RESUMEN
Lymphoma is a recognized cause of liver damage and in rare instances presents as ALF. In such cases, the underlying malignancy is often difficult to detect. Historically, the prognosis has been poor. Cure has occasionally been achieved with chemotherapy alone. LT in this setting is controversial, but has contributed to successful outcomes, as in the case of the five-yr-old girl reported here.
Asunto(s)
Enfermedad de Hodgkin/terapia , Fallo Hepático Agudo/terapia , Trasplante de Hígado/métodos , Adulto , Anciano , Anciano de 80 o más Años , Biopsia , Niño , Preescolar , Femenino , Enfermedad de Hodgkin/diagnóstico , Enfermedad de Hodgkin/patología , Humanos , Linfoma/patología , Linfoma/terapia , Masculino , Persona de Mediana Edad , RecurrenciaRESUMEN
A prospective study of renal function was undertaken on an unselected group of 8 children with chronic progressive liver disease on whom a renal biopsy was performed subsequently at the time of orthotopic liver transplantation. Two patients had abnormal urinalyses and 2 elevated urinary albumin/creatinine ratios. The remainder had no clinical evidence of renal dysfunction. All had normal serum creatinine concentrations. Glomerular abnormalities were present in all renal biopsies and were of two types: hepatic glomerulosclerosis (n = 5) and minor glomerular abnormalities (n = 3). IgM immunofluorescence was present in all biopsies and IgA in 6. Elevated serum immunoglobulin levels were observed in all patients, with IgM elevation in 6, IgA in 4 and IgG in 6. C3 and/or C4 were reduced in 5 patients and increased circulating immune complexes containing IgM were noted in 4. The clinical significance of these cirrhosis-associated glomerular abnormalities can only be established by long-term follow-up studies after orthotopic liver transplantation.
Asunto(s)
Glomérulos Renales/anomalías , Trasplante de Hígado/patología , Albuminuria/metabolismo , Biopsia , Preescolar , Creatinina/orina , Femenino , Técnica del Anticuerpo Fluorescente , Humanos , Inmunoglobulina A/análisis , Inmunoglobulina G/análisis , Inmunoglobulina M/análisis , Lactante , Enfermedades Renales/epidemiología , Enfermedades Renales/patología , Enfermedades Renales/fisiopatología , Glomérulos Renales/patología , Hepatopatías/complicaciones , Hepatopatías/patología , Hepatopatías/cirugía , Masculino , Estudios ProspectivosRESUMEN
Malnutrition is common in children with end-stage liver disease (ESLD) awaiting orthotopic liver transplantation (OLT), and nutritional support is assuming an important role in preoperative management. To evaluate preoperative nutritional therapy, 19 children (median age 1.25 y) with ESLD awaiting OLT were prospectively studied. Two high-energy, isoenergetic and isonitrogenous nutritional formulations delivered nasogastrically were compared: a branched-chain amino acid (BCAA)-enriched semielemental formulation and a matched standard semielemental formation. Twelve of 19 patients completed a randomized controlled study before OLT and 10 of 19 completed a full crossover study. Improvements in weight and height occurred during the BCAA supplements, with no statistical change on the standard formulation. Significant increases in total body potassium, midupper arm circumference, and subscapular skinfold thickness occurred during the BCAA supplements, whereas no significant changes occurred during the standard formulation period. Significantly fewer albumin infusions were required during the BCAA supplement. These findings suggest that BCAA-enriched formulas have advantages over standard semielemental formulas in improving nutritional status in children with ESLD, and are deserving of wider application and study.
