RESUMEN
BACKGROUND: Menkes disease is a copper metabolism disorder caused by mutations in ATP7A, a copper-transporting P-type ATPase. In this study, oral copper supplementation via glyoxal-bis(N(4)-methylthiosemicarbazonato)-copper(II) (CuGTSM), a lipophilic copper complex, was investigated in male hemizygous macular (MoMl/y) mice, a mouse model of Menkes disease. METHODS: CuGTSM was administered by oral gavage on postnatal days 5, 8, 11, 17, 23, and 32. The copper levels in the organs and serum, copper-dependent enzyme activities in the brain, and ceruloplasmin (Cp) activity in the serum were measured at 15 days and 3 and 8 months of age. Histological analysis of the intestines and the rotarod test were also performed. RESULTS: CuGTSM treatment extended the lifespan of MoMl/y mice and partly restored the copper concentrations and cytochrome oxidase and DBH activities in the brain; however, the rotarod test showed impaired motor performance. The treatment also increased copper concentrations and Cp activity in the serum. In suckling MoMl/y mice, CuGTSM treatment transiently induced diarrhea accompanied by copper accumulation and altered villus morphology in the ileum. CONCLUSION: Oral administration of CuGTSM extended the lifespan of MoMl/y mice. Oral administration is attractive, but pharmaceutical studies are needed to reduce the adverse enteral effects.
Asunto(s)
Complejos de Coordinación/uso terapéutico , Cobre/farmacocinética , Síndrome del Pelo Ensortijado/tratamiento farmacológico , Tiosemicarbazonas/uso terapéutico , Administración Oral , Animales , Complejos de Coordinación/administración & dosificación , Complejos de Coordinación/farmacología , Cobre/sangre , ATPasas Transportadoras de Cobre/genética , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Masculino , Ratones , Mutación , Tasa de Supervivencia , Tiosemicarbazonas/administración & dosificación , Tiosemicarbazonas/farmacología , Distribución Tisular , Aumento de Peso/efectos de los fármacosRESUMEN
BACKGROUND: The aim of this study was to review our experience of mitral valve (MV) repair for acute and active infective endocarditis (AAIE) and to identify the feasibility of a new approach together with the mid-term results. MethodsâandâResults: A retrospective analysis was performed on 35 consecutive AAIE patients surgically treated in the isolated mitral position. Mean follow-up after the surgery was 4.3±3.7 years. 30 of the 35 patients were successfully treated by MV plasty (MVP); however, MV replacement (MVR) was necessary in the remaining 5 patients. Our novel approach included resection of the infective lesion, approximation with direct suture and/or patch repair with bovine or autopericardium after 2-min treatment of it and the defective leaflet edge(s) with 0.625% glutaraldehyde solution, reconstruction with artificial chordae and ring annuloplasty. The success rate of MVP was 85.7%. The longest postoperative follow-up echocardiography showed no mitral regurgitation (MR) in 4, trivial MR in 4, mild MR in 16 and moderate MR in 5 patients in the MVP group. The 5-year survival rate in the MVP group was 89±6%. MVR was required in 1 patient 2 months after MVP because of increasing MR. Recurrence of endocarditis has not been observed in any case. CONCLUSIONS: Glutaraldehyde was safely used in a surgical intervention for AAIE in the mitral position with acceptable early and mid-term results.
Asunto(s)
Endocarditis/tratamiento farmacológico , Glutaral/uso terapéutico , Válvula Mitral/microbiología , Animales , Procedimientos Quirúrgicos Cardíacos , Bovinos , Enfermedades de las Válvulas Cardíacas/tratamiento farmacológico , Enfermedades de las Válvulas Cardíacas/microbiología , Humanos , Válvula Mitral/efectos de los fármacos , Válvula Mitral/cirugía , Insuficiencia de la Válvula Mitral , Pericardio/trasplante , Estudios Retrospectivos , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
A 41-year-old female with hereditary deficiency of antithrombin III (ATIII) was diagnosed with atrial septal defect( ASD) and scheduled for the closure of ASD. She had been taking warfarin since she suffered from deep vein thrombosis 10 years ago. Preoperative management of anticoagulation included discontinuation of warfarin, and supplementation of antithrombin with heparin infusion. On the day of operation, antithrombin activity was maintained above 80% by administering antithrombin, and closure of ASD was carried out under standard cardiopulmonary bypass support using heparin. Heparin infusion was continued with antithrombin supplementation until prothrombin time-international normalized ratio(PT-INR) recovered to around 2.5 with warfarin. Her intra-and postoperative courses did not show any thromboembolic events, and she was discharged 20 days after the surgery.
