Progression of steroid-associated osteoporosis after heart transplantation.

BACKGROUND: Osteoporosis has been recognized as an important side effect of long-term and of pulsed steroid application after heart transplantation. METHODS: In June 1989 a prospective clinical trial was started to study bone demineralization by quantitative computed tomographic scan. All patients received vitamin D and calcium. In group I (n = 30) synthetic calcitonin (40 Medical Research Council Standard Units subcutaneously per day was administered in 14-day cycles, whereas group II patients (n = 31) received a placebo preparation. Repeat trabecular and cortical quantitative computed tomographic scans of the thoracic (T12) and lumbar spine (L1, L2, L3) were obtained within 48 weeks after heart transplantation. RESULTS: Expressed as the means of T12, L1, L2, and L3, trabecular bone density decreased significantly from 100+/-24 to 79+/-29 mg/mL within 3 weeks after heart transplantation, followed by a further reduction to 67+/-29 mg/mL after 3 months in the calcitonin group. The values for cortical bone density decreased significantly from 229+/-37 to 202+/-40 mg/mL (calcitonin) 3 weeks after heart transplantation. Comparable results were obtained in the placebo group. In both groups bone density remained stable thereafter. Intergroup differences were not of statistical significance. CONCLUSIONS: In heart transplant recipients progressive trabecular bone demineralization is limited to the first 3 postoperative months. Thereafter, bone density remained stable. A positive effect of synthetic calcitonin in addition to prophylactic calcium and vitamin D application could not be proved by repeat quantitative computed tomography.

University of Wisconsin versus St. Thomas' Hospital solution for human donor heart preservation.

Prolongation of the safe period of ischemia of the heart is an efficient way to overcome donor organ shortage, as demonstrated in renal and hepatic transplantation. We present the results of a prospective, randomized study comparing preservation with University of Wisconsin solution (UWS) versus St. Thomas' Hospital solution (STS) in clinical heart transplantation. A total of 39 patients were enrolled in the study (n = 20 for UWS and n = 19 for STS). Hemodynamic, electron microscopic, and biochemical evaluation did not reveal any significant differences in postoperative myocardial performance. Only the number of intraoperative defibrillations (0.82 for UWS versus 1.7 for STS) and the rhythm stability after reperfusion (13/20 UWS hearts versus 6/19 STS hearts in sinus rhythm) were significantly different. Heart preservation with UWS and STS appears to be of comparable efficacy at mean ischemic times of less than 4 hours.

Nosocomial hepatitis B virus infections in cardiac transplant recipients transmitted during transvenous endomyocardial biopsy.

Between March 1986 and September 1990, 67 of 243 cardiac transplant recipients in outpatient care at our clinic became hepatitis B virus surface antigen (HBsAg) positive after operation. The HBsAg of 63 patients belonged to the subtype ay, suggesting a common source of infection. These 63 cases and 103 controls with negative hepatitis B virus (HBV) serology were studied in order to analyse the outbreak. The sources of infection were patients who were chronic HBsAg carriers. Infection was transmitted at the time of endomyocardial biopsy, if performed on the same day and in the same room after biopsy of an HBsAg positive patient. The most likely mode of HBV transmission was droplet contamination of instruments and/or medication vials used for subsequent patients. Performing biopsies on HBsAg positive and negative patients in separate rooms resulted in the termination of the outbreak.

The impact of early postoperative cyclosporine serum levels on the incidence of cardiac allograft rejection.

The introduction of cyclosporine A (CyA) into the immunosuppressive therapy has significantly improved the results of heart transplantation (HTX). Its nephrotoxicity and hepatotoxicity, however, often limit the perioperative and postoperative use of this drug. The purpose of this retrospective study was to evaluate the effect of early postoperative CyA blood levels on the incidence of early as well as late cardiac rejection and patients' survival. Between October 1985 and June 1991, HTX was performed in 311 patients. Standard immunosuppression consisted of azathioprine (1-2 mg/kg), prednisolone (0.5 to 0.1 mg/kg) and CyA. Rabbit-antithymocyte-globulin (RATG - 1.5 mg/kg) was administered for the first 4 days postoperatively. Moderate rejection was treated with 3 x 500 mg methylprednisolone, severe rejection with RATG (1.5 mg/kg three times a day). Patients were excluded from this study because of a positive cross-matching, early death unrelated to rejection or alternate forms of immunosuppression (n = 111). Follow-up was complete in 200 patients (mean age 44 +/- 11; 18 female, 182 male; 204,233 patient days) with a total of 5380 biopsies. The cohort was divided into group I (no CyA for day 0 to 2; n = 108) and group II (CyA during day 0 to 2; n = 92) according to the onset of CyA therapy. In 101 patients (group A) the mean CyA blood level was less than 150 ng/ml from day 0 to 14 and in 99 patients more than 150 ng/ml (group B).(ABSTRACT TRUNCATED AT 250 WORDS)

Evaluation of the inotropic function at rest and the effect of enoximone in heart transplanted recipients. Assessment by left ventricular endsystolic pressure volume relationship.

