RESUMEN
The angiotensin blocker (ARB) eprosartan (600 mg once daily) and the calcium antagonist diltiazem (90 mg twice daily) were studied in a 24-month prospective, randomized, double-blind trial involving 53 heart transplant patients. The study compared their effects on the development of post-transplant cardiac allograft vasculopathy, a condition that frequently impairs long-term post-transplantation survival and where angiotensin blockers might be expected to play a preventive role. From baseline to month 12, the mean plaque volume increased by 7.7 mm(3) for eprosartan-treated patients and by 34.4 mm(3) for diltiazem-treated patients, but the eprosartan-related trend for reduced myointimal hyperplasia was not statistically significant. The trend in favour of eprosartan for secondary parameters (mean intimal index, vessel volume, lumen volume and coronary flow reserve) also failed to reach significance. The lack of effect might be due to a lower than planned sample size and observation periods due to recruitment difficulties. A larger study is required to confirm these preliminary findings.
Asunto(s)
Acrilatos/uso terapéutico , Bloqueadores del Receptor Tipo 1 de Angiotensina II/uso terapéutico , Trasplante de Corazón/efectos adversos , Imidazoles/uso terapéutico , Tiofenos/uso terapéutico , Trasplante Homólogo , Ultrasonografía Intervencional , Enfermedades Vasculares , Adulto , Anciano , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Resultado del Tratamiento , Enfermedades Vasculares/tratamiento farmacológico , Enfermedades Vasculares/etiología , Enfermedades Vasculares/prevención & controlRESUMEN
Chronic hepatitis B progresses to cirrhosis in the majority of immunosuppressed patients. The outcome of long-term antiviral therapy in HBV-infected organ transplant recipients is unknown. In 1996, we included 20 heart transplant (HT) recipients in a pilot trial to treat chronic hepatitis B with famciclovir. At that time, bridging fibrosis or cirrhosis was evident in 15 individuals (75%). From 1998 onwards, patients were switched to lamivudine in case of primary or secondary virological nonresponse to famciclovir. Adefovir or tenofovir became available at our centre for HT recipients in 2002. After 103 months, one patient was still on famciclovir showing a complete virological response. Sixteen patients were switched to lamivudine after 0.5-4 years of famciclovir therapy. Six of those showed a long-term response to lamivudine therapy lasting for up to 7 years. Lamivudine resistance developed in the remaining 10 patients (63%), in 4 of them successful rescue therapy (adefovir n = 3, tenofovir n = 1) could be initiated. Only one hepatocellular carcinoma developed, which was successfully treated by locoregional ablative therapy. Nine patients died (45%), with lamivudine-resistance-related liver failure as the cause of death in five cases. Significant improvement of Ishak fibrosis scores could be demonstrated in six of the seven patients with more than two sequential liver biopsies available. Long-term antiviral therapy of chronic hepatitis B can lead to regression of liver cirrhosis in patients after organ transplantation, unless viral resistance occurs. This study demonstrates the urgent need for further antivirals to overcome antiviral resistance.
Asunto(s)
2-Aminopurina/análogos & derivados , Antivirales/administración & dosificación , Trasplante de Corazón/inmunología , Hepatitis B Crónica/tratamiento farmacológico , Hepatitis B Crónica/inmunología , Inmunosupresores/uso terapéutico , Lamivudine/administración & dosificación , 2-Aminopurina/administración & dosificación , 2-Aminopurina/efectos adversos , Adulto , Anciano , Antivirales/efectos adversos , Carcinoma Hepatocelular/virología , Famciclovir , Femenino , Hepatitis B Crónica/patología , Humanos , Lamivudine/efectos adversos , Neoplasias Hepáticas/virología , Masculino , Persona de Mediana EdadRESUMEN
Predominantly elderly and multimorbide patients require frequently intensive care observation and treatment due to acute gastrointestinal and renal disease. Manifest circulatory and rhythm instability, acute heart failure and severe metabolic or electrolyte derangements present indications for submission to a critical care unit. Stabilization of vital functions, control of specific therapeutic procedures (e. g. renal replacement therapy), and early recognition of secondary complications belong to the tasks of intensive care. Beyond a baseline monitoring available procedures comprises a broad spectrum from pulseoxymetrie to pulmonary artery catheter monitoring depending of the need of the individual patient.
