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1.
Am J Transplant ; 15(6): 1692-700, 2015 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-25645705

RESUMEN

Here we introduce a novel method of transplanting human fetal kidneys into adult rats. To overcome the technical challenges of fetal-to-adult organ transplantation, we devised an arterial flow regulator (AFR), consisting of a volume adjustable saline-filled cuff, which enables low-pressure human fetal kidneys to be transplanted into high-pressure adult rat hosts. By incrementally withdrawing saline from the AFR over time, blood flow entering the human fetal kidney was gradually increased until full blood flow was restored 30 days after transplantation. Human fetal kidneys were shown to dramatically increase in size and function. Moreover, rats which had all native renal mass removed 30 days after successful transplantation of the human fetal kidney were shown to have a mean survival time of 122 days compared to 3 days for control rats that underwent bilateral nephrectomy without a prior human fetal kidney transplant. These in vivo human fetal kidney models may serve as powerful platforms for drug testing and discovery.


Asunto(s)
Equipos y Suministros , Bombas de Infusión , Trasplante de Riñón , Riñón/embriología , Riñón/crecimiento & desarrollo , Trasplante Heterólogo , Animales , Proliferación Celular/fisiología , Proteínas de Unión al ADN/deficiencia , Proteínas de Unión al ADN/genética , Técnicas de Inactivación de Genes , Supervivencia de Injerto/fisiología , Humanos , Riñón/irrigación sanguínea , Corteza Renal/citología , Modelos Animales , Nefrectomía , Ratas , Ratas Mutantes , Flujo Sanguíneo Regional/fisiología
2.
Pediatr Transplant ; 18(5): 446-52, 2014 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-24930482

RESUMEN

Management of pediatric renal transplant patients involves multifactorial monitoring modalities to ensure allograft survival and prevent opportunistic infection secondary to immunosuppression. An ICFA, which utilizes CD4 T-cell production of ATP to assess immune system status, has been used to monitor transplant recipients and predict susceptibility of patients to rejection or infection. However, the validity of this assay to reflect immune status remains unanswered. In a two-yr retrospective study that included 31 pediatric renal transplant recipients, 42 patient blood samples were analyzed for immune cell function levels, creatinine, WBC (white blood cell) count, immunosuppressive drug levels, and viremia, concurrent with renal biopsy. T-cell ATP production as assessed by ICFA levels did not correlate with allograft rejection or with the presence or absence of viremia. ICFA levels did not correlate with serum creatinine or immunosuppressive drug levels, but did correlate with WBC count. The ICFA is unreliable in its ability to reflect immune system status in pediatric renal transplantation. Further investigation is necessary to develop methods that will accurately predict susceptibility of pediatric renal transplant recipients to allograft rejection and infection.


Asunto(s)
Biopsia , Rechazo de Injerto/diagnóstico , Trasplante de Riñón , Insuficiencia Renal/cirugía , Adenosina Trifosfato/metabolismo , Adolescente , Aloinjertos , Linfocitos T CD4-Positivos/inmunología , Niño , Preescolar , Femenino , Supervivencia de Injerto , Humanos , Terapia de Inmunosupresión , Inmunosupresores/efectos adversos , Lactante , Riñón/inmunología , Recuento de Leucocitos , Masculino , Infecciones Oportunistas/diagnóstico , Insuficiencia Renal/complicaciones , Insuficiencia Renal/inmunología , Estudios Retrospectivos , Viremia/sangre , Adulto Joven
3.
Transpl Infect Dis ; 13(3): 312-7, 2011 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-21235711

RESUMEN

A patient developed West Nile virus (WNV) encephalitis 2 weeks after receiving a liver transplant and recovered fully, following treatment with intravenous immunoglobulin (IVIg). Laboratory testing documented transmission from the organ donor. Clinicians should be suspicious for organ-transmitted WNV in any post-transplant patient who develops fever and neurological symptoms. We review previous cases of organ-transmitted WNV, the use of IVIg for WNV encephalitis, and the issue of organ donor screening.


Asunto(s)
Inmunoglobulinas Intravenosas/uso terapéutico , Trasplante de Hígado/efectos adversos , Donantes de Tejidos , Fiebre del Nilo Occidental/terapia , Fiebre del Nilo Occidental/transmisión , Virus del Nilo Occidental , Humanos , Hígado/virología , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , Fiebre del Nilo Occidental/fisiopatología , Fiebre del Nilo Occidental/virología
4.
Am J Transplant ; 9(6): 1362-72, 2009 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-19459814

