[Liver and intestinal transplant in paediatric population]. / El trasplante hepático e intestinal en la población pediátrica.

Our organizational model allows an annual 1,000 liver transplants. Pediatric liver transplantation constitutes 5% of such activity and provides, in children with severe, progressive and irreversible liver disease, a 1 year-survival of 90% and more than 80% after 15 years of follow-up. The main indication is biliary atresia followed by metabolic liver disease and acute liver failure. Around half of the procedures are performed in children under two years and 25-30% in the first year of life. The waiting list remains at around 35 patients, with an average of 100 patients enrolled annually and 60 of them finally transplanted after an average of 136.3 days on the waiting list. The prioritization of the candidates uses the PELD as an objective tool for decision-making. However, the progressive aging of donors, with a profile increasingly different from the requirements of the pediatric patients included in the waiting list, requires strategies such as living donor liver transplantation and the split liver transplantation, to increase the probability of transplant while reducing both time and mortality on the waiting list at the same time. Pediatric intestinal transplantation registers a low indication but involves strict requirements that outline a very uncommon donor in our country which, together with the absence of alternatives that outweigh the impact of these difficulties, penalizes the chances of transplant for these patients.

Simeprevir with peginterferon/ribavirin for treatment of chronic hepatitis C virus genotype 1 infection: pooled safety analysis from Phase IIb and III studies.

This pooled analysis of five Phase IIb and III studies evaluated the safety and tolerability of simeprevir, a once daily, oral hepatitis C virus (HCV) NS3/4A protease inhibitor. Data were summarised for patients who received simeprevir 150 mg once daily (n = 924) or placebo (n = 540) plus pegylated interferon-α/ribavirin for 12 weeks. During the first 12 weeks of treatment, few patients discontinued simeprevir or placebo due to adverse events (AEs) (both 2.2%). Pruritus (23.8% vs 17.4%), rash (any; 22.9% vs 16.7%) and photosensitivity (3.2% vs 0.6%) [Correction added on 16 January 2015, after first online publication: In the above sentence, the values in 'Photosensitivity' were previously incorrect and have now been changed to 3.2% vs 0.6%.] were more prevalent in the simeprevir vs the placebo groups. Most AEs were grade 1/2 (72.4% for simeprevir vs 71.3% for placebo). All grade 3/4 AEs occurred in <5.0% of patients, except neutropenia (9.8% vs 7.6%). Overall incidence of neutropenia was similar (17.3% vs 15.7%). Incidence of anaemia was 13.2% for simeprevir vs 10.9% for placebo, and incidence of increased bilirubin was 8.4% vs 2.8%. Bilirubin increases were mild-to-moderate and transient without concurrent transaminase increases or association with hepatic injury. Safety and tolerability did not vary with METAVIR score, although increased bilirubin and anaemia were more frequent in simeprevir-treated patients with METAVIR F4 (increased bilirubin, 13.0% vs 3.3%; anaemia, 19.0% vs 14.8%). Serious AEs were infrequent (2.1% for simeprevir vs 3.0% for placebo). No deaths were reported during the first 12 weeks of treatment. Patient-reported fatigue and other outcomes were comparable for both groups, but were of shorter duration for simeprevir due to the use of response-guided therapy. Simeprevir is well tolerated in HCV genotype 1-infected patients.

In vivo mitochondrial inhibition alters corticostriatal synaptic function and the modulatory effects of neurotrophins.

