RESUMEN
The number of donor organs suitable for liver transplantation is restricted by cold preservation and ischemia-reperfusion injury. We present the first patients transplanted using a normothermic machine perfusion (NMP) device that transports and stores an organ in a fully functioning state at 37°C. In this Phase 1 trial, organs were retrieved using standard techniques, attached to the perfusion device at the donor hospital, and transported to the implanting center in a functioning state. NMP livers were matched 1:2 to cold-stored livers. Twenty patients underwent liver transplantation after NMP. Median NMP time was 9.3 (3.5-18.5) h versus median cold ischaemia time of 8.9 (4.2-11.4) h. Thirty-day graft survival was similar (100% NMP vs. 97.5% control, p = 1.00). Median peak aspartate aminotransferase in the first 7 days was significantly lower in the NMP group (417 IU [84-4681]) versus (902 IU [218-8786], p = 0.03). This first report of liver transplantation using NMP-preserved livers demonstrates the safety and feasibility of using this technology from retrieval to transplantation, including transportation. NMP may be valuable in increasing the number of donor livers and improving the function of transplantable organs.
Asunto(s)
Hepatopatías/cirugía , Trasplante de Hígado/métodos , Preservación de Órganos/métodos , Perfusión/métodos , Recolección de Tejidos y Órganos/métodos , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Isquemia Fría , Estudios de Factibilidad , Femenino , Supervivencia de Injerto , Humanos , Trasplante de Hígado/instrumentación , Masculino , Persona de Mediana Edad , Preservación de Órganos/instrumentación , Donantes de Tejidos , Recolección de Tejidos y Órganos/instrumentación , Isquemia Tibia , Adulto JovenAsunto(s)
Trasplante de Hígado , Isquemia Tibia , Conductos Biliares , Muerte , Humanos , Terapia Trombolítica , Donantes de TejidosRESUMEN
Shortage of organs for transplantation has led to the renewed interest in donation after circulatory-determination of death (DCDD). We conducted a retrospective analysis (2001-2009) and a subsequent prospective validation (2010) of liver Maastricht-Category-3-DCDD and donation-after-brain-death (DBD) offers to our program. Accepted and declined offers were compared. Accepted DCDD offers were divided into donors who went on to cardiac arrest and those who did not. Donors who arrested were divided into those producing grafts that were transplanted or remained unused. Descriptive comparisons and regression analyses were performed to assess predictor models of donor cardiac arrest and graft utilization. Variables from the multivariate analysis were prospectively validated. Of 1579 DCDD offers, 621 were accepted, and of these, 400 experienced cardiac arrest after withdrawal of support. Of these, 173 livers were transplanted. In the DCDD group, donor age < 40 years, use of inotropes and absence of gag/cough reflexes were predictors of cardiac arrest. Donor age >50 years, BMI >30, warm ischemia time >25 minutes, ITU stay >7 days and ALT ≥ 4× normal rates were risk factors for not using the graft. These variables had excellent sensitivity and specificity for the prediction of cardiac arrest (AUROC = 0.835) and graft use (AUROC = 0.748) in the 2010 prospective validation. These models can feasibly predict cardiac arrest in potential DCDDs and graft usability, helping to avoid unnecessary recoveries and healthcare expenditure.
Asunto(s)
Muerte Encefálica , Supervivencia de Injerto/fisiología , Paro Cardíaco/etiología , Trasplante de Hígado/métodos , Modelos Estadísticos , Preservación de Órganos/métodos , Donantes de Tejidos/provisión & distribución , Obtención de Tejidos y Órganos/estadística & datos numéricos , Adulto , Anciano , Niño , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Estudios RetrospectivosRESUMEN
Bile leak in split and living donor liver transplantation is not an uncommon postoperative complication with significant morbidity to both donor and recipients. Nonanastomotic bile leaks in these transplants are less well characterized and generally described as cut-surface leaks. A proportion of these leaks may derive from biliary radicles draining the caudate lobe. Based on the caudate lobe biliary anatomy the authors describe measures that may help to reduce such complications after segmental liver transplantation.
