ABO-incompatible liver transplantation: a new therapeutic option for patients with acute liver failure in Chile

Different ways have been suggested to expand donor numbers for liver transplantation. Transplantation using ABO-incompatible hepatic grafts has recently been a controversial issue due to the high risk of hyperacute rejection mediated by preformed anti-ABO antibodies. We report three patients with acute liver failure who were transplanted with ABO-incompatible livers: A to O in two patients and A to B in one case. We used pre- and posttransplant total plasma exchange, splenectomy, and triple immunosuppression. All three patients are alive; one graft was lost, probably secondary to thrombotic microangiopathy with low isohemagglutinin titers of 1:8. One patient developed acute cellular rejection that was reversed with a bolus of methylprednisolone. No antibody-mediated rejection occurred. Financial and infectious considerations have to be considered. In our series, the final liver transplantation cost was higher than average for acute liver failure. Plasmapheresis has the highest cost of all the additional procedures. ABO-incompatible liver transplantation, because of the splenectomy it requires, has been associated with more infections due to encapsulated organisms. However, with splenectomy in our three patients, none had infections due to these bacteria. In our country, we do not consider ABO-incompatible liver transplantation as a first-line option, except for highly selected patients.     

Pediatric renal transplantation: 13 years of experience--report from the Chilean Cooperative Multicenter Group

Between 1989 and 2002, 178 renal transplants were performed in 168 pediatric patients in Chile. The mean age was 10.9 +/- 3.7 years (range 1 to 17.9). End-state renal disease etiologies were: congenital renal hypoplasia/dysplasia, chronic glomerulonephritis, and reflux nephropathy. Seventy received a graft from a living donor (LD), and 108 from a cadaveric donor (CD). Only 9% received antibody induction. Acute rejection episodes were reported in 76 patients: 38% in LD recipients and 48% in CD recipients (P = NS). One-, 3-, and 5-year graft survivals were 88%, 84%, and 76%, respectively, for LD and 86%, 79%, and 68% for CD recipients. Actuarial graft survival was significantly better among those patients with serum creatinine < 1 mg/dL at 1 year posttransplant compared with those with creatinine > 1 mg/dL (P < .05). The graft survival rate has improved from the first period (1989 to 1996) to the second period (1997 to 2002); (P = .05). Patient survival rates at 1, 3, and 5 years were 98%, 98%, and 98%, respectively, for LD, and 95%, 94%, and 94% for CD. Global height/age Z-score decreased from -0.7 at birth to -1.5 when dialysis started, and to -2.4 at the time of transplantation. The Z-score height/age at 1, 3, and 5 years posttransplantation was -2.25, -2.24, and -2.5. No significant differences were observed in transplant outcomes comparing patients younger than 7 years with those older ones. In conclusion, pediatric renal transplant has been performed in Chile with acceptable morbidity. The patient and graft survivals are similar to the reported international experience. In the last period there was a significant improvement in graft survival.     

Pediatric liver transplantation: ten years of experience in a multicentric program in Chile

Liver transplantation is the only treatment for patients with terminal acute and chronic diseases. Liver transplantation was started in Chile in 1985; our pediatric program began in 1993. The aim of this paper work was to present our experience from 1993 through 2004. One hundred and thirty two orthotopic liver transplants (OLT) were performed in children of mean age 5 years and median age 4 years (8 months to 15 years). The most frequent indications were biliary atresia, (43.1%) and acute liver failure (ALF; 20.4%), whose frequent cause was unknown but viral hepatitis A was the second one. A complete liver was transplanted in 59 patients, reduced in 39, split in one, and as an auxiliary liver in another one. Living related liver transplantation was performed in 32 cases (24.2%), of which thirty included segments II and III, and two, a right liver. A terminal arterial anastomosis was performed in 102 (77.2%) recipients and a graft interposition in 32 patients (24.2%). In 16 cases, biliary reconstruction was performed through an enterobiliary anastomosis. Immunosuppression included cyclosporine (Neoral), steroids, and azathioprine with conversion to tacrolimus (Prograf) as indicated. Rejection episodes, which were always biopsy-proven, were treated either with methylprednisolone or with antibodies. Biliary complications were the most frequent (21.4%) and the second cause was vascular complications (13%). Sixty-six patients suffered an acute rejection episode. Actuarial graft survival was 81.3% at 1 year and 72% at 5 years, while actuarial graft survival for ALF was 75.9% at 1 year and 67.8% at 5 years. Our results are comparable to those reported by most international groups.     

Melioidosis in New Caledonia

Recognized melioidosis-endemic areas are widening. In the South Pacific, melioidosis is endemic in New Caledonia, northern Australia, and Papua New Guinea. We report the first 4 documented cases of human melioidosis from New Caledonia. Molecular typing of 2 Burkholderia pseudomallei isolates suggests a link to Australian strains.     