Experimental evidence has revealed the role of mitochondria in various aspects of neuronal physiology. Mitochondrial failure results in alterations that underlie the pathogeneses of many neurodegenerative disorders, such as Parkinson's disease, Alzheimer's disease, Huntington's disease (HD) and amyotrophic lateral sclerosis. The mitochondrial toxin 3-nitropropionic acid (3-NP) has been used to model failure; for example, systemic administration of 3-NP imitates the striatal degeneration that is exhibited in the postmortem tissue of patients afflicted with HD. We have demonstrated that low, sub-chronic doses of 3-NP are sufficient to initiate the damage to striatal neurons that is associated with changes in neurotrophin expression levels. However, the mechanisms underlying the alterations in neuronal activity and neurotransmission due to 3-NP-induced mitochondrial dysfunction remain to be elucidated. In this paper, we focus on how corticostriatal transmission and its modulation by neurotrophins are altered in vivo after 5 days of mitochondrial inhibition with 3-NP. Recordings of population spikes and a paired pulse (PP) stimulation protocol were used to document changes in corticostriatal synapses in 3-NP-treated brain slices. The corticostriatal synapses were modulated by neurotrophins but displayed differential amplitude increases in the presence of brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), or neurotrophin-4/5 (NT-4/5) under control conditions. Neurotrophin-mediated synaptic modulation was decreased in slices from 3-NP-treated mice. The protein and mRNA levels of neurotrophins and their receptors were also modified in the 3-NP-treated tissue. Neuronal structural evaluation demonstrated that synaptic length and density were reduced in the 3-NP-treated mice, which partially explained the changes in the amplitudes of the synaptic field responses. Our results demonstrate that corticostriatal synapses are differentially modulated by neurotrophins and that this modulation is altered by mitochondrial failure. Mitochondrial dysfunction also affects neurotransmitter release in corticostriatal synapses, neurotrophin availability, dendritic arborization and the lengths of the striatal medium spiny neurons (MSNs).

Impact of ghosts on the viscoelastic response of gelatinized corn starch dispersions subjected to small strain deformations.

Corn starch dispersions (5.0% w/w) were gelatinized by heating at 90°C for 20 min using gentle stirring. Under these conditions, ghosts, which are insoluble material with high amylopectin content, were detected by optical microscopy. Strain sweep tests showed that the gelatinized starch dispersions (GSD) exhibited a loss modulus (G″) overshoot at relatively low strains (∼1%). In order to achieve a greater understanding as to the mechanisms giving rise to this uncharacteristic nonlinear response at low strains, very small constant torques (from 0.05 to 0.5 µN m) were applied in the bulk of the GSD with a rotating biconical disc. This resulted in small deformations exhibiting torque-dependent inertio-elastic damped oscillations which were subjected to phenomenological modelling. Inertial effects played an important role in the starch mechanical response. The model parameters varied with the magnitude of constant small applied torque and could be related to microstructural changes of ghosts and to the viscoelastic response of GSD.

Continuously evaluating performance in deceased donation: the Spanish quality assurance program.

The Spanish Quality Assurance Program applied to the process of donation after brain death entails an internal stage consisting of a continuous clinical chart review of deaths in critical care units (CCUs) performed by transplant coordinators and periodical external audits to selected centers. This paper describes the methodology and provides the most relevant results of this program, with information analyzed from 206,345 CCU deaths. According to the internal audit, 2.3% of hospital deaths and 12.4% of CCU deaths in Spain yield potential donors (clinical criteria consistent with brain death). Out of the potential donors, 54.6% become actual donors, 26% are lost due to medical unsuitability, 13.3% due to refusals to donation, 3.1% due to maintenance problems and 3% due to other reasons. Although the national pool of potential donors after brain death has progressively decreased from 65.2 per million population (pmp) in 2001 to 49 pmp in 2010, the number of actual donors after brain death has remained at about 30 pmp. External audits reveal that the number of actual donors could be 21.6% higher if all potential donors were identified and preventable losses avoided. We encourage other countries to develop similar comprehensive approaches to deceased donation performance.

Benchmarking in the process of donation after brain death: a methodology to identify best performer hospitals.

A benchmarking approach was developed in Spain to identify and spread critical success factors in the process of donation after brain death. This paper describes the methodology to identify the best performer hospitals in the period 2003-2007 with 106 hospitals throughout the country participating in the project. The process of donation after brain death was structured into three phases: referral of possible donors after brain death (DBD) to critical care units (CCUs) from outside units, management of possible DBDs within the CCUs and obtaining consent for organ donation. Indicators to assess performance in each phase were constructed and the factors influencing these indicators were studied to ensure that comparable groups of hospitals could be established. Availability of neurosurgery and CCU resources had a positive impact on the referral of possible DBDs to CCUs and those hospitals with fewer annual potential DBDs more frequently achieved 100% consent rates. Hospitals were grouped into each subprocess according to influencing factors. Hospitals with the best results were identified for each phase and hospital group. The subsequent study of their practices will lead to the identification of critical factors for success, which implemented in an adapted way should fortunately lead to increasing organ availability.