RESUMEN

Despite early promising patient and graft outcomes with steroid-free (SF) immunosuppression in pediatric kidney transplant recipients, data on long-term safety and efficacy results are lacking. We present our single-center experience with 129 consecutive pediatric kidney transplant recipients on SF immunosuppression, with a mean follow-up of 5 years. Outcomes are compared against a matched cohort of 57 concurrent recipients treated with steroid-based (SB) immunosuppression. In the SF group, 87% of kidney recipients with functioning grafts remain corticosteroid-free. Actual intent-to-treat SF (ITT-SF) and still-on-protocol SF patient survivals are 96% and 96%, respectively, actual graft survivals for both groups are 93% and 96%, respectively and actual death-censored graft survivals for both groups are 97% and 99%, respectively. Unprecedented catch-up growth is observed in SF recipients below 12 years of age. Continued low rates of acute rejection, posttransplant diabetes mellitus (PTDM), hypertension and hyperlipidemia are seen in SF patients, with sustained benefits for graft function. In conclusion, extended enrollment and longer experience with SF immunosuppression for renal transplantation in low-risk children confirms protocol safety, continued benefits for growth and graft function, low acute rejection rates and reduced cardiovascular morbidity.


Asunto(s)
Corticoesteroides/uso terapéutico , Terapia de Inmunosupresión/métodos , Trasplante de Riñón , Adolescente , Niño , Preescolar , Femenino , Rechazo de Injerto/inmunología , Supervivencia de Injerto/inmunología , Humanos , Hipercolesterolemia/etiología , Hipertensión/etiología , Hipertrigliceridemia/etiología , Inmunosupresores/inmunología , Estimación de Kaplan-Meier , Trasplante de Riñón/efectos adversos , Trasplante de Riñón/inmunología , Trasplante de Riñón/mortalidad , Masculino
5.
Pediatr Transplant ; 12(6): 701-7, 2008 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-18179640

RESUMEN

With the increasing adoption of steroid-sparing immunosuppression protocols in renal transplantation, it is important to evaluate any adverse effects of steroid avoidance on graft function. Early graft function, measured by CrCl was retrospectively studied in 158 consecutive pediatric renal transplant recipients from 1996 to 2005, receiving either steroid-free or steroid-based immunosuppression. Patients receiving steroid-free immunosuppression vs. steroid-based immunosuppression had no difference change in CrCl (DeltaCrCl) in the first week post-transplantation (p = 0.12). When stratified by corticosteroid usage, patients with higher tacrolimus trough levels (> or =14 ng/mL) had slower graft function recovery in the first week post-transplantation than those with lower tacrolimus trough levels (p = 0.008) in the steroid-free group only. Despite initial slower graft function recovery in this subgroup, there was no negative impact on graft function in the steroid-free group; in fact steroid-free patients trended towards better CrCl at six months (p = 0.047) and 12 months (p < 0.001) post-transplant than the steroid-based group. With the improved immunological outcomes with steroid avoidance, close surveillance should be performed of tacrolimus levels to avoid levels >14 ng/mL. In patients with slow recovery of early graft function, short-term perioperative steroids may be considered.


Asunto(s)
Inmunosupresores/uso terapéutico , Trasplante de Riñón/métodos , Pediatría/métodos , Esteroides/química , Tacrolimus/uso terapéutico , Corticoesteroides/farmacología , Antiinflamatorios/farmacología , Niño , Femenino , Supervivencia de Injerto , Humanos , Masculino , Estudios Retrospectivos , Esteroides/metabolismo , Factores de Tiempo , Resultado del Tratamiento
6.
Semin Oncol ; 18(1): 24-8, 1991 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-1992520

RESUMEN

Two children with biopsy-proven LCH underwent successful hepatic transplantation for end-stage liver disease. These patients were thought not to have active LCH disease at the time of transplantation, although one had developed a new osteolytic lesion a few months before the operation and the other had suspicious osteolytic lesions at the time of transplantation. The histologic examination of the excised liver showed features consistent with primary sclerosing cholangitis. The two patients had an excellent recovery with no evidence of progression of LCH or recurrence of the underlying disease in the hepatic allograft at 1 and 3 years after organ transplantation.


Asunto(s)
Histiocitosis de Células de Langerhans/cirugía , Trasplante de Hígado , Adolescente , Preescolar , Femenino , Histiocitosis de Células de Langerhans/complicaciones , Humanos
7.
Transplantation ; 65(1): 77-82, 1998 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-9448148