Asunto(s)
Vesícula Biliar/anatomía & histología , Vesícula Biliar/metabolismo , Trasplante de Hígado/efectos adversos , Complicaciones Posoperatorias/prevención & control , Adulto , Anastomosis Quirúrgica , Niño , Hepatectomía/métodos , Humanos , Hígado/anatomía & histología , Trasplante de Hígado/métodos , Donadores Vivos , Recolección de Tejidos y Órganos/métodosRESUMEN
BACKGROUND: Living related liver transplantation (LRLT) has become established for treating children with end-stage liver disease. The aim of this study was to review a single-centre experience of left lateral segment liver transplants from living donors in children. METHODS: Fifty left lateral segment LRLT procedures have been performed since 1993. There were 17 girls and 33 boys, of median age 1.5 years (range 0.5 to 13 years), with a median weight of 10 (range 0.7-44) kg. Donors included 23 mothers, 26 fathers and one uncle, with a median age of 33 (range 19-46) years. RESULTS: At a median follow-up of 86 months, there was no donor mortality and low morbidity. Patient and graft survival rates were 98, 96 and 96 per cent, and 98, 96 and 93 per cent at 1, 3 and 5 years respectively. Three children had a second transplant at a median of 9 years after the first. The incidence of hepatic artery thrombosis, portal vein thrombosis and biliary complications was 6, 4 and 14 per cent respectively. CONCLUSION: Living related liver transplantation has good long-term results in children.
Asunto(s)
Hepatopatías/cirugía , Neoplasias Hepáticas/cirugía , Trasplante de Hígado/métodos , Donadores Vivos , Adolescente , Adulto , Niño , Preescolar , Padre , Femenino , Rechazo de Injerto , Humanos , Terapia de Inmunosupresión/métodos , Lactante , Trasplante de Hígado/efectos adversos , Masculino , Persona de Mediana Edad , Madres , Cuidados Posoperatorios/métodosRESUMEN
Non-heart-beating donor (NHBD) transplants have been reintroduced into clinical practice because of the progressively rising number of patients on the transplant waiting list and relatively static numbers of cadaver organ donors. Several units have undertaken NHBD programs utilizing category 3 of Maastricht criteria. The current data show encouraging outcomes, which give rise to further interest in this donor pool. This manuscript briefly summarizes the most recent reports in this field.
Asunto(s)
Paro Cardíaco , Trasplante de Corazón/métodos , Donantes de Tejidos , Cadáver , Humanos , Trasplante de Riñón/fisiología , Trasplante de Hígado/fisiología , Resultado del TratamientoRESUMEN
An in vitro study was carried out to verify whether the chain length of a substituent on an indolinic nitroxide could influence its antioxidant activity in different biological environments subjected to oxidative stress. Three distinct indolinic nitroxides were synthesized and compared with vitamin E and Trolox (a hydrophilic analogue of vitamin E), where the only difference between the nitroxides was the length of the hydrocarbon chain in the 2-position of indole, namely 2 (C2), 10 (C10), and 18 (C18) carbons. All the nitroxides were effective in preventing oxidation of bovine serum albumin, but to different extents, with the longer chain derivatives being more efficient. However, the C2 compound was the most efficient in preventing lipid peroxidation in microsomal membranes. The C2 and C18 compounds, Trolox, and vitamin E protected microsomal protein oxidation to the same extent at the highest concentration used (13 microM). The nitroxide with a C10 chain was less effective in this system. The influence of these compounds on the enzymatic activity of two mitochondrial proteins subjected to oxidative stress was also studied by means of oxygraph measurements. Mitochondrial rotenone-sensitive NADH oxidase and succinate oxidase responded differently to BuOOH-induced radical chemistry, and the compounds under study also protected the activity of the two enzymes but to different extents. The results clearly demonstrate that indolinic nitroxides are very efficient antioxidants, protecting both lipids and proteins from peroxidation. The indole structure influences the antioxidant efficacy in biological systems.
Asunto(s)
Antioxidantes/química , Indoles/química , Microsomas Hepáticos/efectos de los fármacos , Óxidos de Nitrógeno/química , Estrés Oxidativo/efectos de los fármacos , Albúmina Sérica Bovina/metabolismo , Animales , Antioxidantes/farmacología , Cromanos/farmacología , Radicales Libres , Técnicas In Vitro , Indoles/farmacología , Mitocondrias Hepáticas/efectos de los fármacos , Estructura Molecular , Óxidos de Nitrógeno/farmacología , Ratas , Relación Estructura-Actividad , Vitamina E/análogos & derivados , Vitamina E/farmacologíaRESUMEN
Glutathione and glyoxalase II levels were evaluated in cytosolic and mitochondrial compartments of rat liver after 7 and 24 hr of cold storage in University of Wisconsin (UW) and Euro-Collins solutions. 1-4 A similar time-dependent depletion of cytosolic glutathione up to about 60% of control values was observed in both Euro-Collins and UW solutions. Cytosolic glyoxalase II showed activity oscillations in livers stored in Euro-Collins but not in UW. Mitochondrial glutathione and glyoxalase II were severely depleted soon after 7 hr of cold storage in Euro-Collins, whereas the same parameters did not change in liver stored in UW after 24 hr. UW is confirmed to be the most suitable solution for liver cold storage and we conclude that mitochondrial glutathione and glyoxalase II can be important parameters in assessing mitochondrial and cell function.
