Intramyocardial electrograms for monitoring of allograft rejection after heart transplantation.
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Biomedical subjects
Publications and source records attributed to F Iberer.
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During CMV viremia, the CMV specific lower matrix protein CMV pp65 can be detected in the nucleus of polymorphonuclear cells. A relationship has been found between the number of CMV pp65 positive cells, the clinical course and the effect of antiviral treatment on CMV disease. From 1990, heart recipients (triple drug therapy) were screened for CMV pp65 (antigenemia, according to the method described by The et al.), anti-CMV-IgM and -IgG. Tests were repeated at least every 4 weeks. Group 1 consisted of 23 patients who had been transplanted at least one year before the introduction of CMV testing as described. Between 1990 and 1992 26 patients were followed up during the first year after transplantation and represent group 2. In group 1, 1184 antigenemia assays were performed and 13 tested positive. In group 2 (1195 tests, 261 positive results), 20 out of the 26 recipients tested positive for CMV pp65. Without preceding evidence of a positive CMV pp65, no rise of IgM or IgG antibodies was observed. The time until the first antigenemia (time from detection until a subsequent test remains negative); 13 were found in group 1, 84 in group 2. In group 2, 46 episodes of antigenemia (mean duration 24.5 +/- 27.1 days) consisted of more than 1 consecutive positive result of the antigenemia assay (4.8 +/- 4.1). During these episodes the white blood cell count was 3460 +/- 1790/mm3. After the episodes, the mean leucocyte count was 6320 +/- 1870/mm3. The detection of CMV antigenemia indicated the initiation of antiviral treatment (hyperimmune globulin and ganciclovir). Therapy was stopped again when the antigenemia assay tested negative again. Antigenemia disappeared in all patients after initiation of antiviral treatment, CMV disease was not observed. CMV antigenemia mainly cumulates within the first year after heart transplantation. Antigenemia directed antiviral therapy does not prevent infection or repeated antigenemia but prevents CMV disease after heart transplantation.
Besides the current classification of cytomegalovirus (CMV) infection and disease we defined "CMV antigenaemia" as the marker for initiation of antiviral therapy (CMV hyperimmune globulin 2 ml/kg/d and ganciclovir 1000 mg/d), and "episodes of CMV antigenaemia"(the time from detection of antigenaemia until a subsequent antigenaemia assay tested negative again) indicated the time period of antiviral treatment. Patients were at highest risk for antigenaemia at day 38.2 +/- 20.9 after heart transplantation. We observed 50 episodes of antigenaemia in 18 patients. The mean duration was 7.3 +/- 6.4 days. No antigenaemia associated symptoms and no anti-CMV IgM was observed without preceding evidence of antigenaemia. Antigenaemia-associated symptoms and antigenaemia disappeared after antiviral therapy was initiated. Our therapy did not prevent CMV infection, but despite the repeated evidence of active CMV infection, no patient suffered CMV disease.
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Six years after the first aortic valve replacement with the Starr-Edwards Silastic ball prosthesis at Oregon Health Sciences University, the model 1260 was implanted in a 44-year-old patient at our department. During 24 years no signs of dysfunction, thromboembolism, thrombosis, periprosthetic leaks or hemolysis were observed. Material test showed no signs of fatigue. The dimension of the Silastic poppet was found to be one millimeter less than the original specifications of these poppets and there were some lipid infiltrations. Functionally the poppet was found to be nonvariant. Histologic findings detected focal hyalinization and giant cells without signs of acute inflammation or ulceration. With regard to its reliability and durability, the Starr-Edwards valve prosthesis should not be viewed with disfavor.
