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Biomedical subjects

P Jara

Publications and source records attributed to P Jara.

At least 19 recordsLinked to original sources
PubMed2006

Liver transplantation for malignant tumours in children.

OBJECTIVE: The object of this study was to analyse our results with liver transplantation (LTX) for primitive malignant unresectable liver tumours in children and to discuss the controversial indications, based on our experience. METHODS/PATIENTS: We report on 12 patients, aged 6 months to 14 years, with hepatic malignant tumours: 11 with hepatoblastoma and 1 with fibrolamellar hepatocelullar carcinoma without cirrhosis. LTX was the primary treatment in 10 patients (PRETEXT IV or any grade, if there was extension to the retrohepatic vena cava, 3 hepatic veins or portal vein) and a rescue therapy after recurrence for 1 and for persistence of unresectable macroscopic residuals in 2 patients. One of the patients who underwent a LTX as primary therapy had lung metastases previously resolved with chemotherapy. We used entire liver (n = 5), left lateral segment from cadaveric donor (n = 3), living related donor (n = 3; 2 segments II-III and 1 right lobe) and left lateral segment from split liver (n = 1). All children received chemotherapy prior and post transplantation following the SIOPEL protocol. We analysed procedure tolerance, survival, recurrence rate, disease-free period and risk factors for adverse evolution. RESULTS: All patients overcame LTX and no early graft loss was recorded. Two cases died because of tumour relapse, 1 after primary LTX and 1 after rescue LTX (survival rate of both groups, 90% and 50%). Graft and patient survival rates at 1 year, 3 years, 5 years and 14 years were 91%, 91%, 82% and 82% respectively. The boy who presented with lung metastases developed new ones one year after LTX that were removed and he is currently free of disease. The disease-free period has a probability at 1, 3 and 5 years of 91%, 75% and 75%, respectively. Tumour tissue persistence was the only risk factor for an adverse clinical course in our series. CONCLUSIONS: LTX is a reasonable therapeutic approach for unresectable malignant liver tumours, providing outcomes comparable to those for resectable tumours. Results obtained with LTX are better when it is used as a primary treatment than when used as a rescue procedure. Proper staging and early referral to centres with enough expertise optimise the results. LTX for patients with lung metastases could be a controversial option. Living related-donor transplantation is an excellent alternative to avoid disease progression while on the waiting list for cadaveric donors.

Adolescent↗
PubMed2006

Cold stress induces metabolic activation of thyrotrophin-releasing hormone-synthesising neurones in the magnocellular division of the hypothalamic paraventricular nucleus and concomitantly changes ovarian sympathetic activity parameters.

Recent studies suggest thyrotrophin-releasing hormone (TRH) serves as a neurotransmitter and thereby provides a functional vegetative connection between the brain and the ovary. In the present study, magnocellular neurones of the paraventricular nucleus (PVN) in animals subjected to cold exposure were studied to determine the hypothalamic origin of the TRH involved in this pathway. In situ hybridisation analysis of hypothalamic tissue showed that cold exposure causes a two-fold increase in the total number of neurones expressing TRH mRNA in the PVN. Immunohistochemical studies showed that TRH peptide is localised to the magnocellular PVN and that the number of TRH immunoreactive cells increases two-fold following 64 h of cold exposure. Double-immunostaining for MAP-2 and TRH revealed that TRH peptide is localised in the perikarya of the magnocellular neurones. TRH release was measured in vivo from the magnocellular portion of the PVN using push-pull perfusion. Although controls exhibited a very low level of TRH release, animals subjected to cold showed a pulsatile-like TRH release profile with two different patterns of release: (i) low basal level with small bursts of TRH release and (ii) a profile with an up to seven-fold increase in TRH release compared to controls. The colocalisation of TRH with the specific somato-dendritic marker MAP-2 in processes of the magnocellular neurones suggested a local release of TRH. Additional studies demonstrated a reduction in ovarian noradrenaline content after 48 h of cold exposure, a feature indicative of nerve activation at the terminal organ. After 64 h of cold exposure, the ovarian noradrenaline returned to control values but the noradrenaline content of the coeliac ganglia was increased, suggesting a compensatory effect originating in the cell bodies of the sympathetic neurones that innervate the ovary. The correlation between the local release of TRH from dendrites within the magnocellular PVN in conditions of cold and the activation of the sympathetic nerves supplying the ovary raises the possibility that TRH contributes to the processing regulating sympathetic outflow and may thereby impact on the functional activity of the ovary.