Asunto(s)
Aminoácidos de Cadena Ramificada/uso terapéutico , Hepatopatías/dietoterapia , Trasplante de Hígado , Cuidados Preoperatorios , Desnutrición Proteico-Calórica/prevención & control , Albúminas/administración & dosificación , Aminoácidos/sangre , Antropometría , Niño , Preescolar , Femenino , Humanos , Lactante , Hepatopatías/complicaciones , Hepatopatías/cirugía , Pruebas de Función Hepática , Masculino , Potasio/análisis , Estudios ProspectivosRESUMEN
To evaluate malnutrition in chronic liver disease, and its relationship to nutrient deficiencies and hepatic dysfunction, 27 children with end-stage liver disease were studied. Mean protein-energy intakes were 70% of recommended daily intakes. The patients were underweight and stunted with reduced mean triceps and subscapular skinfold thicknesses and midupper arm circumference. Mean total body potassium was only 63 +/- 18% of that expected for age and sex. Deficiency of essential fatty acids (32%), and low concentrations of fat-soluble vitamins (A, 92%; E, 32%), iron (32%), zinc (42%), and selenium (13%) were common. Serum ammonia concentrations were raised in all patients, and increased methionine, tyrosine, and glutamic acid, and reduced glutamine concentrations were noted. There was no correlation between the degree of malnutrition and the degree of liver synthetic function, the degree of cholestasis, or the degree of liver injury. We suggest that potentially correctable factors in addition to liver failure (eg, inadequate absorbed intake) were important determinants of malnutrition in these patients.
Asunto(s)
Hepatopatías/complicaciones , Trasplante de Hígado , Desnutrición Proteico-Calórica/etiología , Aminoácidos/sangre , Amoníaco/sangre , Antropometría , Composición Corporal , Ácidos Grasos Esenciales/sangre , Humanos , Hierro/sangre , Hepatopatías/cirugía , Potasio/análisis , Desnutrición Proteico-Calórica/patología , Selenio/sangre , Vitaminas/sangre , Zinc/sangreRESUMEN
The aims of this study were to investigate outcome and to evaluate areas of potential ongoing concern after orthotopic liver transplantation (OLT) in children. Actuarial survival in relation to age and degree of undernutrition at the time of OLT was evaluated in 53 children (age 0.58-14.2 years) undergoing OLT for endstage liver disease. Follow-up studies of growth and quality of life were undertaken in those with a minimum follow-up period of 12 months (n = 26). The overall 3 year actuarial survival was 70%. Survival rates did not differ between age groups (actuarial 2 year survival for ages less than 1, 1-5 and greater than 5 years were 70, 70 and 69% respectively) but did differ according to nutritional status at OLT (actuarial 2 year survival for children with Z scores for weight less than -1 was 57%, greater than -1 was 95%; P = 0.004). Significant catch-up weight gain was observed by 18 months post-transplant, while height improved less rapidly. Quality of life (assessed by Vineland Adaptive Behaviour Scales incorporating socialization, daily living skills, communication and motor skills) was good (mean composite score 91 +/- 19). All school-aged children except one were attending normal school. Two children had mild to moderate intellectual handicap related to post-operative intracerebral complications. Satisfactory long-term survival can be achieved after OLT in children regardless of age but the importance of pre-operative nutrition is emphasized. Survivors have an excellent chance of a good quality of life and of satisfactory catch-up weight gain and growth.
Asunto(s)
Crecimiento/fisiología , Trasplante de Hígado , Calidad de Vida , Actividades Cotidianas , Análisis Actuarial , Adolescente , Estatura/fisiología , Peso Corporal/fisiología , Niño , Preescolar , Femenino , Estudios de Seguimiento , Humanos , Lactante , Hepatopatías/cirugía , Trasplante de Hígado/mortalidad , Trasplante de Hígado/fisiología , Trasplante de Hígado/psicología , Masculino , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
The nutritional profiles of 37 children (aged 0.5-14.0 years) with chronic liver disease at the time of acceptance for orthotopic liver transplantation (OLTP) have been evaluated using clinical, biochemical and body composition methods. Nutritional progress while waiting for a donor has been related to outcome, whether transplanted or not. At the time of acceptance, most children were underweight (mean standard deviation (s.d.) weight = -1.4 +/- 0.2) and stunted (mean s.d. height = -2.2 +/- 0.4), had low serum albumin (27/35) and had reduced body fat and depleted body cell mass (measured by total body potassium--mean % expected for age = 58 +/- 5%, n = 15). Mean ad libitum nutrient intake was 63 +/- 5% of recommended daily intake (RDI). Those who died while waiting (n = 8) had significantly lower mean initial s.d. weight compared with those transplanted. The overall actuarial 1 year survival of those who were transplanted (mean waiting time = 75 days) was 81% but those who were initially well nourished (s.d. weight greater than -1.0) had an actuarial 1 year survival of 100%. There were no significant differences in actuarial survival in relationship to age, type of transplant (whole liver or segmental), liver biochemistry or the presence or absence of ascites. Of the total group accepted for OLTP, whether transplanted or not, the overall 1 year survival for those who were relatively well nourished was 88% and for those undernourished (initial s.d. weight less than -1.0) was 38% (P less than 0.003). Declining nutritional status during the waiting period also adversely affected outcome.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Trastornos de la Nutrición del Niño/etiología , Hepatopatías/complicaciones , Trasplante de Hígado , Adolescente , Niño , Trastornos de la Nutrición del Niño/terapia , Preescolar , Enfermedad Crónica , Femenino , Humanos , Lactante , Hepatopatías/mortalidad , Hepatopatías/cirugía , Trasplante de Hígado/mortalidad , Masculino , Pronóstico , Tasa de SupervivenciaRESUMEN
