Treatment of leukopenia with granulocyte-macrophage colony-stimulating factor after heart transplantation.
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Biomedical subjects
Publications and source records attributed to A Wasler.
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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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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.
The HeartMate left ventricular assist system (LVAS) is being used with increasing frequency as a bridge to heart transplantation and for long-term support of chronic heart failure patients who are not transplant candidates. The surgical techniques and anatomic placement of the HeartMate are factors in minimizing complications that occur during long-term use. Device related bleeding, infection, and other intraabdominal complications are serious adverse events associated with the position of the LVAS. Clinical data from 48 HeartMate supported patients were analyzed retrospectively to determine differences in serious complication rates between intraperitoneal (IP) and extraperitoneal (EP) LVAS placement. The LVAS was placed IP in 37 patients (77%) and EP in 11 patients (23%). The occurrence of postoperative bleeding that required reoperation was 57% in the IP group and 64% in the EP group. Device related bleeding was 8% in the IP group and 29% in the EP. Neither difference in bleeding rate was statistically significant. The overall infection rate during the entire period of LVAS support was similar between groups (IP, 45.7%; EP, 46.2%; p = 0.25); however, device related infection occurred more often in the EP group (46%; IP, 14%; p = 0.025). All patients who recovered from LVAS implantation experienced mild early satiety, but were otherwise free of intra-abdominal complications. The transplantation rate was 64% for the IP group and 78% for the EP group. IP LVAS placement may offer additional protection against device related infections.
Infection is a problem in patients undergoing support with left ventricular assist systems. To better understand the nature of this problem, we retrospectively analyzed data on 56 patients supported by the HeartMate (Thermo Cardiosystems, Inc, Woburn, MA) left ventricular assist system. Infection was defined as fever > 38 degrees C, white blood count > 12,000 cells/ml, and a need for antimicrobial therapy. Of the 56 patients, 25 (41%) had an infection. Device related infections (as determined by positive culture from driveline, housing, or inflow or outflow tract) occurred in eight patients (14.3%). The most common sites of infection were the respiratory system (42.4%), the central venous catheter (27.8%), and blood (18.3%). Of the positive cultures, 84% were bacterial and 16% fungal. There were no positive viral cultures. Positive cultures from left ventricular assist system related sites made up only 8.7% of the total. All but one of the patients with device related infections survived to transplantation. The long-term survival rate for patients in this group after transplantation was 77.8%. Two patients required surgical revision of the driveline because of infection. Both were free of infection postoperatively. Patients who stayed in the intensive care unit for longer periods had a greater risk of infection (uninfected, 35 days; infected, 78 days). In conclusion, although infection is a problem in patients undergoing support with left ventricular assist systems, it does not preclude survival to transplantation or alter the survival rate after transplantation.
BACKGROUND: Overweight is defined with a body mass index (BMI) >25. A BMI >25 is known as an independent risk factor for increased morbidity and mortality. The influence of an increased BMI on the development of diabetes and on survival after heart transplantation (HTX) was investigated. METHODS: A total of 137 patients (116 men, 21 women), who underwent HTX at our Department from 1986 to 2002, were included in the study. For group stratification, the pre-operative BMI values were taken (group I: BMI 25). Groups were compared for primary disease, age and sex, development of renal failure, development of diabetes, and survival. The probability of survival and the freedom-from-diabetes interval were calculated by the use of Kaplan-Meier method. RESULTS: No significant differences between groups I and II were found concerning primary disease, age and sex, and occurrence of renal failure. There was a tendency towards increased survival (p = 0.18) in group I. Patients of group II developed diabetes after HTX more frequently than those of group I (p < 0.001). Cox regression revealed that pre-operative BMI >25 is a highly significant independent risk factor for post-operative development of diabetes mellitus (DM) (p < 0.001). CONCLUSION: Overweight prior to HTX appears to negatively influence long-term survival after HTX, although this difference did not reach statistical significance. Pre-operative overweight is a significant and independent risk factor for the development of post-transplant diabetes.
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.
Forty-three consecutive patients who were being treated with digitalis, angiotensin converting enzyme inhibitors, and diuretics were evaluated for orthotopic heart transplantation. After right heart catheterization in patients with more than 3 Wood units or with a mean pulmonary artery pressure higher than 30 mm Hg (n = 13; group 1), prostaglandin E1 (PGE1) therapy was initiated at a dosage of 5 ng/kg/min and was increased stepwise (mean maintenance dosage, 35 ng/kg/min) until side effects (joint pain, digital edema) occurred. After 6 days of PGE1 administration, dosage decreased stepwise. One week after PGE1 was stopped, right heart recatheterization was performed, and the patients were listed on the waiting list. Hemodynamic data significantly improved in PGE1-treated patients. Patients without pulmonary hypertension (group 2, n = 30) were put directly on the waiting list. No oversized or local donor was required for transplantation. Eight of 13 patients in group 1 underwent transplantation. The other five patients died while on the waiting list. In group 2, 15 patients underwent transplantation, and 15 patients died while on the waiting list. A prolonged mean survival time on the waiting list (6.0 versus 3.1 months, p < 0.005) was noticed in group 1. PGE1 was administered after orthotopic heart transplantation whenever indicated; no death was related to right ventricular failure in group 1. The results after orthotopic heart transplantation in patients treated with PGE1 were comparable to the control group. PGE1 therapy enabled us to perform orthotopic heart transplantation on patients with pulmonary hypertension at a comparable risk with normal heart transplant recipients.