Outcome of HCV/HIV-coinfected liver transplant recipients: a prospective and multicenter cohort study.

Eighty-four HCV/HIV-coinfected and 252-matched HCV-monoinfected liver transplant recipients were included in a prospective multicenter study. Thirty-six (43%) HCV/HIV-coinfected and 75 (30%) HCV-monoinfected patients died, with a survival rate at 5 years of 54% (95% CI, 42-64) and 71% (95% CI, 66 to 77; p = 0.008), respectively. When both groups were considered together, HIV infection was an independent predictor of mortality (HR, 2.202; 95% CI, 1.420-3.413 [p < 0.001]). Multivariate analysis of only the HCV/HIV-coinfected recipients, revealed HCV genotype 1 (HR, 2.98; 95% CI, 1.32-6.76), donor risk index (HR, 9.48; 95% CI, 2.75-32.73) and negative plasma HCV RNA (HR, 0.14; 95% CI, 0.03-0.62) to be associated with mortality. When this analysis was restricted to pretransplant variables, we identified three independent factors (HCV genotype 1, pretransplant MELD score and centers with <1 liver transplantation/year in HIV-infected patients) that allowed us to identify a subset of 60 (71%) patients with a similar 5-year prognosis (69%[95% CI, 54-80]) to that of HCV-monoinfected recipients. In conclusion, 5-year survival in HCV/HIV-coinfected liver recipients was lower than in HCV-monoinfected recipients, although an important subset with a favorable prognosis was identified in the former.

[Microbiological profile of infections in the Intensive Care Units of Colombia (EPISEPSIS Colombia]. / Perfil microbiológico de la Infecciones en Unidades de Cuidados Intensivos de Colombia (EPISEPSIS Colombia).

BACKGROUND AND OBJECTIVE: Valid and reliable data regarding sepsis is lacking in Colombia. Our aim was to determine the prevalence of the microorganisms in the main infections treated in Intensive Care Units (ICUs) in our country. METHODS: This is a sub-study of a prospective cohort with 10 general hospitals in Colombia during a 6-month period. The inclusion criteria were hospitalization in ICU and confirmation of infection according to the CDC definitions. Patients were classified into three groups, that is, community, hospital and intensive care, according to the site where the infection was acquired. RESULTS: A total of 826 patients were included in this analysis. Of these, 51% developed infections in the community, 5.33% in the hospital and 43.7% in intensive care unit. Overall, the most common diagnoses were pneumonia (29.54%), intra-abdominal infection (18.16%) and urinary tract infection (11.62%). The most frequent germ in community-acquired infections was E. coli -lung (16. 4%), peritoneum (57.7%), urine (55.5%), blood (22.4%)-. E. coli -peritoneum (29.3%), urine (52.9%)- also predominated in the ICU-acquired infections, except for lung and blood in which Staphylococcus aureus (32.4%) and Klebsiella pneumoniae (15.7%) were the most prevalent. Cultures were requested from 655 patients, 40% of them having received antibiotics before cultures were taken, although this did not affected the percentages of positive cultures (P=0.583). CONCLUSIONS: Pneumonia was the main cause of infection regardless of the site of acquisition. E. coli was the most prevalent germ, except in the pulmonary infections acquired in UCI in which S. aureus was the most prevalent.

The 40 donors per million population plan: an action plan for improvement of organ donation and transplantation in Spain.