Acclimatization↗
PubMed2005

Comparative study between living and cadaveric donors in pediatric liver transplantation.

UNLABELLED: We examined whether the results in living-related hepatic transplantation (LRLT) are better than those from a cadaveric donor (CDLT). MATERIAL AND METHODS: The last 27 consecutive LRLT, performed from 1998 to 2005, were compared with 27 CDLT matched for age, weight, date, and diagnosis. Grafts in LRLT group were left lateral segment (n = 22), left lobe (n = 3), and right lobe (n = 2). In the CDLT group, the grafts were split in situ (n = 10), hepatic reduction (n = 9) and whole liver (n = 8). We analyzed the actuarial survivals (grafts and children), retransplantation, primary nonfunction, initial graft malfunction (liver enzymes >2000 U/L), surgical complications, rejection, and resource consumption. RESULTS: Patient survivals at 6 months, 1 year, and 5 years were 100%, 96%, and 96% in LRLT and 100%, 100%, and 100% in CDLT (P = NS). Graft survivals were 93%, 89%, and 89% versus 96%, 96%, and 96%, respectively (P = NS). Complications were biliary complications (LRLT, 25% vs CDLT, 3%; P = .021); portal vein thrombosis (LRLT, 7% vs CDLT, 3%; NS), and hepatic artery thrombosis (LRLT, 0% vs CDLT, 3%; NS). The overall incidence of acute rejection was slightly higher (NS) in LRLT (LRLT, 18% vs CDLT, 11%; NS). Liver enzyme levels were higher in the CDLT group, but initial malfunction rate was not statistically different. Regarding resource consumption: blood product needs were higher in LRLT (P < .05) and hospital stay and ICU stay were longer, although not significantly, among LRLT. CONCLUSIONS: The results in LRLT among children are similar to those obtained in CDLT. We found a trend towards less initial graft malfunction in LRLT. Blood product needs were higher in LRLT. Hospital and ICU stay were longer, but not significantly different in LRLT. The benefits of LRLT are saving a scarce resource: a cadaveric donor liver graft.

Body Weight↗
PubMed2005

Intestinal transplantation in children: differences between isolated intestinal and composite grafts.

The results of the isolated intestinal grafts were compared with those of composite grafts (intestinal graft + liver) in a series of 18 transplantations performed in 17 children; 5 isolated intestinal grafts, 12 hepatointestinal grafts, and 1 multivisceral graft. Causes of intestinal failure were short bowel syndrome (n = 13), motility disorders (n = 2) and congenital epithelial disorders (n = 2). Transplantation was indicated due to end-stage liver disease (n = 14), loss of venous access (n = 2), untreatable diarrhea (n = 1) and high morbidity associated with a poor quality of life (n = 1). Six children, all with a composite graft, died after transplantation due to lymphoma (n = 2), sepsis (n = 1); intraabdominal bleeding (n = 1); pneumonia (n = 1); and overwhelming adenoviral infection (n = 1). Digestive autonomy was achieved in 16 of 18 grafts, the 11 surviving children are free of parenteral nutrition with a reasonably good quality of life. In conclusion, intestinal transplantation is a viable therapeutic alternative for children with permanent intestinal failure. The results of transplantation with an isolated intestine are clearly better that those with a composite graft.

Adolescent↗
PubMed2005

Mutation analysis of Wilson disease in the Spanish population -- identification of a prevalent substitution and eight novel mutations in the ATP7B gene.