Asunto(s)
Anticoagulantes/administración & dosificación , Deficiencia de Antitrombina III/congénito , Procedimientos Quirúrgicos Cardíacos , Defectos del Tabique Interatrial/cirugía , Complicaciones Posoperatorias/prevención & control , Cuidados Preoperatorios/métodos , Trombosis de la Vena/prevención & control , Adulto , Antitrombina III/administración & dosificación , Femenino , Heparina/administración & dosificación , Humanos , Relación Normalizada Internacional , Tiempo de Trombina , Resultado del Tratamiento , Warfarina/administración & dosificaciónRESUMEN
Endothelial Notch signaling is critical for tumor angiogenesis. Notch1 blockade can interfere with tumor vessel function but causes tissue hypoxia and gastrointestinal toxicity. Notch4 is primarily expressed in endothelial cells, where it may promote angiogenesis; however, effective therapeutic targeting of Notch4 has not been successful. We developed highly specific Notch4-blocking antibodies, 6-3-A6 and humanized E7011, allowing therapeutic targeting of Notch4 to be assessed in tumor models. Notch4 was expressed in tumor endothelial cells in multiple cancer models, and endothelial expression was associated with response to E7011/6-3-A6. Anti-Notch4 treatment significantly delayed tumor growth in mouse models of breast, skin, and lung cancers. Enhanced tumor inhibition occurred when anti-Notch4 treatment was used in combination with chemotherapeutics. Endothelial transcriptomic analysis of murine breast tumors treated with 6-3-A6 identified significant changes in pathways of vascular function but caused only modest change in canonical Notch signaling. Analysis of early and late treatment timepoints revealed significant differences in vessel area and perfusion in response to anti-Notch4 treatment. We conclude that targeting Notch4 improves tumor growth control through endothelial intrinsic mechanisms. SIGNIFICANCE: A first-in-class anti-Notch4 agent, E7011, demonstrates strong antitumor effects in murine tumor models including breast carcinoma. Endothelial Notch4 blockade reduces perfusion and vessel area.
Asunto(s)
Anticuerpos Neutralizantes , Neovascularización Patológica , Receptor Notch4 , Animales , Receptor Notch4/metabolismo , Ratones , Humanos , Neovascularización Patológica/tratamiento farmacológico , Neovascularización Patológica/patología , Neovascularización Patológica/metabolismo , Femenino , Anticuerpos Neutralizantes/farmacología , Anticuerpos Neutralizantes/uso terapéutico , Línea Celular Tumoral , Transducción de Señal/efectos de los fármacos , Ensayos Antitumor por Modelo de Xenoinjerto , Modelos Animales de Enfermedad , Células Endoteliales/efectos de los fármacos , Células Endoteliales/metabolismo , Proliferación Celular/efectos de los fármacos , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Neoplasias de la Mama/metabolismoRESUMEN
The causes of mitral valve operation for patients who underwent aortic valve replacements (AVR)are rheumatic heart diseases, nonrheumatic insufficiency, infective endocarditis, prosthetic valve dysfunction and so on. No specific recommendation for surgical strategy of mitral valve surgery for those patients has been described and surgical strategy should be selected to each patient. The patients with rheumatic heart disease had higher risk for reoperation as compared with those with nonrheumatic heart disease and majority of patients with AVR who need reoperation because of mitral valve diseases had history of open or closed mitral commissurotomy. Therefore, mitral valve repair should be limited to lesions in which excellent durability of the repair can be expected to prevent re-operation.
