RESUMEN
BACKGROUND: Renal allograft outcome in heart-kidney transplantation (HKTx) might be affected by hemodynamic instability and high levels of calcineurin inhibitor-dependent immunosuppression. METHODS: From November 1999 to March 2008, 13 patients who received HKTx were compared with a matched control group of 13 kidney transplantation (KTx) recipients with similar cardiovascular risk factors. Graft function, rejection periods, and patient survival were analyzed. RESULTS: Renal allograft rejection was noted in three patients (23%) after HKTx and in four patients (31%) after KTx. Serum creatinine levels were comparable at 1 week, 1 month, 1, 2, and 3 years after transplantation. Patient survival rates at 1, 2, and 3 years were 100% for HKTx recipients and 100, 92, and 92% for isolated KTx patients. Graft survival was 92% at 1, 2, and 3 years after HKTx and 100% at 1 year and 92% at 2 and 3 years after isolated KTx. CONCLUSIONS: Our results with excellent long-term graft function and survival after combined HKTx indicate that this procedure is a valuable option for a growing number of patients suffering from coexistent cardiac and renal failure.
Asunto(s)
Supervivencia de Injerto , Cardiopatías/cirugía , Trasplante de Corazón , Inmunosupresores/uso terapéutico , Trasplante de Riñón , Insuficiencia Renal/cirugía , Adolescente , Adulto , Anciano , Biomarcadores/sangre , Estudios de Casos y Controles , Creatinina/sangre , Alemania , Rechazo de Injerto/etiología , Rechazo de Injerto/prevención & control , Supervivencia de Injerto/efectos de los fármacos , Cardiopatías/complicaciones , Cardiopatías/mortalidad , Trasplante de Corazón/efectos adversos , Trasplante de Corazón/mortalidad , Humanos , Estimación de Kaplan-Meier , Trasplante de Riñón/efectos adversos , Trasplante de Riñón/mortalidad , Masculino , Persona de Mediana Edad , Insuficiencia Renal/complicaciones , Insuficiencia Renal/mortalidad , Estudios Retrospectivos , Factores de Tiempo , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Everolimus is a proliferation-signal inhibitor which was introduced for heart transplant recipients in 2004. To date, there are only sparse data about long-term calcineurin inhibitor (CNI)-free immunosuppression using everolimus. METHODS: After heart transplantation, patients receiving everolimus were consecutively enrolled. Reasons for switching to everolimus were side effects of CNI immunosuppression, such as deterioration of kidney function and recurrent rejection episodes. All 60 patients underwent standardized switching protocols, 42 patients completed 24-month follow-up. Blood was sampled for lipid status, renal function, routine controls, and levels of immunosuppressive agents. On days 0, 14, and 28, and then every 3 months, echocardiography and physical examination were performed. RESULTS: After switching to everolimus, most patients recovered from the side effects. Renal function improved significantly after 24 months (creatinine, 2.1 ± 0.6 vs 1.8 ± 1 mg/dL; P < .001; creatinine clearance, 41.8 ± 22 vs 48.6 ± 21.8 mL/min; P < .001). Median blood pressure increased from 120.0/75.0 mm Hg at baseline to 123.8/80.0 mm Hg at month 24 (P values .008 and .003 for systolic and diastolic pressures, respectively). Tremor, peripheral edema, hirsutism, and gingival hyperplasia markedly improved. Levels of interleukin-6 were stable between baseline and 24-month levels. Temporary adverse events occurred in 8 patients [13.3%: interstitial pneumonia (n = 2), skin disorders (n = 2); reactivated hepatitis B (n = 1), and fever of unknown origin (n = 3)]. CONCLUSION: CNI-free immunosuppression using everolimus is safe, with excellent efficacy in maintenance of heart transplant recipients. Arterial hypertension and renal function significantly improved. CNI-induced side effects, such as tremor, peripheral edema, hirsutism, and gingival hyperplasia, markedly improved in most patients.
