Effects of l-Acetylcarnitine on Cirrhotic Patients with Hepatic Coma: Randomized Double-Blind, Placebo-Controlled Trial

Multiple therapeutic modalities have been used to treat hepatic encephalopathy. l-Acetylcarnitine (LAC) is a physiologically active substance that improves both the energetic and the neurotransmission profiles. LAC is able to cross the hematoencephalic barrier and reach the cerebral regions, where the acetylic group may be utilized. The aim of this work was to evaluate the efficacy of LAC in the treatment of hepatic coma in cirrhotic patients. Twenty-four suitably selected patients were enrolled in the study and, following randomization, received either LAC (n=13) or placebo (n=11). Statistically significant differences in neurological findings, as evaluated by the Glasgow Scale, as well as in ammonia serum levels and BUN were found following LAC treatment. In the placebo group we observed two cases of improved neurological findings as well as one case of improved EEG grading. In the other group we observed an improvement of neurological findings and of EEG grade in 10 and 8 subjects, respectively. Noteworthily, seven (54%) patients went from grade 4 down to grade 3, and one from grade 4 down to grade 1. The improvement in the neurological picture was evident at between 1 and 4 hr after the end of treatment, remaining until 24 hr after. No side effects were observed in our study series. Our study demonstrates that LAC administration improved neurological and biohumoral symptoms in selective cirrhotic patients with hepatic coma.     

Usefulness of aspirin resistance after percutaneous coronary intervention for acute myocardial infarction in predicting one-year major adverse coronary events

Recently, great interest has focused on the phenomenon of aspirin resistance, which may be defined as clinical or laboratory resistance. Monitoring the antiplatelet effect appears to be relevant in the presence of clinical implications, but no data are available on the possible clinical implications of the failure of aspirin to inhibit tests of platelet function in the setting of acute coronary syndromes. This study evaluated the role of aspirin resistance in the occurrence of 1-year major adverse coronary events (MACEs) in patients with acute myocardial infarction (AMI) who have undergone percutaneous coronary intervention (PCI). We prospectively evaluated 146 patients (115 men and 31 women; median age 65 years, range 30 to 84) with AMI who underwent primary PCI. Exclusion criteria were the use of glycoprotein IIb/IIIa inhibitors, hematocrit 相似文献   

Population pharmacokinetics of gentamicin in premature newborns

OBJECTIVES: To determine the pharmacokinetic parameters of gentamicin in a population of 200 premature newborns and to investigate the influence of several clinical and physiopathological covariates on the pharmacokinetics of the drug. To validate the pharmacokinetic analysis performed in another population of 50 premature newborns. METHODS: A total of 200 premature newborns were evaluated at the neonatal intensive care unit of Severo Ochoa Hospital (Madrid, Spain). Four hundred and seventeen serum drug concentrations were included. Mean gestational age (GA) was 32.19+/-2.97 weeks, mean postnatal age (PNA) was 5.49+/-5.41 days and mean body weight (BW) was 1.68+/-0.63 kg. Fifty additional newborns were studied for validation (mean GA 32.62+/-3.07 weeks, mean PNA 5.17+/-3.77 days and mean BW 1.80+/-0.67 kg). Dosing, serum gentamicin concentrations and 15 covariates were collected. Data analysis was performed with NONMEM. One- and two-compartment open models were evaluated. Four parameters were analysed with the two-compartment open model: clearance (CL), central volume (Vc), peripheral volume (Vp) and intercompartmental clearance (Q). RESULTS AND CONCLUSIONS: The two-compartment open model was found to significantly better describe gentamicin pharmacokinetics in the neonate. More than PNA or GA, creatinine clearance (CLCR) plays an important role in the elimination of gentamicin in premature newborns. Creatinine clearance is also related to GA. The appropriate dosing regimens given in accordance with the characteristics of the patients are 5 mg/kg/48 h and 4 mg/kg/24 or 36 h for neonates<32 weeks and >or=32 weeks of GA, respectively.     