Four thousand, seven hundred and fifty-nine form 1 intermediate school children (aged 11 years) in the south Auckland health district were screened in 1987. There were 88 (1.8%) new visual defects detected (defined as a visual acuity (VA) of 6/12 or worse in one or both eyes), while 103 (2.2%) wore glasses and a further 22 (0.5%) did not have their glasses available at the time of the VA test. The total prevalence of screening visual defects was 4.5%. A survey was carried out of those pupils who failed the VA screening test in the previous year and those recorded as wearing glasses. Sixty-seven (76%) of 88 children with newly detected visual defects were interviewed. An abnormal VA test was confirmed in 59 (88%), of which 39 (66%) required treatment. Thirty were prescribed glasses, of which 27 purchased them, but at the time of interview nine did not have them available. Twenty-one (20%) of the 103 children tested with glasses failed the VA test. Twenty-two children had glasses but were not wearing them at the time of the VA test. Only three of these children had a VA better than 6/12 bilaterally. These results highlight the importance of the vision screening programme in this age group and the follow up of children with known visual defects.
Asunto(s)
Evaluación de Programas y Proyectos de Salud/métodos , Trastornos de la Visión/prevención & control , Selección Visual/métodos , Niño , Anteojos , Estudios de Seguimiento , Humanos , Entrevistas como Asunto , Nueva Zelanda/epidemiología , Derivación y Consulta , Trastornos de la Visión/epidemiología , Agudeza Visual/fisiologíaRESUMEN
Pre-operative nutritional support was studied in 28 children with end-stage liver disease awaiting orthotopic liver transplantation. Nasogastric supplemental administration of a standard semi-elemental enteral nutritional formula was compared with a similar formula enriched with branched chain amino acids, and with a group receiving oral nutrition only. The duration of treatment in all groups was similar (mean 90 days). Energy intakes in the supplemented groups were 120-150% of recommended daily intakes (RDI), whereas ad libitum intakes in the oral group ranged 58-100% RDI. A significant improvement in mean Z-score for body weight (denoting catch-up) was noted only in those children who received nasogastric supplements enriched with branched-chain amino acids. The standard enterally-fed group maintained their body weight and Z-scores did not change significantly. In contrast, body weight Z-scores in those fed orally declined significantly. Nutritional supportive therapy of malnourished children with end-stage liver disease can minimize or improve nutritional status in children awaiting liver transplantation. The use of nutritional formulae rich in branched-chain amino acids may have nutritional advantages in children with chronic liver disease which require further study and evaluation.
Asunto(s)
Atresia Biliar/cirugía , Nutrición Enteral , Alimentos Formulados , Trasplante de Hígado , Trastornos Nutricionales/terapia , Aminoácidos de Cadena Ramificada/administración & dosificación , Ingestión de Energía , Femenino , Humanos , Lactante , Masculino , Estado Nutricional , Cuidados PreoperatoriosRESUMEN
An open-label inpatient study is in progress to compare the efficacy and safety of two oral rehydration solutions in children and infants with acute diarrhea and mild to moderate dehydration. One solution (ORS-60) contains 60 mmol/L of sodium and 1.8% glucose, with a total osmolality of 240 mosm/kg; the other (ORS-26) contains 26 mmol/L of sodium, 2.7% glucose, and 3.6% sucrose, with a total osmolality of 340 mosm/kg. An outcome analysis of 28 children with gastroenteritis indicated that ORS-60 (n = 13) reduced stool volume during the first eight hours after admission to a significantly greater (P less than 0.05) extent than did ORS-26 (n = 15). Diarrhea had ceased by 24 hours in 64% of ORS-60 patients but in only 31% of ORS-26 patients, and the patients' clinical condition was improved at eight hours in 84% of ORS-60 patients versus 60% of ORS-26 patients. Differences between treatments in degree of dehydration at each follow-up point, total duration of diarrhea, and duration of hospital stay were not detected. No adverse drug reactions occurred. Four patients received intravenous rehydration therapy, but none was considered a treatment failure. We conclude that the lower osmolar solution, ORS-60, conferred earlier recovery and reduced continuing fluid losses in the management of gastroenteritis.