Asunto(s)
Inhibidores de la Calcineurina , Trasplante de Corazón , Inmunosupresores/administración & dosificación , Sirolimus/análogos & derivados , Anciano , Presión Sanguínea , Creatinina/sangre , Creatinina/orina , Everolimus , Femenino , Estudios de Seguimiento , Alemania , Hospitales Universitarios , Humanos , Inmunosupresores/efectos adversos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Sirolimus/administración & dosificaciónRESUMEN
Instrumentation with cement-augmented pedicle screws has expanded the therapeutic spectrum. This technique is useful for the palliation of bone metastases and in generalized osteoporosis. Serious complications such as pulmonary embolism have been described following percutaneous vertebroplasty, a frequently used technique. We report the case of a 55-year-old patient with a large central Palacos embolism of the right pulmonary artery after corporectomy of the lumbar vertebrae 3 and 4 and reconstruction using autologous pelvic bone. The large Palacos embolism was removed successfully from the right pulmonary artery with extracorporeal circulation.
Asunto(s)
Cementos para Huesos/efectos adversos , Migración de Cuerpo Extraño/etiología , Fijación de Fractura/efectos adversos , Vértebras Lumbares/cirugía , Embolia Pulmonar/etiología , Fracturas de la Columna Vertebral/cirugía , Antibacterianos/uso terapéutico , Antihipertensivos/uso terapéutico , Embolectomía , Circulación Extracorporea , Migración de Cuerpo Extraño/diagnóstico por imagen , Migración de Cuerpo Extraño/terapia , Humanos , Vértebras Lumbares/diagnóstico por imagen , Vértebras Lumbares/lesiones , Masculino , Persona de Mediana Edad , Embolia Pulmonar/diagnóstico por imagen , Embolia Pulmonar/terapia , Fracturas de la Columna Vertebral/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
Drug treatment of chronic systolic heart failure usually includes angiotensin-converting enzyme inhibitor, or an angiotensin II receptor blocker, and a beta blocker, as prognostic benefit of these agents has been demonstrated in a large body of clinical trials. Depending on the stage of the disease and concomitant factors, an aldosterone antagonist and/or a digitalis glycoside may provide additional benefit. Most patients also receive a diuretic for symptomatic relief. Conversely, some drugs may precipitate or aggravate chronic systolic heart failure.
Asunto(s)
Insuficiencia Cardíaca Sistólica/tratamiento farmacológico , Antagonistas Adrenérgicos beta/uso terapéutico , Bloqueadores del Receptor Tipo 1 de Angiotensina II/uso terapéutico , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Enfermedad Crónica , Glicósidos Digitálicos/uso terapéutico , Diuréticos/uso terapéutico , Antagonistas de Receptores de Mineralocorticoides/uso terapéutico , Resultado del TratamientoRESUMEN
The German Disease Management Guideline "Chronic Heart Failure" intends to guide physicians working in the field of diagnosis and treatment of heart failure. The guideline provides a tool on the background of evidence based medicine. The following short review wants to give insights into the role of some surgical treatment options to improve heart failure, such as revascularization, ventricular reconstruction and aneurysmectomy, mitral valve reconstruction, ventricular assist devices and heart transplantation.
Asunto(s)
Insuficiencia Cardíaca/cirugía , Guías de Práctica Clínica como Asunto , Medicina Basada en la Evidencia , Femenino , Alemania , Humanos , Masculino , Resultado del TratamientoRESUMEN
The Eurotransplant International Foundation in Leiden, the Netherlands, is responsible for mediation and allocation of organ donation procedures to its member countries Austria, Belgium, Croatia, Germany, Luxembourg, the Netherlands and Slovenia. To provide organs for the patients who require urgent transplantation, the "high urgent (HU)" status was introduced in 2001 in Germany . This new HU allocation system is applicable to neonates as well as adults. However, waiting times on HU status exceed several weeks to months. Therefore an increasing number of pediatric patients has to undergo implantation of a ventricular assist device (VAD). In the present report we discuss the current Eurotransplant heart allocation system for pediatric heart transplantation in the light of a neonate with 452 days on mechanical support. We compare the average waiting time of patients on HU status at our center and their outcome in 2007 and 2008 (Data obtained from Eurotransplant International Foundation). Waiting time on HU status in our center increased significantly from 2007 to 2008. Therefore more patients require VAD support as bridging to transplantation. The case of a neonate under long-term VAD support is an outstanding example of the negative effects of this development.