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Lesión Renal Aguda/terapia , Cuidados Críticos , Urgencias Médicas , Várices Esofágicas y Gástricas/terapia , Hemorragia Gastrointestinal/terapia , Monitoreo Fisiológico , Úlcera Péptica Hemorrágica/terapia , Lesión Renal Aguda/etiología , Lesión Renal Aguda/mortalidad , Lesión Renal Aguda/fisiopatología , Ecocardiografía , Várices Esofágicas y Gástricas/etiología , Várices Esofágicas y Gástricas/mortalidad , Várices Esofágicas y Gástricas/fisiopatología , Hemorragia Gastrointestinal/etiología , Hemorragia Gastrointestinal/mortalidad , Hemorragia Gastrointestinal/fisiopatología , Hemodinámica/fisiología , Humanos , Oximetría , Úlcera Péptica Hemorrágica/etiología , Úlcera Péptica Hemorrágica/mortalidad , Úlcera Péptica Hemorrágica/fisiopatología , Pronóstico , Tasa de SupervivenciaAsunto(s)
Aneurisma de la Aorta , Disección Aórtica , Enfermedad Aguda , Disección Aórtica/diagnóstico , Disección Aórtica/diagnóstico por imagen , Disección Aórtica/mortalidad , Disección Aórtica/cirugía , Aneurisma de la Aorta/diagnóstico , Aneurisma de la Aorta/diagnóstico por imagen , Aneurisma de la Aorta/mortalidad , Aneurisma de la Aorta/cirugía , Dolor en el Pecho/diagnóstico , Diagnóstico Diferencial , Ecocardiografía Transesofágica , Medicina Basada en la Evidencia , Estudios de Seguimiento , Humanos , Sensibilidad y Especificidad , Factores de Tiempo , Tomografía Computarizada por Rayos XRESUMEN
BACKGROUND: Quality of life in lung transplant recipients (LTR) is reported to be comparable with that of the general population. However, previous studies have shown that exercise capacity was reduced to 30 - 40 % of normal values. The purpose of this study was to investigate the gap between good self-reported quality of life and reduced exercise capacity in LTR, to describe possible correlations and to compare the results with those of a control group (CG). METHODS: 27 LTR 208 +/- 67 days after bilateral lund transplantation (16 male, 11 female; age: 46 +/- 10 years; body mass index: 24 +/- 3 kg x m (- 2), FEV (1) % 75 +/- 27 %) and 30 controls (17 male 13 female; age 47 +/- 15 years; BMI: 26 +/- 4 kg x m (- 2), FEV (1) % 103 +/- 15 %) performed cardiopulmonary exercise testing and were interviewed with the standardized German "Quality of life profile for chronic disease" self-rating questionnaire. RESULTS: Significant differences were shown in objective exercise related variables (peak oxygen consumption: LTR 15.1 +/- 1.8, CG 34.5 +/- 9.1 ml x min (- 1) x kg (- 1); p < 0,01); peak workload: LTR 1.0 +/- 0.2; CG 2.4 +/- 1.0 W. kg (- 1); p < 0.01); percentage of predicted workload: LTR 44 +/- 12, CG 115 +/- 33 %; p < 0.01). The rating of subjective quality of life in physical, psychological and social domains of LTR did not differ from values of the CG or of the general population (n = 1143). The quality of life in the physical domain correlated significantly with peak exercise capacity (LTR r = 0.44, p < 0.05; CG r = 0.37; p < 0.05). CONCLUSION: Patients 7 months after lung transplantation described their physical, social and psychological quality of life as equally good as the healthy control group. However, peak exercise capacity and oxygen consumption were markedly reduced. To improve physical capacity in the range of daily activities, an exercise training program should be offered to patients after lung transplantation.
