Phenotyping spinal abnormalities in patients with Neurofibromatosis type 1 using whole-body MRI.

Neurofibromatosis Type 1 (NF1) has been reported to be associated with a variety of spinal abnormalities. The purpose of this study was to quantify the prevalence of spinal abnormalities in a collective of NF1 patients that is representative for the general NF1 population, to associate the co-appearance of spinal abnormalities with both NF1 and clinical symptoms and to investigate if different mutations of the NF1 gene affect the prevalence of these abnormalities. Retrospectively, 275 patients with NF1 and an age- and sex-matched collective of 262 patients were analyzed. The prevalence of spinal abnormalities was recorded. Mutational analysis of the NF1 gene was obtained in 235 NF1 patients. Associations between spinal abnormalities, clinical symptoms and genotype were investigated by binary logistic regression analysis. Prevalence of all spinal abnormalities was higher in NF1 patients than in the control group. Six characteristics of spinal abnormalities were significantly associated with NF1 (all p < 0.05). An influence of scalloping on scoliosis (OR 3.01; p = 0.002); of meningoceles (OR 7.63) and neuroforaminal tumors (OR 2.96) on scalloping, and of dural ectasia on neuroforaminal tumors (OR 1.93) was identified. Backpain and loss of motor function were associated with neuroforaminal tumors, spinal tumors and scalloping of vertebral bodies (all p < 0.05). Specific mutations of the NF1 gene were not relevantly associated with the development of spinal abnormalities. These findings can aid clinicians to improve clinical care of NF1 patients by creating awareness for co-appearences of specific spinal abnormalities and associated symptoms.

Antimicrobial susceptibility of Listeria monocytogenes isolates from human cases in northern Italy, 2008-2010: MIC determination according to EUCAST broth microdilution method.

Susceptibility of 96 Listeria monocytogenes human isolates collected in northern Italy between 2008 and 2010, to 15 antimicrobials, was investigated. Minimum inhibitory concentration (MIC) was evaluated by means of the standardized broth microdilution method, according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST) international guidelines. All L. monocytogenes human isolates were susceptible to penicillin G (MIC(90)≤0·06 µg/ml), meropenem (MIC(90)≤0·06 µg/ml), and erythromycin (MIC(90) = 0·12 µg/ml). Susceptibility to the other tested antimicrobials could not be interpreted due to the lack of breakpoint values although two (2%) isolates were shown to have tetracycline MICs above EUCAST epidemiological cut-off values (ECOFF). Bactericidal activity for amoxicillin, gentamicin, and levofloxacin was generally observed at concentrations 2-4 times higher than MIC values. Though L. monocytogenes human strains, isolated in the north of Italy, appear to be susceptible to most antimicrobial agents used in human therapy, this study provides new data for epidemiological surveillance and clinical breakpoints definition.

Additional evidence that pityriasis rosea is associated with reactivation of human herpesvirus-6 and -7.

To elucidate the role of human herpesvirus (HHV)-6 and -7 (HHV-7) in pityriasis rosea (PR), we measured their DNA load in plasma, peripheral blood mononuclear cells (PBMC), and tissues using a calibrated quantitative real-time PCR assay. We also studied HHV-6- and HHV-7-specific antigens in skin by immunohistochemistry and anti-HHV-7 neutralizing activity using a syncytia-inhibition test. Plasma and PBMC were obtained from 31 PR patients (14 children, 17 adults), 12 patients with other dermatites, and 36 blood donors. Skin biopsies were obtained from 15 adults with PR and 12 with other dermatites. HHV-6 and HHV-7 DNA were detected in 17% and in 39% of PR plasmas, respectively, but in no controls. HHV-7 viremia was associated with a higher PBMC load and, in adults, with systemic symptoms. HHV-7, but not HHV-6, levels in PBMC were higher in PR patients than in controls. HHV-6 and HHV-7 antigens were found only in PR skin (17% and 67% of patients analyzed, respectively), indicating a productive infection. Syncytia-neutralizing antibodies were found in PR patients and controls, but their titers were lower in patients with HHV-7 viremia. These data confirm the causal association between PR and active HHV-7 or, to a lesser extent, HHV-6 infection.

Detection of DNA of lymphotropic herpesviruses in plasma of human immunodeficiency virus-infected patients: frequency and clinical significance.

The frequency and clinical significance of detection of DNA of cytomegalovirus (CMV), Epstein-Barr virus (EBV), human herpesvirus 6 (HHV-6), HHV-7, and HHV-8 in plasma were investigated by PCR. The plasma was obtained from 120 selected human immunodeficiency virus (HIV)-infected patients, of whom 75 had AIDS-related manifestations, 32 had primary HIV infection (PHI), and 13 had asymptomatic infections. Nested PCR analysis revealed that none of the lymphotropic herpesviruses tested were found in patients with PHI, in asymptomatic HIV-positive individuals, or in HIV-negative controls. By contrast, DNA of one or more of the viruses was found in 42 (56%) of 75 patients with AIDS-related manifestations, including CMV disease (CMV-D) or AIDS-related tumors. The presence of CMV DNA in plasma was significantly associated with CMV-D (P < 0.001). By contrast, EBV detection was not significantly associated with AIDS-related lymphomas (P = 0.31). Interestingly, the presence of HHV-8 DNA in plasma was significantly associated with Kaposi's sarcoma (KS) disease (P < 0.001) and with the clinical status of KS patients (P < 0.001). CMV (primarily), EBV, and HHV-8 were the viruses most commonly reactivated in the context of severe immunosuppression (P < 0.05). In contrast, HHV-6 and HHV-7 infections were infrequent at any stage of disease. In conclusion, plasma PCR was confirmed to be useful in the diagnosis of CMV-D but not in that of tumors or other conditions possibly associated with EBV, HHV-6, and HHV-7. Our findings support the hypothesis of a direct involvement of HHV-8 replication in KS pathogenesis, thus emphasizing the usefulness of sensitive and specific diagnostic tests to monitor HHV-8 infection.

Retrospective analysis of HHV-8 viremia and cellular viral load in HIV-seropositive patients receiving interleukin 2 in combination with antiretroviral therapy.

The combination of interleukin 2 (IL-2) and antiretroviral therapy (ART) represents an emerging strategy in the treatment of patients infected with HIV. Aside from its immunomodulatory role, however, IL-2 may induce replication of human herpesvirus 8 (HHV-8)/Kaposi sarcoma (KS)-associated herpesvirus. We retrospectively evaluated HHV-8 plasma viremia and cellular load, as well as anti-HHV-8 antibody titers, in sequential samples from 84 patients receiving ART alone or in combination with IL-2. At baseline, HHV-8 plasma viremia was present only in 2 HHV-8-seropositive patients in whom KS subsequently developed during or immediately after termination of IL-2 therapy. The level of viremia increased during follow-up and peaked at the time of the clinical manifestation of KS. Moreover, transient peaks of HHV-8 viremia were temporally associated with administration of IL-2. HHV-8 plasma viremia was never detected in the other 47 patients receiving IL-2 nor in 35 controls treated only with ART. Thus, IL-2 therapy seems safe in most patients infected with both HIV and HHV-8, except for those with detectable HHV-8 viremia, who may not be eligible for IL-2 treatment.