This study describes clinical experience with a rapid method for diagnosis of cytomegalovirus infection in organ-transplanted patients, based on the detection of CMV-specific antigens in peripheral polymorphonuclear cells with a mixture of monoclonal antibodies. This CMV-pp65 assay was formerly called the "CMV immediate early antigen assay." A group of 180 organ-transplanted patients were examined with this assay; 75 of them could be observed from the date of transplantation. These 75 patients consisted of two groups: 59 kidney transplant patients receiving no CMV hyperimmunoglobulin prophylaxis (group I), 13 heart-transplanted patients, and 3 liver transplanted patients receiving prophylaxis (group II). Group III consisted of 105 patients who had been transplanted ca. 2 years before starting this study. In group I, 26 (44%) were CMV-pp65-positive (13 primary and 13 secondary infections). Fifteen of these 26 (58%) positive patients showed clinical symptoms of CMV infection. Eleven of these 15 (73%) were primary infections. Symptomatic patients had significantly more CMV-pp65-positive cells than asymptomatic patients; 12 patients showed a high number of positive cells and 11 of them developed severe CMV illness. Thirty-three patients were CMV-pp-65-negative (22 CMV IgG-sero-positive, 11 CMV IgG-seronegative). None of them had symptoms of CMV infection. In all patients of group I there were 36 periods of graft dysfunction in which CMV infection had to be differentiated from transplant rejection. In 10 out of 36 there was a CMV-pp65-positive test result and subsequent seroconversion. Treatment of viral infection resulted in improvement of clinical problems. In the remaining 26 episodes no CMV-pp65-positive cells were detected: in 17 cases graft dysfunction was caused by rejection, in 9 cases by other complications. In group II, 13 of 16 patients (81%) were positive in the CMV-pp65 assay (6 primary infections, 7 secondary infections). However, none of them showed clinical signs of CMV infection, regardless of the number of positive cells. No CMV-related graft dysfunction was observed. In group III, CMV infections did not play an important role. The experiences described suggest that this test is a valuable tool in early CMV diagnosis and in differentiating CMV-dependent graft dysfunction from other graft dysfunctions. It allows prompt therapeutic intervention.
Elevated pulmonary vascular resistance (PVR) and pulmonary hypertension (PH) are high risk factors for early graft failure in orthotopic heart transplantation (oHTx). The need for an oversized donor in patients with elevated PVR aggravates the shortage of suitable donor organs. To decrease the elevated PVR to values suitable for orthotopic heart transplantation prostaglandin E1 (PGE1) was administered in 11 patients (11 male, mean age 49.2 years, mean dosage 35 ng/kg per min over 6-8 days). Ten days after the discontinuation of the PGE1 therapy, recatheterization was done. All haemodynamic data were determined by right heart catheterization using a Swan Ganz catheter and thermodilution technique before, and 10 days after, PGE1 treatment. The Wilcoxon signed ranks test was used for statistics. PVR significantly decreased in all patients (5.5 to 2.8 Wood units, P < 0.005). All patients were considered to be suitable for oHTX and put on the waiting list. At the time of writing, in eight of these patients (eight male, mean age 49.6 years; four ischemic, four dilatative CMP) oHTX had been successfully performed. No right ventricular failure occurred in the postoperative phase. These results sugest that long-term moderation of elevated PVR by PGE1 therapy weeks or months before transplantation enables oHTX in patients with elevated PVR.
In view of the numerous techniques known for noninvasive rejection monitoring for heart transplant recipients, it is important, especially for small transplant centres, to select suitable parameters for routine monitoring. We verified the methods for rejection monitoring and on the basis of the good results after orthotopic heart transplantation in our unit (33 patients, 78% overall survival, no death later than 6 months after transplantation), consider the following parameters useful for small transplant centres: heart/thorax ratio, echocardiography and neopterin. The Fast-Fourier analysis should prove of great value for small transplant units, given the availability of suitable apparatuses.