Asunto(s)
Trasplante de Pulmón/rehabilitación , Calidad de Vida , Adulto , Anciano , Índice de Masa Corporal , Femenino , Humanos , Trasplante de Pulmón/psicología , Masculino , Persona de Mediana Edad , Consumo de Oxígeno , Factores de TiempoRESUMEN
INTRODUCTION: Longterm treatment after heart transplantation (HTX) improves survival, although the quality of life and exercise tolerance decreased continuously between one and ten years after transplantation. The role of physical exercise and psychological support in longterm treatment after HTX has not been determined. We analyzed the effects of a one year outpatient rehabilitation program in combination with a home based, computer assisted training program on exercise capacity, coronary risk factors and quality of life. METHODS: 20 heart transplant recipients in an intervention group and 12 patients after HTX in a control group participated in the study (IG (CG); 5.1+/-2.2 (4.5+/-2.3) years after HTX; age: 55+/-7 (54+/-8) years; body mass index: 28.3+/-1.0 (28.7+/-0.9) kg.m(-2)). Before and after the intervention, maximum and constant load exercise capacity, and self-reported quality of life were evaluated. The 12 month intervention period included 10 days of exercise testing as well as medical and psychological support. Furthermore, the IG group performed a computer-assisted and controlled home ergometer training every second day. RESULTS: After one year with 114+/-18 exercise training sessions, maximum oxygen consumption increased in the IG from 18.8+/-4.2 to 20.1+/-4.2 ml.min(-1).kg(-1) (p<0.05; CG 19.3+/- 4.5 to 18.5+/-2.8 ml.min(- 1).kg(-1); p<0.01 IG vs CG). In the IG, lower back pain, body fat, and blood pressure were all reduced, while the self-reported quality of life, endurance exercise capacity and HDL cholesterol were increased. No significant changes occurred in the control group. CONCLUSIONS: When initiated years after heart transplantation, longterm rehabilitation reduced coronary risk factors and significantly improved both the subjects' quality of life, as well as a near to normal capacity for physical work.
Asunto(s)
Electrocardiografía , Prueba de Esfuerzo , Terapia por Ejercicio , Trasplante de Corazón/rehabilitación , Calidad de Vida , Procesamiento de Señales Asistido por Computador , Terapia Asistida por Computador , Atención Ambulatoria , Terapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Grupo de Atención al Paciente , Complicaciones Posoperatorias/rehabilitación , Estudios Prospectivos , Factores de RiesgoRESUMEN
BACKGROUND: Quality of life late after heart transplantation is reported to be comparable with that of the general population. However, peak exercise capacity remained approximately 60% of what was normal between 1 and 10 years after transplantation. The gap between patients' good quality of life and their impaired exercise tolerance is not yet explained. The purpose of our study was to examine the relation between quality of life and exercise- related variables in heart transplant recipients (HTR). Then, the results of these examinations were compared with those of patients having congestive heart failure (CHF), with the use of controls (C), respectively. METHODS: (Mean values+/-SD) 29 HTR 4.4 +/- 2.1 years after transplantation, 29 CHF (NYHA II n = 22, III n = 7) and 29 C (age 54 +/- 9, 61 +/- 10, 56 +/- 10 years, body mass index 28 +/- 3, 29 +/- 5, 28 +/- 4 kg x m(-2), body fat 25 +/- 4, 27 +/- 6, 26 +/- 5%, respectively) performed cardiopulmonary exercise testing and were interviewed with the standardized German "Quality of life profile for chronic diseases" questionnaire. RESULTS: Peak oxygen consumption was impaired in HTR and in CHF compared with C (19.0 +/- 4.5, 18.6 +/- 4.3, and 30.2 +/- 6.6 ml x min x kg(-1), respectively; p < 0.01 vs. C each). HTR and CHF patients' quality of life in the physical scores were both impaired (p < 0.05 or p < 0.01 vs. C, respectively), but HTRs have reported better scores than CHF (p < 0.05). In the psychological role, CHF was impaired against C (p < 0.05), and HTR scores were comparable with C. In social functioning HTR and CHF patients both showed reduced quality of life dimensions. The Pearson correlation analysis showed that quality of life in physical functioning was related to peak oxygen consumption (p < 0.001) and percentage of predicted workload (p < 0.001). Quality of life in the social and psychological domains showed no association to exercise-related values. CONCLUSIONS: In HTR and in CHF, exercise testing variables were dominant predictors among the physical scales in quality of life, but not among social or psychological scales. Therefore, even late after heart transplantation, improving physical capacity should be a therapeutic goal with the intention of further increasing the quality of life.