RESUMEN

BACKGROUND: To assess the feasibility and outcome of a piggyback technique without caval occlusion or veno-venous bypass (VB), we retrospectively reviewed 131 consecutive adult orthotopic liver transplantation (OLT) performed in 129 patients between May 1993 and February 1995. Six were second transplants, and six were combined liver-kidney transplants. The piggyback technique was attempted in all cases. METHODS: We were able to perform the piggyback technique in 98 OLTs (75%). The remaining 33 OLTs (25%) were converted to the standard technique; of these, 20 (15%) required VB. The reasons for conversion to the standard technique were: anatomical (22 transplants), severe portal hypertension requiring VB (8 transplants), tumor (1 transplant), and other reasons (2 transplants). Six retransplantations were performed (four piggyback, two standard). RESULTS: There was no significant difference in age, United Network for Organ Sharing status, Child's classification, and diagnosis between the patients in whom piggyback was possible or not. The actuarial patient and graft survival at 1 year were similar between the piggyback group and the group of patients converted to standard technique (87/85% vs. 86/86%, respectively). No death was related to either technique. With piggyback, the average operative time was 8.6+/-1.9 hr, median amount of blood transfused intraoperatively was 2 U (33% did not require transfusion), and median intensive care unit and hospital stays were 3 and 11 days, respectively. With the piggyback technique, the mean preoperative and maximum postoperative serum creatinine levels were 1.4+/-1.0 and 1.8+/-1.5 mg/dl. CONCLUSION: The piggyback technique without caval occlusion is possible in the majority of patients. It is safe and has reduced the use of VB to 15% of our adult OLTs. The piggyback technique avoids retrocaval dissection, facilitates retransplantation, and is associated with a short anhepatic phase, low blood product usage, and short intensive care unit stay.


Asunto(s)
Trasplante de Hígado/métodos , Vena Cava Inferior/cirugía , Adolescente , Adulto , Anastomosis Quirúrgica/métodos , Femenino , Venas Hepáticas/cirugía , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Técnicas de Sutura , Resultado del Tratamiento
8.
Transplantation ; 60(7): 757-60, 1995 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-7570989

RESUMEN

The present study examined 144 pediatric liver transplants to determine the impact of ABO matching on liver allograft outcome. Pediatric transplants were divided into 3 groups: ABO identical (ABO-Id; n = 108), ABO-compatible nonidentical (ABO-Comp; n = 22), and ABO incompatible (ABO-Inc; n = 14). A higher proportion of United Network for Organ Sharing status 4 recipients in the ABO-Comp group (50% vs. 22% and 36% for ABO-Id and ABO-Inc, P < 0.05) and less time spent on the waiting list for ABO-Inc recipients (46 +/- 12 vs. 87 +/- 11 and 61 +/- 20 days for ABO-Id and ABO-Comp, P < 0.01) were noted. OKT3 induction therapy was greater in ABO-Inc grafts (57% vs. 19% and 14% for ABO-Id and ABO-Comp, P < 0.05), as was incidence of acute cellular rejection (79% vs. 59% and 41% for ABO-Id and ABO-Comp, P = 0.08). One- and 3-year patient survival rates were 87% and 83% in the ABO-Id group, 95% and 88% in the ABO-Comp group, and 79% and 79% in the ABO-Inc group (P = NS). One- and 3-year graft survival rates were 83% and 78% in the ABO-Id group, 87% and 80% in the ABO-Comp group, and 71% and 71% in the ABO-Inc group (P = NS). ABO-Inc transplantations can be performed successfully in pediatric recipients and warrant a reassessment of the utilization of ABO-Inc livers.


Asunto(s)
Sistema del Grupo Sanguíneo ABO , Incompatibilidad de Grupos Sanguíneos/diagnóstico , Trasplante de Hígado/inmunología , Preescolar , Estudios de Seguimiento , Supervivencia de Injerto/inmunología , Humanos , Terapia de Inmunosupresión/métodos , Lactante , Estudios Retrospectivos , Resultado del Tratamiento
9.
Transplantation ; 57(8): 1169-73, 1994 Apr 27.
Artículo en Inglés | MEDLINE | ID: mdl-7513911

RESUMEN

The safety and efficacy of conversion to FK506 after failing immunosuppression with cyclosporine was prospectively evaluated in 31 pediatric liver transplant recipients between April 1991 and March 1993. The patients, who ranged in age from 40 days to 14 years, accounted for 28 primary transplantations and 3 retransplantations. The initial immunosuppression regimen consisted of cyclosporine in combination with prednisone. The indications for conversion were acute or chronic rejection refractory to OKT3, Minnesota antilymphocyte globulin, or steroids (13 patients); hypertension (8 patients); inability to reach a therapeutic level of cyclosporine (6 patients); hirsutism (3 patients); and growth retardation (1 patient). After an average follow-up of 10 months (range, 2 to 25 months), 27 (87%) of the patients are alive and have functioning grafts. Of the 13 patients who were converted for refractory rejection, 9 are alive. Six of these 9 patients experienced a complete biochemical reversal of the rejection process within 3 months of conversion; 2 had a partial response to conversion, and 1 patient failed but underwent successful retransplantation. Three of the 4 patients who died did so without showing any improvement. The remaining 18 patients who were converted for various other reasons are alive and have functioning grafts. Of the 8 patients who developed hypertension on cyclosporine and prednisone, 6 experienced a resolution of this problem within 3 months of conversion. Three of the 18 children who underwent rescue therapy for reasons other than refractory rejection experienced rejection episodes after conversion to FK506. Two of these 3 children achieved resolution with either steroid therapy or an increased dosage of FK506, while the third child developed chronic rejection. The side effects of FK506 were generally minor and resolved by lowering the dose. Lymphoproliferative disease developed in 2 patients (6%). The present study suggests that FK506 is a relatively safe and effective rescue therapy for pediatric liver transplant recipients who have failed immunosuppression with cyclosporine. Longer follow-up is needed to assess the effect of FK506 on growth.