Human serum lipoproteins form complexes with cyclosporine-A and act as a carrier of cyclosporine-A in vivo. We compared the immunosuppressive effects of free cyclosporine-A, a complex composed of cyclosporine-A and lipoproteins, free cyclosporine-A in the presence of each unbound lipoprotein, and each lipoprotein without cyclosporine-A with one another at concentrations comparable with in vivo conditions on PHA-stimulated peripheral blood mononuclear cells. Free cyclosporine-A reduced the proliferation of the PHA-stimulated mononuclear cells to 50% at a concentration of 300 ng ml-1 (SD +/- 30, n = 12) lipoprotein-deficient medium. Cyclosporine-A loaded into VLDL showed a 50% proliferation rate reduction at 60 micrograms VLDL ml-1 (SD +/- 10, n = 12) and 180 ng cyclosporine-A ml-1. In the presence of 100 ng ml-1 cyclosporine-A 180 micrograms ml-1 VLDL (SD +/- 25, n = 12) showed a proliferation rate reduction of 50%. In the same way VLDL without cyclosporine-A induced a reduction to 50% at 740 micrograms ml-1 (SD +/- 30, n = 12). Cyclosporine-A loaded into LDL showed a 50% proliferation rate reduction at 27 micrograms ml-1 LDL (SD +/- 5, n = 12) with 80 ng ml-1 cyclosporine-A. In the presence of 100 ng ml-1, cyclosporine-A 150 micrograms ml-1 LDL (SD +/- 25, n = 12) showed a proliferation rate reduction of 50%. In the same way, LDL without cyclosporine-A induced a reduction to 50% at 950 micrograms ml-1 (SD +/- 50, n = 12).(ABSTRACT TRUNCATED AT 250 WORDS)
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We report on a 14-years old boy with isolated interruption of the aortic arch (type B). By the use of extracorporal circulation complete relief could be achieved by interposing a large Dacron tube. Follow up restudy demonstrated a normotensive patient without residual gradient of the systemic blood pressure.
Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Beside surgical resection, orthotopic liver transplantation (OLT) is not only effective but also the only potentially curable treatment in selected cases of small tumors. We report our experience in 11 male patients transplanted for HCC from August 1998 to July 2002. Selection criteria for OLT were unresectability of the hepatic tumor and severity of the underlying liver disease. The tumor diagnosis was confirmed by histology, imaging techniques, and tumor markers. All patients received an orthotopic liver allograft using a modified piggyback technique. Six of the 11 patients are alive; one died due to acute rejection and four died from recurrent disease. In all four patients with recurrent disease, vascular invasion was shown histologically, whereas only one patient without evidence of recurrence showed vascular invasion. To prevent recurrence after OLT the immunosuppressive regime was adjusted to the underlying disease by early cessation of prednisolone and reduction in the long-term exposure to immunosuppressive drugs. Patients were screened for recurrence by ultrasound and computed tomography. Recurrent HCC were treated symptomatically. OLT is an effective treatment for subgroups of patients with HCC. It might be possible to downstage the liver tumor by chemoembolization and/or radiofrequency ablation and allow the patients to wait for a suitable donor. After OLT the early withdrawal of prednisolone and the reduction of other immunosuppression is feasible. In conclusion, OLT can be a potentially curative therapy for HCC.
One hundred fifty million people suffer from diabetes mellitus worldwide. Modern exogenous insulin therapy cannot prevent late complications. Islet cell transplantation could be a sufficient therapeutic option but the shortage of human organs limits this option. The use of xenogeneic porcine islet cells may also be a viable alternative. One way to manage hyperacute rejection is by the protection of xenogeneic cells from the immune system by microencapsulation. In this study sodium cellulose sulfate (NaCS) was evaluated as a material for encapsulation. An insulin-producing cell line (HIT-T15) was established in our laboratory. Glucose-dependent insulin production and cell growth were monitored. Cells were encapsulated with NaCS by Austrianova, Vienna. The insulin production and mitosis rate were examined. Cell growth and insulin production by HIT-T15 cells affected the glucose levels in the nutrient solution. Cell viability and glucose-dependent insulin production were not influenced by NaCS. Encapsulation with NaCS is feasible and it could be shown that the material is permeable to nutrients and metabolic side products. The encapsulated cells are able to detect the glucose concentration in the nutrient solution and to react in a proper way by producing insulin. Encapsulation with NaCS, which is more biocompatible and less immunogenic than other materials, seems to be a promising method for immunoisolation of porcine beta cells for xenotransplantation to replace the endocrine pancreas in a physiologic way.