Asunto(s)
Fluidoterapia , Gastroenteritis/terapia , Australia , Niño , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Concentración Osmolar , SolucionesRESUMEN
Uptake of the bifunctional alkylating agent, PTT.119, p-F-Phe-m-bis-(2-chloroethyl)amino-L-Phe-Met-ethoxy-HCl, by the MJY-alpha mammary tumor and B16 melanoma cell lines occurred via two natural pathways for amino acid transport. The primary route of PTT.119 entry was the classical L System, whereas, the ASC System carrier was inconsistently operational for uptake of the tripeptide accounting for 5-6% of PTT.119 transport in the B16 melanoma cells. Tripeptide uptake by MJY-alpha mammary tumor cells did not occur via ASC carriers indicating that the mechanism of drug transport was dissimilar among the tumor cells. In spite of these differences the results support the hypothesis that amino acid residues covalently linked to an alkylating moiety do serve as carriers to enhance drug delivery.
Asunto(s)
Aminoácidos/metabolismo , Antineoplásicos/metabolismo , Neoplasias Mamarias Experimentales/metabolismo , Melanoma/metabolismo , Compuestos de Mostaza Nitrogenada/metabolismo , Animales , Transporte Biológico , Receptores de Aminoácidos , Receptores de Superficie Celular/metabolismo , Células Tumorales Cultivadas/metabolismoRESUMEN
Delivery of the bifunctional alkylating agent, PTT.119 [p-F-L-Phe-m-bis-(2-chloroethyl)amino-L-Phe-Met-ethoxy-HCl], into tumor cells is significantly greater compared to L-phenylalanine mustard (L-PAM) as demonstrated by the 2-fold reduction in PTT.119 dosage required to reduce the viable L1210 cell fraction by 50% (TCD50). This increased uptake and consequent cytolytic efficacy observed in Dulbecco's phosphate buffer was more apparent in culture medium; under this physiologic condition the TCD50 concentration of PTT.119 was 5 times lower than L-PAM. PTT.119 entry into leukemia cells was examined using competition transport assays assessing the ability of the tripeptide to compete with various amino acids and nonmetabolizable substrates for carrier receptors of the L, A and ASC transport systems. A 1-min exposure to a 1- to 50-fold excess of PTT.119 prior to addition of radiolabeled substrates significantly reduced within 60 s both sodium-dependent and sodium-independent uptake of leucine, methionine, threonine and alpha-[1-14C]-aminoisobutyric acid (AIB), but not MeAIB. In complimentary studies, L1210 cells were protected from PTT.119 cytolysis by an 8,000-fold excess of AIB, whereas beta-2-aminobicyclo[2.2.1]heptane-2-carboxylic acid (BCH) only abrogated tripeptide cytotoxicity by 95-97% even at BCH:PTT.119 ratios of 200,000. Leucine and methionine protection were significantly less effective; the TCD50 of leucine and methionine were 3.23 and 2.4 microM, respectively, compared to 11.41 microM for AIB and 7.96 microM for BCH. In addition, MeAIB and phenylalanine were totally unable to protect L1210 cells from PTT.119-induced cytolysis. The data indicate that L121 cells actively transport PTT.119 primarily by the BCH-sensitive, AIB-sensitive, MeAIB-insensitive L carrier system. A second, BCH-insensitive, AIB-sensitive and MeAIB-insensitive carrier which is also involved in tripeptide uptake is probably the ASC system.