Asunto(s)
Corazón Auxiliar , Femenino , Trasplante de Corazón , Humanos , Recién Nacido , Masculino , Factores de Tiempo , Listas de EsperaRESUMEN
Left ventricular assist devices (LVADs) offer the opportunity to substantially improve the clinical conditions and to interrupt hospitalization of patients suffering from end-stage heart failure awaiting heart transplantation. The authors report a case of a 66-year old patient suffering from end-stage idiopathic dilative cardiomyopathy who needed the implantation of a LVAD and later developed a sepsis with a methicillin resistant Staphylococcus aureus (MRSA) which could be recovered by a differentiated antibiotic regimen.
Asunto(s)
Corazón Auxiliar , Staphylococcus aureus Resistente a Meticilina , Complicaciones Posoperatorias/tratamiento farmacológico , Complicaciones Posoperatorias/microbiología , Infecciones Estafilocócicas/tratamiento farmacológico , Anciano , Humanos , Masculino , Inducción de RemisiónRESUMEN
Left ventricular assist devices (LVADs) offer the opportunity to substantially improve the clinical condition and to interrupt the hospitalization of patients suffering from end-stage heart failure awaiting heart transplantation.We report a case of a 30-year-old patient (body surface area 2.49 m2) suffering from idiopathic dilative cardiomyopathy who was primarily given an LVAD with a free floating impeller pump and was finally switched to a total artificial heart due to the demand for a higher cardiac output.
Asunto(s)
Gasto Cardíaco , Cardiomiopatía Dilatada/cirugía , Corazón Artificial , Corazón Auxiliar , Adulto , Cardiomiopatía Dilatada/fisiopatología , Trasplante de Corazón , Humanos , Masculino , Resultado del Tratamiento , Listas de EsperaRESUMEN
In the view of off-label use, special concern should be granted to obtaining informed consent from the patient. It is important to point out the test character of the treatment. The patient has to be informed about the risks that exist with the treatment. The patient has to know that a drug not yet approved for this treatment is being used and the risks linked with its use have to be addressed. In addition, informed consent has to be documented and the differences compared with the standard treatment have to be pointed out.
RESUMEN
Vascular remodeling is influenced by trauma and proatherogenic factors such as cholesterol. It has been shown that cholesterol exerts a direct effect on vessel wall structure. In this study we evaluated the effects of vascular trauma and cholesterol treatment on vascular remodeling and plaque integrity in carotid ligated ApoE-deficient mice. The right carotid artery was ligated in mice fed regular chow or cholesterol and fat containing diet. After 4 weeks left (non-ligated) and right (ligated) carotids were prepared. For studying vascular remodeling the vascular areas were evaluated morphometrically by calculating the areas from circumference measurements on Verhoff-van Gieson stains. The cellular and structural features of the plaque were analyzed by histological staining and immunohistochemistry. Under regular chow total vessel area decreased by 35% (p<0.001); cholesterol-rich diet led to an increase by 20% (p<0.05). In both feeding groups ligated carotids presented neointima development. The medial area increased only in mice fed regular chow. The luminal area was reduced by 80% (regular chow: p<0.001) and by 90% (cholesterol-rich diet: p<0.01). Regular chow led to structured plaques showing the typical features of stable plaques. Under cholesterol diet well defined plaque structures were missing. These lesions were characterized by numerous macrophages, few mostly PCNA positive smooth muscle cell (SMC) and less collagen particularly in the shoulder region. Our data indicate that in ApoE-deficient mice both direction of the remodeling response and lesion integrity are due to the diet applied: regular chow led to constrictive remodeling, whereas cholesterol and fat containing diet was associated with an adaptive response. Our data further indicate that the direction of response is not only related to the macrophage content but also to a proliferative intimal SMC-phenotype. Our data implicate that high serum cholesterol levels are not only inducers of plaque instability but also of the so far "positively recorded" compensatory remodeling.