Asunto(s)
Trasplante de Corazón , Calidad de Vida , Anciano , Interpretación Estadística de Datos , Ejercicio Físico , Prueba de Esfuerzo , Femenino , Estudios de Seguimiento , Insuficiencia Cardíaca/metabolismo , Insuficiencia Cardíaca/fisiopatología , Trasplante de Corazón/psicología , Humanos , Masculino , Persona de Mediana Edad , Consumo de Oxígeno , Encuestas y Cuestionarios , Factores de TiempoRESUMEN
OBJECTIVE: Acute dissection of the ascending aorta requires immediate surgical intervention. In this study, we report our first results with valve sparing aortic root reconstruction removing all the diseased tissues. METHODS: From August 1995 to December 2000, 22 patients with acute aortic dissection of the ascending aorta (Stanford type A) underwent valve sparing aortic root reconstruction. Their ages ranged from 20 to 76 years (52+/-15, 68% males). Dissection was found in the ascending aorta (3 patients) or both in the ascending aorta and aortic arch (19 patients; 86%). Course and length of hospitalization, echocardiographic and clinical follow-up, complications and mortality were analysed. RESULTS: Mean cardiopulmonary bypass time was 212+/-56 min (134-352 min), mean aortic cross clamp time was 157+/-24 min (114-205 min). In patients undergoing additional arch replacement (n=19), circulatory arrest was 35+/-18 min (11-75 min). After reconstruction, intraoperative echocardiography showed aortic insufficiency (AI) grade 0 in 16 patients (84%) and grade 1 in three patients (16%). Stay in intensive care unit was 2.1+/-0.7 days, and postoperative hospitalization was 21+/-14.4 days. There were three perioperative deaths (14%). Mean post-operative follow-up was 18.4+/-18 months (0.4-65.4 month). One patient died 10 months postoperatively. At follow-up, no patient suffered AI grade 2 or higher, and no reoperation for aortic valve failure was necessary. All patients presented with a favorable exercise tolerance being in New York Heart Association functional class I or II. CONCLUSION: Valve sparing aortic root reconstruction in patients with type A dissection can be performed with acceptable intraoperative mortality and morbidity and excellent results during follow-up. The complete resection of the diseased aorta is particularly appealing.
Asunto(s)
Aneurisma de la Aorta/cirugía , Disección Aórtica/cirugía , Insuficiencia de la Válvula Aórtica/cirugía , Válvula Aórtica/cirugía , Enfermedad Aguda , Adulto , Anciano , Disección Aórtica/mortalidad , Aneurisma de la Aorta/mortalidad , Implantación de Prótesis Vascular , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
BACKGROUND: With evolving medical techniques and post-operative care, the quality of life after cardiac transplantation is improving over the recent years. However, the need for continuous immunosuppressive therapy may result in restrictions from some social and recreational activities, including traveling. The aim of this study was to analyze traveling activities and complications in a large cohort of heart transplant recipients, with the intention to develop adequate safety and behavioral guidelines. METHODS: Using a standardized questionnaire, 103 consecutive patients (pts) were asked to report about time and destination of their traveling activities, predominant activities, as well as potential travel-related complications. Documented rejection episodes as well as laboratory data are listed. RESULTS: Feedback was 97% (of 103 pts asked). Out of 100 pts who responded, [82 males, 18 females, mean age 52.3 +/- 12.4 yr, 6.9 +/- 3.8 yr post-heart transplantation (HTX)] 95 reported on traveling activities (95%). Concomitant disease was present in form of diabetes (n=8), renal insufficiency (n=5) and cardiac allograft vasculopathy (n=12). Mean cumulative traveling time was 120 +/- 125 d (3-560 d). Except from domestic journeys, 79 pts chose destinations within Europe, and 29 to overseas countries. Complications were reported by 15 of 95 pts (15.8%), being mostly small accidents and febrile episodes. Rejection episodes or other life threatening events were not observed. There was no significant correlation between observed complications and gender, age, time post-HTX, immunosuppression or comorbidities. CONCLUSIONS: Traveling after HTX appears to be safe and favorably improves quality of life, if certain precautions are met.