INTRODUCTION: Spain has been showing the highest rate of deceased donor organ recovery in the world for a whole country, namely, 33-35 donors per million population (pmp) during the last years. This activity is attributed to the so-called Spanish Model of organ donation, an integrated approach to improve organ donation since the start of the Organización Nacional de Trasplantes (ONT) in 1989. However, in 2007 there were 7/17 regions with >40 donors pmp and a marked regional variability. Thus, ONT has set a large-scale, comprehensive strategy to achieve a substantial improvement in donation and transplantation in Spain in the coming years: The 40 Donors pmp Plan. PURPOSE AND SCOPE: The overall objective is to increase the average rate of deceased donors to 40 pmp between 2008 and 2010. The areas of improvement, specific objectives, and actions have come from deep reflection on the data and the material generated from multidisciplinary discussions and open consultation with the donation and transplantation community. KEY AREAS SELECTED FOR ACTION: Detection and management of brain-dead donors, with 4 specific subareas: access to intensive care units, new forms of hospital management, foreigners and ethnic minorities, and evaluation/maintenance of thoracic organ donors. Expanded criteria donors, with 3 subareas: aging, donors with positive tests to certain viral serologies, and donors with rare diseases. Special surgical techniques. Donation after cardiac death.

[Prophylaxis of postoperative endophthalmitis with intracameral cefuroxime: a five years' experience]. / Profilaxis de la endoftalmitis postquirúrgica con cefuroxima intracamerular: experiencia de cinco años.

PURPOSE: To present the outcomes of prophylaxis of postoperative endophthalmitis following cataract surgery with intracameral Cefuroxime. METHOD: A retrospective study was done on 4281 eyes that underwent cataract surgery from October 2003 to September 2008. All patients underwent phacoemulsification cataract surgery. All cases received an injection of 0.1 ml intracameral Cefuroxime (1 mg) at the end of surgery except those patients allergic to penicillin and cephalosporin until September 2007 and thereafter only those with demonstrated allergy to cefuroxime. RESULTS: The rate of postoperative endophthalmitis was 0.11% (5 cases). Four of them had a positive culture. We found no evidence of clinical ocular toxicity. CONCLUSIONS: Intracameral cefuroxime works very well for reducing the incidence of postoperative endophthalmitis. It appears safe to use and is easy to prepare.

[Cervical cancer and DNA microarrays: tumour marker identification]. / Microarreglos de ADN y cáncer cervicouterino: identificación de marcadores tumorales.

Microarray technology has remarkably accelerated the understanding of the molecular events of neoplasias. By means of gene expression profiles, a molecular subclassification of cancer patients and the identification of thousand of genes involved in this pathology have been achieved. Herein, the general use of DNA microarrays in cervical cancer tumorigenesis is reviewed. Finally, putative molecular tumour markers as useful factors in diagnosis, prognosis, and tailor-made therapy for this disease are proposed.

SED-brachydactyly and distinctive speech: report of two new cases.

We describe two unrelated patients and the mother of one of them showing clinical and radiological features as those previously described in the spondyloepiphyseal dysplasia-brachydactyly and distinctive speech (SED-BDS, also named Fantasy Island syndrome or Tattoo dysplasia) clinically characterized by short stature with acral shortness, distinctive face, mild blepharophimosis, upslanted palpebral fissures, abundant eyebrows and eyelashes, thick and abundant hair and coarse voice; and radiologically by brachymetacarpalia, brachymetatarsalia and brachyphalangia of all fingers and toes, short and broad long bones with normal morphology and small pelvis. The clinical and radiological features present in mother and son suggest a probable autosomal dominant mode of inheritance and variable expressivity.

Trisomy 3q25.1-qter and monosomy 8p23.1-pter in a patient: cytogenetic and molecular analysis with delineation of the phenotype.

We describe a 4-year-old boy with partial 3q trisomy and distal 8p monosomy. The patient presented with mental retardation, dysmorphic face, congenital heart defect, brain and genital anomalies, and behavioral problems. The conventional cytogenetic analysis showed a 46,XY,add(8p) karyotype. Reverse painting and microsatellite analysis demonstrated a partial monosomy of 8p23.1 --> pter and a partial trisomy of 3q25.1 --> qter. The data suggest that the chromosomal rearrangement originated from a de novo translocation in a paternal germinal cell. The phenotype observed in our patient resulted from the combination of those defects described in the isolated dup(3q) and distal del(8p) syndromes.

Differential uptake and transport of trivalent and hexavalent chromium by tumbleweed (Salsola kali).