Hematopoietic stem cells provide repair functions after laser-induced Bruch's membrane rupture model of choroidal neovascularization

Vascular repair by adult hematopoietic stem cells (HSCs) is well-appreciated because these cells are known for their plasticity. We have shown that adult HSCs differentiate into endothelial cells and participate in both retinal and choroidal neovascularization. We asked whether HSCs participated in the wounding response by forming astrocytes, retinal pigment epithelia (RPE), macrophages, and pericytes. Lethally irradiated C57BL6/J mice were reconstituted with HSCs from mice homozygous for green fluorescent protein (GFP) and then subjected to laser-induced rupture of Bruch's membrane. After immunohistochemical examination of ocular tissue, GFP(+) astrocytes were observed concentrated along the edge of the laser wound, where they and mural cells closely ensheathed the neovasculature. GFP(+) vascular endothelial cells and macrophages/microglia were also evident. Large irregularly shaped GFP(+) RPE cells constituted approximately 93% of RPE cells adjacent to the edge of the denuded RPE area. In regions farther away from the wound, GFP(+) RPE cells were integrated among the GFP(-) host RPE. Thus, postnatal HSCs can differentiate into cells expressing markers specific to astrocytes, macrophages/microglia, mural cells, or RPE. These studies suggest that HSCs could serve as a therapeutic source for long-term regeneration of injured retina and choroid in diseases such as age-related macular degeneration and retinitis pigmentosa.     

A new prognostic model identifies patients aged 80 years and older with diffuse large B‐cell lymphoma who may benefit from curative treatment: A multicenter,retrospective analysis by the Spanish GELTAMO group

The means of optimally managing very elderly patients with diffuse large B‐cell lymphoma (DLBCL) has not been established. We retrospectively analyzed 252 patients aged 80‐100 years, diagnosed with DLBCL or grade 3B follicular lymphoma, treated in 19 hospitals from the GELTAMO group. Primary objective was to analyze the influence of the type of treatment and comorbidity scales on progression‐free survival (PFS) and overall survival (OS). One hundred sixty‐three patients (63%) were treated with chemotherapy that included anthracyclines and/or rituximab, whereas 15% received no chemotherapeutic treatment. With a median follow‐up of 44 months, median PFS and OS were 9.5 and 12.5 months, respectively. In an analysis restricted to the 205 patients treated with any kind of chemotherapy, comorbidity scales did not influence the choice of treatment type significantly. Independent factors associated with better PFS and OS were: age < 86 years, cumulative illness rating scale (CIRS) score < 6, intermediate risk (1‐2) R‐IPI, and treatment with R‐CHOP at full or reduced doses. We developed a prognostic model based on the multivariate analysis of the 108 patients treated with R‐CHOP‐like: median OS was 45 vs. 12 months (P = .001), respectively, for patients with 0‐1 vs. 2‐3 risk factors (age > 85 years, R‐IPI 3‐5 or CIRS > 5). In conclusion, treatment with R‐CHOP‐like is associated with good survival in a significant proportion of patients. We have developed a simple prognostic model that may aid the selection patients who could benefit from a curative treatment, although it needs to be validated in larger series.     

Multidimensional Poverty Among Adolescents in 38 Countries: Evidence from the Health Behaviour in School-aged Children (HBSC) 2013/14 Study

This study applied UNICEF’s Multiple Overlapping Deprivation Analysis (MODA) framework to adolescents (aged 11, 13 and 15) in 37 European countries and Canada using data from the 2013/14 Health Behaviour in School-aged Children survey. It is one of the first applications of MODA based entirely on data collected from adolescents themselves rather than from household reference persons on their behalf. Unlike most other multidimensional child poverty studies, the present analysis focuses on non-material, relational aspects of child poverty. Substantial cross-country variation was found in the prevalence of adolescent deprivations in nutrition, perceived health, school environment, protection from peer violence, family environment and information access. These single dimensions of poverty did not closely relate to national wealth and income inequality. However, when we looked at deprivation in three or more dimensions (i.e., multidimensional poverty), we found association with income inequality. In most countries, girls were at a higher risk of multidimensional poverty than boys. In addition, adolescents who lived with both parents in the household or reported higher family wealth were consistently less poor than other adolescents, in both single and multiple dimensions. The results of this study show the interconnectedness of social (family, school support) and psychological (health and violence) dimensions of poverty for adolescents in higher income countries. Children poor in the domains of family and school environment are also likely to be poor in terms of perceived health and protection from peer violence.     

Incisions in cataract surgery through phacoemulsification

Cataract surgery begins and ends with the incision. Incision has evolved also after the advent of facoemulsification, as the current trend is to smaller safer, less astigmatogen and fast healing incisions.     