Wilson disease (WD) is a copper metabolism disorder characterized by hepatic and/or neurological damage. More than 200 mutations in the ATP7B gene causing this autosomal recessive defect have been reported. In certain populations, a high prevalence of particular mutations allows rapid screening and diagnosis of the disease. We identified the ATP7B alterations in Spanish patients with WD. Mutations in the ATP7B gene were analysed in a total of 64 individuals from 40 different WD families by PCR amplification, single-strand conformation polymorphism (SSCP) analysis and sequencing. Twenty-one different ATP7B gene mutations were identified, eight of which were novel. 74% of the disease alleles were characterized among the 40 unrelated probands. We identified a prevalent mutation in our population (Met645Arg), present in 55% of this 40 patients. The frequency of the remaining ATP7B alterations was low. In addition, 17 different polymorphic variants were found. There is remarkable allele heterogeneity in WD in the Spanish population. Nevertheless, SSCP screening for the most frequent mutations in our population is feasible and leads to the detection of about 74% of the mutated chromosomes. Molecular diagnosis of WD is very useful in clinical practice to confirm or support clinical suspicion.

Adenosine Triphosphatases↗
PubMed2005

[Pediatric liver transplantation].

There are no differences in results between pediatric liver transplantation and liver transplantation in adults. The reverts of the liver disease prior to transplantation (particularly the need of intensive care is the best predictor of perspective mortality. Therefore, liver transplantation in children should be indicated prior a severe decompensation of the disease.

Alagille Syndrome↗
PubMed2004

[The multifocal hepatic hemangioendothelioma. Is always a benign tumor?].

UNLABELLED: The hepatic multicentric haemangioma is defined by its extension, affecting all the mass of the liver. The high mortality associated with it is mostly related with the complications produced by its enormous size (haemodynamic, platelet trapping, spontaneous rupture and bleeding). There is a general belief that is a benign tumor with possibility of spontaneous regression and cure. AIM: Retrospective analysis of our recent cases of MHH with the purpose of: 1 degrees) To show the evolution and results. 2 degrees) To realize if the "benign character" of the tumor is real or if some cases may be considered as malignant tumors. MATERIAL AND METHODS: 10 cases of MHH treated in the last 10 years. In 9 the age of presentation was less than 6 months and one patient was diagnosed at 3 and half years. The diagnosis was confirmed by image techniques in 7 cases and by biopsy in 3. In 7 patients extrahepatic vascular lesions were associated prior to the treatment. Methylprednisolone was given to all the cases and alpha-2-interferon was administered to the patients that not responded to the steroids. Vincristine was added to 2 patients. In two cases the hepatic artery embolization was tried and one patient had a liver transplant. RESULTS: Four children had at least one episode of congestive cardiac insufficiency, two patients suffered a consumption coagulopathy (Kasabach Merrit syndrome), and one presented acute hepatic failure. In six children it has been complete regression of the tumor, one more is still under treatment and three died. The dead were produced by the malignant behavior of the tumor in one case (tumoral rupture of a MHH recurrence in the transplanted liver), and possibly in other (intracranial haemorrhage and hepatic failure in a liver transplantation candidate without demonstrated extrahepatic extension in the previous studies, but with multiorgan dissemination at autopsy. In both cases it was impossible to discover signs of histologic or biologic malignancy neither in the primitive lesion nor in the metastasis. CONCLUSIONS: 1a) The regression of the MHH, spontaneous or induced by the treatment is frequent. 2a) Some cases of MHH are aggressive and develop local recurrences and distant metastasis. 3a) The discrimination between MHH of "benign" or "malignant" behaviour is not possible. 4a) Despite of the unpredictable biological conduct of the tumor, the liver transplantation must be considered as an option in the symptomatic cases that not respond to the conventional treatment.

Child, Preschool↗
PubMed2004

[Results of an intestinal transplantation program in Spain. Five years later].

