1,721,004 research outputs found
Pharmacokinetic/pharmacodynamic evaluation of linezolid in hospitalized paediatric patients: a step toward dose optimization by means of therapeutic drug monitoring and Monte Carlo simulation.
No full textObjectives: To report on linezolid exposure in a paediatric population who routinely underwent therapeutic drug monitoring (TDM) for dosage optimization and to assess the factors affecting interpatient variability. Methods: We performed a retrospective study of patients whose plasma Cmin and Cmax levels were measured during linezolid treatment. Adequate exposure was defined as a Cmin of 2-7 mg/L and/or an estimated AUC24 of 160-300 mg·h/L. Patients were divided into two subgroups (Group 1, 2-11 years; Group 2, 12-18 years). Monte Carlo simulation was performed to investigate whether or not the currently recommended dosages might enable a high probability of target attainment (PTA) of two thresholds for linezolid efficacy (AUC24/MIC ≥ 80 or ≥ 100). Data on demographic characteristics, disease, microbiology and haematochemical parameters and outcomes were collected. Results: A total of 23 patients were included. Standard dosages were suboptimal in 50.0% and 44.4% of patients in Group 1 and Group 2, respectively. Among those who underwent multiple instances of TDM, the dosages were increased in 33.3% of cases in both groups, and decreased in 6.6% and 9.5% of cases in Group 1 and Group 2, respectively. Co-treatment with phenobarbital, proton pump inhibitors and amiodarone accounted for most of the variability in Cmin (adjusted R2 of 0.692). Simulations showed a PTA of ≥90% with the current dosing regimens in both groups only for pathogens with an MIC ≤1 mg/L. Conclusions: Higher dosages of linezolid may be needed, especially in Group 1 when in the presence of pathogens with an MIC >1 mg/L. The role of TDM should be encouraged for optimization of linezolid exposure in the paediatric setting in the presence of infections caused by pathogens with borderline susceptibility and/or for patients co-treated with drugs that may alter linezolid exposure. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved
Design of a system to achieve diagnosis of brain lesions of suspected infectious origin from a database and a radiologic software
No full textThis project aims at creating an international database including an extensive collection of radiologic images of brain lesions and the relevant clinical, laboratory and microbiological data, and a software, to highlight and differentiate the minimal alteration in the radiologic footprint related to the local alterations of brain tissue produced by each individual pathogen that will become an objective diagnostic tool. Clinical parameters will be taken into account in defining a measure to estimate the probability that the difference between an image and a template be due to a specific pathological agent
What is known about deferasirox chelation therapy in pediatric HSCT recipients: two case reports of metabolic acidosis
No full textCarmen Fucile,1 Francesca Mattioli,1 Valeria Marini,1 Massimo Gregori,2 Aurelio Sonzogni,3 Antonietta Martelli,1 Natalia Maximova4 1Pharmacology and Toxicology Unit, University of Genoa, Genoa, Italy; 2Department of Pediatric Radiology, Institute for Maternal and Child Health – IRCCS Burlo Garofalo, Trieste, Italy; 3Department of Pathology, Ospedale Beato Papa Giovanni XIII, Bergamo, Italy; 4Bone Marrow Transplant Unit, Institute for Maternal and Child Health – IRCCS Burlo Garofalo, Trieste, Italy Abstract: To date, in pediatric field, various hematological malignancies are increasingly treated with allogeneic hematopoietic stem cell transplantation (allo-HSCT). Iron overload and systemic siderosis often occur in this particular cohort of patients and are associated with poor prognosis. We describe herein the case of two allo-HSCT patients, on treatment with deferasirox; they showed histopathological elements compatible with venoocclusive disease or vanishing bile duct syndrome in ductopenic evolution before deferasirox started. The first patient developed drug-induced liver damage with metabolic acidosis and the second one a liver impairment with Fanconi syndrome. After withdrawing deferasirox treatment, both patients showed improvement. Measurements of drug plasma concentrations were performed by HPLC assay. The reduction and consequent disappearance of symptoms after the suspension of deferasirox substantiate its role in inducing hepatic damage, probably enabling the diagnosis of drug-induced liver damage. But the difficulties in diagnosing drug-related toxicity must be underlined, especially in compromised subjects. For these reasons, in patients requiring iron-chelating therapy, close and careful drug therapeutic monitoring is strongly recommended. Keywords: deferasirox, allogeneic hematopoietic stem cell transplantation, allo-HSCT, pediatric, ductopenia, therapeutic drug monitoring, adverse event
INTERNATIONAL MULTI-CENTRE DATA GATHERING FOR THE ESTABLISHMENT OF A DATABASE AND A RADIOLOGIC SOFTWARE THAT CAN BE USED FOR THE DIFFERENTIAL DIAGNOSIS OF BRAIN LESIONS OF AN INFECTIOUS ORIGIN
No full textHematopoietic stem cell transplantation effects on spinal cord compression in Hurler.