Asunto(s)
Válvula Aórtica/cirugía , Válvula Mitral/cirugía , Humanos , Insuficiencia de la Válvula Mitral/cirugía , Estenosis de la Válvula Mitral/cirugía , ReoperaciónRESUMEN
Lower body ischemia due to bending of a stented graft at the thoracic aorta was rare, particularly when it occurred in several days after surgery. We experienced this complication and performed the 3rd-time thoracic endovascular repair( TEVAR).A 49-year-old man with a chronic aortic dissection of Stanford type B underwent TEVER;however we failed to close the entry because of the tortuously bended distal arch of the aorta. Then it was decided the patient undergo a hybrid treatment with arch replacement and frozen elephant trunk. Seventeen days after the surgery, the blood pressure of the patient's lower limb was reduced rapidly and his renal function deteriorated. Bending of the stent was revealed by computed tomography( CT). The patient underwent the 3rd-time emergency TEVAR, and his symptoms improved.
Asunto(s)
Aorta Torácica/cirugía , Aneurisma de la Aorta Torácica/cirugía , Disección Aórtica/cirugía , Implantación de Prótesis Vascular/métodos , Isquemia/etiología , Extremidad Inferior/irrigación sanguínea , Complicaciones Posoperatorias/etiología , Stents/efectos adversos , Disección Aórtica/clasificación , Aneurisma de la Aorta Torácica/clasificación , Enfermedad Crónica , Urgencias Médicas , Humanos , Masculino , Persona de Mediana Edad , Reoperación , Resultado del TratamientoRESUMEN
Leaflet resection for posterior leaflet prolapse has been a standard repair procedure with good longterm durability. The aim of this study was to review our experience of mitral valve repair, in which resection of the anterior and/or posterior leaflets was performed. Between October 1991 and December 2010, 172 patients with degenerative mitral valve regurgitation underwent mitral valve reconstruction,including 98 patients with the posterior leaflet prolapse, 47 patients with the anterior leaflet prolapse, 17 patients with both leaflets and 10 patients with the commissure prolapse. Most patients in this study were supposed to be caused by fibroelastic deficiency and we have not experienced systolic anterior motion after repair. The mean follow-up period was 8.7 ± 5.5 years. The freedom from reoperation rates at 15 years in 88.7 ± 5.3% of the anterior leaflet procedure, 96.6 ± 2.5% of the posterior leaflet, and 100% of both leaflets. The results of resection of a diseased prolapsed mitral leaflet have been promising so far. However, reoperation was required in 7 patients (4.1%) and reoperation rate was higher in patients with anterior prolapse and longer follow-up will evaluate precisely be benefit.
Asunto(s)
Insuficiencia de la Válvula Mitral/cirugía , Válvula Mitral/cirugía , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
Hemolytic anemia due to a periprosthetic leak is a rare complication of valve replacement that has a poor prognosis. Herein are reported the details of two women (aged 62 and 74 years) who had undergone mitral valve surgery four times each; in both cases, a fifth operation was performed because of hemolytic anemia due to periprosthetic leak. An anterior repair of the leaks was performed instead of re-replacing the valve or standard repair, because the extensively calcified annulus led to sufficient space, and viable tissue was available to place direct sutures. Both patients made a rapid and uneventful recovery, with satisfactory short-term results; however, the long-term outcomes remain uncertain.
