Measurement of antibodies to varicella-zoster virus in a tropical population by enzyme-linked immunosorbent assay.

We used the recently developed enzyme-linked immunosorbent assay for antibody to varicella-zoster virus to study the prevalence and titers of virus-specific antibody in a south Indian population of 171 individuals 0 to 25 years old. The antibody prevalence rate was less than 15% in individuals under 5 years of age and gradually rose to a maximum of 72% in young adults 15 to 25 years of age. The median age of primary infection was 12.25 years. The geometric mean antibody titers were between 1:80 and 1:160 in the age groups with antibody. These results are different from the pattern of seroepidemiology of varicella-zoster virus infection in temperate countries and indicate that varicella is predominantly a disease of young adults in the population studied.     

Standardized nested polymerase chain reaction-based assay for detection of human immunodeficiency virus type 1 DNA in whole blood lysates.

The routine detection of human immunodeficiency virus type 1 (HIV-1) proviral DNA in clinical samples requires a standardized, simple, and sensitive test. To identify the HIV-1 proviral DNA in blood, we used a solid-phase assay based on the affinity capture and the gamma counting of the amplified product after a nested polymerase chain reaction (AMPLICIS test). In order to simplify the general process, whole-blood lysates rather than peripheral blood mononuclear cell lysates were used for the amplifications. The solid-phase capture and counting of the final amplified products allowed us to define precise interpretive criteria to determine the positivity level of the test. Three new primer sets located in the gag and pol structural genes and in the tat regulatory gene of HIV-1 were studied. The results obtained in 54 seropositive and 120 seronegative individuals demonstrated the ability of the AMPLICIS test to be used for HIV-1 provirus detection: 53 of 54 of the seropositive specimens were found to be positive with at least two primer sets. We also assessed the usefulness of this test for the estimation of the HIV-1 DNA load by the end point dilution method with serial dilutions of blood lysates from 26 HIV-1-seropositive patients.     

Multiple sclerosis retrovirus particles and recombinant envelope trigger an abnormal immune response in vitro, by inducing polyclonal Vbeta16 T-lymphocyte activation

A retroviral element (MSRV) defining a family of genetically inherited endogenous retroviruses (HERV-W) has recently been characterized in cell cultures from patients with multiple sclerosis (MS). To address the possible relationship with MS, direct detection of circulating virion RNA was proposed but revealed technically difficult to perform in standardized conditions, in the face of multiple endogenous HERV-W copies. A parallel approach has evaluated MSRV potential pathogenicity in relation to characteristic features of multiple sclerosis, in particular, T-lymphocyte-mediated immunopathology. We report here that MSRV particles induce T-lymphocyte response with a bias in the Vbeta16 chain usage in surface receptor, whatever the HLA DR of the donor. A recombinant MSRV envelope-but not core-protein reproduced similar nonconventional activation. Molecular analysis of Vbeta CDR3 showed that Vbeta16 expansions are polyclonal. Our results thus provide evidence that MSRV envelope protein can trigger an abnormal immune response with similar characteristics to that of superantigens.     

T-cell death by apoptosis in vertically human immunodeficiency virus- infected children coincides with expansion of CD8+/interleukin-2 receptor-/HLA-DR+ T cells: sign of a possible role for herpes viruses as cofactors?

One mechanism proposed to play a role in T-cell depletion in human immunodeficiency virus (HIV) infection is apoptosis (activation-induced cell death). We assessed whether apoptosis is related to activation of T cells in vivo and its possible triggers. DNA was extracted from peripheral blood mononuclear cells (PBMC) taken from 16 vertically HIV- infected children and 9 HIV-negative children born to HIV-positive mothers (controls) and tested by agarose gel electrophoresis for the presence of DNA fragments specific for apoptosis. Signs of apoptosis were found on in vitro culture of PBMC from 12 of 16 HIV-infected children, but not in PBMC from the nine controls. Eleven of the 12 HIV- infected children with apoptosis showed an elevated (> 15%) proportion of CD3+/HLA-DR+ cells. This was due to an increased proportion of CD8+/HLA-DR+ cells, as shown in 7 of 7 further tested patients. In none of the probands an increased (> 5%) proportion of IL-2 receptor expressing CD3+ cells was found. T cells undergoing apoptosis were preferentially of the CD8+ phenotype. Expansion of circulating CD8+/interleukin-2 receptor (IL-2R)-/HLA-DR+ T cells is known to occur during active infection with herpes viruses. To investigate the possible role of herpes viral coinfections for apoptosis in HIV infection, we focused on Epstein-Barr virus (EBV) as an example for a herpes virus usually acquired during childhood. In 10 of 12 patients with apoptosis, we found increased levels of EBV genome in PBMC and/or tissues, indicating active EBV replication. By contrast, no increased burden of EBV was found in the four HIV-infected patients without apoptosis or in the controls. Our data indicate that in children the occurrence of apoptosis in HIV infection is closely related to activation of CD8+ T cells. Furthermore, primoinfection with or reactivation of herpes viruses, such as EBV, may substantially contribute to such T-cell activation and the ensuing apoptosis. Additional studies are warranted to evaluate the contribution of herpes virus-triggered apoptosis to the T-cell loss leading to the acquired immunodeficiency syndrome.     