No full textHurler syndrome type 1 (MPS-1) is an autosomal recessive lysosomal disorder due to the deficiency of the enzyme alpha-L-iduronidase which is necessary for the degradation of dermatan and heparan sulfate. It is characterized by deposit of glycosaminoglycans in tissues, progressive multisystem dysfunction, and early death. HSCT for children with MPS-I is effective, resulting in increased life expectancy and improvement of clinical parameters. The spinal MRI performed on a female 10 yr old undergoing HSCT at the age of 18 months and receiving ERT revealed a considerable decrease in soft tissue around the tip of odontoid causing a significant reduction in spinal cord compression. In light of this result, we suppose that combined ERT and HSCT are successful in Hurler I disease
First description of Merkel Cell polyomavirus DNA detection in a patient with Stevens-Johnson syndrome
No full textMerkel Cell polyomavirus (MCPyV), a ubiquitous DNA tumor virus, has been found to be associated with Merkel cell carcinoma and chronic lymphocytic leukaemia while other associations are still being explored. MCPyV sequences have also been detected in normal tissues of tumor patients and in the blood of healthy donors. This report documents a new MCPyV association with the Stevens-Johnson syndrome, a rare immune-modulated mucocutaneous process particularly associated with specific drugs and infective agents. A high MCPyV viral load was detected simultaneously in fluid from skin lesions (2.0 × 10(4) copies/ml) and in matched blood (7.4 × 10(5) copies/ml) from a young adult patient after bone marrow transplant for a relapsed T-cell acute lymphatic leukaemia. MCPyV clearance concurred with the complete resolution of skin lesions after 5 days of cidofovir treatment. DNA sequencing classified the amplicons as the European/Italian MKL-1 strain. Given its ubiquitous nature, MCPyV could account for part of Stevens-Johnson syndrome idiopathic case
Hemorrhagic cystitis in children undergoing bone marrow transplantation: aputative role for simian virus 40
No full textBACKGROUND: Late-onset hemorrhagic cystitis (HC) is a well-known severe complication of bone marrow transplantation (BMT), both in adults and in children. Protracted postengraftment HC is associated with graft-versus-host disease and viral infections, mainly caused by BK virus (BKV) or adenovirus (AV). This study investigated whether simian virus 40 (SV40) DNA sequences can be detected in specimens from pediatric patients affected by severe postengraftment HC. METHODS: The clinical diagnosis of HC was made in 7 of 28 BMT children. DNA from peripheral blood mononuclear cells (PBMC) and urine sediment cells and supernatants was analyzed by polymerase chain reaction (PCR) for human cytomegalovirus (HCMV), AV, BKV, JC virus (JCV), and SV40. DNA filter hybridization and sequencing was carried out in SV40-positive samples. RESULTS: SV40 footprints were detected in two of seven cases of HC. Specific SV40 DNA sequences were detected by PCR and by filter hybridization both in urine and in PBMC samples at the HC onset and during the follow-up. The DNA sequencing proved that the amplicons belonged to the SV40 wild-type. Urine samples of the two HC cases tested negative by cell cultures, PCR, or both for HCMV, BKV, JCV, and AV. CONCLUSIONS: The detection of SV40 DNA sequences suggest that this simian polyomavirus could be involved, at least in some cases, in the HC occurring in children after BMT
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
- …