Asunto(s)
Calcinosis/complicaciones , Prótesis Valvulares Cardíacas/efectos adversos , Insuficiencia de la Válvula Mitral/cirugía , Estenosis de la Válvula Mitral/cirugía , Anciano , Anemia Hemolítica/etiología , Femenino , Implantación de Prótesis de Válvulas Cardíacas/efectos adversos , Implantación de Prótesis de Válvulas Cardíacas/instrumentación , Humanos , Persona de Mediana Edad , Insuficiencia de la Válvula Mitral/patología , Estenosis de la Válvula Mitral/patología , Reoperación , Cardiopatía Reumática/cirugíaRESUMEN
OBJECTIVE: Prosthetic annuloplasty rings play an important role in mitral valve repair. This clinical study was undertaken to evaluate the midterm results obtained with the Carpentier-Edwards rigid ring. METHODS: Between October 1991 and March 2005, 112 patients (mean age 53.0 years) underwent mitral valve repair with a Carpentier-Edwards rigid ring at our institution. Degenerative disease was the most frequent cause and a small number had other conditions such as endocarditis and rheumatic disease. Ten patients were in Carpentier's functional class Type I, 101 patients in Type II and 1 patient in Type III, based on valve pathology. Ischemic mitral regurgitation was excluded. The mean follow-up time was 5.3+/-3.6 years (range: 8 days to 12.3 years). All patients were completely followed by echocardiography. RESULTS: The rigid ring ranged from 26 to 36 mm in diameter and the most common size was 30 mm. Although the mitral orifice area was decreased after mitral valve repair in all patients, none of them required reoperation because of mitral stenosis or left ventricular outflow tract obstruction (systolic anterior motion). Reduction of both systolic and diastolic left ventricular volumes was observed postoperatively. Ejection fractions were preserved in all cases. The actuarial survival rate was 92.0+/-3.0% at 10 years and the reoperation-free rate at 10 years was 96.0+/-2.0%. CONCLUSION: The rigid ring has produced promising midterm results in terms of reoperation-free and survival rates.
Asunto(s)
Prótesis Valvulares Cardíacas , Válvula Mitral/cirugía , Adolescente , Adulto , Anciano , Ecocardiografía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Insuficiencia de la Válvula Mitral/cirugíaRESUMEN
PURPOSE: The aim of this study was to evaluate the long-term results of aortic valve replacement (AVR) with mechanical (M) and bioprosthetic (B) valves as recommended by the Japanese guidelines. METHODS: From April 1995 to March 2014, 366 adult patients underwent AVR. Of these, 127 (35%) patients received M and 239 patients (65%) received B valves. A retrospective analysis of the entire and the selected 124 patients aged 60 to 70 years was carried out. RESULTS: In patients aged 60 to 70 years, the 15-year survival and freedom from reoperation were 88% ± 7% and 100% for the M group and 34% ± 25% (p <0.001) and 73% ± 14% (p = 0.059) for the B group, respectively. Among propensity score matching of the subgroup, there was no significant difference in survival and freedom from reoperation. The rate of thromboembolism was higher in the M (M: 0.58% vs B: 0.35% patient per year, p <0.001) and the rate of hemorrhage was higher in the M group (M: 0.34% vs B: 0.12% patient per year, p <0.001). CONCLUSION: The current strategy of aortic valve choice based on the Japanese guidelines has provided excellent long-term results so far.
Asunto(s)
Envejecimiento , Válvula Aórtica/cirugía , Bioprótesis , Enfermedades de las Válvulas Cardíacas/cirugía , Implantación de Prótesis de Válvulas Cardíacas/instrumentación , Prótesis Valvulares Cardíacas , Diseño de Prótesis , Adulto , Factores de Edad , Anciano , Válvula Aórtica/fisiopatología , Supervivencia sin Enfermedad , Femenino , Enfermedades de las Válvulas Cardíacas/diagnóstico , Enfermedades de las Válvulas Cardíacas/fisiopatología , Implantación de Prótesis de Válvulas Cardíacas/efectos adversos , Humanos , Japón , Estimación de Kaplan-Meier , Modelos Logísticos , Longevidad , Masculino , Persona de Mediana Edad , Selección de Paciente , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/cirugía , Puntaje de Propensión , Falla de Prótesis , Reoperación , Estudios Retrospectivos , Factores de Riesgo , Factores de Tiempo , Resultado del TratamientoRESUMEN
Left ventricular pseudoaneurysm is a rare, but potentially fatal, condition that generally occurs as a complication of myocardial infarction, infective endocarditis, or cardiac surgery. Surgical repair is the treatment of first choice because of the marked risk of rupture, but deteriorated hemodynamics and complicated procedures to treat the pseudoaneurysm may lead to a high mortality rate. We report a 62-year-old woman with a large left ventricular pseudoaneurysm after mitral valve replacement for rheumatic mitral valve stenosis. Surgical repair was not performed due to the patient's refusal, but her pseudoaneurysm resolved spontaneously by 2 years after mitral valve replacement. Spontaneous obliteration of a large left ventricular pseudoaneurysm is very rare in a patient on warfarin therapy. This case suggests that a left ventricular pseudoaneurysm with a narrow neck may resolve spontaneously in rare settings.