Experiments were conducted to determine the differential absorption of Cr species by tumbleweed (Salsola kali) as well as the effect of this heavy metal on plant growth and nutrient uptake. Tumbleweed seeds were grown in an agar-based media containing different concentrations of either Cr(III) or Cr(VI). The results demonstrated that the uptake of Cr was influenced by the Cr concentration in the growth medium and the speciation of this heavy metal. When supplied in the hexavalent form, the concentration of Cr in the different plant parts (2900, 790, and 600 mg kg(-1) for roots, stems, and leaves, respectively) was between 10 and 20 times higher than the amounts found when Cr was supplied in the trivalent form. In addition, it was found that in most of the experiments, Cr(III) exhibited more toxic effects on tumbleweed plants than Cr(VI). The size of roots of plants grown in 20 mg L(-1) Cr(III) were significantly smaller (p < 0.05) than those grown in 20 mg L(-1) Cr(VI). Plants exposed to 20 mg L(-1) Cr(III) produced shoots significantly shorter (p < 0.05) compared with the size of control plants and with those grown in 20 mg L(-1) Cr(VI). In addition, the absorption of macronutrients and microelements was in general lower when the plants were grown in the medium containing Cr(III). The amounts of Cr concentrated in the aerial plant parts under experimental conditions may indicate tumbleweed as a new option for the phytoremediation of Cr-contaminated soil.

Gold binding by native and chemically modified hops biomasses.

Heavy metals from mining, smelting operations and other industrial processing facilities pollute wastewaters worldwide. Extraction of metals from industrial effluents has been widely studied due to the economic advantages and the relative ease of technical implementation. Consequently, the search for new and improved methodologies for the recovery of gold has increased. In this particular research, the use of cone hops biomass (Humulus lupulus) was investigated as a new option for gold recovery. The results showed that the gold binding to native hops biomass was pH dependent from pH 2 to pH 6, with a maximum percentage binding at pH 3. Time dependency studies demonstrated that Au(III) binding to native and modified cone hops biomasses was found to be time independent at pH 2 while at pH 5, it was time dependent. Capacity experiments demonstrated that at pH 2, esterified hops biomass bound 33.4 mg Au/g of biomass, while native and hydrolyzed hops biomasses bound 28.2 and 12.0 mg Au/g of biomass, respectively. However, at pH 5 the binding capacities were 38.9, 37.8 and 11.4 mg of Au per gram of native, esterified and hydrolyzed hops biomasses, respectively.

Chemistry and nanoparticulate compositions of a 10,000 year-old ice core melt water.

Particulates extracted from a single section of a 10,000 year-old ice core melt sample exhibited characteristics of contemporary, airborne fine particulates: a majority were microcrystalline particulates and aggregated microcrystals, including some mixtures of microcrystals and carbonaceous matter. Particularly significant were the presence of carbon nanotubes and fullerene nanocrystals composing aggregated particulates reflecting global combustion products similar to contemporary, airborne carbon nanocrystal aggregates. ICP elemental analysis of the melt water showed significant concentrations of Ca, K and especially Na (corresponding to K, NaCl), S, Si, Se, and Zn. Overall, the elemental analysis of the melt water is similar to local tap water. However, lead was absent in the local tap water and only half the concentration of selenium was present in the tap water in contrast to the ice core water. While these observations cannot be generalized, the methodology illustrates the potential to characterize and compare airborne particulate regimes and water chemistries in antiquity.

Mycobacterium tuberculosis at a comprehensive cancer centre: active disease in patients with underlying malignancy during 1990-2000.

Thirty HIV-seronegative cancer patients with active tuberculosis were evaluated. Eighteen (60%) were immigrants, 19 (63%) had haematological malignancy, and fever was the most common presentation (97%). Of 19 (63%) patients with pulmonary tuberculosis, 11 (58%) were misdiagnosed initially as suffering from cancer following radiography. Death was attributed to tuberculosis for six (21%) of 29 patients who received anti-mycobacterial therapy. All four patients who had received high-dose systemic corticosteroids within 4 weeks of diagnosis of infection died, whereas two (8%) deaths occurred in 25 individuals without corticosteroid exposure (p < 0.001; OR 8.67). At this institution, active tuberculosis was rare, and was seen mostly in immigrants. Recent high-dose corticosteroid therapy is a significant predictor of mortality in cancer patients with tuberculosis.