Denervation of the heart involves an alteration (density, distribution of beta 1-beta 2-types) of beta-adrenoceptors in long-term follow-up. To elucidate the influence of these changes on left ventricular contractility and to provide an effective alternative treatment to re-transplantation in cases of chronic rejection (coronary vasculopathy-CVP, unspecific myocardial allograft failure-UMAF) a clinical study on 19 male transplant recipients after orthotopic heart transplantation without CVP and UMAF in the non-rejecting state was undertaken. Six male patients served as a control group to compare the systolic function at rest. Left ventricular end-systolic pressure-volume relationships (ESPVR) (k-slope) were registered and computer measured using a conductance catheter-technique under conditions of a transiently occluded vena cava and at a fixed heart rate (atrial pacing) in all patients (n = 25). In the transplanted patient group the acute response of enoximone (0.75 mg/kg) administered intravenously was recorded. The position of the ESPVR in the transplanted hearts were not different as compared to the data obtained from the non-transplanted hearts at rest. The k-slope increased from the baseline data after the acute infusion of enoximone in the transplanted hearts. The dosage of enoximone used produced a significant leftward shift in the ESPVR in most patients (89%). In addition, 42% of the patients showed an insignificant drop in left ventricular systolic pressure. Thus, the baseline contractile characteristics of the heart transplant recipients without chronic rejection and in the non-rejecting state is not obviously different from those in non-transplanted patients at rest independent of the time since operation.(ABSTRACT TRUNCATED AT 250 WORDS)

[Phagocyte function in immunosuppressed allograft recipients (author's transl)]. / Phagocytenfunktion bei immunsupprimierten Transplantaträgern.

Phagocyte function in immunosuppressed allograft recipients is regularly diminished and correlates to leucopenia in only 50% of cases. Significantly reduced phagocyte function carries a 50% risk of septic complications. Monitoring of phagocyte function can be helpful in assessing defense reserves in the compromised host.

[The status of echocardiography within the scope of routine cardiologic diagnosis]. / Stellenwert der Echokardiographie im Rahmen der kardiologischen Routinediagnostik.

In particular since the introduction of the two-dimensional approach, echocardiography as a non-invasive and easily repeatable bedside-technique without side-effects plays a central role within the diagnostic tools of cardiology. The following applications of cardiac ultrasound are commonly accepted and sufficiently validated: Assessment of the size of cardiac chambers including qualitative and quantitative evaluation of left ventricular function, detection of pericardial effusion, diagnosis of intra- and extracardiac tumors and thrombi, analysis of complex congenital diseases. Without the use of Doppler, valvular regurgitations can only be suspected by indirect parameters; in contrast, stenotic lesions as well as a variety of other valve abnormalities (calcifications/partial rupture/prolapse/vegetations) can be diagnosed with a high accuracy. Transesophageal echocardiography guarantees not only an optimal imaging quality in virtually all patients, in addition, the technique allows the routine visualization of the thoracic descending aorta and the left atrial appendage which is of importance for the diagnosis of aortic dissection and isolated left atrial appendage thrombi. Transesophageal echocardiography is also superior to the conventional precordial approach concerning the assessment of prosthetic valve malfunction (in particular in mitral position) and endocarditis-associated abscesses. Today, the echocardiographic visualization of coronary arteries is without clinical relevance.

Failure of vaccination against hepatitis B with Gen H-B-Vax-D in immunosuppressed heart transplant recipients.

Some 86 heart transplant recipients under immunosuppressive therapy were vaccinated against hepatitis B using the vaccine Gen H-B-Vax-D, but 95.3% failed to develop protective levels of HBs-specific antibody (more than 10 U/l) after the third vaccination.

Structure, synthesis and orientation of microfibrils. V. On the recovery of Oocystis solitaria from microtubule inhibitor treatment.