Asunto(s)
Glutatión/metabolismo , Hígado/metabolismo , Mitocondrias Hepáticas/metabolismo , Soluciones Preservantes de Órganos , Tioléster Hidrolasas/metabolismo , Adenosina , Alopurinol , Animales , Frío , Citosol/metabolismo , Soluciones Hipertónicas , Insulina , Preservación de Órganos , Rafinosa , Ratas , Ratas WistarRESUMEN
A method is presented for forming short, mucosa-lined vocal shunt in cases of supracricoid laryngectomy with preservation of one or two arytenoids, or the interarytenoid fold alone. On the basis of radiologic and particularly radiocinematographic examinationion of the anterior pharyngeal wall is of paramount importance. In cases of complete absence of leakage, said wall lies in the plane of the arytenoids or somewhat posteriorly. After simple supracricoid laryngectomy it is possible to prevent aspiration also by translocation of the anterior pharyngeal wall into the plane of the cricoid cartilage plate. The clinical experience with this supracricoid shunt is still scanty. Of 25 cases with the arytenoid vocal shunt, phonation was possible in 22 cases under the expiratory pressure of 20-45 cm H2O; in one under the more elevated pressure, and in the last two the result is still not known. Loudness of speech was 70-100 db and its comprehensibility 73-90 percent. Complete absence of leakage was observed in 17 cases, "practical" prevention of aspiration (some drops of thin fluids, no saliva) in seven cases, profuse leakage in one case (ceased after correction), In the last 10 consecutive cases the problem of aspiration was completely eliminated. Advantages and disadvantages of our own method in comparison with Asai's method have been presented.
Asunto(s)
Cartílagos Laríngeos/cirugía , Neoplasias Laríngeas/rehabilitación , Laringectomía/métodos , Faringe/cirugía , Deglución , Cartílagos Laríngeos/fisiología , Neoplasias Laríngeas/cirugía , Faringe/fisiología , HablaRESUMEN
BACKGROUND: The allocation of cadaveric livers for transplantation in the United States is now based on the severity of illness as determined by the Model for End-Stage Liver Disease (MELD), which was developed to predict short-term mortality in patients with cirrhosis. However, its impact to predict posttransplantation survival is controversial. The objective of this study was to determine the association of various pretransplantation risk factors, including the MELD score and whether its use to allocate organs is likely to lead to overall poorer outcomes of liver transplantation. METHODS: The 1,032 consecutive adult liver transplantation patients at King's College Hospital between 2 January 1994 and 29 December 2001 were examined for 9 preoperative risk factors, including MELD score, using univariate and multivariate techniques. Based on their pretransplantation MELD scores, we categorized recipients as low (<15) medium (15-25), or high (>25). Kaplan-Meier patient survival analysis was used to identify differences in outcomes. RESULTS: The patients had a mean age of 47.2 years and mean posttransplantation follow-up of 5.3 years. Univariate analysis showed recipient diabetes mellitus, renal dysfunction, and pretransplantation MELD score to be associated with patient survival. Multivariate analysis showed the MELD score to be significantly associated with death during long-term follow-up. CONCLUSIONS: A high pretransplantation MELD score was associated with poor posttransplantation outcomes.
Asunto(s)
Indicadores de Salud , Hepatopatías/diagnóstico , Hepatopatías/cirugía , Trasplante de Hígado , Adulto , Femenino , Humanos , Estimación de Kaplan-Meier , Hepatopatías/mortalidad , Trasplante de Hígado/efectos adversos , Trasplante de Hígado/mortalidad , Londres , Masculino , Persona de Mediana Edad , Análisis Multivariante , Valor Predictivo de las Pruebas , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Índice de Severidad de la Enfermedad , Factores de Tiempo , Obtención de Tejidos y Órganos , Resultado del TratamientoRESUMEN
We report our experience of pediatric liver transplantation with partial grafts from non-heart beating donors (NHBD). Controlled donors less than 40 years of age with a warm ischemia time (WI) of less than 30 min were considered for pediatric recipients. Death was declared 5 min after asystole. A super-rapid recovery technique with aortic and portal perfusion was utilized. Mean donor age was 29 years and WI 14.6 min (range 11-18). Seven children, mean age 4.9 years (0.7-11), median weight 20 kg (8.4-53) received NHBD segmental liver grafts. Diagnoses included seronegative hepatitis, neonatal sclerosing cholangitis, familial intrahepatic cholestasis, hepatoblastoma, primary hyperoxaluria and factor VII deficiency (n=2). The grafts included four reduced and one split left lateral segments, one left lobe and one right auxiliary graft. Mean cold ischemia was 7.3 h (6.2-8.8). Complications included one pleural effusion and one biliary collection drained percutaneously. At 20 months (10-36) follow-up all children are alive and well with functioning grafts. Donation after cardiac death is a significant source of liver grafts for adults and children with careful donor selection and short cold ischemic times.
