Frequent occurrence of parvovirus B19 DNAemia in the first year after kidney transplantation

Described for the first time in 1986, Parvovirus B19 (B19V) infection in kidney transplant recipients remains little‐known and probably underestimated. The aims of this study were to establish B19V infection frequency during the first year after kidney transplant and to determine predisposing factors and manifestations of the infection in renal transplant recipients. Sixty consecutive adult patients, transplanted less than a year before, were included in this study. B19V and other opportunistic viral infections were detected retrospectively in plasma samples collected every 15 days during the first 3 months and every month from 3 months to 1 year following the kidney transplant. Demographic characteristics, immunosuppressive treatment and biological findings were recorded on each sampling date. Six patients (10%) presented B19V viremia, while eight CMV (13.3%), seven EBV (11.7%), five HHV‐6 (8.3%), five BKV (8.3%), and two adenovirus (3.3%) infections were detected. The mean value of B19V viral load was 149 UI/ml. B19V infections were either reactivation or reinfection due to genotype two in five cases, while one case of primary infection with genotype 1 was observed. Neither risk factors nor biological consequences of B19V infection have been identified. These results rank B19V third among opportunistic viral infections occurring during the first year after a kidney transplant. With regard to this high incidence, and even if the risk factors and biological consequences of the infection should be assessed in larger studies, the question of systematic screening and follow‐up of B19V infection in kidney transplant recipients is relevant. J. Med. Virol. 85: 1115–1121, 2013. © 2013 Wiley Periodicals, Inc.     

Dissecting the Structure and Mechanism of a Complex Duplication–Triplication Rearrangement in the DMD Gene

Pathogenic complex genomic rearrangements are being increasingly characterized at the nucleotide level, providing unprecedented opportunities to evaluate the complexities of mutational mechanisms. Here, we report the molecular characterization of a complex duplication–triplication rearrangement involving exons 45–60 of the DMD gene. Inverted repeats facilitated this complex rearrangement, which shares common genomic organization with the recently described duplication‐inverted triplication–duplication (DUP–TRP/INV‐DUP) events; specifically, a 690‐kb region comprising DMD exons from 45 to 60 was duplicated in tandem, and another 46‐kb segment containing exon 51 was inserted inversely in between them. Taking into consideration (1) the presence of a predicted PRDM9 binding site in the near vicinity of the junction involving two inverted L1 elements and (2) the inherent properties of X–Y chromosome recombination during male meiosis, we proposed an alternative two‐step model for the generation of this X‐linked DMD DUP–TRP/INV‐DUP event.     

Evaluating the landscape of gene cooperativity with receptor tyrosine kinases in liver tumorigenesis using transposon-mediated mutagenesis

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Serum-free liquid marrow culture in patients with acute lymphoblastic leukaemia: a potential application to purge marrow for autologous transplantation

We have previously established a serum-free (SF) culture medium, which supports normal haemopoietic progenitor cell growth for at least 4 weeks as does conventional serum dependent (SD) medium. In the present study, we investigated the efficacy of such a defined SF liquid medium which sustained in vitro residual normal haemopoietic proliferation of marrow derived from ALL patients and which was detrimental for the leukaemic population. Evidence for a potential selective effect of SF culture was obtained by a leukaemic progenitor cell assay (ALL-CFU) and the detection of the bcr/abl translocation by polymerase chain reaction (PCR). In 13 experiments including 12 patients, morphological blast cells and ALL-CFU were dramatically reduced within 3 weeks of incubation in both SF and SD cultures. Likewise, in 5/5 experiments in SD and 2/5 experiments in SF conditions, leukaemic cells expressing the bcr/abl fusion gene disappeared within 3-4 weeks. In contrast, the absolute numbers of supernatant cells harvested weekly from SF and SD cultures were similar. No difference in CFU-GM production was detected for the two culture systems. Erythropoiesis in SF medium exhibited a slower decline than that found in SD. These results indicate that liquid marrow culture may selectively deplete leukaemic lymphoblastic cells and enable repopulation by residual normal haemopoietic cells. This technique may be useful to purge leukaemic cells for clinical autologous bone marrow transplantation in patients with ALL.     

Efficacy and safety of leflunomide and predisposing factors for treatment response in patients with active rheumatoid arthritis: RELIEF 6-month data

OBJECTIVE: The RELIEF investigation was a 48-week, multicenter, international study comprising 2 phases. Results from the first phase, a 24-week open-label cohort study that evaluated the safety and efficacy of leflunomide, as well as predisposing factors to treatment response, are reported here. METHODS: Patients received leflunomide 100 mg once daily for 3 days, followed by 20 mg once daily thereafter. All adverse events were documented. Efficacy variables were the European League Against Rheumatism (EULAR) response criteria using the Disease Activity Score (DAS 28) responder rate and the response rate according to American College of Rheumatology (ACR) criteria. At Week 24, baseline data were analyzed to determine predictive factors for treatment response. RESULTS: A total of 969 patients were entered in the trial. No adverse events that have not previously been seen with leflunomide were reported. Among 968 evaluable patients, 673 (69.6%) completed 24 weeks of treatment and were responders according to DAS 28 response rate, and 587 (60.6%) completed 24 weeks of treatment and were responders according to ACR 20%. Thus, there was a high correlation between the EULAR and ACR criteria in determining treatment response. In addition, 240 (24.8%) patients had a low DAS 28 (< or = 3.2) and 123 (12.7%) patients fulfilled the disease remission criteria (DAS 28 < 2.6) at the end of the study. CONCLUSION: This study demonstrates that leflunomide is well tolerated, with a safety profile similar to that seen previously in Phase III studies, and confirms the efficacy of leflunomide across a range of patient categories.