Asunto(s)
Alquilantes/farmacocinética , Aminoácidos/farmacocinética , Leucemia L1210/metabolismo , Compuestos de Mostaza Nitrogenada/farmacocinética , Alquilantes/farmacología , Animales , Transporte Biológico Activo/efectos de los fármacos , Melfalán/farmacocinética , Melfalán/farmacología , Compuestos de Mostaza Nitrogenada/farmacología , Sodio/farmacología , Células Tumorales CultivadasRESUMEN
PTT.119 [p-fluoro-L-Phe-m-bis-(2-chloroethyl)-amino-L-Phe-Met ethoxy HCl] is a new bifunctional alkylating compound that possesses both cytolytic and antiviral activities. Continuous treatment of mouse mammary tumor cells with 15 microM PTT.119 reduced production of the B-type retrovirus murine mammary tumor virus (MuMTV). MuMTV levels in PTT.119-treated cultures were reduced by 31% in the first 24 hours; an additional 24 hours of treatment resulted in a further reduction of 70%. These reductions were significantly greater than could be accounted for by the effects of PTT.119 tumor cell metabolism and viability. Under identical treatment conditions, equimolar concentrations of L-phenylalanine mustard reduced MuMTV production by only 3%. PTT.119 inhibition of MuMTV replication was also apparent when mammary tumor cells were exposed for periods as short as 0.5-4 hours; persistent decreases in virus production were detected even 7 days following tripeptide treatment. Analyses of the polypeptide composition of MuMTV by sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed that virions from these PTT.119-treated mammary tumor cultures contained significant reductions in the relative level of the nonglycosylated 24,000-dalton (p24) viral polypeptide associated with the nucleoprotein core. Decreases in p24 were observed in MuMTV produced in the presence of the tripeptide and 1-7 days after removal of PTT.119. Examination of the steady-state levels and rates of intracellular MuMTV protein synthesis suggested that PTT.119 interferes with late steps in MuMTV processing and maturation.
Asunto(s)
Antineoplásicos/farmacología , Virus del Tumor Mamario del Ratón/efectos de los fármacos , Compuestos de Mostaza Nitrogenada/farmacología , Replicación Viral/efectos de los fármacos , Animales , Antineoplásicos/uso terapéutico , Células Cultivadas , Ensayo de Inmunoadsorción Enzimática , Femenino , Glicoproteínas/análisis , Virus del Tumor Mamario del Ratón/fisiología , Ratones , Compuestos de Mostaza Nitrogenada/uso terapéutico , ARN Viral/biosíntesis , Retroviridae/efectos de los fármacos , Proteínas de los Retroviridae/análisis , Proteínas de los Retroviridae/biosíntesisRESUMEN
PTT.119 [p-F-Phe-m-bis-(2-chloroethyl)amino-L-Phe-Met ethoxy HCl], a new synthetic tripeptide, was highly effective against the L-phenylalanine mustard (L-PAM) resistant (L1210/L-PAM and P388/L-PAM) tumor lines, as well as the sensitive L1210 leukemia. Cytolytic activity of PTT.119 against all three leukemias was significantly greater than equimolar doses of L-PAM. These in vitro results paralleled the significant increases in mean survival times of hosts and, in some cases, abrogations of tumor formation observed in the in vivo bioassays of PTT.119-treated L1210 and L1210/L-PAM cells. Dose-response studies failed to demonstrate cross-resistance to the tripeptide by L-PAM resistant cells. Doses of PTT.119 required to reduce the viable fraction by 50% (tissue culture dose 50, TCD50) or 100% (TCD100) were 1.3- to 3-fold lower for the L-PAM resistant cells than for the L1210 leukemia. In comparison, L-PAM was unable to completely eliminate cell survival; 0.2 to 3% of the cells in all three leukemias remained viable even at doses of 75 and 163 microM. In similar studies, L1210 leukemia cells made resistant to methotrexate (L1210 MTX) and cisplatin (L1210DDP) were also completely susceptible to PTT.119; TCD50 values of the two resistant lines were 1.94 microM for L1210 MTX and 0.525 microM for L1210DDP compared to 2.38 microM for the susceptible parent L1210S leukemia. Continuous low-dose PTT.119 treatment of MJY-alpha mammary tumor cells for 8 months and exposure of L1210 leukemia to escalating levels of tripeptide for over 100 passages failed to select or induce drug-resistant phenotypes in either cell line. PTT.119 appears to be a poor mutagen and is unlikely to readily increase the probability of drug-resistant mutants in the tumor cell populations.