Evaluation of an intervention to improve blood culture practices: a cluster randomised trial

This study aimed to evaluate an intervention to improve blood culture practices. A cluster randomised trial in two parallel groups was performed at the Grenoble University Hospital, France. In October 2009, the results of a practices audit and the guidelines for the optimal use of blood cultures were disseminated to clinical departments. We compared two types of information dissemination: simple presentation or presentation associated with an infectious diseases (ID) specialist intervention. The principal endpoint was blood culture performance measured by the rate of patients having one positive blood culture and the rate of positive blood cultures. The cases of 130 patients in the “ID” group and 119 patients in the “simple presentation” group were audited during the second audit in April 2010. The rate of patients with one positive blood culture increased in both groups (13.62 % vs 9.89 % for the ID group, p?=?0.002, 15.90 % vs 13.47 % for the simple presentation group, p?=?0.009). The rate of positive blood cultures improved in both groups (6.68 % vs 5.96 % for the ID group, p?=?0.003, 6.52 % vs 6.21 % for the simple presentation group, p?=?0.017). The blood culture indication was significantly less often specified in the request form in the simple presentation group, while it remained stable in the ID group (p?=?0.04). The rate of positive blood cultures and the rate of patients having one positive blood culture improved in both groups. The ID specialist intervention did not have more of an impact on practices than a simple presentation of audit feedback and guidelines.     

Idarubicin vs doxorubicin in transarterial chemoembolization of intermediate stage hepatocellular carcinoma

BACKGROUND Liver cancer is the fifth most common cancer and the second cause of cancerrelated deaths worldwide.Transarterial chemoembolization(TACE)is the best treatment of intermediate hepatocellular carcinoma(HCC).Doxorubicin is the most commonly used drug despite a low level of evidence.AIM To compare the objective response rate of idarubicin-based TACE(Ida-TACE)against doxorubicin-based TACE(Dox-TACE)in intermediate stage HCC.METHODS Between January 2012 and December 2014,all patients treated with TACE at our academic hospital were screened.Inclusion criteria were patients with Child-Pugh score A or B,a performance status below or equal to 1,and no prior TACE.Either lipiodol TACE or drug-eluting beads TACE could be performed with 10 mg of idarubicin or 50 mg of doxorubicin.Each patient treated with idarubicin was matched with two doxorubicin-treated patients.The TACE response was assessed by independent radiologists according to the mRECIST criteria.RESULTS Sixty patients were treated with doxorubicin and thirty with idarubicin.There were 93%and 87%of cirrhotic patients and 87%and 70%of Child-Pugh A in the doxorubicin and idarubicin groups,respectively.The median number of HCC per patient was two in both groups with 31%and 26%of single nodules in doxorubicin and idarubicin groups,respectively.Objective response rate after first TACE was 76.7%and 73.3%(P=0.797)with 41.7%and 40.0%complete response in doxorubicin and idarubicin groups,respectively.Progression-free survival was 7.7 mo in both groups,and liver transplant-free survival was 24.9 mo and 21.9 mo in doxorubicin and idarubicin groups,respectively.Safety profiles were similar in both groups,with grade 3-4 adverse events in 35%of Dox-TACE and 43%of Ida-TACEs.CONCLUSION Ida-TACE and Dox-TACE showed comparable results in terms of efficacy and safety.Ida-TACE may represent an interesting alternative to Dox-TACE in the management of patients with intermediate stage HCC.     