BACKGROUND: More than two thirds of all intestinal transplantations (ITx) performed around the world correspondent to recipients younger than 18. OBJECTIVE: To analyze our 5-year experience in pediatric ITx. PATIENTS: We assessed the outcome of the 19 children included in list out of 41 patients considered for ITx from 1997. The main cause of intestinal failure was short bowel syndrome (14) followed by intestinal motility disorders (3) and congenit disorders of intestinal epithelium (CDIE) (2). The median of age, at the moment of including in the list, was 0.9 years (range 0.4-17) and median of weight was 6.4kg (range 0.4-29.3). Ten children were included for liver and small bowel transplantation (LSBTx), 7 to isolated small bowel (SBTx), and 2 for multivisceral transplantation (MVTx). Indications for SBx were hepatic fibrosis/cirrhosis (10), hepatic fibrosis in evolution (5) (to avoid later LSBTx), intractable diarrhoea (1), recurrent line infections (1), lost of central vein access (1), and bad quality of life in one. RESULTS: Five children died in the waiting list, after a median time of 325 days (range 19-581). Seven remain in the waiting list (median 139 days, range 30-778). In 3 of these the indication changed from SBTx to LSBTx because of progression to end stage liver disease. Six children recieved seven grafts (1 MVTx, 4 LSBTx, 2 SBx) after a median time in the waiting list of 352 days (range 66-732). Six out of seven grafts achieved normal function and all survivals reached full digestive autonomy after Tx. We had to rejection episodes, one with good response to medical treatment and one that required removal of intestinal allograft and later LSBTx. Two children died 1 because of problem not related to the procedure (hemorrage following liver biopsy) and one girl died 29 months after transplant due to post-transplantation lymphoproliferative disease. CONCLUSIONS: ITx is a realistic alternative in our country for children with intestinal failure. The main problems are immunologic (rejection, lynphoproliferative and disease) Shortage of small weight donors is a dramatic limitation that prompts the discussion of surgical alternatives.

Adolescent↗
PubMed2003

Pediatric living donor liver transplantation.

AIM: The aim of this study was to analyze the results of living donor in a pediatric liver transplantation program. PATIENTS: Twenty-six living donor liver transplantations were performed in children from 0.5 to 14.8 years of age. The main indication was biliary atresia (72%) followed by tumors (2 hepatoblastomas and 1 hepatocarcinoma). Left lateral segments were used in 23 (1 transformed into a monosegment), 1 left lobe was used in 1, and right lobes were used in 2. Arterial reconstruction employed saphenous venous grafts in the first 3 cases and end-to-end anastomoses with a microsurgical technique in the following 22 cases. RESULTS: There has been no major morbidity in the donors, with a median hospitalization of 6 days. Four grafts have been lost; 2 in the first 3 cases. In only 1 case, the graft loss was related to the procedure saphenous venous graft thrombosis). Early biliary complications were frequent (23%). Six month, 1 year, and 5 year graft and patient survival rates were 91%, 85%, and 85% and 100%, 96%, and 96%, respectively. CONCLUSIONS: Living donor liver transplantation is an excellent option for transplantation in children.

Adolescent↗
PubMed2003

Pediatric intestinal transplantation.

AIM: Analyze the results of a paediatric intestinal transplantation (IT) program in Spain. PATIENTS: During an 5-year period, 18 children were included as candidates for IT. The causes for intestinal failure (IF) were short bowel syndrome (n=13), motility disorders (n=3), and congenital epithelial disorders (n=2). Nine children were admitted for a combined liver-small bowel transplant (LSBT), seven for an isolated intestinal transplantation (IIT) and two for a multivisceral transplantation (MVT). In three of the candidates for IIT the indication had to be changed to LSBT because of progression of the liver damage. RESULTS: Eight candidates are on the waiting list: four for LSBT, two for IIT, and two for MVT. Four children died before transplantation. All were children under 1 year and candidates for LSBT. One child died during an attempted MVT. Five children underwent transplantation. Grafts were IIT in two and LSBT in three. Of these children, two are on a normal diet (respective follow-up times: 40 and 18 months), two died, both with functioning liver and intestinal grafts (hemorrage after liver biopsy and lymphoproliferative disease), and one developed an untreatable rejection that lead to loss of the intestinal graft; currently, she is on the waiting list for LSBT. CONCLUSIONS: The morbidity and mortality of IT are high, but it is the only possible treatment for children in IF who cannot be adequately managed with parenteral nutrition. A severe problem is the the scarcity of suitable donors for the very low weight children who are candidates for LSBT.

Adolescent↗
PubMed2003

Two pathogenic mutations in the mitochondrial DNA tRNA Leu(UUR) gene (T3258C and A3280G) resulting in variable clinical phenotypes.

We studied two patients with ragged-red fibers and combined defects of the mitochondrial respiratory chain in their muscle biopsy. One had mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes, and harbored a T3258C transition in the tRNA(Leu(UUR)) gene. The other showed myopathy plus cardiomyopathy and had an A3280G mutation in the same gene. Both mutations were heteroplasmic, abundant in muscle of the patients, less abundant in blood, and still less abundant in blood from their maternal relatives. In both patients, single muscle fiber analysis revealed greater abundance of mutant genomes in ragged-red fibers than in normal fibers, supporting the pathogenicity of both mutations.