Differential effects of interleukin-1beta on neurotoxicity, cytokine induction and glial reaction in specific brain regions

An appropriate inflammatory response is crucial for the maintenance of tissue homeostasis. The inflammatory responses seen in the brain parenchyma differ from those elicited in the periphery, ventricles and meninges. However, although an inflammatory component has been associated with many CNS diseases, the differences among parenchymal inflammatory responses in different brain regions have not yet been fully elucidated. Here, we performed a systematic comparison of the effects of a common pro-inflammatory stimulus, IL-1beta, on the hippocampus, substantia nigra, striatum and cortex. We determined various responses, including cytokine mRNA induction, glial activation, immune cell infiltration and changes in neuronal integrity, in both injected and adjacent regions 1 and 6 days after the injection of IL-1beta. We found that the mRNA for TGF-beta was up-regulated in a region-specific manner after IL-1beta administration. Contrary to its response in the periphery, IL-1alpha showed no detectable induction in the tested parenchymal regions. In addition, cytokine induction was also sometimes observed in regions distant from the site of injection. Interestingly, IL-1beta-mediated neurodegeneration was observed in the dentate gyrus of the hippocampus, but not in the other tested regions. The cellular recruitment mediated by IL-1 beta injection consisted mainly of polymorphonuclear cells (PMN), which correlated with IL-1betamRNA induction even in regions far from the injection site. These results indicate that various parenchymal regions show different inflammatory responses and neurodegeneration in response to IL-1beta. Taken together, our results provide a more precise picture of regional inflammation in the brain and should provide a basis for differential interpretation of results based on regional inflammatory differences.     

Effects of chronic administered guanosine on behavioral parameters and brain glutamate uptake in rats

Oral and intraperitoneal administration of the nucleoside guanosine have been shown to prevent quinolinic acid- (QA) and alpha-dendrotoxin-induced seizures, impair memory, and impair anxiety in rats and mice. We investigated the effect of 2-weeks ad lib orally administered guanosine (0.5 mg/ml) on seizures induced by QA, inhibitory avoidance memory, and locomotor performance in rats. We also studied the mechanism of action of guanosine through the measurement of its concentration in the cerebrospinal fluid (CSF) and its effect on glutamate uptake in cortical slices of rats. QA produced seizures in 85% of rats, an effect partially prevented by guanosine (53% of seizures; P = 0.0208). Guanosine also impaired retention on the inhibitory avoidance task (P = 0.0278) and decreased locomotor activity on the open field test (P = 0.0101). The CSF guanosine concentration increased twofold in the treated group compared to that in the vehicle group (P = 0.0178). Additionally, QA promoted a 30% decrease in glutamate uptake as compared to that with intracerebroventricular saline administration, an effect prevented by guanosine in animals protected against QA-induced seizures. Altogether, these findings suggest a potential role of guanosine for treating diseases involving glutamatergic excitotoxicity such as epilepsy. These effects seem to be related to modulation of glutamate uptake.     

Mitochondrial dysfunction in autism spectrum disorders: a population-based study

A minority of cases of autism has been associated with several different organic conditions, including bioenergetic metabolism deficiency. In a population-based study, we screened associated medical conditions in a group of 120 children with autism (current age range 11y 5mo to 14y 4mo, mean age 12y 11mo [SD 9.6mo], male:female ratio 2.9:1). Children were diagnosed using Diagnostic and Statistical Manual of Mental Disorders criteria, the Autism Diagnostic Interview--Revised, and the Childhood Autism Rating Scale; 76% were diagnosed with typical autism and 24% with atypical autism. Cognitive functional level was assessed with the Griffiths scale and the Wechsler Intelligence Scale for Children and was in the normal range in 17%. Epilepsy was present in 19 patients. Plasma lactate levels were measured in 69 patients, and in 14 we found hyperlactacidemia. Five of 11 patients studied were classified with definite mitochondrial respiratory chain disorder, suggesting that this might be one of the most common disorders associated with autism (5 of 69; 7.2%) and warranting further investigation.     

The influence of filling technique on depth of tubule penetration by root canal sealer: a study using light microscopy and digital image processing

The purpose of this study was to compare the depth of sealer penetration into dentinal tubules by three root-filling techniques using light microscopy and digital image processing. Thirty-two maxillary central incisors were prepared. Two teeth were separated for the control group. The rest were divided into three equal groups and obturated as following--G1: lateral condensation; G2: warm vertical compaction of gutta-percha and G3: Thermafil system. Each sample was sectioned longitudinally and prepared for microscopic analysis. A sequence of photomicrographs with magnifications of X50, X200 and X500 were taken. Through digital image analysis and processing, measurements for each field were obtained. A non-parametric ANOVA Kruskal-Wallis analysis was used to determine whether there were significant differences among the groups. Significant differences between G2 and G1 (p = 0.034) and between G3 and G1 (p = 0.021) were identified. There were no significant differences between G2 and G3 (p > 0.05). The results of this research suggest that samples root-filled by thermoplasticised gutta-percha techniques lead to deeper penetration of the root canal sealer into the dentinal tubules.