(ABSTRACT TRUNCATED AT 250 WORDS)
Chromatography, High Pressure Liquid↗
Neopterin and interferon gamma serum levels in patients with heart and kidney transplants.
The main problem in the follow-up of patients receiving organ allografts is the early differential diagnosis of rejection episodes and infections. Serum levels of interferon gamma, a marker of T-lymphocyte activity, were determined with an immunoradiometric assay, specific for biologically active interferon gamma and sufficiently sensitive (20 U/l) for the determination of circulating interferon gamma. Neopterin, a pteridine released from stimulated macrophages, was determined by radioimmunoassay. Both rejection crises and infections are accompanied by distinct increases of serum neopterin (median values 124 and 128 nmol/l; N = 98). Interferon gamma levels are elevated for a short period one or two days earlier, the maximal values during infections (median 430 U/l, range 120-1220 U/l, N = 25) being higher than those during rejection episodes (median 120 U/l, range less than 20-330 U/l, N = 73). Each rise of interferon gamma was followed by an increase of neopterin, but not every neopterin increase was preceded by a interferon gamma peak. Neither of these parameters showed an increase during deterioration of kidney function due to cyclosporin toxicity. The determination of interferon gamma, a lymphokine involved in the activation of alloreactivity, reflecting T-cell stimulation, and the measurement of neopterin, a secretory product of activated macrophages, allows the simple, quick and reliable monitoring of the immune status of transplant recipients.
Adolescent↗
[Rare cause of a left ventricular aneurysm in a 10-year-old boy].
A 3-year-old boy had an accident with a blunt chest trauma, 9 years later a left ventricular aneurysm was diagnosed by echocardiography and angiography. The 12-year-old-boy was operated successfully. The pathogenesis of cardiac lesions in association with blunt chest traumas is described, and frequent control examinations in the affected patients are recommended.
Adolescent↗
[The problem of scars in heart surgery with special reference to the use of static magnetic fields].
An attempt is made to survey the pathophysiology of wound healing, as well as the aetiological factors involved and the possibilities of therapeutic intervention to prevent the formation of hypertrophic scars and keloid after cardiac operations. Several prophylactic measures are discussed, with special reference to the use of static magnetic fields. Their application to scars after cardiac operations was carried out by energy pak foils. Patients treated with these foils showed slightly improved results as compared with a control group. The results, however, were not statistically significant.
Adult↗
[Causes of death in patients with pacemakers - with respect to the indication for implantation].
We compared the life expectancy of 1559 patients with an implanted pacemaker (PM) with a normal age-matched population and found a significantly reduced survival rate in paced patients. Patients paced for heart failure have the lowest survival rate, whilst those paced for Adams-Stokes attacks do slightly better. Patients with Adams-Stokes equivalents do not differ significantly from our normal population. 54% of patients with PM implanted for heart failure died due to heart failure despite PM implantation. The relative percentage of sudden death after PM implantation is high in groups with Adams-Stokes attacks (16%) and Adams-Stokes equivalents (20%). In both of these groups sudden death occurred especially during the first two years after PM implantation. The high risk of sudden death after PM implantation should increase our efforts to monitor patients carefully after PM implantation for the occurrence of malignant tachyarrhythmias.
Adams-Stokes Syndrome↗
Fever, leucocytosis and infection after open heart surgery. A log-linear regression analysis of 115 cases.
A prospective investigation was undertaken in adults to assess the specificity and sensitivity of fever (greater than 38 degrees C) and leucocytosis (greater than 10 000/microliters) for the diagnosis of infection after operations with cardiopulmonary bypass. A log-linear model analysis of a multiway frequency table was used for statistical evaluation. The model parameters were separately evaluated for 2 periods: the early one until the 6th day, the late period from the 7th postoperative day until discharge. Seven out of 115 patients suffered infections during their hospital stay: Bacteremia occurred in 3, pneumonia in 2, and deep sternal wound infection in 2 patients, and a superficial wound infection in one. No significant interactions between fever, leucocytosis and/or infection were found in the first period, except an inverse relation between fever and elevated WBC (p = 0.0197). After the 6th postoperative day the model parameters did show significant interactions, fever and leucocytosis being more frequent in infected patients. However, the specificity was low: only 15% of the patients with fever or elevated WBC had an infection. The risk of in-hospital infection was significantly higher after a long duration of cardiopulmonary bypass (p = 0.009), and after transfusion of more than 2500 ml of blood on the day of operation (p = 0.001).
Adolescent↗
The central venous blood temperature as a guide for rate control in pacemaker therapy.