Acidosis, Lactic↗
PubMed2003

[Activity of a pediatric intestinal transplantation program in Spain].

AIM: To analyze the outcome of children with intestinal failure (IF) included as candidates for intestinal transplantation (IT). Patients, Eight out of 23 children with IF assessed since July 1997 met criteria for IT and were included on the waiting list. The causes of IT were Short Bowel Syndrome (SBS) in 6 and Microvillus Inclusion Disease (MID) in 2. The indication of IT were end stage liver disease (ESLD) in 5 (related to total parenteral nutrition administration, TPN), progressive hepatic fibrosis in 2 and loss of venous access in 1. The patients with ESLD were included for combined liver-small bowel transplantation (LSBT) and the remaining for isolated intestinal transplantation (IIT). RESULTS: Two children died waiting for LSBT, 4 patients are on the waiting list, 2 for LSBT and 2 for IIT (length of stay: 4-11 months). Two children were transplanted, one with IIT in a 2.5 years old boy with MID, and one with LSBT in a 22 months girl with SBS and ESLD. Both patients recovered intestinal function after transplantation and are a live (follow-up of 19 and 10 months respectively). The LSBT's patient is under treatment for postransplant lymphoproliferative disease (PTLD). CONCLUSIONS: The lack of suitable donors for the small children candidate to IT explains the long period of stay on the waiting list and the high pretransplant mortality. Two strategies are possible; early referral of children with IF to a transplant center and surgical techniques like ex vivi-hepatic reductions of the LSB graft.

Child↗
PubMed2003

[Prognostic factors in pediatric liver transplantation. Multivariate analysis].

AIM: To analyze independent risk factors associated with poor graft and patient survival in a series of 292 pediatric liver transplants (PLT) performed in 234 children during a 15 years period. MATERIAL AND METHODS. 1. Univariate graft and patient survival analysis in 45 variables related to pretransplant patient status, surgical technique and donor conditions. 2. Variables found with univariate analysis to be associated with outcome were entered into a stepwise backward proportional hazard model (Cox), to determine independent prediction of outcome. RESULTS: 11 variables influence the graft survival: recipient age, z-score recipient height, UNOS status, recipient and donor weight, transplant for immune hepatitis, platelet transfusion during the transplant, blood index > 4 during the surgery, type of arterial reconstruction, retransplantation and era of the transplant (first er: 1986-1990; 2nd. era: 1991-1995; 3rd. era: 1996-2000). Four of those variables are independent in the multivariate analysis: UNOS 1 status (Odds Ratio, OR = 2.82, 95% confidence interval = 1.36-5.85), recipient < 3 years (OR = 3.76, 95% CI = 2.13-6.63), transplants for autoimmune hepatitis and era (OR of first and second versus third era respectively 3.93 and 2.81). The independent variables influencing the patient survival were: children receiving more than one graft children less than 3 years old and transplant era. CONCLUSIONS: Liver transplant in small children is associated with an increased risk of graft loss and patient dead. The experience of the hospital in pediatric liver transplantation improves the results, particularly in small children.

Adolescent↗
PubMed2002

[Drug-induced hepatotoxicity in children. Where we are and where we are going].

Childhood is characterized by continuous growth and development during which the organs and systems gradually mature. Because drug pharmacokinetics and pharmacodynamics in children differ from those in adults, pediatric patients are highly susceptible to adverse drug reactions. Surprisingly, very few studies have been designed to study the efficacy and safety of drugs in this population and consequently dosage regimens are based on the assumption that children are small adults. We present a detailed review of these controversial aspects and propose the establishment of a multicenter, multidisciplinary network to monitor drug-induced liver disease in children. This project represents the integration of an epidemiological approach into routine clinical care. A protocol agreed by consensus for the collection of data on cases of hepatotoxicity with uniform and internationally accepted criteria for causality assessment and the classification of drug-induced liver injuries is proposed.

Chemical and Drug Induced Liver Injury↗