Asunto(s)
Rechazo de Injerto/prevención & control , Trasplante de Hígado/inmunología , Tacrolimus/uso terapéutico , Adolescente , Niño , Preescolar , Ciclosporina/uso terapéutico , Evaluación de Medicamentos , Femenino , Humanos , Hipertensión/tratamiento farmacológico , Lactante , Trasplante de Hígado/estadística & datos numéricos , Masculino , Periodo Posoperatorio , Estudios Prospectivos , Tacrolimus/efectos adversos , Tacrolimus/normas
10.
Transplantation ; 62(1): 130-2, 1996 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-8693530

RESUMEN

Children who experience acute liver failure following liver transplantation will have multiple organ failure and a high rate of mortality unless emergency retransplantation can be performed. Transplant hepatectomy with portocaval shunting has been described as a bridge to transplantation in the most severe cases, as well as in patients with fulminant hepatic failure at high risk for mortality who have not undergone liver transplantation. Patients with multiple organ failure who have undergone hepatectomy require renal replacement therapy. Continuous hemofiltration may be used in patients with fulminant hepatic failure to facilitate fluid removal and circulatory and metabolic balance. We used continuous venovenous hemofiltration with dialysis following hepatectomy with portocaval shunting in a patient who remained anhepatic for 66 hr in order to achieve circulatory and metabolic homeostasis as well as stable neurologic function prior to successful retransplantation.


Asunto(s)
Trasplante de Hígado/métodos , Preescolar , Diálisis , Hemofiltración , Hepatectomía , Humanos , Fallo Hepático Agudo/cirugía , Masculino , Derivación Portocava Quirúrgica
11.
Transplantation ; 64(2): 242-8, 1997 Jul 27.
Artículo en Inglés | MEDLINE | ID: mdl-9256181

RESUMEN

The technical and medical management of small infants requiring orthotopic liver transplantation remains a challenge. The present study examined 117 orthotopic liver transplantations performed in 101 infants from <1 to 23 months of age between March 1988 and February 1995 to determine factors that influence patient and graft outcome. Factors analyzed included etiology of liver disease, recipient and donor age and weight, United Network for Organ Sharing (UNOS) status, retransplantation, ABO-compatibility, full-size (FS) versus reduced-size grafts, vascular thrombosis (VT), including hepatic artery and portal vein (PVT), and the presence of lymphoproliferative disease (LPD). UNOS status 1, fulminant hepatic failure, and the development of Epstein-Barr virus-associated LPD were each associated with 10-20% lower patient and graft survival rates. Of 101 infants, 11 (11%) developed LPD with an associated 36% mortality. VT occurred in 10 (9 hepatic artery and 1 portal vein) of 117 orthotopic liver transplantations (9%), all less than 1 year of age, and was associated with significantly poorer 1-year (50% vs. 85% no VT, P<0.01) and 5-year patient survival rates (50% vs. 83% no VT, P<0.01). One-year graft survival rates for FS grafts in recipients <12 months versus 12-23 months were 67% vs. 94% (P<0.01); the patient survival rate was also significantly lower in FS graft recipients <12 months (76% vs. 100%, P<0.05). Recipients <5 months of age had the worst survival rates: 1-year and 5-year patient survival rates were 65% and 46% for recipients 0-4 months (n=17) versus 82% and 82% for recipients 5-11 months (n=56), and 93% and 93% for recipients age 12-23 months (n=28; P<0.05). In summary, factors associated with reduced survival rates include recipient age <5 months, recipient age <12 months who received FS grafts, development of VT and donor weight <6 kg. There was a trend for UNOS status 1, fulminant hepatic failure, and presence of LPD to be associated with reduced survival rates.