Asunto(s)
Aneurisma Falso/etiología , Aneurisma Cardíaco/etiología , Implantación de Prótesis de Válvulas Cardíacas/efectos adversos , Estenosis de la Válvula Mitral/cirugía , Femenino , Rotura Cardíaca/etiología , Prolapso de las Válvulas Cardíacas , Ventrículos Cardíacos/cirugía , Humanos , Persona de Mediana Edad , Válvula Mitral/cirugía , Complicaciones Posoperatorias/etiología , Remisión EspontáneaRESUMEN
Postoperative left ventricular pseudoaneurysm is a rare, but potentially lethal, complication because of the high risk of rupture and high mortality of repair. We report a 64-year-old man with Marfan syndrome who underwent the reimplantation valve-sparing aortic root replacement complicated by a postoperative left ventricular pseudoaneurysm that required urgent repair. Careful handling of the aortic root is required to avoid a left ventricular pseudoaneurysm, particularly in patients with connective tissue disorder.
Asunto(s)
Aneurisma Falso/etiología , Aneurisma Cardíaco/etiología , Implantación de Prótesis de Válvulas Cardíacas/efectos adversos , Reimplantación/efectos adversos , Aneurisma Falso/cirugía , Insuficiencia de la Válvula Aórtica/cirugía , Enfermedades del Tejido Conjuntivo/complicaciones , Aneurisma Cardíaco/cirugía , Ventrículos Cardíacos , Humanos , Masculino , Síndrome de Marfan/complicaciones , Persona de Mediana Edad , ReoperaciónRESUMEN
Human induced pluripotent stem cells (iPSCs) can provide a promising source of midbrain dopaminergic (mDA) neurons for cell replacement therapy for Parkinson's disease (PD). However, iPSC-derived donor cells inevitably contain tumorigenic or inappropriate cells. To eliminate these unwanted cells, cell sorting using antibodies for specific markers such as CORIN or ALCAM has been developed, but neither marker is specific for ventral midbrain. Here we employ a double selection strategy for cells expressing both CORIN and LMX1A::GFP, and report a cell surface marker to enrich mDA progenitors, LRTM1. When transplanted into 6-OHDA-lesioned rats, human iPSC-derived LRTM1+ cells survive and differentiate into mDA neurons in vivo, resulting in a significant improvement in motor behaviour without tumour formation. In addition, there was marked survival of mDA neurons following transplantation of LRTM1+ cells into the brain of an MPTP-treated monkey. Thus, LRTM1 may provide a tool for efficient and safe cell therapy for PD patients.