Asunto(s)
Apolipoproteínas E/deficiencia , Traumatismos de las Arterias Carótidas/patología , Arteria Carótida Común/patología , Hipercolesterolemia/patología , Animales , Apolipoproteínas E/genética , Traumatismos de las Arterias Carótidas/genética , Traumatismos de las Arterias Carótidas/metabolismo , Arteria Carótida Común/metabolismo , Arteria Carótida Común/cirugía , Colesterol en la Dieta/metabolismo , Colágeno/metabolismo , Hipercolesterolemia/genética , Hipercolesterolemia/metabolismo , Ligadura , Macrófagos/metabolismo , Macrófagos/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Rotura Espontánea , Factores de TiempoAsunto(s)
Antihipertensivos/farmacología , Ciclosporina/farmacología , Hemodinámica/efectos de los fármacos , Isoquinolinas/farmacología , Losartán/farmacología , Microcirculación/efectos de los fármacos , Circulación Renal/efectos de los fármacos , Tetrahidroisoquinolinas , Animales , Presión Sanguínea/efectos de los fármacos , Inmunosupresores/farmacología , Flujometría por Láser-Doppler , Masculino , Quinapril , Ratas , Ratas WistarAsunto(s)
Alopurinol/farmacología , Ciclosporina/toxicidad , Hemodinámica/fisiología , Circulación Renal/fisiología , Animales , Presión Sanguínea/efectos de los fármacos , Hemodinámica/efectos de los fármacos , Masculino , Ratas , Ratas Endogámicas WKY , Flujo Sanguíneo Regional/efectos de los fármacos , Circulación Renal/efectos de los fármacosRESUMEN
The short- and long-term effect of radiofrequency (RF) modification of the AV junction on ventricular rate and left ventricular function and the different types of ventricular response during energy application under autonomic nervous blockade were assessed in 28 patients with medically refractory atrial fibrillation. During the successful RF application, ventricular rate slowed progressively (type I response, ten patients) or accelerated at first and then slowed (type II response, 11 patients). Type II response was associated with a more anterior ablation site compared to Type I response. A primary successful outcome was achieved in 21 patients. Inadvertent complete AV block developed in three patients, while in four patients AV nodal ablation was performed after an unsuccessful modification attempt. During 6-month follow-up, the ventricular rate was adequately controlled in only four patients. Among the 16 patients with a recurrence of uncontrolled AF were all 10 patients with type I response and 6 of 11 patients with type II response. One patient died suddenly 10 weeks after the procedure.
Asunto(s)
Fibrilación Atrial/cirugía , Nodo Atrioventricular/cirugía , Bloqueo Nervioso Autónomo , Sistema Nervioso Autónomo/fisiopatología , Ablación por Catéter , Corazón/inervación , Anciano , Anciano de 80 o más Años , Fibrilación Atrial/fisiopatología , Nodo Atrioventricular/fisiopatología , Electrocardiografía Ambulatoria , Femenino , Estudios de Seguimiento , Bloqueo Cardíaco/diagnóstico , Bloqueo Cardíaco/fisiopatología , Frecuencia Cardíaca/fisiología , Humanos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/fisiopatología , Estudios Prospectivos , Función Ventricular Izquierda/fisiologíaRESUMEN
Lovastatin has been proven to effectively lower circulating LDL cholesterol and to exert antiproliferative effects on various cell lines, the latter effect being only incompletely understood. We found that lovastatin modulates the signal transducing phosphorylation cascade in vascular smooth muscle cells in a mevalonate-independent manner. Lovastatin was found to distinctively increase total phosphotyrosine levels in smooth muscle cells, an effect which could not be restored by mevalonate. At a concentration of 5 micromol/L lovastatin had a highly specific effect on the mitogen-activated protein kinase pathway. The expression of p42/44 mitogen-activated protein kinase (MAPK) was clearly reduced, but could be restored by addition of mevalonate, while the phosphorylation of p44 was mildly suppressed and the phosphorylation of p42 MAPK was reduced to non-detectable levels. While the phosphorylation of p44 MAPK could partially be restored by addition of mevalonate, the reduced phosphorylation of p42 MAPK could not be restored by addition of excessive doses of mevalonate or stimulation of the cells with basic fibroblast growth factor. Concurrently the expression of the GTP-binding Ras protein was significantly elevated at 5 and 20 micromol/L lovastatin, this effect being attenuated by addition of mevalonate to cell cultures. The data indicate that lovastatin is capable of modulating cellular signaling independently of the cholesterol synthesis pathway.