Asunto(s)
Trasplante de Hígado/mortalidad , Envejecimiento/fisiología , Suero Antilinfocítico/uso terapéutico , Causas de Muerte , Ciclosporina/uso terapéutico , Rechazo de Injerto/etiología , Rechazo de Injerto/prevención & control , Supervivencia de Injerto/fisiología , Humanos , Lactante , Trasplante de Hígado/efectos adversos , Trasplante de Hígado/inmunología , Trastornos Linfoproliferativos/etiología , Trastornos Linfoproliferativos/mortalidad , Vena Porta , Estudios Retrospectivos , Tasa de Supervivencia , Trombosis/etiología
12.
Transplantation ; 58(4): 447-50, 1994 Aug 27.
Artículo en Inglés | MEDLINE | ID: mdl-8073514

RESUMEN

Neurological complications are important contributors to morbidity and mortality after liver transplantation. We reviewed 391 patients who underwent 427 consecutive orthotopic liver transplantations to analyze the clinical features of patients who experienced one or more neurological complication (74 patients [19%]) and to compare postoperative neurological problems in adults versus children. Neurological complications were more frequent in adults (64 of 273 patients [23%]) than children (10 of 118 patients [8%]) (P < 0.01). The most common neurological complication was encephalopathy (59%), which ranged widely in severity and occurred with similar frequency in adults and children. Other common neurological complications were seizures (12 patients), brachial plexus and peripheral nerve injuries (16 patients, 15 of whom were adults), stroke (5 patients), and central nervous system infections (5 patients). In 27 patients, drug toxicity was the primary cause of neurological complications, all of which reversed with dosage reduction or discontinuation of drug. Cyclosporine and FK506, primarily during intravenous administration for induction of immunosuppression, accounted for 25 of 27 drug-induced neurological complications, which included encephalopathy, seizures, severe tremor, and severe headache. Despite a higher rate of neurological complications in adults, those in children were more severe and associated with a higher mortality rate. When compared with liver transplant recipients without neurological complications, patients with neurological complications had a higher posttransplant mortality rate (14% vs. 5% for adults, and 50% vs. 7% for children). In conclusion, neurological complications after liver transplantation are more common in adults, more severe and associated with a higher mortality rate in children, and associated with a higher mortality rate in both children and adults when compared with transplant recipients without neurological complications.


Asunto(s)
Trasplante de Hígado/efectos adversos , Enfermedades del Sistema Nervioso/etiología , Adulto , Encefalopatías/etiología , Preescolar , Supervivencia de Injerto/efectos de los fármacos , Humanos , Inmunosupresores/administración & dosificación , Inmunosupresores/efectos adversos , Incidencia , Enfermedades del Sistema Nervioso Periférico/etiología , Estudios Retrospectivos
13.
Transplantation ; 66(7): 851-6, 1998 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-9798693

RESUMEN

BACKGROUND: Epstein-Barr virus (EBV) infection is common after liver transplantation in children and is associated with the risk of posttransplant lymphoproliferative disorders (PTLD). METHODS: This retrospective study examined the frequency of gastrointestinal (GI) symptoms and the risk of PTLD in pediatric liver recipients who developed symptomatic EBV infection. We reviewed 172 children who received orthotopic liver transplants between March 1988 to December 1994. Twenty-two cases were retransplants. The mean age at transplantation was 3.7 years (range, 0.1-17 years). The immunosuppressive regimens consisted of induction therapy with Minnesota antilymphocyte globulin/antithymocyte globulin/OKT3 in most cases and maintenance therapy with prednisone and either cyclosporine or tacrolimus (FK506). RESULTS: After 1 year of minimum follow-up, 54 of 172 patients had symptomatic EBV infections (confirmed by serology, histology, or whole blood polymerase chain reaction. At the time of infection, 38.5% (21/54) had either diarrhea or GI bleeding or both. PTLD developed in 11 patients (6.4%). The incidence of PTLD was 42.9% (9/21) when GI bleeding or diarrhea was associated with EBV infections, compared with 6.1% (2/33) when EBV infection was not associated with GI symptoms. Seven of 10 (70%) patients with GI bleeding and 2 of 11 (18.2%) with diarrhea developed PTLD. Of seven patients examined by endoscopy for GI bleeding, two had biopsy-proven PTLD of the GI tract, whereas one of two patients examined by endoscopy for diarrhea had biopsy-proven PTLD. DISCUSSION: In summary, a high incidence of PTLD was found in patients who developed GI bleeding or diarrhea associated with EBV infection after pediatric liver transplantation. In these patients, endoscopy and biopsy may lead to early diagnosis of PTLD.


Asunto(s)
Infecciones por Virus de Epstein-Barr/etiología , Enfermedades Gastrointestinales/virología , Trasplante de Hígado , Trastornos Linfoproliferativos/etiología , Complicaciones Posoperatorias , Adolescente , Niño , Preescolar , Infecciones por Virus de Epstein-Barr/complicaciones , Enfermedades Gastrointestinales/epidemiología , Enfermedades Gastrointestinales/patología , Humanos , Incidencia , Lactante , Trastornos Linfoproliferativos/epidemiología , Estudios Retrospectivos , Factores de Riesgo , Factores de Tiempo
14.
Transplantation ; 61(8): 1188-92, 1996 Apr 27.
Artículo en Inglés | MEDLINE | ID: mdl-8610416