This retrospective study was carried out to evaluate the effect of prostaglandin E1 on the frequency of rejection in 36 heart transplant recipients who survived orthotopic heart transplantation for 60 days or longer. The therapy for both groups was the same except group 1 (n = 12) was given PGE1 for 6 to 14 days. Indication for the PGE1 was right ventricular mismatch or failure. The prostaglandin administration started during the transplantation procedure. The dosage was 28 to 64 ng/kg/min and was tapered down from 14.7 to 32 ng later. No major side effects related to PGE1 have been observed. During the first 60 days after heart transplantation, in the group treated with prostaglandin, rejection grade 2 or higher was evident in 0.91 biopsies/patient versus 2.2 in nontreated patients, (p less than 0.05). A prolonged interval free from rejection (p less than 0.05) was observed in the patients treated with prostaglandin.
During the first year after orthotopic heart transplantation 39 recipients (given prophylactic immunosuppression with antithymocyte globulin for 7 days after orthotopic heart transplantation and triple drug maintenance therapy) were screened for cytomegalovirus antigenemia and anti-cytomegalovirus immunoglobulin M (index) and immunoglobulin G levels (antibody units) by MEIA-method. Until day 14, all recipients received cytomegalovirus hyperimmunoglobulin at a dosage of 2 ml/kg/day. Four patient groups were defined: group 1 (n = 15) seropositive recipient/seropositive donor, group 2 (n = 9) seronegative recipient/seropositive donor, group 3 (n = 8) seropositive recipient/seronegative donor and group 4 (n = 7) seronegative recipient/seronegative donor. Twenty-four donors and 23 recipients were seropositive for anti-cytomegalovirus immunoglobulin G. After transplantation, 31 recipients tested positive for cytomegalovirus antigenemia before immunoglobulin M elevation and at least 7 days before the onset of clinical symptoms of cytomegalovirus. In group 2, episodes of cytomegalovirus antigenemia appeared earlier, were more frequent, and lasted longer than in groups 1 and 3. Without previous evidence of positive cytomegalovirus antigenemia testing, no sign of cytomegalovirus disease was seen. When cytomegalovirus antigenemia was positive, cytomegalovirus hyperimmunoglobulin was readministered at the same dosage and gancyclovir (1000 mg/day) was given until cytomegalovirus antigenemia disappeared. However, episodes of recurrent cytomegalovirus were observed (2.6 +/- 1.9, 4.3 +/- 1.0, and 2.3 +/- 1.2 in groups 1, 2 and 3, respectively). In groups 1 and 3, the anti-cytomegalovirus immunoglobulin G antibody level remained high during the observation period. In groups 2 and 4 anti-cytomegalovirus immunoglobulin G antibodies were positive because of hyperimmunoglobulin prophylaxis but immunoglobulin G decreased again after discontinuation of the prophylaxis.(ABSTRACT TRUNCATED AT 250 WORDS)
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Hearts from brain dead victims of carbon monoxide poisoning have been reported to be unsuitable for heart transplantation. We present the case of a 30-year-old male donor who was the victim of carbon monoxide poisoning. He was on ventilation for 16 days before the organs were offered for harvesting. A liver biopsy indicated focal liver cell necrosis. The liver graft was not used. Heart transplantation was performed successfully. No evidence of ischemic areas or myocardial cell necrosis could be found in all heart biopsy specimens. Four months after transplantation, graft function remains excellent.