Asunto(s)
Trasplante de Corazón , Viaje , Adulto , Estudios de Cohortes , Comorbilidad , Femenino , Trasplante de Corazón/efectos adversos , Humanos , Inmunosupresores/administración & dosificación , Masculino , Persona de Mediana Edad , Calidad de Vida , Encuestas y Cuestionarios , Factores de Tiempo , Viaje/estadística & datos numéricosRESUMEN
BACKGROUND: Cardiac allograft vascular disease (CAVD) represents one of the most accelerated progressing coronary syndromes in the human heart. A variety of risk factors have been identified over recent years; however, little is known about the influence of physical forces. As a model for differences in focal blood flow dynamics, we analyzed progression of intimal hyperplasia at vascular bifurcational sites using intravascular ultrasound (IVUS). METHODS: The most diseased vascular sites ("worst sites") in 59 coronary arteries were assessed (30 MHz, motorized pull back) in 25 consecutive heart transplant recipients at baseline (52.8+/-15.3 days postoperatively) and after 1 year of follow up (360.5+/-24.9 days). Progression of intimal hyperplasia was compared between branching and non-branching lesions as well as in focal relation to the position of the flow divider. RESULTS: A total of 41 (69.5%) worst sites were identified at branching locations. Progression of intimal hyperplasia was found to be significantly more severe at bifurcational sites with an increase in plaque area by 1.5+/-1.8 mm(2) in branching versus 0.4+/-0.6 mm(2) in non-branching lesions (P=0.015). The highest rate in focal progression was found at the opposite site of the flow divider with an increase in maximal intimal thickness by 0.3+/-0.23 mm (180 degrees ) as compared to 0.11+/-0.15 mm (90 degrees, P<0.001) and 0.15+/-0.15 mm (P=0.014) at 270 degrees. CONCLUSIONS: Using serial intravascular ultrasound examinations, vascular branching sites could be identified to be predisposing locations not only for a donor related arteriosclerosis, but also for progression of intimal hyperplasia within transplanted hearts. The highest regional increase in intimal thickness was found at the outer wall of the flow divider, suggesting focal shear or wall stress to be involved in pathogenesis.
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Enfermedad Coronaria/patología , Trasplante de Corazón/efectos adversos , Enfermedad Coronaria/diagnóstico por imagen , Enfermedad Coronaria/etiología , Vasos Coronarios/diagnóstico por imagen , Vasos Coronarios/patología , Progresión de la Enfermedad , Femenino , Hemorreología , Humanos , Hiperplasia , Masculino , Persona de Mediana Edad , Estrés Mecánico , Túnica Íntima/patología , Ultrasonografía IntervencionalRESUMEN
Growing evidence suggests that elevated total plasma homocysteine (tHCY) levels are associated with cardiac allograft vasculopathy following heart transplantation. To assess the effect of folic acid supplementation on tHCY levels, we performed a prospective study in a cohort of 69 patients (7.0 +/- 3.2 years after heart transplantation; mean age, 55.0 +/- 9.6 years; 61 male) treated with 5 mg folic acid/day (n = 34) vs no medication (n = 35). Therapy with folic acid resulted in significantly decreased tHCY levels, from 22.6 +/- 9.6 micromol/liter to 17.3 +/- 5.5 micromol/liter (p = 0.001) within 3 months, whereas values in the control group remained unchanged. We conclude that folic acid supplementation (5 mg per day) provides a simple and effective measure to lower elevated tHCY levels in heart transplant recipients.
Asunto(s)
Trasplante de Corazón/efectos adversos , Hiperhomocisteinemia/etiología , Hiperhomocisteinemia/terapia , Anciano , Estudios de Cohortes , Ciclosporina/efectos adversos , Suplementos Dietéticos , Femenino , Ácido Fólico/sangre , Ácido Fólico/uso terapéutico , Deficiencia de Ácido Fólico/diagnóstico , Deficiencia de Ácido Fólico/etiología , Humanos , Hiperhomocisteinemia/sangre , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Piridoxina/sangre , Factores de Riesgo , Trasplante Homólogo/efectos adversos , Deficiencia de Vitamina B 6/etiologíaRESUMEN