RESUMEN

We have adopted the use of an oral tacrolimus induction protocol in pediatric liver transplantation since the commercial release of tacrolimus in 1994. In this study we analyzed the efficacy of oral tacrolimus induction therapy in 17 consecutive transplants (15 patients) performed between 6/94 and 2/95 and 4 additional patients who were retransplanted between 11/93-5/94 and received compassionate oral tacrolimus induction. Sixteen transplants were treated with oral tacrolimus induction only; 5 transplants, oral tacrolimus + ATGAM/OKT3 induction. The protocol consisted of 0.2 mg/kg of tacrolimus orally on the first postoperative day with a corticosteroid taper. Oral tacrolimus was started at day 1-8 in the 5 patients receiving ATGAM/OKT3 induction. Dosages were adjusted over time to maintain a whole-blood trough level of 12-15 ng/ml at 0-1 month, 10-12 ng/ml at 1-3 months, and 5-10 ng/ml after 3 months. The incidence of acute rejection was 50% (8/16) in children on oral tacrolimus induction alone and 80% (4/5) in the tacrolimus + ATGAM/OKT3 group. Epstein-Barr virus infection occurred in 6 of 19 children (32%), with no child developing lymphoproliferative disorder. No adverse effect on renal function was noted. Serum fasting glucose was stable over time while a trend was noted in decreasing serum cholesterol levels at 6 months. Antihypertensive medication was required in 4 of 19 children (21%) posttransplantation. Corticosteroids were withdrawn in 11% (2/19) of patients. Actuarial 1-year patient and graft survivals were 95% and 86%, respectively. The use of oral tacrolimus induction therapy was associated with excellent survival and a low incidence of complications.


Asunto(s)
Rechazo de Injerto/prevención & control , Inmunosupresores/administración & dosificación , Trasplante de Hígado , Tacrolimus/administración & dosificación , Administración Oral , Adolescente , Niño , Preescolar , Estudios de Seguimiento , Supervivencia de Injerto , Humanos , Lactante
15.
J Thorac Cardiovasc Surg ; 92(1): 1-5, 1986 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-3523049

RESUMEN

Technical details of investigational orthotopic cardiac transplantation for management of hypoplastic left heart syndrome in a neonate are presented. Extracorporeal perfusion technique and need for extensive aortic arch reconstruction are emphasized. Although this experience was with a subhuman primate (baboon) donor, source of donor graft makes little difference with regards to the unique technical aspects of cardiac transplantation in a ductus-dependent newborn infant with a diminutive aortic arch.


Asunto(s)
Cardiopatías Congénitas/cirugía , Trasplante de Corazón , Papio , Trasplante Heterólogo/métodos , Animales , Aorta Torácica/cirugía , Coartación Aórtica/cirugía , Femenino , Humanos , Recién Nacido , Cuidados Intraoperatorios , Premedicación , Técnicas de Sutura
16.
Surgery ; 113(2): 155-62, 1993 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-7679224

RESUMEN

BACKGROUND: Several studies examined in vivo and in vitro biologic activity of the human gallbladder in response to cholecystokinin (CCK). However, few studies have demonstrated directly the interaction of CCK with receptors on the human gallbladder, which is responsible for this biologic activity. METHODS: To characterize CCK receptors on human gallbladder tissue, gallbladders were removed from human donor grafts that were being used for liver transplantation. The gallbladders were rapidly frozen and sectioned for measurement of binding of 125I-Bolton-Hunter-labeled-CCK-8 and were cut into strips for in vitro bioassay. RESULTS: Binding of 125I-BH-CCK-8 to human gallbladder was saturable, specific, and dependent on time, pH, and temperature. The binding was inhibited only by cholecystokinin-related peptides including CCK-8 (IC50 10 +/- 1.0 nmol/L) (mean +/- SD), des(SO3) CCK-8 (IC50 0.9 +/- 0.2 mumol/L), and gastrin-17-I (IC50 9.0 +/- 2.0 mumol/L) or specific CCK receptor antagonist L-364,718. Computer analysis of binding of 125I-BH-CCK-8 to gallbladder tissue showed a single class of binding sites with high affinity for CCK-8. Autoradiography localized binding of 125I-BH-CCK-8 only to the smooth muscle layer of the gallbladder. In the bioassay des(SO3) CCK-8 (EC50 1.2 +/- 0.7 mumol/L) and gastrin-17-I (EC50 4.5 +/- 2.4 mumol/L) were 150- and 563-fold less potent than CCK-8 (EC50 8.0 +/- 2.2 nmol/L). The relative potencies of CCK agonists for inhibiting binding of 125I-BH-CCK-8 agreed closely with their relative potencies for causing gallbladder contraction. The dose-response curve for CCK-8 alone to induce gallbladder contraction was not significantly different from those caused by CCK-8 plus 1 mumol/L tetrodotoxin or 1 mumol/L atropine. CONCLUSIONS: These results characterized the CCK receptors on smooth muscle of human gallbladder as sulfate dependent and causing gallbladder contraction.