Asunto(s)
Paro Cardíaco , Donantes de Tejidos , Adolescente , Adulto , Niño , Preescolar , Femenino , Hepatectomía/métodos , Humanos , Lactante , Hepatopatías/clasificación , Hepatopatías/cirugía , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Recolección de Tejidos y Órganos/métodosRESUMEN
An attempt was made to see whether realizations of eight different pitch patterns can be classified automatically by subjecting fundamental frequency curves to statistical treatment using two kinds of discriminant functions. The materials consisted of 150 imitations of each of the eight prototypes (eight intonations of a short Polish phrase). Approximately 80% of the time the statistical procedures assigned the individual tokens to the appropriate classes. Most of the misassignments were due to wrong imitations. The discriminant functions also indicated similarities and dissimilarities among the pitch patterns. It is suggested that perceptually and linguistically, some differences between pitch patterns may not be quite categorical.
Asunto(s)
Fonética , Percepción del Habla , Algoritmos , Humanos , Conducta Imitativa , Modelos EstadísticosRESUMEN
Word lists used for speech audiometry should fulfill a number of conditions in order that the results of hearing tests be unambiguous and directly interpretable not only in terms of possible hearing loss but also in terms of the neurolinguistic decoding process. In order to construct a proper word list, it was decided to attempt to estimate the subjective probability of word occurrence in schoolchildren. Nine different lists of over 300 words each were prepared, containing words of all assumed degrees of familiarity. In the preliminary stage, the lists were presented to 600 children in primary and secondary schools. The children were asked to mark each word with a number indicating their relative familiarity with the word. The answers were examined for homogeneity.
Asunto(s)
Audiometría , Habla , Percepción Auditiva , Niño , Femenino , Humanos , Masculino , Discriminación de la Altura Tonal , PoloniaRESUMEN
297 children aged 9-14 with normal hearing and intelligence level were examined by speech audiometry. Ten lists with monosyllabic meaningful and nonsense words were used. All the lists were phonemically and structurally balanced in the same way and were applied with an intensity level varying between 26 dB and 61 dB. The identification and discrimination scores for Polish speech sounds were calculated from written-response sheets. The identification scores were generally significantly lower for nonsense words, and up to a certain extent, increased with age. An examination of the discrimination scores showed that confusions were related to the distinctive features of the phonemes. The results represent the first stage of a project on speech sound identification in children and may have practical implications for the rehabilitation of children with hearing loss.
Asunto(s)
Fonética , Adolescente , Factores de Edad , Audiometría , Niño , Pruebas Auditivas , HumanosRESUMEN
BACKGROUND: Liver ischemia/reperfusion injury is a severe problem in transplantation, and preservation solutions could be critical for liver viability. The aim of our study was to evaluate the cytosolic and mitochondrial glutathione levels, the glyoxalase II activity, and the mitochondrial hydroperoxide contents of livers stored in different preservation solutions for 7 or 24 h and after transplantation. MATERIALS AND METHODS: Orthotopic liver transplantation was performed without reconstruction of the hepatic artery. The livers were stored at 4 degrees C for 7 or 24 h in University of Wisconsin or Euro-Collins solutions. Portions of livers before and after transplantation were homogenized and mitochondria isolated. RESULTS: Cytosolic glutathione levels were decreased in all stored livers and after transplantation. In livers stored with University of Wisconsin solution, mitochondrial glutathione was unchanged during cold storage and no significant decrease has been found after reperfusion, whereas in livers stored in Euro-Collins solution, mitochondrial glutathione was decreased and a further significant decrease was found 30 min after reperfusion. Mitochondrial hydroperoxides were higher in livers stored in Euro-Collins solution than in University of Wisconsin solution after 30 min of reperfusion. Mitochondrial glyoxalase II did not show any change by reperfusion. CONCLUSION: We have demonstrated that rat liver stored in Euro-Collins solution suffered a severe depletion of mitochondrial GSH and a concomitant increase of hydroperoxides. The data obtained suggested that the livers stored with University of Wisconsin solution were probably less prone to ischemia/reperfusion injury after liver transplantation.