Real-time quantitative PCR for assessment of antiviral drug effects against Epstein-Barr virus replication and EBV late mRNA expression

This study assesses the ability of quantitative real-time PCR to measure the effects of virus DNA polymerase inhibitors on EBV DNA and late mRNAs syntheses in EBV-producing cell lines. In-house real-time quantitative PCRs were used to measure EBV DNA (thymidine kinase) and mRNAs (BLLF1 gene/gp350/220, BVRF2 gene/protease) in P3HR-1 and B95-8 cells induced for EBV production by PMA and exposed to ganciclovir, cidofovir and foscarnet. The calculated 50% effective concentrations (EC(50)) for viral DNA replication inhibition in P3HR-1 cells after 7 days of drug exposure were 0.28+/-0.06, 0.29+/-0.01 and 13.6+/-0.17 microg/mL for ganciclovir, cidofovir and foscarnet, respectively. The EC(50) for B95-8 cells were 0.44+/-0.02, 0.70+/-0.06 and 46.8+/-0.5 microg/mL, respectively. The quantitation of the late viral mRNAs showed a decrease of 79-89% in the mRNA amount after 4 days of antiviral treatment. Nevertheless, a substantial amount of mRNA still remained detectable after drug exposure. The real-time PCR is an improvement in the attempt to simplify EBV DNA-quantitation for antiviral assays. The quantitation of late mRNA does not appear as more informative than DNA quantitation for the assessment of the DNA polymerase inhibitor activity, but it may be useful to assess the antiviral activity of drugs acting by another mechanism.     

Plasma cell beta-glucuronidase and monoclonal gammapathies (author's transl)]

beta-glucuronidase activity, estimated cytochemically, is, in more than half cases of myeloma, very increased or decreased, compared to that found in benign dysglobulinemias, where this activity is normal. A very high or very low score makes sure the diagnostic of myeloma. The relations between the beta-glucuronidase activity and the myeloma clinical stade according to Durie and Salmon and the bone lysis are discussed.     

Antibody response against the Epstein-Barr virus-coded nuclear antigen2 (EBNA2) in different groups of individuals

Specific antibody responses against the 2 major subcomponents of EBNA, EBNA1 and EBNA2 were evaluated, in order to study whether this serological study was beneficial compared to classical EBV serology. During this investigation, 491 sera, obtained from blood donors and patients with Burkitt's lymphoma (BL), nasopharyngeal carcinoma (NPC), infectious mononucleosis (IM), Hodgkin's disease, renal transplantation, rheumatoid arthritis and Human Immunodeficiency Virus (HIV) infection, were tested. While the anti-EBNA1 response followed the classical anti-EBNA/Raji response (99% of anti-EBNA/Raji-positive sera also recognize EBNA1), the anti-EBNA2 response was much less frequent and did not correlate with either anti-EBNA/Raji or anti-EA antibodies. In a control population, 8% of individuals had antiEBNA2 antibodies at titers greater than or equal to 10. The percentage was 45% in NPC and 38% in EBV-associated BL; thus, although not detected in all patients with EBV-associated tumors, anti-EBNA2 serology might be a useful marker in BL and NPC. No antibody was detected in the early course of IM, but in rheumatoid arthritis and in HIV-infected patients, the percentage of positive individuals reached 54 and 68, respectively. Seroconversion to EBNA2 was noted in a few cases, including renal transplant recipients, AIDS patients, and complicated IM. This suggests that in these situations, EBNA 2 serology might represent a useful marker related to modulation of the immune status or EBV reactivation.     

Artefact-free trends in breast cancer incidence over two decades in a whole French Département

The objective was to discuss the evolution of the real incidence of breast cancer. Observed incidence as calculated by cancer registries differs from the real incidence because of the artifacts brought by diagnostic procedures and case collection. Age-period-cohort models were applied to nearly 11,200 incident breast cancers collected by the Cancer Registry of Isère from 1983 to 2002 in women aged 30–84. We took into account prior knowledge and assumptions concerning the evolution of real incidence, diagnostic procedures, and collection of cases. In the age group 30–49, no real incidence increase was seen if we assume that diagnostic procedures and collection of cases were not impaired. In women aged 50–69, an increase of real incidence and intensive screening could explain the increase of observed incidence but exact quantifications are difficult. At most, the increase due to screening would reach 50%. In women aged 70–84, no real incidence increase was suspected if we assume that changes in clinical practices and screening led to more breast cancer cases collected.