Asunto(s)
Vesícula Biliar/metabolismo , Contracción Muscular/fisiología , Músculo Liso/metabolismo , Receptores de Colecistoquinina/metabolismo , Autorradiografía , Benzodiazepinonas/farmacología , Sitios de Unión , Carbacol/farmacología , Devazepida , Relación Dosis-Respuesta a Droga , Vesícula Biliar/efectos de los fármacos , Vesícula Biliar/fisiología , Gastrinas/farmacología , Hormonas/farmacología , Humanos , Concentración de Iones de Hidrógeno , Técnicas In Vitro , Radioisótopos de Yodo/metabolismo , Contracción Muscular/efectos de los fármacos , Músculo Liso/efectos de los fármacos , Receptores de Colecistoquinina/efectos de los fármacos , Valores de Referencia , Secretina/farmacología , Serotonina/farmacología , Sincalida/análogos & derivados , Sincalida/farmacología , Sustancia P/farmacología , Temperatura , Péptido Intestinal Vasoactivo/farmacología
17.
Surgery ; 114(5): 942-50, 1993 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-8236019

RESUMEN

BACKGROUND: The present in vitro study investigated the interaction between cholecystokinin (CCK) and receptors on human sphincter of Oddi tissue obtained from donated human livers that were being transplanted. METHODS: Radiolabeled ligands with cholecystokinin receptor specificity, autoradiography, and crystal scintillation counting were used to directly characterize cholecystokinin receptors on tissue sections. RESULTS: The binding of 125I-BH-CCK-8 to the tissue was saturable, specific, and dependent on time, pH, and temperature. Saturable binding of 125I-BH-CCK-8 was localized on the smooth muscle layer, and binding was inhibited only by cholecystokinin-related peptides. Computer analysis of 125I-BH-CCK-8 binding indicated the presence of two classes of binding sites, one with a high affinity and the other with a low affinity for CCK-8. CCK-8 caused relaxation (half-maximal concentration, 6 nmol/L) and carbachol caused contraction (half-maximal concentration, 10 nmol/L) of circular, cross-sectional strips of the tissue. Longitudinal strips were less responsive. The relative 125I-BH-CCK-8 binding inhibition potency of CCK-8 agreed closely with its relative ability to cause sphincter relaxation. Tetrodotoxin (1 mumol/L) and atropine (1 mumol/L) caused a rightward shift of the dose-response curve for CCK-8-stimulated sphincter relaxation. CONCLUSIONS: The present results indicate that cholecystokinin receptors on the human sphincter of Oddi are sulfate dependent and mediate sphincter relaxation.


Asunto(s)
Receptores de Colecistoquinina/análisis , Esfínter de la Ampolla Hepatopancreática/química , Atropina/farmacología , Sitios de Unión , Colecistoquinina/metabolismo , Humanos , Concentración de Iones de Hidrógeno , Técnicas In Vitro , Contracción Muscular , Relajación Muscular , Músculo Liso/química , Esfínter de la Ampolla Hepatopancreática/metabolismo , Temperatura , Tetrodotoxina/farmacología
18.
Surgery ; 110(1): 80-6, 1991 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-1866698

RESUMEN

We investigated the effect of the addition of chlorpromazine to a new, simplified organ preservation solution, sodium lactobionate sucrose (SLS), for 20-hour hypothermic rat liver preservation. Survival beyond 7 days after orthotopic transplantation of the stored liver was eight of eight rats in control groups (immediate transplantation, less than 1-hour preservation), one of 14 rats with the University of Wisconsin (UW) solution, four of 14 rats with SLS, seven of eight rats with SLS + chlorpromazine, 1 mg/L, and seven of eight rats with SLS + chlorpromazine, 10 mg/L. The differences is survival between UW and SLS and between SLS and SLS + chlorpromazine were significant (p less than 0.05). Lactic dehydrogenase levels in the effluent after reflushing through the portal vein at the time of transplantation were 145 +/- 20 IU/L (mean +/- SEM) in the controls, 525 +/- 78 IU/L in UW, 492 +/- 44 IU/L in SLS, 290 +/- 39 IU/L in SLS + chlorpromazine, 1 mg/L, 290 +/- 11 IU/L in SLS + chlorpromazine, 10 mg/L. The values for the SLS + chlorpromazine were significantly lower than for SLS and UW (p less than 0.05). The pH of the effluent was 7.10 +/- 0.10 in controls, 6.42 +/- 0.12 in UW, 6.64 +/- 0.18 in SLS, and 7.07 +/- 0.02 in SLS + chlorpromazine, 1 mg/L and 10 mg/L. The pH drop was significantly greater in the groups without chlorpromazine (p less than 0.01). This study shows that superior rat liver preservation was achieved with a simplified lactobionate solution containing sodium as the principal cation, sucrose in place of raffinose, and omitting the colloid and several of the other UW components. The addition of low concentrations of chlorpromazine further enhanced the effectiveness of this solution, without the need for donor pretreatment.