Asunto(s)
Anticolesterolemiantes/farmacología , Vasos Coronarios/citología , Vasos Coronarios/efectos de los fármacos , Lovastatina/farmacología , Ácido Mevalónico/metabolismo , Músculo Liso Vascular/citología , Músculo Liso Vascular/efectos de los fármacos , Fosforilación/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Animales , Aorta/citología , Aorta/efectos de los fármacos , Bovinos , Técnicas de Cultivo de Célula , Quinasas de Proteína Quinasa Activadas por Mitógenos/efectos de los fármacos , Quinasas de Proteína Quinasa Activadas por Mitógenos/fisiología , Proteínas Quinasas Activadas por Mitógenos/efectos de los fármacos , Proteínas Quinasas Activadas por Mitógenos/fisiología , Ratas , Proteínas ras/efectos de los fármacos , Proteínas ras/fisiologíaAsunto(s)
Vasos Sanguíneos/metabolismo , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Hipercolesterolemia/metabolismo , Interleucina-8/metabolismo , Ácido Mevalónico/antagonistas & inhibidores , Regulación hacia Arriba , Anticuerpos Monoclonales , Arteriosclerosis/metabolismo , Arteriosclerosis/patología , Arteriosclerosis/prevención & control , Biomarcadores , Vasos Sanguíneos/patología , División Celular , Humanos , Hipercolesterolemia/tratamiento farmacológico , Hipercolesterolemia/patología , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patologíaRESUMEN
We investigated the influence of lovastatin, simvastatin and pravastatin on proliferation and viability of vascular smooth muscle cells (SMC) in vitro and studied the effects of lovastatin on a mouse SMC line transgenic for a temperature-sensitive mutant of SV40 large T antigen (TAg), known to inhibit the function of p53 and pRb family members. We found that lovastatin and simvastatin inhibited cell proliferation by provoking G0/G1 phase arrest with concomitant depression of the proliferation antigen Ki-67/MIB-1. Lovastatin at high concentrations of 20 micromol/l caused cell death in the presence of serum but not under serum starved conditions, which was verified on the basis of increased DNA strand breaks, decreased DNA content and morphological alterations seen by electron microscopy. Cell death was also found for simvastatin, whereas pravastatin did not exhibit antiproliferative or cytotoxic effects. Mouse SMC transgenic for TAg did not show any impaired sensitivity to the antiproliferative and cell death inducing effect of lovastatin, but both effects could be antagonized by the supplementation of mevalonate. The data indicate that antiproliferative and cytotoxic effects of lovastatin are caused by the using up of products of mevalonate metabolism and do not require the presence of p53 or pRb.