Depending on the type of the inhibitor and its concentration one can experimentally induce two forms of aberrant microfibril orientations in O. solitaria cell walls through microtubule inhibitor application. The first form, designated "Intermediate", is characterized by the presence of cortical microtubules together with a spiral arrangement of microfibrils. The second form, designated "Parrallel", shows a wall with bundles of parallel oriented microfibrils without cortical microtubules. Taking colchicine as an example for a microtubule-inhibitor the "Parallel" form may be obtained with 10mM and the "Intermediate" with 5 to 1 mM solutions. Some microtubule-inhibitors such as methylbenzimidazole-2yl-carbamate (MBC) produce the "intermediate" form only. The recovery of normal microfibril orientation after inhibitor treatment is dependent on three factors: a) the developmental stage--young autospores just beginning to synthesize a wall are absolutely necessary; b) the application of inhibitors with the lowest effective concentration for c) the shortest possible time. Minimal concentrations for obtaining a "Full" effect range from 10 mM for colchicine to 1 micrometer for amiprophosmethyl (APM) with incubation periods from 3 to 9 hours. The return to the normal microfibril orientation has been achieved in all cases except after podophyllotoxin treatment. Since APM has been claimed to act selectively on tubulin synthesis in Chlamydomonas it was decided to compare the effects of this compound with cycloheximide (10 microgram/ml) on the recovery of microfibril orientation after colchicine treatment. In both cases no orientation recovery is possible although in the case of cycloheximide, synthesis of cellulose is drastically inhibited. This cycloheximide inhibition is fully reversible. During cycloheximide, but not APM, inhibition cortical microtubules return; however, due to the inhibition of cellulose synthesis itself, they cannot exert their orienting influence.

Renal artery embolism: thrombolysis with recombinant tissue-type plasminogen activator.

The case of a patient with acute occlusion of the right renal artery due to an embolus is described. Using transoesophageal echocardiography, the left atrial appendage could be identified as the source of embolism. Twenty hours after the onset of symptoms, the embolus could be successfully dissolved with an intra-arterial low-dose infusion of recombinant tissue-type plasminogen activator (10 mg loading dose, 20 mg continuous infusion within 12 h).

Hepatitis B vaccination of immunosuppressed heart transplant recipients with the vaccine Hepa Gene 3 containing pre-S1, pre-S2, and S gene products.

The antibody response of immunosuppressed heart transplant recipients to vaccination with the hepatitis B (HB) virus vaccine Hepa Gene 3 (HG-3), containing HB virus pre-S1, pre-S2, and S gene products, was examined. Three heart transplant recipients who had been vaccinated preoperatively against HB responded well to the vaccination. Five of 38 patients (13.2%) vaccinated postoperatively before HG-3 vaccination with the second-generation vaccine Gen-H-B-Vax-D (37 without and 1 with detectable anti-HBs response) and 3 of 24 (12.5%) without previous HB vaccination developed protective anti-HBs titers (greater than 10 U/l) after immunization with the HG-3 vaccine. The low response rate (8/62, 12.9%) found for postoperatively vaccinated patients indicates that heart transplant recipients should be vaccinated against HB before immunosuppressive medication.

Heart transplantation: intraoperative management, postoperative therapy and complications.

Currently, heart transplantation (HTX) is performed as an orthotopic cardiac replacement according to the technique of Lower and Shumway in over 95% of the cases with good results. Survival after heterotopic HTX, by contrast, remain poor (one year survival: 50%). Postoperative therapy compiles primarily prophylactic measures to prevent complications, especially organ rejection and infections. Immunosuppressive prophylaxis generally includes a triple drug therapy consisting of cyclosporin, prednisolone, and azathioprine for maintenance therapy. Initially there is often an additional application of poly- or monoclonal antibodies. The prime measure to prevent infection during the initial hospital stay will be reversed isolation of the recipient. Initial antibiotic prophylaxis resembles that of conservative cardiac surgery, but in addition antiviral and antifungal prophylaxis is applied. The most common postoperative complication following HTX is cardiac rejection, which is detected by routine endomyocardial biopsies. At our institution the incidence of rejection decreases from 3.07 episodes per patient in the first 3 months to 1.97 episodes during the last 6 months of the first year after HTX. In general, acute rejection is treated by methylprednisolone (3 x 500 mg/day) or anti-T-cell-antibodies. Infections often occur following intervals of increased immunosuppression, usually early postoperatively and following therapy of acute rejections. Often, invasive diagnostic measures have to be taken rapidly in order to allow for specific therapy (antibiotics, antimycotic treatment, virostatic agents). Close follow-up of the heart transplant recipient and rapid therapy of possible postoperative complications enable the current one-year survival rates of 80% or more.