Asunto(s)
Clorpromazina , Disacáridos , Hígado , Soluciones Preservantes de Órganos , Preservación de Órganos , Sacarosa , Adenosina , Alopurinol , Bilis/fisiología , Glutatión , Humanos , Concentración de Iones de Hidrógeno , Insulina , L-Lactato Deshidrogenasa/metabolismo , Trasplante de Hígado , Rafinosa , Soluciones , Factores de Tiempo
19.
Surgery ; 111(1): 37-47, 1992 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-1728073

RESUMEN

This paper describes an en bloc total abdominal evisceration (TAE) technique that has been used successfully in 81 consecutive multi-organ procurements in donors ranging from 2.5 to 85 kg. Preliminary dissection performed by the surgeon and physician's assistant averaged 30 to 45 minutes before aortic cross-clamping. Removal of all abdominal organs (liver, kidneys, pancreas, bowel) en bloc averaged 16 to 24 minutes after aortic cross-clamping, depending on the speed of the thoracic procurement. Organ grafts were preserved with the University of Wisconsin preservation solution. Total procurement time for the removal of the liver, pancreas, and kidneys averaged 1.5 to 2.25 hours. Because all vascular anomalies were easily recognized ex vivo, vascular reconstruction was possible, so that all donors could potentially provide for combined liver, pancreas, and kidney transplantation. In the TAE group, primary liver graft nonfunction was 1.2% (1/81 grafts), which is less than the non-TAE liver graft nonfunction rate of 7% (7/99 grafts); this is statistically significant (p less than 0.05). Also, the incidence of fresh frozen plasma support after liver transplantation in the TAE group (2/81 transplantations) was lower than the non-TAE group (9/99 transplantations) (p less than 0.05). The overall liver recipient survival rate was 87% (non-TAE; 78/94 recipients; TAE; 65/70 recipients). Kidney-graft initial function has been similar in both the TAE and non-TAE groups. All pancreas tissue was histologically normal, and extraction of viable islet cells (average, 3600 islets per gram pancreas) was possible with yields similar to standard pancreatic (average, 379 islets per gram pancreas) harvest techniques. Preliminary experience with combined liver and whole-organ pancreas transplantations has been encouraging, with immediate discontinuation of intraoperative insulin during transplantation.


Asunto(s)
Disección/métodos , Trasplante de Órganos/métodos , Humanos , Preservación de Órganos , Estudios Retrospectivos , Donantes de Tejidos
20.
Surgery ; 120(4): 698-704; discussion 704-5, 1996 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-8862380

RESUMEN

BACKGROUND: This study examines factors associated with the performance of orthotopic liver transplantation (OLT) without red blood cell (RBC) transfusion. METHODS: Between January 1992 and December 1994, 306 primary OLTs were performed with recipients divided into two groups: group 1 patients (61 recipients, 20% of total) underwent transplantation without packed RBCs, and group 2 patients (245 recipients, 80% of cases) received a transfusion of at least 1 unit of RBCs during operation. RESULTS: Recipients in group 1 compared with group 2 had less advanced liver disease (20% hospitalized and 48% Child's class C versus 58% hospitalized and 73% Child's class C, p < 0.01) and lower frequency of right upper quadrant surgery (13% versus 25%, p < 0.05). Group 1 recipients also had significantly higher preoperative hematocrits (38% versus 33%, p < 0.01), lower prothrombin times (15.4 versus 16.7 seconds, p < 0.001) and partial thromboplastin times (36.9 versus 42.2 seconds, p < 0.01), a greater proportion of patients transplanted by piggyback technique (87% versus 59%, p < 0.001), and shorter operative times (7.9 hours versus 9.2 hours, p < 0.001). Moreover, a greater percentage of patients underwent OLT without RBC transfusion in each successive year: 9% in 1992, 21% in 1993, and 31% in 1994 (p < 0.001). Logistic regression analysis showed the following factors to be independent predictors of OLT without RBC transfusion. Preoperative Hct, United Network of Organ Sharing status, piggyback technique, operative time, and year of transplantation. CONCLUSIONS: OLT can be performed without transfusion of RBCs in recipients with less advanced liver disease, and surgical technique, along with increased experience by the transplant team, are important factors.


Asunto(s)
Transfusión de Eritrocitos , Trasplante de Hígado , Adolescente , Adulto , Factores de Edad , Niño , Preescolar , Femenino , Humanos , Lactante , Periodo Intraoperatorio , Masculino , Persona de Mediana Edad , Transfusión de Plaquetas , Análisis de Regresión , Estudios Retrospectivos , Resultado del Tratamiento
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