Asunto(s)
Quinasas CDC2-CDC28 , División Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/farmacología , Músculo Liso Vascular/efectos de los fármacos , Animales , Antígenos Nucleares , Aorta/efectos de los fármacos , Aorta/metabolismo , Aorta/ultraestructura , Apoptosis/efectos de los fármacos , Bovinos , Células Cultivadas , Vasos Coronarios/efectos de los fármacos , Vasos Coronarios/metabolismo , Vasos Coronarios/ultraestructura , Quinasa 2 Dependiente de la Ciclina , Quinasas Ciclina-Dependientes/metabolismo , ADN/biosíntesis , ADN/genética , Humanos , Hidroximetilglutaril-CoA Reductasas/efectos de los fármacos , Hidroximetilglutaril-CoA Reductasas/metabolismo , Etiquetado Corte-Fin in Situ , Antígeno Ki-67/metabolismo , Lovastatina/farmacología , Ácido Mevalónico/farmacología , Ratones , Ratones Transgénicos , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/ultraestructura , Proteínas Nucleares/metabolismo , Pravastatina/farmacología , Proteínas Serina-Treonina Quinasas/metabolismo , Ratas , Proteína de Retinoblastoma/metabolismo , Simvastatina/farmacología , Proteína p53 Supresora de Tumor/metabolismoAsunto(s)
Arteriopatías Oclusivas/diagnóstico , Prótesis Vascular , Heparina , Músculo Liso Vascular/efectos de los fármacos , Animales , Arteriopatías Oclusivas/fisiopatología , Arteriopatías Oclusivas/cirugía , Proteínas Quinasas Dependientes de Calcio-Calmodulina/efectos de los fármacos , División Celular/efectos de los fármacos , Factor 2 de Crecimiento de Fibroblastos/efectos de los fármacos , Humanos , Técnicas In Vitro , Músculo Liso Vascular/fisiopatología , Valor Predictivo de las Pruebas , Pronóstico , RecurrenciaRESUMEN
Basic fibroblast growth factor (bFGF), a potent mitogen for arterial smooth muscle cells, has been shown to play a fundamental role in the pathogenesis of arteriosclerosis and restenosis by stimulating the proliferation of vascular smooth muscle cells. We found that partially phosphorothioate-modified 15-residue antisense oligodeoxynucleotides complementary to bFGF mRNA at 0.1-2.0 microM block growth and division of cultured human and bovine coronary smooth muscle cells in a dose-dependent manner. The effect is sequence specific at low (0.1-0.5 microM) nontoxic concentrations. It is associated with inhibition of expression of pericellular and intracellular bFGF, with a decreased de novo synthesis of bFGF and is partly reversible by the addition of exogenous (recombinant) bFGF. The antisense effect lasts 48-72 h and diminishes thereafter. If the antisense oligodeoxynucleotide medium is replaced by an oligonucleotide-free medium after 24 h, the [3H]thymidine incorporation rate returns to control levels. Under the same conditions, the corresponding sense oligodeoxynucleotide exerts negligible nonspecific inhibitory actions. The antiproliferative potency of the 15-residue antisense oligodeoxynucleotide is markedly enhanced by adding 3-4 nonbase-pairing guanosine residues at the 5'- and 3'-termini of the 15-residue antisense oligonucleotide. The data implicate bFGF in the process of smooth muscle cell proliferation and an effective and specific antiproliferative potency of bFGF-specific antisense oligonucleotides. The results point to possible new therapeutic strategies for the use of antisense methodology in the suppression of post-angioplasty restenosis.
Asunto(s)
Vasos Coronarios/efectos de los fármacos , Factor 2 de Crecimiento de Fibroblastos/genética , Músculo Liso Vascular/citología , Oligonucleótidos Antisentido/química , Oligonucleótidos Antisentido/farmacología , Animales , Bovinos , División Celular/efectos de los fármacos , Factor 2 de Crecimiento de Fibroblastos/efectos de los fármacos , Factor 2 de Crecimiento de Fibroblastos/metabolismo , Guanosina/química , Humanos , Músculo Liso Vascular/efectos de los fármacos , Pirimidinas/química , ARN Mensajero/efectos de los fármacos , Transducción de Señal , Relación Estructura-ActividadRESUMEN
Flow cytometry has become a widely used technique for the quantitative analysis of antigens at the single cell level. In the past, several protocols have been published for the detection of cytoplasmic and nuclear antigens in various cell lines, especially blood cells or cells growing in fluid culture. The applicability of these protocols to cells growing in a monolayer, such as smooth muscle cells (SMC) is often restricted, although flow cytometry is of great interest in the fields of arteriosclerosis and cancer research. We here describe a simple and reproducible method for the flow cytometric analysis of intracellular antigens such as cyclin-dependent kinase 2 (Cdk2) in rat aortic SMC. The sensitivity of the method was analyzed under growth and growth-inhibitory conditions using lovastatin, a cholesterol-lowering compound with antiproliferative capacity. Various antigens (Ras-protein, protein kinase C-alpha (PKC-alpha), Ki-67/MIB-1) in rat and bovine SMC were detectable using this methodology which should have a wide range of applications.