OBJECTIVE: In patients with aneurysm of the ascending aorta, dilatation of the sinotubular junction is the major cause of aortic valve regurgitation. Valve sparing aortic root replacement in patients without valvular structural defects offers a new form of treatment. The aim of this study was the assessment of the perioperative course and early complications of this method compared to composite replacement in a large single center cohort. METHODS: From 1992 to 1999, valve sparing replacement of the ascending aorta (recon) has been performed in 78 patients, while 269 patients underwent replacement by a composite graft (comp). A comparison of matched pairs (n=52) with respect to age, gender, presence of Marfan's syndrome, aortic dissection as well as date of surgery, was chosen. Aortic insufficiency was 2.8+/-0.7 for recon vs. 2.2+/-1.1 for comp preoperatively. Course and length of hospitalization, echocardiographic follow-up, complications, and mortality were compared at 1-year follow-up. RESULTS: There were no operative deaths. During follow-up, one patient (2%) died 5 months postoperatively (recon) vs. two patients (3.9%) in the comp group. Bypass-time (123+/-31 vs. 153+/-31 min, P<0.0001) and cross-clamp-time (82+/-22 vs. 120+/-23 min, P<0.0001) were significantly shorter in comp. Stay in ICU (1.9+/-1.6 for recon vs. 2.3+/-2.1 days for comp) and post-op hospitalization (18.3+/-5.7 vs. 21.2+/-11.1 days) were comparable. Improvement of NYHA-class was significant after both operations (recon 2.6+/-0.8 vs. 1.3+/-0.5 and for comp 2.4+/-0.6 vs. 1.5+/-0.7, both P<0.0001). One patient (1.9%) in the recon group had to be reoperated for valve failure. Thrombembolic or bleeding complications were observed in 6 patients (12%) in comp, zero in recon (P=0.027). CONCLUSION: Valve sparing aortic root reconstruction is feasible with low perioperative morbidity and mortality and good early results. Major advantages of recon are significant reduction of thrombembolic and anticoagulation related complications as opposed to longer cross-clamp and bypass times as well as a valve failure in one patient. Further follow-up is needed to confirm our data in a long-term perspective.
Asunto(s)
Aorta/cirugía , Aneurisma de la Aorta/cirugía , Válvula Aórtica/cirugía , Complicaciones Posoperatorias/epidemiología , Aneurisma de la Aorta/complicaciones , Insuficiencia de la Válvula Aórtica/etiología , Estudios de Casos y Controles , Femenino , Estudios de Seguimiento , Humanos , Tiempo de Internación/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Factores de TiempoRESUMEN
Preexisting pulmonary hypertension in pediatric patients is associated with poor outcome after cardiac transplantation because of donor right ventricular dysfunction. To avoid a combined heart-lung transplantation in a 17-year-old patient, we used an intensified pretreatment with intravenous prostacyclin and dobutamine combined with an inhalative therapy with the aerosolized prostacyclin-analog Iloprost. With this regimen, the patient was hemodynamically stabilized for the waiting period of 21 days after which an uneventful cardiac transplantation was performed.
Asunto(s)
Fármacos Cardiovasculares/administración & dosificación , Trasplante de Corazón , Hipertensión Pulmonar/tratamiento farmacológico , Iloprost/administración & dosificación , Cuidados Preoperatorios , Adolescente , Aerosoles , Humanos , Masculino , Índice de Severidad de la EnfermedadAsunto(s)
Endotelio Vascular/metabolismo , Trasplante de Corazón , Proteínas Proto-Oncogénicas c-sis/análisis , Receptor beta de Factor de Crecimiento Derivado de Plaquetas/análisis , Enfermedades Vasculares/metabolismo , Vasos Coronarios/metabolismo , Humanos , Trasplante Homólogo , Túnica Íntima/metabolismo , Enfermedades Vasculares/etiologíaRESUMEN
The load of Epstein-Barr virus (EBV) in peripheral blood mononuclear cells of transplant recipients represents a predictive parameter for posttransplant lymphoproliferative disorders (PTLD). The aim of our work was to develop a rapid and reliable PCR protocol for the quantification of cell-associated EBV DNA in transplant recipients. In contrast to previous studies, a protocol that facilitated quantification independent of photometric nucleic acid analysis was established. We took advantage of the real-time PCR technology which allows for single-tube coamplification of EBV and genomic C-reactive protein (CRP) DNA. EBV copy numbers were normalized by division by the amount of CRP DNA, with the quotient representing the actual amount of amplifiable genomic DNA per reaction. Coamplification of CRP DNA did not result in a diminished detection limit for EBV. By using the protocol without normalization, EBV copy numbers in 4 out of 10 PTLD patients were within the normal range determined with data for 114 transplant recipients that served as controls. After normalization, however, all of the PTLD patients had a higher viral load than the control population, indicating an increased sensitivity of the assay. Moreover, EBV copy numbers obtained for one patient by conventional quantification and suggestive of relapsing PTLD were within normal range after normalization. We conclude that normalization of PCR signals to coamplified genomic DNA allows a more accurate quantification of cell-bound EBV.