True physiologic pacing is only feasible in patients with heart block and normal sinus rhythm using atrial synchronized pacing. In sick sinus syndrome (SSS) or atrial fibrillation no adequate sensing possibility is present. For these conditions something other than electrical signals must be found to guide rate control. In clinical experiments a thermistor integrated in a bipolar pacing lead was implanted in one of the authors as well as in a pacemaker patient. Treadmill tests at 3, 6, and 10 km per hour have shown no substantial increase of the central venous temperature (CVT) in the lower effort range; an increase of 0.6-0.75 degrees Celsius (degrees C) in the medium range; and an increase of 1.35 degrees C in the higher range, respectively. External pacing in the author, or rate variations by programming the VVI, M unit in the patient at rest do not influence CVT. CVT correlates well in the medium-range group, which mostly reflects the capabilities of the average pacemaker patient. In the higher effort range a delay between rate increase and increase of CVT is noticed. There is no increase in CVT beyond the physiologic variations in the lower effort range.
Body Temperature↗
Reversible end-of-life indicator leading to erroneous pacemaker replacement-pitfalls of telemetry.
In several modern pacemakers, end-of-life (EOL) is indicated by a single-step rate drop, which is initiated by a voltage-sensitive electronic switch. This switch may also be activated by other causes, such as very short voltage drops, low temperatures, and electrocautery. We report a case in which a Cordis 233 F Sequicor II pulse generator was operating at 51.6 bpm in VOO mode at the time of implantation. As telemetry seemed to indicate that back-up pacing (the EOL indicator in this model) was "off," it was erroneously assumed that the pacemaker was not working properly. The unit was replaced by another impulse generator. At laboratory testing, the pacemaker was within specifications, when back-up pacing was separately programmed off. In conclusion, physicians should be aware of the new phenomenon of reversible EOL indicators, and that they may not rely on telemetry in this respect. Future pacemakers should incorporate a telemetry message which prevents similar misunderstandings.
Equipment Design↗
[A cosmetically advantageous approach to median sternotomy].
A horizontal submammary skin incision was chosen as approach route to median sternotomy in 36 patients undergoing cardiac operations. The low complication rate in conjunction with a cosmetically acceptable result makes this procedure the method of choice for selected patients. The potentially higher risk of infection should not be overlooked when planning the operation.
Adolescent↗
Reversible EOL-indicator: a new cause for low pacemaker rate.
A case is presented in which a new cause for decrease in pacemaker rate was encountered: six months after implantation of a Medtronic 5967 pacemaker, the first routine check-up revealed a rate of 62.5 ppm instead of 70 ppm. After application of a magnet, all measurements returned to normal. The cause for this phenomenon, which could not be attributed to battery depletion or oversensing, was probably a change of state of the flip-flop which is responsible for the sudden rate drop of 10% which serves as the end-of-life (EOL)-indicator in this pacemaker. This change of state may result from a very short decrease of power supply voltage during shipment or at the time of implant, and is fully and permanently reversible by performance of the magnet test. In order to prevent unnecessary pacemaker explants, future pacemaker circuits should be redesigned to eliminate the effect of very short voltage changes. Meanwhile, a routine magnet test should be performed immediately after implantation.
Electric Power Supplies↗
[Postoperative arrhythmias in heart surgery].
After a brief comment on the origin and a summing up of types of postoperative cardiac arrhythmias in open heart surgery, mainly the therapy of these arrhythmias is discussed Besides drug therapy (antiarrhythmica) and cardioversion resp. pacing especially the possibility of a metabolic therapy is presented. In the postoperative phase after the trauma by the operation with the heart lung machine - which is similar to the shock phase after a myocardial infarction - a disordered energy metabolism with a decreased effectiveness of insulin occurs. It exists a diminished intracellular potassium-shifting, which causes an insufficient myocardial cell membrane potential. By means of exogenous high insulin and potassium supply with glucose infusion the potassium-shifting is improved, the FFA-level is lowered and the incidence of arrhythmias is reduced as sinusrhythm is induced.
Anti-Arrhythmia Agents↗
[The ECG in physiologic pacing (author's transl)].
Hemodynamic advantages led to an increasing number of implantations of so called "physiologic pacemakers", which preserve the natural sequence of atria and ventricles. The growing complexity of these systems renders ECG evaluation increasingly difficult. 85 patients had physiologic pacemakers implanted during the last 4 years and were controlled in our pacemaker outpatient clinic. Typical problems in ECG evaluation of the different pacemaking modes are discussed.
Arrhythmias, Cardiac↗
[Optimized sequential pacing of atrium and ventricle (author's transl].
A new stimulation system for pacemaker is described, which was implanted in a 49 years old patient. The new pacemaker stimulates the atrium when needed, the ventricle when needed and both when needed and can be inhibited completely. At a faster atrial activity and disturbed atrio-ventricular conduction the pacemaker synchronizes the ventricle at the appropriate rate. Thus the optimized stimulation comes very near to the physiologic rhythm of the heart.
Echocardiography↗