Clinical relevance of quantitative varicella-zoster virus (VZV) DNA detection in plasma after stem cell transplantation

Detection of Varicella-Zoster virus (VZV) DNA in plasma can facilitate the early recognition of complicated VZV-infection in immunocompromised hosts. The correlation of VZV-DNA in plasma with clinical presentations of VZV-infection and subsequent aciclovir treatment in allogeneic stem cell transplant (allo-SCT) recipients was studied. In 81 consecutive VZV-IgG positive allo-SCT recipients, VZV-DNA was measured at regular time points (1, 2 and 4 months) following allo-SCT and patient records were screened for VZV-related symptoms and aciclovir treatment. Subsequently, possible VZV-cases were studied in detail for the course of VZV-DNA and treatment effects. During the initial screening, VZV-DNA was detectable in seven patients. The survey of VZV-related symptoms revealed five additional possible VZV-cases. In cases where suitable plasma samples were available (10 out of 12), VZV-DNA was present almost simultaneously with the first clinical manifestations. No evidence of a preceding phase detectable by VZV-DNA only could be observed. Treatment with aciclovir was associated with a prompt reduction of VZV-DNA load. Detection of VZV-DNA in plasma in allo-SCT recipients accurately reflected the clinical presentation of VZV-infection and treatment with aciclovir. VZV-DNA detection in plasma of allo-SCT recipients appears clinically relevant as this may support early recognition and therapeutic management of VZV-infections following allo-SCT.     

Characterization of the genome of human enteroviruses: design of generic primers for amplification and sequencing of different regions of the viral genome

Human enteroviruses are among the most common viruses infecting humans and can cause diverse clinical syndromes ranging from minor febrile illness to severe and potentially fatal diseases. Biodiversity and evolution of human enterovirus genomes are shaped by frequent recombination events. Therefore, identification and characterization of circulating strains of enteroviruses require partial determination of different genomic regions. The development is described of a simple method allowing amplification and partial sequencing of the P1, P2 and P3 genomic regions of field human enterovirus strains isolated in cell cultures, by performing PCR on cDNAs generated through a single RT reaction. A set of generic primers were designed and tested on a panel of 90 field and prototype viruses belonging to the five species of human enteroviruses. This assay was shown to amplify efficiently the targeted regions of all the 90 genomes tested. The generated amplicons were sequenced successfully without the need for gel purification. This assay could be a valuable tool for laboratories interested in molecular epidemiology and evolution studies implicating a great number of human enterovirus strains isolated from human or environmental samples.     

Results of hematopoietic stem cell transplantation after treatment with different high-dose total-body irradiation regimens in five Dutch centers

PURPOSE: To evaluate results of high-dose total-body irradiation (TBI) regimens for hematopoietic stem cell transplantation. METHODS AND MATERIALS: A total of 1,032 patients underwent TBI in one or two fractions before autologous or allogeneic hematologic stem cell transplantation for acute leukemia and non-Hodgkin's lymphoma. The TBI regimens were normalized by using the biological effective dose (BED) concept. The BED values were divided into three dose groups. Study end points were relapse incidence (RI), non-relapse mortality (NRM), relapse-free survival (RFS), and overall survival (OS). Multivariate analysis was performed, stratified by disease. RESULTS: In the highest TBI dose group, RI was significantly lower and NRM was higher vs. the lower dose groups. However, a significant influence on RFS and OS was not found. Relapses in the eye region were found only after shielding to very low doses. Age was of significant influence on OS, RFS, and NRM in favor of younger patients. The NRM of patients older than 40 years significantly increased, and OS decreased. There was no influence of age on RI. Men had better OS and RFS and lower NRM. Type of transplantation significantly influenced RI and NRM for patients with acute leukemia and non-Hodgkin's lymphoma. There was no influence on RFS and OS. CONCLUSIONS: Both RI and NRM were significantly influenced by the size of the BED of single-dose or two-fraction TBI regimens; OS and RFS were not. Age was of highly significant influence on NRM, but there was no influence of age on RI. Hyperfractionated TBI with a high BED might be useful, assuming NRM can be reduced.     

Hodgkin's and non-Hodgkin's hepatic lymphoma: Sonographic findings

The sonographic studies of 72 patients with pathologically proven Hodgkin's or non-Hodgkin's hepatic lymphoma were retrospectively reviewed. Sixty-eight patients (94%) had secondary hepatic lymphoma (nine of them had AIDS-related lymphoma) and four patients (6%) had primary lymphoma of the liver. Forty-six of 72 patients (64%) had diffuse hepatic involvement, and 26 of 72 patients (36%) had focal liver lesions as demonstrated by sonography. Four patterns of disease were identified: (a) hepatomegaly was depicted by sonography in 26 of the 59 patients with secondary hepatic lymphoma not related to AIDS, in two of the nine patients with AIDS-related secondary hepatic lymphoma, and in one of the four patients with primary hepatic lymphoma; (b) multiple rounded well-delineated hypoechoic liver lesions were found in 22 of the 68 patients with secondary hepatic lymphoma; (c) a large heterogeneous echoic mass, which was an evocating clue to the diagnosis of primary lymphoma of the liver, was found in the four patients with primary lymphoma of the liver; and (d) an absence of sonographic abnormalities was found in 20 of the 59 patients with secondary lymphoma not related to AIDS. Liver involvement with lymphoma should be considered in any patient who develops multiple homogeneous hypoechoic liver masses, even in the absence of known underlying lymphomatous disease.     

Solid lipid nanoparticles carrying lipophilic derivatives of doxorubicin: preparation,characterization, and in vitro cytotoxicity studies

Doxorubicin (DOXO) lauroyl ester and amide were proposed as lipophilic derivatives and entrapped in SLNs. DOXO derivatives-loaded SLNs were spherical shaped, had 200–300?nm mean diameters and showed 80–94% w/w drug entrapment efficiencies. The effect of DOXO derivatives-loaded SLNs and free DOXO on cell growth was examined by MTT and colony-forming assays on four different tumour cell lines: a pancreatic, CFPAC-1, a lung, A549, and two ovarian, A2780 and A2780res (DOXO-resistant). The results obtained with MTT and colony-forming assay show that although DOXO displayed an inhibition of cell proliferation greater or similar to DOXO lauroyl amide-loaded SLNs on all cell types, the effect induced by DOXO lauroyl ester-loaded SLNs was higher and concentration-dependent, and it was the only one maintained at 10^?5?mM concentration. Only DOXO lauroyl ester-loaded SLNs were able to induce a 40% inhibitory effect on A2780 res cell line up to 10^?4?mM concentration.