Asunto(s)
Infecciones por Virus de Epstein-Barr/diagnóstico , Herpesvirus Humano 4/aislamiento & purificación , Trastornos Linfoproliferativos/virología , Trasplante de Órganos , Complicaciones Posoperatorias , Calibración , Línea Celular , Niño , Infecciones por Virus de Epstein-Barr/sangre , Infecciones por Virus de Epstein-Barr/etiología , Femenino , Trasplante de Corazón , Humanos , Trasplante de Riñón , Trasplante de Hígado , Trastornos Linfoproliferativos/diagnóstico , Masculino , Reacción en Cadena de la Polimerasa/métodos , Valores de Referencia , Reproducibilidad de los Resultados , Carga ViralRESUMEN
BACKGROUND: Cardiac allograft vascular disease is (CAVD) the most important cause of death following heart transplantation (HTX). Although in the past, researchers focused predominantly on mechanisms of endothelial injury, the possible role of recipient-related and genetically determined factors has not been studied in detail. METHODS: Stimulated by recent observations in native coronary artery disease, we analyzed the potential impact of angiotensin-converting enzyme (ACE) polymorphism (insertion/deletion [I/D], intron 16) on development and progression of CAVD. We characterized genotype in 146 patients 1 to 12 years after HTX (121 men; mean age, 46.2+/-11.3 years; observation period, 6.1+/-3.8 years) and correlated genotype to the onset and progression of CAVD, defined as luminal obstruction > 50%. RESULTS: We found allelic frequencies to be 28.8% (n = 42) for ACE-DD, 49.3% (n = 72) for ACE-DI, and 21.9% (n = 32) for ACE-II. Differences in actuarial freedom from vasculopathy were significant 6 years after transplantation, with 84.6% for ACE-II compared with 54.4% for ACE-DD. We observed intermediate results for ACE-DI genotype (77.3%, p = 0.015). CONCLUSIONS: In this large cohort study, we demonstrated a close relationship between the recipient-related ACE-D genotype and development of advanced CAVD. These observations suggest that gene-environment interactions might be clinically important in coronary vasculopathy after HTX.
Asunto(s)
Enfermedad Coronaria/etiología , Trasplante de Corazón/efectos adversos , Peptidil-Dipeptidasa A/genética , Polimorfismo Genético/genética , Análisis Actuarial , Adulto , Alelos , Análisis de Varianza , Distribución de Chi-Cuadrado , Estudios de Cohortes , Enfermedad Coronaria/genética , Progresión de la Enfermedad , Ambiente , Femenino , Estudios de Seguimiento , Eliminación de Gen , Frecuencia de los Genes , Genotipo , Humanos , Intrones/genética , Modelos Logísticos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Mutagénesis Insercional/genética , Fenotipo , Análisis de Supervivencia , Trasplante HomólogoRESUMEN
BACKGROUND: Tissue engineering using in vitro-cultivated autologous vascular wall cells is a new approach to biological heart valve replacement. In the present study, we analyzed a new concept to process allogenic acellular matrix scaffolds of pulmonary heart valves after in vitro seeding with the use of autologous cells in a sheep model. METHODS AND RESULTS: Allogenic heart valve conduits were acellularized by a 48-hour trypsin/EDTA incubation to extract endothelial cells and myofibroblasts. The acellularization procedure resulted in an almost complete removal of cells. After that procedure, a static reseeding of the upper surface of the valve was performed sequentially with autologous myofibroblasts for 6 days and endothelial cells for 2 days, resulting in a patchy cellular restitution on the valve surface. The in vivo function was tested in a sheep model of orthotopic pulmonary valve conduit transplantation. Three of 4 unseeded control valves and 5 of 6 tissue-engineered valves showed normal function up to 3 months. Unseeded allogenic acellular control valves showed partial degeneration (2 of 4 valves) and no interstitial valve tissue reconstitution. Tissue-engineered valves showed complete histological restitution of valve tissue and confluent endothelial surface coverage in all cases. Immunohistological analysis revealed cellular reconstitution of endothelial cells (von Willebrand factor), myofibroblasts (alpha-actin), and matrix synthesis (procollagen I). There were histological signs of inflammatory reactions to subvalvar muscle leading to calcifications, but these were not found in valve and pulmonary artery tissue. CONCLUSIONS: The in vitro tissue-engineering approach using acellular matrix conduits leads to the in vivo reconstitution of viable heart valve tissue.