Asunto(s)
Neuronas Dopaminérgicas/metabolismo , Células Madre Embrionarias Humanas/metabolismo , Células Madre Pluripotentes Inducidas/metabolismo , Proteínas/metabolismo , Animales , Diferenciación Celular/genética , Separación Celular/métodos , Células Cultivadas , Neuronas Dopaminérgicas/citología , Femenino , Humanos , Macaca fascicularis , Masculino , Mesencéfalo/citología , Mesencéfalo/metabolismo , Ratones Endogámicos C57BL , Enfermedad de Parkinson/genética , Enfermedad de Parkinson/metabolismo , Enfermedad de Parkinson/terapia , Proteínas/genética , Ratas Sprague-Dawley , Serina Endopeptidasas/genética , Serina Endopeptidasas/metabolismo , Trasplante de Células Madre/métodos , Trasplante HeterólogoRESUMEN
OBJECTIVE: Surgical strategies for patients who have a small aortic annulus associated with a small mitral annulus remain controversial. The objective of this study was to assess the validity of the Manouguian procedure for double valve replacement with patch enlargement of the annuli. METHODS: We reviewed 57 consecutive patients who underwent double valve replacement for combined aortic and mitral disease between September 1991 and October 2000. Thirty patients underwent the Manouguian procedure with patch enlargement of the aortic and mitral annuli, and the other 27 patients had standard double valve replacement. The Manouguian procedure was selected for a small aortic annulus of less than 21 mm in diameter. The patients were followed for a median of 7.5 years. Results of echocardiography and the dobutamine stress test were compared postoperatively. RESULTS: Double valve replacement with the Manouguian procedure did not increase the early or midterm mortality because the survival (including operative death) at 8 years was 83% in the Manouguian group and 84% in the double valve replacement group (P = .82). The event-free rate at 8 years was 79% in the Manouguian group and 84% in the double valve replacement group (P = .6). The prostheses implanted at the aortic and mitral positions were smaller in the Manouguian group, even after annular enlargement. However, the transprosthetic gradient across the aortic valve evaluated by means of dobutamine stress echocardiography did not differ between the 2 groups, possibly because of a smaller body surface area in the Manouguian group. CONCLUSIONS: The Manouguian patch enlargement procedure is useful during double valve replacement when associated with the problem of small-valve annuli.
Asunto(s)
Válvula Aórtica/cirugía , Implantación de Prótesis de Válvulas Cardíacas/métodos , Válvula Mitral/cirugía , Adulto , Anciano , Estenosis de la Válvula Aórtica/cirugía , Superficie Corporal , Puente Cardiopulmonar , Causas de Muerte , Ecocardiografía , Ecocardiografía de Estrés , Femenino , Estudios de Seguimiento , Prótesis Valvulares Cardíacas , Humanos , Masculino , Persona de Mediana Edad , Pericardio/trasplante , Estudios Retrospectivos , Tasa de Supervivencia , Presión Ventricular/fisiologíaRESUMEN
Postmitotic neural precursors are generated in the ventricular zone (VZ) of the developing neural tube and immediately migrate to the mantle layer (ML) where they differentiate into mature neurons. Although the regulation of neuronal differentiation and migration has extensively been studied, the behavior of the early postmitotic precursors migrating toward the ML is largely unknown. In this study, we have identified Neph3 as a specific marker for early postmitotic neural precursors in the VZ of the developing spinal cord. Analysis of Neph3 localization by immunofluorescence and immunoelectron microscopy revealed that early neural precursors in the VZ possessed not only pia-connected processes but also ones that reached the ventricle. This apical extension of processes was confirmed by analyzing another early postmitotic marker, Dll1 mRNA, which was actively transported toward the ventricle and accumulated at the termini of the processes. Furthermore, adherens junctions (AJs) were formed around the apical end of processes extending from Neph3- and Dll1 mRNA-positive postmitotic precursors. Taken together, these observations suggest that migrating early postmitotic neural precursors in the VZ of the developing spinal cord form a neuroepithelial cell-like bipolar morphology and communicate with their neighboring cells through AJs.