Species Identification and Antifungal Susceptibility Patterns of Species Belonging to Aspergillus Section Nigri

A phylogenetic analysis was performed for 34 Aspergillus strains belonging to section Nigri. Molecular methods allowed for the correct classification into three different clades (A. niger, A. tubingensis, and A. foetidus). Correlation with in vitro itraconazole susceptibility distinguished the following three profiles: susceptible, resistant, and showing a paradoxical effect. A number of different species whose morphological features resemble those of A. niger showed unusual MICs to itraconazole that have never been described for the Aspergillus genus.Black aspergilli are widely distributed in nature (16); they are common food spoilers but are also well used for industrial purposes (15). Among Aspergillus species of the Nigri group, A. niger constitutes the most frequent etiological agent of otomycosis (13) and is considered the third cause of pulmonary aspergillosis (10). Nevertheless, the clinical implications of other species are rarely reported, and they are generally identified as A. niger (14, 22).Clinically, identification of unknown Aspergillus clinical isolates to the species level may be important given that different species have dissimilar susceptibilities to antifungal drugs. Thus, the knowledge of the species identity may influence the choice of appropriate antifungal therapy (2, 4). Furthermore, since the antifungal susceptibility patterns for most of the species within section Nigri have been poorly investigated, their identification and antifungal susceptibility profiles appear to be of clinical interest for further research.Black aspergilli belong to one of the most difficult groups concerning classification and identification (18), and so a number of different techniques have been developed in order to solve this issue. Among them, molecular tools are the gold standard (1, 18), as the sequencing of the β-tubulin or calmodulin gene is suitable, and enough, to discriminate between species within section Nigri (3, 18, 21).Thirty-four Aspergillus section Nigri strains belonging to the Mold Collection of the Centro Nacional de Microbiologia and collected since 2004 were analyzed. Thirty-three strains were independent clinical isolates, and 1 had an environmental origin. All strains were identified as A. niger using conventional methods of morphology at the macroscopic as well as microscopic levels (9). Species identification analysis was addressed using sequences of the β-tubulin gene from all the strains included in this study together with the sequences of different Aspergillus section Nigri type strains and others that were available at GenBank as follows: A. tubingensis {"type":"entrez-nucleotide","attrs":{"text":"AY820007","term_id":"65307061","term_text":"AY820007"}}AY820007^T, {"type":"entrez-nucleotide","attrs":{"text":"AY820009","term_id":"65307063","term_text":"AY820009"}}AY820009, and {"type":"entrez-nucleotide","attrs":{"text":"AY585527","term_id":"53830386","term_text":"AY585527"}}AY585527; A. foetidus {"type":"entrez-nucleotide","attrs":{"text":"AY585533","term_id":"53830397","term_text":"AY585533"}}AY585533^T, {"type":"entrez-nucleotide","attrs":{"text":"AY585534","term_id":"53830399","term_text":"AY585534"}}AY585534, and {"type":"entrez-nucleotide","attrs":{"text":"DQ768454","term_id":"111609935","term_text":"DQ768454"}}DQ768454; and A. niger {"type":"entrez-nucleotide","attrs":{"text":"FJ629288","term_id":"225904264","term_text":"FJ629288"}}FJ629288^T, {"type":"entrez-nucleotide","attrs":{"text":"EF422213","term_id":"126105445","term_text":"EF422213"}}EF422213, and {"type":"entrez-nucleotide","attrs":{"text":"AY585537","term_id":"53830403","term_text":"AY585537"}}AY585537. Partial sequences of the β-tubulin gene were amplified using the primer set βtubAniger1 and βtubANiger2 (11) and were carried out according to standard PCR guidelines (Applied Biosystems). Sequences were assembled and edited using the SeqMan II and EditSeq software packages (Lasergene 8.0; DNAStar, Inc., Madison, WI).All phylogenetic analyses were conducted with InfoQuest FP software, version 4.50 (Bio-Rad). The methodology used was maximum parsimony clustering. Phylogram stability was assessed by using parsimony bootstrapping with 2,000 simulations and by using the Aspergillus clavatus {"type":"entrez-nucleotide","attrs":{"text":"AY214441","term_id":"32441964","term_text":"AY214441"}}AY214441^T sequence as the out-group.The phylogenetic tree grouped the 34 clinical isolates into three different clades consisting of 13 A. niger isolates, 18 A. tubingensis isolates, and 3 A. foetidus isolates (Fig. ​(Fig.1).1). Table ​Table11 shows β-tubulin gene identification, as well as the origin and susceptibility profiles of the isolates.Open in a separate windowFIG. 1.Phylogenetic tree using maximum parsimony phylogenetic analysis and 2,000 bootstrap simulations based on β-tubulin gene sequences from all the Aspergillus section Nigri strains included in the study. Percentages indicate the bootstrap support for each group of sequences. (T), type strain.

TABLE 1.

Source, molecular identification, MICs, and MECs for species of Aspergillus section Nigri^a