Asunto(s)
Uniones Adherentes/fisiología , Movimiento Celular/fisiología , Ventrículos Cerebrales/citología , Neuronas/fisiología , Médula Espinal/citología , Células Madre/fisiología , Uniones Adherentes/ultraestructura , Animales , Northern Blotting , Cadherinas/metabolismo , Agregación Celular/fisiología , Células Cultivadas , Ventrículos Cerebrales/embriología , Ventrículos Cerebrales/ultraestructura , Clonación Molecular/métodos , Proteínas de Unión al ADN/metabolismo , Proteínas de Drosophila/metabolismo , Embrión de Mamíferos , Regulación del Desarrollo de la Expresión Génica/fisiología , Vectores Genéticos/fisiología , Proteínas de Homeodominio/metabolismo , Inmunohistoquímica/métodos , Hibridación in Situ/métodos , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Ratones , Microscopía Inmunoelectrónica , Proteínas de Neurofilamentos/metabolismo , Neuronas/ultraestructura , Fosfoproteínas/metabolismo , ARN Mensajero/biosíntesis , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/métodos , Médula Espinal/embriología , Tubulina (Proteína)/metabolismo , Proteína de la Zonula Occludens-1RESUMEN
OBJECTIVE: The objective of the present study was to compare long-term results of single aortic valve replacement (AVR) with mechanical (St. Jude Medical valves: standard) and biologic (the Carpentier-Edwards pericardial) prostheses. METHOD: Between 1995 and 2002, 95 patients who underwent single AVR with mechanical (n= 46) or biologic (n= 49) prostheses were enrolled in this study. The mean age at the operation was 54.0 +/- 9.6 years (range: 20 to 69 years) with the mechanical and 68.8 +/- 7.1 years (range: 44 to 85 years) with the biologic prosthesis. RESULTS: The 9-year actuarial survival rate, which was calculated by taking perioperative mortality into account, was 90.3 +/- 4.6% for patients with mechanical valves and 87.6 +/- 4.8% for patients with bioprostheses, with no difference between the two groups (p=0.342). The 9-year freedom rate from thromboembolism, reoperation, endocarditis was 94.8 +/- 3.6%, 100% and 97.8 +/- 2.2% for patients with mechanical valves and 98.0 +/- 2.0%, 97.5 +/- 3.4% and 95.0 +/- 3.4% for those with bioprostheses, respectively. After 9 years, freedom from cardiac death averaged 97.8% in the group with mechanical valves compared with 95.3% in those with bioprostheses (p=0.541). CONCLUSION: We conclude that the mid-term durability of the Carpentier-Edwards pericardial valve in the aortic position for the elderly is excellent. Nevertheless, the risk of tissue valve reoperation progressively increases with time, and a longer follow-up may be necessary to provide its value compared with the mechanical valves in a country like Japan with a high life expectancy.
Asunto(s)
Válvula Aórtica/cirugía , Bioprótesis , Implantación de Prótesis de Válvulas Cardíacas , Prótesis Valvulares Cardíacas , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Bioprótesis/efectos adversos , Femenino , Estudios de Seguimiento , Prótesis Valvulares Cardíacas/efectos adversos , Implantación de Prótesis de Válvulas Cardíacas/efectos adversos , Implantación de Prótesis de Válvulas Cardíacas/mortalidad , Humanos , Japón , Masculino , Persona de Mediana Edad , Falla de Prótesis , Reoperación/estadística & datos numéricos , Estudios Retrospectivos , Tasa de Supervivencia , Tromboembolia/epidemiología , Tromboembolia/etiología , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: Nonspecific inflammation is the primary cause of early islet graft loss. We have shown in mice that pravastatin, a 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor, prevents primary nonfunction of islet isografts by reducing inflammatory reactions at the graft site. This study was designed to test the effectiveness of this agent in a large animal model, dogs, by transplanting autologous islets. METHODS: After total pancreatectomy, islets were isolated by using a two-step digestion method, followed by discontinuous gradient centrifugation on EuroFicoll. A known number of freshly isolated islets were immediately transplanted back into the same dog via the portal vein. RESULTS: First, we determined the minimal islet number required to reverse diabetes by transplanting 3,000-10,000 IEQ/kg with no additional treatment. The number was found to be 4,000 IEQ/kg, and islets less than 4,000 IEQ/kg consistently failed. To test the effect of pravastatin, 3,000 IEQ/kg were transplanted into dogs that either received no further treatment or were treated daily with 20 mg/kg of pravastatin from days -2 to 14. Without pravastatin, this number of islets lowered blood glucose only transiently, and all four of these dogs became hyperglycemic within 1 week. In contrast, four of the five dogs treated with pravastatin became normoglycemic (<150 mg/dL) and maintained this level during the observation period of 12 weeks (P<0.05). Postprandial plasma glucose and insulin levels returned to normal, and K values of intravenous glucose tolerance tests were significantly higher in pravastatin-treated dogs than in controls (P<0.04 at week 2 and P<0.01 at week 4). CONCLUSION: Peritransplant pravastatin treatment reduced the number of autologous islets required to reverse diabetes in totally pancreatectomized dogs. These results suggest that pravastatin may also facilitate better islet graft survival and function in clinical transplantation.
Asunto(s)
Supervivencia de Injerto/fisiología , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Trasplante de Islotes Pancreáticos/fisiología , Pravastatina/uso terapéutico , Animales , Glucemia/metabolismo , Separación Celular/métodos , Perros , Ayuno , Femenino , Supervivencia de Injerto/efectos de los fármacos , Insulina/sangre , Islotes Pancreáticos/citología , Masculino , Pancreatectomía , Periodo Posprandial , Trasplante Autólogo , Trasplante IsogénicoRESUMEN
Postoperative myocardial global dysfunction causes mortality and morbidity in cyanotic congenital defects. This study investigates whether leukocyte depletion during coronary perfusion following reoxygenation can maintain endothelial and myocyte function, or less oxidant damage in a porcine neonatal model. After 30 minutes hypoxemia, 13 piglets underwent 60 minutes reoxygenation. The aorta was clamped and coronary reperfusion was either with normal blood (N=6), or leukocyte free blood by an inline filter (N=7). Cardiac function and endothelial response were assessed before and after cardiopulmonary bypass (CPB). Contractile recovery was improved by leukocyte depletion. Additionally, the antioxidant reserve capacity reserved more (534 36 versus 772 91; p<0.05) than reoxygenation without a leukocyte-depleting filter. Leukocyte depletion returned more extreme relaxation to acetylcholine (71.8 20.4% versus 41.2 9.8%; p<0.05), but did not change the endothelium-independent relaxation to sodium nitroprusside in either group. Activated leukocytes release oxygen free radicals that play a role in deterioration of the endothelial/myocardial function after reoxygenation and this deterioration in cyanotic heart diseases may be avoided by the use of the leukocyte-depleting filter.
Asunto(s)
Endotelio Vascular/fisiopatología , Leucocitos , Daño por Reperfusión Miocárdica/fisiopatología , Función Ventricular , Animales , Animales Recién Nacidos , Puente Cardiopulmonar , Constricción , Endotelio Vascular/citología , Filtración , Radicales Libres/sangre , Leucocitos/fisiología , Peroxidación de Lípido , Modelos AnimalesRESUMEN
OBJECTIVE: To investigate the effects of hemorrhagic shock and intra-abdominal hypertension (IAH) on inflammatory responses of peripheral circulating neutrophils such as intracellular cytokine production, phagocytic capacity and expression of nuclear factor (NF)- kappaB. METHODS: Twenty-four rabbits were divided equally into 4 groups including a hemorrhagic shock (HS) group complicated by abdominal compartment syndrome (ACS) (Group A), a HS group (Group B), a ACS group (Group C) and a normal control group (Group D). Intracellular interleukin (IL)-8 production in the peripheral neutrophils were measured in the rabbits by flow cytometry, phagocytic function of the neutrophils evaluated by a chemiluminescence method and the NF-kappaB expression detected by immunocytochemistry before, immediately and 4 h after the traumatization. RESULTS: Four hours after the trauma, decreased intracellular IL-8 production and impaired phagocytic function of the peripheral neutrophils were observed in Group A along with suppressed NF-kappaB expression. But in Group B and Group C, the intracellular IL-8 production, phagocytic function and expression of NF-kappaB returned to the normal levels 4 hours after the trauma following the early-stage changes. In Group D, no significant changes occurred during the observation. CONCLUSIONS: Responsiveness and function of the neutrophils to the stimuli by endotoxin are suppressed by the sequential second-hit of IAH after hemorrhagic shock, which may contribute to the occurrence of sepsis in ACS.